Percutaneous Microwave Ablation versus Cryoablation for Small Renal Masses (≤4 cm): 12-Year Experience at a Single Center.

PURPOSE: To determine whether microwave ablation (MWA) has equivalent outcomes to those of cryoablation (CA) in terms of technical success, adverse events, local tumor recurrence, and survival in adult patients with solid enhancing renal masses ≤4 cm. MATERIALS AND METHODS: A retrospective review was performed of 279 small renal masses (≤4 cm) in 257 patients (median age, 71 years; range, 40-92 years) treated with either CA (n = 191) or MWA (n = 88) between January 2008 and December 2020 at a single high-volume institution. Evaluations of adverse events, treatment effectiveness, and therapeutic outcomes were conducted for both MWA and CA. Disease-free, metastatic-free, and cancer-specific survival rates were tabulated. The estimated glomerular filtration rate was employed to examine treatment-related alterations in renal function. RESULTS: No difference in patient age (P = .99) or sex (P = .06) was observed between the MWA and CA groups. Cryoablated lesions were larger (P < .01) and of greater complexity (P = .03). The technical success rate for MWA was 100%, whereas 1 of 191 cryoablated lesions required retreatment for residual tumor. There was no impact on renal function after CA (P = .76) or MWA (P = .49). Secondary analysis using propensity score matching demonstrated no significant differences in local recurrence rates (P = .39), adverse event rates (P = .20), cancer-free survival (P = .76), or overall survival (P = .19) when comparing matched cohorts of patients who underwent MWA and CA. CONCLUSIONS: High technical success and local disease control were achieved for both MWA and CA. Cancer-specific survival was equivalent. Higher adverse event rates after CA may reflect the tendency to treat larger, more complex lesions with CA.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Ultrasound Pressure Estimation for Diagnosing Portal Hypertension in Patients Undergoing Dialysis for Chronic Kidney Disease.

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.

Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent.

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.

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

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.

Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension.

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 whether 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 (> 5 and > 10 mmHg, respectively), and 67 had normal HVPG values (< 5 mmHg). Two readers performed independent, binary qualitative assessments of the acquired digital clips. Reader one (experienced radiologist) achieved for the subclinical subgroup sensitivity of 98%, specificity of 88%, and ROC area of 0.93 and for the clinical subgroup sensitivity of 100% and specificity of 61%, with an ROC area of 0.74. Reader two (less experienced radiologist) achieved for the subclinical subgroup sensitivity of 77%, specificity of 76%, and ROC area of 0.76 and for the clinical subgroup sensitivity of 88% and specificity of 63%, with an ROC area of 0.70. Readers agreement was of 83% with kappa value of 0.66. CONCLUSION: The presence of optimized SHI signals inside the hepatic vein can be a qualitative screening test for portal hypertension, which could reduce the need for invasive diagnostic procedures.

Contrast-enhanced ultrasound evaluation of residual blood flow to hepatocellular carcinoma after treatment with transarterial chemoembolization using drug-eluting beads: a prospective study.

OBJECTIVES: To evaluate the accuracy and change over time of contrast-enhanced ultrasound (US) imaging for assessing residual blood flow after transarterial chemoembolization of hepatocellular carcinoma with drug-eluting beads at 2 different follow-up intervals. METHODS: Data from 16 tumors treated by transarterial chemoembolization with drug-eluting beads were successfully obtained. As part of the study, patients provided consent to undergo contrast-enhanced US examinations the morning before embolization, 1 to 2 weeks after embolization, and the morning before follow-up contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) (1 month after embolization). Blinded review of contrast-enhanced US and MRI/CT studies were performed by 2 radiologists who evaluated residual flow as no change, partial change, or no residual flow. Inter- and intra-reader variability rates were calculated before discordant individual reads were settled by consensus. RESULTS: The only adverse event reported during the contrast-enhanced US examinations was a single episode of transient back pain. Contrast-enhanced US at 1 to 2 weeks after embolization (n = 14) resulted in 100% sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Contrast-enhanced US 1 month after embolization (n = 15) resulted in 75% sensitivity, 100% specificity, 100% positive predictive value, 92% negative predictive value, and 93% accuracy. Inter-reader agreement was 86% for contrast-enhanced US at 1 to 2 weeks, 93% for contrast-enhanced US at 1 month, and 100% for contrast-enhanced MRI/CT at 1 month, whereas intra-reader agreement was 71% for contrast-enhanced US at 1 to 2 weeks, 87% for contrast-enhanced US at 1 month, and 91% for MRI/CT. CONCLUSIONS: Contrast-enhanced US imaging at 1 to 2 weeks after the procedure may be a viable alternative to MRI/CT for evaluating residual blood flow after transarterial chemoembolization with drug-eluting beads, albeit with a higher degree of reader variability.

Efficacy and safety of portal vein embolization for two-stage hepatectomy in patients with colorectal liver metastasis.

PURPOSE: To examine the efficacy and safety of portal vein embolization (PVE) when used during two-stage hepatectomy for bilobar colorectal liver metastases (CLM). MATERIALS AND METHODS: PVE was performed as an adjunct to two-stage hepatectomy in 56 patients with CLM. Absolute future liver remnant (FLR) volumes, standardized FLR ratios, degree of hypertrophy (DH), and complications were analyzed. Segment II and III volumes and DH were also measured separately. All volumetric measurements were compared with a cohort of 96 patients (n = 37 right portal vein embolization [RPVE], n = 59 right portal vein embolization extended to segment IV portal veins [RPVE+4]) in whom PVE was performed before single-stage hepatectomy. RESULTS: For patients who completed RPVE during two-stage hepatectomy (n = 17 of 17), mean absolute FLR volume increased from 272.1 cm(3) to 427.0 cm(3) (P < .0001), mean standardized FLR ratio increased from 0.17 to 0.26 (P < .0001), and mean DH was 0.094. For patients who completed RPVE+4 during two-stage hepatectomy (n = 38 of 39), mean FLR volume increased from 288.7 cm(3) to 424.8 cm(3) (P < .0001), mean standardized FLR increased from 0.18 to 0.26 (P < .0001), and mean DH was 0.083. DH of the FLR was not significantly different between two-stage hepatectomy and single-stage hepatectomy. Complications after PVE occurred in five (8.9%) patients undergoing two-stage hepatectomy. CONCLUSIONS: PVE effectively and safely induced a significant DH in the FLR during two-stage hepatectomy in patients with CLM.

Microwave ablation as a primary versus secondary treatment for hepatocellular carcinoma

PURPOSE: The purpose of this study was to analyze and compare the outcomes of percutaneous microwave ablation (MWA) when used as a primary vs. secondary treatment for hepatocellular carcinoma (HCC). METHODS: The clinical data of 192 patients with HCC treated with MWA between January 2012 and July 2021 were reviewed retrospectively, with 152 patients being treatment naïve (primary treatment) vs. 40 who had residual or recurrent disease following previous trans-arterial chemoembolization or trans-arterial radioembolization (secondary treatment). The primary outcomes were primary technical efficacy, 1- and 3-year local recurrence-free survival (RFS) and overall survival (OS), local recurrence rates, and adverse events. Pre- and post-intervention liver function tests were compared using a Wilcoxon signed rank test. Univariate and multivariate analyses were also performed, looking at prognostic factors associated with OS and local RFS. RESULTS: There was no significant difference in 1-year local RFS (primary 93.6% vs. secondary 93.7; P = 0.97) and 3-year local RFS (primary 80.6% vs. secondary 86.5%; P = 0.37) rates. There was no significant difference in 1-year OS (primary 82.4% vs. secondary 86.6%; P = 0.51) and 3-year OS (primary 68.3% vs. secondary 77.4%; P = 0.25) between the two groups. The local recurrence rate (primary 9.8% vs. secondary 14.6%; P = 0.37), primary technical efficacy (primary 96.2% vs. secondary 95%; P = 0.73), and adverse events (primary 8.0% vs. secondary 11.6%; P = 0.45) were also similar between the two groups. CONCLUSION: Microwave ablation is safe and effective as a secondary treatment for patients with HCC in a clinical salvage scenario and should be utilized more frequently.

Imaging appearance of residual HCC following incomplete trans-arterial chemoembolization on contrast-enhanced imaging.

PURPOSE: The aim of this study was to describe changes in contrast agent kinetics in HCC following incomplete trans-arterial chemoembolization (TACE) on contrast-enhanced ultrasound (CEUS) and MRI/CT. METHODS: Patients with residual HCC proven by biopsy, retreatment angiography, or 4-8 month MRI demonstrating tumor progression were identified. Pre-treatment and 4-6-week follow-up CE-MRI/CT and CEUS exams were collected for blinded reads by two experienced readers for each modality to evaluate arterial phase hyper-enhancement (APHE) and washout within the residual HCC. A third reader provided tie-breaking decisions for any disagreements. RESULTS: Contrast-enhanced imaging data were collected from 29 patients with residual HCC post-TACE. On CEUS, 84.2% of patients with baseline APHE demonstrated APHE post-TACE (p = 0.25). On CE-MRI/CT, 57.1% of patients with baseline APHE later demonstrated APHE (p = 0.004). As for washout, on CEUS 33.3% of patients with baseline washout retained washout post-TACE (p = 0.01), while on CE-MRI/CT only 18.8% of patients with baseline washout later demonstrated washout (p < 0.001). Among CEUS readers, reader agreement was 100% for baseline APHE, 66.7% for baseline washout (K = 0.35), 84.2% for post-TACE APHE (K = 0.35), and 57.9% for post-TACE washout (K = - 0.09). On CE-MRI/CT, reader agreement was 65.5% for baseline APHE (K = 0.19), 55.2% for baseline washout (K = 0.12), 48.3% for post-TACE APHE (K = - 0.07), and 58.6% for post-TACE washout (K = 0.04). CONCLUSION: Common diagnostic features of treatment-naïve HCC like APHE and washout can be substantially altered by TACE and should be considered when diagnosing residual disease on contrast-enhanced imaging.

Optional vena cava filter use in the elderly population.

PURPOSE: To review utility, safety, and efficacy of optional inferior vena cava (IVC) filters in patients 65 years or older at a single institution over a 6-year period. MATERIALS AND METHODS: Retrospective review of permanent and optional IVC filters placed in elderly patients was performed. Older and younger groups were compared based on technical success of filter placement and clinical success measured by recurrent pulmonary embolism (PE) or thrombotic complications. The rate of successful filter removal was compared with that in the cohort of patients of all ages who received optional filters. RESULTS: Fifty-three patients received an optional filter and 445 received a permanent filter. Technical success rates for filter placement in the permanent and optional filter groups were 99.8% (447 of 448) and 98.1% (53 of 54), respectively (P = .51). Rates of PE after filter placement were 0% and 1.4% (five of 359) in the optional and permanent filter groups, respectively (P = .87). Incidences of deep vein thrombosis were 12% (six of 50) and 4.5% (16 of 359) in optional and permanent filter recipients, respectively (P = .06). Filter retrieval was attempted in 55.6% of optional filter recipients (30 of 54), similar to that seen in patients of any age with optional filters. Retrieval was unsuccessful in one patient in whom a suprarenal IVC filter was placed. CONCLUSIONS: Optional filters are safe and effective in patients aged 65 years or older. Age alone is a poor predictor of a clinical opportunity to remove a filter. With appropriate patient selection and aggressive follow-up, retrieval rates comparable with those in younger populations can be achieved.

Acute Thrombosis of Left Portal Vein during Right Portal Vein Embolization Extended to Segment 4.

Portal vein thrombosis (PVT) is an uncommon, but potentially devastating complication of portal vein embolization (PVE). Its occurrence relates to both local and systemic risk factors. In the setting of PVE, precipitating factors include injury to the vessel wall and reduced portal flow. Contributory factors include portal hypertension, hypercoagulopathy, inflammatory processes, malignancy, pregnancy, oral contraceptive use, and asplenia. The goal of therapy is to prevent thrombus progression and lyse existing clot. Hepatectomy is impossible if adequate recanalization has not occurred and/or overt portal hypertension develops. The mechanisms for thrombus development, its diagnosis, management, and prognosis are discussed.

Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences.

Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

A Noninvasive Ultrasound Based Technique to Identify Treatment Responders in Patients with Portal Hypertension.

RATIONALE AND OBJECTIVE: Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of ultrasound contrast microbubbles and ambient pressure. The aim of this study was to verify if SHAPE can accurately monitor disease progression in patients identified with portal hypertension. MATERIALS & METHODS: A modified Logiq 9 scanner with a 4C curvi-linear probe (GE, Waukesha, WI) was used to acquire SHAPE data (transmitting and receiving at 2.5 and 1.25 MHz, respectively) using Sonazoid (GE Healthcare, Oslo, Norway; FDA IND 124,465). Twenty-one (median age 59 years; 12 Males) of the 178 patients enrolled in this institutional review board approved study (14F.113) were identified as having clinically significant portal hypertension based on their hepatic venous pressure gradient results ≥ 10 mmHg. Repeat SHAPE examinations were done every 6.2 months. Liver function tests and clinical indicators were used to establish treatment response. RESULTS: Of the 21 portal hypertensive subjects, 11 had successful follow up scans with an average follow up time of 6.2 months. There was a significantly larger SHAPE signal reduction in the group who were classified as treatment responders (n = 10; -4.01±3.61 dB) compared to the single nonresponder (2.33 dB; p < 0.001). Results for responders matched the corresponding clinical outcomes of improved model for end stage liver disease (MELD) scores, improvement in underlying cause of portal hypertension, improved liver function tests and reduced ascites. CONCLUSION: SHAPE can potentially monitor disease progression in portal hypertensive patients and hence, may help clinicians in patient management. A larger study would further validate this claim.

Contrast-Enhanced Subharmonic Aided Pressure Estimation (SHAPE) using Ultrasound Imaging with a Focus on Identifying Portal Hypertension.

Noninvasive, accurate measurement of pressures within the human body has long been an important but elusive clinical goal. Contrast agents for ultrasound imaging are gas-filled, encapsulated microbubbles (diameter < 10 µm) that traverse the entire vasculature and enhance signals by up to 30 dB. These microbubbles also produce nonlinear oscillations at frequencies ranging from the subharmonic (half of the transmit frequency) to higher harmonics. The subharmonic amplitude has an inverse linear relationship with the ambient hydrostatic pressure. Here an ultrasound system capable of performing real-time, subharmonic aided pressure estimation (SHAPE) is presented. During ultrasound contrast agent infusion, an algorithm for optimizing acoustic outputs is activated. Following this calibration, subharmonic microbubble signals (i.e., SHAPE) have the highest sensitivity to pressure changes and can be used to noninvasively quantify pressure. The utility of the SHAPE procedure for identifying portal hypertension in the liver is the emphasis here, but the technique has applicability across many clinical scenarios.

Contrast-enhanced Ultrasound Identifies Patent Feeding Vessels in Transarterial Chemoembolization Patients With Residual Tumor Vascularity.

Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) often requires retreatment and identification of feeding vessels supplying the residual/recurrent tumor is an important step in treatment planning. The objective of this study was to determine if contrast-enhanced ultrasound (CEUS) could correctly identify the vessel supplying the residual tumor. To date, 69 patients have undergone CEUS follow-up of HCC TACE therapy at our institution as part of an ongoing institutional review board approved trial (NCT02764801). The CEUS examinations were performed before HCC TACE as well as 1 to 2 weeks and 1 month after treatment using a Logiq E9 scanner with a C1-6 curved array transducer (GE Healthcare, Waukesha, WI). The CEUS images obtained 2 weeks after initial TACE treatment were reviewed, and any feeding vessels supplying the residual HCC were identified. Digital subtraction angiograms during the retreatment TACE were used as reference standard for feeding vessel identification. Thirteen patients with viable HCC post-TACE were included in this study. In these cases, the sonographer correctly identified 85% (11 of 13) of the feeding vessels later confirmed by angiography. Importantly, one of the false-negative cases involved a segment 8 tumor with parasitic blood supply from the medial left hepatic artery. In this case, CEUS identified a largely treated tumor with some residual internal flow, but was unable to visualize any major hepatic vascularity supplying the tumor. In conclusion, CEUS appears to be a valuable tool for planning retreatment of residual HCC post-TACE.

Perfusion-guided sonopermeation of neuroblastoma: a novel strategy for monitoring and predicting liposomal doxorubicin uptake in vivo.

Neuroblastoma (NB) is the most common extracranial solid tumor in infants and children, and imposes significant morbidity and mortality in this population. The aggressive chemoradiotherapy required to treat high-risk NB results in survival of less than 50%, yet is associated with significant long-term adverse effects in survivors. Boosting efficacy and reducing morbidity are therefore key goals of treatment for affected children. We hypothesize that these may be achieved by developing strategies that both focus and limit toxic therapies to the region of the tumor. One such strategy is the use of targeted image-guided drug delivery (IGDD), which is growing in popularity in personalized therapy to simultaneously improve on-target drug deposition and assess drug pharmacodynamics in individual patients. IGDD strategies can utilize a variety of imaging modalities and methods of actively targeting pharmaceutical drugs, however in vivo imaging in combination with focused ultrasound is one of the most promising approaches already being deployed for clinical applications. Over the last two decades, IGDD using focused ultrasound with "microbubble" ultrasound contrast agents (UCAs) has been increasingly explored as a method of targeting a wide variety of diseases, including cancer. This technique, known as sonopermeation, mechanically augments vascular permeability, enabling increased penetration of drugs into target tissue. However, to date, methods of monitoring the vascular bioeffects of sonopermeation in vivo are lacking. UCAs are excellent vascular probes in contrast-enhanced ultrasound (CEUS) imaging, and are thus uniquely suited for monitoring the effects of sonopermeation in tumors. Methods: To monitor the therapeutic efficacy of sonopermeation in vivo, we developed a novel system using 2D and 3D quantitative contrast-enhanced ultrasound imaging (qCEUS). 3D tumor volume and contrast enhancement was used to evaluate changes in blood volume during sonopermeation. 2D qCEUS-derived time-intensity curves (TICs) were used to assess reperfusion rates following sonopermeation therapy. Intratumoral doxorubicin (and liposome) uptake in NB was evalauted ex vivo along with associated vascular changes. Results: In this study, we demonstrate that combining focused ultrasound therapy with UCAs can significantly enhance chemotherapeutic payload to NB in an orthotopic xenograft model, by improving delivery and tumoral uptake of long-circulating liposomal doxorubicin (L-DOX) nanoparticles. qCEUS imaging suggests that changes in flow rates are highly sensitive to sonopermeation and could be used to monitor the efficacy of treatment in vivo. Additionally, initial tumor perfusion may be a good predictor of drug uptake during sonopermeation. Following sonopermeation treatment, vascular biomarkers show increased permeability due to reduced pericyte coverage and rapid onset of doxorubicin-induced apoptosis of NB cells but without damage to blood vessels. Conclusion: Our results suggest that significant L-DOX uptake can occur by increasing tumor vascular permeability with microbubble sonopermeation without otherwise damaging the vasculature, as confirmed by in vivo qCEUS imaging and ex vivo analysis. The use of qCEUS imaging to monitor sonopermeation efficiency and predict drug uptake could potentially provide real-time feedback to clinicians for determining treatment efficacy in tumors, leading to better and more efficient personalized therapies. Finally, we demonstrate how the IGDD strategy outlined in this study could be implemented in human patients using a single case study.

Consensus review of discordant findings maximizes cancer detection rate in double-reader screening mammography: Irish National Breast Screening Program experience.

PURPOSE: To assesses consensus review of discordant screening mammography findings in terms of its sensitivity, safety, and effect on overall performance in the first 6 years of operation of the Irish National Breast Screening Program (NBSP). MATERIALS AND METHODS: Women who participated in the Irish NBSP gave written informed consent for use of their data for auditing purposes. Local ethics committee approval was obtained. The study population consisted of women who participated in the Irish NBSP and underwent initial screening mammography at one of the two screening centers serving the eastern part of Ireland between 2000 and 2005. Independent double reading of mammograms was performed. When the readers disagreed regarding referral, the case was reviewed by a consensus panel. Of the 128 569 screenings performed, 1335 (1%) were discussed by consensus. RESULTS: Of the 1335 cases discussed by consensus, 606 (45.39%) were recalled for further assessment. This resulted in an overall recall rate of 4.41%. In those recalled to assessment, 71 cases of malignant disease were diagnosed (ductal carcinoma in situ, n = 24; invasive cancer, n = 47). The remaining 729 patients were returned to biennial screening. Of these 729 patients, seven had false-negative findings that were identified in the subsequent screening round. Use of the highest reader recall method, in which a patient is recalled if her findings are deemed abnormal by either reader, could potentially increase the cancer detection rate by 0.6 per 1000 women screened but would increase the recall rate by 12.69% and the number of false-positive findings by 15.37%. CONCLUSION: The consensus panel identified 71 (7.33%) of 968 cancers diagnosed. Consensus review substantially reduced the number of cases recalled and was associated with a low false-negative rate.