Fully automatic online geometric calibration for non-circular cone-beam CT orbits using fiducials with unknown placement.

BACKGROUND: Cone-beam CT (CBCT) with non-circular scanning orbits can improve image quality for 3D intraoperative image guidance. However, geometric calibration of such scans can be challenging. Existing methods typically require a prior image, specialized phantoms, presumed repeatable orbits, or long computation time. PURPOSE: We propose a novel fully automatic online geometric calibration algorithm that does not require prior knowledge of fiducial configuration. The algorithm is fast, accurate, and can accommodate arbitrary scanning orbits and fiducial configurations. METHODS: The algorithm uses an automatic initialization process to eliminate human intervention in fiducial localization and an iterative refinement process to ensure robustness and accuracy. We provide a detailed explanation and implementation of the proposed algorithm. Physical experiments on a lab test bench and a clinical robotic C-arm scanner were conducted to evaluate spatial resolution performance and robustness under realistic constraints. RESULTS: Qualitative and quantitative results from the physical experiments demonstrate high accuracy, efficiency, and robustness of the proposed method. The spatial resolution performance matched that of our existing benchmark method, which used a 3D-2D registration-based geometric calibration algorithm. CONCLUSIONS: We have demonstrated an automatic online geometric calibration method that delivers high spatial resolution and robustness performance. This methodology enables arbitrary scan trajectories and should facilitate translation of such acquisition methods in a clinical setting.

Current and future directions in interventional neuro-oncology-are we there yet?

Advancements in technology and technical expertise increasingly enable neurointerventionalists to deliver safer and more effective endovascular treatments to cancers of the brain, spine, head, and neck. In addition to established neuro-oncological interventions such as pre-surgical tumor embolization and percutaneous ablation, newer modalities focused on direct arterial infusion of chemotherapy, radioisotopes, and radiosensitizers continue to gain traction as complementary treatment options, while stem cell-mediated delivery of theranostic nanoparticles and oncolytic virus are being explored for even greater specificity in targeting cancers across the blood-brain barrier. This article aims to provide an overview of the current state of the art and future directions for the field of interventional neuro-oncology, as well as opportunities and challenges presented by this emerging treatment modality.

FABRICATION OF MULTILUMEN MICROFLUIDIC TUBING FOR EX SITU DIRECT LASER WRITING.

Among the numerous additive manufacturing or "three-dimensional (3D) printing" techniques, two-photon Direct Laser Writing (DLW) is distinctively suited for applications that demand high geometric versatility with micron-to-submicron-scale feature resolutions. Recently, "ex situ DLW (esDLW)" has emerged as a powerful approach for printing 3D microfluidic structures directly atop meso/macroscale fluidic tubing that can be manipulated by hand; however, difficulties in creating custom esDLW-compatible multilumen tubing at such scales has hindered progress. To address this impediment, here we introduce a novel methodology for fabricating submillimeter multilumen tubing for esDLW 3D printing. Preliminary fabrication results demonstrate the utility of the presented strategy for resolving 743 µm-in-diameter tubing with three lumens-each with an inner diameter (ID) of 80 µm. Experimental results not only revealed independent flow of discrete fluorescently labelled fluids through each of the three lumens, but also effective esDLW-printing of a demonstrative 3D "MEMS" microstructure atop the tubing. These results suggest that the presented approach could offer a promising pathway to enable geometrically sophisticated microfluidic systems to be 3D printed with input and/or output ports fully sealed to multiple, distinct lumens of fluidic tubing for emerging applications in fields ranging from drug delivery and medical diagnostics to soft surgical robotics.

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.

Magnetic resonance - guided treatment of low-flow vascular malformations and the technologies to potentiate adoption.

Vascular malformations are congenital, non-neoplastic lesions that arise secondary to defects in angiogenesis. Vascular malformations are divided into high-flow (arteriovenous malformation) and low-flow (venous malformations and lymphatic malformations). Magnetic resonance imaging (MRI) is the standard for pre-and post-intervention assessments, while ultrasound (US), X-ray fluoroscopy and computed tomography (CT) are used for intra-procedural guidance. Sclerotherapy, an image-guided therapy that involves the injection of a sclerosant directly into the malformation, is typically the first-line therapy for treating low-flow vascular malformations. Sclerotherapy induces endothelial damage and necrosis/fibrosis with eventual involution of the malformation. Image-guided thermal therapies involve freezing or heating target tissue to induce cell death and necrosis. MRI is an alternative for intra-procedural guidance and monitoring during the treatment of vascular malformations. MR can provide dynamic, multiplanar imaging that delineates surrounding critical structures such as nerves and vasculature. Multiple studies have demonstrated that MR-guided treatment of vascular malformations is safe and effective. This review will detail (1) the use of MR for the classification and diagnosis of vascular malformations, (2) the current literature surrounding MR-guided treatment of vascular malformations, (3) a series of cases of MR-guided sclerotherapy and thermal ablation for the treatment of vascular malformations, and (4) a discussion of technologies that may potentiate interventional MRI adoption including high intensity focused ultrasound and guided laser ablation.

Patient Characteristics Associated With Embolization Versus Hysterectomy for Uterine Fibroids: A Systematic Review and Meta-Analysis.

INTRODUCTION: Black and underinsured women in the United States are more likely than their counterparts to develop uterine fibroids (UFs) and experience more severe symptoms. Uterine artery embolization (UAE), a uterine-sparing therapeutic procedure, is less invasive than the common alternative, open hysterectomy. To determine whether demographic disparities persist in UF treatment utilization, we reviewed patient characteristics associated with UAE versus hysterectomy for UF among studies of US clinical practices. METHODS: A systematic literature review was conducted via PubMed, Embase, and CINAHL (PROSPERO CRD42023455051), yielding 1,350 articles (January 1, 1995, to July 15, 2023) that outlined demographic characteristics of UAE compared with hysterectomy. Two readers screened for inclusion criteria, yielding 13 full-text US-based comparative studies specifying at least one common demographic characteristic. Random effects meta-analysis was performed on the data (STATA v18.0). Egger's regression test was used to quantify publication bias. RESULTS: Nine (138,960 patients), four (183,643 patients), and seven (312,270 patients) studies were analyzed for race, insurance status, and age as predictors of treatment modality, respectively. Black race (odds ratio = 3.35, P < .01) and young age (P < .05) were associated with UAE, whereas private insurance (relative to Medicare and/or Medicaid) was not (odds ratio = 1.06, P = .52). Between-study heterogeneity (I2 > 50%) was detected in all three meta-analyses. Small-study bias was detected for age but not race or insurance. CONCLUSIONS AND IMPLICATIONS: Knowledge of demographic characteristics of patients with UFs receiving UAE versus hysterectomy is sparse (n = 13 studies). Among these studies, which seem to be racially well distributed, Black and younger women are more likely to receive UAE than their counterparts.

Radiomics Features Extracted From Pre- and Postprocedural Imaging in Early Prediction of Treatment Response in Patients Undergoing Transarterial Radioembolization of Hepatic Lesions: A Systematic Review, Meta-Analysis, and Quality Appraisal Study.

INTRODUCTION: Transarterial radioembolization (TARE) is one of the most promising therapeutic options for hepatic masses. Radiomics features, which are quantitative numeric features extracted from medical images, are considered to have potential in predicting treatment response in TARE. This article aims to provide meta-analytic evidence and critically appraise the methodology of radiomics studies published in this regard. METHODS: A systematic search was performed on PubMed, Scopus, Embase, and Web of Science. All relevant articles were retrieved, and the characteristics of the studies were extracted. The Radiomics Quality Score and Checklist for Evaluation of Radiomics Research were used to assess the methodologic quality of the studies. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve in predicting objective response were determined. RESULTS: The systematic review included 15 studies. The average Radiomics Quality Score of these studies was 11.4 ± 2.1, and the average Checklist for Evaluation of Radiomics Research score was 33± 6.7. There was a notable correlation (correlation coefficient = 0.73) between the two metrics. Adherence to quality measures differed considerably among the studies and even within different components of the same studies. The pooled sensitivity and specificity of the radiomics models in predicting complete or partial response were 83.5% (95% confidence interval 76%-88.9%) and 86.7% (95% confidence interval 78%-92%), respectively. CONCLUSION: Radiomics models show great potential in predicting treatment response in TARE of hepatic lesions. However, the heterogeneity seen between the methodologic quality of studies may limit the generalizability of the results. Future initiatives should aim to develop radiomics signatures using multiple external datasets and adhere to quality measures in radiomics methodology.

Prospective Study of Polytetrafluoroethylene-Covered Microplugs and Detachable Coils for Embolization of Pulmonary Arteriovenous Malformations: Technical Results, Procedure Times, and Costs.

PURPOSE: To determine time to occlusion and procedure costs of embolization of pulmonary arteriovenous malformations (PAVMs) using a polytetrafluoroethylene-covered microplug compared with embolization using detachable coils. MATERIALS AND METHODS: In this prospective study, 37 patients (mean age, 39.1 years [SD ± 17.6]) with 82 PAVMs underwent embolization with microplug or detachable coils between April 2019 and January 2023. Technical success, procedure time intervals, and costs were analyzed. RESULTS: In 37 patients, 82 PAVMs and 101 feeding arteries were successfully treated (microplug, 64; microplug + another device, 5; detachable coils alone, 32). Time from embolic device inserted into the catheter to device deployed and time to occlusion differed significantly between microplug and detachable coil cohorts (P < .0001 for both). Embolization with ≥1 microplug had a significantly shorter occlusion time than embolization with detachable coils (median, 10.0 minutes saved per feeding artery) (P < .0001). Compared with detachable coil embolization, microplug embolization saved a median of 9.0 minutes per feeding artery (P < .0001) and reduced room cost by a median of $429 per feeding artery (P < .0001). Device costs per feeding artery did not differ significantly between microplug ($2,790) and detachable coil embolization ($3,147) (P = .87). CONCLUSIONS: Compared with coils, microplugs had an equally high technical success rate but significant time to occlusion and room costs savings per feeding artery. Total room cost and device cost together did not differ significantly between microplugs and coils. Microplugs may be considered technically effective and at least cost-neutral for PAVM embolization where clinically appropriate.

Deformable Motion Compensation for Intraprocedural Vascular Cone-beam CT with Sequential Projection Domain Targeting and Vessel-Enhancing Autofocus.

Purpose: Cone-beam CT (CBCT) is used in interventional radiology (IR) for identification of complex vascular anatomy, difficult to visualize in 2D fluoroscopy. However, long acquisition time makes CBCT susceptible to soft-tissue deformable motion that degrades visibility of fine vessels. We propose a targeted framework to compensate for deformable intra-scan motion via learned full-sequence models for identification of vascular anatomy coupled to an autofocus function specifically tailored to vascular imaging. Methods: The vessel-targeted autofocus acts in two stages: (i) identification of vascular and catheter targets in the projection domain; and, (ii) autofocus optimization for a 4D vector field through an objective function that quantifies vascular visibility. Target identification is based on a deep learning model that operates on the complete sequence of projections, via a transformer encoder-decoder architecture that uses spatial-temporal self-attention modules to infer long-range feature correlations, enabling identification of vascular anatomy with highly variable conspicuity. The vascular autofocus function is derived through eigenvalues of the local image Hessian, which quantify the local image structure for identification of bright tubular structures. Motion compensation was achieved via spatial transformer operators that impart time dependent deformations to NPAR = 90 partial angle reconstructions, allowing for efficient minimization via gradient backpropagation. The framework was trained and evaluated in synthetic abdominal CBCTs obtained from liver MDCT volumes and including realistic models of contrast-enhanced vascularity with 15 to 30 end branches, 1 - 3.5 mm vessel diameter, and 1400 HU contrast. Results: The targeted autofocus resulted in qualitative and quantitative improvement in vascular visibility in both simulated and clinical intra-procedural CBCT. The transformer-based target identification module resulted in superior detection of target vascularity and a lower number of false positives, compared to a baseline U-Net model acting on individual projection views, reflected as a 1.97x improvement in intersection-over-union values. Motion compensation in simulated data yielded improved conspicuity of vascular anatomy, and reduced streak artifacts and blurring around vessels, as well as recovery of shape distortion. These improvements amounted to an average 147% improvement in cross correlation computed against the motion-free ground truth, relative to the un-compensated reconstruction. Conclusion: Targeted autofocus yielded improved visibility of vascular anatomy in abdominal CBCT, providing better potential for intra-procedural tracking of fine vascular anatomy in 3D images. The proposed method poses an efficient solution to motion compensation in task-specific imaging, with future application to a wider range of imaging scenarios.

Abdominal computed tomography measurements of body composition and waitlist mortality in kidney transplant candidates.

Body mass index is often used to determine kidney transplant (KT) candidacy. However, this measure of body composition (BC) has several limitations, including the inability to accurately capture dry weight. Objective computed tomography (CT)-based measures may improve pre-KT risk stratification and capture physiological aging more accurately. We quantified the association between CT-based BC measurements and waitlist mortality in a retrospective study of 828 KT candidates (2010-2022) with clinically obtained CT scans using adjusted competing risk regression. In total, 42.5% of candidates had myopenia, 11.4% had myopenic obesity (MO), 68.8% had myosteatosis, 24.8% had sarcopenia (probable = 11.2%, confirmed = 10.5%, and severe = 3.1%), and 8.6% had sarcopenic obesity. Myopenia, MO, and sarcopenic obesity were not associated with mortality. Patients with myosteatosis (adjusted subhazard ratio [aSHR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; after confounder adjustment) or sarcopenia (probable: aSHR = 1.78, 95% CI: 1.10-2.88; confirmed: aSHR = 1.68, 95% CI: 1.01-2.82; and severe: aSHR = 2.51, 95% CI: 1.12-5.66; after full adjustment) were at increased risk of mortality. When stratified by age, MO (aSHR = 2.21, 95% CI: 1.28-3.83; P interaction = .005) and myosteatosis (aSHR = 1.95, 95% CI: 1.18-3.21; P interaction = .038) were associated with elevated risk only among candidates <65 years. MO was only associated with waitlist mortality among frail candidates (adjusted hazard ratio = 2.54, 95% CI: 1.28-5.05; P interaction = .021). Transplant centers should consider using BC metrics in addition to body mass index when a CT scan is available to improve pre-KT risk stratification at KT evaluation.

Balancing Safety and Efficacy to Determine the Most Suitable Size of Imaging-Visible Embolic Microspheres for Bariatric Arterial Embolization in a Preclinical Model.

OBJECTIVES: To identify the most suitable size of imaging-visible embolic agents with balanced safety and efficacy for bariatric arterial embolization (BAE) in a preclinical model. MATERIALS AND METHODS: Twenty-seven pigs were divided into 3 cohorts. In Cohort I, 16 pigs were randomized to receive (n = 4 each) 40-100-µm microspheres in 1 or 2 fundal arteries, 70-340-µm radiopaque microspheres in 2 fundal arteries, or saline. In Cohort II, 3 pigs underwent renal arterial embolization with either custom-made 100-200-µm, 200-250-µm, 200-300-µm, or 300-400-µm radiopaque microspheres or Bead Block 300-500 µm with microsphere distribution assessed histologically. In Cohort III, 8 pigs underwent BAE in 2 fundal arteries with tailored 100-200-µm radiopaque microspheres (n = 5) or saline (n = 3). RESULTS: In Cohort I, no significant differences in weight or ghrelin expression were observed between BAE and control animals. Moderate-to-severe gastric ulcerations were noted in all BAE animals. In Cohort II, renal embolization with 100-200-µm microspheres occluded vessels with a mean diameter of 139 µm ± 31, which is within the lower range of actual diameters of Bead Block 300-500 µm. In Cohort III, BAE with 100-200-µm microspheres resulted in significantly lower weight gain (42.3% ± 5.7% vs 51.6% ± 2.9% at 8 weeks; P = .04), fundal ghrelin cell density (16.1 ± 6.7 vs 23.6 ± 12.6; P = .045), and plasma ghrelin levels (1,709 pg/mL ± 172 vs 4,343 pg/mL ± 1,555; P < .01) compared with controls and superficial gastric ulcers (5/5). CONCLUSIONS: In this preclinical model, tailored 100-200-µm microspheres were shown to be most suitable for BAE in terms of safety and efficacy.

EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35-50 kg/m2.

INTRODUCTION: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. METHODS AND ANALYSIS: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18-70 with a body mass index 35-50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. ETHICS AND DISSEMINATION: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial's development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN16158402.

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.

Intraoperative Neuromonitoring during Peripheral Arteriovenous Malformation Embolization.

PURPOSE: To evaluate whether intraoperative neuromonitoring (IONM), including pre-embolization lidocaine injection challenge ("provocative testing") is associated with reduced risk of irreversible nerve injury during embolization of peripheral arteriovenous malformations (AVMs). MATERIALS AND METHODS: Medical records of patients with peripheral AVMs who underwent embolotherapy with IONM with provocative testing between 2012 and 2021 were reviewed retrospectively. Data collected included patient demographic characteristics, AVM location and size, embolic agent used, IONM signal changes after lidocaine and embolic agent injections, postprocedural adverse events, and clinical outcomes. Decisions regarding whether embolization would proceed at specific locations were based on IONM findings after the lidocaine challenge and as embolization proceeded. RESULTS: A cohort of 17 patients (mean age, 27 years ± 19; 5 women) who underwent 59 image-guided embolization procedures with adequate IONM data was identified. No permanent neurologic deficits occurred. Transient neurologic deficits were observed in 3 patients (4 sessions), comprising skin numbness (2 patients), extremity weakness (1 patient), and extremity weakness and numbness (1 patient). All neurologic deficits resolved by postoperative day 4 without additional treatment. CONCLUSIONS: IONM, including provocative testing, during AVM embolization may minimize potential nerve injury.

Venous malformation may be a feature of EXT1-related hereditary multiple exostoses: A report of two unrelated probands.

Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in exostosin-1 or -2 (EXT1 or EXT2). It is characterized by the formation of multiple benign growing osteochondromas (exostoses) that most commonly affect the long bones; however, it may also occur throughout the body. Although many of these lesions are clinically asymptomatic, some can lead to chronic pain and skeletal deformities and interfere with adjacent neurovascular structures. Here, we report two unrelated probands that presented with a clinical and molecular diagnosis of HME with venous malformation, a clinical feature not previously reported in individuals with HME.

Responsiveness of the Patient-Reported Outcome Measure for Vascular Malformation Questionnaire in Patients with Low-Flow Vascular Malformations.

PURPOSE: To assess the responsiveness, defined as the ability to detect change in a patient's health or function, of the Patient-Reported Outcome Measure for Vascular Malformation (PROVAM) questionnaire in a cohort of patients with low-flow vascular malformations (VMs). MATERIALS AND METHODS: PROVAM was previously developed to assess symptoms, functional limitations, and social/emotional effects experienced by patients with VMs. This is a prospective cohort study of 56 patients with venous and lymphatic VMs who completed at least 2 PROVAM questionnaires, of whom 43 had undergone treatment with sclerotherapy in the interim between questionnaires. External responsiveness was assessed using a receiver operating characteristic (ROC) curve to ascertain whether a change in the total PROVAM score predicts whether patients reported symptom improvement and by correlating the change in the total PROVAM score and change in symptoms reported during clinic visit. Internal responsiveness was evaluated using Wilcoxon signed rank test, Cohen d effect size (ESp), and standard response mean difference (SRM). RESULTS: The total PROVAM score demonstrated excellent discrimination for symptom improvement with an area under the ROC curve of 0.856. There was a statistically significant, moderate positive correlation between the change in the total PROVAM score and the change in patient symptoms as determined from clinical visits (Spearman correlation coefficient [rs] = 0.67, P < .001). The total PROVAM score and all subdomain scores improved significantly after treatment (all P < .05). ESp and SRM were 0.80 and 0.83, respectively. CONCLUSIONS: PROVAM is responsive to improvement after treatment and may be useful to assess health-related quality of life in patients treated for VMs.

Genetic testing in the evaluation of individuals with clinical diagnosis of atypical Sturge-Weber syndrome.

Sturge-Weber Syndrome (SWS) is a rare vascular malformation disorder characterized by abnormal blood vessels in the brain, skin, and eye. SWS is most commonly caused by a somatic mosaic GNAQ-p.Arg183Gln variant. In this series, 12 patients presented for clinical evaluation of SWS but were noted to have atypical features, and therefore germline and/or somatic genetic testing was performed. Atypical features included extensive capillary malformation on the body as well as the face, frontal bossing, macrocephaly, telangiectasia, overgrowth of extremities, absence of neurologic signs and symptoms, and family history of vascular malformations. Five patients had a somatic GNAQ or GNA11 pathogenic variant, one patient had a somatic mosaic likely-pathogenic variant in PIK3CA, and another one had a somatic mosaic deletion that disrupted PTPRD. The other five patients had germline variants in RASA1, EPHB4, or KIT. Our findings suggest that patients presenting for SWS evaluation who have atypical clinical characteristics may have pathogenic germline or somatic variants in genes other than GNAQ or GNA11. Broad germline and somatic genetic testing in these patients with atypical findings may have implications for medical care, prognosis, and trial eligibility.