OBJECTIVE:Contrast-enhanced ultrasound (CEUS) can be used to effectively monitor hepatocellular carcinoma (HCC) treatment response to percutaneous ablation and transarterial chemoembolization. Here, we performed a supplementary analysis of a prospective study to evaluate HCC participants treated with yttrium-90 transarterial radioembolization (Y90-TARE). We evaluated the utility of quantifiable parameters obtained from CEUS up to 2 weeks posttreatment for predicting treatment response compared with the standard of care cross-sectional imaging performed 2 to 6 months posttreatment (reference standard). MATERIALS AND METHODS:In this IRB-approved, prospective clinical trial, participants with HCC scheduled for Y90-TARE underwent 3 CEUS sessions. These sessions occurred 1 to 4 hours post-Y90-TARE, 1 week, and 2 weeks posttreatment. Each CEUS examination involved a 10-minute infusion of Optison (GE HealthCare) using an Acuson Sequoia 2.0 or a HELX S3000 scanner (Siemens Healthineers) with 6C1 transducer. During each CEUS examination, flash-replenishment sequences were performed at the tumor midline for CEUS replenishment imaging. Changes between baseline and 1 or 2 weeks were used for quantitative analyses. Fractional tumor vascularity (FTV in %), perfusion (in mL/s*mg), peak enhancement (au), and time to peak (TTP in seconds) were calculated offline using Matlab (MathWorks) to quantitatively evaluate TARE response. Two abdominal radiologists read the reference standard MRI or CT obtained post-Y90-TARE and characterized the tumor as nonviable (complete response) or viable (partial response/stable disease). Unpaired t tests were performed to evaluate differences in nonviable versus viable disease. ROC analysis and logistic regression were evaluated to determine diagnostic performance and disease prediction. RESULTS:Final analysis included 38 participants. Of these, 22 had nonviable disease (58%, 22/38) and 16 had viable disease (42%, 16/38). FTV showed a difference between nonviable and viable tumors at 2 weeks post-Y90-TARE (38% ± 24% vs 62% ± 28%, P = 0.008). In addition, there was a statistically significant difference in the change in FTV from immediately post-Y90-TARE to 2 weeks after treatment between participants with viable and nonviable disease (41% ± 31% vs 11% ± 26%, P = 0.006). No significant difference was found between viable and nonviable disease across examinations for any of the other variables ( P > 0.13). CONCLUSIONS:Quantitative CEUS appears to provide an early indicator of treatment response ∼2 weeks post-Y90-TARE.

Background US contrast agents are gas-filled microbubbles that can be disrupted locally, such as via ultrasound-triggered microbubble destruction (UTMD), which can cause bioeffects that sensitize tumors to radiation. However, the efficacy and safety of UTMD combined with radiation therapy in participants with hepatocellular carcinoma (HCC) are unknown. Purpose To determine the treatment efficacy and safety of UTMD in participants with HCC receiving yttrium 90 (90Y) transarterial radioembolization (TARE). Materials and Methods In this prospective phase II clinical trial conducted from July 2017 to February 2024, participants with HCC scheduled for 90Y-TARE were randomly assigned to undergo 90Y-TARE with three UTMD sessions (treatment group) or 90Y-TARE alone (control group). The primary end point was treatment response evaluated at MRI or CT using modified Response Evaluation Criteria in Solid Tumors. Secondary end points included safety, overall survival, time to next treatment, rate of liver transplantation, and pathologic response in the event of transplantation. Changes in general laboratory values and vital signs were compared using unpaired and paired t tests, survival and time to next treatment between groups were compared between groups using log-rank tests, and treatment response distribution was compared between groups using the Mann-Whitney U test. Results The study sample consisted of 98 participants (mean age, 69 years ± 8.4 [SD]; 71 men). The safety analysis showed no evidence of a difference in vital signs before versus after the initial UTMD session in the treatment group (all P ≥ .07). There was also no evidence of a difference in changes in general laboratory values from before to after treatment between the treatment and control groups (all P ≥ .08). In the control group, 34% (17 of 50) of participants had stable disease, 22% (11 of 50) had partial response, and 44% (22 of 50) had complete response; in the treatment group, 4% (two of 48) had stable disease, 35% (17 of 48) had partial response, and 60% (29 of 48) had complete response. Thus, UTMD increased the proportion of participants who experienced complete or partial response by 30 percentage points (96% [46 of 48] vs 66% [33 of 50]; P = .01). Overall survival was higher in the treatment group than in the control group (mortality hazard ratio, 0.51 [95% CI: 0.28, 0.95]; P = .03). Conclusion Compared with only 90Y-TARE, adding microbubble-based radiosensitization via UTMD to 90Y-TARE in the treatment of HCC had similar safety, provided improved treatment response, and prolonged survival. ClinicalTrials.gov Identifier: NCT03199274 © RSNA, 2025 Supplemental material is available for this article.

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.

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.

The 2017 LI-RADS treatment response (LR-TR) algorithm classifies hepatocellular carcinoma (HCC) post-locoregional therapies as non-viable, viable, and equivocal. The equivocal category denotes an uncertain enhancement pattern not aligned with that of viable tumor. The purpose of this study was to evaluate the survival of HCC patients categorized as LR-TR equivocal post-transarterial radioembolization (TARE). This retrospective study consists of HCC patients who underwent TARE at a single institution from 2017-2022. Three post-TARE LR-TR reads were collected. Patients were classified into 3 groups based on LR-TR category of the first scan post-TARE (average 1.4 ± 2.8 months): equivocal, viable, and nonviable. Equivocal patients were further stratified by clinical course based on the third post-TARE read into viable, nonviable, or equivocal. Median survival was compared between groups. 141 patients were examined in the study, with 72 equivocal (51.1%), 25 viable (17.7%), and 44 nonviable (31.2%) post-TARE. Median survival was 2.3 years for equivocal, 1.9 years for viable, and 3.6 years for nonviable (P = 0.10). Of the equivocal patients, 28 were retreated with locoregional therapy (11 TACE, 8 ablations, 9 TARE) 6.8 ± 4.9 months after initial TARE. The clinical course of the equivocal group after the first equivocal scan and following retreatment if necessary was 16 equivocal (22.2%), 11 viable (15.3%), and 45 nonviable (62.5%) (average follow-up time post-TARE 8.7 ± 4.8 months). When stratified by eventual clinical course, median survival of the initial equivocal cohort post-TARE was 2.6 years for equivocal, 3.1 years for viable, and 4.1 years for non-viable (P = 0.13). Characterizing clinical outcomes post-TARE elucidates the implications of an equivocal read. Several equivocal patients post-TARE were retreated with subsequent locoregional therapy, and most were eventually nonviable after 3 post-TARE scans. Of the equivocal patients post-TARE, the patients who remained equivocal had the shortest survival, suggesting that equivocal tumors are potentially more pathologically advanced, complicated to treat, and have difficult-to-interpret enhancement patterns.

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.

To evaluate the safety, efficacy, and outcomes of percutaneous ablation of synchronous or metachronous SRM. A single-center retrospective review of percutaneous ablations of SRM performed between 2010 and 2021 was performed. Patients who underwent ablation of more than one kidney lesion, either in a single or multiple encounter(s), were included. Lesions were limited to T1a or T1b. Patients with metastatic disease at presentation or treatments for recurrence were excluded. Wilcox rank sum test was used to compare pre- and post-ablation creatinine. Kaplan-Meier analysis was performed to assess overall survival (OS) and cancer specific survival (CSS) from index ablation. A total of 54 lesions were ablated in 24 patients (22 males) across 40 encounters. Nineteen patients had two, four patients had three, and one patient had four lesions treated. The mean ± SD lesion diameter was 2.5 cm ± 1.0 cm and the median lesion nephrometry score was 6 (range, 4-10). The majority of lesions were right-sided (n = 32, 59%). Mean ± SD patient age was 69 ± 2.1 years and median Charlson Comorbidity index was 6 (range, 2-10) at the time of treatment. Biopsy was performed for 45 lesions (83%) with malignancy present in 30. Ablation techniques were cryoablation (n = 22, 41%) and microwave ablation (n = 32, 59%). Median number of probes placed per lesion was 2 (range, 1-5). Pyeloperfusion was performed for 3 lesions (6%) and hydrodissection for 15 (28%). Technical success was achieved in 100%. Median length of hospital stay was 1 day (range, 0-7 days). Major complication occurred in one patient (Society of Interventional Radiology (SIR) class D) who had an acute ischemic stroke requiring extended hospitalization. Minor complication (SIR class B) occurred in one patient who had subcapsular hematoma managed conservatively. There was a statistically significant increase in creatinine 3-12 months following ablation (1.9 to 2.1 mg/dL, P = 0.009). However, no patients required subsequent hemodialysis initiation. Follow-up imaging was obtained in 23 patients (96%) with no instances of residual disease or local recurrence. Mean ± SD follow-up time was 4.6 ± 4.0 years. The 5-year OS was 80% for both the entire cohort and the subset of patients with documented malignancy on biopsy (n = 17). CSS was 96% for the entire cohort. A single patient died from complications related to metastatic renal cell carcinoma. Percutaneous ablation of synchronous or metachronous SRM demonstrated similar safety, efficacy, and outcomes compared with historical data for ablation of a solitary lesion.

To evaluate the diagnostic performance of the LI-RADS treatment response algorithm in hepatocellular carcinoma (HCC) patients treated with radioembolization (Y-90)

AbstractLocoregional therapies (LRTs) are an essential management tool in the treatment of primary liver cancers or metastatic liver disease. LRTs include curative and palliative modalities. Monitoring treatment response of LRTs is crucial for maximizing benefit and improving clinical outcomes. Clinical use of contrast-enhanced ultrasound (CEUS) was introduced more than two decades ago. Its portability, cost effectiveness, lack of contraindications and safety make it an ideal tool for treatment monitoring in numerous situations. Two-dimensional dynamic CEUS has been proved to be equivalent to the current imaging standard in the guidance of LRTs, assessment of their adequacy, and detection of early tumor recurrence. Recent technical advances in ultrasound transducers and image processing have made 3D CEUS scanning widely available on most commercial ultrasound systems. 3D scanning offers a broad multiplanar view of anatomic structures, overcoming many limitations of two-dimensional scanning. Furthermore, many ultrasound systems provide real-time dynamic 3D CEUS, also known as 4D CEUS. Volumetric CEUS has shown to perform better than 2D CEUS in the assessment and monitoring of some LRTs. CEUS presents a valid alternative to the current imaging standards with reduced cost and decreased risk of complications. Future efforts will be directed toward refining the utility of 4D CEUS through approaches such as multi-parametric quantitative analysis and machine learning algorithms.

The incidence of renal cell carcinoma (RCC) has more than doubled in the USA since 1975, accounting for more than 75,000 diagnoses per year. Concomitant with the rising incidence, thermal ablation is now considered an acceptable alternative to partial nephrectomy for all patients with cT1a small renal masses. The purpose of this study was to compare the safety and efficacy of microwave ablation (MWA) and cryoablation (CA) in the treatment of cT1a renal masses.

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. 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. 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). 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.

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). Twentyone (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 A would further validate this claim.

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.

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.

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.

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.

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.

Hepatocellular carcinoma (HCC) is prevalent worldwide. Among the various therapeutic options, transarterial chemoembolization (TACE) can be applied to the tumor vascular network by restricting the nutrients and oxygen supply to the tumor. Unique morphologic properties of this network may provide information predictive of future therapeutic responses, which would be significant for decision making during treatment planning. The extraction of morphologic features from the tumor vascular network depicted in abdominal contrast-enhanced ultrasound (CEUS) images faces several challenges, such as organ motion, limited resolution caused by clutter signal and segmentation of the vascular structures at multiple scales. In this study, we present an image processing and analysis approach for the prediction of HCC response to TACE treatment using clinical CEUS images and known pathologic responses. This method focuses on addressing the challenges of CEUS by incorporating a two-stage motion correction strategy, clutter signal removal, vessel enhancement at multiple scales and machine learning for predictive modeling. The morphologic features, namely, number of vessels (NV), number of bifurcations (NB), vessel to tissue ratio (VR), mean vessel length, tortuosity and diameter, from tumor architecture were quantified from CEUS images of 36 HCC patients before TACE treatment. Our analysis revealed that NV, NB and VR are the dominant features for the prediction of long-term TACE response. The model had an accuracy of 86% with a sensitivity and specificity of 89% and 82%, respectively. Reliable prediction of the TACE therapy response using CEUS-derived image features may help to provide personalized therapy planning, which will ultimately improve patient outcomes.