Changes in renal-mesenteric duplex ultrasound velocities after fenestrated and branched endovascular aortic aneurysm repair.

OBJECTIVE: Stenting of renal and mesenteric vessels may result in changes in velocity measurements due to arterial compliance, potentially giving rise to confusion about the presence of stenosis during follow-up. The aim of our study was to compare preoperative and postoperative changes in peak systolic velocity (PSV, cm/s) after placement of the celiac axis (CA), superior mesenteric artery (SMA) and renal artery (RAs) bridging stent grafts during fenestrated-branched endovascular aortic repair (FB-EVAR) for treatment of complex abdominal aortic aneurysms (AAA) and thoracoabdominal aortic aneurysms. METHODS: Patients were enrolled in a prospective, nonrandomized single-center study to evaluate FB-EVAR for treatment of complex AAA and thoracoabdominal aortic aneurysms between 2013 and 2020. Duplex ultrasound examination of renal-mesenteric vessels were obtained prospectively preoperatively and at 6 to 8 weeks after the procedure. Duplex ultrasound examination was performed by a single vascular laboratory team using a predefined protocol including PSV measurements obtained with <60° angles. All renal-mesenteric vessels incorporated by bridging stent grafts using fenestrations or directional branches were analyzed. Target vessels with significant stenosis in the preoperative exam were excluded from the analysis. The end point was variations in PSV poststent placement at the origin, proximal, and mid segments of the target vessels for fenestrations and branches. RESULTS: There were 419 patients (292 male; mean age, 74 ± 8 years) treated by FB-EVAR with 1411 renal-mesenteric targeted vessels, including 260 CAs, 409 SMAs, and 742 RAs. No significant variances in the mean PSVs of all segments of the CA, SMA, and RAs at 6 to 8 weeks after surgery were found as compared with the preoperative values (CA, 135 cm/s vs 141 cm/s [P = .06]; SMA, 128 cm/s vs 125 cm/s [P = .62]; RAs, 90 cm/s vs 83 cm/s [P = .65]). Compared with baseline preoperative values, the PSV of the targeted vessels showed no significant differences in the origin and proximal segment of all vessels. However, the PSV increased significantly in the mid segment of all target vessels after stent placement. CONCLUSIONS: Stent placement in nonstenotic renal and mesenteric vessels during FB-EVAR is not associated with a significant increase in PSVs at the origin and proximal segments of the target vessels. Although there is a modest but significant increase in velocity measurements in the mid segment of the stented vessel, this difference is not clinically significant. Furthermore, PSVs in stented renal and mesenteric arteries were well below the threshold for significant stenosis in native vessels. These values provide a baseline or benchmark for expected PSVs after renal-mesenteric stenting during FB-EVAR.

What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

OBJECTIVE: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. MATERIALS AND METHODS: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. RESULTS: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). CONCLUSION: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. CLINICAL RELEVANCE STATEMENT: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. TRIAL REGISTRATION: Clinical trial ID: NCT01285960. KEY POINTS: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

Factors Associated With Ultrasound Color Doppler Twinkling by Breast Biopsy Markers: In Vitro and Ex Vivo Evaluation of 35 Commercially Available Markers.

BACKGROUND. Targeted axillary lymph node dissection after neoadjuvant systemic therapy (NST) for breast cancer depends on identifying marked metastatic lymph nodes. However, ultrasound visualization of biopsy markers is challenging. OBJECTIVE. The purpose of our study was to identify biopsy markers that show actionable twinkling in cadaveric breast and to assess the association of actionable twinkling with markers' surface roughness. METHODS. Commercial breast biopsy markers were evaluated for twinkling artifact in various experimental conditions relating to scanning medium (solid gel phantom, ultrasound coupling gel, cadaveric breast), transducer (ML6-15, 9L, C1-6), and embedding material (present vs absent). Markers were assigned twinkling scores from 0 (confident in no twinkling) to 4 (confident in exuberant twinkling); a score of 3 or greater represented actionable twinkling (sufficient confidence to rely solely on twinkling for target localization). Markers were hierarchically advanced to evaluation with increasingly complex media if showing at least minimal twinkling for a given medium. A 3D coherence optical profiler measured marker surface roughness. Mixed-effects proportional odds regression models assessed associations between twinkling scores and transducer and embedding material; Wilcoxon rank sum test evaluated associations between actionable twinkling and surface roughness. RESULTS. Thirty-five markers (21 with embedding material) were evaluated. Ten markers without embedding material advanced to evaluation in cadaveric breast. Higher twinkling scores were associated with presence of embedding material (odds ratio [OR] = 5.05 in solid gel phantom, 9.84 in coupling gel) and transducer (using the C1-6 transducer as reference; 9L transducer: OR = 0.36, 0.83, and 0.04 in solid gel phantom, ultrasound coupling gel, and cadaveric breast; ML6-15 transducer: OR = 0.07, 0.18, and 0.00 respectively; post hoc p between 9L and ML6-15: p < .001, p = .02, and p = .04). In cadaveric breast, three markers (Cork, Professional Q, MRI [Flex]) exhibited actionable twinkling for two or more transducers; surface roughness was significantly higher for markers with than without actionable twinkling for C1-6 (median values: 0.97 vs 0.35, p = .02) and 9L (1.75 vs 0.36; p = .002) transducers. CONCLUSION. Certain breast biopsy markers exhibited actionable twinkling in cadaveric breast. Twinkling was observed with greater confidence for the C1-6 and 9L transducers than the ML6-15 transducer. Actionable twinkling was associated with higher marker surface roughness. CLINICAL IMPACT. Use of twinkling for marker detection could impact preoperative or intraoperative localization after NST.

MRI-guided focused ultrasound ablation of painful lumbar facet joints: a retrospective assessment of safety and tolerability in human subjects.

OBJECTIVE: To evaluate the safety and tolerability of MRI-guided focused ultrasound (MRgFUS) for the treatment of facet joint-mediated pain in human subjects for whom conventional treatment had failed. Secondarily, to evaluate effectiveness of the procedure. METHODS: Consecutive patients who underwent MRgFUS at our institution were retrospectively identified. Chart review was performed to obtain relevant clinical and technical data. All patients had chronic low back pain and positive comparative medial branch blocks. RESULTS: Twenty-six MRgFUS treatments in 20 patients were included. Mean sonication energy was 1436.6 Joules. The procedure was technically successful in all patients. Of the treated patients, 29.6% experienced short-term worsening of low back pain immediately after the procedure, all by 1-4 points on a 0-10 scale. One patient (3.8%) reported temporary worsening of preexisting radicular symptoms after the procedure. Of 21 treatments with clinical follow-up of at least 3 months available, 12 (57.1%) had >3 months' pain relief, 2 (10%) had <3 months' benefit, 6 (30%) reported no benefit, and 1 (5%) patient was lost to follow-up. In patients who reported at least some benefit with prior conventional radiofrequency ablation, 8/10 (80%) benefited from the MRgFUS procedure. CONCLUSION: The present study demonstrates that MRgFUS ablation of the lumbar facet joints is a safe and tolerable procedure in human subjects and could provide another option for patients for whom radiofrequency ablation had failed. More than half of all patients received significant durable pain relief, which jumped to 80% for patients who had experienced at least some benefit from prior radiofrequency ablations.

Lymphatic Mapping Using US Microbubbles before Lymphaticovenous Anastomosis Surgery for Lymphedema.

Background Lymphaticovenous anastomosis (LVA) surgery is an effective surgical treatment of secondary lymphedema in the extremities, but indocyanine green (ICG) fluorescent lymphography, the reference standard for imaging target lymphatic vessels, has several limitations. More effective methods are needed for preoperative planning. Purpose To evaluate whether contrast-enhanced US (CEUS) can be used to identify target lymphatic vessels for LVA surgery in patients with secondary upper extremity lymphedema and compare the results with those from ICG fluorescent lymphography. Materials and Methods In this single-center retrospective review, CEUS with intradermal injection of microbubbles was performed in patients before LVA surgery in the upper extremities between October 2019 and September 2021. All patients had secondary upper extremity lymphedema from breast cancer treatment. Technical success rate was defined as lymphatic vessels identified with use of CEUS that led to successful LVAs. Descriptive statistics were used. Results All 11 patients were women (mean age, 56 years ± 8 [SD]). The median number of microbubble injection sites was 11 (range, 8-14). CEUS helped identify lymphatic vessels in all 11 women, including in six women in whom ICG fluorescent lymphography could not be performed or failed to help identify any targets. Thirty-five explorations (median, three per patient; range, two to four) were performed, and 24 LVAs (median, three per patient; range, zero to four) were created. Of the anastomoses, 33% (eight of 24) were mapped with use of both CEUS and ICG fluorescent lymphography, 58% (14 of 24) with CEUS only, and 8% (two of 24) with ICG fluorescent lymphography only. Among the 33 explorations on targets mapped with CEUS, an anastomosis could be made at 22 sites, for a technical success rate of 67%. Seven women had at least one additional LVA created from the use of CEUS. Conclusion Contrast-enhanced US is a promising tool for identifying lymphatic vessels in the upper extremities, especially when indocyanine green fluorescent lymphography fails to depict targets or cannot be used. Published under a CC BY 4.0 license.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Periprocedural outcomes comparing fibroid embolization and focused ultrasound: a randomized controlled trial and comprehensive cohort analysis.

BACKGROUND: Uterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. OBJECTIVE: The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. RESULTS: Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P <.001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self-rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median [interquartile range], 5 [1-7] vs 1 [1-4]; P = .002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < .001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < .001) and to have a longer median (interquartile range) recovery time (days off work, 8 [6-14] vs 4 [2-7]; P < .001; days until return to normal, 15 [10-29] vs 10 [10-15]; P = .02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities (P < .001 for each). Results were similar when restricted to the randomized controlled trial. CONCLUSION: Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.

Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial.

BACKGROUND: Uterine fibroids are an important source of morbidity for reproductive-aged women. Despite an increasing number of alternatives, hysterectomies account for about 75% of all fibroid interventional treatments. Evidence is lacking to help women and their health care providers decide among alternatives to hysterectomy. Fibroid Interventions: Reducing Symptoms Today and Tomorrow (NCT00995878, clinicaltrials.gov) is a randomized controlled trial to compare the safety, efficacy, and economics of 2 minimally invasive alternatives to hysterectomy: uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery. Although randomized trials provide the highest level of evidence, they have been difficult to conduct in the United States for interventional fibroid treatments. Thus, contemporaneously recruiting women declining randomization may have value as an alternative strategy for comparative effectiveness research. OBJECTIVE: We sought to compare baseline characteristics of randomized participants with nonrandomized participants meeting the same enrollment criteria and to determine whether combining the 2 cohorts in a comprehensive cohort design would be useful for analysis. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seeking interventional therapy at 3 US academic medical centers were randomized (1:1) in 2 strata based on calculated uterine volume (<700 and ≥700 cc(3)) to undergo embolization or focused ultrasound surgery. Women who met the same inclusion criteria but declined randomization were offered enrollment in a parallel cohort. Both cohorts were followed up for a maximum of 36 months after treatment. The measures addressed in this report were baseline demographics, symptoms, fibroid and uterine characteristics, and scores on validated quality-of-life measures. RESULTS: Of 723 women screened, 57 were randomized and 49 underwent treatment (27 with focused ultrasound and 22 with embolization). Seven of the 8 women randomized but not treated were assigned to embolization. Of 34 women in the parallel cohort, 16 elected focused ultrasound and 18 elected embolization. Compared with nonrandomized participants, randomized participants had higher mean body mass index (28.7 vs 25.3 kg/m(2); P = .01) and were more likely to be gravid (77% vs 47%; P = .003) and smokers (42% vs 12%; P = .003). Age, race, uterine volume, number of fibroids, and baseline validated measures of general and disease-specific quality of life, pain, depression, and sexual function did not differ between the groups. When we performed a comprehensive cohort analysis and analyzed by treatment arm, the only baseline difference observed was a higher median McGill Pain Score among women undergoing focused ultrasound (10.5 vs 6; P = .03); a similar but nonsignificant trend was seen in visual analog scale scores for pain (median, 39.0 vs 24.0; P = .06). CONCLUSION: Using a comprehensive cohort analysis of study data could result in additional power and greater generalizability if results are adjusted for baseline differences.

The Timing and Presentation of Major Hemorrhage After 18,947 Image-Guided Percutaneous Biopsies.

OBJECTIVE: The objective of our study was to characterize the temporal and clinical manifestation of major bleeding events after biopsy to guide clinicians in the institution of appropriate surveillance. MATERIALS AND METHODS: We performed a retrospective review of percutaneous image-guided biopsies performed between September 1, 2005, and May 31, 2012, including 18,947 biopsy events. According to routine protocol, follow-up telephone calls were made to patients 24 hours after biopsy, and chart review was performed 3 months after biopsy. Bleeding complications were defined using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) established by the National Cancer Institute. In patients with a grade 3 or greater bleeding complication, a retrospective chart review was performed to characterize the details of the complication including the timing of the complication and the primary clinical presentation of the event. RESULTS: Grade 3 hemorrhage was associated with 64 of 18,947 (0.3%) procedures, and there were three deaths associated with the biopsy event (0.02% or ≈ 2/10,000). Hemorrhage was most commonly associated with biopsy of a native kidney (17/1407, 1.2%). Twenty patients (31%) presented with a bleeding complication within 1 hour of biopsy. Twenty-seven patients (42%) presented within 2 hours of biopsy. Fifty-two patients (81%) presented within 24 hours, and the remaining 12 patients (19%) presented more than 24 hours after biopsy. Pain was the most common presentation of patients with bleeding complications, occurring in 39 (61%) patients. CONCLUSION: The incidence of major bleeding after percutaneous biopsies is very low, but delayed complications occur more frequently than anticipated. Pain is the most common clinical presentation of major bleeding complications.

Incidence of additional treatments in women treated with MR-guided focused US for symptomatic uterine fibroids: review of 138 patients with an average follow-up of 2.8 years.

PURPOSE: To assess long-term outcomes of magnetic resonance (MR)-guided focused ultrasound (US) treatments of uterine fibroids. MATERIALS AND METHODS: A retrospective follow-up of 138 patients treated at a single institution between March 2005 and November 2011 was conducted. The patients were not part of a clinical study and were followed through retrospective review of their medical records and telephone interviews to assess additional treatments for fibroid-related symptoms. Survival methods, including Cox proportional hazards models, were used to assess the association between incidence of additional treatments and patient data obtained during screening before treatment. RESULTS: The average length of follow-up was 2.8 years (range, 1-7.2 y). The cumulative incidence of additional treatments at 36 months and 48 months after MR-guided focused US was 19% and 23%, respectively. Women who did not need additional treatment were older than women who did (46.3 y ± 5.6 vs 43.0 y ± 5.8; P = .006; hazard ratio, 0.855; 95% confidence interval, 0.789-0.925). Additionally, women with heterogeneous or bright fibroids on T2-weighted MR imaging were more likely to require additional treatment compared with women with homogeneously dark fibroids (hazard ratio, 5.185 or 5.937, respectively; 95% confidence interval, 1.845-14.569 or 1.401-25.166, respectively). Physician predictions of treatment success, recorded during the screening process, had significant predictive value (P = .018). CONCLUSIONS: The long-term rates of additional interventions after MR-guided focused US of symptomatic uterine fibroids were found to be comparable with other uterine-sparing procedures, such as uterine artery embolization or myomectomy. Older patient age and homogeneously dark fibroids were associated with fewer additional treatments. Physician assessment of treatment success was found to be a valuable tool in patient screening.

Premedication of patients for prior urticarial reaction to iodinated contrast medium.

PURPOSE: The purpose of this study was to determine whether premedication of patients with a history of urticaria after low osmolality contrast media (LOCM) results in fewer subsequent reactions, and if a benefit is seen, to determine which premedication regimen results in the fewest reactions. MATERIALS AND METHODS: The subsequent contrast enhanced studies of patients who experienced urticaria after intravenous LOCM between 2002 and 2009 were reviewed to determine whether an additional reaction occurred. Patients undergoing subsequent studies received either no premedication, or premedication with diphenhydramine alone, corticosteroid alone, or corticosteroid plus diphenhydramine. Reactions occurring without premedication were termed repeat reactions and reactions occurring after premedication were termed breakthrough reactions. RESULTS: Fifty patients with a history of urticaria after LOCM met the inclusion criteria and underwent 133 subsequent contrast enhanced studies. Repeat reactions occurred in 7.6% (5/66) of subsequent studies in patients receiving no premedication. Breakthrough reactions occurred in 8% (2/25), 46% (12/26), and 44% (7/16) of subsequent studies in patients receiving premedication with diphenhydramine, corticosteroid, and corticosteroid plus diphenhydramine, respectively. All subsequent reactions consisted of urticaria as the most severe manifestation; no hemodynamic instability or respiratory compromise occurred. In multivariate analysis, premedication with corticosteroid was significantly associated with higher rate of breakthrough reaction relative to no premedication (OR 14.3, 95% CI: 4.1-50.4), as was premedication with corticosteroid plus diphenhydramine (OR 8.3, 95% CI: 1.8-37.9). CONCLUSION: The results suggest that premedication of patients with a history of urticaria after LOCM may not be necessary.

An Allergic Reaction in Contrast-enhanced Ultrasound Lymphography for Lymphovenous Bypass Surgery.

Lymphedema following oncologic intervention can cause significant lifelong morbidity for patients in whom conservative management fails. The associated swelling, discomfort, pain, and recurrent cellulitis greatly diminish quality of life. Surgical procedures, including suction-assisted lipectomy, lymphovenous anastomosis (LVA), and vascularized lymph node transfers, show effectiveness in both volume reduction in affected extremities and symptom relief. However, the success of procedures like LVA is dependent on effective preoperative lymphatic mapping to identify suitable vessels for anastomosis. Traditional superficial lymphatic mapping uses near infrared fluorescence indocyanine green (ICG) imaging. Moreover, recent advances in contrast-enhanced ultrasound (CEUS) lymphography increased lymphovenous bypass target identification for LVA in the extremities.7 CEUS lymphography uses microbubbles as a contrast-enhancing agent injected intradermally into the affected extremity with subsequent identification of superficial collecting lymphatic vessels using ultrasound. Although a recent report noted an uptick in severe and critical adverse drug reactions to an ultrasound contrast agent injected intravenously in stress echocardiography, adverse drug reactions associated with ultrasound contrast-enhancing agents in body ultrasound are rare. The safety profile and potential complications from CEUS lymphography in the lymphedema population have yet to be fully characterized. In this case report, the authors present the first cutaneous adverse drug event following a secondary exposure to the contrast used for CEUS imaging. Mechanisms and justifications for an immune-mediated process are explored, and a review of similar manifestations in other related contrast applications is discussed.

Technical note: Impact of linear array transducer Doppler aperture location on spectral peak velocity measurements - A phantom study.

OBJECTIVE: Ultrasound beams sometimes need to be steered from the edge of linear array transducers to reach the sample volume with a desired Doppler angle in vascular exams. This phantom study aims to evaluate the impact of apertures located at the array edge on peak velocity (PV) measurements. METHODS: Three ultrasound scanner systems equipped with eight transducers from 3 major ultrasound vendors were tested using a flow phantom with a horizontal tube. Five spectral Doppler measurements with the aperture positioned at one edge of the array and 5 with the aperture at the center of the array were obtained using all available scanner-transducer combinations while maintaining all scan parameters and the sample volume in the same tube location. Differences in PVs between center and edge apertures were compared across 4 constant flow rates. RESULTS: The averaged PVs for all phantom flow rates ranged from 24.4 cm/s to 138.2 cm/s from the array center. The averaged PVs from the center aperture were significantly greater than the corresponding measurements from the edge aperture for each flow rate (all p < 0.001). The relative PV differences ranged from 6.7% to 19.4% across all transducers and flow rates. CONCLUSION: Significantly lower PVs were consistently shown with the Doppler beam aperture at the array edge compared to center among all tested systems. This may be due to a narrower aperture width, shifted central axis, and less intrinsic spectral broadening error at the array edge. Controlling variations in Doppler aperture location is important in clinical applications which depend on consistent velocity measurements.

Long-Term Ultrasound Twinkling Detectability and Safety of a Polymethyl Methacrylate Soft Tissue Marker Compared to Conventional Breast Biopsy Markers-A Preclinical Study in a Porcine Model.

OBJECTIVE: We have studied the use of polymethyl methacrylate (PMMA) as an alternative biopsy marker that is readily detectable with ultrasound Doppler twinkling in cases of in vitro, ex vivo, or limited duration in vivo settings. This study investigates the long-term safety and ultrasound Doppler twinkling detectability of a PMMA breast biopsy marker following local perturbations and different dwell times in a 6-mo animal experiment. METHODS: This study, which was approved by our Institutional Animal Care and Use Committee, involved three pigs and utilized various markers, including PMMA (Zimmer Biomet), 3D-printed, and Tumark Q markers. Markers were implanted at different times for each pig. Mesh material or ethanol was used to induce a local inflammatory reaction near certain markers. A semiquantitative twinkling score assessed twinkling for actionable localization during monthly ultrasounds. At the primary endpoint, ultrasound-guided localization of lymph nodes with detectable markers was performed. Following surgical resection of the localized nodes, histomorphometric analysis was conducted to evaluate for tissue ingrowth and the formation of a tissue rind around the markers. RESULTS: No adverse events occurred. Twinkling scores of all markers for all three pigs decreased gradually over time. The Q marker exhibited the highest mean twinkling score followed by the PMMA marker, PMMA with mesh, and Q with ethanol. The 3D-printed marker with mesh and PMMA with ethanol had the lowest scores. All wire-localized lymph nodes were successfully resected. Despite varying percentages of tissue rind around the markers and a significant reduction in overall twinkling (p < 0.001) over time, mean PMMA twinkling scores remained clinically actionable at 6 and 5 mo using a General Electric C1-6 probe and 9L-probe, respectively. CONCLUSIONS: In this porcine model, the PMMA marker demonstrates an acceptable safety profile. Clinically actionable twinkling aids PMMA marker detection even after 6 mo of dwell time in porcine lymph nodes. The Q marker maintained the greatest twinkling over time compared to all the other markers studied.

Using US Twinkling Artifact to Identify Breast Biopsy Markers: Brief Report.

Breast biopsy markers play an essential role in the surgical management of patients with clinically node-positive breast cancer. Marking a pathology-proven lymph node ensures accurate imaging assessment of response to neoadjuvant systemic therapy and decreased false-negative rates in sentinel lymph node biopsy. There is a clinically unmet need to make breast biopsy markers, particularly in the axilla, more sonographically visible or identifiable for preoperative localization purposes. Previously described color Doppler US twinkling artifact of some breast biopsy markers in in vitro gel phantoms and in ex vivo cadaveric breasts suggests that twinkling of such markers can be leveraged for improved in vivo detection. In this retrospective case series of eight female patients (mean age, 58.6 years ± 12.3 [SD]), conventional B-mode US imaging failed to identify the biopsy marker associated with a surgical target in the breast or in an axillary lymph node. However, in each patient, the marker was successfully identified with the help of color Doppler US twinkling. Keywords: Breast, Ultrasound, Color Doppler US, Lymphatic, Artifacts, Biopsy Marker Published under a CC BY 4.0 license.

Lymphatic Mapping with Contrast-enhanced Ultrasound for Lymphaticovenous Anastomosis Surgery: How We Do It.

Lymphaticovenous anastomosis (LVA) surgery is an effective surgery for the treatment of lymphedema in the extremities. Indocyanine green lymphography is the reference standard for visualizing lymphatics for LVA surgery, but it has several limitations; most notably, superficial dermal congestion can mask deeper lymphatic vessels. To overcome the limitations, we add contrast-enhanced ultrasound (CEUS) lymphography. We have previously reported that CEUS lymphography can identify lymphatic vessels for LVA surgery that indocyanine green lymphography does not. Here, we describe how we perform CEUS lymphography, including workflow, technique, and documentation. Before informed consent, the patient must be screened for possible adverse reactions to microbubbles. The procedure involves multiple intradermal injections of the microbubble agent at various sites along the extremity. After each injection, imaging for microbubble uptake by lymphatic vessels is performed using an ultrasound scanner with contrast-specific software. We use sulfur hexafluoride lipid-type A microspheres (Lumason/SonoVue; Bracco Suisse SA), but we are investigating the performance of other Food & Drug Administration-approved microbubble agents for CEUS lymphography. Having a systematic approach to marking the skin can mitigate the hindrance of marking over ultrasound coupling gel. Another benefit of CEUS lymphography is the rapid identification of neighboring veins compatible in size and location for anastomosis. We hold regular scheduled multidisciplinary meetings for coordination of care, discussion of outcomes, quality assurance, and ongoing innovation.

Urgent and emergent breast lesions - A primer for the general radiologist, on-call resident and sonographer.

There are very few true breast emergencies. While infrequent, women do present to emergency departments or urgent care centres with breast-related concerns. In this case-based review, both common and uncommon urgent and emergent breast lesions are presented, emphasising ultrasound characteristics and imaging optimisation to improve accurate diagnosis and appropriate recommendations.

Uterine and Fibroid Imaging Analysis from the FIRSTT Study.

Background: Women with uterine fibroids often seek uterine-preserving treatments, rather than hysterectomy. Imaging-defined endpoints following nonsurgical treatments for fibroids are limited. Materials and Methods: Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT), a randomized controlled trial of uterine artery embolization (UAE) versus magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS), enrolled premenopausal women with symptomatic uterine fibroids. In this subanalysis, we report imaging results up to 36 months after UAE or MRgFUS. Magnetic resonance imaging (MRI) was performed at baseline for all women and during the 36 months after treatment if they did not meet other study endpoints. The main outcome of this subanalysis was fibroid volume reduction (defined both in terms of total fibroid load and volume of the largest fibroid), uterine volume reduction, and nonperfused volume. Results: During 2010-2014, 25 of the 37 women who were randomized and treated at Mayo Clinic had a 24-month follow-up MRI (11 UAE; 14 MRgFUS); among these women, 15 (7 UAE and 8 MRgFUS) had a 36-month follow-up MRI. Average age for the cohort was 44.1 (standard deviation, SD = 4.4) years. Nine patients had a second fibroid procedure by 36 months (seven in the MRgFUS arm and two in UAE arm). Median total fibroid load reduction was ∼50% in both treatment arms at both 24- and 36-month follow-up. Volume of the largest fibroid decreased more in the MRgFUS arm, whereas uterine volume decreased more in the UAE arm (neither reached statistical significance). At 24 months, median nonperfused volume was higher in the UAE arm (92%) than the MRgFUS arm (10%). Conclusions: Similar fibroid volume reduction was seen for the MRgFUS and UAE treatments in this comparative effectiveness study. Nonperfused volume 24 months after the procedure was higher in the UAE arm than in the MRgFUS arm. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov.

Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker: a comparative investigation.

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored.

Ultrasonographic Detection and Surgical Retrieval of a Nonmetallic Twinkle Marker in Breast Cancer: Pilot Study.

Purpose To evaluate the short-term safety of a nonmetallic twinkle marker and compare its conspicuity at color Doppler US with that of standard breast biopsy clips and radioactive seeds by using B-mode US in axillary lymph nodes. Materials and Methods This prospective study (November 2020-July 2021) of participants with node-positive breast cancer who completed chemotherapy involved placing a twinkle marker at the time of preoperative radioactive seed localization. A five-point scoring system (1 = easiest, 5 = most difficult) was used to rate the ease of identifying the clip, seed, and twinkle marker on postlocalization sonograms, mammograms, specimen radiographs, and gross pathologic specimens. Descriptive statistics were used. Results Eight women (mean age, 57 years ± 16 [SD]) were enrolled. The median scores for US conspicuity of each device were 3.9 (range, 3.7-5.0) for the radioactive seed, 2.4 (range, 1.0-5.0) for the clip, and 2.0 (range, 1.0-4.3) for the twinkle marker. In six of eight participants, the twinkle marker was the most identifiable at US. The seeds, clips, and twinkle markers were scored "very easy" to identify on seven of eight postlocalization mammograms. The surgeon retrieved all eight twinkle markers 1-3 days after localization. In all 16 interpretations, the seeds, clips, and twinkle markers were rated as very easy to identify on specimen radiographs. The clip was the most difficult device to identify at pathologic examination in all participants, and the twinkle marker was the easiest to identify in seven of eight participants. Conclusion This pilot study demonstrates that the safety and ease of US detection of a twinkling tissue marker may be comparable to a biopsy clip. Keywords: Ultrasonography, US-Doppler, Breast, Localization, Surgery Clinical trial registration no. NCT04674852 © RSNA, 2022.