Breast cancer is the most frequent type of cancer among women. This multi-center study assessed the ability of 3D contrast-enhanced ultrasound to characterize suspicious breast lesions using clinical assessments and quantitative parameters.Women with suspicious breast lesions scheduled for biopsy were enrolled in this prospective, study. Following 2D grayscale ultrasound and power Doppler imaging (PDI), a contrast agent (Definity; Lantheus) was administrated. Contrast-enhanced 3D harmonic imaging (HI; transmitting/receiving at 5.0/10.0 MHz), as well as 3D subharmonic imaging (SHI; transmitting/receiving at 5.8/2.9 MHz), were performed using a modified Logiq 9 scanner (GE Healthcare). Five radiologists independently scored the imaging modes (including standard-of-care imaging) using a 7-point BIRADS scale as well as lesion vascularity and diagnostic confidence. Parametric volumes were constructed from time-intensity curves for vascular heterogeneity, perfusion, and area under the curve. Diagnostic accuracy was determined relative to pathology using receiver operating characteristic (ROC) and reverse, step-wise logistical regression analyses. The κ-statistic was calculated for inter-reader agreement.Data were successfully acquired in 219 cases and biopsies indicated 164 (75%) benign and 55 (25%) malignant lesions. SHI depicted more anastomoses and vascularity than HI (P < .021), but there were no differences by pathology (P > .27). Ultrasound achieved accuracies of 82 to 85%, which was significantly better than standard-of-care imaging (72%; P < .03). SHI increased diagnostic confidence by 3 to 6% (P < .05), but inter-reader agreements were medium to low (κ < 0.52). The best regression model achieved 97% accuracy by combining clinical reads and parametric SHI.Combining quantitative 3D SHI parameters and clinical assessments improves the characterization of suspicious breast lesions.

Rationale and Objectives: Breast cancer is the leading type of cancer among women. Visualization and characterization of breast lesions based on vascularity kinetics was evaluated using three-dimensional (3D) contrast-enhanced ultrasound imaging in a clinical study. Materials and Methods: Breast lesions (n = 219) were imaged using power Doppler imaging (PDI), 3D contrast-enhanced harmonic imaging (HI), and 3D contrast-enhanced subharmonic imaging (SHI) with a modified Logiq 9 ultrasound scanner using a 4D10L transducer. Quantitative metrics of vascularity derived from 3D parametric volumes (based on contrast perfusion; PER and area under the curve; AUC) were generated by off-line processing of contrast wash-in and wash-out. Diagnostic accuracy of these quantitative vascular parameters was assessed with biopsy results as the reference standard. Results: Vascularity was observed with PDI in 93 lesions (69 benign and 24 malignant), 3D HI in 8 lesions (5 benign and 3 malignant), and 3D SHI in 83 lesions (58 benign and 25 malignant). Diagnostic accuracy for vascular heterogeneity, PER, and AUC ranged from 0.52 to 0.75, while the best logistical regression model (vascular heterogeneity ratio, central PER, and central AUC) reached 0.90. Conclusion: 3D SHI successfully detects contrast agent flow in breast lesions and characterization of these lesions based on quantitative measures of vascular heterogeneity and 3D parametric volumes is promising. (c) 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

The ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D nonlinear ultrasound imaging was investigated in a clinical population. Patients (n = 236) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3D HI, and 3D SHI on a modified Logiq 9 scanner (GE Healthcare). Time-intensity curve volumes were developed corresponding to ultrasound contrast agent flow in the lesions after being identified in 4DView (GE Medical Systems). Time-points corresponding to baseline, peak intensity and complete washout of contrast were identified to generate vascular heterogeneity plots of the lesion volume (in the center and periphery as well as the ratio of the two). Vascularity was observed with power Doppler imaging in 93 lesions (69 benign and 24 malignant). The 3D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3D SHI visualized flow in 83 lesions (58 benign and 25 malignant). Parametric volumes, that contained a single parametric value for every voxel within the 3D volume, were generated based on perfusion (PER) and area under the curve (AUC). ROC analysis and reverse, step-wise logistical regression were used to assess diagnostic accuracy with biopsy results as the reference. Analysis of vascular heterogeneity in the 3D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.8 ± 0.16 vs. 1.2 ± 0.09 dB, p = 0.0003, respectively), whereas malignant lesions showed no difference (1.7 ± 0.33 vs. 1.3 ± 0.21 dB, p = 0.23), indicative of more vascular coverage. Diagnostic accuracy (i.e., area under the ROC curve) for heterogeneity, PER and AUC ranged from 0.52 to 0.75. The best logistical regression model (heterogeneity ratio, PER central and AUC central) achieved an area of 0.88. In conclusion, 3D SHI is able to detect UCA flow in vascular breast masses. Evaluation of vascular heterogeneity and parametric maps suggests such quantitative parameters might aid in the characterization of breast lesions.

Interstitial fluid pressure (IFP) in rats with breast cancer xenografts was non-invasively estimated using subharmonic-aided pressure estimation (SHAPE) versus an invasive pressure monitor. Moreover, monitoring of IFP changes after chemotherapy was assessed. Eighty-nine rats (calibration n = 25, treatment n = 64) were injected with 5 x 10(6) breast cancer cells (MDA-MB-231). Radiofrequency signals were acquired (39 rats successfully imaged) with a Sonix RP scanner (BK Ultrasound, Richmond, BC, Canada) using a linear array (L9-4, transmit/receive: 8/4 MHz) after administration of Definity (Lantheus Medical Imaging, North Billerica, MA, USA; 180 mu L/kg) and compared with readings from an invasive pressure monitor (Stryker, Berkshire, UK). An inverse linear relationship was established between tumor IFP and SHAPE (y = -1.06x + 28.27, r = -0.69, p = 0.01) in the calibration group. Use of this relationship in the treatment group resulted in r = 0.74 (p < 0.05) between measured (pressure monitor) and SHAPE-estimated IFP (average error: 6.24 mmHg). No significant before/after differences were observed with respect to paclitaxel treatment (5 mg/kg, Mayne Pharma, Paramus, NJ, USA) with either method (p >= 0.15). (E-mail: flemming.forsberg@jefferson.edu) (C) 2017 World Federation for Ultrasound in Medicine & Biology.

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 drugeluting 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 (Mill) 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 = IS) 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.

In this preliminary study, we compared two noninvasive techniques for imaging intratumoral physiological conditions to immunohistochemical staining in a murine breast cancer model. MDA-MB-231 tumors were implanted in the mammary pad of 11 nude rats. Ultrasound and photoacoustic (PA) scanning were performed using a Vevo 2100 scanner (Visualsonics, Toronto, Canada). Contrast-enhanced ultrasound (CEUS) was used to create maximum intensity projections as a measure of tumor vascularity. PAs were used to determine total hemoglobin signal (HbT), oxygenation levels in detected blood (SO2 Avg), and oxygenation levels over the entire tumor area (SO2 Tot). Tumors were then stained for vascular endothelial growth factor (VEGF), cyclooxygenase-2 (Cox-2), and the platelet endothelial cell adhesion molecule CD31. Correlations between findings were analyzed using Pearson’s coefficient. Significant correlation was observed between CEUS-derived vascularity measurements and both PA indicators of blood volume ( r = 0.49 for HbT, r = 0.50 for SO2 Tot). Cox-2 showed significant negative correlation with SO2 Avg ( r = −0.49, p = 0.020) and SO2 Tot ( r = −0.43, p = 0.047), while CD31 showed significant negative correlation with CEUS-derived vascularity ( r = −0.47, p = 0.036). However, no significant correlation was observed between VEGF expression and any imaging modality ( p > 0.08). Photoacoustically derived HbT and SO2 Tot may be a good indicator of tumor fractional vascularity. While CEUS correlates with CD31 expression, photoacoustically derived SO2 Avg appears to be a better predictor of Cox-2 expression.

RATIONALE AND OBJECTIVES:The objective of this study was to evaluate and compare contrast-enhanced subharmonic and harmonic ultrasound as tools for characterizing solid renal masses and monitoring their response to cryoablation therapy.MATERIALS AND METHODS:Sixteen patients undergoing percutaneous ablation of a renal mass provided informed consent to undergo ultrasound examinations the morning before and approximately 4 months after cryoablation. Ultrasound contrast parameters during pretreatment imaging were compared to biopsy results obtained during ablation (n = 13). Posttreatment changes were evaluated by a radiologist and compared to contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) follow-up.RESULTS:All masses initially showed heterogeneous enhancement with both subharmonic and harmonic ultrasound. Early contrast washout in the mass relative to the cortex was observed in 6 of 9 malignant and 0 of 4 benign lesions in subharmonic mode and 8 of 9 malignant and 1 of 4 benign lesions in harmonic imaging. In cases where the lesion was adequately visualized at follow-up (n = 12), subharmonic and harmonic ultrasound showed accuracies of 83% and 75%, respectively, in predicting treatment outcome. Although harmonic imaging showed less overall error, no significant differences (P > .29) in ablation cavity volumes were observed between MRI/CT and either contrast-imaging mode.CONCLUSIONS:Subharmonic and harmonic contrast-enhanced ultrasound may be a safe and accurate imaging alternative for characterizing renal masses and evaluating their response to cryoablation therapy. Although subharmonic imaging was more accurate in detecting effective cryoablation, harmonic imaging was superior in quantifying ablation cavity volumes.

Work-related musculoskeletal disorders (WRMSDs) are widely recognized as serious occupational health problems for sonographers, echocardiographers and vascular technologists. Industry Standards for the Prevention of WRMSDs in Sonography outline three types of control measures: 1) Equipment Control Measures; 2) Administrative Control Measures; and 3) Professional Control Measures. This presentation will focus on Equipment Control Measures that can be employed to reduce the likelihood of WRMSDs. Changes in ultrasound equipment design have resulted in smaller, lighter cart-based scanners that have a variety of ergonomic features including articulating monitors and user-interfaces to enhance operator comfort. Furthermore, the latest ultrasound probes are light-weight and have thin, flexible cables to reduce arm and wrist strain. There is also a variety of ultrasound-related equipment including specially-designed exam tables, operator stools, supports and other devices that can enhance ergonomic scanning. New software features, such as those that reduce key-strokes, have enhanced the overall examination process while reducing operator musculoskeletal stress. The combination of equipment control measures with administrative and professional controls measures can reduce the likelihood of sonographer WRMSDs. Objectives: At the completion of this lecture the participant should be able to: Describe sonographers' workplace activities that can contribute to the development of work-related musculoskeletal disorders (WRMSDs). Describe recent Industry Standards that have been developed regarding WRMSDs in sonography. List recent advances in sonography equipment designs that can help to reduce WRMSDs. Describe changes to the way that scans are performed that sonography professionals can practice to reduce the occurrence of WRMSDs.

ObjectivesTo investigate the use of contrast‐enhanced ultrasound imaging (US) for detection of secondary lymph nodes (LNs) in a naturally occurring melanoma swine model compared to surgery and pathologic assessment.MethodsTwenty‐seven Sinclair swine were studied. The perfluorobutane microbubble contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was administered (1.0 mL total dose) around the melanoma, and contrast‐enhanced US was used to localize contrast‐enhanced sentinel lymph nodes (SLNs). Then Sonazoid (dose, 0.25–1.0 mL) was injected into the SLNs to detect contrast‐enhanced efferent lymphatic channels and secondary LNs. After peritumoral injection of blue dye, a surgeon (blinded to the contrast‐enhanced US results) performed a radical LN dissection. Contrast‐enhanced US was used to guide removal of any enhanced secondary LNs left after radical LN dissection. Clustered conditional logistic regression analyzed the benefit of contrast‐enhanced US–directed secondary LN dissection over radical LN dissection using pathologic findings as the reference standard.ResultsA total of 268 secondary LNs were resected, with 59 (22%) containing metastases. Contrast‐enhanced US detected 92 secondary LNs; 248 were identified by radical LN dissection; and 68 were identified by both methods. Metastases were detected in 20% (51 of 248) and 40% (37 of 92) of the secondary LNs identified by radical LN dissection and contrast‐enhanced US, respectively. Thus, secondary LNs detected by contrast‐enhanced US were nearly 5 times more likely to contain metastases than secondary LNs removed by radical LN dissection (odds ratio, 4.8; P < .0001). Twenty‐two of the 180 secondary LNs (12%) identified only by radical LN dissection contained metastases, whereas contrast‐enhanced US identified 20 secondary LNs after the surgeon completed the radical LN dissection, of which 8 (40%) contained metastases.ConclusionsSecondary LNs can be detected by using contrast‐enhanced US after injection of Sonazoid into SLNs. Secondary LNs detected with contrast‐enhanced US are significantly more likely to contain metastases than those removed by radical LN dissection.

The development of antiangiogenic therapies has stimulated interest in noninvasive imaging methods to monitor response. We investigated whether the effects of a vascular endothelial growth factor decoy receptor (VEGF Trap, Regeneron Pharmaceuticals, Tarrytown, NY) could be monitored in vivo using contrast-enhanced ultrasonography (CEUS). Twenty nude mice (in two groups) were implanted with a human melanoma cell line (DB-1). The active group received VEGF Trap (4 × 25 mg/kg over 2 weeks), whereas the control group received an inactive protein. An ultrasound contrast agent was injected followed by power Doppler imaging (PDI) and pulse inversion harmonic imaging (PIHI; regular and intermittent). Specimens were sectioned in the same planes as the images and stained for endothelial cells (CD31), cyclooxygenase-2 (COX-2), VEGF, and hypoxia (Glut1). Measures of tumor vascularity obtained with the different imaging modes were compared to immunohistochemical markers of angiogenesis. Mean tumor volume was smaller in the active group than in the control group (656 ± 225 vs 1,160 ± 605 mm 3 ). Overall, PDI and VEGF correlated ( r = .34; p = .037). Vascularity decreased from control to treated mice with intermittent PIHI, as did the expression of CD31 and COX-2 ( p # .02), whereas VEGF increased ( p = .05). CEUS appears to allow in vivo monitoring of the antiangiogenic effects of VEGF Trap in the DB-1 human melanoma xenograft model.

The development of anti-angiogenic therapies has stimulated interest in non-invasive imaging methods to monitor response. We investigated whether the effects of a vascular endothelial growth factor decoy receptor (VEGF Trap; Regeneron Pharmaceuticals, Tarrytown, NY) could be monitored in vivo using contrast-enhanced ultrasound (CEUS). Twenty nude mice (in two groups) were implanted with a human melanoma cell line (DB-1). The active group received VEGF Trap (4×25mg/kg over 2 weeks), while the control group received an inactive protein. An ultrasound contrast agent was injected followed by power Doppler imaging (PDI) and pulse inversion harmonic imaging (PIHI; regular and intermittent). Specimens were sectioned in the same planes as the images and stained for endothelial cells (CD31), cyclooxygenase-2 (COX-2), VEGF and hypoxia (Glut1). Measures of tumor vascularity obtained with the different imaging modes were compared to immunohistochemical markers of angiogenesis. Mean tumor volume was smaller in the active than in the control group (656±225 vs 1160±605mm3). Overall, PDI and VEGF correlated (r=0.34; p=0.037). Vascularity decreased from control to treated mice with intermittent PIHI as did the expression of CD31 and COX-2 (p≤0.02), while VEGF increased (p=0.05). CEUS appears to allow in vivo monitoring of the anti-angiogenic effects of VEGF Trap in the DB-1 human melanoma xenograft model.

OBJECTIVES/HYPOTHESIS:Sentinel lymph node biopsy (SLNB) has been utilized for cutaneous melanoma and other malignancies arising from the eye and ocular adnexa. Currently, SLNB requires blue dyes and/or radiopharmaceuticals; both of which have significant shortcomings. This study sought to evaluate the feasibility of SLNB with the use of real-time, contrast-enhanced ultrasound (CEUS) as an alternative technique for tumors arising in the conjunctiva. STUDY DESIGN:Prospective feasibility study in a porcine model. METHODS:Twelve experiments were performed on six non-tumor-bearing Yorkshire swine. An ultrasound contrast agent, Sonazoid (GE Healthcare, Oslo, Norway), (99m) technetium ((99m) Tc), and methylene blue (MB) (Covidien, Mansfield, MA) were injected in the ocular conjunctiva. Sentinel lymph nodes (SLNs) were localized with CEUS and findings were compared to that of MB and (99m) Tc. Fisher exact test was used. RESULTS:Contrast-enhanced SLNs were identified within an average of 6.2 minutes from time of injection of Sonazoid. A total of 17 SLNs were identified by at least one of the three techniques. Correlation between Sonazoid and (99m) Tc was 94.1% (16/17 SLNs). Correlation between (99m) Tc and MB was 88.2% (15/17). One SLN that was positive for (99m) Tc but negative for Sonazoid and was considered to be a false positive (1/17); findings were similar for MB (1/17). Differences between the three techniques were not significant (P = .886). CONCLUSIONS:CEUS-guided injection of conjunctiva for SLNB is technically feasible and correlates well with standard detection techniques. This technique shows promise for rapid, real-time, intraoperative imaging for SLNB, using a widely available imaging modality and avoiding the need for radiopharmaceuticals. LEVEL OF EVIDENCE:NA

The objective of this study was to compare coded harmonic imaging (HI) to pulse-inversion subharmonic imaging (SHI) in the characterization of renal masses. Twelve patients with 13 renal masses provided informed consent for an off-label CEUS exam prior to renal mass biopsy and cryoablation. All scanning was performed on a modified Logiq 9 ultrasound scanner with a 4C probe (GE Healthcare, Milwaukee, WI). Following baseline imaging, patients received a 2 ml bolus IV injection of the ultrasound contrast agent Optison (GE Healthcare, Princeton, NJ) and 10 ml flush during simultaneous 2D dual imaging in both grayscale (f=4.0 MHz) and SHI (f(transmit) =2.5 MHz, f(recieve)=1.25 MHz). Following a 15 min wait, patients received a 1 ml contrast injection during imaging with the unit's HI package (f(transmit)=2.0 MHz, f(recieve)=4.0 MHz). A blinded radiologist with experience in CEUS evaluated the heterogeneity, intensity, and wash-in/wash-out kinetics of enhancement in the mass relative to the renal cortex. Additionally, contrast signal time intensity curves (TICs) were constructed from both the renal mass and cortex, fit to a contrast wash-in model, and used to calculate the time to peak, perfusion, maximum intensity, and area under the curve. Finally, the radiologist and TIC findings from each CEUS imaging mode were compared to pathology. Biopsy findings showed the 13 renal masses consisted of 9 renal cell carcinomas, 2 areas of benign renal parenchyma, 1 area of renal necrosis, and 1 oncocytoma. All masses showed heterogeneous enhancement with both SHI and HI. Increased enhancement of the mass relative to the renal cortex was observed during the early contrast wash-in phase in 2/9 malignant and 3/4 benign lesions on SHI, and 3/9 malignant and 1/4 benign lesions on HI. Early contrast wash out in the mass relative to the cortex was observed in 6/9 malignant and 0/4 benign lesions in SHI (sensitivity=67%, specificity=100%), and 8/9 malignant and 1/4 benign lesions in HI (sensitivity=89%, specificity=75%). Comparison of the TIC parameters obtained from the renal mass and cortex of malignant lesions showed no statistically significant differences when compared to benign lesions (p > 0.2). Thus, visualization of early contrast washout on HI or SHI appears to be a reliable indicator of renal carcinoma on CEUS; albeit based on a limited sample size.

PURPOSETo compare subharmonic aided pressure estimation (SHAPE) with pressure catheter-based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy.MATERIALS AND METHODSThis HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive 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.RESULTSThe 45 study patients included 27 men and 18 women (age range, 19-71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG ≥ 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB ± 0.61 [standard deviation] vs -1.47 dB ± 0.29, P < .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension.CONCLUSIONPreliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension.

An aged male rhesus macaque in our colony had decreased appetite and a loss of interest in behavioral testing. CBC analysis revealed a regenerative, microcytic, hypochromic anemia with thrombocytosis, consistent with iron deficiency. A fecal occult blood test was positive. Ultrasound imaging revealed numerous, vascularized focal liver lesions that suggested metastases. The macaque's appetite continued to decrease, and he became more lethargic. At this point, the investigator elected to euthanize the macaque. At necropsy, the ileocolic junction was white and abnormally thickened, and the liver was pale tan with approximately 18 discrete white masses randomly scattered throughout the hepatic parenchyma. Histologically, the mass at the ileocolic junction was identified as an intestinal adenocarcinoma, whereas the liver masses were confirmed to be undifferentiated hepatic sarcomas. This case report describes a rhesus macaque that had 2 unrelated primary neoplasms. A review of the literature indicates that this rhesus macaque is the first reported to have an adenocarcinoma of the ileocolic junction and multiple hepatic sarcomas simultaneously.

Effective animal models are needed to evaluate the feasibility of new techniques to assess portal hypertension (PH). Here we developed 2 canine models of acute PH by increasing intrasinusoidal resistance and by increasing the portal vein (PV) flow volume to test the efficacy of a noninvasive technique to evaluate PH. The acute low-flow PH model was based on embolization of liver circulation by using a gelatin sponge material. The acute high-flow PH model was based on increasing the PV flow volume by using an arteriovenous (A-V) shunt from the femoral artery and saline infusion. PV pressures and diameters were assessed before and after inducing PH. Pressure values and diameters were obtained from the inferior vena cava in 3 unmanipulated controls. The low-flow model of PH was repeatable and successfully increased PV pressure by an average of 16.5 mm Hg within 15 min. The high-flow model of PH failed to achieve increased PV pressures. However, saline supplementation of the portal circulation in the high-flow model led to mean increases in PV pressures of 12.8 mm Hg within 20 min. Pulsatility in the PV was decreased in the low-flow model and increased in the high-flow model relative to baseline. No changes in PV diameter were noted in either model. These acute PH models are relatively straightforward to implement and may facilitate the evaluation of new techniques to assess PH.

Lymph node dissection is a widely used surgical procedure to treat and stage metastatic lymph nodes but has substantial side effects, such as lymphedema. Histotripsy is a noninvasive ultrasonic therapy that creates well-demarcated tissue fractionation using high-pressure and short acoustic shockwave pulses. This study investigates the possibility using of histotripsy to ablate lymph nodes noninvasively. Experiments were performed on 6 mixed breed healthy pigs, 11 - 12 weeks old and weighing 31 - 43 kg. Their superficial inguinal lymph nodes were treated in vivo with 5- or 10-cycle histotripsy pulses generated by focused, 1MHz therapy transducers, delivered at 50Hz pulse repetition frequency and peak rarefaction pressure above 21MPa. The treatment was guided by ultrasound imaging probes (either ATL CL15-7 or ATL L12-5) with a commercial ultrasound imaging system, HDI 5000. In one selected case, contrast-specific ultrasound was performed after perimammary injection of Sonazoid (GE Healthcare, Oslo, Norway) to localize the lymph nodes. Anatomical landmarks were then used to identify the same nodes for targeted therapy. The histological results show that, after histotripsy treatment, only the targeted lymph nodes were affected and they had demarcated foci of necrosis with minimal damage to the adjacent and intervening tissue. This in vivo acute study demonstrates the capability of histotripsy to noninvasively generate tissue fractionation within targeted lymph nodes, suggesting that histotripsy has the potential in noninvasive lymph node ablation.