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Ultrasound articles from across Nature Portfolio

Ultrasound is a non-invasive imaging technique that uses the differential reflectance of acoustic waves at ultrasonic frequencies to detect objects and measure distances. It is commonly used for medical imaging of internal organs and developing fetuses during pregnancy.

Latest Research and Reviews

topics for research in ultrasound

In vivo phenotypic vascular dysfunction extends beyond the aorta in a mouse model for fibrillin-1 ( Fbn1 ) mutation

  • M. E. Barrameda
  • M. Esfandiarei

topics for research in ultrasound

An ultrasensitive and broadband transparent ultrasound transducer for ultrasound and photoacoustic imaging in-vivo

Transparent ultrasound transducers suffer from practical limitations due to acoustic impedance mismatch. By using a transparent adhesive based on silicon dioxide epoxy, the authors demonstrate a broadband, ultrasensitive transparent ultrasound transducer, advancing the possibilities of sensor fusion.

  • Seonghee Cho
  • Chulhong Kim

topics for research in ultrasound

Sarcopenia prediction using shear-wave elastography, grayscale ultrasonography, and clinical information with machine learning fusion techniques: feature-level fusion vs. score-level fusion

  • Young Han Lee

topics for research in ultrasound

Non-contrast ultrasound image analysis for spatial and temporal distribution of blood flow after spinal cord injury

  • Denis Routkevitch
  • Amir Manbachi

topics for research in ultrasound

Tethered spinal cord tension assessed via ultrasound elastography in computational and intraoperative human studies

Kerensky et al. quantify tension across human spinal cords in computational simulations, a cadaveric benchtop model, and a neurosurgical case series. Their direct methodology successfully differentiates stretched spinal cords from healthy states in all sub-studies.

  • Max J. Kerensky
  • Abhijit Paul

topics for research in ultrasound

Ultrafast longitudinal imaging of haemodynamics via single-shot volumetric photoacoustic tomography with a single-element detector

Photoacoustic tomography using a single laser pulse and a single element functioning as thousands of virtual detectors allows for the volumetric capture of fast haemodynamic changes in the feet of human volunteers.

  • Lihong V. Wang


News and Comment

Mid-ir optoacoustic microscopy.

  • Rita Strack

Ultrasound success removes barriers to targeted drug delivery in amyotrophic lateral sclerosis

topics for research in ultrasound

A sound strategy for gene expression

A new study in Science reports a synthetic biology approach to encode an ultrasound-based gene expression reporter that is applicable to mammalian cells in vitro and in vivo.

  • Darren J. Burgess

Unbiased, whole-brain imaging of neural circuits

Functional ultrasound imaging enables unbiased identification of behaviorally relevant brain regions across the whole brain.

topics for research in ultrasound

Hyperthermia-induced drug delivery in humans

A clinical study shows the feasibility and safety of the intratumoral release of an anticancer drug encapsulated in thermosensitive liposomes by heating the patient’s tumour via focused ultrasound.

  • Kullervo Hynynen

topics for research in ultrasound

Non-invasive chemogenetics

A technique combining focused ultrasound for opening the blood–brain barrier and virally encoded engineered G-protein-coupled receptors for promoting the expression of a gene targeting excitatory neurons enables the non-invasive stimulation of specific brain regions and cell types in mice.

  • Caroline Menard
  • Scott J. Russo

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topics for research in ultrasound

59 Ultrasound Essay Topic Ideas & Examples

🏆 best ultrasound topic ideas & essay examples, ✅ good essay topics on ultrasound, 📑 interesting topics to write about ultrasound.

  • The Biological Effects of Ultrasound The paper also evaluates the physical mechanisms for the biological effects of ultrasound and the effects of ultrasound on living tissues in vivo and vitriol.
  • Ultrasound Technology in Podiatry Surgery First, it is important to briefly outline the peculiarities of the RCT to understand the researchers’ point. They will be able to use the technology in numerous settings. We will write a custom essay specifically for you by our professional experts 808 writers online Learn More
  • Use of Ultrasound-Guidance for Arterial Puncture All the anthropometric and demographic variables were recorded, as well as the main diagnosis of admission, comorbidities, the placement of the central venous catheter, and the course of the procedure.
  • MRI and Ultrasound for Determining Abnormalities in Preterm Infants Neonatal cranial ultrasound is used in detecting brain injury in preterm infants and can be used repetitively without harming the infant.
  • Benefits of 3D Ultrasound to Pregnant Mothers This is coherent to the 3D planar imaging are improved technology previously applied in the 2D ultrasound technology. As an extrapolation from 3D technology, 3D ultrasound is applied as a medical diagnostic technique that utilizes […]
  • The Recent Advances in Real Time Imaging in Ultrasound In point of fact, Medical imaging provides the most perfect task of diagnostic to Ultrasound, whereas, the main usage of therapeutic Ultrasound is to treat the numerous types of diseases and disorders in human beings.
  • Comparison of MRI and Ultrasound for Determining Abnormalities in Preterm Infants Medical Imaging helps in detecting and diagnosing diseases at its earliest and treatable stage and helps in determining most appropriate and effective care for the patient.”Medical imaging provides a picture of the inside of the […]
  • Ultrasound Techniques Applied to Body Fat Measurement in Male and Female The main objective of this paper is to evaluate the accuracy of body fat by using portable ultra sound device which results are reliable and authentic. The ultra sound technique is widely used to measure […]
  • Benefits of 3D/4D Ultrasound in Prenatal Care The information that is obtained from this exam assists the health care providers in counseling parents on the development of the fetus especially in the nature of anomalies, prognosis, and the postnatal consideration of the […]
  • Biologic Effects of Ultrasound in Healthcare Setting The instrument performing the emission of the sound waves and the recording of their bouncing back is referred to as the transducer and the medical practitioner generally gently presses the transducer against the skin of […]
  • Ultrasound Scanning: Diagnosing Health Conditions The calculation is based on the time taken by the wave to return by measuring the distance, mass, nature, and stability of the object hit.
  • Mammography vs. Ultrasound for Breast Tissue Analysis Mammography screening is one of the most recognized options for analyzing breast tissue in adult women. In contrast, the accuracy of this procedure allows it to be an alternative for women who cannot undergo mammography […]
  • Ultrasound Physics and Instrumentation The camera is often not in harmony with the perception of the depth of a human vision. The level of such an acoustic signal distortion within a tissue is dependent on the emitted pulse’s amplitude […]
  • Low-Back Pain and Ultrasound Therapy In the meantime, their opponents highlight that the beneficial aspects of the treatment course outweigh the risks related to the use of ultrasound equipment.
  • Ultrasound in Treatment and Side-Effect Reduction Within the framework of the research project conducted by Ebadi et al, the research problem consisted in the fact that the effects of continuous ultrasound were underresearched.
  • Ultrasound in Achilles Tendinitis Diagnosis In this research, the case study approach is applicable due to the fact that various patients suffering from tendon Achilles problem will be used as a basis for gauging the effectiveness of the method of […]
  • Abdominal Ultrasound and Diagnoses The examiner explains to the patient how the procedure will be performed and how much time is necessary to finish the examination.
  • Ultrasound and Color Doppler-Guided Surgery The purpose of the study is to examine the opinions of the trainees attending a training course concerning the use of technology.
  • Contrast-Enhanced Ultrasound in Focal Liver Lesions In addition, inaccessibility to the eighth of the liver is a major setback in detecting lesions in the segment. With the advent of Doppler ultrasound, more insight in the diagnosis of liver lesions has been […]
  • Ultrasound in Chemistry: Sonochemistry
  • Intravascular Ultrasound: Current Role and Future Perspectives
  • The Difference Between an Echocardiogram and an Ultrasound of the Heart
  • Cooperative Control With Ultrasound Guidance for Radiation Therapy
  • Optically Generated Ultrasound: A New Paradigm for Intracoronary Imaging
  • Nondestructive Testing: Principle of Flaw Detection With Ultrasound
  • Closed-Loop Transcranial Ultrasound Stimulation for Real-Time Non-invasive Neuromodulation
  • Consumer Application of Ultrasound: A Television Remote
  • Roles of Low-Intensity Ultrasound in Differentiating Cell Death
  • High-Intensity Focused Ultrasound Development: Destroying the Target Tissue
  • Using Ultrasound to Enhance the Mechanical and Physical Properties of Metals
  • The Security Implications of the Machine-Learning Supply Chain: Professionalism in the Ultrasound Department
  • Ultrasound Neuromodulation: Mechanisms and the Potential of Multimodal Stimulation for Neuronal Function Assessment
  • How Ultrasound Can Produce Sonoluminescence
  • Preparation for an Ultrasound of a Gallbladder and a Pelvic
  • Endorectal and Endoanal Ultrasound Technique
  • Transvaginal Ultrasound: Is It Painful, Purpose, and Results
  • Endoscopic Ultrasound in Diagnosing Cancer: One of the Most Common Imaging Procedures
  • Ultrasound Skin Imaging in Dermatology, Aesthetic Medicine, and Cosmetology
  • Ultrasound Physical Medical Treatment in Healing Following an Acute Injury or a Chronic Condition
  • How Do Ultrasound Scans Work
  • Americas Ultrasound Systems Market: From USD 7.9 Billion to USD 10.23 Billion
  • How Ultrasound Imaging Helps Us Understand Speech and Accent Variation
  • Cerebral Ultrasound Time-Harmonic Elastography: Softening of the Human Brain Due to Dehydration
  • Wireless Communication in “Audio Beacons” Using Ultrasound
  • Low-Intensity Focused Ultrasound for Posttraumatic Stress Disorder
  • Thyroid Ultrasound: Purpose, Procedure, Benefits
  • Blood Pressure Modulation With Low-Intensity Focused Ultrasound
  • Accuracy of Ultrasounds in Diagnosing Birth Defects
  • Functional Ultrasound During Awake Brain Surgery
  • Live Animal Ultrasound Explained by Dr. Allen Williams
  • Ultrasound Waves in Acoustic Microscopy
  • Chemical and Physical Effects of Ultrasound: Sonoluminescence and Materials
  • Focused Ultrasound for Noninvasive, Focal Pharmacologic Neurointervention
  • Lung Ultrasound Findings in COVID-19 Pneumonia
  • High-Power Ultrasound in Dry Corn Milling Plants
  • History of Ultrasound of Physics and the Properties of the Transducer
  • Relationship Between Ultrasound Viewing and Proceeding to Abortion
  • Transrectal Ultrasound of the Prostate With a Biopsy
  • Iron-Based Catalysts Used in Water Treatment Assisted by Ultrasound
  • Chicago (A-D)
  • Chicago (N-B)

IvyPanda. (2023, January 24). 59 Ultrasound Essay Topic Ideas & Examples.

"59 Ultrasound Essay Topic Ideas & Examples." IvyPanda , 24 Jan. 2023,

IvyPanda . (2023) '59 Ultrasound Essay Topic Ideas & Examples'. 24 January.

IvyPanda . 2023. "59 Ultrasound Essay Topic Ideas & Examples." January 24, 2023.

1. IvyPanda . "59 Ultrasound Essay Topic Ideas & Examples." January 24, 2023.


IvyPanda . "59 Ultrasound Essay Topic Ideas & Examples." January 24, 2023.

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Home > Books > Medical Imaging

Ultrasound Imaging - Current Topics

Ultrasound Imaging

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3,603 Chapter Downloads

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Gregory University , Nigeria

Published 11 May 2022

Doi 10.5772/intechopen.95178

ISBN 978-1-78985-186-1

Print ISBN 978-1-78984-877-9

eBook (PDF) ISBN 978-1-78985-331-5

Copyright year 2022

Number of pages 154

Ultrasound Imaging - Current Topics presents complex and current topics in ultrasound imaging in a simplified format. It is easy to read and exemplifies the range of experiences of each contributing author. Chapters address such topics as anatomy and dimensional variations, pediatric gastrointestinal emergencies, musculoskeletal and nerve imaging as well as molecular sonography. The book is...

Ultrasound Imaging - Current Topics presents complex and current topics in ultrasound imaging in a simplified format. It is easy to read and exemplifies the range of experiences of each contributing author. Chapters address such topics as anatomy and dimensional variations, pediatric gastrointestinal emergencies, musculoskeletal and nerve imaging as well as molecular sonography. The book is a useful resource for researchers, students, clinicians, and sonographers looking for additional information on ultrasound imaging beyond the basics.

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topics for research in ultrasound


Ultrasound News

Top headlines, latest headlines.

  • Biomedical Imaging Technology
  • Ultrasound and Oxygen Saturation in Blood
  • Ultrasound Imaging: Ultrafast Tech
  • Soundwaves Harden 3D-Printed Treatments in Body
  • Network of Robots to Monitor Pipes Acoustically
  • 2 Droplets Levitated and Mixed
  • New Laser Setup Probes Metamaterials
  • Medical Imaging Fails Dark Skin: Researchers ...
  • Ultrasound May Rid Groundwater of Toxic ...
  • Ultra-Sensitive Photoacoustic Microscopy

Earlier Headlines

Friday, july 28, 2023.

  • A Wearable Ultrasound Scanner Could Detect Breast Cancer Earlier

Wednesday, July 26, 2023

  • A Quick Look Inside a Human Being

Tuesday, June 27, 2023

  • Researchers Use Ultrasound to Control Orientation of Small Particles

Thursday, June 22, 2023

  • When Soft Spheres Make Porous Media Stiffer

Thursday, June 15, 2023

  • A 'spy' In the Belly

Wednesday, June 7, 2023

  • Sponge Makes Robotic Device a Soft Touch

Monday, May 22, 2023

  • A Giant Leap Forward in Wireless Ultrasound Monitoring for Subjects in Motion

Tuesday, May 2, 2023

  • Wearable Ultrasound Patch Provide Non-Invasive Deep Tissue Monitoring

Tuesday, April 4, 2023

  • Detecting, Predicting, and Preventing Aortic Ruptures With Computational Modeling

Friday, March 10, 2023

  • New Ultrasound Method Could Lead to Easier Disease Diagnosis

Wednesday, March 1, 2023

  • The Future of Touch

Tuesday, February 28, 2023

  • Ultrasound Device May Offer New Treatment Option for Hypertension

Friday, February 24, 2023

  • Faster and Sharper Whole-Body Imaging of Small Animals With Deep Learning

Thursday, February 23, 2023

  • Making Engineered Cells Dance to Ultrasound

Wednesday, February 22, 2023

  • Study Offers Details on Using Electric Fields to Tune Thermal Properties of Ferroelectric Materials

Monday, February 13, 2023

  • Creating 3D Objects With Sound

Tuesday, January 31, 2023

  • Focused Ultrasound Technique Leads to Release of Neurodegenerative Disorders Biomarkers

Wednesday, January 25, 2023

  • Wearable Sensor Uses Ultrasound to Provide Cardiac Imaging on the Go

Friday, January 13, 2023

  • A Precision Arm for Miniature Robots

Tuesday, January 3, 2023

  • Tracking Radiation Treatment in Real Time Promises Safer, More Effective Cancer Therapy
  • Team Writes Letters With Ultrasonic Beam, Develops Deep Learning Based Real-Time Ultrasonic Hologram Generation Technology

Thursday, December 1, 2022

  • An Exotic Interplay of Electrons

Wednesday, September 21, 2022

  • The Super-Fast MRI Scan That Could Revolutionize Heart Failure Diagnosis

Friday, August 12, 2022

  • Using Sound and Bubbles to Make Bandages Stickier and Longer Lasting

Tuesday, August 9, 2022

  • Ultrasound Could Save Racehorses from Bucked Shins

Thursday, July 28, 2022

  • Engineers Develop Stickers That Can See Inside the Body

Thursday, July 21, 2022

  • Flexible Method for Shaping Laser Beams Extends Depth-of-Focus for OCT Imaging

Wednesday, June 15, 2022

  • High-Intensity Focused Ultrasound (HIFU) Can Control Prostate Cancer With Fewer Side Effects
  • Moth Wing-Inspired Sound Absorbing Wallpaper in Sight After Breakthrough

Tuesday, May 31, 2022

  • Direct Sound Printing Is a Potential Game-Changer in 3D Printing

Monday, May 30, 2022

  • Ultrasound-Guided Microbubbles Boost Immunotherapy Efficacy

Thursday, May 5, 2022

  • How MRI Could Revolutionize Heart Failure Diagnosis

Wednesday, April 27, 2022

  • 3D Bimodal Photoacoustic Ultrasound Imaging to Diagnose Peripheral Vascular Diseases

Monday, April 18, 2022

  • Tumors Partially Destroyed With Sound Don't Come Back

Tuesday, April 12, 2022

  • Ultrasound Gave Us Our First Baby Pictures Can It Also Help the Blind See?

Monday, April 4, 2022

  • Dual-Mode Endoscope Offers Unprecedented Insights Into Uterine Health

Wednesday, March 23, 2022

  • Concert Hall Acoustics for Non-Invasive Ultrasound Brain Treatments

Tuesday, March 22, 2022

  • Quantum Dots Shine Bright to Help Scientists See Inflammatory Cells in Fat

Friday, March 11, 2022

  • Acoustic Propulsion of Nanomachines Depends on Their Orientation

Monday, February 28, 2022

  • Ultrasound Scan Can Diagnose Prostate Cancer

Friday, February 25, 2022

  • Ultrasounds for Endangered Abalone Mollusks

Thursday, February 24, 2022

  • Transparent Ultrasound Chip Improves Cell Stimulation and Imaging

Tuesday, February 22, 2022

  • Low-Cost, 3D Printed Device May Broaden Focused Ultrasound Use

Tuesday, February 15, 2022

  • Speed of Sound Used to Measure Elasticity of Materials

Tuesday, January 25, 2022

  • Ultrasound Technique Predicts Hip Dysplasia in Infants

Wednesday, January 5, 2022

  • The First Topological Acoustic Transistor

Friday, December 17, 2021

  • New Research Sheds Light on How Ultrasound Could Be Used to Treat Psychiatric Disorders

Wednesday, December 8, 2021

  • CRISPR/Cas9 Gene Editing Boosts Effectiveness of Ultrasound Cancer Therapy

Wednesday, November 10, 2021

  • A Personalized Exosuit for Real-World Walking

Monday, November 1, 2021

  • Noninvasive Imaging Strategy Detects Dangerous Blood Clots in the Body

Friday, September 10, 2021

  • Acoustic Illusions

Tuesday, August 24, 2021

  • Researchers Developing New Cancer Treatments With High-Intensity Focused Ultrasound

Tuesday, August 17, 2021

  • Prediction Models May Reduce False-Positives in MRI Breast Cancer Screening

Tuesday, August 3, 2021

  • Does Visual Feedback of Our Tongues Help in Speech Motor Learning?

Tuesday, July 27, 2021

  • Researchers Demonstrate Technique for Recycling Nanowires in Electronics

Thursday, July 22, 2021

  • Soft Skin Patch Could Provide Early Warning for Strokes, Heart Attacks

Monday, July 12, 2021

  • Magnetic Field from MRI Affects Focused-Ultrasound-Mediated Blood-Brain Barrier

Monday, June 21, 2021

  • A Tiny Device Incorporates a Compound Made from Starch and Baking Soda to Harvest Energy from Movement

Friday, May 28, 2021

  • New Tool Activates Deep Brain Neurons by Combining Ultrasound, Genetics

Monday, May 24, 2021

  • Silicon Chips Combine Light and Ultrasound for Better Signal Processing

Tuesday, May 11, 2021

  • Tiny, Wireless, Injectable Chips Use Ultrasound to Monitor Body Processes

Wednesday, May 5, 2021

  • Release of Drugs from a Supramolecular Cage
  • Focused Ultrasound Enables Precise Noninvasive Therapy

Wednesday, April 14, 2021

  • Using Sound Waves to Make Patterns That Never Repeat
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topics for research in ultrasound

Head Start Your Radiology Residency [Online] ↗️

  • Radiology Thesis – More than 400 Research Topics (2022)!

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Radiology Thesis Topics


A thesis or dissertation, as some people would like to call it, is an integral part of the Radiology curriculum, be it MD, DNB, or DMRD. We have tried to aggregate radiology thesis topics from various sources for reference.

Not everyone is interested in research, and writing a Radiology thesis can be daunting. But there is no escape from preparing, so it is better that you accept this bitter truth and start working on it instead of cribbing about it (like other things in life. #PhilosophyGyan!)

Start working on your thesis as early as possible and finish your thesis well before your exams, so you do not have that stress at the back of your mind. Also, your thesis may need multiple revisions, so be prepared and allocate time accordingly.

Tips for Choosing Radiology Thesis and Research Topics

Keep it simple silly (kiss).

Retrospective > Prospective

Retrospective studies are better than prospective ones, as you already have the data you need when choosing to do a retrospective study. Prospective studies are better quality, but as a resident, you may not have time (, energy and enthusiasm) to complete these.

Choose a simple topic that answers a single/few questions

Original research is challenging, especially if you do not have prior experience. I would suggest you choose a topic that answers a single or few questions. Most topics that I have listed are along those lines. Alternatively, you can choose a broad topic such as “Role of MRI in evaluation of perianal fistulas.”

You can choose a novel topic if you are genuinely interested in research AND have a good mentor who will guide you. Once you have done that, make sure that you publish your study once you are done with it.

Get it done ASAP.

In most cases, it makes sense to stick to a thesis topic that will not take much time. That does not mean you should ignore your thesis and ‘Ctrl C + Ctrl V’ from a friend from another university. Thesis writing is your first step toward research methodology so do it as sincerely as possible. Do not procrastinate in preparing the thesis. As soon as you have been allotted a guide, start researching topics and writing a review of the literature.

At the same time, do not invest a lot of time in writing/collecting data for your thesis. You should not be busy finishing your thesis a few months before the exam. Some people could not appear for the exam because they could not submit their thesis in time. So DO NOT TAKE thesis lightly.

Do NOT Copy-Paste

Reiterating once again, do not simply choose someone else’s thesis topic. Find out what are kind of cases that your Hospital caters to. It is better to do a good thesis on a common topic than a crappy one on a rare one.

Books to help you write a Radiology Thesis

Event country/university has a different format for thesis; hence these book recommendations may not work for everyone.

How to Write the Thesis and Thesis Protocol: A Primer for Medical, Dental, and Nursing Courses: A Primer for Medical, Dental and Nursing Courses

  • Amazon Kindle Edition
  • Gupta, Piyush (Author)
  • English (Publication Language)
  • 206 Pages - 10/12/2020 (Publication Date) - Jaypee Brothers Medical Publishers (P) Ltd. (Publisher)

In A Hurry? Download a PDF list of Radiology Research Topics!

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List of Radiology Research /Thesis / Dissertation Topics

  • State of the art of MRI in the diagnosis of hepatic focal lesions
  • Multimodality imaging evaluation of sacroiliitis in newly diagnosed patients of spondyloarthropathy
  • Multidetector computed tomography in oesophageal varices
  • Role of positron emission tomography with computed tomography in the diagnosis of cancer Thyroid
  • Evaluation of focal breast lesions using ultrasound elastography
  • Role of MRI diffusion tensor imaging in the assessment of traumatic spinal cord injuries
  • Sonographic imaging in male infertility
  • Comparison of color Doppler and digital subtraction angiography in occlusive arterial disease in patients with lower limb ischemia
  • The role of CT urography in Haematuria
  • Role of functional magnetic resonance imaging in making brain tumor surgery safer
  • Prediction of pre-eclampsia and fetal growth restriction by uterine artery Doppler
  • Role of grayscale and color Doppler ultrasonography in the evaluation of neonatal cholestasis
  • Validity of MRI in the diagnosis of congenital anorectal anomalies
  • Role of sonography in assessment of clubfoot
  • Role of diffusion MRI in preoperative evaluation of brain neoplasms
  • Imaging of upper airways for pre-anaesthetic evaluation purposes and for laryngeal afflictions.
  • A study of multivessel (arterial and venous) Doppler velocimetry in intrauterine growth restriction
  • Multiparametric 3tesla MRI of suspected prostatic malignancy.
  • Role of Sonography in Characterization of Thyroid Nodules for differentiating benign from
  • Role of advances magnetic resonance imaging sequences in multiple sclerosis
  • Role of multidetector computed tomography in evaluation of jaw lesions
  • Role of Ultrasound and MR Imaging in the Evaluation of Musculotendinous Pathologies of Shoulder Joint
  • Role of perfusion computed tomography in the evaluation of cerebral blood flow, blood volume and vascular permeability of cerebral neoplasms
  • MRI flow quantification in the assessment of the commonest csf flow abnormalities
  • Role of diffusion-weighted MRI in evaluation of prostate lesions and its histopathological correlation
  • CT enterography in evaluation of small bowel disorders
  • Comparison of perfusion magnetic resonance imaging (PMRI), magnetic resonance spectroscopy (MRS) in and positron emission tomography-computed tomography (PET/CT) in post radiotherapy treated gliomas to detect recurrence
  • Role of multidetector computed tomography in evaluation of paediatric retroperitoneal masses
  • Role of Multidetector computed tomography in neck lesions
  • Estimation of standard liver volume in Indian population
  • Role of MRI in evaluation of spinal trauma
  • Role of modified sonohysterography in female factor infertility: a pilot study.
  • The role of pet-CT in the evaluation of hepatic tumors
  • Role of 3D magnetic resonance imaging tractography in assessment of white matter tracts compromise in supratentorial tumors
  • Role of dual phase multidetector computed tomography in gallbladder lesions
  • Role of multidetector computed tomography in assessing anatomical variants of nasal cavity and paranasal sinuses in patients of chronic rhinosinusitis.
  • magnetic resonance spectroscopy in multiple sclerosis
  • Evaluation of thyroid nodules by ultrasound elastography using acoustic radiation force impulse (ARFI) imaging
  • Role of Magnetic Resonance Imaging in Intractable Epilepsy
  • Evaluation of suspected and known coronary artery disease by 128 slice multidetector CT.
  • Role of regional diffusion tensor imaging in the evaluation of intracranial gliomas and its histopathological correlation
  • Role of chest sonography in diagnosing pneumothorax
  • Role of CT virtual cystoscopy in diagnosis of urinary bladder neoplasia
  • Role of MRI in assessment of valvular heart diseases
  • High resolution computed tomography of temporal bone in unsafe chronic suppurative otitis media
  • Multidetector CT urography in the evaluation of hematuria
  • Contrast-induced nephropathy in diagnostic imaging investigations with intravenous iodinated contrast media
  • Comparison of dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging and single photon emission computed tomography in patients with little’s disease
  • Role of Multidetector Computed Tomography in Bowel Lesions.
  • Role of diagnostic imaging modalities in evaluation of post liver transplantation recipient complications.
  • Role of multislice CT scan and barium swallow in the estimation of oesophageal tumour length
  • Malignant Lesions-A Prospective Study.
  • Value of ultrasonography in assessment of acute abdominal diseases in pediatric age group
  • Role of three dimensional multidetector CT hysterosalpingography in female factor infertility
  • Comparative evaluation of multi-detector computed tomography (MDCT) virtual tracheo-bronchoscopy and fiberoptic tracheo-bronchoscopy in airway diseases
  • Role of Multidetector CT in the evaluation of small bowel obstruction
  • Sonographic evaluation in adhesive capsulitis of shoulder
  • Utility of MR Urography Versus Conventional Techniques in Obstructive Uropathy
  • MRI of the postoperative knee
  • Role of 64 slice-multi detector computed tomography in diagnosis of bowel and mesenteric injury in blunt abdominal trauma.
  • Sonoelastography and triphasic computed tomography in the evaluation of focal liver lesions
  • Evaluation of Role of Transperineal Ultrasound and Magnetic Resonance Imaging in Urinary Stress incontinence in Women
  • Multidetector computed tomographic features of abdominal hernias
  • Evaluation of lesions of major salivary glands using ultrasound elastography
  • Transvaginal ultrasound and magnetic resonance imaging in female urinary incontinence
  • MDCT colonography and double-contrast barium enema in evaluation of colonic lesions
  • Role of MRI in diagnosis and staging of urinary bladder carcinoma
  • Spectrum of imaging findings in children with febrile neutropenia.
  • Spectrum of radiographic appearances in children with chest tuberculosis.
  • Role of computerized tomography in evaluation of mediastinal masses in pediatric
  • Diagnosing renal artery stenosis: Comparison of multimodality imaging in diabetic patients
  • Role of multidetector CT virtual hysteroscopy in the detection of the uterine & tubal causes of female infertility
  • Role of multislice computed tomography in evaluation of crohn’s disease
  • CT quantification of parenchymal and airway parameters on 64 slice MDCT in patients of chronic obstructive pulmonary disease
  • Comparative evaluation of MDCT  and 3t MRI in radiographically detected jaw lesions.
  • Evaluation of diagnostic accuracy of ultrasonography, colour Doppler sonography and low dose computed tomography in acute appendicitis
  • Ultrasonography , magnetic resonance cholangio-pancreatography (MRCP) in assessment of pediatric biliary lesions
  • Multidetector computed tomography in hepatobiliary lesions.
  • Evaluation of peripheral nerve lesions with high resolution ultrasonography and colour Doppler
  • Multidetector computed tomography in pancreatic lesions
  • Multidetector Computed Tomography in Paediatric abdominal masses.
  • Evaluation of focal liver lesions by colour Doppler and MDCT perfusion imaging
  • Sonographic evaluation of clubfoot correction during Ponseti treatment
  • Role of multidetector CT in characterization of renal masses
  • Study to assess the role of Doppler ultrasound in evaluation of arteriovenous (av) hemodialysis fistula and the complications of hemodialysis vasular access
  • Comparative study of multiphasic contrast-enhanced CT and contrast-enhanced MRI in the evaluation of hepatic mass lesions
  • Sonographic spectrum of rheumatoid arthritis
  • Diagnosis & staging of liver fibrosis by ultrasound elastography in patients with chronic liver diseases
  • Role of multidetector computed tomography in assessment of jaw lesions.
  • Role of high-resolution ultrasonography in the differentiation of benign and malignant thyroid lesions
  • Radiological evaluation of aortic aneurysms in patients selected for endovascular repair
  • Role of conventional MRI, and diffusion tensor imaging tractography in evaluation of congenital brain malformations
  • To evaluate the status of coronary arteries in patients with non-valvular atrial fibrillation using 256 multirow detector CT scan
  • A comparative study of ultrasonography and CT – arthrography in diagnosis of chronic ligamentous and meniscal injuries of knee
  • Multi detector computed tomography evaluation in chronic obstructive pulmonary disease and correlation with severity of disease
  • Diffusion weighted and dynamic contrast enhanced magnetic resonance imaging in chemoradiotherapeutic response evaluation in cervical cancer.
  • High resolution sonography in the evaluation of non-traumatic painful wrist
  • The role of trans-vaginal ultrasound versus magnetic resonance imaging in diagnosis & evaluation of cancer cervix
  • Role of multidetector row computed tomography in assessment of maxillofacial trauma
  • Imaging of vascular complication after liver transplantation.
  • Role of magnetic resonance perfusion weighted imaging & spectroscopy for grading of glioma by correlating perfusion parameter of the lesion with the final histopathological grade
  • Magnetic resonance evaluation of abdominal tuberculosis.
  • Diagnostic usefulness of low dose spiral HRCT in diffuse lung diseases
  • Role of dynamic contrast enhanced and diffusion weighted magnetic resonance imaging in evaluation of endometrial lesions
  • Contrast enhanced digital mammography anddigital breast tomosynthesis in early diagnosis of breast lesion
  • Evaluation of Portal Hypertension with Colour Doppler flow imaging and magnetic resonance imaging
  • Evaluation of musculoskeletal lesions by magnetic resonance imaging
  • Role of diffusion magnetic resonance imaging in assessment of neoplastic and inflammatory brain lesions
  • Radiological spectrum of chest diseases in HIV infected children High resolution ultrasonography in neck masses in children
  • with surgical findings
  • Sonographic evaluation of peripheral nerves in type 2 diabetes mellitus.
  • Role of perfusion computed tomography in the evaluation of neck masses and correlation
  • Role of ultrasonography in the diagnosis of knee joint lesions
  • Role of ultrasonography in evaluation of various causes of pelvic pain in first trimester of pregnancy.
  • Role of Magnetic Resonance Angiography in the Evaluation of Diseases of Aorta and its Branches
  • MDCT fistulography in evaluation of fistula in Ano
  • Role of multislice CT in diagnosis of small intestine tumors
  • Role of high resolution CT in differentiation between benign and malignant pulmonary nodules in children
  • A study of multidetector computed tomography urography in urinary tract abnormalities
  • Role of high resolution sonography in assessment of ulnar nerve in patients with leprosy.
  • Pre-operative radiological evaluation of locally aggressive and malignant musculoskeletal tumours by computed tomography and magnetic resonance imaging.
  • The role of ultrasound & MRI in acute pelvic inflammatory disease
  • Ultrasonography compared to computed tomographic arthrography in the evaluation of shoulder pain
  • Role of Multidetector Computed Tomography in patients with blunt abdominal trauma.
  • The Role of Extended field-of-view Sonography and compound imaging in Evaluation of Breast Lesions
  • Evaluation of focal pancreatic lesions by Multidetector CT and perfusion CT
  • Evaluation of breast masses on sono-mammography and colour Doppler imaging
  • Role of CT virtual laryngoscopy in evaluation of laryngeal masses
  • Triple phase multi detector computed tomography in hepatic masses
  • Role of transvaginal ultrasound in diagnosis and treatment of female infertility
  • Role of ultrasound and color Doppler imaging in assessment of acute abdomen due to female genetal causes
  • High resolution ultrasonography and color Doppler ultrasonography in scrotal lesion
  • Evaluation of diagnostic accuracy of ultrasonography with colour Doppler vs low dose computed tomography in salivary gland disease
  • Role of multidetector CT in diagnosis of salivary gland lesions
  • Comparison of diagnostic efficacy of ultrasonography and magnetic resonance cholangiopancreatography in obstructive jaundice: A prospective study
  • Evaluation of varicose veins-comparative assessment of low dose CT venogram with sonography: pilot study
  • Role of mammotome in breast lesions
  • The role of interventional imaging procedures in the treatment of selected gynecological disorders
  • Role of transcranial ultrasound in diagnosis of neonatal brain insults
  • Role of multidetector CT virtual laryngoscopy in evaluation of laryngeal mass lesions
  • Evaluation of adnexal masses on sonomorphology and color Doppler imaginig
  • Role of radiological imaging in diagnosis of endometrial carcinoma
  • Comprehensive imaging of renal masses by magnetic resonance imaging
  • The role of 3D & 4D ultrasonography in abnormalities of fetal abdomen
  • Diffusion weighted magnetic resonance imaging in diagnosis and characterization of brain tumors in correlation with conventional MRI
  • Role of diffusion weighted MRI imaging in evaluation of cancer prostate
  • Role of multidetector CT in diagnosis of urinary bladder cancer
  • Role of multidetector computed tomography in the evaluation of paediatric retroperitoneal masses.
  • Comparative evaluation of gastric lesions by double contrast barium upper G.I. and multi detector computed tomography
  • Evaluation of hepatic fibrosis in chronic liver disease using ultrasound elastography
  • Role of MRI in assessment of hydrocephalus in pediatric patients
  • The role of sonoelastography in characterization of breast lesions
  • The influence of volumetric tumor doubling time on survival of patients with intracranial tumours
  • Role of perfusion computed tomography in characterization of colonic lesions
  • Role of proton MRI spectroscopy in the evaluation of temporal lobe epilepsy
  • Role of Doppler ultrasound and multidetector CT angiography in evaluation of peripheral arterial diseases.
  • Role of multidetector computed tomography in paranasal sinus pathologies
  • Role of virtual endoscopy using MDCT in detection & evaluation of gastric pathologies
  • High resolution 3 Tesla MRI in the evaluation of ankle and hindfoot pain.
  • Transperineal ultrasonography in infants with anorectal malformation
  • CT portography using MDCT versus color Doppler in detection of varices in cirrhotic patients
  • Role of CT urography in the evaluation of a dilated ureter
  • Characterization of pulmonary nodules by dynamic contrast-enhanced multidetector CT
  • Comprehensive imaging of acute ischemic stroke on multidetector CT
  • The role of fetal MRI in the diagnosis of intrauterine neurological congenital anomalies
  • Role of Multidetector computed tomography in pediatric chest masses
  • Multimodality imaging in the evaluation of palpable & non-palpable breast lesion.
  • Sonographic Assessment Of Fetal Nasal Bone Length At 11-28 Gestational Weeks And Its Correlation With Fetal Outcome.
  • Role Of Sonoelastography And Contrast-Enhanced Computed Tomography In Evaluation Of Lymph Node Metastasis In Head And Neck Cancers
  • Role Of Renal Doppler And Shear Wave Elastography In Diabetic Nephropathy
  • Evaluation Of Relationship Between Various Grades Of Fatty Liver And Shear Wave Elastography Values
  • Evaluation and characterization of pelvic masses of gynecological origin by USG, color Doppler and MRI in females of reproductive age group
  • Radiological evaluation of small bowel diseases using computed tomographic enterography
  • Role of coronary CT angiography in patients of coronary artery disease
  • Role of multimodality imaging in the evaluation of pediatric neck masses
  • Role of CT in the evaluation of craniocerebral trauma
  • Role of magnetic resonance imaging (MRI) in the evaluation of spinal dysraphism
  • Comparative evaluation of triple phase CT and dynamic contrast-enhanced MRI in patients with liver cirrhosis
  • Evaluation of the relationship between carotid intima-media thickness and coronary artery disease in patients evaluated by coronary angiography for suspected CAD
  • Assessment of hepatic fat content in fatty liver disease by unenhanced computed tomography
  • Correlation of vertebral marrow fat on spectroscopy and diffusion-weighted MRI imaging with bone mineral density in postmenopausal women.
  • Comparative evaluation of CT coronary angiography with conventional catheter coronary angiography
  • Ultrasound evaluation of kidney length & descending colon diameter in normal and intrauterine growth-restricted fetuses
  • A prospective study of hepatic vein waveform and splenoportal index in liver cirrhosis: correlation with child Pugh’s classification and presence of esophageal varices.
  • CT angiography to evaluate coronary artery by-pass graft patency in symptomatic patient’s functional assessment of myocardium by cardiac MRI in patients with myocardial infarction
  • MRI evaluation of HIV positive patients with central nervous system manifestations
  • MDCT evaluation of mediastinal and hilar masses
  • Evaluation of rotator cuff & labro-ligamentous complex lesions by MRI & MRI arthrography of shoulder joint
  • Role of imaging in the evaluation of soft tissue vascular malformation
  • Role of MRI and ultrasonography in the evaluation of multifidus muscle pathology in chronic low back pain patients
  • Role of ultrasound elastography in the differential diagnosis of breast lesions
  • Role of magnetic resonance cholangiopancreatography in evaluating dilated common bile duct in patients with symptomatic gallstone disease.
  • Comparative study of CT urography & hybrid CT urography in patients with haematuria.
  • Role of MRI in the evaluation of anorectal malformations
  • Comparison of ultrasound-Doppler and magnetic resonance imaging findings in rheumatoid arthritis of hand and wrist
  • Role of Doppler sonography in the evaluation of renal artery stenosis in hypertensive patients undergoing coronary angiography for coronary artery disease.
  • Comparison of radiography, computed tomography and magnetic resonance imaging in the detection of sacroiliitis in ankylosing spondylitis.
  • Mr evaluation of painful hip
  • Role of MRI imaging in pretherapeutic assessment of oral and oropharyngeal malignancy
  • Evaluation of diffuse lung diseases by high resolution computed tomography of the chest
  • Mr evaluation of brain parenchyma in patients with craniosynostosis.
  • Diagnostic and prognostic value of cardiovascular magnetic resonance imaging in dilated cardiomyopathy
  • Role of multiparametric magnetic resonance imaging in the detection of early carcinoma prostate
  • Role of magnetic resonance imaging in white matter diseases
  • Role of sonoelastography in assessing the response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.
  • Role of ultrasonography in the evaluation of carotid and femoral intima-media thickness in predialysis patients with chronic kidney disease
  • Role of H1 MRI spectroscopy in focal bone lesions of peripheral skeleton choline detection by MRI spectroscopy in breast cancer and its correlation with biomarkers and histological grade.
  • Ultrasound and MRI evaluation of axillary lymph node status in breast cancer.
  • Role of sonography and magnetic resonance imaging in evaluating chronic lateral epicondylitis.
  • Comparative of sonography including Doppler and sonoelastography in cervical lymphadenopathy.
  • Evaluation of Umbilical Coiling Index as Predictor of Pregnancy Outcome.
  • Computerized Tomographic Evaluation of Azygoesophageal Recess in Adults.
  • Lumbar Facet Arthropathy in Low Backache.
  • “Urethral Injuries After Pelvic Trauma: Evaluation with Uretrography
  • Role Of Ct In Diagnosis Of Inflammatory Renal Diseases
  • Role Of Ct Virtual Laryngoscopy In Evaluation Of Laryngeal Masses
  • “Ct Portography Using Mdct Versus Color Doppler In Detection Of Varices In
  • Cirrhotic Patients”
  • Role Of Multidetector Ct In Characterization Of Renal Masses
  • Role Of Ct Virtual Cystoscopy In Diagnosis Of Urinary Bladder Neoplasia
  • Role Of Multislice Ct In Diagnosis Of Small Intestine Tumors
  • “Mri Flow Quantification In The Assessment Of The Commonest CSF Flow Abnormalities”
  • “The Role Of Fetal Mri In Diagnosis Of Intrauterine Neurological CongenitalAnomalies”
  • Role Of Transcranial Ultrasound In Diagnosis Of Neonatal Brain Insults
  • “The Role Of Interventional Imaging Procedures In The Treatment Of Selected Gynecological Disorders”
  • Role Of Radiological Imaging In Diagnosis Of Endometrial Carcinoma
  • “Role Of High-Resolution Ct In Differentiation Between Benign And Malignant Pulmonary Nodules In Children”
  • Role Of Ultrasonography In The Diagnosis Of Knee Joint Lesions
  • “Role Of Diagnostic Imaging Modalities In Evaluation Of Post Liver Transplantation Recipient Complications”
  • “Diffusion-Weighted Magnetic Resonance Imaging In Diagnosis And
  • Characterization Of Brain Tumors In Correlation With Conventional Mri”
  • The Role Of PET-CT In The Evaluation Of Hepatic Tumors
  • “Role Of Computerized Tomography In Evaluation Of Mediastinal Masses In Pediatric patients”
  • “Trans Vaginal Ultrasound And Magnetic Resonance Imaging In Female Urinary Incontinence”
  • Role Of Multidetector Ct In Diagnosis Of Urinary Bladder Cancer
  • “Role Of Transvaginal Ultrasound In Diagnosis And Treatment Of Female Infertility”
  • Role Of Diffusion-Weighted Mri Imaging In Evaluation Of Cancer Prostate
  • “Role Of Positron Emission Tomography With Computed Tomography In Diagnosis Of Cancer Thyroid”
  • The Role Of CT Urography In Case Of Haematuria
  • “Value Of Ultrasonography In Assessment Of Acute Abdominal Diseases In Pediatric Age Group”
  • “Role Of Functional Magnetic Resonance Imaging In Making Brain Tumor Surgery Safer”
  • The Role Of Sonoelastography In Characterization Of Breast Lesions
  • “Ultrasonography, Magnetic Resonance Cholangiopancreatography (MRCP) In Assessment Of Pediatric Biliary Lesions”
  • “Role Of Ultrasound And Color Doppler Imaging In Assessment Of Acute Abdomen Due To Female Genital Causes”
  • “Role Of Multidetector Ct Virtual Laryngoscopy In Evaluation Of Laryngeal Mass Lesions”
  • MRI Of The Postoperative Knee
  • Role Of Mri In Assessment Of Valvular Heart Diseases
  • The Role Of 3D & 4D Ultrasonography In Abnormalities Of Fetal Abdomen
  • State Of The Art Of Mri In Diagnosis Of Hepatic Focal Lesions
  • Role Of Multidetector Ct In Diagnosis Of Salivary Gland Lesions
  • “Role Of Virtual Endoscopy Using Mdct In Detection & Evaluation Of Gastric Pathologies”
  • The Role Of Ultrasound & Mri In Acute Pelvic Inflammatory Disease
  • “Diagnosis & Staging Of Liver Fibrosis By Ultraso Und Elastography In
  • Patients With Chronic Liver Diseases”
  • Role Of Mri In Evaluation Of Spinal Trauma
  • Validity Of Mri In Diagnosis Of Congenital Anorectal Anomalies
  • Imaging Of Vascular Complication After Liver Transplantation
  • “Contrast-Enhanced Digital Mammography And Digital Breast Tomosynthesis In Early Diagnosis Of Breast Lesion”
  • Role Of Mammotome In Breast Lesions
  • “Role Of MRI Diffusion Tensor Imaging (DTI) In Assessment Of Traumatic Spinal Cord Injuries”
  • “Prediction Of Pre-eclampsia And Fetal Growth Restriction By Uterine Artery Doppler”
  • “Role Of Multidetector Row Computed Tomography In Assessment Of Maxillofacial Trauma”
  • “Role Of Diffusion Magnetic Resonance Imaging In Assessment Of Neoplastic And Inflammatory Brain Lesions”
  • Role Of Diffusion Mri In Preoperative Evaluation Of Brain Neoplasms
  • “Role Of Multidetector Ct Virtual Hysteroscopy In The Detection Of The
  • Uterine & Tubal Causes Of Female Infertility”
  • Role Of Advances Magnetic Resonance Imaging Sequences In Multiple Sclerosis Magnetic Resonance Spectroscopy In Multiple Sclerosis
  • “Role Of Conventional Mri, And Diffusion Tensor Imaging Tractography In Evaluation Of Congenital Brain Malformations”
  • Role Of MRI In Evaluation Of Spinal Trauma
  • Diagnostic Role Of Diffusion-weighted MR Imaging In Neck Masses
  • “The Role Of Transvaginal Ultrasound Versus Magnetic Resonance Imaging In Diagnosis & Evaluation Of Cancer Cervix”
  • “Role Of 3d Magnetic Resonance Imaging Tractography In Assessment Of White Matter Tracts Compromise In Supra Tentorial Tumors”
  • Role Of Proton MR Spectroscopy In The Evaluation Of Temporal Lobe Epilepsy
  • Role Of Multislice Computed Tomography In Evaluation Of Crohn’s Disease
  • Role Of MRI In Assessment Of Hydrocephalus In Pediatric Patients
  • The Role Of MRI In Diagnosis And Staging Of Urinary Bladder Carcinoma
  • USG and MRI correlation of congenital CNS anomalies
  • HRCT in interstitial lung disease
  • X-Ray, CT and MRI correlation of bone tumors
  • “Study on the diagnostic and prognostic utility of X-Rays for cases of pulmonary tuberculosis under RNTCP”
  • “Role of magnetic resonance imaging in the characterization of female adnexal  pathology”
  • “CT angiography of carotid atherosclerosis and NECT brain in cerebral ischemia, a correlative analysis”
  • Role of CT scan in the evaluation of paranasal sinus pathology
  • USG and MRI correlation on shoulder joint pathology
  • “Radiological evaluation of a patient presenting with extrapulmonary tuberculosis”
  • CT and MRI correlation in focal liver lesions”
  • Comparison of MDCT virtual cystoscopy with conventional cystoscopy in bladder tumors”
  • “Bleeding vessels in life-threatening hemoptysis: Comparison of 64 detector row CT angiography with conventional angiography prior to endovascular management”
  • “Role of transarterial chemoembolization in unresectable hepatocellular carcinoma”
  • “Comparison of color flow duplex study with digital subtraction angiography in the evaluation of peripheral vascular disease”
  • “A Study to assess the efficacy of magnetization transfer ratio in differentiating tuberculoma from neurocysticercosis”
  • “MR evaluation of uterine mass lesions in correlation with transabdominal, transvaginal ultrasound using HPE as a gold standard”
  • “The Role of power Doppler imaging with trans rectal ultrasonogram guided prostate biopsy in the detection of prostate cancer”
  • “Lower limb arteries assessed with doppler angiography – A prospective comparative study with multidetector CT angiography”
  • “Comparison of sildenafil with papaverine in penile doppler by assessing hemodynamic changes”
  • “Evaluation of efficacy of sonosalphingogram for assessing tubal patency in infertile patients with hysterosalpingogram as the gold standard”
  • Role of CT enteroclysis in the evaluation of small bowel diseases
  • “MRI colonography versus conventional colonoscopy in the detection of colonic polyposis”
  • “Magnetic Resonance Imaging of anteroposterior diameter of the midbrain – differentiation of progressive supranuclear palsy from Parkinson disease”
  • “MRI Evaluation of anterior cruciate ligament tears with arthroscopic correlation”
  • “The Clinicoradiological profile of cerebral venous sinus thrombosis with prognostic evaluation using MR sequences”
  • “Role of MRI in the evaluation of pelvic floor integrity in stress incontinent patients” “Doppler ultrasound evaluation of hepatic venous waveform in portal hypertension before and after propranolol”
  • “Role of transrectal sonography with colour doppler and MRI in evaluation of prostatic lesions with TRUS guided biopsy correlation”
  • “Ultrasonographic evaluation of painful shoulders and correlation of rotator cuff pathologies and clinical examination”
  • “Colour Doppler Evaluation of Common Adult Hepatic tumors More Than 2 Cm  with HPE and CECT Correlation”
  • “Clinical Relevance of MR Urethrography in Obliterative Posterior Urethral Stricture”
  • “Prediction of Adverse Perinatal Outcome in Growth Restricted Fetuses with Antenatal Doppler Study”
  • Radiological evaluation of spinal dysraphism using CT and MRI
  • “Evaluation of temporal bone in cholesteatoma patients by high resolution computed tomography”
  • “Radiological evaluation of primary brain tumours using computed tomography and magnetic resonance imaging”
  • “Three dimensional colour doppler sonographic assessment of changes in  volume and vascularity of fibroids – before and after uterine artery embolization”
  • “In phase opposed phase imaging of bone marrow differentiating neoplastic lesions”
  • “Role of dynamic MRI in replacing the isotope renogram in the functional evaluation of PUJ obstruction”
  • Characterization of adrenal masses with contrast-enhanced CT – washout study
  • A study on accuracy of magnetic resonance cholangiopancreatography
  • “Evaluation of median nerve in carpal tunnel syndrome by high-frequency ultrasound & color doppler in comparison with nerve conduction studies”
  • “Correlation of Agatston score in patients with obstructive and nonobstructive coronary artery disease following STEMI”
  • “Doppler ultrasound assessment of tumor vascularity in locally advanced breast cancer at diagnosis and following primary systemic chemotherapy.”
  • “Validation of two-dimensional perineal ultrasound and dynamic magnetic resonance imaging in pelvic floor dysfunction.”
  • “Role of MR urethrography compared to conventional urethrography in the surgical management of obliterative urethral stricture.”

Search Diagnostic Imaging Research Topics

You can also search research-related resources on our custom search engine .

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Free Resources for Preparing Radiology Thesis

  • Radiology thesis topics- Benha University – Free to download thesis
  • Radiology thesis topics – Faculty of Medical Science Delhi
  • Radiology thesis topics – IPGMER
  • Fetal Radiology thesis Protocols
  • Radiology thesis and dissertation topics
  • Radiographics

Proofreading Your Thesis:

Make sure you use Grammarly to correct your spelling ,  grammar , and plagiarism for your thesis. Grammarly has affordable paid subscriptions, windows/macOS apps, and FREE browser extensions. It is an excellent tool to avoid inadvertent spelling mistakes in your research projects. It has an extensive built-in vocabulary, but you should make an account and add your own medical glossary to it.

Grammarly spelling and grammar correction app for thesis

Guidelines for Writing a Radiology Thesis:

These are general guidelines and not about radiology specifically. You can share these with colleagues from other departments as well. Special thanks to Dr. Sanjay Yadav sir for these. This section is best seen on a desktop. Here are a couple of handy presentations to start writing a thesis:

Read the general guidelines for writing a thesis (the page will take some time to load- more than 70 pages!

A format for thesis protocol with a sample patient information sheet, sample patient consent form, sample application letter for thesis, and sample certificate.

Resources and References:

  • Guidelines for thesis writing.
  • Format for thesis protocol
  • Thesis protocol writing guidelines DNB
  • Informed consent form for Research studies from AIIMS 
  • Radiology Informed consent forms in local Indian languages.
  • Sample Informed Consent form for Research in Hindi
  • Guide to write a thesis by Dr. P R Sharma
  • Guidelines for thesis writing by Dr. Pulin Gupta.
  • Preparing MD/DNB thesis by A Indrayan
  • Another good thesis reference protocol

Hopefully, this post will make the tedious task of writing a Radiology thesis a little bit easier for you. Best of luck with writing your thesis and your residency too!

More guides for residents :

  • Guide for the MD/DMRD/DNB radiology exam!
  • Guide for First-Year Radiology Residents
  • FRCR Exam: THE Most Comprehensive Guide (2022)!
  • Radiology Practical Exams Questions compilation for MD/DNB/DMRD !
  • Radiology Exam Resources (Oral Recalls, Instruments, etc )!

Tips and Tricks for DNB/MD Radiology Practical Exam

Frcr 2b exam- tips and tricks .

  • FRCR exam preparation – An alternative take!
  • Why did I take up Radiology?
  • Radiology Conferences – A comprehensive guide!
  • ECR (European Congress Of Radiology)
  • European Diploma in Radiology (EDiR) – The Complete Guide!
  • Radiology NEET PG guide – How to select THE best college for post-graduation in Radiology (includes personal insights)!
  • Interventional Radiology – All Your Questions Answered!
  • What It Means To Be A Radiologist: A Guide For Medical Students!
  • Radiology Mentors for Medical Students (Post NEET-PG)
  • MD vs DNB Radiology: Which Path is Right for Your Career?
  • DNB Radiology OSCE – Tips and Tricks

More radiology resources here: Radiology resources This page will be updated regularly. Kindly leave your feedback in the comments or send us a message here . Also, you can comment below regarding your department’s thesis topics.

Note: All topics have been compiled from available online resources. If anyone has an issue with any radiology thesis topics displayed here, you can message us here , and we can delete them. These are only sample guidelines. Thesis guidelines differ from institution to institution.

Image source: Thesis complete! (2018). Flickr. Retrieved 12 August 2018, from by Victoria Catterson

About The Author

Dr. amar udare, md, related posts ↓.

FRCR 2b exam Tips and tricks

7 thoughts on “Radiology Thesis – More than 400 Research Topics (2022)!”

Amazing & The most helpful site for Radiology residents…

Thank you for your kind comments 🙂

Dr. I saw your Tips is very amazing and referable. But Dr. Can you help me with the thesis of Evaluation of Diagnostic accuracy of X-ray radiograph in knee joint lesion.

Wow! These are excellent stuff. You are indeed a teacher. God bless

Glad you liked these!

happy to see this

Glad I could help :).

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What is medical ultrasound?

How does it work, what is ultrasound used for, are there risks, what are examples of nibib-funded projects using ultrasound.

This is a picture of a fetal ultrasound

Medical ultrasound falls into two distinct categories: diagnostic and therapeutic.

Diagnostic ultrasound can be further sub-divided into anatomical and functional ultrasound. Anatomical ultrasound produces images of internal organs or other structures. Functional ultrasound combines information such as the movement and velocity of tissue or blood, softness or hardness of tissue, and other physical characteristics, with anatomical images to create “information maps.” These maps help doctors visualize changes/differences in function within a structure or organ.

Therapeutic ultrasound also uses sound waves above the range of human hearing but does not produce images. Its purpose is to interact with tissues in the body such that they are either modified or destroyed. Among the modifications possible are: moving or pushing tissue, heating tissue, dissolving blood clots, or delivering drugs to specific locations in the body. These destructive, or ablative, functions are made possible by use of very high-intensity beams that can destroy diseased or abnormal tissues such as tumors. The advantage of using ultrasound therapies is that, in most cases, they are non-invasive. No incisions or cuts need to be made to the skin, leaving no wounds or scars.

This is a picture of a technician giving a pregnant woman an ultrasound.  There is an image of the fetus on the computer monitor.

Ultrasound waves are produced by a transducer, which can both emit ultrasound waves, as well as detect the ultrasound echoes reflected back. In most cases, the active elements in ultrasound transducers are made of special ceramic crystal materials called piezoelectrics. These materials are able to produce sound waves when an electric field is applied to them, but can also work in reverse, producing an electric field when a sound wave hits them. When used in an ultrasound scanner, the transducer sends out a beam of sound waves into the body. The sound waves are reflected back to the transducer by boundaries between tissues in the path of the beam (e.g. the boundary between fluid and soft tissue or tissue and bone). When these echoes hit the transducer, they generate electrical signals that are sent to the ultrasound scanner. Using the speed of sound and the time of each echo’s return, the scanner calculates the distance from the transducer to the tissue boundary. These distances are then used to generate two-dimensional images of tissues and organs.

Image of an ultrasound transducer

During an ultrasound exam, the technician will apply a gel to the skin. This keeps air pockets from forming between the transducer and the skin, which can block ultrasound waves from passing into the body.

Click here to watch a short video about how ultrasound works.

Diagnostic ultrasound. Diagnostic ultrasound is able to non-invasively image internal organs within the body. However, it is not good for imaging bones or any tissues that contain air, like the lungs. Under some conditions, ultrasound can image bones (such as in a fetus or in small babies) or the lungs and lining around the lungs, when they are filled or partially filled with fluid. One of the most common uses of ultrasound is during pregnancy, to monitor the growth and development of the fetus, but there are many other uses, including imaging the heart, blood vessels, eyes, thyroid, brain, breast, abdominal organs, skin, and muscles. Ultrasound images are displayed in either 2D, 3D, or 4D (which is 3D in motion).

Illustration of a women getting an ultrasound of blood flow in her carotid arteries

Functional ultrasound. Functional ultrasound applications include Doppler and color Doppler ultrasound for measuring and visualizing blood flow in vessels within the body or in the heart. It can also measure the speed of the blood flow and direction of movement. This is done using color-coded maps called color Doppler imaging. Doppler ultrasound is commonly used to determine whether plaque build-up inside the carotid arteries is blocking blood flow to the brain.

Another functional form of ultrasound is elastography, a method for measuring and displaying the relative stiffness of tissues, which can be used to differentiate tumors from healthy tissue. This information can be displayed as either color-coded maps of the relative stiffness; black-and white maps that display high-contrast images of tumors compared with anatomical images; or color-coded maps that are overlayed on the anatomical image. Elastography can be used to test for liver fibrosis, a condition in which excessive scar tissue builds up in the liver due to inflammation.

Ultrasound is also an important method for imaging interventions in the body. For example, ultrasound-guided needle biopsy helps physicians see the position of a needle while it is being guided to a selected target, such as a mass or a tumor in the breast. Also, ultrasound is used for real-time imaging of the location of the tip of a catheter as it is inserted in a blood vessel and guided along the length of the vessel. It can also be used for minimally invasive surgery to guide the surgeon with real-time images of the inside of the body.

Therapeutic or interventional ultrasound. Therapeutic ultrasound produces high levels of acoustic output that can be focused on specific targets for the purpose of heating, ablating, or breaking up tissue. One type of therapeutic ultrasound uses high-intensity beams of sound that are highly targeted, and is called High Intensity Focused Ultrasound (HIFU). HIFU is being investigated as a method for modifying or destroying diseased or abnormal tissues inside the body (e.g. tumors) without having to open or tear the skin or cause damage to the surrounding tissue. Either ultrasound or MRI is used to identify and target the tissue to be treated, guide and control the treatment in real time, and confirm the effectiveness of the treatment. HIFU is currently FDA approved for the treatment of uterine fibroids, to alleviate pain from bone metastases, and most recently for the ablation of prostate tissue. HIFU is also being investigated as a way to close wounds and stop bleeding, to break up clots in blood vessels, and to temporarily open the blood brain barrier so that medications can pass through.

Diagnostic ultrasound is generally regarded as safe and does not produce ionizing radiation like that produced by x-rays. Still, ultrasound is capable of producing some biological effects in the body under specific settings and conditions. For this reason, the FDA requires that diagnostic ultrasound devices operate within acceptable limits. The FDA, as well as many professional societies, discourage the casual use of ultrasound (e.g. for keepsake videos) and recommend that it be used only when there is a true medical need.

The following are examples of current research projects funded by NIBIB that are developing new applications of ultrasound that are already in use or that will be in use in the future:

An illustration of a robotic arm connected to a focused ultrasound transducer that rests above a human chest. A microcatheter injects an ink into a region below the transducer.

3D printing through the skin : Researchers at Duke University have developed a method to 3D print biocompatible structures through thick, multi-layered tissues. The approach entails using focused ultrasound to solidify a special ink that has been injected into the body to repair bone or repair soft tissues, for example. Initial experiments in animal tissue suggest the method could turn highly invasive surgical procedures into safer, less invasive ones. (Image on left courtesy of Junjie Yao (Duke University) and Yu Shrike Zhang (Harvard Medical School and Brigham and Women’s Hospital)). 

A graphic shows a mouse before and after an ultrasound device fixed to its head is activated. The mouse is standing prior to activation and is laying down after.

Inducing a hibernation-like state : Researchers at Washington University in St. Louis used ultrasound waves directed into the brain to lower the body temperature and metabolic rates of mice, inducing a hibernation-like state, called torpor. The researchers replicated some of these results in rats, which, like humans, don’t naturally enter torpor. Inducing torpor could help minimize damage from stroke or heart attack and buy precious time for patients in critical care. (Image on right courtesy of  Yang et al./Washington University in St. Louis).

A view of the ultrasound probe and the interior of the circuit.

High-quality imaging at home : Brigham and Women’s Hospital researchers compared ultrasound scans acquired by experts with those taken by inexperienced volunteers, finding little difference in the image quality of the two groups. The unconventional approach of having patients take ultrasound images of themselves at home and share them with healthcare professionals could allow for remote monitoring and reduce the need for hospitalization. (Image on right courtesy of Duggan et al./Brigham and Women's Hospital). 

Reviewed December 2023

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The Ultrasound Journal Cover Image

Volume 5 Supplement 1

Topics in emergency abdominal ultrasonography

Edited by Luca Brunese and Antonio Pinto

Publication of this suppement has been funded by the University of Molise, Universiy of Siena, University of Cagliari, University of Ferrara and University of Turin. The Supplement Editors declare that they have no competing interests.

Sources of error in emergency ultrasonography

To evaluate the common sources of diagnostic errors in emergency ultrasonography.

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Accuracy of ultrasonography in the diagnosis of acute appendicitis in adult patients: review of the literature

Ultrasound is a widely used technique in the diagnosis of acute appendicitis; nevertheless, its utilization still remains controversial.

US detection of renal and ureteral calculi in patients with suspected renal colic

The purpose of this study was to determine whether the color Doppler twinkling sign could be considered as an additional diagnostic feature of small renal lithiasis (_5mm).

Gastrointestinal perforation: ultrasonographic diagnosis

Gastrointestinal tract perforations can occur for various causes such as peptic ulcer, inflammatory disease, blunt or penetrating trauma, iatrogenic factors, foreign body or a neoplasm that require an early re...

Sigmoid diverticulitis: US findings

Acute diverticulitis (AD) results from inflammation of a colonic diverticulum. It is the most common cause of acute left lower-quadrant pain in adults and represents a common reason for acute hospitalization, ...

The role of US examination in the management of acute abdomen

Acute abdomen is a medical emergency, in which there is sudden and severe pain in abdomen of recent onset with accompanying signs and symptoms that focus on an abdominal involvement. It can represent a wide sp...

Intestinal Ischemia: US-CT findings correlations

Intestinal ischemia is an abdominal emergency that accounts for approximately 2% of gastrointestinal illnesses. It represents a complex of diseases caused by impaired blood perfusion to the small and/or large ...

US in the assessment of acute scrotum

The acute scrotum is a medical emergency . The acute scrotum is defined as scrotal pain, swelling, and redness of acute onset. Scrotal abnormalities can be divided into three groups , which are extra-testicula...

Contrast enhanced ultrasound ( CEUS ) in blunt abdominal trauma

In the assessment of polytrauma patient, an accurate diagnostic study protocol with high sensitivity and specificity is necessary. Computed Tomography (CT) is the standard reference in the emergency for evalua...

Abdominal vascular emergencies: US and CT assessment

Acute vascular emergencies can arise from direct traumatic injury to the vessel or be spontaneous (non-traumatic).

Accuracy of ultrasonography in the diagnosis of acute calculous cholecystitis: review of the literature

To evaluate the accuracy of ultrasonography in the diagnosis of acute calculous cholecystitis in comparison with other imaging modalities.

Ultrasonography (US) in the assessment of pediatric non traumatic gastrointestinal emergencies

Non traumatic gastrointestinal emergencies in the children and neonatal patient is a dilemma for the radiologist in the emergencies room and they presenting characteristics ultrasound features on the longitudi...

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Mechanisms of action, thermal ablation, targeted drug delivery, blood brain barrier opening, neuromodulation, clinical applications, musculoskeletal, soft tissue oncologic, desmoid tumors, soft tissue sarcomas, hypothalamic hamartoma and other benign brain tumors, diffuse intrinsic pontine glioma, congenital vascular malformations, twin-twin transfusion syndrome, pulmonary hypertension, conclusions, focused ultrasound for pediatric diseases.

CONFLICT OF INTEREST DISCLOSURES: Dr Leblang is funded at 0.5 FTE by the Focused Ultrasound Foundation. Dr Ghanouni receives funding from Insightec for clinical trials and serves on advisory boards for Insightec and SonALAsense. Professor Hennekens reports that he is funded at 0.61 FTE by the Charles E. Schmidt College of Medicine at Florida Atlantic University, serves as an independent scientist in an advisory role to investigators and sponsors as Chair of data monitoring committees for Amgen, British Heart Foundation, Cadila, Canadian Institutes of Health Research, DalCor, and Regeneron; to the Collaborative Institutional Training Initiative (CITI), legal counsel for Pfizer, the United States Food and Drug Administration, and UpToDate; receives royalties for authorship or editorship of 3 textbooks and as co-inventor on patents for inflammatory markers and vascular disease that are held by Brigham and Women’s Hospital; has an investment management relationship with the West-Bacon Group within SunTrust Investment Services, which has discretionary investment authority; does not own any common or preferred stock in any pharmaceutical or medical device company. The other authors have indicated they have no financial relationships relevant to this article to disclose.

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Rohan Janwadkar , Suzanne Leblang , Pejman Ghanouni , Jacqueline Brenner , John Ragheb , Charles H. Hennekens , AeRang Kim , Karun Sharma; Focused Ultrasound for Pediatric Diseases. Pediatrics March 2022; 149 (3): e2021052714. 10.1542/peds.2021-052714

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Focused ultrasound (FUS) is a noninvasive therapeutic technology with multiple pediatric clinical applications. The ability of focused ultrasound to target tissues deep in the body without exposing children to the morbidities associated with conventional surgery, interventional procedures, or radiation offers significant advantages. In 2021, there are 10 clinical pediatric focused ultrasound studies evaluating various musculoskeletal, oncologic, neurologic, and vascular diseases of which 8 are actively recruiting and 2 are completed. Pediatric musculoskeletal applications of FUS include treatment of osteoid osteoma and bone metastases using thermal ablation and high-intensity FUS. Pediatric oncologic applications of FUS include treatment of soft tissue tumors including desmoid tumors, malignant sarcomas, and neuroblastoma with high-intensity FUS ablation alone, or in combination with targeted chemotherapy delivery. Pediatric neurologic applications include treatment of benign tumors such as hypothalamic hamartomas with thermal ablation and malignant diffuse intrinsic pontine glioma with low-intensity FUS for blood brain barrier opening and targeted drug delivery. Additionally, low-intensity FUS can be used to treat seizures. Pediatric vascular applications of FUS include treatment of arteriovenous malformations and twin-twin transfusion syndrome using ablation and vascular occlusion. FUS treatment appears safe and efficacious in pediatric populations across many subspecialties. Although there are 7 Food and Drug Administration–approved indications for adult applications of FUS, the first Food and Drug Administration approval for pediatric patients with osteoid osteoma was obtained in 2020. This review summarizes the preclinical and clinical research on focused ultrasound of potential benefit to pediatric populations.

The primary goal of this State of the Art Review is to educate readers about focused ultrasound and highlight some of the promising published and ongoing research of potential benefits to pediatric populations. Focused ultrasound (FUS) is a noninvasive therapeutic technology with multiple applications for the treatment of various pediatric diseases. FUS concentrates multiple intersecting beams of ultrasound energy on a precise target in the body. Imaging guidance precisely identifies anatomic targets and monitors efficacy and safety. Each individual beam passing through tissue has no effect, but multiple beams of ultrasound energy converging at a single focal point result in important biological effects. 1   FUS may be especially advantageous in the pediatric population because it targets tissues deep in the body without exposing children to the morbidities associated with conventional surgery or the risks of radiation.

The Food and Drug Administration (FDA) has approved numerous FUS treatments for adults for uterine fibroids, painful bone metastases, prostate enlargement and cancer, essential tremor, and tremor-dominant Parkinson’s disease. In November 2020, the FDA approved FUS (with Humanitarian Device Exemption) as a treatment of osteoid osteoma (OO) in the extremities, which typically impacts the pediatric population. 2   The feasibility, safety, and efficacy of FUS are being studied for over 131 clinical indications, and recent studies evaluating FUS for pediatric applications have increased from 3 in 2012 to 17 in 2019. 3   Table 1 highlights current clinical trials for pediatric-focused ultrasound applications.

Pediatric Focused Ultrasound Clinical Trials

HIFU, high intensity focused ultrasound; N/A, not applicable; NCT, National clinical trial identifier number.

A literature review was conducted through PubMed, Google Scholar, Medline, and Elsevier to identify English language studies using combinations of the following search terms: “pediatric,” “focused ultrasound,” “treatment,” and “high intensity focused ultrasound.” Primary articles within the last 20 years that included technical explanations of the focused ultrasound machines and published clinical studies if the patients/subjects were pediatric patients (age 0–21 years) with some adult patients (>21 years) exhibiting typical pediatric diseases were identified. Further analysis of these articles’ references identified preclinical papers within the last 30 years addressing disease processes and mechanisms of action. The various diseases were separated into the following major categories: musculoskeletal, oncologic, neurologic, and vascular applications.

FUS can produce mechanical or thermal energy to elicit a range of permanent or reversible bioeffects on treated tissue. Although over 60 different mechanisms of action are being investigated, 4 mechanisms are currently applied to pediatric diseases ( Fig 1 ). High-intensity focused ultrasound (HIFU) using a 650-kHz transducer can induce thermal ablation and mild hyperthermia for targeted drug delivery while low-intensity focused ultrasound (LIFU) using a 220-kHz transducer can be used for neuromodulation and blood brain barrier (BBB) opening. Various clinical FUS devices are listed in Table 1 with details regarding the type of imaging guidance, manufacturer, and number of transducer elements.

A, Thermal ablation. As the HIFU beam (yellow) focuses on a targeted anatomic lesion, the area is heated to a threshold temperature causing coagulative necrosis. The nontargeted healthy cells remain intact immediately adjacent to the ablated, necrotic cells with a narrow zone of transition. B, Targeted Drug Delivery. The focused ultrasound beam (yellow) enhances drug delivery by releasing medications from thermosensitive liposomes only within the tumor vessels, sparing surrounding and distant normal cells from potential drug toxicity. C, Blood Brain Barrier Opening. The focused ultrasound beam opens the BBB in a target location by oscillating the injected intravenous microbubbles that exert mechanical pressure on the endothelium and subsequently widen the tight junctions to allow molecules such as drugs, viral vectors, and antibodies to pass into the brain. D, Neuromodulation. With various parameters of the LIFU beam (yellow), neuronal signal may be suppressed (red axons) or stimulated (green axons).

A, Thermal ablation. As the HIFU beam (yellow) focuses on a targeted anatomic lesion, the area is heated to a threshold temperature causing coagulative necrosis. The nontargeted healthy cells remain intact immediately adjacent to the ablated, necrotic cells with a narrow zone of transition. B, Targeted Drug Delivery. The focused ultrasound beam (yellow) enhances drug delivery by releasing medications from thermosensitive liposomes only within the tumor vessels, sparing surrounding and distant normal cells from potential drug toxicity. C, Blood Brain Barrier Opening. The focused ultrasound beam opens the BBB in a target location by oscillating the injected intravenous microbubbles that exert mechanical pressure on the endothelium and subsequently widen the tight junctions to allow molecules such as drugs, viral vectors, and antibodies to pass into the brain. D, Neuromodulation. With various parameters of the LIFU beam (yellow), neuronal signal may be suppressed (red axons) or stimulated (green axons).

In general, thermal ablation via HIFU has been approved by numerous regulatory bodies worldwide to treat malignant and benign tumors of the breast, prostate, and liver, as well essential tremor, tremor-dominant Parkinson’s disease, and uterine fibroids. 3   Thermal ablation occurs as acoustic energy is absorbed, elevating temperature in a precise location and causing cell death by coagulative necrosis with minimal damage to surrounding tissue 4   ( Fig 1A ). Imaging guidance for HIFU ablation can be performed with either MRI or ultrasound (US). Magnetic resonance HIFU (MR-HIFU) allows for precise anatomic guidance and monitoring of tissue temperatures to ensure successful heating above a dose threshold. US-HIFU allows for improved temporal resolution along with the usual anatomic targeting, but does not allow for direct measurement of temperature. Instead, US-HIFU provides observable changes in tissue echogenicity that can monitor treatment in real time using a centrally located diagnostic transducer. 5   The volume of HIFU ablation lesions can be as small as a grain of rice (10 mm 3 ) and as large as 10 mm × 40 mm with a sharp border between treated and untreated areas. 4  

FUS can increase the local delivery and absorption of various therapeutics into tumors and thus improve efficacy due to a variety of mechanisms. These mechanisms include vasodilation, most plausibly through release of nitric oxide, increasing cell membrane permeability, or sonoporation, and hyperthermia. 6   FUS-mediated local hyperthermia can release encapsulated therapeutic agents ranging from genes to chemotherapies from a carrier vehicle such as a temperature-sensitive liposome, microbubble, or nanoparticle. Such agents are only released into the target by the FUS beam ( Fig 1B ), delivering them in high concentrations to a precise location while minimizing systemic side effects.

The blood brain barrier (BBB) is a layer of tightly joined cells lining cerebral blood vessels that selectively limits substances from entering neural tissue. However, this barrier also limits approximately 99% of potential therapeutic agents from entering the brain and only allows molecules <400 Da to pass. 7   LIFU allows for three main effects: (1) controlled, temporary, and reversible opening of BBB tight junctions via mechanical stretching from oscillating microbubbles, (2) Increases in transcytotic vesicles along the BBB, (3) decreases in efflux proteins reducing the amount of molecules pumped out of cerebral tissue 8 , 9   ( Fig 1C ). LIFU allows for diffusion of molecules as large as 185 kd. 10   LIFU has been shown to disrupt the BBB in a noninvasive, safe, and targeted manner for a therapeutic window up to 24 hours immediately after treatment. 11 , 12   To date, numerous clinical studies for adults are currently investigating BBB opening with LIFU to deliver a variety of neurotherapeutics for glioblastomas and metastatic disease to the brain. 13   Recently, the first clinical study for LIFU BBB opening in the pediatric population is now recruiting patients with diffuse intrinsic pontine glioma (DIPG).

Neuromodulation refers to the alteration of nerve activity by delivering changes directly to a targeted area. Neuromodulation is achieved using pulsed LIFU which is based on repeated bursts of energy of short duration. The mechanical effects of pulsed LIFU can either reversibly decrease the functionality of targeted neurons or trigger the activation and propagation of neural signals 14 , 15   ( Fig 1D ). The thermal effects of LIFU can also temporarily suppress neural signals in a targeted area by slightly raising the temperature without cell death. 16   These neuromodulatory effects can cause a range of therapeutic benefits such as suppressing epileptic seizures, modulating targets responsible for psychiatric disorders, and blocking nerves to treat pain.

Osteoid Osteoma

OO accounts for 11% of benign bone tumors and is most commonly found in the diaphysis of long bones in patients 10 to 30 years of age. 17   It characteristically causes severe nocturnal pain due to prostaglandin release, with symptoms typically alleviated by nonsteroidal anti-inflammatory drugs (NSAIDs). 18   However, this treatment only provides short-term relief and long-term use can lead to gastrointestinal and other side effects. 19   Current standard treatment uses computer tomography image–guided percutaneous radiofrequency ablation (CT-RFA), which is less invasive than surgical resection with a higher efficacy. 20   However, potential complications of CT-RFA include bleeding, infection, skin and muscle burns, and nerve injury. 21  

MR-HIFU ablation of OO has FDA and international approval in Europe, Russia, and China as a noninvasive alternative treatment option to precisely target OO lesions without damaging surrounding healthy tissue ( Fig 2 ). Napoli et al reported that the first use of MRI-HIFU to treat a cohort of 6 patients with painful OO revealed that it was technically feasible and safe with clinical improvement in pain at 6 months. 20   In 2017, the same authors reported in a prospective study that 42 out of 50 patients (mean age: 18, age range: 16–25) with OO demonstrated a 3-year clinical benefit with improvements in pain, sleep, and overall quality of life. 22   Arrigoni et al reported 32 of 33 pediatric patients with OO had complete pain relief after one MR-HIFU treatment session. All patients stopped NSAID use after the procedures. 23   In a prospectively enrolled safety and feasibility study, Sharma et al published that 8 of 9 patients treated with MR-HIFU and 9 of 9 patients treated with RFA (entire cohort mean age: 16, age range: 7–24) had total pain resolution and cessation of analgesics after 4 weeks and suggested MR-HIFU offers a noninvasive, precisely-controlled ablation of OO without the need for ionizing radiation. 24   In all of the FUS studies detailed above, there were no serious adverse events or skin burns. 20 , 22 , 24  

Osteoid osteoma. 17-year-old boy with left leg pain worse at night and temporarily relieved with Ibuprofen. No history of trauma. A, Diagnostic. Axial CT (left) and MRI (middle and right) images demonstrate the central nidus and periosteal reaction along the tibia (arrows). B, Focused ultrasound. MRI planning image (left) with beam path (yellow lines) focused on the nidus (green circle). Elevated temperature in nidus (yellow/orange) during sonication on MR thermometry image (center). Posttreatment postcontrast image (right) demonstrates nonperfusion (arrow) of the nidus.

Osteoid osteoma. 17-year-old boy with left leg pain worse at night and temporarily relieved with Ibuprofen. No history of trauma. A, Diagnostic. Axial CT (left) and MRI (middle and right) images demonstrate the central nidus and periosteal reaction along the tibia (arrows). B, Focused ultrasound. MRI planning image (left) with beam path (yellow lines) focused on the nidus (green circle). Elevated temperature in nidus (yellow/orange) during sonication on MR thermometry image (center). Posttreatment postcontrast image (right) demonstrates nonperfusion (arrow) of the nidus.

At present, there is an ongoing randomized Phase III trial at the University of California, San Francisco and Stanford University designed to compare the effectiveness of MR-HIFU with CT-RFA for OO (NCT02923011). A pivotal trial on safety and efficacy of MR-HIFU ablation of OOs in children is ongoing (NCT04658771). Courtesy of Karun Sharma, MD, PhD.

Bone Metastases

Skeletal metastases may occur in pediatric patients with cancer, including those with hematologic and solid tumor malignancies. 25   A study of 2652 children in Denmark reported the incidence of bone metastases as 1.9 per 1000 person-years during a mean follow-up of 7 years. 26   These metastases can cause severe pain, reduced quality of life, increased health care costs, and increased risk of death. The primary options for treatment of painful bone metastases include pain medication, radiation therapy, and surgery.

MR-HIFU has been proven to be effective for pain palliation in adult patients with bone metastases. A phase III randomized, placebo-controlled, multicenter trial of MR-HIFU performed with 147 patients (median age: 61.7, range: 19.1–83.6) found that 64% of patients reported pain reduction at 3 months, with 20% obtaining complete pain relief and two-thirds of patients achieving clinical response within 3 days. The most common complication was procedure-related pain, however 60% of all adverse-effects resolved on the same day. 27  

HIFU has worldwide approval to treat painful bone metastases. MR-HIFU is currently recommended as a second-line therapy after radiation failure and as a first-line therapy with any contraindication to radiation therapy. 27   Importantly, HIFU can be repeated as necessary as there is no radiation toxicity, although patients with bone metastases to the skull and vertebrae are currently excluded.

Due to the proven efficacy in adults, there is now a clinical trial in Toronto, Canada (NCT02616016), investigating MR-HIFU for pain palliation in patients 5 to 17 years of age with bone metastases.

Desmoid tumors are locally aggressive soft tissue tumors that can occur anywhere in the body. These tumors affect an estimated 1 to 2 per 500 000 people worldwide with almost 900 to 1500 new cases per year in the United States. 28   The median age at diagnosis is close to 30 years and the clinical course in children is similar to adults. 29   Desmoid tumors can infiltrate surrounding tissues and thus can be very difficult to resect, leading to a 50% recurrence rate after surgery. 30   Radiotherapy (RT) can be a therapeutic option for patients who cannot undergo or decline surgery. RT alone or combined with surgery in patients with incomplete resection can achieve long-term local control in approximately 70% to 80% of desmoids, regardless of the volume of the initial tumor. 31   However, Rutenberg et al reported that pediatric patients had lower rates of locoregional control than adults with control rates of 20% versus 63% in those less than 18 years and 18 to 30 years old respectively ( P = .08). 32   RT is therefore often avoided in the pediatric population due to reduced efficacy, impact on growth of normal structures, and risk of secondary malignancy. In patients without clinical symptoms, desmoid tumors can be observed and for those cases which are unresectable, medical therapy with systemic chemotherapy or molecularly targeted agents can be used. 33  

US-HIFU and MR-HIFU have been used to treat extra-abdominal desmoid tumors in pediatric patients with most reported cases in the lower extremities and buttocks. In 2011, five pediatric patients with an average initial tumor volume of 9.92 mL were treated with a maximum of two US-HIFU treatments, resulting in ablation of 86% (range: 78%–92%) of the tumor volume. 34   In 2017, seven pediatric patients with an average initial tumor vol of 240 mL (range: 4–772 mL) had an average decrease in tumor vol of 73% (range: 39%–100%) over a maximum of four MR-HIFU treatments. 35   An additional four pediatric patients with extra-abdominal desmoid tumors treated with MR-HIFU showed similar success rates with an initial average tumor volume of 321 mL (range: 98–770 mL) and mean tumor ablation of 66% (range: 15%–85%). 36 , 37   A teenager with a debilitating desmoid in the palm of his right hand in close proximity to the nerves was successfully treated with MR-HIFU 35   and remains symptom-free without recurrence at five years ( Fig 3 ).

Desmoid tumor. A 14-year-old boy with lump on palm of right hand unable to play lacrosse. A, Axial MRI 6 months before HIFU treatment (upper left) demonstrates enhancing desmoid (arrow). Immediate post treatment scan (middle) shows nonperfusion and ablation with some surrounding enhancement (arrow). Twelve months after treatment (lower right) confirms no tumor or residual enhancement. B, Picture of hand with mass before (left) and 12 months after (right) HIFU procedure with complete resolution. Courtesy of Pejman Ghanouni, MD, PhD.

Desmoid tumor. A 14-year-old boy with lump on palm of right hand unable to play lacrosse. A, Axial MRI 6 months before HIFU treatment (upper left) demonstrates enhancing desmoid (arrow). Immediate post treatment scan (middle) shows nonperfusion and ablation with some surrounding enhancement (arrow). Twelve months after treatment (lower right) confirms no tumor or residual enhancement. B, Picture of hand with mass before (left) and 12 months after (right) HIFU procedure with complete resolution. Courtesy of Pejman Ghanouni, MD, PhD.

The most common adverse effects of HIFU therapy were skin burns, most of which were reversible and treated with topical ointments, although a few patients had more severe burns or burns complicated by infection. 33   Skin burns are a complication of HIFU but not LIFU and most commonly with desmoids and fibroids compared with OO. In a case series of 15 patients with desmoids aged 7 to 66 years, 7 of whom were under 18, Ghanouni et al 35   reported that 8 of 15 had a skin burn. Of the 6 with a second-degree burn, the average distance between the tumor and skin was 4 mm. Of the two with a first-degree burn, both occurred along a surgical scar. Some patients also suffered from nerve injury after HIFU therapy due to the desmoid tumor abutting or encasing the nerve. 33   However, an active skin cooling device has been introduced to reduce the risk of skin burns, which may mitigate some of these events. 38   Overall, the rate of these adverse effects should also decrease with increased physician experience and improved software targeting.

There is currently an ongoing safety and feasibility clinical study at Children’s National Hospital in Washington, DC, and Cincinnati Children’s Hospital investigating the use of MR-HIFU in thermal ablation of relapsed and refractory pediatric solid tumors including desmoid tumors (NCT02076906).

Osteosarcoma, Ewing sarcoma, and soft tissue sarcomas account for nearly 14% of all pediatric malignancies. 39   Children with metastatic or recurrent sarcoma have a poor prognosis with a five-year overall survival rate of 20% to 25%. 39   Neuroblastoma is the most common extracranial pediatric tumor, and is responsible for greater than 10% of childhood cancer-related mortality. 40   Current standard therapy for most sarcomas and high-risk neuroblastomas is systemic chemotherapy combined with surgery and/or radiation.

A preclinical study in mice models with subcutaneous neuroblastoma shows benefit of HIFU thermal ablation alone and in combination with Adriamycin. 41   In addition, HIFU histotripsy combined with checkpoint blockade immunotherapy (αCTLA-4 and αPD-L1) shows impressive survival benefit in a murine neuroblastoma model. 42   The advantage of HIFU and immunotherapy combined is synergistic in enhancing the antitumor response and triggering an abscopal effect in which the local therapy can upregulate immunomodulators that target cancer cells distant to the primary malignancy. This upregulation of immunomodulators is thought to confer long-term immunity and slow subsequent de novo tumorigenesis. 43  

In a study investigating the anatomic feasibility of MR-HIFU therapy in 121 pediatric patients with sarcoma and 61 patients with neuroblastoma, 64% of primary sarcomas and 25% of primary neuroblastomas were targetable with MR-HIFU. However, less than 20% of sarcoma and neuroblastoma metastases were targetable with most targetable lesions located in the extremities or pelvis. 39   In the future, respiratory motion compensation may increase the percentage of targetable tumors. 39   In a study with MR-HIFU and abdominal neuroblastomas, the majority of patients had potentially targetable lesions with a mean targetable volume ranging from 15% to 79%. 44   The potential benefits of FUS therapy for these pediatric tumors include increased efficacy and fewer complications compared with invasive surgeries and RT. Currently, there are Phase 1 clinical studies investigating the safety and feasibility of using MR-HIFU for refractory and relapsed solid tumors with targeted drug delivery (NCT02536183) and thermal ablation (NCT02076906) as demonstrated in Table 1 .

An estimated 3 million adults and 470 000 children in the United States have active epilepsy. 45   Current treatments include medication, surgery, radiofrequency or laser ablation, deep brain stimulation (DBS), and stereotactic radiosurgery, all of which have limitations and side effects. FUS therapy has shown success in both preclinical studies and clinical case reports at reducing seizure frequency in adult patients with active epilepsy.

There are several mechanisms by which FUS can treat epilepsy: thermal ablation, neuromodulation, and BBB opening and targeted drug delivery. In 2016, Monteith et al reported that HIFU thermal ablation of mesial temporal lobe epileptic foci is feasible in laboratory models. 46   In 2020, Chen et al found that pulsed LIFU effectively suppressed epileptic activity in animal models and Lin et al reported that pulsed LIFU suppressed epileptiform activities in human pathologic slices by increasing the neural excitability of local inhibitory neurons. 47 , 48   In preclinical studies, MR-LIFU opened the BBB allowing for the delivery of drugs to targeted epileptic foci, leading to an overall decrease in seizure frequency. 49   Airan et al reported a novel method for using FUS to deliver drugs across the blood brain barrier, 50   which successfully released propofol from nanoparticles silencing drug-induced seizures in rats. 51  

With respect to clinical applications, Parker et al conducted a modeling and feasibility study of MR-HIFU for ablation of mesial temporal circuits in 10 adult patients with essential tremor and 2 patients with mesial temporal sclerosis. 52   The theoretical modeling concluded that MR-HIFU offers a noninvasive option for seizure tract disruption that could result in immediate seizure relief in certain candidates. A recent case report published by Abe et al demonstrated the success of MR-HIFU in treatment of mesial temporal lobe epilepsy in a 36-year-old woman. After a short temporary interval of increased frequency of seizures 1 month post-MR-HIFU treatment, she remained seizure-free with the ability to slowly wean her seizure medication without relapse. Although thermal ablation was the intended mechanism of action for this patient, suboptimal temperatures were achieved during FUS treatment, leading the authors to conclude that neuromodulation was the probable mechanism of action. 53   As part of an ongoing study at Brigham and Women’s Hospital, entitled, “Low Intensity Focused Ultrasound Treatment for Drug Resistant Epilepsy: An Efficacy Trial” (NCT 03868293), a 26-year-old woman with drug-resistant epilepsy and mesial temporal lobe sclerosis with a baseline of 1 to 2 seizures per month was treated with LIFU neuromodulation and remained seizure-free for 6 consecutive weeks after 8 sonication sessions over 4 weeks. 54 , 55  

Currently, there are no clinical studies involving the pediatric population, but there are 6 clinical trials worldwide studying FUS therapy for epilepsy in adults applying thermal ablation and neuromodulation.

Hypothalamic hamartomas (HHs) are rare, benign tumors that emerge during fetal development. HH is estimated to occur in 1 in every 50 000 to 100 000 patients worldwide. 56   There are 2 major clinical phenotypes of HH: (1) central precocious puberty and (2) epilepsy and neurobehavioral symptoms. Historically, treatment has been related to the clinical presentation with medical management to suppress pubertal development and stereotactic targeted radiation therapy, radiofrequency lesioning, or surgery for epilepsy. 57   In 11 patients treated with surgical resection, 3 patients became seizure-free, 8 had over 90% reduction in seizures, and all patients experienced significant improvement in behavior and cognition. 58  

HIFU therapy is a noninvasive alternative to surgical resection or disconnection of the HH and can potentially be used to treat other centrally located benign brain tumors in the pediatric population. Using MRI guidance, the FUS beams can ablate the hamartoma or ablate the connection between the hamartoma and hypothalamus to “disconnect” it from the surrounding brain circuitry ( Fig 4 ). The Focused Ultrasound Foundation newsletter highlighted 2 cases in which pediatric patients with symptomatic HH were treated. The first patient suffering from debilitating seizures initially responded to surgical resection but reoccurred after several years. After a single FUS procedure, MRI scans showed complete ablation of the residual hamartoma and the patient was discharged the following day and “remains seizure-free 59   .” The second patient was a 15-year-old girl with hyperphagia gaining an average of 18 pounds every 6 months, but immediately after FUS treatment, her hyperphagia symptoms disappeared. She has experienced no side effects and has lost 28 pounds since the procedure. 60  

Hypothalamic hamartoma. Twenty-one-year-old woman with gelastic seizures and hypothalamic obesity. After HIFU, she became seizure-free and her weight stabilized. A, Coronal T2 image demonstrates remnant of previously resected hamartoma (yellow arrow) along left side of third ventricle. B, Post-HIFU treatment coronal T2 image with new hyperintensity at targeted location (yellow arrow). Courtesy of John Ragheb, MD.

Hypothalamic hamartoma. Twenty-one-year-old woman with gelastic seizures and hypothalamic obesity. After HIFU, she became seizure-free and her weight stabilized. A, Coronal T2 image demonstrates remnant of previously resected hamartoma (yellow arrow) along left side of third ventricle. B, Post-HIFU treatment coronal T2 image with new hyperintensity at targeted location (yellow arrow). Courtesy of John Ragheb, MD.

Currently a phase I clinical trial at Nicklaus Children’s Hospital in Miami, Florida, is investigating the use of the Insightec Exablate Neuro system in treating benign intracranial tumors, including HH, in pediatric and young adult subjects (NCT03028246).

DIPG is an extremely aggressive brain tumor arising from the brain stem and affecting nearly 200 to 400 children in the United States every year. 61   DIPG is uniformly fatal and is the leading cause of childhood brain tumor death. Median survival is nine months with 90% of children dying from the disease within 2 years of initial diagnosis. 62  

A preclinical study by Sewing et al stated that high-grade glioma and DIPG cells were sensitive to anthracyclines, specifically doxorubicin, while sparing normal human astrocytes. Convection-enhanced delivery allowed for adequate concentrations of doxorubicin at the tumor site. 63   Alli et al published that brain stem MR-LIFU BBB opening was feasible and effective allowing for increased and focal doxorubicin delivery in mice. 64  

As there is now ample data from adult clinical trials demonstrating safety and feasibility of BBB opening in patients with brain tumors, a pediatric clinical trial using FUS to improve the delivery of oral Panobinostat in DIPG tumors has started recruitment at Columbia University (NCT04804709).

Congenital vascular malformations (CVM) have a prevalence of 4.5% and can be divided into high-flow (arteriovenous malformations and fistulas) and low-flow (venous and lymphatic malformations) lesions. Venous malformations (VM) are the most common subtype of CVM with an incidence of 1 to 2 in 10 000 and a prevalence of 1%, most frequently seen in the head and neck (40%), extremities (40%), and trunk (20%). 65   Though VMs are present at birth, they are not always clinically evident until later in life and can cause local and systemic complications leading to significant morbidity, pain, and discomfort. 66  

The current first-line treatment of VMs is sclerotherapy, which requires a safe route of access and ability to visualize the vascular malformation continuously throughout the procedure. 67   However, if the lesion is unable to be visualized or if access is unfeasible, other treatment modalities such as surgical resection or ablation are considered.

In 2015, van Breugel et al 68   published a case report of an 18-year-old boy with a VM in the lower extremity treated with MR-HIFU with qualitatively sustained pain reduction for 13 months posttreatment. In 2017, Ghanouni et al reported statistically significant improvement in pain and reduction in lesion size without any complications in five patients (median age: 36 years, range: 18–54 years) with painful VM of the extremities treated with MR-HIFU 67   ( Fig 5 ).

Vascular malformation. An 18-year-old boy with pain in lateral right thigh. A, Axial MRI with enhancing vascular malformation before surgery (red arrow). B, Axial MRI 3 months postsurgical excision with recurrence (red arrow). C, Immediate post-HIFU MRI with nonperfusion and ablation of the nidus on postcontrast MRI (red arrow). D, Three-month post-HIFU axial MRI with no residual malformation or pain. Courtesy of Pejman Ghanouni, MD, PhD.

Vascular malformation. An 18-year-old boy with pain in lateral right thigh. A, Axial MRI with enhancing vascular malformation before surgery (red arrow). B, Axial MRI 3 months postsurgical excision with recurrence (red arrow). C, Immediate post-HIFU MRI with nonperfusion and ablation of the nidus on postcontrast MRI (red arrow). D, Three-month post-HIFU axial MRI with no residual malformation or pain. Courtesy of Pejman Ghanouni, MD, PhD.

Twin-twin transfusion syndrome (TTTS) is a severe complication occurring in 15% of monochorionic-diamniotic twin pregnancies caused by abnormal placental anastomoses that create unbalanced blood flow among twins in utero. 69   TTTS, if left untreated, is 80% to 100% fatal for fetuses, and is the leading cause of death and disability in twins. 69   Fetoscopic laser photocoagulation of placental anastomoses is considered the current standard of treatment, despite meta-analysis data showing no significant survival or neurologic benefit. Laser-treated TTTS is still associated with a perinatal mortality rate of 30% to 50% and a 5% to 20% chance of long-term neurologic deficit. 69  

HIFU therapy has the potential to be effective in treatment of TTTS via vascular occlusion, based on preclinical results reporting the consistent occlusion of placental vessels and cessation of blood flow in a pregnant sheep model. 70   The vascular and metabolic fetal responses and short-term safety suggest potential translation to human pregnancies. Okai et al described the successful use of HIFU to noninvasively occlude blood flow for twin reversed arterial perfusion in a human fetus, which offers potential for HIFU treatment of conditions resulting from abnormal placental vasculature. 71   Compared with more conventional invasive therapies for maternofetal vascular complications, HIFU may provide a noninvasive alternative to occlude vascular anomalies while minimizing injury to the mother, the fetus, and the uterus.

Currently, the Imperial College London is planning a first in-human phase 1a study of noninvasive HIFU vascular ablation in the treatment of TTTS (Integrated Research Application System Project ID: 260359).

There are two published preclinical studies exploring the potential benefit of using FUS to treat pulmonary hypertension by creating atrial septal defects in large animal models, one in dogs 72   and the other in pigs. 73  

This review highlights a wide range of current and potential pediatric applications amenable to treatment with FUS. This unique and noninvasive therapy can treat pediatric musculoskeletal conditions including OO and bone metastases using ablation. Soft tissue tumors including desmoids, sarcomas and neuroblastomas can be treated with HIFU ablation alone, or in combination with targeted chemotherapy delivery. Neurologic applications with FUS include treatment of benign and malignant brain tumors with thermal ablation and BBB opening with targeted drug delivery respectively as well as ablation and neuromodulation for epilepsy. Pediatric vascular applications of FUS include treatment of both CVM and TTTS using ablation with vascular occlusion. With increasing FUS experience in the adult population, other pediatric applications will likely follow and improve the care of children with a variety of diseases.

Dr LeBlang and Mr Janwadkar were responsible for conceptualization, data curation, formal analysis, methodology, and drafted the initial manuscript and reviewed and revised the manuscript; Drs Ghanouni, Ragheb, Kim, Sharma, and Hennekens contributed to supervision, writing review and drafting, validation, and providing resources; Ms Brenner contributed resources, writing review, drafting, and illustrations for figures; all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

blood brain barrier

computer tomography image–guided percutaneous radiofrequency ablation

congenital vascular malformations

diffuse intrinsic pontine glioma

focused ultrasound

hypothalamic hamartoma

high-intensity focused ultrasound

low-intensity focused ultrasound

magnetic resonance–guided high-intensity focused ultrasound

nonsteroidal anti-inflammatory drug

osteoid osteoma


twin-twin transfusion syndrome

ultrasound-guided high-intensity focused ultrasound

venous malformation

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Illustration of human lungs affected by coronavirus

Credit: Ilya Lukichev / Getty Images

AI can now detect COVID-19 in lung ultrasound images

An automated detection tool developed by johns hopkins researchers could help er doctors diagnose patients quickly and accurately.

By Roberto Molar Candanosa

Artificial intelligence can spot COVID-19 in lung ultrasound images much like facial recognition software can spot a face in a crowd, new research shows.

The findings boost AI-driven medical diagnostics and bring health care professionals closer to being able to quickly diagnose patients with COVID-19 and other pulmonary diseases with algorithms that comb through ultrasound images to identify signs of disease.

The findings, newly published in Communications Medicine , culminate an effort that started early in the pandemic when clinicians needed tools to rapidly assess legions of patients in overwhelmed emergency rooms.

"We developed this automated detection tool to help doctors in emergency settings with high caseloads of patients who need to be diagnosed quickly and accurately, such as in the earlier stages of the pandemic," said senior author Muyinatu Bell , an associate professor in the Department of Electrical and Computer Engineering in the Whiting School of Engineering at Johns Hopkins University. "Potentially, we want to have wireless devices that patients can use at home to monitor progression of COVID-19, too."

The tool also holds potential for developing wearables that track such illnesses as congestive heart failure, which can lead to fluid overload in patients' lungs, not unlike COVID-19, said co-author Tiffany Fong , an assistant professor of emergency medicine at Johns Hopkins Medicine.

"What we are doing here with AI tools is the next big frontier for point of care," Fong said. "An ideal use case would be wearable ultrasound patches that monitor fluid buildup and let patients know when they need a medication adjustment or when they need to see a doctor."

The AI analyzes ultrasound lung images to spot features known as B-lines, which appear as bright, vertical abnormalities and indicate inflammation in patients with pulmonary complications. It combines computer-generated images with real ultrasounds of patients — including some who sought care at Johns Hopkins.

"We had to model the physics of ultrasound and acoustic wave propagation well enough in order to get believable simulated images," Bell said. "Then we had to take it a step further to train our computer models to use these simulated data to reliably interpret real scans from patients with affected lungs."

Early in the pandemic, scientists struggled to use artificial intelligence to assess COVID-19 indicators in lung ultrasound images because of a lack of patient data and because they were only beginning to understand how the disease manifests in the body, Bell said.

Her team developed software that can learn from a mix of real and simulated data and then discern abnormalities in ultrasound scans that indicate a person has contracted COVID-19. The tool is a deep neural network, a type of AI designed to behave like the interconnected neurons that enable the brain to recognize patterns, understand speech, and achieve other complex tasks.

"Early in the pandemic, we didn't have enough ultrasound images of COVID-19 patients to develop and test our algorithms, and as a result our deep neural networks never reached peak performance," said first author Lingyi Zhao, who developed the software while a postdoctoral fellow in Bell's lab and is now working at Novateur Research Solutions. "Now, we are proving that with computer-generated datasets we still can achieve a high degree of accuracy in evaluating and detecting these COVID-19 features."

This work was supported by NIH Trailblazer Award Supplement R21EB025621-03S1.

The team's code and data are publicly available here .

Posted in Science+Technology

Tagged artificial intelligence , covid-19

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March 20, 2024

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AI can now detect COVID-19 in lung ultrasound images

by Roberto Molar Candanosa, Johns Hopkins University

AI can now detect COVID-19 in lung ultrasound images

Artificial intelligence can spot COVID-19 in lung ultrasound images, much like facial recognition software can spot a face in a crowd, new research shows.

The findings boost AI-driven medical diagnostics and bring health care professionals closer to being able to quickly diagnose patients with COVID-19 and other pulmonary diseases with algorithms that comb through ultrasound images to identify signs of disease.

The findings, newly published in Communications Medicine , culminate an effort that started early in the pandemic when clinicians needed tools to rapidly assess legions of patients in overwhelmed emergency rooms.

"We developed this automated detection tool to help doctors in emergency settings with high caseloads of patients who need to be diagnosed quickly and accurately, such as in the earlier stages of the pandemic," said senior author Muyinatu Bell, the John C. Malone Associate Professor of Electrical and Computer Engineering, Biomedical Engineering, and Computer Science at Johns Hopkins University. "Potentially, we want to have wireless devices that patients can use at home to monitor progression of COVID-19, too."

The tool also holds potential for developing wearables that track such illnesses as congestive heart failure , which can lead to fluid overload in patients' lungs, not unlike COVID-19, said co-author Tiffany Fong, an assistant professor of emergency medicine at Johns Hopkins Medicine.

"What we are doing here with AI tools is the next big frontier for point of care," Fong said. "An ideal use case would be wearable ultrasound patches that monitor fluid buildup and let patients know when they need a medication adjustment or when they need to see a doctor."

The AI analyzes ultrasound lung images to spot features known as B-lines, which appear as bright, vertical abnormalities and indicate inflammation in patients with pulmonary complications. It combines computer-generated images with real ultrasounds of patients—including some who sought care at Johns Hopkins.

"We had to model the physics of ultrasound and acoustic wave propagation well enough in order to get believable simulated images," Bell said. "Then we had to take it a step further to train our computer models to use these simulated data to reliably interpret real scans from patients with affected lungs."

Early in the pandemic, scientists struggled to use artificial intelligence to assess COVID-19 indicators in lung ultrasound images because of a lack of patient data and because they were only beginning to understand how the disease manifests in the body, Bell said.

Her team developed software that can learn from a mix of real and simulated data and then discern abnormalities in ultrasound scans that indicate a person has contracted COVID-19. The tool is a deep neural network, a type of AI designed to behave like the interconnected neurons that enable the brain to recognize patterns, understand speech, and achieve other complex tasks.

"Early in the pandemic, we didn't have enough ultrasound images of COVID-19 patients to develop and test our algorithms, and as a result our deep neural networks never reached peak performance," said first author Lingyi Zhao, who developed the software while a postdoctoral fellow in Bell's lab and is now working at Novateur Research Solutions. "Now, we are proving that with computer-generated datasets we still can achieve a high degree of accuracy in evaluating and detecting these COVID-19 features."

The team's code and data are publicly available here .

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Photo illustration of a gloved hand holding a tiny ultrasound machine

A startling change in medical ultrasound is working its way through hospitals and physicians’ offices. The long-standing, state-of-the-art ultrasound machine that’s pushed around on a cart, with cables and multiple probes dangling, is being wheeled aside permanently in favor of handheld probes that send images to a phone.

These devices are small enough to fit in a lab coat pocket and flexible enough to image any part of the body, from deep organs to shallow veins, with sweeping 3D views, all with a single probe. And the AI that accompanies them may soon make these devices operable by untrained professionals in any setting—not just trained sonographers in clinics.

The first such miniaturized, handheld ultrasound probe arrived on the market in 2018, from Butterfly Network in Burlington, Mass. Last September, Exo Imaging in Santa Clara, Calif., launched a competing version.

Making this possible is silicon ultrasound technology, built using a type of microelectromechanical system (MEMS) that crams 4,000 to 9,000 transducers—the devices that convert electrical signals into sound waves and back again—onto a 2-by-3-centimeter silicon chip. By integrating MEMS transducer technology with sophisticated electronics on a single chip, these scanners not only replicate the quality of traditional imaging and 3D measurements but also open up new applications that were impossible before.

How does ultrasound work?

To understand how researchers achieved this feat, it’s helpful to know the basics of ultrasound technology. Ultrasound probes use transducers to convert electrical energy to sound waves that penetrate the body. The sound waves bounce off the body’s soft tissue and echo back to the probe. The transducer then converts the echoed sound waves to electrical signals, and a computer translates the data into an image that can be viewed on a screen.

Conventional ultrasound probes contain transducer arrays made from slabs of piezoelectric crystals or ceramics such as lead zirconium titanate (PZT). When hit with pulses of electricity, these slabs expand and contract and generate high-frequency ultrasound waves that bounce around within them.

To be useful for imaging, the ultrasound waves need to travel out of the slabs and into the soft tissue and fluid of the patient’s body. This is not a trivial task. Capturing the echo of those waves is like standing next to a swimming pool and trying to hear someone speaking under the water. The transducer arrays are thus built from layers of material that smoothly transition in stiffness from the hard piezoelectric crystal at the center of the probe to the soft tissue of the body.

The frequency of energy transferred into the body is determined mainly by the thickness of the piezoelectric layer. A thinner layer transfers higher frequencies, which allow smaller, higher-resolution features to be seen in an ultrasound image, but only at shallow depths. The lower frequencies of thicker piezoelectric material travel further into the body but deliver lower resolutions.

As a result, several types of ultrasound probes are needed to image various parts of the body, with frequencies that range from 1 to 10 megahertz. To image large organs deep in the body or a baby in the womb, physicians use a 1- to 2-MHz probe, which can provide 2- to 3-millimeter resolution and can reach up to 30 cm into the body. To image blood flow in arteries in the neck, physicians typically use an 8- to 10-MHz probe.

How MEMS transformed ultrasound

The need for multiple probes along with the lack of miniaturization meant that conventional medical ultrasound systems resided in a heavy, boxy machine lugged around on a cart. The introduction of MEMS technology changed that.

Over the last three decades MEMS has allowed manufacturers in an array of industries to create precise, extremely sensitive components at a microscopic scale. This advance has enabled the fabrication of high-density transducer arrays that can produce frequencies in the full 1- to 10-MHz range, allowing imaging of a wide range of depths in the body, all with one probe. MEMS technology also helped miniaturize additional components so that everything fits in the handheld probe. When coupled with the computing power of a smartphone, this eliminated the need for a bulky cart.

The first MEMS-based silicon ultrasound prototypes emerged in the mid-1990s when the excitement of MEMS as a new technology was peaking. The key element of these early transducers was the vibrating micromachined membrane, which allowed the devices to generate vibrations in much the same way that banging on a drum creates sound waves in the air.

Two architectures emerged. One of them, called the capacitive micromachined ultrasonic transducer , or CMUT, is named for its simple capacitor-like structures. Stanford University electrical engineer Pierre Khuri-Yakub and colleagues demonstrated the first versions .

The CMUT is based on electrostatic forces in a capacitor formed by two conductive plates separated by a small gap. One plate—the micromachined membrane mentioned before—is made of silicon or silicon nitride with a metal electrode. The other—typically a micromachined silicon wafer substrate—is thicker and more rigid. When a voltage is applied, placing opposite charges on the membrane and substrate, attractive forces pull and flex the membrane toward the substrate. When an oscillating voltage is added, that changes the force, causing the membrane to vibrate, like a struck drumhead.

When the membrane is in contact with the human body, the vibrations send ultrasound frequency waves into the tissue. How much ultrasound is generated or detected depends on the gap between the membrane and the substrate, which needs to be about one micrometer or less. Micromachining techniques made that kind of precision possible.

The other MEMS-based architecture is called the piezoelectric micromachined ultrasonic transducer , or PMUT, and it works like a miniaturized version of a smoke alarm buzzer. These buzzers consist of two layers: a thin metal disk fixed around its periphery and a thin, smaller piezoelectric disk bonded on top of the metal disk. When voltages are applied to the piezoelectric material, it expands and contracts in thickness and from side to side. Because the lateral dimension is much larger, the piezo disk diameter changes more significantly and in the process bends the whole structure. In smoke alarms, these structures are typically 4 cm in diameter, and they’re what generates the shrieking sound of the alarm, at around 3 kilohertz. When the membrane is scaled down to 100 μm in diameter and 5 to 10 μm in thickness, the vibration moves up into megahertz frequencies, making it useful for medical ultrasound.

Honeywell in the early 1980s developed the first micromachined sensors using piezoelectric thin films built on silicon diaphragms. The first PMUTs operating at ultrasound frequencies didn’t emerge until 1996 , from the work of materials scientist Paul Muralt at the Swiss Federal Institute of Technology Lausanne (EPFL), in Switzerland.

Early years of CMUT

A big challenge with CMUTs was getting them to generate enough pressure to send sound waves deep into the body and receive the echoes coming back. The membrane’s motion was limited by the exceedingly small gap between the membrane and the substrate. This constrained the amplitude of the sound waves that could be generated. Combining arrays of CMUT devices with different dimensions into a single probe to increase the frequency range also compromised the pressure output because it reduced the probe area available for each frequency.

The solution to these problems came from Khuri-Yakub’s lab at Stanford University. In experiments in the early 2000s , the researchers found that increasing the voltage on CMUT-like structures caused the electrostatic forces to overcome the restoring forces of the membrane. As a result, the center of the membrane collapses onto the substrate.

A collapsed membrane seemed disastrous at first but turned out to be a way of making CMUTs both more efficient and more tunable to different frequencies. The efficiency increased because the gap around the contact region was very small, increasing the electric field there. And the pressure increased because the large doughnut-shaped region around the edge still had a good range of motion. What’s more, the frequency of the device could be adjusted simply by changing the voltage. This, in turn, allowed a single CMUT ultrasound probe to produce the entire ultrasound frequency range needed for medical diagnostics with high efficiency.

From there, it took more than a decade to understand and model the complicated electromechanical behavior of CMUT arrays and iron out the manufacturing. Modeling these devices was tricky because thousands of individual membranes interacted in each CMUT array.

On the manufacturing side, the challenges involved finding the right materials and developing the processes needed to produce smooth surfaces and a consistent gap thickness. For example, the thin dielectric layer that separates the conductive membrane and the substrate must withstand about 100 volts at a thickness of 1 μm. If the layer has defects, charges can be injected into it, and the device can short at the edges or when the membrane touches the substrate, killing the device or at least degrading its performance.

Eventually, though, MEMS foundries such as Philips Engineering Solutions in Eindhoven, Netherlands, and Taiwan Semiconductor Manufacturing Co. (TSMC), in Hsinchu, developed solutions to these problems. Around 2010, these companies began producing reliable, high-performance CMUTs.

Early development of PMUTs

Early PMUT designs also had trouble generating enough pressure to work for medical ultrasound. But they could bang out enough to be useful in some consumer applications, such as gesture detection and proximity sensors . In such “in-air ultrasound” uses, bandwidth isn’t critical, and frequencies can be below 1 MHz.

In 2015, PMUTs for medical applications got an unexpected boost with the introduction of large 2D matrix arrays for fingerprint sensing in mobile phones. In the first demonstration of this approach, researchers at the University of California, Berkeley, and the University of California, Davis, connected around 2,500 PMUT elements to CMOS electronics and placed them under a silicone rubberlike layer. When a fingertip was pressed to the surface, the prototype measured the amplitudes of the reflected signals at 20 MHz to distinguish the ridges in the fingertip from the air pockets between them.

This was an impressive demonstration of integrating PMUTs and electronics on a silicon chip, and it showed that large 2D PMUT arrays could produce a high enough frequency to be useful for imaging of shallow features. But to make the jump to medical ultrasound, PMUT technology needed more bandwidth, more output pressure, and piezoelectric thin films with better efficiency.

Help came from semiconductor companies such as ST Microelectronics , based in Geneva, which figured out how to integrate PZT thin films on silicon membranes. These films require extra processing steps to maintain their properties. But the improvement in performance made the cost of the extra steps worthwhile.

To achieve a larger pressure output, the piezoelectric layer needed to be thick enough to allow the film to sustain the high voltages required for good ultrasound images. But increased thickness leads to a more rigid membrane, which reduces the bandwidth.

One solution was to use an oval-shaped PMUT membrane that effectively combined several membranes of different sizes into one. This is similar to changing the length of guitar strings to generate different tones. The oval membrane provides strings of multiple lengths on the same structure with its narrow and wide sections. To efficiently vibrate wider and narrower parts of the membrane at different frequencies, electrical signals are applied to multiple electrodes placed on corresponding regions of the membrane. This approach allowed PMUTs to be efficient over a wider frequency range.

From academia to the real world

In the early 2000s, researchers began to push CMUT technology for medical ultrasound out of the lab and into commercial development. Stanford University spun out several startups aimed at this market. And leading medical ultrasound imaging companies such as GE, Philips, Samsung, and Hitachi began developing CMUT technology and testing CMUT-based probes.

But it wasn’t until 2011 that CMUT commercialization really began to make progress. That year, a team with semiconductor electronics experience founded Butterfly Network. The 2018 introduction of the IQ Probe was a transformative event. It was the first handheld ultrasound probe that could image the whole body with a 2D imaging array and generate 3D image data. About the size of a TV remote and only slightly heavier, the probe was initially priced at US $1,999—one-twentieth the cost of a full-size, cart-carried machine.

Around the same time, Hitachi in Tokyo and Kolo Medical in Suzhou, China (formerly in San Jose, Calif.), commercialized CMUT-based probes for use with conventional ultrasound systems. But neither has the same capabilities as Butterfly’s. For example, the CMUT and electronics aren’t integrated on the same silicon chip, which means the probes have 1D arrays rather than 2D. That limits the system’s ability to generate images in 3D, which is necessary in advanced diagnostics, such as determining bladder volume or looking at simultaneous orthogonal views of the heart.

Exo Imaging’s September 2023 launch of its handheld probe, the Exo Iris, marked the commercial debut of PMUTs for medical ultrasound. Developed by a team with experience in semiconductor electronics and integration, the Exo Iris is about the same size and weight as Butterfly’s IQ Probe. Its $3,500 price is comparable to Butterfly’s latest model, the IQ+, priced at $2,999.

The ultrasound MEMS chips in these probes, at 2 by 3 cm, are some of the largest silicon chips with combined electromechanical and electronic functionality. The size and complexity impose production challenges in terms of the uniformity of the devices and the yield.

These handheld devices operate at low power, so the probe’s battery is lightweight, lasts for several hours of continuous use while the device is connected to a cellphone or tablet, and has a short charging time. To make the output data compatible with cellphones and tablets, the probe’s main chip performs digitization and some signal processing and encoding.

Chris Philpot; Source: Alessandro Stuart Savoia

Two MEMS ultrasound architectures have emerged. In the capacitive micromachined ultrasonic transducer (CMUT) design, attractive forces pull and flex the membrane toward the substrate. When an oscillating voltage is added, the membrane vibrates like a struck drumhead. Increasing the voltage causes the electrostatic forces to overcome the restoring forces of the membrane, causing the membrane to collapse onto the substrate. In the piezoelectric micromachined ultrasonic transducer (PMUT) architecture, voltages applied to the piezoelectric material cause it to expand and contract in thickness and from side to side. Because the lateral dimension is much larger, the piezo disk diameter changes significantly, bending the whole structure.

To provide 3D information, these handheld probes take multiple 2D slices of the anatomy and then use machine learning and AI to construct the necessary 3D data. Built-in AI-based algorithms can also help doctors and nurses precisely place needles in desired locations, such as in challenging vasculature or in other tissue for biopsies.

The AI developed for these probes is so good that it may be possible for professionals untrained in ultrasound, such as nurse midwives, to use the portable probes to determine the gestational age of a fetus, with accuracy similar to that of a trained sonographer, according to a 2022 study in NEJM Evidence . The AI-based features could also make the handheld probes useful in emergency medicine, in low-income settings, and for training medical students.

Just the beginning for MEMS ultrasound

This is only the beginning for miniaturized ultrasound. Several of the world’s largest semiconductor foundries, including TSMC and ST Microelectronics, now do MEMS ultrasound chip production on 300 and 200 mm wafers, respectively.

In fact, ST Microelectronics recently formed a dedicated “Lab-in-Fab” in Singapore for thin-film piezoelectric MEMS, to accelerate the transition from proofs of concept to volume production. Philips Engineering Solutions offers CMUT fabrication for CMUT-on-CMOS integration, and Vermon in Tours, France, offers commercial CMUT design and fabrication. That means startups and academic groups now have access to the base technologies that will make a new level of innovation possible at a much lower cost than 10 years ago.

With all this activity, industry analysts expect ultrasound MEMS chips to be integrated into many different medical devices for imaging and sensing. For instance, Butterfly Network, in collaboration with Forest Neurotech , is developing MEMS ultrasound for brain-computer interfacing and neuromodulation. Other applications include long-term, low-power wearable devices, such as heart, lung, and brain monitors, and muscle-activity monitors used in rehabilitation.

In the next five years, expect to see miniature passive medical implants with ultrasound MEMS chips, in which power and data are remotely transferred using ultrasound waves. Eventually, these handheld ultrasound probes or wearable arrays could be used not only to image the anatomy but also to read out vital signs like internal pressure changes due to tumor growth or deep-tissue oxygenation after surgery. And ultrasound fingerprint-like sensors could one day be used to measure blood flow and heart rate.

One day, wearable or implantable versions may enable the generation of passive ultrasound images while we sleep, eat, and go about our lives.

  • Wearable Ultrasound Sees Deep Tissue on the Move ›
  • Beyond Touch: Tomorrow’s Devices Will Use MEMS Ultrasound to Hear Your Gestures ›
  • MEMS ultrasonic transducers for safe, low-power and portable eye ... ›
  • MEMS Ultrasound Transducers for Endoscopic Photoacoustic ... ›

F. Levent Degertekin is the George W . Woodruff chair in mechanical systems at Georgia Tech’s School of Mechanical Engineering in Atlanta. 

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A Review on Biological Effects of Ultrasounds: Key Messages for Clinicians

Carla maria irene quarato.

1 Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, Policlinico Universitario “Riuniti” di Foggia, University of Foggia, 71122 Foggia, Italy

Donato Lacedonia

Michela salvemini, giulia tuccari.

2 Department of Medical and Surgical Sciences, Institute of Geriatric, Policlinico Universitario “Riuniti” di Foggia, University of Foggia, 71122 Foggia, Italy

Grazia Mastrodonato

3 Department of Basic Medical Science, Neuroscience and Sensory Organs, Institute of Sports Medicine, University “Aldo Moro” of Bari, 70122 Bari, Italy

Rosanna Villani

4 Department of Medical and Surgical Sciences, Institute of Internal Medicine, Liver Unit, Policlinico Universitario “Riuniti” di Foggia, University of Foggia, 71122 Foggia, Italy

Lucia Angela Fiore

Giulia scioscia, antonio mirijello.

5 Department of Internal of Medicine, IRCCS Fondazione Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy

Annarita Saponara

6 Unità Sanitaria Locale (ASL) di Potenza, 85100 Potenza, Italy

Marco Sperandeo

7 Unit of Interventional and Diagnostic Ultrasound of Internal Medicine, IRCCS Fondazione Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy

Associated Data

Not applicable.

Ultrasound (US) is acoustic energy that interacts with human tissues, thus, producing bioeffects that may be hazardous, especially in sensitive organs (i.e., brain, eye, heart, lung, and digestive tract) and embryos/fetuses. Two basic mechanisms of US interaction with biological systems have been identified: thermal and non-thermal. As a result, thermal and mechanical indexes have been developed to provide a means of assessing the potential for biological effects from exposure to diagnostic US. The main aims of this paper were to describe the models and assumptions used to estimate the “safety” of acoustic outputs and indices and to summarize the current state of knowledge about US-induced effects on living systems deriving from in vitro models and in vivo experiments on animals. This review work has made it possible to highlight the limits associated with the use of the estimated safety values of thermal and mechanical indices relating above all to the use of new US technologies, such as contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) shear wave elastography (SWE). US for diagnostic and research purposes has been officially declared safe, and no harmful biological effects in humans have yet been demonstrated with new imaging modalities; however, physicians should be adequately informed on the potential risks of biological effects. US exposure, according to the ALARA (As Low As Reasonably Achievable) principle, should be as low as reasonably possible.

1. Introduction

The first application of ultrasound (US) was performed during World War I for the detection of submarines (sonar) [ 1 ]. Since then, US has been successfully used for a wide range of medical and non-medical applications.

In industrial applications, low-power USs with high frequencies are employed to test and measure materials and detect cracks, fractures, moving components, and defects in objects. High-power USs (lower frequencies and higher power) are used for cleaning, welding plastics and metals, cutting and forming materials, separating, mixing, de-gassing, atomizing, localizing, and many others processes [ 2 ]. In the food industry, ultrasound technology is generally used in the processing, chilling, and preservation of food products because it is a clean and efficient technique. Ultrasound can be used as an alternative method to thermal treatments for the elimination of microorganisms and enzymes without destroying the nutrients in foods [ 3 ]. Another area of ultrasound use is the field of sonobioreactors, which use sound waves to increase the metabolic productivity of microbes, plants, and animal cells [ 4 ]. New, promising fields of ultrasound applications include environmental protection and technological procedures to meet industry demands, such as prevention or elimination of existing pollution, water purification, atmospheric decontamination, and soil remediation [ 5 ].

In the last decades, there has been extraordinary growth in the use of US imaging as a diagnostic tool in medicine. This has led to the development of sophisticated and powerful modern diagnostic equipment, with significant improvements in resolution, image quality, and gray-scale definition [ 6 ]. Nowadays, medical US is used across all medical disciplines ( Table 1 ).

Applications of ultrasound across different medical disciplines.

The main advantages of diagnostic US in medicine include real-time assessment, absence of radiation, reduced cost, and portability. Additionally, it can be safely and successfully used to perform biopsies and fine-needle aspirations in parenchymal tissues, such as the lung, kidney, liver, breast, and lymph nodes [ 7 ].

At the same time, medical US has also seen development as a therapeutic modality in which energy is deposited in tissue to induce various biological effects [ 8 , 9 ]. Some examples include the use, in surgery, of high-power US for the thermal ablation of tissues and US-guided extracorporeal shock wave lithotripsy (ESWL), which uses high-energy shock waves to break up large kidney and ureteral stones so that stone fragments can be eliminated through the urinary tract. The use of shock waves to treat gallbladder stones has been explored, but the technique has not achieved widespread usage [ 9 ]. In dentistry, high-frequency sonic vibrations are used to break apart and remove plaque and tartar during teeth cleaning. High-intensity focused US (HIFU) procedures are used to treat cancer patients. By focusing high-power US onto a target area, the temperature is raised enough to destroy the target tissue. More moderate US power levels are used in physical therapy and sports medicine to deliver moderate heat directly to damaged tissues and to increase and improve the healing of tears, strains, and bruises. Finally, microbubble-based therapeutic strategies are under study for US-directed and targeted therapy. In these strategies, external US exposure activates microbubbles in the circulation, which may act as drug carriers at a desired treatment site [ 9 ].

In 1917, Paul Langevin observed for the first time that exposure to high-intensity US was able to kill fish placed in a small tank immediately. Later, some animal studies suggested that prolonged exposure to ultrasound waves could damage neurological, immunological, and hematological systems, as well as the genetic code of the fetus [ 10 ]. On the contrary, studies investigating the potentially harmful effects of diagnostic US on human tissues and organs are few, and those available did not show any effect [ 11 ]. Based on the currently available data, there is a generally accepted view that the diagnostic use of US is harmless for humans [ 12 ]. However, the current state of knowledge does not answer the question of whether there are no side effects associated with ultrasound propagation in human tissues. Although in vitro studies indicate the types of biophysical interactions that may occur and the nature of cellular responses, cell culture conditions may not reflect the in vivo situation. Animal studies are more directly relevant, but transposition between species may be problematic [ 13 ]. Given the multiple uses and the exponential development of ultrasound in medical fields, understanding the mechanisms of interaction between ultrasound and biological tissues and their effects on living systems is mandatory.

The purpose of this review was to understand the possible physical interactions of diagnostic ultrasound with biological tissues and the underlying principles for the assumption of the “safety” of acoustic outputs and indices. Observations from in vitro and in vivo studies on the embryo/fetus and specific tissues/organs, even if deriving from outputs exposures above those used in diagnostic ultrasound, have also been reviewed to provide insight into possible bio-effects of ultrasound for the practicing clinician.

2. Ultrasound Physics

The term “ultrasound” refers to all acoustic energy with a frequency above human hearing (20,000 hertz or 20 kilohertz). Unlike electromagnetic radiation, which is capable of spreading even in a vacuum, US (as well as sound waves) requires a physical support medium to propagate. US consists of a series of mechanical waves originating from the vibrations of an elastic body that propagate, generally longitudinally, by alternating phases of compression (high density or pressure) with phases of rarefaction (low density or pressure) of the atoms and molecules that constitute the physical medium crossed (solid, liquid, or gaseous).

Like any other type of wave phenomenon, US can be described by its physical properties such as:

  • Frequency (f): indicates the number of compression and rarefaction cycles (oscillations) of the medium particles that occur in one second. Its unit of measurement in acoustic is Hertz, which corresponds to one oscillation (or cycle) per second (s): 1 hertz (Hz) = 1 (cycle) x s. In diagnostic ultrasound, sound frequencies from 1 to 10 MHz are normally used.
  • Period (T): represents the time that a wave takes to complete a complete cycle, i.e., the duration of an oscillation. It is measured in seconds (s). Therefore, the period will be shorter the higher the frequency:

As the period is inversely related to frequency, “f” can also be expressed as 1/s.

  • Wavelength (λ): represents the space traveled by an oscillation in the time interval of a period or even the minimum distance between two points in which the displacement from the equilibrium configuration assumes the same value (i.e., the distance between two peaks or two troughs of the wave). It is expressed in meters (m).
  • Longitudinal wave velocity (v): consists of the speed at which sound waves propagate within a physical medium. Frequency, “f”, wavelength, “λ”, and longitudinal wave velocity, “v”, are linked together by the formula:

Expressing “f” in 1/s and “λ” in m, “v” is expressed in m/s.

Frequency and wavelength are inversely proportional to each other. As the frequency changes, the wavelength automatically changes as well.

The transducers (or probes) used in diagnostic ultrasound are different and work at different central frequencies depending on the type ( Table 2 ). The frequency used influences the theoretical limit of the spatial resolution of the probe (i.e., the ability to discriminate between two distinct but close targets). The higher the frequency, the better the image resolution, but the smaller the depth; conversely, the lower the frequency, the greater the depth; however, the image resolution is reduced. In US equipment, the frequency is selected automatically with the choice of the probe or, in the case of multi-frequency probes, with the choice of a specific pre-set.

Different types of ultrasound probes with their characteristics and uses.

The longitudinal wave velocity “v” of the ultrasound is also inversely proportional to the density, “ρ”, and directly proportional to the elastic modulus (or stiffness), “E”, of the transmission material medium, according to the following relationship:

where “E” is expressed in kg/ms 2 and “ρ” is expressed in kg/m 3 .

As a result, the longitudinal wave speed of US is modest in gases, while it becomes progressively greater in solids and liquids. The longitudinal wave velocity of US in the air at room temperature is around 343 m/s, while the longitudinal wave velocity in a liquid medium such as water is approximately 1480 m/s. In most human soft tissues, the longitudinal wave speed varies between 1500 and 1600 m/s, with an average longitudinal wave velocity of about 1540 m/s (which is the value on which all US machines used in diagnostics are normally calibrated); adipose tissue is at the lower limits of this range, while muscle tissue is at the higher limits. In bone tissue, longitudinal wave velocity shows values 2–3 times higher than in most soft tissues. The slowest longitudinal wave velocity of US is recorded in lung tissue due to the air content of the alveoli.

  • Acoustic impedance (Z): consists of the resistance that a material (or tissue) opposes to the propagation of US waves through itself. It is expressed by the product of the density of the crossed medium, “ρ”, by the propagation velocity of US in the medium itself, “v”:

As “ρ” is expressed in Kg/m 3 and “v” is expressed in m/s, Z is expressed in Kg/m 2 s. Human tissues are not homogeneous in terms of composition. Table 3 shows approximate densities, acoustic impedances, and US longitudinal wave velocities for a variety of biological tissues [ 14 , 15 , 16 , 17 ].

Density, acoustic impedance, and longitudinal wave velocity of US in biological tissues.

The amount of change in acoustic impedance encountered by the US beam as it passes through biological tissues will determine the amount of US signal that will be reflected (i.e., come back towards the transducer), refracted (i.e., deflected from a straight path), dispersed from the microscopic inhomogeneities of tissues (i.e., scattering), or absorbed.

  • Amplitude, acoustic power, and intensity are quantities that variously define the mechanical energy carried by the US. Amplitude (A) defines the maximum compression peak of the wave, and it is generally expressed in Pascal (Pa). Acoustic power (P) is the amount of sound energy carried in the unit of time, and it is expressed in Watts (W). Intensity (I) is a measure of acoustic power per unit area and, thus, the amount of sound energy delivered to biological tissues. It is expressed in W/cm 2 . As it will be shown, intensity determines the biological effects of US, and its values are regulated on the basis of parameters established by competent governmental agencies at the national and international levels. In B-Mode applications, the acoustic power of the transducer ranges from 10 to 18 mW. In M-Mode applications, the transmitted acoustic power is less than 4 mW, while in Doppler and color-Doppler applications, the transmitted acoustic power is 30 mW and 80 mW, respectively. Alternatively, in acoustics, the intensity level of a sound may be expressed in decibels (dB), defined as the logarithmic ratio of the intensity, “I”, with respect to a reference sound intensity, “I 0 ”, which coincides with that of the lowest sound perceivable by the human ear: dB = 10 Log (I/I 0 ).

3. Quantifying Biological Effects

The need to identify a physical quantity that can be directly related to the biological response is an essential prerequisite for understanding the potential risks of ultrasound interaction with biological tissues in controlled experimental studies [ 13 ]. The most widely used quantity in the study of the bioeffects of US is the intensity expressed in W/cm 2 . Regulatory authorities for the use of diagnostic US mainly consider the spatial-peak temporal-average intensity (I SPTA ), which is the maximum intensity in the beam averaged over the pulse repetition period (PRP). This is because the higher the “pulse on” time, the greater the acoustic energy delivered to biological tissues. However, this does not provide a real measure of the absorbed “dose”. Indeed, the distribution of acoustic energy across the scanned area varies from point to point, also depending on the duration of the examination, the acoustic impedance of the organs examined, and the penetration capacity of the US beam. As a result, the measure of acoustic power alone incompletely describes tissue exposure and the potential biological danger.

Two basic mechanisms of US interaction with biological tissues have been identified: thermal and non-thermal. Usually, both effects occur simultaneously but with different intensities.

In 1992, in a joint conference between the American Institute of Ultrasound in Medicine (AIUM) and the National Electrical Manufacturers Association (NEMA) (AIUM/NEMA, 1992 [ 18 ]), two standard indicators of acoustic power and biological risk from ultrasound were defined: the Mechanical Index (MI) and the Thermal index (TI).

The thermal index (TI) is the indicator of the potential temperature increase resulting from the friction of interfaces stressed by compression and rarefaction waves.

The mechanical index (MI) is the indicator of potential non-thermal mechanical effects of cavitation determined by the negative pressure peak or rarefaction of the US beam.

The same 1992 AIUM/NEMA joint conference also first defined and published the so-called “Output Display Standard” (ODS), in which it was mandated that diagnostic US machines be able to display on the screen a thermal index and a mechanical index as safety indices to standardize diagnostic US examinations and provide information to the user related to safety [ 18 ].

In the USA, the Food and Drug Administration (FDA) developed guidelines on acoustic output levels considered acceptable and demanded that the ODS information be provided by the manufacturers [ 19 ], while in Europe, ultrasound imaging scanners are required to meet the standard requirements for safety and effectiveness set by the International Electrotechnical Commission (IEC) to be sold. IEC standards for diagnostic and monitoring equipment (IEC 60601-2-37:2007+AMD1:2015 CSV [ 20 ]) set no upper limit on output exposure quantities but specified methods for the determination of TI and MI under a set of particular conditions and explained how a user should be informed about potential hazard through its displayed values.

4. Thermal Effects

As the propagation of the US energy, and thus, the distance traveled in a material (e.g., a tissue) increases, there is a corresponding decrease in the amplitude of the wave. This is due to absorption and/or dispersion (scattering) of the US signal. Absorption is the portion of the wave energy converted into heat energy in the biological structures traversed by the US beam; dispersion is the portion of the wave that changes direction. As the tissue can absorb energy to produce heat, an increase in temperature may occur. The increase in temperature will be as greater as the rate of ultrasound heat production exceeds dissipation.

Assuming the case of an US beam passing through an absorbing target, the energy deposited as heat, “Q”, in an ultrasound field of intensity, “I”, is given using the following equation [ 21 ]:

where “α” is the absorption coefficient depending on various media or tissues.

As a result, an increase in the input intensity (or in the power) of the US beam will result in an increased potential for tissue heating. In addition, since the acoustic intensity describes the acoustic power passing through a unit area of tissue, the smaller the scanned area, the greater the energy passing through it. This will also result in a greater amount of heat deposited. Powerful transducers and strongly focused fields, therefore, will produce particularly significant temperature increases. On the other hand, intensity and heat production decrease when ultrasound energy is distributed over a larger area (unfocused). However, the condition described is an oversimplification. In modern ultrasound scanners, where a focused imaging beam typically originates from more than 100 array elements, the intensity at the focus is much higher than that at the input. Furthermore, over the past decade, improvements in transducer design and manufacturing techniques have led to two-dimensional matrix arrays and multi-focal imaging beams, particularly found in four-dimensional (4D) fetal ultrasound scanners, greatly increasing the ultrasound intensity delivered to the imaged volume.

Deposited heat increases linearly with the absorption of the medium. In general, the concentration of proteins increases the absorption of ultrasound, so tissues with greater collagen content absorb more energy. Attenuation coefficients have been measured for a range of biological tissues in vitro and in animal studies and are available in the literature [ 14 , 15 , 17 , 22 , 23 ]. ( Table 4 ). However, caution needs to be exercised in using some of the published thermal property values for tissues, in particular for values obtained in vitro and from post-mortem studies. Indeed, heat transfer in biological media is affected by manifold in vivo conditions, including the effect of blood perfusion and heat generation due to metabolism.

Attenuation coefficients of various media or tissues.

Although attenuation includes the small additional contribution from the scattering of an ultrasound beam by tissue, the contribution of absorption to attenuation may be 60–80% of the total [ 23 ]. Therefore, in tissues such as skeletal muscle or even bone—which are characterized by a higher attenuation coefficient and, thus, absorption—we will expect a greater increase in temperature than, for example, in adipose tissue.

In addition, the absorption coefficient, “α”, is a function of frequency, “f”, of the ultrasound energy, according to the following relation [ 22 ]:

where a and b are tissue-specific constants.

As stated above, higher acoustic frequency waves display better spatial resolution, but they imply less beam penetration depth. Additionally, as the highest frequency beams are also absorbed more strongly, they have the potential to produce heating in superficial tissue.

Increasing the time that any particular region is exposed to an US beam (dwell time) may increase the temperature rise produced. For a given US field of intensity, “I”, assuming that no heat is lost by conduction, convection, or any other heat removal processes, the energy deposited as heat, “Q”, is approximately described by the equation formulated by Fry and Fry in 1953 [ 24 ]:

where “ρ” represents the tissue density, “c” is the specific heat of the tissue (i.e., the amount of heat required to increase the temperature of tissue by 1 °C per unit of mass), “δT” is the local temperature increase, and “δt” is the time duration of exposure.

Equation (7) is valid only for short exposure times. For longer exposure times, heat removal processes become significant.

As noted above, in living tissue, heat transfer depends partly on the rate of heat conduction due to temperature gradient, partly on the rate at which the heat is removed by blood flow (i.e., blood perfusion), and partly on the thermal contribution due to the metabolism. Each of these mechanisms is taken into account in the partial derivative Pennes bio-heat equation [ 25 ], which is given by:

where “k” is the tissue thermal conductivity (i.e., the tissue capability to conduct heat), while “δx”, “δy”, and “δz” describe the change in the temperature, “T”, over the directions x, y, and z. ω b c b (T a − T) is the blood perfusion term, where “ω b ” is the mass flow rate of blood per unit volume, “c b ” represents the specific heat of the blood, and T a is the temperature of the arterial blood. “Q met ” represents the metabolic heat generated per volume unit of tissue.

Although the Pennes equation configures a simplified bio-heat transfer model in which the metabolic heat generation and the blood perfusion effect are assumed to be homogeneously distributed, it provides the best mathematical description for the propagation of thermal energy through living tissues. In general, well-perfused tissues are less susceptible to US-induced temperature rise because local perfusion, mainly by convection, allows some of the produced heat to be transported away from the site of generation. On the contrary, poorly perfused biological tissues, such as lens, cornea, tendon, and adipose tissue, may be particularly susceptible to the thermal effects of US. Similar concerns have been raised about early gestation because of the lack of or the minimal perfusion of the first-trimester embryo. Moreover, cells are more susceptible to external stimuli during periods of rapid division, such as embryogenesis. For these reasons, the embryo/fetus should be considered to be at risk of thermal effects, and operators should attempt to ensure that the exposure is well managed [ 26 ].

Absorption of US, together with losses due to dispersion, reflection, and refraction, leads to a greater reduction in ultrasonic intensity in the propagation path. Therefore, US beam intensity is greatest near interfaces, and maximum temperature shifts closer to these passage points. The presence of bone within the US path greatly increases the likelihood of thermal effects for adjacent tissues because of bone’s high absorption coefficient and heat conduction from bone itself to interface structures. The very high attenuation and absorption coefficients exhibited by lung tissue can be explained by the absorption and radiation of acoustic energy from gas bubbles enclosed in alveoli. This should imply caution for eventual thermal effects [ 14 ].

Finally, different machine settings may affect heating through their effect on the acoustic power or the beam area. Scanned modes such as B-mode real-time imaging and color-flow Doppler distribute the beam’s energy over a wide area, whereas unscanned modes such as spectral Doppler and M-mode concentrate the energy along a stationary line, resulting in potentially increased temperatures. Similarly, continuous-wave US concentrates more energy in tissue than the on/off cycle of pulsed wave US [ 26 ].

5. The Thermal Index

The thermal index (TI) provides information about the increase in tissue temperature.

The TI is defined as the ratio between the acoustic power output from the ultrasonic transducer (anywhere in the US field), “P 0 ”, and the acoustic power required to increase tissue temperature of 1 °C, contributed by US absorption alone under specific and conservative conditions, “P deg ” (ODS, 2004 [ 18 ]):

In biological models, a TI = 1 corresponds to 1 centigrade degree (°C) of increase in temperature for a given transmission power, probe frequency, scan area, and exposure time, considering the attenuation and absorption characteristics of biological structures. It should be stressed that the displayed TI is not the actual temperature increase in °C generated in tissue while scanning. TI is, however, the best indication of thermal hazard available to the user and allows risk to be quickly assessed during an US examination [ 12 ].

In the USA, where the acoustic output levels are limited by the FDA, the higher-output devices are allowed to produce a maximum ISPTA of 720 mW/cm 2 for all applications. US is not recommended when the TI is greater than 6.0. An exception is related to ophthalmic application, for which the FDA limits the ISPTA to 50 mW/cm 2 and does not recommend US examination when the TI is greater than 1.0 [ 19 , 27 ]. The lower limits applied for eye scanning reflect concerns that the eye may be particularly susceptible to thermal damage as a result of very low blood perfusion.

Regular cellular activity depends on chemical reactions occurring at a certain rate. The rates of chemical reactions and, thus, enzyme activity depend on temperature. An immediate consequence of an increase in temperature is an increase in the speed of biochemical reactions. However, when the temperature becomes sufficiently high, enzymes become denatured. Subsequently, enzyme activity decreases and eventually ceases, which can have a significant impact on the structure and function of cells. At higher temperatures, protein coagulation may occur. Harmful effects in vitro are generally noted at temperatures of 39–43 °C if kept for a sufficient period of time [ 28 ].

Depending on US intensity, a particular exposure period is required before the tissue reaches a harmful temperature increase. The British Medical Ultrasound Society (BMUS) guidelines for the safe use of diagnostic US equipment [ 29 ] recommend limiting exposure time at higher TI values.

Starting from theoretical (Jago et al. 1999 [ 30 ]) and experimental (Shaw et al. 1998 [ 31 ]) studies, BMUS guidelines stated that, in some circumstances, TI could underestimate the temperature elevation by a factor of up to two. For example, a TI value of 1 is considered to correspond to a worst-case temperature elevation of 2 °C.

In adult tissue, for temperature increases less than or equal to 2 °C above normal (i.e., 37 °C), there have been no significant adverse biological effects observed for durations of temperature elevation up to 50 h.

For temperature increases more than 2 °C above normal (1.0 < TI ≤ 6.0), scanning times have to be limited, as follows:

  • 1.0 < TI ≤ 1.5: 120 min;
  • 1.5 < TI ≤ 2.0: 60 min;
  • 2.0 < TI ≤ 2.5: 15 min;
  • 2.5 < TI ≤ 3.0: 4 min;
  • 3.0 < TI ≤ 4.0: 1 min;
  • 4.0 < TI ≤ 5.0: 15 s;
  • 5.0 < TI ≤ 6.0: 5 s;
  • TIB > 6: not recommended.

Three different thermal indices were developed to address three different tissue models, namely the Thermal Index of Soft Tissue (TIS), the Thermal Index of Bone (TIB), and the Thermal Index of Cranial bone (TIC).

  • Thermal Index of Soft tissue (TIS): The soft tissue model assumes a uniform homogeneous soft tissue beam path. There is no bone, developing bone, or cartilage anywhere in the region being scanned.
  • Thermal Index of Bone (TIB): This model assumes a layer of strongly absorbing material (bone) within the soft tissue model.
  • Thermal Index of Cranial bone (TIC): This model omits soft tissue and considers the absorption of ultrasound in a bone layer located directly under the transducer.

These three different tissue models can be used to estimate TI in two different scan modes, namely the scanned mode and unscanned mode, resulting in six combination conditions.

The scanned mode is associated with pulsed B-mode ultrasound and Doppler imaging of cross-sections of tissue. The unscanned mode is typically used clinically for M-mode and spectral Doppler studies. The need for two exposure conditions arises from the different geometric distributions of acoustic power; the unscanned mode concentrates the power of the ultrasound beam on a stationary focal region, which can be as narrow as 1 mm 2 . In scanned mode, the acoustic power extends over a much larger region of exposed tissue, typically covering 100 mm 2 or more. The IEC standard specifies how to derive the TI value under each of the six circumstances described using measurements of acoustic quantities at prescribed positions within the beam [ 32 ].

5.1. Thermal Index of Soft Tissue (TIS)

The Soft Tissue Thermal Index (TIS) provides information on the temperature rise in areas in which only soft tissues are scanned, such as in abdominal examination or during obstetric scanning earlier than 10 weeks of gestation. The soft tissue model assumes a uniform homogeneous medium with an attenuation coefficient of 0.3 dB/cmMHz. Actually, the average attenuation coefficient for fatty and non-fatty soft tissues is about 0.4 and 0.6 dB/cmMHz, respectively [ 32 ]. The use of an absorption coefficient somewhat lower than soft tissue in this model allows us to safely assume the inclusion in the propagation path of areas in which the ultrasonic pulse passes through a fluid space, such as amniotic fluid or urine (where the attenuation coefficient is much lower than that of soft tissues). The soft tissue model also allows us to make assumptions about heat loss from blood perfusion.

5.2. Thermal Index of Bone (TIB)

The Thermal Bone Index provides information on the increase in temperature in or around strongly absorbing bone structures within the soft-tissue model. In this model, US passes through a homogeneous tissue and then reflects off the plane of the bone perpendicular to the beam. If the bone is within the focus, then the temperature in the bone will increase. Examples of the application of TIB are the second and third trimesters of fetal imaging, adult thoracic examination, and musculoskeletal scan of the upper and lower limbs. The attenuation and absorption coefficients of the layer are not defined [ 32 ]. However, the formula assumes that half of the incident power is absorbed in this model.

5.3. Cranial Bone Thermal Index (TIC)

The Cranial Bone Thermal Index (TIC) assumes a near-surface bone model. In this case, all the US power is assumed to be absorbed by the bone, which is coupled directly to the transducer, omitting the presence of soft tissue [ 12 , 32 ].

6. Acoustic Cavitation Effects

The concept of cavitation refers to phenomena related to the vibrations and motion dynamics of gas microbubbles located in an ultrasonic field.

For cavitation to occur, gas bubbles or nucleation sites within the fluid or tissue are required. There is no evidence for the presence in vivo of cavitation nuclei that may be excited by diagnostic ultrasound. Viscous and other forces within solid tissues seem to make the probability of cavitation events quite small [ 33 ]. On the contrary, cavitation bubble formation has been observed with very high amplitude ultrasound pulses used in lithotripsy, where bubble collapse can generate high-speed fluid microjets used in stone fragmentation [ 34 ]. Gas-containing tissues, such as the lung and the intestine, may be more vulnerable to damage from diagnostic exposures than apparently gas-free tissues [ 35 ]. Furthermore, the introduction of gas microbubbles used as US contrast agents into the body by intravenous injection significantly increases the potential for cavitation during clinical ultrasound examinations.

When a fluid with microbubbles is exposed to an acoustic field, gas-filled microbubbles undergo oscillating changes in volume due to the acoustic wave. They expand in size during the period of decreased pressure and contract during compression to an extent dependent on the acoustic pressure. This phenomenon is known as cavitation [ 26 ].

Two types of cavitation phenomena exist, non-inertial cavitation and inertial cavitation [ 34 ].

Non-inertial cavitation, sometimes also known as “stable” cavitation, describes a repetitive oscillation around the equilibrium radius of a bubble in a liquid exposed to an acoustic field without large changes in volume. The maximum expansion of a gas microbubble in non-inertial cavitation typically does not exceed more than two times the equilibrium radius. However, a variety of non-linear physical phenomena can be associated with non-inertial cavitation; bubble oscillations can result in heat generation, microflow of fluid near the bubble, and localized shear forces (shear stress).

In inertial cavitation, sometimes called “collapse cavitation”, the bubble can expand more than twice its initial radius and then rapidly collapse. The collapse may generate a strong shock wave, which is accompanied by extremely high local temperature values that are associated with the release of free radicals. Free radicals can cause undesirable biological effects, such as biochemical reactions between tissues.

According to the theoretical model postulated by Holland and Apfel in 1989 [ 36 ], the initial size of the cavitation nuclei determines the minimum acoustic pressure and the optimal frequency required for significant bubble growth. An initially smaller-sized microbubble needs a higher acoustic pressure amplitude to overcome the stronger surface tension. Higher frequencies require a very specific and small bubble radius for cavitation. At lower acoustic pressure, oscillations in bubble size occur broadly according to variations in acoustic pressure in a stable fashion, making stable cavitation more likely. However, if the peak acoustic pressure increases, different motions may be induced until, finally, the bubble becomes unstable and collapses under the inertia of the surrounding liquid. Higher frequencies shorten the interval between the compressive phases of the US wave, thus reducing the growth of gas-filled bubbles. On the other hand, lower frequencies increase the probability that the microbubble will collapse.

At the MHz frequencies used in diagnostic ultrasound (i.e., 1–10 MHz), the most efficiently echogenic (i.e., resonant) pre-existing gas bodies have to be few in diameter (i.e., about 1–5 µm) [ 36 ]. However, for diagnostic ultrasound, which operates at higher acoustic frequencies and lower pressure amplitudes than lithotripsy, the possibility of gas body activation and inertial cavitation in solid tissues is likely null. Church [ 33 ] reported that the threshold pressure for acoustic cavitation to occur within soft tissue without pre-existing nuclei is greater than 4 MPa at 1 MHz for a 1 ms pulse and, therefore, is above those used in current diagnostic practice.

Cavitation bioeffects have been observed in tissues naturally containing gas pockets in vivo. Pulsed ultrasound within the range of parameters of diagnostic ultrasound was found to induce lung and intestinal hemorrhage in animal models, while such effects have never been reported in humans [ 37 ]. Anatomical structural differences among species and a different distribution of gaseous cavitation sites have been suggested to influence the susceptibility to pulsed ultrasound [ 11 ]. However, the potential risk of harm to patients is still not clearly understood, and caution is required in clinical practice.

Holland et al. [ 38 ] reported that US contrast agents could significantly lower the threshold required for acoustic cavitation. Ultrasound contrast agents consist of a suspension of gas-filled microbubbles, typically ranging in size from less than 1 to 10 µm in diameter. The non-linear behavior of pulsing microbubbles has a key role in their effectiveness as US contrast agents. When pulsing, the bubbles send secondary sound waves in all directions. These secondary sound waves enhance US images because they also reflect back to the transducer. However, microbubble compression cycles with negative and positive pressures also result in secondary motion, high shear stress or local shear forces, and microstreaming of the surrounding fluid. These events may result in the fragmentation of subcellular and cellular structures. Furthermore, the gas bodies can destabilize and act as inertial cavitation nuclei. Reported bioeffects following US contrast microbubble injection and US exposure in vivo include hemolysis, damage to the microvasculature, glomerular capillary hemorrhage, the opening of the blood–brain barrier, inflammatory cell infiltration, cardiomyocyte death, and effects on cardiac rhythm [ 39 , 40 ]. These effects are most likely to arise from the destruction of the microbubbles [ 41 ]. Over the years, advanced and more stabilized contrast microbubbles have been designed to improve persistence in the circulation, and new ultrasound imaging modes have been developed specifically for imaging contrast agent gas bodies [ 42 ]. Prudent use of diagnostic ultrasound with contrast agents is always recommended, particularly in patients with a history of myocardial infarction or unstable cardiovascular disease [ 43 ].

7. Mechanical Index (MI)

The mechanical index (MI) is an indication of an US beam’s ability to cause cavitation-related bioeffects.

This index is based on the theoretical model assumed by Apfel and Holland in 1991 [ 44 ], who, describing the behavior of a cloud of air bubbles of a wide range of diameters in water and blood, determined the approximate acoustic pressure amplitude required to cause a bubble to undergo inertial cavitation (i.e., a large expansion followed by a rapid and violent collapse).

The MI is defined as the estimated peak rarefactional pressure “P r ” (anywhere in the US field) adjusted for tissue attenuation “α”, divided by the square root of the center frequency “f” of the US beam [ 44 ]:

MI allows the acoustic pressure threshold necessary to cause cavitation and, thus, potential damage, to be identified.

The threshold pressure for acoustic cavitation is above that used in diagnostic ultrasound. In HIFU lithotripsy, the peak acoustic pressure is typically in the order of 10–100 MPa compared to approximately 1 MPa for diagnostic ultrasound, and the acoustic frequency of HIFU pulses is much lower than diagnostic pulses. These factors make the eventual tiny cavitation nuclei present in all liquids and tissues more likely to become activated and cavitate. The FDA approved a MI value of 1.9 as the maximum threshold for diagnostic imaging [ 19 ]. Apfel and Holland [ 44 ] showed that the minimum threshold for inertial cavitation of optimally sized nuclei is roughly near a MI value of 0.5 in blood conditions. However, gas bodies suitable for nucleation of ultrasonic cavitation (i.e., about 1–5 µm) are normally unlikely to exist in the human body (due to surface tension and rapid dissolution of the gas), minimizing the possibility of cavitational bioeffects for diagnostic ultrasound. BMUS set a MI value of 0.7 as the threshold for cavitation if an ultrasound contrast agent containing gas microspheres is being used [ 29 ]. The American Institute of Ultrasound in Medicine issued an official statement informing the clinical ultrasound community of the potential for bioeffects from diagnostic ultrasound with US contrast agents for MI values above about 0.4 [ 43 ].

8. Other Non-Thermal Mechanical Effects

In addition to heating and cavitation, US has the potential to induce other bioeffects by non-thermal mechanisms. These secondary effects tend to increase with increasing intensity and are generally relatively small. However, due to the essential non-linearity of the acoustic equations, they have the potential to produce forces and motions at frequencies much lower than those of incident ultrasonic waves [ 45 ]. Typically, when an object is placed in the path of the ultrasound beam, a force acts upon it. This force, also called acoustic radiation force (ARF), develops in the direction of the US wave propagation and results in a transfer of energy from the US field to the object. The magnitude of the ARF depends on the characteristics of both the US field and the object within it. Obviously, ARF is most relevant for structures that are free to move, such as fluid particles; solid tissue is only slightly compressed.

For a plane wave incident normally on an object, it can be expressed using the following equation [ 45 ]:

where “α” is the absorption coefficient of the object, “I” is the average temporal intensity of the acoustic wave (W/cm 2 ), and “v” is the propagation speed of US in the medium (cm/s).

For the case of a plane wave normally incident on a perfectly absorbing target, the radiation force is equal to I/v. On the other hand, the ARF normally exerted by a plane wave on a perfectly reflecting target is twice that of a perfectly absorbing target since the wave now also travels in the opposite direction. For partly absorbent and partly reflecting interfaces, the ARF varies between I/v and 2I/v. These plane wave approximations provide adequate estimates of the ARF [ 34 ]. In the case of a continuous wave signal, the ARF will be a constant pressure. If, however, the acoustic signal is pulsed or modulated, the ARF will vary periodically at the pulse or modulation frequency.

ARF is the mechanism behind phenomena such as radiation momentum and acoustic streaming.

If US radiation pulses are transmitted into a tissue, the radiation momentum of the ultrasound waves will be transferred to the tissue, and it will be pushed on in the direction of ultrasound propagation. When the ARF ceases, the tissue will return to its equilibrium position. When this occurs, waves of axially polarized motion will propagate transverse to the direction of the US ARF application [ 34 ]. These displacements can be monitored both spatially and temporally and are called shear waves. The shear wave velocity (SWV) is proportional to the elastic characteristics of the tissue being examined. This phenomenon is utilized in ultrasonic elastography using Acoustic Radiation Force Impulse (ARFI) imaging.

An acoustic field propagating in a fluid medium can give rise to a flow called “acoustic streaming” [ 46 ]. When a continuous sinusoidal ultrasound wave propagates through a fluid, it forces the fluid particles to oscillate sinusoidally in the wave propagation direction. In linear acoustics, it is assumed that the wave shape does not change over time and that particles in the medium simply vibrate around their equilibrium position. Consequently, no net flow is assumed. However, the attenuation of an ultrasonic beam with distance can be considered as creating a “radiation pressure gradient” in the medium. As a result of such a gradient, each fluid element experiences a net body force that gives rise to a net flow. Typically, the flow may be away from the transducer axis, but recirculation vortices may be created that bring the fluid back toward the transducer surface [ 45 ]. The trajectory of fluid particles will be governed by the balance between the viscous drag force and the acoustic radiation force [ 34 ]. The phenomenon of acoustic streaming can assist in the diagnosis of fluid-filled cysts versus solid tumors using the pulsed-Doppler mode to produce and observe the fluid motion [ 47 ].

Another important mechanical action of US is the phenomenon of so-called “acoustic microstreaming”. Acoustic microstreaming specifically refers to the streaming flow of fluid around an oscillating gas microbubble [ 46 ]. When microbubbles are close to endothelial cells, such microstreaming may result in shear stress of the endothelium and changes in membrane permeability [ 32 ]. One acute effect of endothelium shear stress (occurring from seconds to minutes) is flow-dependent dilation. This effect relies on factors secreted by the endothelium, such as nitric oxide (NO). However, shear stress also modulates the formation of superoxide anions, whose excessive production has been shown to be harmful to the membrane integrity of the cell [ 48 , 49 ]. Acoustic microstreaming was also postulated as a direct mechanism by which ultrasound causes changes in membrane permeability, and this action may result from a mechanical effect on ion channels [ 49 ]. A further indirect effect of endothelium shear stress is platelet “activation” with the consequent production of pro-coagulant and pro-inflammatory mediators [ 50 ]. The effect of microstreaming has been confirmed with microbubbles injected into the vascular system in the form of contrast media [ 51 ]. The average distance of microbubbles from the endothelium increases with vessel size, and the effects of microstreaming may be dominant in the capillary bed. However, a damaged endothelium can lead to the attachment of microbubbles even in large vessels [ 49 ]. Lindner et al. [ 52 ] observed prolonged dwell time of Albunex microbubbles in sites where the endothelial glycocalyx was damaged. Yasu et al. [ 53 ] observed the retention of microbubbles in inflamed venules. In therapeutic or experimental applications, disruption of endothelial integrity may be intentional, such as for the delivery of genetic material or drugs [ 53 , 54 ]. However, for the diagnostic application of microbubbles as contrast agents, endothelial disruption is clearly undesirable [ 49 ].

9. Strengths and Limitations in the Use of TI and MI Indices in Clinical Practice and Further Safety Recommendations

Safety index values displayed on the monitor can give very valuable information, previously hidden from the user, about the potential mechanical and thermal risks associated with each US examination. Typically, the values of MI and TI alter dynamically as the practitioner changes the mode of operation or output power. For example, higher TI values may be shown when the mode of operation of the scanner is changed from conventional B-mode imaging to Doppler-mode imaging or when a deeper focal zone or a smaller field of view is selected. Higher MI values may be expected when harmonic imaging is used.

However, the use of the above-presented indices has some limitations that need to be considered. First, TI and MI indices are mainly related to the transposition of tissue model assumptions to the human being. They may be under- or over-estimated in poorly or highly perfused tissues and do not take into account inter-human variability. The TI and MI indices do not consider either the scanning time, the possibility of non-linear effects, or the self-heating of the transducer that could lead to an increase in the surface temperature of the scanned area. Thermal indices are steady-state estimates and may not be appropriate for new imaging techniques [ 55 ]. The TI value displayed on the screen does not correlate directly with the actual temperature change. TI and MI values are not valid for US contrast agent applications because contrast agents lower the cavitation threshold. Finally, the method used by the manufacturer to update the index dynamically may use algorithms that are not specified by the ODS, with resulting errors that can be as large as 100% and should be described in the machine manual [ 56 ].

As a consequence, the responsibility for the safe use of diagnostic US has to be transferred to the user. According to the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) [ 57 ], US should be used only by qualified health professionals who can quantify the potential benefits and risks to the patient during each type of examination. In addition, both the EFSUMB [ 57 ] and the American Institute of Ultrasound in Medicine (AIUM) [ 58 ] recommend the following ALARA (As Low As Reasonably Achievable) [ 59 ] general principles of prudent use of diagnostic methods based on the interaction of US energy with biological tissues.

  • Apply the presets of an examination correctly if they are integrated into the US diagnostic device. Reviewing the factory default presets to verify their suitability is encouraged.
  • Adjust the power to the lowest setting available to produce diagnostic-quality images. If appropriate, reduce the power at the end of each examination so that the next patient starts at the lowest sound setting.
  • Monitor the mechanical index (MI) and thermal index (TI). Get to know the recommended upper limit of MI, TI, and related duration limitations for the type of examination to be performed.
  • Move/remove the transducer when stationary imaging is not needed so as to reduce the time spent on a particular anatomical structure. Whenever possible, avoid scan fields that include sensitive tissues such as the eye, gas-filled tissues (lung and intestines), and calcified fetal structures (skull and spine).
  • Minimize the overall scan time to obtain the required diagnostic information [ 27 ].

10. Observation of Biological and Clinical Effects of Ultrasound

In vitro and in vivo animal studies have shown that US can cause a wide range of effects at the molecular, cellular and organ level. Understanding these effects can improve our knowledge on the complex interactions between US and biological tissues, so that new avenues for new diagnostic therapeutic applications can be opened.

10.1. Molecular Effects

In 2001, Keychain et al. [ 60 ] demonstrated that diagnostic US can greatly enhance endothelial uptake of bioactive proteins in vivo. In vitro experiments on cultured human umbilical vein endothelial cells (HUVECs) have shown that internalization of caveolae without alteration of cell membrane integrity is a novel mechanism of US-induced protein uptake by endothelial cells associated with phosphorylation/activation of ERK1/2 [ 35 , 61 ]. Diagnostic US, with its energy, allows the transition from the latent enzyme-purified human precallicrein into the active enzyme kallikrein [ 62 ]. This explains the triggering action of US on the intrinsic human coagulation pathway. As a clinical consequence, patients at risk of thrombosis and patients with liver failure should be protected by low-molecular-weight heparin before US exposure, especially if prolonged.

10.2. Cellular Effects

US may be responsible for the production of reactive oxygen species (ROS) that cause cell apoptosis. Andreassi et al. [ 63 ] concluded that cardiac US (1–3.6 MHz and MI 1.5) in vitro increases intracellular oxidative stress. The increased production of reactive oxygen species (ROS) was confirmed by morphological evidence of endothelial damage only after longer exposure times (30 s), while US exposure longer than 15 s has been shown to induce significant DNA scattering and a loss of lactate dehydrogenase (LDH). These results were obtained in vitro and, of course, cannot be confirmed in vivo, where various antioxidant systems (i.e., glutathione, ascorbate, catalase) can rapidly inactivate H . and OH . radicals, making the production of ROS due to US negligible [ 35 ]. Exposure to US in Doppler mode has been shown to increase antioxidant enzyme activity in rat liver and brain. In contrast, after B-mode (4 MHz) US exposure, antioxidant enzyme activity was decreased in fetal brain tissue due to its higher lipid concentration [ 64 ]. In neural cells, heat shock proteins (HSPs) are constitutively expressed and prevent or correct polypeptide folding, thus protecting neurons from injury [ 65 ]. A rapid increase in temperature associated with US exposure (30 min at 1.2 W/cm 2 ) increases the production of HSPs and may, therefore, produce a neuroprotective effect. Furthermore, the upregulation of HPSs may have an additive therapeutic role in relation to its believed importance in sensitizing tissue to radiotherapy and chemotherapy in non-ablation thermal treatments [ 66 ]. When combined with systemic hyperthermia, however, US-induced temperature increases may contribute to the development of congenital malformations in experimental animals [ 67 ]. US can also influence cell regeneration. In the study by Tarantal et al. [ 68 ], repeated US exposure reduced leucocyte production in monkeys’ uteri. Similarly, a decrease in the number of somites was noted when embryo cultures were exposed to US for 15 min at 40 °C [ 67 ]. A non-thermal injury mechanism has been proposed as responsible for these effects.

10.3. Genetic Effects

Genetic, chromosomal, and other mutations have been extensively studied as possible consequences of exposure to US waves, but whether these can lead to physiological consequences is still controversial [ 10 ]. These effects presumably occur due to the increase in oxygen free radicals and their action on the cellular nuclei.

10.4. Fetal Effects

There is no evidence of immediate or long-term harm to a developing fetus from exposure to B-mode US. Available evidence does not support an association between the use of US for fetal imaging with cancer or with adverse effects on birth weight, growth, or neurodevelopment during childhood [ 69 ]. Multiple exposures to US in utero was associated with a small increase in the incidence of low birth weight compared to a single exposure, but this difference was not statistically significant and disappeared as the babies grew up [ 70 ]. A delay in language development in children exposed to US was also reported, but this difference was not maintained during later development [ 71 ].

However, national and international societies continue to urge caution about the use of US in obstetric applications, particularly regarding the possibility of thermal effects [ 72 ]. Conditions present in early pregnancy, such as lack of perfusion, may favor US-induced temperature rise. Furthermore, the rapid cellular division occurring during embryogenesis increases the vulnerability of DNA to thermal insults. The teratogenic effect of heat on mammals is well recognized, with the developing central nervous systems exhibiting the greatest sensitivity [ 73 ]. In view of these considerations, the World Federation for Ultrasound in Medicine and Biology (WFUMB, 1998 [ 74 ]) concluded that an US exposure that elevates human embryonic or fetal temperature by 4 °C above normal for 5 min should be considered potentially hazardous.

In particular, the use of color flow or pulsed Doppler increases the potential temperature rise by an unknown factor and makes thermal indices exceeding three times the recommended limit possible. Indeed, in animal models, Doppler US exposure in utero has been shown to give rise to increased apoptosis [ 75 ]. Moreover, the thermal hazard has been greatly increased with the development of US applications in fetal imaging beyond medical practice into commercial souvenir scans, such as 3D imaging systems, that can provide clearer images of fetus anatomy recognizable to the family and 4D sonographic equipment that further facilitates observing fetus movements. In particular, continuous exposure in 4D sonography has the potential to prolong examination times and, thus, increase the risk for bioeffects.

As there is very little information currently available regarding possible subtle biological effects of diagnostic levels of US on the developing human embryo or fetus, care should be taken to limit the TI and MI and the exposure time to the minimum commensurate with an acceptable clinical assessment. In general, US examinations in obstetrics should be as short as possible. Ultrasound scans should not be performed solely for producing souvenir images or recordings of a fetus or embryo. According to BMUS guidelines [ 29 ], for obstetric and neonatal scanning, there is no known reason to restrict scanning times with a TI value between 0–0.7. The test time should be reduced if TI > 0.7, as follows:

  • 0.7 < TI ≤ 1.0: 60 min;
  • 1.0 < TI ≤ 1.5: 30 min;
  • 1.5 < TI ≤ 2.0: 15 min;
  • 2.0 < TI ≤ 2.5: 4 min;
  • 2.5 < TI ≤ 3.0: 1 min;
  • TI should never exceed 3.0.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommends a TI < 1.0 for first-trimester screening (11 weeks to 13 weeks, 6 days); pulsed Doppler and color Doppler should not be used routinely. If a Doppler test is required, it can be performed maintaining a TI < 1.0 for no more than 5–10 min. Examination of the uterine vessels of the mother is safe when the fetus is outside the irradiated field [ 72 ]. Special care should be taken to reduce the risk of thermal and non-thermal effects during cardiac, pulmonary, and cranial investigations of neonates. As there is experimental evidence that self-heating of the transducer can lead to a significant increase in skin surface temperature, scan times and exposure levels should be kept as low as possible. For neonatal ultrasound, there is a potential risk of lung damage; for MI > 0.7, the risk of cavitation increases, especially in studies with contrast media. The exposure time should be shortened if the lung or intestine is scanned at MI values above 0.3 [ 29 ]. When attempting to obtain fetal heart rate with a diagnostic US system, the AIUM recommends using M-mode [ 76 ]. The power levels used for fetal heart rate monitoring (cardiotocography—CTG) are sufficiently low, so the use of this mode is not contraindicated for safety reasons, even with prolonged use [ 77 ].

10.5. Organs Effects

10.5.1. brain.

Diagnostic ultrasonic investigation of the brain is limited because the bones of the skull block most of the transmission of US. However, transcranial Doppler (TCD) and transcranial color Doppler (TCCD) can be used to study the brain’s circulation and diagnose emboli, stenosis, vasospasm from subarachnoid hemorrhage, and other problems. Recording may be performed through the squama of the temporal bone, above the zygomatic arch, through the eyes, below the jaw, and from the post-auricular area. Brain ultrasound requires a low-frequency transducer (1–5 MHz) together with the transcranial Doppler software for image optimization [ 78 ]. US measurement of the optic nerve sheath diameter (ONSD) may aid in the diagnosis of intracranial hypertension (IH). A high-frequency (7–10 MHz) linear transducer is required [ 79 ]. US is useful in assessing the structure, function, and stability of the spine, also providing guidance in therapeutic interventions. US imaging of the spine typically requires the use of low-frequency US (2–5 MHz) and curved array transducers [ 80 ]. A high-frequency linear array probe (8–15 MHz) has to be used to imagine peripheral nerves [ 81 ].

Brain tissue has a relatively low absorption coefficient. However, as the skull temperature increases during ultrasound exposure, the temperature of the adjacent brain increases through conduction mechanisms [ 82 ]. This phenomenon is particularly important in the fetus when using the Doppler US modality.

In addition to these indirect thermal effects, US also causes direct neural effects. High-intensity focused US can produce destructive lesions in the brain [ 83 ]. Focused US beams that create therapeutic lesions in the subthalamic nucleus have been proposed to treat motor features of Parkinson’s disease [ 84 ]. The same technique has also been proposed for the treatment of some brain tumors [ 85 ].

Histological analysis on mammalian peripheral nerves revealed that US exposure might lead to neuronal and myelin destruction in the spinal cord [ 86 ]. Myelin, and especially the smaller myelinated fibers, are the structures most sensitive to US injury, thus leading to impaired neural conduction [ 87 ]. The damage seems to depend on both the thermal effect and the cavitation phenomenon [ 88 , 89 ]. Sodium and potassium channels open with increases in temperature during exposure to US, thus affecting conduction velocity [ 90 ]. Auditory evoked potentials can also be transiently suppressed after exposure to US in the diagnostic interval [ 91 ].

10.5.2. Eye

Both B-mode and Doppler sonography have been used effectively and safely to diagnose many ophthalmic conditions, including intraocular or periorbital foreign bodies, globe rupture, lens dislocation, retinal and vitreous detachment and hemorrhage, neoplasm, and vascular pathologies [ 92 , 93 ]. However, exposure levels exceeding those encountered in diagnostic systems are capable of damaging the ocular structures.

The cornea and the lens of the eye, due to the lack of blood vessels and the large amount of collagen in their structures, are more prone to the absorption of US energy and, thus, are more likely to develop increased temperature during prolonged US exposure. Lizzi et al. [ 94 ] demonstrated that permanent lesions of the retina, choroid, and sclera could be produced with the use of focused US at 9.8 MHz in a rabbit model. Transient chemosis, conjunctival injection, and occasional hemorrhage were also reported. The different degrees of lesions depended on the duration and intensity of exposure. This evidence, in addition to histological examination of tissue samples, suggested that thermal mechanisms are the principal cause of permanent tissue alterations. High-intensity US is clinically used to fragment and emulsify the lens during cataract surgery. Corneal endothelial damage is a known risk of ultrasound phacoemulsification [ 95 ]. Both thermal and cavitation-related mechanisms are believed to be responsible for corneal endothelial damage induced by high-intensity focused US [ 96 ].

Due to the concern about intraocular damage, the FDA limited ocular exposure to a spatial peak, average temporal intensity (I SPTA ) of 50 mW/cm 2 [ 19 ]. Similarly, the BMUS recommended limiting thermal and mechanical indices to less than 1 and 0.7, respectively, during ocular exposure to ultrasound [ 29 ].

10.5.3. Heart

Echocardiography is routinely used in the diagnosis, management, and follow-up of patients with any suspected or known heart diseases. It provides helpful information on the size and shape of the heart, wall motion, ejection fraction, diastolic function, and assessment of valves [ 97 ].

US has been shown to act on both cardiac rhythm and contractility. Single high-amplitude US pulses used in lithotripsy can produce premature ventricular contractions in frogs [ 98 ]. The most sensitive phase of the cardiac cycle to produce a premature contraction with an acoustic pulse is during the diastole. Therefore, in clinical practice, the administration of US pulses is synchronized with the electrocardiogram (ECG) to avoid effects on heart rhythm. In frogs and mice, the “threshold” for producing a premature contraction with a single 5 ms US pulse at 1.2 MHz was about 2–5 MPa. This threshold showed increases with decreasing pulse duration and increasing frequency [ 99 ]. However, the relatively long pulse durations and high-pressure amplitudes required to produce this effect are not characteristic of exposures used for diagnostic US.

Gaseous microbubbles or acoustic cavitation may play a role in the generation of premature cardiac contractions with US [ 100 , 101 ]. Premature ventricular contractions have occurred in men exposed to diagnostic US when an experimental contrast agent was present in the blood [ 102 ]. In laboratory animals injected with contrast agents, the threshold for producing a premature contraction with a single 10 μs pulse of US at 1 MHz was of the order of 1 MPa [ 103 ]. Microvascular damage has also been observed in hearts exposed to US contrast medium. However, the relationship between arrhythmia generation and microvascular effects is uncertain [ 34 , 103 ].

A single high-amplitude US pulse can also affect cardiac contractility. In frogs, pulsed US has been shown to produce a decrease in the maximum aortic pressure, an abnormal relaxation, or a combination of both effects. The threshold for this effect was about 5 MPa using a 5 ms pulse at a frequency of 1.2 MHz [ 99 ]. Aortic pressure returned to control values within one or two beats after US exposure, suggesting that the contractile components of the tissue were not damaged. For this effect, an US pulse is most effective when the heart is scanned during systole. A number of experimental investigations suggest that ARF is the main acoustic mechanism acting on cardiac contractility [ 104 ].

10.5.4. Skeletal Muscle

Diagnostic US is useful for the evaluation of normal and pathological muscle tissue. It is used to help diagnose sprains, strains, and tears [ 105 ]. Atrophy can be objectified by measuring muscle thickness, while degenerative changes, such as infiltration of fat and fibrous tissue, increases muscle echo intensity [ 106 ].

US-induced temperature elevation could damage muscular structures. In vitro experiments on chick embryonic skeletal muscle cells have shown that low-intensity pulsed ultrasound wave (pulsed 0.5 W/cm 2 intensity for 5 min) induced cell proliferation, low-intensity continuous ultrasound wave (continuous 0.5 W/cm 2 intensity for 5 min) induced muscle differentiation, and high-intensity pulsed ultrasound wave (pulsed 1.0 W/cm 2 intensity for 10 min) induced cellular death [ 107 ]. Miller and Quddus [ 108 ] observed the induction of petechiae in the abdominal muscles of mice using diagnostic ultrasound associated with the use of contrast microbubbles. The petechiae number was approximately proportional to the contrast agent dose. Skyba et al. [ 109 ] used intravital microscopy to visualize bioeffects resulting from contrast gas body destruction using diagnostic ultrasound in the spinotrapezious muscle in rats. Harmonic mode imaging of muscle was performed with a phased array diagnostic ultrasound system and a mean frequency of 2.3 MHz. A single-image frame was obtained with MIs of 0.4, 0.5, 0.7, and 1.0 for each animal. After exposure, the muscle was examined for microvessel rupture and dead cells (i.e., stained with Propidium Iodide). Capillary rupture sites and stained cells were absent at an MI of about 0.4 but increased rapidly for higher MI values.

In recent decades, low-intensity pulsed ultrasound (LIPUS) has been suggested to have a role in assisting muscle restoration after injuries. LIPUS is a form of ultrasound therapy typically used in rehabilitation medicine that employs low-intensity radiation in pulsed-wave form. Spatial-average temporal-average intensities (ISATA) used in LIPUS are determined by the amplitude of the “on” period, varying from 0.02 to 1 W/cm 2 at frequencies ranging from 1 to 3 MHz. Low-intensity exposure minimizes the possibility of thermal effects. Shu et al. [ 110 ] demonstrated the effectiveness of LIPUS treatment at different doses (0.25 W/cm 2 , 0.5 W/cm 2 , and 0.75 W/cm 2 ) in a rat contusion injury model. Piedade et al. [ 111 ] found that US was able to stimulate myoregeneration and collagen deposition in an experimental rat model of lacerative gastrocnemius muscle lesion. Moreover, Karnes et al. [ 112 ] reported that LIPUS treatment increased fibroblast proliferation, capillarization, and myofiber formation in a rat muscle injury model. Even if the real mechanism underlying LIPUS effectiveness is not yet understood, it is plausible to hypothesize a role for non-thermal phenomena, such as acoustic streaming, microstreaming, and mechanical stimulation. The vibratory effect of ultrasonic energy on the cell surface can activate some mechanically sensitive ion channels and induce changes in cell membrane permeability, thus stimulating the transport of second messenger substances, such as calcium, across the cell membrane. Second messengers can then up-regulate the production of growth factors and other signaling molecules, promoting the recovery of injured muscles. Reher et al. [ 113 ] observed that LIPU could stimulate the production of interleukin 8 (IL-8), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). VEGF can promote muscle fiber angiogenesis. bFGF can induce activation of quiescent satellite cells (located between the basal lamina and cell membrane of skeletal muscle fibers) into myoblasts, thereby contributing to muscle damage repair. Montalti et al. [ 114 ] showed that LIPUS exposure increased Cyclooxygenase-2 (COX-2) expression in the muscles of rats, and this finding was associated with the formation of new muscle fibers and more organized tissue structure in treated animals. A possible explanation relies on the fact that COX-2 is a key enzyme in converting arachidonic acid into prostanoids or prostaglandins. In particular, prostaglandin E2 (PGE2) is essential for efficacious skeletal muscle stem cell function, augmenting regeneration, and strength. Sugitta et al. [ 115 ] also observed that the stimulation of the abductor muscle in a rabbit model with increasing LIPUS intensity (between 0.21 and 0.48 W/cm 2 ) resulted in increasing NO levels through the induced nitric oxide synthase (iNOS)-dependent pathway, leading to increased vasodilation and blood flow independently of thermic effects. However, the effectiveness of LIPUS as a modality that can modulate muscle regeneration after muscle injury is still debated because some investigations have demonstrated no positive effect [ 116 , 117 , 118 ].

10.5.5. Bone

Diagnostic US performed on post-trauma soft tissues has shown to be able to identify occult fractures undetected by the previous X-ray [ 119 , 120 , 121 ]. Due to the different acoustic impedance between soft tissues and the bone cortex, US only allows the evaluation of the bone surface, which appears as a hyperechoic continuous line. A localized interruption of this hyperechoic line in an US is a hallmark of acute fracture. Associated findings are abnormalities of the periosteum (subperiosteal hematoma), adjacent soft tissues (local hematoma and edema), and joints (articular effusion). US plays a complementary role in the assessment of osteomyelitis, detecting subperiosteal effusion, as well as abscesses and fistula in the adjacent local soft tissues. Osteochondromas can be visualized as localized outgrowths of bone, in continuity with the normal cortex and medullary, covered by a cartilaginous cap. On the contrary, US has very limited capabilities in assessing other bone tumors [ 122 ].

The Food and Drug Administration (FDA) approved the use of low-intensity pulsed ultrasound (LIPUS) to accelerate the healing of fresh fractures in 1994 and for the treatment of non-unions in 2000 [ 123 ]. LIPUS has been shown to significantly increase the rate of fracture repair in various animal models [ 124 , 125 , 126 ]. Furthermore, several clinical trials have confirmed the efficacy of ultrasound in accelerating fracture healing in humans [ 127 , 128 ]. Effective exposure in accelerating fracture healing consists of a 200 µs pulsed burst of 1.5 MHz US waves repeating at 1 kHz and delivering 30 mW/cm 2 spatial-average and temporal-average (SATA) applied at the fracture site for 20 min per day [ 123 ]. Mechano-transduction pathways seem to be involved in cell responses. These include the activation of MAPK and other kinases pathways, gap-junctional cell-to-cell intercellular communication, up-regulation and clustering of integrins, the involvement of the COX-2-PEG2 and the iNOS/NO pathways, and activation of angiotensin II type I (ATI) mechanoreceptor [ 124 ]. Although the mechanisms by which LIPUS can trigger these effects remain unknown, the low-intensity exposures of LIPUS treatment make thermal effects unlikely. Possible mechanisms may, therefore, include mechanical effects, such as acoustic radiation force, acoustic streaming, and propagation of surface waves [ 124 ].

Dalecki et al. [ 129 ] reported that lithotripter pulses with amplitudes less than 1 MPa could produce vascular damage in late-term murine fetuses exposed in utero. Hemorrhages occurred only in tissues near developing bone (head, limbs, and ribs), whereas soft tissues distant from bone were unaltered. Moreover, no damage was observed in murine fetuses exposed to lithotripter pulses at a stage of gestation prior to bone formation. Successively, the same group of authors demonstrated that hemorrhage to tissues near developing fetal bone could also result from exposure of murine fetuses to pulsed ultrasound [ 130 ]. Hemorrhage occurred most frequently in the fetal head. The pressure threshold for producing hemorrhage to the fetal head was about 2.5 MPa negative pressure, and the threshold increased with increasing frequency (2.4 and 3.6 MHz). This threshold is above the current output limits of diagnostic devices. The physical mechanism for damage in tissues near fetal bone as a result of low-amplitude lithotripter fields or pulsed US has yet to be understood. Thermal effects are not justified by US parameters employed in both studies. The authors hypothesized a purely mechanical effect resulting in damage of fragile fetal vessels between partially ossified bones and surrounding tissues.

10.5.6. Lung

A healthy lung is scarcely penetrable for diagnostic US due to its air content. Because of the high difference in acoustic impedance, more than 96% of the US beam is reflected at the interface between chest wall tissues and pulmonary air interface, resulting in the so-called “hyperechoic pleural line”. However, US in the lung may aid in the detection of pleural effusions, pleural alterations, and peripheral pulmonary consolidations adhering to the superficial pleura. Furthermore, US has been demonstrated as safe and effective in guiding thoracentesis and percutaneous needle biopsy of pleural lesions and US-accessible peripheral lung consolidations. Lung examination is generally performed with a low multi-frequency convex probe (3.5–5 MHz). A high-frequency linear probe (8–12.5 MHz) may be used in order to obtain more detailed information on the appearance of the hyperechoic pleural line [ 131 ].

Child et al. [ 132 ] discovered the induction of pulmonary capillary hemorrhage using pulsed US more than 20 years ago. This bioeffect has been extensively studied in mice, rats, rabbits, and pigs. In a major review (AIUM, 2000 [ 37 ]), threshold trends for its occurrence were found to be near an MI value of 0.63. However, only one study each has been conducted on monkeys and humans. Tarantal and Canfield [ 133 ] showed some evidence of pulmonary hemorrhage in monkeys utilizing a commercial diagnostic US machine with a linear array. The hemorrhage itself mostly originated from the microvasculature of the visceral pleura. However, US-induced lung hemorrhage resulting from alveolar injury and congestion in alveolar capillaries was also documented. In contrast with experimental animals, humans did not appear to develop lung hemorrhage as a result of US exposure. A study of 50 humans was conducted by examining the left lungs after routine intraoperative transesophageal echocardiography with the highest MI output of 1.3. The surgery was mostly for coronary artery bypass grafting. None of the patients developed lung hemorrhage [ 134 ]. This result was considered to be uncertain with regard to pulmonary hemorrhage thresholds because the actual direct exposure of the lung to the highest pressure amplitudes was uncertain for these examinations.

In 2000, O’Brien et al. [ 135 ] observed that the occurrence of pulmonary hemorrhage was not inversely correlated with increased overpressure (i.e., hydrostatic pressure), which was used to reduce or eliminate the negative total pressure during the pulse. Furthermore, in another study, O’Brien et al. [ 136 ] observed that the injection of microbubbles did not increase the occurrence of pulmonary capillary hemorrhage during US exposure in rats. Similarly, in the study by Raeman et al. [ 137 ], the injection of contrast-agent microbubbles in mice did not increase the sensitivity to pulmonary hemorrhage compared to saline injection. These authors concluded that the mechanism of US-induced lung hemorrhage might not be directly related to inertial cavitation.

However, the presence of air in the lungs seems to be crucial for lung hemorrhage. In 2002, O’Brien et al. [ 138 ] observed that while pulmonary hemorrhage occurred in pregnant mice for 3.1 MHz pulsed US at 2 MPa, no signs of damage were found in the fetal lung, which lacks gas, even at 20 MPa. Transmission into the lungs varies with the degree of inflation, with deflated lungs more easily damaged than half-inflated lungs. The pulmonary hemorrhage effect did not appear to be caused by the heating of the lung tissue, which might be expected from the relatively high absorption coefficient of lung tissue [ 139 ]. In this regard, Hartman et al. [ 140 ] showed that the temperature elevation produced at the lung’s surface in mice was approximately only 1 °C after 5 min for a 4.2 MHz continuous wave of 1 W/cm 2 . On the other hand, Bayley et al. [ 141 ] showed that peak compressional pressure amplitudes ranging from 1 to 5 MPa are capable of producing hemorrhage in murine lungs in a strongly pressure-dependent manner. This study emphasizes that the threshold for lung hemorrhage is lower than other non-gas-containing tissues and that currently available diagnostic US devices may theoretically produce such injury.

The specific problem of pulmonary bioeffects from diagnostic US remains, therefore, difficult to address in terms of patient safety. However, morphologic studies have suggested that shorter, thinner, and less distensible terminal airways, a reduced alveolar surface tension and capillary surface area, and a lower thickness of the visceral pleura may determine a greater predisposition of mice, rats, and rabbits to the development of ultrasound-induced lung hemorrhage compared to primates and humans [ 11 ].

10.5.7. Digestive Tract

US is a noninvasive imaging test that is currently used in the complementary diagnosis of a wide range of abdominal issues safely.

The digestive tract naturally contains gas. The main segments of the digestive tract that may be exposed to diagnostic US during abdominal examination include the stomach, small intestine, large intestine, cecum, and colon. All these organs share a similar laminar structure organized in four concentric tissue layers. From the outside to the inside, these are the serosa (i.e., the peritoneum), the muscularis propria (consisting of an outer longitudinal and an inner circular smooth muscle layer), the submucosa, and the mucosa (organized in muscular mucosae, lamina propria, and epithelium). The inner mucosal epithelium is supported by a highly vascularised capillary bed within the lamina propria and looks into the internal lumen. Gaseous bodies of different sizes are present within the lumen in each digestive segment. Their amount and dimension can vary from segment to segment due to peristalsis.

Pulsed US exposure can result in the occurrence of intestinal hemorrhage in mice. In a study from Dalecki et al. [ 142 ], mice were irradiated using focused sources operating from 0.7 to 3.6 MHz for 5 min. The pressure threshold varied from 1 to 4 MPa in the frequency range. These thresholds are close to the current upper limit of diagnostic imaging devices. Higher frequencies were less effective in producing intestinal hemorrhage than lower frequencies. A temperature increment of only 1–2 °C degrees was documented at the highest exposure levels. These results suggested that the production of intestinal hemorrhage is consistent with a cavitation-related mechanism of action of pulsed US. Furthermore, lesions appeared to be associated with the mucosal surface and not the serosal surface of the intestine. Hemorrhage occurred in the mucosal-submucosal layer, and blood was evident within the lumen. Hemorrhage in the murine intestine has also been reported to result from exposure of mice to lithotripter fields where the mechanism is clearly non-thermal [ 143 , 144 ]. The presence of gas in the intestine seems to be necessary to produce intestinal hemorrhages with ultrasound. In 1995, Dalecki et al. [ 145 ] exposed pregnant mice to a lithotripter field of higher-pressure amplitude than the threshold causing intestinal damage in adult mice. Although the gas-containing maternal intestines were extensively damaged, the gas-free intestines of fetal mice were not.

Lehmann and Herrick [ 146 ] reported the production of petechial hemorrhage in the abdomen of mice exposed to continuous US waves at 1 MHz. The mechanism of damage was attributed to cavitation by these authors because the lesions had an appearance similar to that of mechanical injuries on histological examination. On the contrary, in the study by Miller and Thomas [ 147 ], the induction of petechiae by continuous US in mice intestines was associated with the occurrence of hyperthermia. These authors, therefore, concluded that the US-induced petechiae were attributable to heating and not cavitation. In addition, these authors observed that the petechiae arising from heating with continuous US were quite different from the intestinal hemorrhages induced by lithotripter shock waves. Ultrasonically-induced thermal petechiae were characterized by leakage of blood from the capillary vessels into the lamina propria (with no evident tissue destruction), while the shock-wave-induced hemorrhages involved blood flowing into the lumen of the intestine with histologically obvious tissue destruction and clotting.

The presence of US microbubble contrast agents in the vascular system has been shown to increase the extent of damage to the murine intestine exposed to both continuous and pulsed US. In general, the threshold for effect increases with increasing frequency and decreasing pulse duration [ 148 , 149 ]. Harmful side effects have not been reported in humans associated with the clinical application of continuous wave US (typical of therapeutic applications) or pulsed US (typical of diagnostic applications). Currently, there are no data indicating significant differences in the gut between or within species that could potentially influence susceptibility to ultrasound-induced intestinal haemorrhage [ 11 ]. These differences must be investigated.

11. Conclusions

To date, there are no reports in the literature of actual biological damage in patients undergoing diagnostic US. This has led to considering US to be a safe and well-tolerated diagnostic method with low biological risk. At present, there are not enough experimental data to concretely define the risk from exposure to low-power diagnostic US. The EFSUMB [ 57 ] and AIUM [ 58 ] have officially declared that acoustic power values commonly used in US diagnostics are safe. However, the use of TI and MI as “safety indices” has clear limitations based on their derivation from calculations giving estimates of “worst-case” average values in tissue model assumptions to the human being. Furthermore, the possibility of non-linear effects is not considered, and TI and MI indices may be inappropriate for new imaging techniques. For example, the use of color flow or pulsed Doppler US may increase the potential temperature rise by an “unknown factor”, and contrast-enhanced US (CEUS) lowers the cavitation threshold. ARFI SWE mode requires the employment of a MI no lower than 1.0 (from 1.3 to 1.6) and much longer pulses than those used in standard ultrasound (30–300 ms) to cause tissue displacement. In addition, the effects of very short-duration focused ARF energy peaks remain unknown and should be explored by further experimental studies. Despite no harmful biological effects yet demonstrated in humans with the new imaging modalities, in-depth knowledge of the potential risks of ultrasound-mediated biological effects is required. While the biological effects of diagnostic ultrasound continue to be investigated in research laboratories, physicians should reduce ultrasound exposure to as little as possible to obtain useful diagnostic information.

Funding Statement

This research received no external funding.

Institutional Review Board Statement

Informed consent statement, data availability statement, conflicts of interest.

The authors declare no conflict of interest.

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Stock symbols you'll LUV. Clever tickers help companies attract investors.

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A clever stock ticker is more than just a gimmick. Whether it's WOOF, EAT, or even the initials of a former president , a memorable stock symbol can help companies attract investors.

One 2006 study from Princeton University psychologists found that stocks with ticker symbols that are easier to pronounce tend to perform better in the days immediately after they start trading. Another from Pomona College in 2019 verified earlier research that found clever tickers tend to perform better, partly because they are more memorable to investors.

“There’s evidence that having a company name and ticker that investors like, that's easy to process, is valuable,” says Russell Jame , associate professor of finance at the University of Kentucky. “It generates more trading in the firm, so that improves the stock liquidity and it also results in a larger breadth of ownership and, ultimately, higher valuation ratios.”

One example of stock-ticker branding could hit the market next week. The parent company of  Truth Social , the social media platform that Donald Trump  launched  after getting booted from Facebook and Twitter after the Jan. 6 Capitol attack, may start trading on the stock market .

The ticker symbol? DJT, for Donald J. Trump. 

Here are just some of the more creative stock market symbols trading today.

WOOF: Petco Health and Wellness Company has been trading under the ticker “WOOF” since its IPO in 2021, amid the lockdown-fueled pet boom.

LUV: Southwest Airlines has had close ties to the word “love” since its inception in 1971 , when it announced its first service from Love Field in Dallas. The carrier's marketing team leaned into the name, and sold tickets to ride in “LUV seats” and served “LUV bites” and “LUV potions” to customers. 

Trump's financial woes: Can Truth Social deal save him from his cash crunch? Maybe.

TAP: Molson Coors Beverage, the parent company to Coors, Blue Moon, Keystone and other adult beverages, tapped into its brewery roots when picking a ticker symbol.

EAT: This one belongs to Brinker International. If the name’s not ringing a bell, you might be more familiar with its restaurant brands: Chili’s Grill & Bar and Maggiano’s Little Italy.

CAKE: What better company to own the CAKE ticker than Cheesecake Factory? 

Trump's Truth Social to go public: Social media platform parent company wins merger vote

FIZZ: National Beverage’s portfolio includes LaCroix and several other sparkling waters, juices, energy drinks, and carbonated soft drinks.

PLAY: Dave & Buster’s locations feature restaurants and bars, but the company emphasizes its video arcade offerings with its ticker symbol.

ZEUS: The ancient Greek god is a perfect fit for Olympic Steel Inc., an Ohio-based metals service center.

FUN: Cedar Fair, an amusement park operator, notes that it has “cornered the market on fun" with its ticker symbol.  

HOG: The nickname for Harley Davidson motorcycles goes back roughly a century. Ray Weishaar , a member of the company’s factory racing team in the early 1900s, adopted a piglet named Johnnie. The pet became a team mascot and would be carried on victory laps . Harley Davidson bikes would become known as hogs.


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