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BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020

Objectives Hepatic venous pressure gradient (HVPG) is considered the standard in quantifying portal hypertension, but can be unreliable in dialysis patients. A noninvasive ultrasound technique, subharmonic-aided pressure estimation (SHAPE), may be a valuable surrogate of these pressure estimates. This study compared SHAPE and HVPG with pathology findings for fibrosis in dialysis patients. Methods This was a subgroup study from an IRB-approved trial that included 20 patients on dialysis undergoing SHAPE examinations of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI), during infusion of Sonazoid (GE Healthcare, Oslo, Norway). SHAPE was compared to HVPG and pathology findings using the Ludwig-Batts scoring system for fibrosis. Logistic regression, ROC analysis, and t-tests were used to compare HVPG and SHAPE with pathological findings of fibrosis. Results Of 20 cases, 5 had HVPG values corresponding to subclinical and clinical portal hypertension (≥6 and ≥10 mmHg, respectively) while 15 had normal HVPG values (≤5 mmHg). SHAPE and HVPG correlated moderately (r = 0.45; P = .047). SHAPE showed a trend toward correlating with fibrosis (r = 0.42; P = .068), while HVPG did not (r = 0.18; P = .45). SHAPE could differentiate between mild (stage 0-1) and moderate to severe (stage 2-4) fibrosis (-10.4 ± 4.9 dB versus -5.4 ± 3.2 dB; P = .035), HVPG could not (3.0 ± 0.6 mmHg versus 4.8 ± 0.7 mmHg; P = .30). ROC curves showed a diagnostic accuracy for SHAPE of 80%, while HVPG reached 76%. Conclusion Liver fibrosis staging in dialysis patients evaluated for portal hypertension appears to be more accurately predicted by SHAPE than by HVPG; albeit in a small sample size.

Background Small intestinal ischemia is a challenging diagnosis to make, even with the combination of imaging, laboratory analysis, and physical exam. This pilot study investigated the role of CEUS in evaluating small bowel wall vascularity in participants with suspected ischemia. Methods In this IRB-approved pilot study, CEUS using perflutren lipid microspheres (DEFINITY®; Lantheus Medical Imaging Inc., N. Billerica, MA) was performed on participants determined by the clinical surgical team to have concerns for small intestinal ischemia. CEUS interpretations were performed at both the bedside and later by a blinded radiologist and compared to clinical imaging, surgical findings, or long-term clinical outcomes. Results Fifteen CEUS examinations were performed on 14 participants. Five of the participants underwent exploratory laparotomy. Of these, one had small intestinal ischemia (without necrosis). Point of care CEUS demonstrated no evidence of bowel necrosis in any case, and delayed enhancement (indicative of intestinal ischemia) in three cases, resulting in a sensitivity of 100% (95% CI 2.5-100%) and specificity of 85.7% (95% CI 57.2-98.2%). CEUS correctly ruled out ischemia in 91.7% of cases with CT suspicion of small bowel obstruction and 60% of cases that underwent surgical intervention. Additionally, the rate of agreement between bedside interpretation and later radiologist read was high (93%). Conclusions CEUS is uniquely positioned for evaluating the small intestine, because of its high temporal resolution and immediacy of results. Combined with multi-sectional imaging for focal areas of ischemia and/or clinical suspicion for pan ischemia, CEUS may be a useful rule out test for small intestinal ischemia.

BACKGROUND: Portal hypertension is the underlying cause of most complications associated with cirrhosis, with the hepatic venous pressure gradient (HVPG) used for diagnosis and disease progression. Subharmonic imaging (SHI) is a contrast-specific imaging technique receiving at half the transmit frequency resulting in better tissue suppression. AIMS: To determine if the presence of optimized SHI signals inside the hepatic vein can be used as a screening test for portal hypertension. METHODS: This prospective trial had 131 patients undergoing SHI examination of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI). Images acquired after infusion of the ultrasound contrast agent Sonazoid (GE Healthcare, Oslo, Norway) were assessed for the presence of optimized SHI signals in the hepatic vein and compared to the HVPG values obtained as standard of care. RESULTS: Of 131 cases, 64 had increased HVPG values corresponding to subclinical (n=31) and clinical (n=33) portal hypertension (>6 and >10 mmHg, respectively) and 67 had normal HVPG values (

Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44; P < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements (r = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.

OBJECTIVES To investigate the long-term impact of contrast-enhanced ultrasound (CEUS) on the treatment of patients with indeterminate renal masses. METHODS In this retrospective study, consecutive charts of all patients receiving renal CEUS at 1 of 2 academic medical centers between January 1, 2014, and December 31, 2018, were reviewed. Patients were included in the study if they had documented chronic renal disease (estimated glomerular filtration rate

Advances in modern clinical ultrasound include developments in ultrasound signal processing, imaging techniques and clinical applications. Improvements in ultrasound processing include contrast and high-fidelity ultrasound imaging to expand B-mode imaging and microvascular (or microluminal) discrimination. Similarly, volumetric sonography, automated or intelligent ultrasound, and fusion imaging developed from the innate limitations of planar ultrasound, including user-operator technical dependencies and complex anatomic spatial prerequisites. Additionally, ultrasound techniques and instrumentation have evolved towards expanding access amongst clinicians and patients. To that end, portability of ultrasound systems has become paramount. This has afforded growth into the point-of-care ultrasound and remote or tele-ultrasound arenas. In parallel, advanced applications of ultrasound imaging have arisen. These include high frequency superficial sonograms to diagnose dermatologic pathologies as well as various intra-cavitary or lesional interrogations by contrast-enhanced ultrasound. Properties such as realtime definition and ease-of-access have spurned procedural and interventional applications for vascular access. This narrative review provides an overview of these advances and potential future directions of ultrasound.

The mainstay of treatment for unresectable hepatocellular carcinoma is locoregional therapy including percutaneous ablation and transarterial chemo- and radioembolization. While monitoring for tumor response after transarterial chemoembolization is crucial, current imaging strategies are suboptimal. The standard of care is contrast-enhanced magnetic resonance imaging or computed tomography imaging performed at least 4 to 6 weeks after therapy. We present a case in which contrast-enhanced ultrasound identified a specific extra-hepatic collateral from the gastroduodenal artery supplying residual viable tumor and assisting with directed transarterial management. Keywords: Transarterial chemoembolization, Contrast-enhanced ultrasound, Hepatocellular carcinoma

Contrast-enhanced ultrasound (CEUS) has evolved from the use of agitated saline to second generation bioengineered microbubbles designed to withstand insonation with limited destruction. While only one of these newer agents is approved by the Food and Drug Administration for use outside echocardiography, interventional radiologists are increasingly finding off-label uses for ultrasound contrast agents. Notably, these agents have an extremely benign safety profile with no hepatic or renal toxicities and no radiation exposure. Alongside diagnostic applications, CEUS has begun to develop its own niche within the realm of interventional oncology. Certainly, the characterization of focal solid organ lesions (such as hepatic and renal lesions) by CEUS has been an important development. However, interventional oncologists are finding that the dynamic and real-time information afforded by CEUS can improve biopsy guidance, ablation therapy, and provide early evidence of tumor viability after locoregional therapy. Even more novel uses of CEUS include lymph node mapping and sentinel lymph node localization. Critical areas of research still exist. The purpose of this article is to provide a narrative review of the emerging roles of CEUS in interventional oncology.

IMPORTANCE: Thyroid nodules are common incidental findings. Ultrasonography and molecular testing can be used to assess risk of malignant neoplasm. OBJECTIVE: To examine whether a model developed through automated machine learning can stratify thyroid nodules as high or low genetic risk by ultrasonography imaging alone compared with stratification by molecular testing for high- and low-risk mutations. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study was conducted at a single tertiary care urban academic institution and included patients (n = 121) who underwent ultrasonography and molecular testing for thyroid nodules from January 1, 2017, through August 1, 2018. Nodules were classified as high risk or low risk on the basis of results of an institutional molecular testing panel for thyroid risk genes. All thyroid nodules that underwent genetic sequencing for cytological results with Bethesda System categories III and IV were reviewed. Patients without diagnostic ultrasonographic images within 6 months of fine-needle aspiration or who received definitive treatment at an outside medical center were excluded. MAIN OUTCOMES AND MEASURES: Thyroid nodules were categorized by the model as high risk or low risk using ultrasonographic images. Results were compared using genetic testing. RESULTS: Among the 134 lesions identified in 121 patients (mean [SD] age, 55.7 [14.2] years; 102 women [84.3%]), 683 diagnostic ultrasonographic images were selected. Of the 683 images, 556 (81.4%) were used for training the model, 74 (10.8%) for validation, and 53 (7.8%) for testing. Most nodules had no mutation (75 [56.0%]), whereas 43 nodules (32.1%) had a high-risk mutation and 16 (11.9%) had an unknown or a low-risk mutation (χ(2) = 39.060; P

This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict long term response of hepatocellular carcinoma (HCC) to Yttrium-90 (Y-90) radioembolization therapy. Twelve patients scheduled for Y-90 radioembolization therapy of a previously untreated HCC underwent CEUS at 3 time points: immediately following treatment, and 7 and 14 days post-treatment. Ultrasound imaging was performed using a Siemens S3000 Helx scanner with a C6-1 probe in dual 2D B-mode/contrast mode. Treatment response was evaluated with MRI 3-4 months post-treatment using modified response evaluation criteria in solid tumors (mRECIST) by two experienced radiologists in consensus. CEUS data was analyzed by quantifying tumor perfusion and residual fractional vascularity, using contrast time intensity curves that were created off-line. At 7 days post-treatment, the patient with stable disease exhibited significantly greater tumor vascularity (70.96 ± 7.63%) than patients with partial response (30.88 ± 20.56%, p < 0.0001) and complete response (13.64 ± 10.97%, p < 0.0001). Additionally, patients with stable disease exhibited significantly greater tumor perfusion 14 days post-treatment (2.33 ± 0.22 ml/s*mg) than both partial response (0.05 ± 0.05 ml/s*mg, p < 0.0001) and complete response patients (0.47 ± 0.46 ml/s*mg, p < 0.0001). Although larger sample sizes and longer follow up are needed to fully evaluate the clinical impact of CEUS, it appears to provide an earlier indicator of Y-90 treatment response than MRI.

Objective: This study evaluated the performance of automated machine-learning to diagnose non-alcoholic fatty liver disease (NAFLD) by ultrasound and compared these findings to radiologist performance.Methods: 96 patients with histologic (33) or proton density fat fraction MRI (63) diagnosis of NAFLD and 100 patients without evidence of NAFLD were retrospectively identified. The “Fatty Liver” label included 96 patients with 405 images and the “Not Fatty Liver” label included 100 patients with 500 images. These 905 images made up a “Comprehensive Image” group. A “Radiology Selected Image” group was then created by selecting only images considered diagnostic by a blinded radiologist, resulting in 649 images. Cloud AutoML Visionbeta (Google LLC, Mountain View, CA) was used for machine learning. The models were evaluated against three blinded radiologists.Results: The “Comprehensive Image” group model demonstrated a sensitivity of 88.6% (73.3-96.8%) and a specificity of 95.3% (84.2-99.4%). Radiologist performance on this image group included a sensitivity of 81.0% (74.3-87.6%) and specificity of 86.0% (72.6-99.5%). The model’s overall accuracy was 92.3% (84.0-97.1%), compared with mean individual performance (83.8%, 78.4-89.1%). The “Radiology Selected Image” group model demonstrated a sensitivity of 88.6% (73.3 - 96.8%) and specificity of 87.9% (71.8-96.6%). Mean radiologist sensitivity was 92.4% (86.9-97.9%) and specificity was 91.9% (83.4-100%). The model’s overall accuracy was 88.2% (78.1-94.8%) which was comparable to the individual radiologist performance (92.2%, 90.1-94.2%) and consensus performance (95.6%, 87.6-99.1%).Conclusions: An automated machine-learning algorithm may accurately detect NAFLD on ultrasound.

Endovascular repair of abdominal aortic aneurysms have been performed successfully since 1991. However, 20% to 50% of these patients may develop an endoleak or continued aneurysmal sac expansion or perfusion despite stent graft coverage. Current recommendations suggest lifelong surveillance with computed tomographic angiography (CTA) at least 1 month after intervention and yearly after that. In select patients with a stable aneurysm sac on computed tomography performed 1 year after treatment, future screening could be performed with ultrasonography. However, color Doppler ultrasound can fail to detect as many as 31% of endoleaks. Contrast-enhanced ultrasound (CEUS) provides an alternative approach to excluded aneurysm sac follow-up imaging. The Society for Vascular Surgery notes a need for further research on the role of CEUS in endovascular aortic repair surveillance. The European Federation of Societies for Ultrasound in Medicine and Biology suggests that early results are promising. Meta-analyses report pooled sensitivities and specificities of CEUS compared with CTA for the detection of endoleak between 89% and 98% and 86% and 88%, respectively. Owing to the dynamic flow information it provides, CEUS may actually be more sensitive than CTA at detection and characterization in select circumstances. Challenges with adoption, patient selection, and operator dependency remain, but current and future research suggests a role for CEUS in endoleak surveillance.

Colon cancer remains the most common abdominal visceral malignancy affecting both men and women in America. Open colectomy has been the standard of care for colon cancer patients the past 100 years; although highly effective, the major trauma associated with it has a significant morbidity rate and represents a large operation for patients to recover from. Minimally invasive colon surgery was developed as a new and alternative option, and surgeons aim to continue to make it simpler, more reproducible, and easier to teach and learn. We describe herein the current state of minimally invasive colorectal surgery for colon cancer and compare it with open surgery to offer insights to future directions.

With almost $35 billion appropriated in government incentives and additional funds spent in development by institutions, the concept of an electronic patient record (EPR) within integrated health information technology (HIT) systems has taken the United States by storm. However, the United Kingdom's expensive struggle to implement a seamless EPR highlights the variety of pitfalls and unforeseen complications ranging from recognizing the importance of accurately assessing EPR-related patient risks to understanding the difficulties in the exchange of information across a gradient of distinct interfaces. Furthermore, the tenuous relationship between HIT implementation and patient outcomes in the short-term draws into question the value of EPR construction costs along with the ethical and privacy issues they create. Nonetheless, experts agree that with future software advances and physician familiarization, a robust HIT will be an important asset to patient autonomy, epidemiologic and clinical research, evidence-based error reduction and the potential for cost reduction. This article seeks to review the current status of this initiative and potential pitfalls that remain.

Although ocular lymphoproliferative diseases may be rarely encountered by dermatopathologists, the frequency may increase particularly as more and more subspecialties rely on dermatopathology services. Emerging data suggest that there are some similarities between ocular and cutaneous lymphoproliferative diseases with respect to their clinical behavior, prognosis, and cytogenetics. In this case report, a patient with ocular follicle center lymphoma who subsequently developed ocular reactive lymphoid hyperplasia is presented with an accompanying review of the literature on the subjects. The encounter of both follicular center lymphoma and reactive lymphoid hyperplasia in the same patient provides a rare opportunity to compare and contrast the clinical, histological, and immunohistochemical findings of the respective lymphoproliferative diseases situated at opposite ends of the spectrum.