Whole-lesion assessment of volume and signal changes after sclerotherapy of extremity venous malformations.

PURPOSE: To investigate quantitative changes in MRI signal intensity (SI) and lesion volume that indicate treatment response and correlate these changes with clinical outcomes after percutaneous sclerotherapy (PS) of extremity venous malformations (VMs). METHODS: VMs were segmented manually on pre- and post-treatment T2-weighted MRI using 3D Slicer to assess changes in lesion volume and SI. Clinical outcomes were scored on a 7-point Likert scale according to patient perception of symptom improvement; treatment response (success or failure) was determined accordingly. RESULTS: Eighty-one patients with VMs underwent 125 PS sessions. Treatment success occurred in 77 patients (95 %). Mean (±SD) changes were -7.9 ± 24 cm3 in lesion volume and -123 ± 162 in SI (both, P <.001). Mean reduction in lesion volume was greater in the success group (-9.4 ± 24 cm3) than in the failure group (21 ± 20 cm3) (P =.006). Overall, lesion volume correlated with treatment response (ρ = -0.3, P =.004). On subgroup analysis, volume change correlated with clinical outcomes in children (ρ = -0.3, P =.03), in sodium tetradecyl sulfate-treated lesions (ρ = -0.5, P =.02), and in foot lesions (ρ = -0.6, P =.04). SI change correlated with clinical outcomes in VMs treated in 1 PS session (ρ = -0.3, P =.01) and in bleomycin-treated lesions (ρ = -0.4, P =.04). CONCLUSIONS: Change in lesion volume is a reliable indicator of treatment response. Lesion volume and SI correlate with clinical outcomes in specific subgroups.

Risk factors and clinical features associated with basal ganglia manganese deposition in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: T1-hyperintensity of the basal ganglia (BG) due to manganese deposition is a known radiologic finding in patients with hereditary hemorrhagic telangiectasia (HHT), but risk factors and associated clinical manifestations are unclear. This study conducted a quantitative analysis of the association of T1-hyperintensity in HHT patients with specific risk factors, signs, and symptoms. METHODS: Patients seen at our center between 2005 and 2020 with a definitive diagnosis of HHT who had an available non-contrast T1-weighted brain MRI were included. Hyperintensity was evaluated using oval regions of interest measurements. The BG: thalamus intensity ratio was used to quantitatively evaluate T1-hyperintensity. Patient laboratory values and clinical findings were collected from electronic medical records. Hyperintensity was analyzed for its association with laboratory values, and clinical findings. Variables were analyzed through regression analysis. RESULTS: A total of 239 patients were included in this study. On 1.5 T scanners, values that were significant on multivariable regression analysis were age (p < .001), hepatic AVMs (p < .001), iron deficiency anemia (p = .0021), and cirrhosis (p = .016). On 3 T scanners, values that were significant on multivariable analysis were hepatic AVMs (p = .0024) and cirrhosis (p = .0056). On 3 T scanners, hyperintensity was significantly associated with tremor (OR = 1.17, p = .033), restless leg syndrome (OR = 1.22, p = .0086), and memory problems (OR = 1.17, p = .046). CONCLUSIONS: BG hyperintensity due to manganese deposition is significantly associated with hepatic risk factors on 1.5 T and 3 T scanners and iron deficiency anemia on 1.5 T scanners. On 3 T scanners, T1-hyperintensity is associated with neuropsychiatric signs and symptoms, such as tremor, restless leg syndrome, and memory problems.

Racial and Ethnic Disparities among Participants in Hepatocellular Carcinoma Clinical Studies Evaluating Transarterial Therapies.

PURPOSE: To evaluate the racial and ethnic representation of transarterial therapy for hepatocellular carcinoma (HCC) clinical trials in the United States. MATERIALS AND METHODS: The ClinicalTrials.gov database was examined to identify all completed studies with transarterial therapies for the management of HCC in the United States and extract information about the observed number of participants for each racial and ethnic group (based on the Office of Management and Budget definitions). The expected number of participants was calculated by multiplying the total number of participants in a trial with the U.S.-population HCC-based proportion for each group. The effects of the study phase, funding source, number of centers involved in the study, and the location of the participating center on racial and ethnic distribution were explored. RESULTS: Seventy-nine relevant studies were identified, of which 27 (34.2%) and 18 (22.8%) reported ethnic and race characteristics, respectively. Most study participants were White (81%, 1,591/1,964) by ethnicity and not Hispanic or Latino (93%, 937/1,008) by race. In terms of the observed-to-expected ratios by race and ethnicity in all trials, White and not Hispanic or Latino participants were overrepresented with a ratio of 1.22 (1.10-1.37) and 1.33 (1.26-1.41), respectively, and all other racial and ethnic groups were underrepresented. The enrollment of African Americans and Asian Americans varied by the study phase, and a higher enrollment of African Americans was noted in the National Institutes of Health-funded and multicenter studies (P < .05). CONCLUSIONS: This cross-sectional study demonstrates that in HCC transarterial therapy clinical trials, racial and ethnic minorities were underrepresented and the majority of the studies identified failed to report this demographic information.

Development of an N-Cadherin Biofunctionalized Hydrogel to Support the Formation of Synaptically Connected Neural Networks.

In vitro models of the human central nervous system (CNS), particularly those derived from induced pluripotent stem cells (iPSCs), are becoming increasingly recognized as useful complements to animal models for studying neurological diseases and developing therapeutic strategies. However, many current three-dimensional (3D) CNS models suffer from deficits that limit their research utility. In this work, we focused on improving the interactions between the extracellular matrix (ECM) and iPSC-derived neurons to support model development. The most common ECMs used to fabricate 3D CNS models often lack the necessary bioinstructive cues to drive iPSC-derived neurons to a mature and synaptically connected state. These ECMs are also typically difficult to pattern into complex structures due to their mechanical properties. To address these issues, we functionalized gelatin methacrylate (GelMA) with an N-cadherin (Cad) extracellular peptide epitope to create a biomaterial termed GelMA-Cad. After photopolymerization, GelMA-Cad forms soft hydrogels (on the order of 2 kPa) that can maintain patterned architectures. The N-cadherin functionality promotes survival and maturation of single-cell suspensions of iPSC-derived glutamatergic neurons into synaptically connected networks as determined by viral tracing and electrophysiology. Immunostaining reveals a pronounced increase in presynaptic and postsynaptic marker expression in GelMA-Cad relative to Matrigel, as well as extensive colocalization of these markers, thus highlighting the biological activity of the N-cadherin peptide. Overall, given its ability to enhance iPSC-derived neuron maturity and connectivity, GelMA-Cad should be broadly useful for in vitro studies of neural circuitry in health and disease.