Virtual Compared With In-Clinic Transvaginal Ultrasonography for Ovarian Reserve Assessment.

OBJECTIVE: To evaluate noninferiority of virtual transvaginal ultrasonography compared with in-clinic ultrasonography for ovarian reserve assessment. METHODS: We conducted a single-site, head-to-head crossover trial. Participants performed self-administered virtual transvaginal ultrasonography at home, guided by a remote-certified ultrasound technologist, then underwent transvaginal ultrasonography in-clinic with another ultrasound technologist. Participants were women in the greater Boston area interested in evaluating ovarian reserve and recruited through social media, health care referrals, and professional networks. The uterus and ovaries were captured in sagittal and transverse views. These randomized recordings were reviewed by two or three independent, blinded reproductive endocrinologists. The primary outcome was noninferiority of the rate of clinical quality imaging produced at home compared with in clinic. Sample size was selected for greater than 90% power, given the 18% noninferiority margin. Secondary outcomes included antral follicle count equivalency and net promoter score superiority. RESULTS: Fifty-six women were enrolled from December 2020 to May 2021. Participants varied in age (19-35 years), BMI (19.5-33.9), and occupation. Ninety-six percent of virtual and 98% of in-clinic images met "clinical quality." The difference of -2.4% (97.5% CI lower bound -5.5%) was within the noninferiority margin (18%). Antral follicle counts were equivalent across settings, with a difference in follicles (0.23, 95% CI -0.36 to 0.82) within the equivalence margin (2.65). Virtual examinations had superior net promoter scores (58.1 points, 97.5% CI of difference 37.3-79.0, P<.01), indicating greater satisfaction with the virtual experience. CONCLUSION: Virtual transvaginal ultrasonography remotely guided by an ultrasonography technologist is noninferior to in-clinic transvaginal ultrasonography for producing clinical quality images and is equivalent for estimating antral follicle count. Virtual transvaginal ultrasonography had superior patient satisfaction and has potential to significantly expand patient access to fertility care. FUNDING SOURCE: This study was sponsored by Turtle Health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04687189.

Imaging features of leadless cardiovascular devices.

Cardiovascular devices and hemodynamic monitoring systems continue to evolve with the goal of allowing for rapid clinical intervention and management. Cardiovascular devices including the CardioMicroelectromechanical (CardioMEMS) device, implantable loop recorder, and right ventricular (RV) leadless pacemaker are now widely used for treatment and monitoring of advanced cardiac conditions, as many of these devices have been shown to significantly improve patient outcomes. Additionally, hemodynamic monitoring devices have shown utility in monitoring patients with aortic aneurysms after endovascular aortic repair (EVAR) for early detection of Type I and Type II endoleaks. There is limited published data regarding the imaging features of these devices. As these devices become more widely used, it is important for radiologists to become familiar with the normal imaging features and potential complications. The goal of this review is to summarize the data regarding the use of leadless cardiovascular devices including the CardioMEMS device, implantable loop recorder, and RV leadless pacemaker, and to present cases demonstrating their utility and normal imaging features.

Incidence and Clinical Significance of Renal Infarct After Fenestrated Endovascular Aortic Aneurysm Repair.

OBJECTIVE: The purpose of this study is to determine the incidence and clinical significance of renal infarcts after fenestrated endovascular aortic aneurysm repair (FEVAR). MATERIALS AND METHODS: All patients who underwent FEVAR with unenhanced and contrast-enhanced CT angiography during a 4-year period were retrospectively reviewed. Two staff radiologists reviewed pre- and post-FEVAR CT examinations for the presence of renal infarcts. Pre- and postoperative serum creatinine levels were examined to determine statistical significance. The incidence of renal infarct and percentage of renal volume reduction were calculated. RESULTS: Ninety patients were included for analysis. All patients had a mild progressive increase in serum creatinine level after FEVAR. Twenty-three patients (26%) had a renal infarct identified on post-FEVAR CT, nine (39%) of which were secondary to intentional exclusion of an accessory renal artery and 14 (61%) of which were presumed to be embolic. Two patients with presumed embolic infarcts and three with exclusion of an accessory renal artery had an increase in serum creatinine level of greater than 0.3 mg/dL at 1 month after FEVAR. CONCLUSION: Although renal infarcts are common after FEVAR, the clinical relevance of these events appears to be limited, with less than one-quarter of patients with renal infarcts experiencing a decline in renal function.

A novel ligand delivery system to non-invasively visualize and therapeutically exploit the IL13Rα2 tumor-restricted biomarker.

Our objective was to exploit a novel ligand-based delivery system for targeting diagnostic and therapeutic agents to cancers that express interleukin 13 receptor alpha 2 (IL13Rα2), a tumor-restricted plasma membrane receptor overexpressed in glioblastoma multiforme (GBM), meningiomas, peripheral nerve sheath tumors, and other peripheral tumors. On the basis of our prior work, we designed a novel IL13Rα2-targeted quadruple mutant of IL13 (TQM13) to selectively bind the tumor-restricted IL13Rα2 with high affinity but not significantly interact with the physiologically abundant IL13Rα1/IL4Rα heterodimer that is also expressed in normal brain. We then assessed the in vitro binding profile of TQM13 and its potential to deliver diagnostic and therapeutic radioactivity in vivo. Surface plasmon resonance (SPR; Biacore) binding experiments demonstrated that TQM13 bound strongly to recombinant IL13Rα2 (Kd∼5 nM). In addition, radiolabeled TQM13 specifically bound IL13Rα2-expressing GBM cells and specimens but not normal brain. Of importance, TQM13 did not functionally activate IL13Rα1/IL4Rα in cells or bind to it in SPR binding assays, in contrast to wtIL13. Furthermore, in vivo targeting of systemically delivered radiolabeled TQM13 to IL13Rα2-expressing subcutaneous tumors was demonstrated and confirmed non-invasively for the first time with 124I-TQM13 positron emission tomography imaging. In addition, 131I-TQM13 demonstrated in vivo efficacy against subcutaneous IL13Rα2-expressing GBM tumors and in an orthotopic synergeic IL13Rα2-positive murine glioma model, as evidenced by statistically significant survival advantage. Our results demonstrate that we have successfully generated an optimized biomarker-targeted scaffolding that exhibited specific binding activity toward the tumor-associated IL13Rα2 in vitro and potential to deliver diagnostic and therapeutic payloads in vivo.

IL-13Rα2-Targeted Therapy Escapees: Biologic and Therapeutic Implications.

Glioblastoma multiforme (GBM) overexpresses interleukin 13 receptor α2 (IL-13Rα2), a tumor-restricted receptor that is not present in normal brain. We and others have created targeted therapies that specifically eradicate tumors expressing this promising tumor-restricted biomarker. As these therapies head toward clinical implementation, it is critical to explore mechanisms of potential resistance. We therefore used a potent IL-13Rα2-targeted bacterial cytotoxin to select for naturally occurring "escapee" cells from three different IL-13Rα2-expressing GBM cell lines. We found that these side populations of escapee cells had significantly decreased IL-13Rα2 expression. We examined clinically relevant biologic characteristics of escapee cell lines compared to their parental cell lines and found that they had similar proliferation rates and equal sensitivity to temozolomide and radiation, the standard therapies given to GBM patients. In contrast, our escapee cell lines were less likely to form colonies in culture and migrated more slowly in wound healing assays. Furthermore, we found that escapee cells formed significantly less neurospheres in vitro, suggesting that IL-13Rα2-targeted therapy preferentially targeted the "stem-like" cell population and possibly indicating decreased tumorigenicity in vivo. We therefore tested escapee cells for in vivo tumorigenicity and found that they were significantly less tumorigenic in both subcutaneous and intracranial mouse models compared to matching parental cells. These data, for the first time, establish and characterize the clinically relevant biologic properties of IL-13Rα2-targeted therapy escapees and suggest that these cells may have less malignant characteristics than parental tumors.