Good Vibration – Ultrasound as a New Mode of Neuromodulation

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Biomedical applications of ultrasound have taken great strides into a new arena of noninvasive brain stimulation (NIBS). The journey can be traced back to the work by E. Newton Harvey (an early 20th-century zoologist, also one of the early pioneers in bioluminescence research), who discovered that ultrasound modifies the function of electrically excitable biological tissues. Subsequent investigations by William and Francis Fry as well as Leonid Gavrilov during the 1950s have demonstrated that ultrasound can temporarily alter the function of the brain and the peripheral nerves.

Ultrasound technology has since evolved, enabling the delivery of highly focused acoustic energy not only to the cortical surface, but also to deep regions of the brain through the intact skull, with a focal size measuring only a few millimeters. The advent of this transcranial focused ultrasound (tFUS) technique is owed to the development of multi-array ultrasound transducer/control systems as well as advances in image-guidance methods through which the location and intensity of the invisible acoustic focus can be accurately controlled after being transmitted through the skull.

Armed with technological advances, together with the wisdom of the past, a series of studies through the last decade have revealed that FUS, given in a batch of pulses at a low intensity (below the threshold for heat generation or mechanical damage), can reversibly modulate (increase or decrease) the excitability of brain tissue.1–3 This revelation has opened new possibilities for tuning up/down regional brain function due to the exquisite spatial selectivity and depth control of tFUS.

Existing NIBS techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct/alternating current stimulation (tDCS/tACS), offer non-pharmacological alternatives for modifying brain function; however, they cannot reach deep brain areas with sufficient spatial selectivity. In addition, emerging evidence indicates that the modulatory effects of tFUS outlast the duration of sonication, which is critical for its therapeutic effects to occur.4,5 Together, noninvasive neuromodulation by ultrasound may present a unique opportunity to treat various brain-related conditions, ranging from neurological to psychiatric.

Although the precise mechanisms that underlie the neuromodulatory effects of ultrasound remain unclear, several candidate mechanisms have been proposed, including transient changes in transmembrane capacitance and subsequent effects on action potential generation, functional modulation of mechanosensitive ion channels, and the modification of glial cell excitability.6 It is quite exciting to witness a rising number of publications interrogating the mechanisms surrounding ultrasound-mediated neuromodulation.

Along with a promising safety record in small/large animals, non-human primates, and studies involving healthy individuals7, various clinical trials are being conducted or completed. Some examples include the treatment of major depressive disorder, epilepsy, Alzheimer’s disease, disorders of consciousness, and substance use disorder. The applications of ultrasound-mediated neuromodulation also extend to treating peripheral nerve diseases or noninvasive evaluation of regional brain function. The scope of clinical application is expected to expand since there are virtually no other known (noninvasive) means to selectively modulate local brain function across the brain volume.

So far, only a very limited number of incidents of minor discomfort (at the scalp) or temporary neurological symptoms (including ones that may not be directly related to the sonication) have been reported, which attest to the encouraging safety profile of this new technique. Notwithstanding, the absence of concrete information on the operational envelope and device characteristics impedes its rapid translation into clinical practice. Fortunately, a group of scientists, doctors, and engineers around the world have formed a consortium called the International Transcranial Ultrasonic Stimulation Safety and Standards (iTRUSST) and started to establish expert opinions and consensus on regulatory guidelines and standardization of the technique.8

With immense potential in introducing new treatment options, it will be interesting and exhilarating to see how ultrasound neuromodulation will become one of the mainstream neurotherapeutic modalities of the future.

References

1. Bystritsky A, Korb AS, Douglas PK, et al. A review of low-intensity focused ultrasound pulsation. Brain Stimul 2011; 4:125–136. doi:10.1016/j.brs.2011.03.007.

2. Darmani G, Bergmann TO, Butts Pauly K, et al. Non-invasive transcranial ultrasound stimulation for neuromodulation. Clin Neurophysiol 2022; 135:51–73. doi:10.1016/j.clinph.2021.12.010.

3. Arulpragasam AR, van ‘t Wout-Frank M, Barredo J, Faucher CR, Greenberg BD, Philip NS. Low intensity focused ultrasound for non-invasive and reversible deep brain neuromodulation-A paradigm shift in psychiatric research. Front Psychiatry 2022; 13:825802. doi:10.3389/fpsyt.2022.825802.

4. Verhagen L, Gallea C, Folloni D, et al. Offline impact of transcranial focused ultrasound on cortical activation in primates. Elife 2019; 8: e40541. doi:10.7554/eLife.40541.

5. Kim HC, Lee W, Weisholtz DS, Yoo SS. Transcranial focused ultrasound stimulation of cortical and thalamic somatosensory areas in human. PLoS ONE 2023; 18:e0288654. doi:10.1371/journal.pone.0288654.

6. Fomenko A, Neudorfer C, Dallapiazza RF, Kalia SK, Lozano AM. Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. Brain Stimul 2018; 11:1209–1217. doi:10.1016/j.brs.2018.08.013.

7. Lee W, Weisholtz DS, Strangman GE, Yoo SS. Safety review and perspectives of transcranial focused ultrasound brain stimulation. Brain Neurorehabil 2021; 14:e4. doi:10.12786/bn.2021.14.e4.

8. Attali D, Tiennot T, Schafer M, et al. Three-layer model with absorption for conservative estimation of the maximum acoustic transmission coefficient through the human skull for transcranial ultrasound stimulation. Brain Stimul 2023; 16:48–55. doi:10.1016/j.brs.2022.12.005.

About the Author

Seung Schik Yoo, PhD, MBA, is an Associate Professor of Radiology at Harvard Medical School, a Director of the Neuromodulation and Tissue Engineering Laboratory (NTEL) at Brigham and Women’s Hospital, and a faculty of Harvard’s Mind Brain Behavior Interfaculty Initiative.

Interested in reading more about neurosonology? Check out these posts from the Scan:

Ultrasound in the Diagnosis and Management of Chronic Obstructive Pulmonary Disease

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Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and debilitating respiratory condition that affects millions of people worldwide. While traditional diagnostic methods like spirometry and imaging techniques such as CT scans have played a vital role in managing this disease, ultrasound is emerging as a powerful tool in both diagnosis and treatment.

The Basics of COPD

COPD is a progressive lung disease characterized by the restriction of airflow due to chronic bronchitis and emphysema. The primary symptoms include breathlessness, coughing, and excessive mucus production. It is typically associated with a history of smoking, but environmental factors also play a role. Diagnosing and monitoring the progression of COPD is crucial for effective management.

The Role of Ultrasound in Diagnosis

Sonographic Assessment of Lung Morphology: Ultrasound imaging offers a noninvasive and radiation-free approach to assess lung morphology. Studies published in the Journal of Ultrasound in Medicine have demonstrated the effectiveness of ultrasound in evaluating lung parenchyma,1 pleura,1 and diaphragm.2 By examining these elements, clinicians can identify changes in the lung structure and rule out other conditions that might mimic COPD symptoms.

Evaluation of Diaphragm Function: COPD often affects diaphragm function, resulting in respiratory muscle weakness. Ultrasound allows for real-time assessment of diaphragm movement, enabling clinicians to detect early signs of diaphragmatic dysfunction.2 This information is valuable in selecting the appropriate treatment strategy for each patient.

Ultrasound-Guided Thoracentesis

In some cases, COPD patients develop pleural effusion, a condition characterized by an abnormal buildup of fluid in the pleural cavity. Ultrasound can be used to guide thoracentesis, a procedure in which this excess fluid is drained. A Journal of Ultrasound in Medicine report has highlighted the accuracy and safety of ultrasound guidance during this procedure, minimizing complications and improving patient outcomes.3

Monitoring Disease Progression

Ultrasound is not limited to the initial diagnosis but also plays a crucial role in monitoring COPD progression. Repeat ultrasound examinations can help evaluate changes in lung structure, assess diaphragm function, and track the effectiveness of ongoing treatments. Regular ultrasound monitoring can lead to more tailored and effective care plans for COPD patients.

Point-of-Care Ultrasound in COPD

Point-of-care ultrasound (POCUS) is a valuable tool for quickly assessing COPD exacerbations in emergency situations. It allows healthcare providers to rapidly evaluate lung abnormalities, pneumothorax, and pleural effusion, guiding immediate treatment decisions.4

Future Implications

As technology continues to advance, ultrasound is likely to play an even more prominent role in the diagnosis and management of COPD. Developments in portable and handheld ultrasound devices are making it easier for clinicians to perform ultrasound examinations at the bedside, providing real-time information to aid in decision-making.

Conclusion

The use of ultrasound in the diagnosis and management of COPD is a promising and evolving field. It offers a noninvasive, safe, and cost-effective means of assessing lung morphology, diaphragm function, and pleural effusion. With continued research and technological advancements, ultrasound is likely to become an indispensable tool in the fight against this chronic respiratory disease, helping patients receive more accurate diagnoses and tailored treatment plans.

References:

1. Martelius L, Heldt H, Lauerma K. B-lines on pediatric lung sonography: comparison with computed tomography. J Ultrasound Med 2016; 35:153–157. doi: 10.7863/ultra.15.01092.

2. Xu JH, Wu ZZ, Tao FY, et al. Ultrasound shear wave elastography for evaluation of diaphragm stiffness in patients with stable COPD: A pilot trial. J Ultrasound Med 2021; 40:2655–2663. doi: 10.1002/jum.15655.

3. Lane AB, Petteys S, Ginn M, Nations JA. Clinical importance of echogenic swirling pleural effusions. J Ultrasound Med 2016; 35:843–847. doi: 10.7863/ultra.15.05009.

4. Copcuoglu Z, Oruc OA. Diagnostic accuracy of optic nerve sheath diameter measured with ocular ultrasonography in acute attack of chronic obstructive pulmonary disease. J Ultrasound Med 2023; 42:989–995. doi: 10.1002/jum.16106.

Cynthia Owens, BA, is the Publications Coordinator for the American Institute of Ultrasound in Medicine (AIUM).

Interested in learning more about lung ultrasound? Check out the following articles from the American Institute of Ultrasound in Medicine’s (AIUM’s) Journal of Ultrasound in Medicine (JUM). After logging into the AIUM, members of AIUM can access them for free. Join the AIUM today!

The Potential of Ultrasound: Earlier Noninvasive Type 2 Diabetes Mellitus Detection

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Are you aware that type 2 diabetes mellitus (T2D) affects approximately 537 million adults worldwide, including 37.3 million in the USA? That is over 10% of the U.S. population! Approximately 79% of the people worldwide with T2D are underserved, underrepresented, impoverished, in lower socioeconomic communities, and in developing countries. Furthermore, the worldwide prevalence of T2D is expected to reach an astonishing 783 million by 2045.1–8

Even more shocking is that approximately 50% (232 million) of those people with T2D worldwide are unaware and undiagnosed! This is a major problem since, when T2D is finally detected, at the time of diagnosis, nearly one-half already have one or more irreversible complications resulting in an at least $966 billion global economic burden.

Also, a vast 81% with prediabetes (PreD), more than 77 million in the USA, are undiagnosed and unaware. However, in PreD, earlier lifestyle modifications reduce the risk of developing T2D by greater than 50%. These high numbers of undiagnosed people may be secondary to the lower accuracy of current screening methods in certain conditions and specific populations.

T2D leads to multiple costly serious end-organ complications, including being the leading cause of both end-stage renal disease and non-traumatic lower extremity amputations. Earlier detection is critical as earlier effective glycemic management reduces the risk of associated ophthalmologic, renal, and neurologic diseases by 40%. The urgency of this important matter has even prompted the United States Preventive Services Task Force to update guidelines in 2021 to help improve earlier T2D and PreD detection.1,3,4,9,10

Given its advantages over MRI, including low cost and portability, musculoskeletal (MSK) ultrasound (US) utilization, especially shoulder US, has significantly increased over the past few decades. Shoulder US is often performed on patients with T2D, given the high prevalence of T2D in society and the increased risk of rotator cuff pathology and adhesive capsulitis in individuals with T2D.9,10

As MSK US use increases, a unique opportunity arises for detecting T2D in those unaware, undiagnosed, and presenting for (seemingly) unrelated care. It is our experience and confirmed in our prior publications9,10 that the incidental detection of a hyperechoic deltoid muscle, on routine shoulder US (Figure 1), has on many occasions resulted in the incidental identification of undiagnosed T2D and even PreD. This abnormality was seen in those with and without obesity. Also, in those uncertain of their T2D status or told they were ‘borderline’, most were not treated, despite having this characteristic US deltoid muscle abnormality. Initial experiments also suggest that the hyperechoic deltoid muscle appearance may predate the elevation of HbA1c levels.

Figure 1. Long-axis US image of the right shoulder. a, Normal appearance of a hypoechoic deltoid muscle (solid arrow) in a 43-year-old woman without T2D or PreD. b, Abnormal hyperechoic deltoid (solid arrow) in a 47-year-old woman with T2D. The empty arrows indicate the supraspinatus tendon inserting on the greater tuberosity (arrowheads).

Skeletal muscle insulin resistance is thought to be the primary defect in T2D development, often occurring decades before β-cell failure and apparent metabolic dysfunction.11 Could this earlier-identified skeletal muscle US abnormality represent the noninvasive detection of early muscle insulin resistance and dysfunction, prior to clinically apparent metabolic dysfunction?

We continue to study this novel sonographic abnormality prospectively, including using histologic analyses. We expect our studies will help elucidate this US skeletal muscle abnormality, which could represent the earlier detection of muscle insulin resistance and dysfunction. This could initiate further studies on earlier noninvasive T2D detection, prevention, treatment, and targeted therapies for potential reversal.

References

1.         International Diabetes Federation. IDF diabetes atlas [Internet]. 10th ed. Brussels, Belgium: International Diabetes Foundation; 2021 [cited October 17, 2023].

2.         Centers for Disease Control and Prevention. National Diabetes Statistics Report website. [Internet]. Atlanta (GA): Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; 2022 [updated June 29, 2022; cited October 17, 2023]. 

3.         National Center for Chronic Disease Prevention and Health Promotion, Center for Disease Control and Prevention. Cost-effectiveness of diabetes interventions [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2022 [updated December 1, 2022; cited October 17, 2023].

4.         US Preventive Services Task Force, Davidson KW, Barry MJ, Mangione CM, et al. Screening for prediabetes and type 2 diabetes: US Preventive Services Task Force recommendation statement. JAMA 2021; 326:736–743. PMID: 34427594.

5.         Boyle JP, Honeycutt AA, Narayan KM, et al. Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U.S. Diabetes Care 2001; 24:1936–1940. PMID: 11679460.

6.         Lin J, Thompson TJ, Cheng YJ, et al. Projection of the future diabetes burden in the United States through 2060. Popul Health Metr 2018; 16(1):9. PMID: 29903012; PMCID: PMC6003101.

7.         Rowley WR, Bezold C, Arikan Y, Byrne E, Krohe S. Diabetes 2030: insights from yesterday, today, and future trends. Popul Health Manag 2017; 20(1):6–12. PMID: 27124621; PMCID: PMC5278808.

8.         National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Diabetes [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2021 [cited October 17, 2023].

9.         Soliman SB, Rosen KA, Williams PC, et al. The hyperechoic appearance of the deltoid muscle on shoulder ultrasound imaging as a predictor of diabetes and prediabetes. J Ultrasound Med 2020; 39:323–329. PMID: 31423604. https://onlinelibrary.wiley.com/doi/10.1002/jum.15110.

10.       Rosen KA, Thodge A, Tang A, Franz BM, Klochko CL, Soliman SB. The sonographic quantitative assessment of the deltoid muscle to detect type 2 diabetes mellitus: a potential noninvasive and sensitive screening method? BMC Endocr Disord 2022; 22(1):193. PMID: 35897066.

11.       DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009; 32(Suppl 2):S157–S163. PMID: 19875544; PMCID: PMC2811436.

Steven B. Soliman, DO, RMSK, FAOCR, is an associate professor and musculoskeletal radiologist at the University of Michigan.

Interested in reading more about MSK ultrasound? Check out these posts from the Scan:

How Can Ultrasound Contrast Agents Be Used to Sensitize Tumors to Radiation?

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Ultrasound contrast agents (UCAs) have the ability to go throughout the body and reach anywhere there is active vascularity. As clinicians and scientists, we use this to our advantage for diagnostic and therapeutic purposes. A unique characteristic of a UCA is its ability to generate nonlinear responses at sufficient pressure. These nonlinear responses produce harmonics in an acoustic field. UCAs undergo natural oscillations, and, at higher pressures, these UCAs can produce bioeffects. Inertial cavitation is the transient destruction of UCAs from increased pressure, while stable cavitation is a constant oscillation. Both of these cavitation states can produce shear stress on vessel walls, particularly endothelial cells.

Endothelial cells are the cell layer that lines all blood vessels in the body and are responsible for many functions but primarily control the passage of nutrients into tissues.1 In normal tissue, endothelial cells are uniform and form an organized monolayer network with tight junction connections.1 However, in tumor endothelial cells (TECs), it is much more of a chaotic process. In TECs, long, fragile cytoplasmic projections extend into the vessel lumen, creating small openings and gaps in the vessel wall.1 In addition to smaller gaps, larger openings (up to 1.5 µm) have also been identified, which make cell closures more difficult. These small and large gaps in TECs can be harnessed to produce endothelial cell apoptosis by destroying UCAs via inertial cavitation. Utilizing inertial cavitation has been shown to produce endothelial cell apoptosis (cell death) by generating bioeffects (ie, shock waves, microjets, micro streams, and thermal effects) that mechanically perturb TEC membranes.

Moreover, there are many components to a cell membrane, which goes beyond the scope of this blog post; however, sphingolipids are an essential enzyme to a cell membrane.2 Sphingolipids help maintain cellular homeostasis and are closely associated with cellular biologic functions, such as proliferation, apoptosis, or oxidative stress on endothelial cells.2 Some sphingolipids, such as ceramide, are important second signaling molecules that determine cell proliferation or death.

Traditionally, radiation therapy has been thought to act by damaging the DNA of cells via double and single DNA strand breaks, resulting in apoptosis. However, more recent studies have suggested that blood vessels are the determining factor of tumor response to radiation therapy at high doses (>8–19 Gy).3 Endothelial cells exposed to high doses of radiation upregulate the acid-sphingomyelinase pathway (ASMASE), which hydrolyzes sphingomyelin (dominant sphingolipid) into apoptosis, with ceramide acting as the second messenger. El Kaffas et al suggest that a primary factor why endothelial cells respond differently than other cell types is because endothelial cells have a 20x enrichment of a nonlyosomal secretory form of the ASMASE enzyme.4,5 This enzyme is associated with membrane remodeling, restructuring, responses to shear stress, and activation of ceramide from cell stressors.6,7 Additionally, endothelial cells are more sensitive to shear stress and mechanical forces.4 Radiation therapy and inertial cavitation treatments separately have been shown to produce tumor cell death. Combining these two treatments results in an increased accumulation of ceramide production and apoptosis, leading to improved tumor radiosensitivity.

Over the past decade, primarily in pre-clinical research, the benefits of combining microbubbles and radiation have been shown. From one of the original pre-clinical studies validating this concept, Czarnota et al showed that inertial cavitation and radiation therapy in a human prostate xenograft model in mice led to a 10-fold increase in ceramide-related endothelial cell death, confirming the benefits of the combined relationship.7 In addition, the study demonstrated a significant effect with a decreased radiotherapy dose (2 Gy versus 8 Gy) when combined with inertial cavitation compared to stand-alone treatment regimens. This mechanism has mainly been validated with in vivo studies. However, my group at Thomas Jefferson University has a first-ever pilot clinical trial incorporating ultrasound-triggered microbubble destruction (UTMD) to sensitize hepatocellular carcinoma in patients that receive the locoregional therapy, trans-arterial radioembolization (TARE).8 In an interim analysis, there was a greater prevalence of tumor response in the patients receiving TARE plus UTMD as opposed to in those who received TARE alone. Additionally, lab values and liver function tests demonstrated no significant differences between study groups, indicating that adding microbubble cavitation does not affect patient safety or liver functions.

This study is an ongoing clinical trial and will complete enrollment within the next 6 months, and this concept has been incorporated in non-HCC tumors in an ongoing pilot clinical trial at Thomas Jefferson University (NCT# 03199274). As a result of our research to date, we have learned that incorporating UTMD with radiation therapy may help sensitize tumors for improved survival and treatment outcomes. Additional clinical research is needed in this field because the combination treatment regimen may be easily incorporated into non-liver tumors.

References

  1. Dudley AC. Tumor endothelial cells. Cold Spring Harb Perspect Med 2012; 2:a006536. doi: 10.1101/cshperspect.a006536.
  2. Lai Y, Tian Y, You X, Du J, Huang J. Effects of sphingolipid metabolism disorders on endothelial cells. Lipids Health Dis 2022: 21(1):101. doi: 10.1186/s12944-022-01701-2.
  3. Paris F et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001; 293(5528):293–297. doi: 10.1126/science.1060191.
  4. El Kaffas A and Czarnota GJ. Biomechanical effects of microbubbles: from radiosensitization to cell death. Future Oncol 2015; 11(7):1093–1108. doi: 10.2217/fon.15.19.
  5. Tabas I. Secretory sphingomyelinase. Chem Phys Lipids 1999; 102(1):123–130. doi: 10.1016/S0009-3084(99)00080-8.
  6. El Kaffas A, Al-Mahrouki A, Hashim A, Law N, Giles A, Czarnota GJ. Role of acid sphingomyelinase and ceramide in mechano-acoustic enhancement of tumor radiation responses. J Natl Cancer Inst 2018; 110(9):1009–1018. doi: 10.1093/jnci/djy011.
  7. Czarnota GJ et al. Tumor radiation response enhancement by acoustical stimulation of the vasculature. Proc Natl Acad Sci U S A  2012; 109(30): E2033-E2041. doi: 10.1073/pnas.1200053109.
  8. Eisenbrey JR et al. US-triggered microbubble destruction for augmenting hepatocellular carcinoma response to transarterial radioembolization: a randomized pilot clinical trial. Radiology 2021; 298:450–457. doi: 10.1148/radiol.2020202321.

Corinne Wessner, MS, MBA, RDMS, RVT, is a research sonographer at Thomas Jefferson University and a PhD candidate at Drexel University in the School of Biomedical Engineering, Science and Health Systems in Philadelphia, PA. She is also Vice Chair of the American Institute of Ultrasound in Medicine’s (AIUM’s) High-Frequency Clinical and Preclinical Imaging Community (2023–2025).

Interested in reading more from Corinne Wessner? Check out these articles from the Journal of Ultrasound in Medicine (JUM). Members of AIUM can access them for free after logging in to the AIUM. Join the AIUM today!):

Ultrasound: How to respond to questions about its safety

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“Is ultrasound safe for my baby?” and “I know someone whose baby was born too small because of all the ultrasound she received during her pregnancy”. These are two sentences that you might hear during your busy day in the ultrasound unit. The AIUM Official Statement “Conclusions Regarding Epidemiology for Obstetric Ultrasound” states: “Based on the available epidemiologic data, there is insufficient justification to warrant conclusion of a causal relationship between diagnostic ultrasound and recognized adverse effects in humans. The epidemiologic evidence is based primarily on exposure conditions existing prior to 1992, the year in which maximum recommended levels of acoustic output for ultrasound machines were substantially increased for fetal/obstetric applications. Some older studies have reported effects of exposure to diagnostic ultrasound during pregnancy, such as low birth weight, delayed speech, dyslexia, and non-right-handedness. Other more recent studies have not demonstrated such effects. The absence of definitive epidemiologic evidence does not preclude the possibility of adverse effects of ultrasound in humans.”

Why is this statement important to all practitioners of ObGyn ultrasound?

Because knowing the information will enable you to answer patient questions and comments mentioned at the beginning of this post. What the AIUM statement explains is that studies performed on specific large human populations, with defined methods did not show that diagnostic ultrasound is responsible for harm in humans. (Studies such as this are what epidemiology does: examine how often diseases occur in different groups of people and why.)

While in the past, there were some publications that suggested some effects, such as low birth weight, more controlled studies have not been able to demonstrate such effects in humans. An important point is that many studies are relatively old and were performed before maximum recommended output of ultrasound machines meant for OB use was increased from 94mW/cm2 to 720mW/cm2.  This increase was intended to obtain more detailed images. The US Food and Drug Administration (USFDA) agreed with ultrasound instrument manufacturers’ requests to allow this increase, on the condition that two numbers were displayed in real-time on the monitor of the ultrasound system:

  • The thermal index (TI) to show the possibility of increased temperature, secondary to energy absorption by the tissues, and
  • The mechanical index (MI) to convey the risk of direct effects of the sound waves.

If these are kept low, no noxious effects are demonstrable, as expressed in the Epidemiology statement. This includes physical as well as mental effects. What are low indices? If the TI is <1 (the scientific number is 0.7, but 1 is easier to remember), there appears to be no risk of thermal effects for exposure under 1 hour. Regarding non-thermal or mechanical effects, based on the absence of gas bubbles in the fetal lungs and bowels (the two organs where effects were shown in animals after birth), no effects are expected in human fetuses. Demonstrating long-term effects or lack thereof, particularly if subtle, is much more complicated.

The statements issued by the AIUM’s Bioeffects Committee are intended as baseline considerations in practice. As ultrasound continues to be adopted into clinical use, the Bioeffects Committee will continue to monitor outcomes in order to inform and educate the community.

Jacques S. Abramowicz, MD, is a professor in the Department of Obstetrics and Gynecology at the University of Chicago.

Interested in learning more about the bioeffects of ultrasound? Check out the following AIUM Official Statements:

Also:

Abramowicz JS, Fowlkes JB, Stratmeyer ME, Ziskin MC. Bioeffects and Safety of Fetal Ultrasound Exposure: Why do we Need Epidemiology? In: Sheiner E, (ed.): Textbook of Epidemiology in Perinatology. New York: Nova Science Publishers, Inc.; 2010.

Screening for Chromosomal and Congenital Anomalies

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Screening for chromosomal and congenital anomalies has evolved significantly with the use of ultrasound. Adding Serum analytes to the evaluation of congenital anomalies has increased the detection rate. This addition includes maternal serum alpha fetoprotein (MSAFP), b-HCG, Estriol, Inhibin A, Free bHCG, and Pregnancy Associated Plasma Protein A (PAPP-A).

Sequential screening consists of two steps:

  1. Nuchal translucency (NT), with Free b-HCG and PAPP-A during the first trimester, and
  2. Quadruple testing during the second trimester.
    This modality takes the detection of trisomy 21 (T21) to 95%.

More recently, tests that measure the cell free fetal DNA (NIPT) in the maternal serum have become commercially available. The detection rate for T21 is 99%.

Many patients have opted for a first-trimester NT measurement, NIPT, and a 20-week ultrasound for anatomical survey. My concern and question to our group is where do we leave the MSAFP screening? Does your practice offer MSAFP to patients that opt for this approach?

Luis A. Izquierdo, MD, MBA, CPE, FAIUM, is a professor of OB GYN and Maternal Fetal Medicine at the University of New Mexico.

The Game-Changing Use of Ultrasound on the Sideline: Revolutionizing Sports Medicine

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In the world of sports, injuries are an unfortunate reality that athletes must face. Rapid and accurate diagnosis is crucial to ensure timely treatment and minimize downtime. Traditionally, athletes would have to undergo imaging scans off-site, resulting in delays and limited access to immediate medical care. However, with recent advancements in medical technology, ultrasound has emerged as a game-changing tool. The terms, “venue ultrasound” and “sideline ultrasound” refer to the use of ultrasonography at a sports venue, in a stadium, on the sideline of a sporting event, or in the athletic training room. Its portability and real-time imaging capabilities make it an invaluable asset for sports medicine providers. In fact, the pilot investigation using venue ultrasound at the 2020 Tokyo Olympic Games was successful in diagnosing injuries among athletes.1

Portable and Convenient
Ultrasound technology has undergone significant advancements, making it more compact, portable, and user-friendly. Modern handheld ultrasound devices are lightweight, battery-operated, and can be easily transported to sporting events or training facilities. This portability allows medical professionals to perform immediate on-site evaluations, enabling faster diagnosis and treatment decisions. The technology continues to evolve with many pocket-sized, handheld devices by leading manufacturers. Examples include the Philips Lumify, GE Vscan, Sonosite iViz, Butterfly iQ, Viatom, and Clarius. In addition, many of the units allow for easy wireless exchange of images and remote access by off-site professionals, if further assistance is needed.

Real-Time Imaging
One of the most significant advantages of sideline or venue ultrasound is its ability to provide real-time imaging. Unlike other imaging modalities, such as X-ray (XR) or magnetic resonance imaging (MRI), which require athletes to wait for results, ultrasound allows for immediate visualization of internal structures. This real-time feedback empowers medical staff to make quick and accurate diagnoses, as well as enables expedited triage of acute athlete conditions. This is particularly useful when XR is not readily available, which is commonplace at many events, particularly non-stadium venues.

Injury Assessment and Diagnosis
Portable handheld ultrasound devices can accurately assess soft tissue injuries, detect fractures, evaluate joint stability, and identify potential nerve or vascular involvement. During the last Olympics, ultrasound showed 100% accuracy in cases that underwent confirmatory imaging.1 In the emergency department (ED), which can be a similar setting to the sports sideline, point-of-care ultrasound (POCUS) enables appropriate medical decision-making using real-time imaging. Applications of POCUS for musculoskeletal conditions in the ED include joint effusions, long bone fractures, and muscle and tendon injuries.2 Long bone fractures can be excluded and tendon injuries can be diagnosed by physicians in the ED using POCUS with high sensitivity and specificity.3,4 Further, POCUS in the ED positively impacts medical decision-making for musculoskeletal complaints.5

Monitor Healing
Once an injury has occurred, ultrasound can be used to monitor the healing progress during the rehabilitation phase. Regular ultrasound assessments allow medical staff to evaluate tissue repair, assess the formation of scar tissue, and track the restoration of normal function. This real-time monitoring provides valuable insights into an athlete’s recovery trajectory, enabling adjustments to treatment plans as needed. This can be particularly helpful in athletic training room situations in determining time to return to play.6

Additional Applications
Sideline ultrasound has numerous applications in the care of athletes, including trauma assessments and guided injections. One notable application is the Focused Assessment with Sonography for Trauma (FAST) exam, which is a POCUS examination used to evaluate potential internal injuries, particularly within the abdomen and chest, in the context of acute trauma. While the FAST exam has more traditionally been utilized in the ED, it is becoming increasingly popular on the sideline. The exam involves using ultrasound to evaluate specific regions of the body quickly, aiding in the identification of potential organ damage or bleeding. It allows for rapid assessment and triage regarding further medical interventions or necessary actions. Meanwhile, ultrasound-guided injections and interventions have long been an essential component of sports medicine. The addition of ultrasound guidance enables medical providers to be more targeted in their treatments.

Limitations and Future Directions
While venue ultrasound has enhanced sports medicine, it is essential to acknowledge its limitations. The depth of penetration, image quality, time from injury, and operator dependence can impact the accuracy of diagnoses. Continued advancements in technology and ongoing training for sports medicine professionals are crucial to maximize the potential of sideline ultrasound.

Conclusion
The use of ultrasound on the sideline has revolutionized sports medicine, enabling rapid and accurate diagnosis of injuries. Its portability, real-time imaging capabilities, and dynamic ability to assess musculoskeletal injuries make it an invaluable tool for healthcare professionals on the sideline and in the training room. With further advancements, ultrasound’s role in sports medicine is poised to continue expanding, benefiting athletes worldwide by providing more immediate and personalized care. For further information on this topic, consider reviewing the AIUM webinar, Sideline Ultrasound (https://www.youtube.com/watch?v=aX-AibSfctc).

Robert Monaco and Lauren Rudolph.
Robert Monaco, MD, MPH, RMSK, is a physician at Atlantic Sports Health and is a team physician for USA Figure Skating. Lauren Rudolph, MD, is a physician at Boulder Biologics, adjunct faculty for ultrasound education at Rocky Vista University, and a traveling physician with the US Ski team.

References:

  1. Onishi K, Engebresten L, Budgett R, Soligard T, Forster BB. The International Olympic Committee venue ultrasound program: A pilot study from Tokyo 2020 Olympic Games. Am J Phys Med Rehabil 2023; 102:449–453. 
  2. Chen KC, Lin A, Chong CF. et al. An overview of point-of-care ultrasound for soft tissue and musculoskeletal applications in the emergency department. J Intensive Care 2016; 4:55.
  3. Waterbrook AL, Adhikari S, Stolz U, Adrion C. The accuracy of point-of-care ultrasound to diagnose long bone fractures in the ED. Am J Emerg Med 2013; 31:1352–1356.
  4.  Wu TS, Roque PJ, Green J, et al. Bedside ultrasound evaluation of tendon injuries. Am J Emerg Med 2012; 30:1617–1621.
  5. Situ-LaCasse E, Grieger RW, Crabbe S, Waterbrook AL, Friedman L, Adhikari L. Utility of point-of-care musculoskeletal ultrasound in the evaluation of emergency department musculoskeletal pathology. World J Emerg Med 2018; 9:262–266.
  6. Bailowitz Z, Visco C, Christen K, Ahmad C. Diagnostic musculoskeletal ultrasound for the acute evaluation and management of soccer players. Curr Sports Med Rep 2021; 20: 525–530.

Ultrasound: The Therapy of the Future Coming to a Clinic Near You!

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Ultrasound is most commonly known for diagnostic imaging and image-guided interventions, but there is also the potential to harness its power for therapeutic benefits. The use of ultrasound as a therapy is growing, with more than 1,900 active clinical investigations underway. There are also avenues to get insurance reimbursement for the treatment of certain ailments with ultrasound therapy, including bone metastases, essential tremor, and prostate.

In order to help guide physicians that may become involved in the use of ultrasound therapies, the Bioeffects Committee of the American Institute of Ultrasound in Medicine (AIUM) has issued new and updated statements on the AIUM website. These statements help to identify what to consider when using ultrasound therapies, including what happens to the targeted tissue and safety. Some highlights from these statements include:

  • Although safe when used properly for imaging, ultrasound can cause biological effects associated with therapeutic benefits when administered at sufficient exposure levels. Ultrasound therapeutic biological effects occur through two known mechanisms: thermal and mechanical. Thermal effects occur as the result of absorption of ultrasound waves within tissue, resulting in heating. Mechanical effects, such as fluid streaming and radiation force, are initiated by the transfer of energy/momentum from the incident pulse to tissue or nearby biofluids. Indirect mechanical effects can also occur through interaction of the ultrasound pulse with microbubbles such as ultrasound contrast agents. Importantly, thermal and mechanical mechanisms can trigger biological responses that result in desired therapeutic endpoints.
  • The type of bioeffects generated by ultrasound depend on many factors, including the ultrasound source, exposure conditions, presence of cavitation nuclei, and tissue type. Different bioeffects will require different amounts of ultrasound, and thermal and mechanical mechanisms can occur simultaneously for some exposure conditions.
  • There is the possibility of adverse effects in therapeutic ultrasound for targeted and untargeted tissue. Practitioners using these modalities must be well trained on the safe and effective use of therapeutic devices, knowledgeable about potential adverse events, aware of contraindications, and diligent in performing safe procedures. Image guidance should be used to ensure accurate targeting and dosing to maximize the outcomes for patients.

The statements issued by the AIUM’s Bioeffects Committee are intended as baseline considerations when a new therapy device is being put into practice. As ultrasound therapies continue to be adopted into clinical use, the Bioeffects Committee will continue to monitor outcomes in order to inform and educate the community.

Interested in learning more about the bioeffects of ultrasound? Check out the following Official Statements from the American Institute of Ultrasound in Medicine (AIUM):

Ultrasound to Differentiate Benign From Malignant Ovarian Tumors—Are We There Yet?

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Adnexal (ovarian) tumors present a complex problem. Ovarian cancer (Ovca) is the second most common gynecologic cancer in the United States with the highest mortality rate of all gynecologic cancer, 7th among all cancers, and with a general survival rate of 50%.1 Thus, missing Ovca when performing any kind of test (false negative) will have grave consequences but suspecting it when not present (false positive) can have almost as critical results with morbidity and mortality secondary to (unnecessary) intervention.

The purpose of this post is not to review the differential diagnosis of ovarian tumors nor to discuss chemical markers such as CA125 or cancer-specific signal found on cell-free DNA (cfDNA) but to concentrate on ultrasound. Some tumors are relatively easy to recognize because of defined ultrasound characteristics: corpus luteum with the classic “ring of fire” or endometrioma with the ground-glass appearance content, for instance (image 1a and b). Conversely, a large, multilocular lesion with solid components and profuse internal Doppler blood flow leaves little doubt about its malignant nature (image 2).

Image 1a: Corpus luteum with the classic
“ring of fire”.
Image 1b: Endometrioma with the
ground-glass appearance.
Image 2: A large, multilocular lesion with solid components.

What are the ultrasound characteristics we look at?

  1. Size: Unilocular cystic ovarian tumor < 10 cm in diameter or simple septated cystic ovarian tumor < 10 cm in diameter rarely, if ever, are neoplastic.2
  2. Volume: Normal volume for premenopausal and postmenopausal ovaries are < 20 cm3 and 10 cm3, respectively.
  3. Appearance: Risk of malignancy in simple, unilocular anechoic cyst, less than 5 cm is < 1% in premenopause and about 2.8% in postmenopause.3
  4. Blood flow criteria: The rationale is that arteries formed by neovascularization in malignant tumors lack tunica media, resulting in lowered impedance (= less resistance to blood flow). Thus, resistance indices will be lower in cancer than in benign tumors. Malignancy was suspected with Doppler indices: pulsatility index (PI)<1 and/or resistive index (RI)<0.4.4 However, too much overlap makes reliance on only Doppler unjustified.

A very important point is that the expert performs very well when analyzing the ultrasound images of an ovarian mass, with a sensitivity of 92–98% and a specificity of 89%. The issue is how to help the non-expert decide whether he/she can continue the care of the patient or needs to refer her to a specialist. Based on several ultrasound criteria, scoring systems were implemented. The first one, in 1990, included appearance (unilocular, unilocular solid, multilocular, multilocular solid, or solid cyst) and presence of papillae (graded according to their number: 0 [none], 1 [one to five], or 2 [more than five]). This method had a sensitivity (true positive rate, or chance that person testing positive actually has Ovca) for malignancy of 82% with a specificity (true negative rate or chance that person with a negative test does not have Ovca) of 92%.5 Two important additional scoring systems were described later: the Morphology Index (MI) combining tumor volume, wall structure, and septal structure and the Risk of Malignancy Index (RMI), the product of ultrasound morphology score, CA 125 level, and menopausal status.6 Additional systems included the Logistic Regression 1 (LR1) and 2 (LR2). None of the published scoring systems were superior to image assessment by an expert, including in a meta-analysis of 47 articles, including over 19000 adnexal masses7 and, in reality, were not used widely in clinical practice.

The International Ovarian Tumor Analysis (IOTA) models

In 2000, a large group of European experts (gynecologists, radiologists, statisticians, biology, and computer experts) published a standardized terminology for the characterization of adnexal masses.8

The two important systems are the Simple Rules (SR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model. These were externally validated in numerous centers across the world but not in the USA.9 Recently, however, validation on the largest hitherto US population was published.10 This study showed for the first time that the models were effective in this population, regardless of menopausal status or race. These models are easy to learn and are geared towards non-experts.11 It is important to note that the IOTA group was one of the first to incorporate acoustic shadow as a key feature, and the acoustic shadow has been shown to be an important sonographic feature to consider.12

  1. Simple Rules: The IOTA Simple-Rules consist of 2 sets of 5 elements each: benign and malignant.13 Three simple rules are applied: if only benign characteristics are present, the mass is classified as benign. If only malignant features are present, the mass is considered malignant. If no features or both are, the findings are inconclusive. This model works well in about 80% of cases. The other 20% should be referred to an expert.
  2. ADNEX model14: This is a multiclass prediction model to differentiate between benign and malignant tumors and allows automatic calculation of sub-classification of malignant tumors into borderline tumors, Stage I, and Stage II–IV primary cancers, and secondary metastatic tumors. “The advantage of this model is that it gives a personalized risk score for each patient, based on age, whether the patient is seen at an oncology center or not, maximal diameters of the lesion and the solid parts, number of cysts and papillary projections, whether acoustic shadows are present, whether ascites is present and CA125 value (if available, not mandatory for calculation). With a cut-off value for malignancy risk set at 10%, the ADNEX model (with CA125) had a sensitivity of 94.3%, with a specificity of 74%, positive predictive value of 76%, and negative predictive value of 93.6%.”14

The O-RADS model

In 2020, the American College of Radiology convened an international multidisciplinary committee that developed an ultrasound model based on an MRI model used in mammography (the BI-RADS atlas), the O-RADS model (the Ovarian-Adnexal Reporting and Data System) to facilitate differentiation between benign and malignant ovarian tumors.15 It relies on the sonographic nomenclature developed by the IOTA group, but it classifies tumors into 1 of 6 categories (O-RADS 0–5), from normal to high risk of malignancy. O-RADS also includes guidelines for the management of the findings. It should be noted that the O-RADS first model did not take into account the presence or absence of an acoustic shadow, although this has now been amended.

A description of the most recent common ultrasound scoring systems (SR, ADNEX, and O-RADS) is available in the Journal of Ultrasound in Medicine (JUM): Yoeli-Bik R, Lengyel E, Mills KA, Abramowicz JS. Ovarian masses: The value of acoustic shadowing on ultrasound examination. J Ultrasound Med 2023; 42:935–945.    

References

  1. https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html
  2. Saunders et al. Risk of malignancy in sonographically confirmed septated cystic ovarian tumors. Gynecol Oncol 2010; 118:278–282.
  3. Valentin et al. Risk of malignancy in unilocular cysts: a study of 1148 adnexal masses classified as unilocular cysts at transvaginal ultrasound and review of the literature. Ultrasound Obstet Gynecol 2013; 41:80–89.
  4. Bourne et al. Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer. BMJ 1989; 299:1367–370.
  5. Granberg S et al. Tumors in the lower pelvis as imaged by vaginal sonography. Gynecol Oncol 1990; 37: 224–229.
  6. Yamamoto Y, Yamada R, Oguri H, Maeda N, Fukaya T. Comparison of four malignancy risk indices in the preoperative evaluation of patients with pelvic masses. Eur J Obstet Gynecol Reprod Biol 2009; 144:163–167.
  7. Meys EM et al. Subjective assessment versus ultrasound models to diagnose ovarian cancer: A systematic review and meta-analysis. Eur J Cancer 2016; 58:17–29.
  8. Timmerman D, Van Calster B, Testa A, et al. Predicting the risk of malignancy in adnexal masses based on the simple rules from the international ovarian tumor analysis group. Am J Obstet Gynecol 2016; 214:424–437.
  9. Abramowicz JS, Timmerman D. Ovarian mass-differentiating benign from malignant: the value of the International Ovarian Tumor Analysis ultrasound rules. Am J Obstet Gynecol 2017; 217:652–660.
  10. Yoeli-Bik R, Longman RE, Wroblewski K, Weigert M, Abramowicz JS, Lengyel E. Diagnostic performance of ultrasonography-based risk models in differentiating between benign and malignant ovarian tumors in a US cohort. JAMA Netw Open 2023; 6:e2323289.
  11. Valentin L, Ameye L, Jurkovic D, et al. Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings and is there a way of making a correct diagnosis? Ultrasound Obstet Gynecol 2006; 27:438–444.
  12. Yoeli-Bik R, Lengyel E, Mills KA, Abramowicz JS. Ovarian masses: The value of acoustic shadowing on ultrasound examination. J Ultrasound Med 2023; 42:935–945.
  13. Timmerman D, Testa AC, Bourne T, et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 2008; 31:681–90.
  14. Van Calster B, et al. Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study. BMJ 2014; 349:g5920.
  15. Andreotti RF, Timmerman D, Strachowski LM, et al. O-RADS US risk stratification and management system: a consensus guide-line from the ACR ovarian-adnexal reporting and data system committee. Radiology 2020; 294:168–185.

Appendix

Classification of primary ovarian tumors

  1. Ovulatory: functional or corpus luteum cyst; theca lutein cyst; polycystic ovary
  2. Infectious or inflammatory: tubo-ovarian abscess; hydrosalpinx
  3. Benign: serous or mucinous cystadenoma; endometrioma; mature cystic teratoma (most common primary benign tumor of the ovary); paraovarian/paratubal cysts
  4. Borderline: serous, mucinous
  5. Malignant
  6. Epithelial: high-grade serous carcinoma (HGSC; 70 to 80%); endometrioid carcinoma (10%); clear cell carcinomas (10%); mucinous carcinoma (3%); Low-grade serous carcinoma (LGSC; <5%); Brenner tumor; carcinosarcoma or malignant mixed müllerian tumor (MMMT); undifferentiated,
  7. Germ cell (20%): teratoma: immature, specialized teratomas of the ovary (struma ovarii, carcinoid tumor); dysgerminoma; yolk sac tumor: endodermal sinus tumor; embryonal carcinoma; choriocarcinoma: <1% of ovarian tumors; malignant mixed germ cell tumor
  8. Sex cord / stromal ovarian tumors (8–10%): fibrothecoma (fibroma, thecoma); Sertoli-Leydig cell tumor; granulosa cell tumor (juvenile or adult); small cell carcinoma

Jacques S. Abramowicz, MD, is a professor in the Department of Obstetrics and Gynecology at the University of Chicago.

Interested in learning more about gynecologic ultrasound? Check out the following posts from the Scan:

Lymphosonography: The use of contrast-enhanced ultrasound as a lymphatic mapping technique

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Ipsilateral axillary diagnostic ultrasound is part of the initial staging for breast cancer to evaluate lymph nodes using a b-mode classification where certain aspects, when present, increase the level of suspicion for metastatic disease, such as cortical thickening and poor hilar visibility.1–3 Diagnostic ultrasound is also used as a method to guide biopsies of the suspicious lymph nodes.1

The majority of patients will have no suspicious lymph nodes findings at the time of diagnosis, the lymphatic system mapping after the injection of blue dye and/or a radioactive tracer followed by a surgical excision becomes the only way to determine the final stage of disease. However, these methods have limitations such as the use of radiation and lack of an imaging component.

In the past, ultrasound could not be used for lymphatic mapping, since mapping requires administration of a tracer. This changed with the use of contrast-enhanced ultrasound (CEUS) to detect lymph nodes after subcutaneous injections of microbubble-based ultrasound contrast agents (UCA), termed “lymphosonography”.4–6 The development of the lymphosonography technique addressed the limitations of the currently used lymphatic mapping techniques.

Our group conducted a clinical trial to evaluate the efficacy of CEUS lymphosonography in the identification of sentinel lymph nodes (SLN) in patients with breast cancer undergoing surgical excision following the injection of blue dye and radioactive tracer as part of their standard of care using pathology results for malignancy as a reference standard.6,7

In the clinical trial, 86 subjects were enrolled and 79 completed the study. The subjects received 4 subcutaneous injections of ultrasound contrast agent around the tumor, for a total of 1.0 ml. A clinical ultrasound scanner with CEUS capabilities was used to identify SLNs. After the ultrasound study examination, the subjects received blue dye and radioactive tracer for guiding SLN excision as part of their standard of care. The SLNs excised during the standard-of-care surgical excision were classified as positive or negative for presence of blue dye, radioactive tracer and UCA, and sent for pathology to determine presence or absence of metastatic involvement.

Example of a sentinel lymph node (SLN) seen with lymphosonography. The arrow indicates the SLN. The arrowhead indicates the lymphatic channel.

A total of 252 SLNs were excised from the 79 subjects. Of the 252 SLNs excised, 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Statistical comparison showed that compared with the reference standards, lymphosonography showed similar accuracy with radioactive tracer (p > 0.15) and higher accuracy (p < 0.0001). The pathology results showed that, of the 252 SLNs excised, 34 had metastatic involvement and were determined malignant by pathology. Of these 34 SLNs, 18 were positive for blue dye (detection rate of 53%), 23 were positive for radioactive tracer (detection rate of 68%) and 34 were positive for UCA (detection rate of 100%; p < 0.0001).

The conclusion of this study indicates that lymphosonography had similar accuracy as the standard-of-care methods for identifying SLNs in breast cancer patients, with the added advantage of an imaging component that allows for a preoperative evaluation of SLNs and that lymphosonography may be a more specific and precise approach to SLN identification in patients with breast cancer.6

Larger multicenter clinical trials are necessary to be able to translate this technique to the clinical setting and to be able to incorporate it as part of the breast cancer patients’ standard of care.

  1. Voit CA, van Akkooi ACJ, Schäfer-Hesterberg G, et al. Rotterdam Criteria for sentinel node (SN) tumor burden and the accuracy of ultrasound (US)-guided fine-needle aspiration cytology (FNAC): can US-guided FNAC replace SN staging in patients with melanoma? J Clinical Oncol 2009; 27(30):4994–5000.
  2. Dialani V, Dogan B, Dodelzon K, Dontchos BN, Modi N, Grimm L. Axillary imaging following a new invasive breast cancer diagnosis—A radiologist’s dilemma. J Breast Imaging 2021; 3:645–658.
  3. Chang JM, Leung JWT, Moy L, Ha SM, Moon WK. Axillary nodal evaluation in breast cancer: state of the art. Radiology 2020; 295:500–515.
  4. Goldberg BB, Merton DA, Liu J-B, Thakur M, et al. Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. Radiology 2004; 230:727–734.
  5. Goldberg BB, Merton DA, Liu J-B, Murphy G, Forsberg F. Contrast‐enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes. J Ultrasound Med 2005; 24:953–965. doi: 10.7863/jum.2005.24.7.953.
  6. Machado P, Liu J-B, Needleman L, et al. Sentinel lymph node identification in patients with breast cancer using lymphosonography. Ultrasound Med Biol 2023; 49:616–625. Epub 2022 Nov 26.
  7. Machado P, Liu JB, Needleman L, et al. Sentinel lymph node identification in post neoadjuvant chemotherapy breast cancer patients undergoing surgical excision using lymphosonography. J Ultrasound Med 2023; 42:1509–1517. doi: 10.1002/jum.16164. Epub 2023 Jan 2.

Priscilla Machado, MD, FAIUM, is a Research Assistant Professor in the Department of Radiology at Thomas Jefferson University in Philadelphia, PA.

Interested in learning more about ultrasound? Check out these posts from the Scan: