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This study evaluated the efficacy of lymphosonography in the identification of sentinel lymph nodes (SLNs) in post neoadjuvant chemotherapy patients with breast cancer scheduled to undergo surgical excision.Seventy-nine subjects scheduled for breast cancer surgery with SLN excision completed this IRB-approved study, out of which 18 (23%) underwent neoadjuvant chemotherapy before surgery. Subjects underwent percutaneous Sonazoid (GE Healthcare) injections around the tumor area for a total of 1.0 mL. Lymphosonography was performed using CPS on an S3000 HELX scanner (Siemens Healthineers) with a linear probe. Subjects received blue dye and radioactive tracer as part of their standard of care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and Sonazoid. The results were compared between methods and pathology findings.Seventy-two SLNs were surgically excised from 18 subjects, 29 were positive for blue dye, 63 were positive for radioactive tracer and 57 were positive for Sonazoid. Comparison with blue dye showed that both radioactive tracer and lymphosonography achieved an accuracy of 53% (P .50). Comparison with radioactive tracer showed that blue dye had an accuracy of 53%, while lymphosonography achieved an accuracy of 67% (P .01). Of the 72 SLNs, 15 were determined malignant by pathology; the detection rate was 47% for blue dye (7/15), 67% for radioactive tracer (10/15) and 100% for lymphosonography (15/15) (P .001).Lymphosonography achieved similar accuracy as radioactive tracer and higher accuracy than blue dye for identifying SLNs. The 15 SLNs positive for malignancy were all identified by lymphosonography.

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.

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.

The performance of ultrasound features from shear wave elastography (SWE) and high-frequency ultrasound imaging was evaluated independently and in combination to diagnose carpal tunnel syndrome (CTS).Twenty-five subjects were imaged in a sitting position with an arm extended and palm facing up. SWE of the medial nerve (MN) was acquired at the wrist level (site 1) and proximal to the pronator quadratus muscle (site 2). Cross-sectional area (CSA) and vascularity of the MN were assessed at the wrist using a 24 MHz probe. Color and power Doppler imaging (CDI and PDI), monochrome and color-coded Superb Microvascular Imaging (SMI) were performed for vascularity assessments. The diagnosis and severity of CTS was determined by clinical and electrodiagnostic tests. Diagnostic performance of the ultrasound features was assessed by t-tests, ANOVAs, and ROC analysis.The study included 20 control hands and 27 hands with CTS. All ultrasound features except for the stiffness ratio were significantly different between the CTS and control wrists (p0.04). The stiffness of MN at site 1 showed a higher accuracy than at site 2. The combination of CSA and MN stiffness from site 2 showed an overall accuracy of 95% with a specificity and sensitivity of 100% and 93%, respectively. The CSA, MN stiffness from site 2, and CDI combination improved the accuracy to 96% with specificity and sensitivity of 100% and 93%, respectively. However, no ultrasound features (independently or in combination) differentiated all stages of CTS severity.SWE with high-frequency ultrasound imaging showed potential for the diagnosis of CTS.

The objective of the work described here was to evaluate the efficacy of lymphosonography in identifying sentinel lymph nodes (SLNs) in patients with breast cancer undergoing surgical excision. Of the 86 individuals enrolled, 79 completed this institutional review board-approved study. Participants received subcutaneous 1.0-mL injections of ultrasound contrast agent (UCA) around the tumor. An ultrasound scanner with contrast-enhanced ultrasound (CEUS) capabilities was used to identify SLNs. Participants were administered with blue dye and radioactive tracer to guide SLN excision as standard-of-care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and UCA, and sent for pathology. Two hundred fifty-two SLNs were excised; 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Comparison with blue dye revealed accuracies of 96.2% for radioactive tracer and 99.4% for lymphosonography (p0.15). Relative to radioactive tracer, blue dye had an accuracy of 68.5%, and lymphosonography achieved 86.5% (p0.0001). Of 252 SLNs excised, 34 were determined to be malignant by pathology; 18 were positive for blue dye (detection rate = 53%), 23 for radioactive tracer (detection rate = 68%) and 34 for UCA (detection rate = 100%) (p0.0001). Lymphosonography was similar in accuracy to radioactive tracer and higher in accuracy than blue dye in identifying SLNs. All 34 malignant SLNs were identified by lymphosonography.

TPS777 Background: Pancreatic ductal adenocarcinoma (PDAC) is 3% of cancers diagnosed in the United States and it is the fourth leading cause of cancer-related deaths. Hence, there is a considerable clinical need to develop innovative strategies for effective drug delivery and treatment. Sonoporation is a novel method that can enhance the therapeutic efficacy of co-administered chemotherapy by localized contrast-enhanced ultrasound imaging (CEUS) of gas-filled microbubbles (ultrasound contrast agent UCA), which temporarily changes tumor vascular microenvironment by increasing angiogenic vessel leakage through microstreaming, shockwaves and the activation of various intracellular signaling responses. Our Phase I clinical trial of sonoporation in 10 PDAC patients treated with Gemcitabine demonstrated no additional toxicity and an increase in median survival compared to 63 historical controls (8.9 vs 17.6 months; p = 0.011). Animal studies investigated 4 commercial UCAs under 2 different acoustic regimes and established the optimal UCA (Sonazoid, GE Healthcare, Oslo, Norway) as well as acoustic settings for sonoporation of PDAC. Methods: This Phase II clinical trial aims to improve standard of care (SoC) chemotherapy treatment by adding sonoporation (i.e., augmenting the SoC treatment with CEUS and microbubbles). Two sites (one in USA and one in Norway) will enroll 120 subjects with PDAC stage III or IIV prior to starting SoC chemotherapy. Exclusion criteria include known allergies to the UCA. The primary objective is to evaluate the safety and therapeutic efficacy of sonoporation on PDAC SoC treatment based on local progression-free and overall survival. Two groups: SoC chemotherapy or SoC chemotherapy followed by sonoporation. The optimal CEUS and microbubble conditions will be applied to a single PDAC tumor imaged by ultrasound. Treatment delivered day of SoC chemotherapeutic treatment for PDAC when the concentration of drugs is maximum. Gehan-Breslow-Wilcoxon test and Log-rank test will be used to compare survival. All clinical variables (e.g., concomitant imaging results, blood tests, etc.) will also be compared between groups with and without sonoporation. Clinical trial information: NCT04821284 .

Penile prosthesis (PP) is a gold standard for treatment of erectile dysfunction given its reliability and efficacy. Infection remains the most feared complication of prosthetic surgery, which usually results in device removal, and places a significant economic burden on the healthcare system. While biofilms have shown to support the persistence of microorganisms, the degree by which this matrix is truly pathogenic remains unknown given its high prevalence even in asymptomatic patients. We aim to review and summarize the current literature pertaining to biofilm formation in the setting of PP surgeries in clinically infected and non-infected cases.Searches were performed in the MEDLINE online database through PubMed using a combination of keywords "penile prosthetic" OR "penile prosthesis" OR "penile implant" AND "biofilm" OR "revision" OR "removal" OR "infection" OR "explant". Eleven articles met inclusion criteria. There were only three studies that explicitly listed the number of biofilms identified in their cohort, but we also included eight articles that mentioned swabbing and culturing of any bacterial biofilm during revision procedures for both clinically infected and non-infected implants.Infected PP yielded a 11-100% rate of biofilm presence, while non-infected PP yielded a 3-70% rate of biofilm presence. Time to reoperation from initial PP placement were also largely variable, ranging from 2 weeks to over 2 years. Coagulase-negative staphylococcus (i.e.,Since the advent of PP surgery, diabetes control, revision washout protocols and antibiotic-impregnated devices have led to an overall decrease in biofilm formation and infectious complications. There is an overall paradigm shift in microbial profiles with more virulent organisms, such as

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.

Resumo: O enlace entre psicanálise e poética é indagado em relação à clínica das psicoses. Inicialmente, o artigo discorre sobre o trabalho da poesia na escuta e leitura do sujeito do inconsciente, quer dizer, na instauração do Discurso da Psicanálise. A noção proposta por Lacan como lalangue subsidia tal articulação. A seguir, na busca do rastro do trabalho da poética (do inconsciente), discutem-se aspectos de três experiências célebres no campo das psicoses: Schreber, Marcelle e Wolfson. Por fim, a sonoridade poética (musicalidade) surge como possibilidade de intervenção na direção de um tratamento que não negligencie o sujeito do inconsciente nas psicoses. Abstract: In this article, the link between psychoanalysis and poetics is questioned in relation to the treatment of psychoses. The work of poetry is investigated in the hearing and reading of the subject of the unconscious, that is, in the establishment of the Discourse of Psychoanalysis. The notion proposed by Lacan as lalangue subsidizes such articulation. Then, in the search for the traces of the work of poetry (of the unconscious), aspects of three famous experiences in the field of psychoses are discussed: Schreber, Marcelle and Wolfson. Finally, poetic sonority (musicality) emerges as a possibility of intervention in the direction of a treatment that does not neglect the subject of the unconscious in psychoses.

Background A variant of unknown significance (VUS) is a variant form of a gene that has been identified through genetic testing, but whose significance to the organism function is not known. An actual challenge in precision medicine is to precisely identify which detected mutations from a sequencing process have a suitable role in the treatment or diagnosis of a disease. The average accuracy of pathogenicity predictors is 85%. However, there is a significant discordance about the identification of mutational impact and pathogenicity among them. Therefore, manual verification is necessary for confirming the real effect of a mutation in its casuistic. Methods In this work, we use variables categorization and selection for building a decision tree model, and later we measure and compare its accuracy with four known mutation predictors and seventeen supervised machine-learning (ML) algorithms. Results The results showed that the proposed tree reached the highest precision among all tested variables: 91% for True Neutrals, 8% for False Neutrals, 9% for False Pathogenic, and 92% for True Pathogenic. Conclusions The decision tree exceptionally demonstrated high classification precision with cancer data, producing consistently relevant forecasts for the sample tests with an accuracy close to the best ones achieved from supervised ML algorithms. Besides, the decision tree algorithm is easier to apply in clinical practice by non-IT experts. From the cancer research community perspective, this approach can be successfully applied as an alternative for the determination of potential pathogenicity of VOUS.

OBJECTIVES—: This pilot study evaluated whether contrast-enhanced subharmonic imaging (SHI) could be used to characterize adnexal masses before surgical intervention. METHODS—: Ten women (with 12 lesions) scheduled for surgery of an ovarian mass underwent an SHI examination of their adnexal region using a modified LOGIQ E9 scanner (GE Healthcare, Waukesha, WI) with an endocavitary transducer, in which digital clips were acquired by pulse destruction-replenishment SHI across the lesions. Time-intensity curves were created offline to quantitatively evaluate SHI parameters (fractional tumor perfusion, peak contrast intensity, time to peak contrast enhancement, and area under the time-intensity curve), which were compared to pathologic characterizations of the lesions. RESULTS—: Of the 12 masses, 8 were benign, and 4 were malignant. A qualitative analysis of the SHI images by an experienced radiologist resulted in diagnostic accuracy of 70%, compared to 56% without contrast, whereas an inexperienced radiologist improved from 50% to 58% accuracy, demonstrating the benefit of SHI. A quantitative analysis of SHI parameters produced diagnostic accuracy as high as 81%. Peak contrast intensity was significantly greater in malignant than benign masses (mean ± SD, 0.109 ± 0.088 versus 0.046 ± 0.030 arbitrary units; P = .046). Malignant masses also showed significantly greater perfusion than benign masses (24.79% ± 25.34% versus 7.62% ± 6.50%; P = .045). When the radiologist reads were combined with the most predictive quantitative SHI parameter (percent perfusion), diagnostic accuracy improved to 84% for the experienced radiologist and 96% for the novice radiologist. CONCLUSIONS—: Results indicate that SHI for presurgical characterization of adnexal masses may improve the determination of malignancy and diagnostic accuracy, albeit based on a small sample size.

The objective was to use two ultrasound image and signal processing techniques (MicroPure and superb microvascular imaging [SMI]; Toshiba Medical, Tokyo, Japan) to investigate carotid plaque calcification and intraplaque neovascularity flow as biomarkers for plaque vulnerability in patients before endarterectomy.Thirty patients, with preoperative computed tomography angiography and scheduled for carotid endarterectomy, were enrolled in an institutional review board-approved study. Bilateral grayscale, power Doppler, SMI and MicroPure imaging of the carotids were performed using an Aplio 500 Platinum scanner (Toshiba). MicroPure combines nonlinear imaging and speckle suppression to mark calcifications as white spots in a blue overlay, and SMI uses clutter suppression to extract microvascular flow signals. Readers counted calcifications and scored them as present or absent; intraplaque neovascularity was scored on a 4-point scale by ultrasound imaging as well as by pathology (as the reference). MicroPure and SMI assessments were compared with conventional ultrasound examination and computed tomography angiography with pathology as the reference standard.Owing to technical difficulties and cancelled operations, 57 carotids were studied; endarterectomies yielded 28 specimens. Intraplaque neovascularization was detected by SMI in significantly more plagues than by power Doppler (41 vs 22 out 57 examined plaques or 72% vs 39%; P .0001). There was no statistical difference between either reader compared with pathology (P.37). Sensitivity specificity and accuracy for detecting intraplaque neovascularity based on color SMI and PDI were 84% (95% confidence interval [CI], 64%-96%), 33% (95% CI, 1%-91%), 79% (95% CI, 59%-92%), and 52% (95% CI, 31%-72%), 100% (95% CI, 23%-100%), and 57% (95% CI, 37%-76%), respectively. MicroPure did not correlate with any measures of intraplaque flow (P.13).SMI may have potential for providing evidence of plaque vulnerability. MicroPure appears less useful in carotid applications.

BACKGROUND This study compared aortic pressures estimated using a SphygmoCor XCEL PWA device (ATCOR, Naperville, IL) noninvasively with aortic pressures obtained using pressure catheters during catheterization procedures and analyzed the impact of a linear-fit function on the estimated pressure values. METHODS One hundred and thirty-six patients scheduled for cardiac catheterization procedure were enrolled in IRB approved studies. Catheterization procedures were performed according to standard-of-care to acquire aortic pressure measurements. Immediately after the catheterization procedure with the pressure catheters removed, while the patients were still in the catheterization laboratory, central aortic pressures were estimated with the SphygmoCor device (using its inbuilt transfer function). The error between measured and estimated aortic pressures was evaluated using Bland–Altman analysis (n = 93). A linear-fit was performed between the measured and estimated pressures, and using the linear equation the error measurements were repeated. A bootstrap analysis was performed to test the generalizability of the linear-fit function. In a subset of cases (n = 13), central aortic pressure values were also obtained using solid-state high-fidelity catheters (Millar, Houston, TX), and the error measurements were repeated. RESULTS The magnitude of errors between the measured and estimated aortic pressures (mean errors >6.4 mm Hg; mean errors >8.0 mm Hg in the subset) were reduced to less than 1 mm Hg after using the linear-fit function derived in this study. CONCLUSIONS For the population examined in this study, the SphygmoCor data must be used with the linear-fit function to obtain aortic pressures that are comparable to the measurements obtained using pressure catheters. CLINICAL TRIALS REGISTRATION Trial Numbers NCT03243942 and NCT03245255.

Low-intensity pulsed ultrasound (LIPUS) accelerates fracture healing by stimulating the production of bone callus and the mineralization process. This study compared a novel bimodal acoustic signal (BMAS) device for bone fracture healing to a clinical LIPUS system (EXOGEN; Bioventus, Durham, NC, USA). Thirty rabbits underwent a bilateral fibular osteotomy. Each rabbits' legs were randomized to receive 20-min treatment daily for 18 days with BMAS or LIPUS. The latter utilizes a longitudinal ultrasonic mode only, while the former employs ultrasound-induced shear stress to promote bone formation. Power Doppler imaging (PDI) was acquired days 0, 2, 4, 7, 11, 14, and 18 post-surgery to monitor treatment response and quantified off-line. X-rays were acquired to evaluate fractures on days 0, 14, 18, and 21. Seventeen rabbits completed the study and were euthanized day 21 post-surgery. The fibulae were analyzed to determine maximum torque, initial torsional stiffness, and angular displacement at failure. ANOVAs and paired t-tests were used to compare pair-wise outcome variables for the two treatment modes on a per rabbit basis. The BMAS system induced better fracture healing with greater stiffness (BMAS 0.21 ± 0.19 versus LIPUS 0.16 ± 0.19 [Formula: see text]cm/°, p = 0.050 ) and maximum torque (BMAS 7.84 ± 5.55 versus LIPUS 6.26 ± 3.46 [Formula: see text]cm, p = 0.022 ) than the LIPUS system. Quantitative PDI assessments showed a higher amount of vascularity with LIPUS than BMAS on days 4 and 18 ( ). In conclusion, the novel BMAS technique achieved better bone fracture healing response than the current Food and Drug Administration (FDA)-approved LIPUS system.

Introduction: The SphygmoCor (ATCOR, Naperville, IL) device utilizes a generalized transfer function based on patient’s age and gender to derive the aortic pressure pulse from the brachial-cuff based pressure measurements. This study compared aortic pressures obtained using SphygmoCor with aortic pressures obtained during cardiac catheterization. Hypothesis: Mean differences in aortic pressures obtained using SphygmoCor and pressure catheters will be less than 5 mmHg. Methods: After IRB approval, 136 patients were enrolled. During standard-of-care catheterization procedure, aortic pressure measurements were obtained using fluid-filled catheters. In a subset of patients (n = 13) the aortic pressure values were also obtained using solid-state high-fidelity Millar catheters. Immediately after the catheterization procedure, while the patients were still in the catheterization laboratory (on the procedure table), central aortic pressures were estimated with the SphygmoCor device. The measured and estimated aortic pressures were compared using linear regression and Bland-Altman analysis. A linear fit was performed to derive an additional transfer function to convert SphygmoCor pressure values to catheter-based aortic pressures, and the resulting differences in pressure values were compared. A bootstrap analysis was performed to test the generalizability of this transfer function. Results: Mean differences in systolic, diastolic and pulse aortic pressures obtained using the two techniques ranged from 6.5 to 18.0 mmHg (p < 0.001). In the subset with high-fidelity catheters, the differences ranged from 8.0 to 18.9 mmHg. With the linear-fit transfer function, the differences in systolic, diastolic and pulse aortic pressures were low (< 1 mmHg) corresponding to a reduction in bias noted with Bland-Altman analysis. The bootstrap analysis of the transfer function (100 iterations) achieved a coefficient of variation for the root mean square error < 8.4% for systolic, diastolic and pulse aortic pressures. Conclusions: The magnitude of the differences between the SphygmoCor-estimated and catheter-based systolic, diastolic and pulse aortic pressures reduced considerably after using the linear-fit transfer function derived in this study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Combining quantitative 3D SHI parameters and clinical assessments improves the characterization of suspicious breast lesions.

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.

Urologists will benefit from an imaging modality which can assess intra and extraluminal characteristics of urethral strictures. We conducted a prospective pilot study evaluating the utility of contrast-enhanced ultrasound and shear wave elastography for the evaluation of bulbar urethral stricture disease.Patients with a single, bulbar urethral stricture were prospectively recruited. Contrast-enhanced ultrasound and shear wave elastography were performed at the time of surgical repair and at 4 months' followup using an Aplio i800 scanner (Canon Medical Systems, Tustin, California) with an i8CX1 transducer. Sulfur hexafluoride lipid-type A microsphere ultrasound contrast (Lumason®, Bracco Imaging, Princeton, New Jersey) was injected retrograde through the urethra. Stiffness of the corpus spongiosum was measured at and adjacent to the stricture site. Stricture lengths based on retrograde urethrogram, grayscale ultrasound and contrast-enhanced ultrasound were correlated with measured intraoperative stricture length.Thirty men were enrolled. Contrast-enhanced ultrasound (RThis pilot study demonstrates the ability of contrast-enhanced ultrasound and shear wave elastography to become safe, accurate, and potentially efficacious modalities for assessing bulbar urethral strictures and spongiofibrosis.

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

OBJECTIVES—: To investigate 3-dimensional subharmonic aided pressure estimation (SHAPE) for measuring intraplaque pressure and the pressure gradient across the plaque cap as novel biomarkers for potentially predicting plaque vulnerability. METHODS—: Twenty-seven rabbits received a high-cholesterol diet for 2 weeks before a balloon catheter injury to denude the endothelium of the aorta, followed by 8 to 10 weeks of the high-cholesterol diet to create arteriosclerotic plaques. SHAPE imagings of the resulting plaques were performed 12, 16, and 20 weeks after injury using a LOGIQ 9 scanner with a 4D10L probe (GE Healthcare, Milwaukee, WI) before and during an infusion of Definity (Lantheus Medical Imaging, North Billerica, MA) and Sonazoid (GE Healthcare, Oslo, Norway). The ratios of the maximum subharmonic magnitudes at baseline and during the infusion were correlated with the intraplaque pressure and pressure gradient across the plaque cap obtained from direct measurements. RESULTS—: Ten rabbits died prematurely after the balloon injury procedure or due to toxicity from the high-cholesterol diet, whereas 2 rabbits were excluded for other conditions. Five rabbits were scanned in the 12-, 16-, and 20-week groups, respectively. Even after 20 weeks, the plaques that developed were very small (mean ± SD, 0.9 ± 0.4 × 0.14 ± 0.05 cm). Definity performed better than Sonazoid in this application but still only achieved a moderate correlation with pressure across the plaque cap (Definity, r = −0.40; Sonazoid, r = 0.22) and intraplaque pressure (Definity, r = −0.19; Sonazoid, r = −0.11). CONCLUSIONS—: Initial findings from plaque pressure estimation using 3-dimensional SHAPE technique showed only moderate correlations with reference standards, but that may be have been due to weaknesses in the animal model studied.

Subharmonic-aided pressure estimation (SHAPE) estimates hydrostatic pressure using the inverse relationship with subharmonic amplitude variations of ultrasound contrast agents (UCAs). We studied the impact of varying incident acoustic outputs (IAO), UCA concentration, and hematocrit on SHAPE. A Logiq 9 scanner with a 4C curvilinear probe (GE, Milwaukee, Wisconsin) was used with Sonazoid (GE Healthcare, Oslo, Norway) transmitting at 2.5 MHz and receiving at 1.25 MHz. An improved IAO selection algorithm provided improved correlations ( r from −0.85 to −0.95 vs. −0.39 to −0.98). There was no significant change in SHAPE gradient as the pressure increased from 10 to 40 mmHg and hematocrit concentration was tripled from 1.8 to 4.5 mL/L (Δ0.00-0.01 dB, p = 0.18), and as UCA concentration was increased from 0.2 to 1.2 mL/L (Δ0.02-0.05 dB, p = 0.75). The results for the correlation between the SHAPE gradient and hematocrit values for patients ( N = 100) in an ongoing clinical trial were also calculated showing a poor correlation value of 0.14. Overall, the SHAPE gradient is independent of hematocrit and UCA concentration. An improved algorithm for IAO selection will make SHAPE more accurate.

PURPOSE—: Left ventricular assist device (LVAD) support is associated with peripheral vascular abnormalities beyond those associated with heart failure (HF). These abnormalities are associated with persistent functional impairments that adversely impact quality of life (QoL). Methods for measuring peripheral vascular function in this population are needed. METHODS—: This pilot study investigated the use of contrast-enhanced ultrasound (CEUS) using standardized protocols to estimate changes in peripheral (quadriceps) muscle perfusion among patients with HF (INTERMACS profile 3) undergoing LVAD implantation (n = 7). Patients were then stratified by those who did (“responders”, n = 4) and did not (“nonresponders”, n = 3) report QoL improvement with LVAD support. RESULTS—: Serial measurements obtained preoperatively and 3 months following LVAD implantation showed no significant change (P > .23) in muscle perfusion by all CEUS-based measures at rest or with an exercise stimulus for the overall population. Responders exhibited improved muscle perfusion at rest (P = .043) and decreased time to peak contrast enhancement (P = .010) at 3 months compared with baseline, suggesting improved delivery of blood to the extremities post-LVAD. Nonresponders showed unchanged resting muscle perfusion (P > .99), time to peak contrast enhancement (P = .59), and response to exercise stimulus (P > .99) following LVAD therapy. CONCLUSION—: Our findings suggest that CEUS evaluation is a promising noninvasive, quantitative modality for real-time assessment of peripheral vasculature and muscle perfusion as an indication of treatment response in LVAD recipients and that this modality may capture perfusion measures important to QoL following LVAD implantation.

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

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/receiving at 2.5/1.25MHz) using Sonazoid (GE Healthcare, Oslo, Norway; IND 124,465). Twenty-one (median age 59 years; 12 Males) of the 178 patients enrolled in this IRB approved study (14F.113) were identified as having clinically significant portal hypertension based on their hepatic venous pressure gradient (HVPG) results (i.e., HVPG ≥ 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 non-responder (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.

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.

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.