The Effect of Mixing Iodinated Contrast Media and Ultrasound Contrast Agents on Subharmonic Signals.

Subharmonic aided pressure estimation (SHAPE) is a technique that utilizes subharmonic signals from microbubble contrast agents for pressure estimation. Validation of the SHAPE technique relies on synchronous measurements of in vivo pressures using contrast microbubbles and a pressure catheter (reference standard). For the guidance and placement of pressure catheter in vivo, iodinated contrast is used with fluoroscopy. Therefore, during data acquisition for validation studies of the SHAPE technique, both contrast microbubbles and iodinated contrast are present simultaneously within the vasculature. This study aims to elucidate the effects of iodinated contrast (Visipaque, GE HealthCare) on subharmonic signal amplitude from contrast microbubbles (Definity, Lantheus Medical Imaging, Inc.). In an acrylic water tank, 0.06 mL of Definity and varied amounts of Visipaque (0.14, 0.43, 0.85, and 1.70 mL) were added to 425 mL of deionized water. Ultrasound scanning was performed with a SonixTablet scanner (BK Medical Systems) using optimized parameters for SHAPE with Definity (ftransmit/receive = 3.0/1.5 MHz; chirp down pulse). Subharmonic data was acquired and analyzed at 9 different incident acoustic outputs (n = 3). Results showed an increase in subharmonic signal amplitude from Definity microbubbles in the presence of 0.14 mL Visipaque by 2.8 ± 1.3 dB (p < .001), no change with 0.85 mL Visipaque (0.7 ± 1.2 dB; p = .09) and a decrease in subharmonic amplitude in the presence of 1.70 mL Visipaque by 1.9 ± 0.7 dB (p < .001). While statistically significant effect on subharmonic signal amplitude of Definity microbubbles was noted due to the mixture, the magnitude of the effect was minimal (~2.8 dB) and unlikely to impact in vivo SHAPE measurements.

Sentinel Lymph Node Identification in Post Neoadjuvant Chemotherapy Breast Cancer Patients Undergoing Surgical Excision Using Lymphosonography.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

In Vitro and In Vivo Evaluation of Ultrasound-Triggered Release From Novel Spinal Device.

OBJECTIVES: Bacterial infection following spinal fusion is a major clinical concern with up to 20% incidence. An ultrasound-triggered bulk-release system to combat postsurgical bacterial survival was designed and evaluated. METHODS: Polylactic acid (PLA) clips were loaded with vancomycin (VAN) and microbubbles (Sonazoid, GE HealthCare) in vitro. Stability was determined over 14 days. VAN-loaded clips were submerged in water and insonated using a Logiq E10 scanner (GE HealthCare) with a curvilinear C6 probe. Doppler-induced VAN release was quantified using spectrophotometry. For in vivo testing, clips were loaded with methylene blue (MeB) solution and Sonazoid. These clips were implanted into a rabbit along the spine at L2 and L5, as well as a pig at L1 and L3, then insonated in Doppler mode using the C6 probe. RESULTS: Sonazoid microbubbles were better preserved when incubated in VAN compared with distilled water at 4°C, 25°C, and 37°C incubation temperatures (P = .0131). Contrast enhancement was observed from both solutions when incubated at 4°C storage conditions. Insonated clips achieved average cumulative VAN release of 101.8 ± 2.8% (81.4 ± 2.8 mg) after 72 hours. Uninsonated clips had only 0.3 ± 0.1% (0.3 ± 0.1 mg) average cumulative VAN release (P < .0001). Clips retrieved from the rabbit did not rupture with insonation nor produce MeB staining of surrounding tissues. In the pig, the PLA film was visibly ruptured and MeB tissue was observed following insonation, whereas the uninsonated clip was intact. CONCLUSION: These results demonstrate ultrasound-triggered release of an encapsulated prophylactic solution and provide an important proof-of-concept for continuing large animal evaluations for translational merit.

Contrast-Enhanced Ultrasound and Shear Wave Elastography: Novel Methods for the Evaluation of Urethral Stricture Disease.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: Thirty men were enrolled. Contrast-enhanced ultrasound (R2=0.709) showed the best correlation with intraoperative measured stricture length compared to retrograde urethrogram (R2=0.016) or grayscale ultrasound (R2=0.471). Stiffness of the spongiosum was greater at the site of the stricture (32.6±5.4 vs 27.3±5.8 kPa, p=0.044) and in narrower caliber strictures (p=0.044) but did not differ by stricture length (p=0.182). At followup (4.3±1.1 months) contrast-enhanced ultrasound detected stricture recurrence with 80% sensitivity, 100% specificity, and 93% accuracy compared to cystoscopy. CONCLUSIONS: This 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.

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

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

3D Harmonic and Subharmonic Imaging for Characterizing Breast Lesions: A Multi-Center Clinical Trial.

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.

Contrast-Enhanced Ultrasound in Small Intestinal Ischemia: Proof of Concept.

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.

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

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

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

BACKGROUND: Portal hypertension is the underlying cause of most complications associated with cirrhosis, with the hepatic venous pressure gradient (HVPG) used for diagnosis and disease progression. Subharmonic imaging (SHI) is a contrast-specific imaging technique receiving at half the transmit frequency resulting in better tissue suppression. AIMS: To determine whether the presence of optimized SHI signals inside the hepatic vein can be used as a screening test for portal hypertension. METHODS: This prospective trial had 131 patients undergoing SHI examination of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI). Images acquired after infusion of the ultrasound contrast agent Sonazoid (GE Healthcare, Oslo, Norway) were assessed for the presence of optimized SHI signals in the hepatic vein and compared to the HVPG values obtained as standard of care. RESULTS: Of 131 cases, 64 had increased HVPG values corresponding to subclinical (n = 31) and clinical (n = 33) portal hypertension (> 5 and > 10 mmHg, respectively), and 67 had normal HVPG values (< 5 mmHg). Two readers performed independent, binary qualitative assessments of the acquired digital clips. Reader one (experienced radiologist) achieved for the subclinical subgroup sensitivity of 98%, specificity of 88%, and ROC area of 0.93 and for the clinical subgroup sensitivity of 100% and specificity of 61%, with an ROC area of 0.74. Reader two (less experienced radiologist) achieved for the subclinical subgroup sensitivity of 77%, specificity of 76%, and ROC area of 0.76 and for the clinical subgroup sensitivity of 88% and specificity of 63%, with an ROC area of 0.70. Readers agreement was of 83% with kappa value of 0.66. CONCLUSION: The presence of optimized SHI signals inside the hepatic vein can be a qualitative screening test for portal hypertension, which could reduce the need for invasive diagnostic procedures.

Contrast-Enhanced Ultrasound of Muscle Perfusion May Indicate Patient Response to Left Ventricular Assist Device Therapy.

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.

Characterization of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study.

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.

Assessing carotid plaque neovascularity and calcifications in patients prior to endarterectomy.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: SMI may have potential for providing evidence of plaque vulnerability. MicroPure appears less useful in carotid applications.

Characterization of Breast Microcalcifications Using a New Ultrasound Image-Processing Technique.

OBJECTIVES: To evaluate a new commercial image-processing technique (MicroPure; Toshiba America Medical Systems, Tustin, CA) for detection and characterization of breast microcalcifications in patients undergoing stereotactic or ultrasound-guided biopsies using mammography as the reference standard. METHODS: One hundred female patients, with a total of 104 lesions, scheduled for an image-guided biopsy of an area with breast microcalcifications (identified on a prior mammogram) underwent MicroPure examinations of the breast using an Aplio XG scanner (Toshiba America Medical Systems) with a broad-bandwidth linear array. MicroPure combines nonlinear imaging and speckle suppression to mark suspected calcifications as white spots in a blue overlay image. Four independent and blinded readers (2 radiologists and 2 physicists) analyzed 208 digital clips consisting of dual grayscale ultrasound and MicroPure imaging, counting the number of microcalcifications seen with MicroPure. The observers also assessed the level of suspicion on a qualitative, visual analog, 6-point scale from 0 (no findings) over 1 (benign) to 5 (malignant). RESULTS: The mean number of microcalcifications ± SD seen was 6.3 ± 3.5, whereas mammography saw 28.9 ± 24.6 (P = .66). When the MicroPure level of suspicion scores were compared with pathologic results using a receiver operating characteristic curve analysis, the areas under the curve ranged from 0.54 to 0.59. Nonetheless, malignant cases were seen to have significantly more microcalcifications than benign cases (mean number of microcalcifications, 6.9 ± 5.1 versus 5.3 ± 3.7; P = .02). CONCLUSIONS: MicroPure can be used to identify areas with breast microcalcifications but cannot effectively characterize such areas. Instead, MicroPure may represent a new imaging method for guiding a biopsy to areas of microcalcifications.

Three-Dimensional Subharmonic Aided Pressure Estimation for Assessing Arterial Plaques in a Rabbit Model.

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.

On Factors Affecting Subharmonic-aided Pressure Estimation (SHAPE).

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.

Subdermal Ultrasound Contrast Agent Injection for Sentinel Lymph Node Identification: An Analysis of Safety and Contrast Agent Dose in Healthy Volunteers.

OBJECTIVES: Mapping of the lymphatic chain for identification of the sentinel lymph node (SLN) is an important aspect of predicting outcomes for patients with breast cancer, and it is usually performed as an intraoperative procedure using blue dye and/or radiopharmaceutical agents. Recently, the use of contrast-enhanced ultrasound (CEUS) has been proposed as an alternative imaging technique for this mapping. The objective of this study was to evaluate the use of subdermal administration of the ultrasound (US) contrast agent Sonazoid (GE Healthcare, Oslo, Norway) in terms of patient safety and to select the dose to be used for lymphatic applications in humans. METHODS: This study was performed in 12 female volunteers who received bilateral subdermal injections of Sonazoid (1 or 2 mL dose) in the mid-upper outer quadrant of their breasts at 2 different time points. Contrast-enhanced US examinations were performed 0, 0.25, 0.5, 1, 2, 4, 6, and 24 hours after injection to identify SLNs. RESULTS: Sentinel lymph nodes were identified within the first hour after injection as enhanced structures, and there was no significant difference by dose in the number of SLNs identified (P = .74). The volunteers only had minor adverse experiences (AEs) that resolved completely without intervention by study completion. CONCLUSIONS: The subdermal use of Sonazoid in this study showed only minor local and nonsignificant AEs that were completely resolved without any intervention. Two different doses were compared with no significant differences observed between them. Hence, the lower dose studied (1 mL) was selected for use in future clinical studies.

Quality of Life Impairment in Children and Adults with Vitiligo: A Cross-Sectional Study Based on Dermatology-Specific and Disease-Specific Quality of Life Instruments.

BACKGROUND: Vitiligo can negatively affect a patient's quality of life (QoL). A specific questionnaire has been developed and validated in the English language: the vitiligo-specific quality-of-life instrument (VitiQoL). The instrument was translated, culturally adapted and validated into Brazilian Portuguese (VitiQoL-PB). OBJECTIVE: The aim of this study was to assess the QoL in adult patients through the VitiQoL and Dermatology Life Quality Index (DLQI) and in pediatric patients through the Children's Dermatology Life Quality Index (CDLQI) in a sample of patients with vitiligo. METHODS: Subjects were selected from a dermatological outpatient clinic and from a private practice in Porto Alegre. The QoL of pediatric patients was evaluated using the CDLQI questionnaire. In adult patients we used the VitiQoL-PB and the DLQI. RESULTS: A strong correlation between the scores of the total VitiQoL and DLQI was observed (r = 0.81; p < 0.001). The factor that most contributed to the final score of VitiQoL was stigma. In our sample, women had higher scores than men (p < 0.05). Psychiatric problems were associated with lower QoL. In the pediatric population, the median score of the CDLQI was 3 (interquartile range 1.3-7.3). There was a statistically significant correlation between the child's age and the CDLQI score (rs = 0.41, p = 0.044). CONCLUSION: This study confirms that the VitiQoL is easy to administer and adds important information about the impact of vitiligo on a South American population. Stigmatization is very present in the disease. There are groups of patients that are more vulnerable, like women, patients with psychiatric diseases and adolescents.