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BackgroundIndividuals typically show a childhood nadir in adiposity termed the adiposity rebound (AR). The AR serves as an early predictor of obesity risk, with early rebounders often at increased risk; however, it is unclear why this phenomenon occurs, which could impede understandings of weight gain trajectories. The brain’s energy requirements account for a lifetime peak of 66% of the body’s resting metabolic expenditure during childhood, around the age of the AR, and relates inversely to weight gain, pointing to a potential energy trade-off between brain development and adiposity. However, no study has compared developmental trajectories of brain metabolism and adiposity in the same individuals, which would allow a preliminary test of a brain-AR link.MethodsWe used cubic splines and generalized additive models to compare age trajectories of previously collected MRI-based 4D flow measures of total cerebral blood flow (TCBF), a proxy for cerebral energy use, to the body mass index (BMI) in a cross-sectional sample of 82 healthy individuals (0–60 years). We restricted our AR analysis to pre-pubertal individuals (0–12 years, n = 42), predicting that peak TCBF would occur slightly after the BMI nadir, consistent with evidence that lowest BMI typically precedes the nadir in adiposity.ResultsTCBF and the BMI showed inverse trajectories throughout childhood, while the estimated age at peak TCBF (5.6 years) was close but slightly later than the estimated age of the BMI nadir (4.9 years).ConclusionsThe timing of peak TCBF in this sample points to a likely concordance between peak brain energetics and the nadir in adiposity. Inverse age trajectories between TCBF and BMI support the hypothesis that brain metabolism is a potentially important influence on early life adiposity. These findings also suggest that experiences influencing the pattern of childhood brain energy use could be important predictors of body composition trajectories.

Extracranial arteriovenous malformations (AVMs) are high-flow vascular malformations that are challenging entities to treat and are primarily managed with embolization alone. Single-stage embolization and resection is a technique occasionally used for treating intracranial arteriovenous malformations. This manuscript describes combined embolization and surgical resection for localized superficial extracranial AVMs by presenting three cases from our experience. A retrospective review of the medical records of patients in this series including clinical notes, procedural imaging, and follow-up documentation was performed. A total of three AVMs near the antecubital fossa, deltoid, and forehead were embolized and resected. There was no evidence of recurrence on follow-up imaging, and no complications were observed, specifically, overlying skin injury. Embolization and resection of localized superficial extracranial AVMs with overlying skin changes offer an alternative treatment option to existing paradigms.

CNS vascular malformation is an umbrella term that encompasses a wide variety of pathologies, with a wide range of therapeutic and diagnostic importance. This range spans lesions with a risk of devastating neurological compromise to lesions with a slow, static or benign course. Advances in neurovascular imaging along with increased utilization of these advances, have resulted in more frequent identification of these lesions. In this article, we provide an overview on definitions and classifications of CNS vascular malformations and outline the etiologic, diagnostic, prognostic, and therapeutic features for each entity. This review covers intracranial and spinal cord vascular malformations and discusses syndromes associated with CNS vascular malformations.

The direct electrochemical reduction of nicotinamide adenine dinucleotide (NAD+) results in various products, complicating the regeneration of the crucial 1,4‐NADH cofactor for enzymatic reactions. Previous research primarily focused on steady–state polarization to examine potential impacts on product selectivity. However, this study explores the influence of dynamic conditions on the selectivity of NAD+ reduction products by comparing two dynamic profiles with steady‐state conditions. Our findings reveal that the main products, including 1,4‐NADH, several dimers, and ADP‐ribose, remained consistent across all conditions. A minor by–product, 1,6‐NADH, was also identified. The product distribution varied depending on the experimental conditions (steady state vs. dynamic) and the concentration of NAD+, with higher concentrations and overpotentials promoting dimerization. The optimal yield of 1,4‐NADH was achieved under steady–state conditions with low overpotential and NAD+ concentrations. While dynamic conditions enhanced the 1,4‐NADH yield at shorter reaction times, they also resulted in a significant amount of unidentified products. Furthermore, this study assessed the potential of using pulsed electrochemical regeneration of 1,4‐NADH with enoate reductase (XenB) for cyclohexenone reduction. This study investigates the direct electrochemical reduction of NAD+ for enzymatic cofactor regeneration. It discovers that dynamic conditions improve the short time selectivity towards 1,4‐NADH, but also result in the production of inactive by–products. The highest yield is achieved under steady–state conditions, marked by minimal overpotential and prolonged operation time. While the reduction of cyclohexenone using XenB in conjunction with the direct electrochemical reduction of NAD+ is possible, practical limitations exist.

Background and Purpose In patients with subarachnoid hemorrhage (SAH), higher hemoglobin (HGB) has been associated with better outcomes, but packed red blood cell (PRBC) transfusions with worse outcomes. We performed a prospective pilot trial of goal HGB after SAH. Methods Forty-four patients with SAH and high risk for vasospasm were randomized to goal HGB concentration of at least 10 or 11.5 g/dl. We obtained blinded clinical outcomes at 14 days (NIH Stroke Scale and modified Rankin Scale, mRS), 28 days (mRS), and 3 months (mRS), and blinded interpretation of brain MRI for cerebral infarction at 14 days. This trial is registered at www.stroketrials.org . Results Forty-four patients were randomized. Patients with goal HGB 11.5 g/dl received more PRBC units per transfusion [1 (1–2) vs. 1 (1–1), P  < 0.001] and more total PRBC units [3 (2–4) vs. 2 (1–3), P  = 0.045]. Prospectively defined safety endpoints were not different between groups. HGB concentration was different between study groups from day 4 onwards. The number of cerebral infarctions on MRI (6 of 20 vs. 9 of 22), NIH Stroke Scale scores at 14 days [1 (0–9.75) vs. 2 (0–16)], and rates of independence on the mRS at 14 days (65% vs. 44%) and 28 days (80% vs. 67%) were similar, but favored higher goal HGB ( P  > 0.1 for all). Conclusions Higher goal hemoglobin in patients with SAH seems to be safe and feasible. A phase III trial of goal HGB after SAH is warranted.

ObjectiveDifferent technical and procedural methods have been introduced to develop low radiation dose protocols in neurointerventional examinations. We investigated the feasibility of minimizing radiation exposure dose by simply decreasing the detector dose during cerebral DSA and evaluated the comparative level of image quality using both subjective and objective methods.MethodsIn a prospective study of patients undergoing diagnostic cerebral DSA, randomly selected vertebral arteries (VA) and/or internal carotid arteries and their contralateral equivalent arteries were injected. Detector dose of 3.6 and 1.2 μGy/frame were selected to acquire standard dose (SD) and low dose (LD) images, respectively. Subjective image quality assessment was performed by two neurointerventionalists using a 5 point scale. For objective image quality evaluation, circle of Willis vessels were categorized into conducting, primary, secondary, and side branch vessels. Two blinded observers performed arterial diameter measurements in each category. Only image series obtained from VA injections opacifying the identical posterior intracranial circulation were utilized for objective assessment.ResultsNo significant difference between SD and LD images was observed in subjective and objective image quality assessment in 22 image series obtained from 10 patients. Mean reference air kerma and kerma area product were significantly reduced by 61.28% and 61.24% in the LD protocol, respectively.ConclusionsOur study highlights the necessity for reconsidering radiation dose protocols in neurointerventional procedures, especially at the level of baseline factory settings.

ObjectiveTo investigate the impact of coil design on the distribution of the coil mass in a controlled in vitro experiment. A secondary objective was to study the relationship between angiographic occlusion, packing density and coil mass uniformity.MethodsSeven silicon side wall aneurysm models were embolized in each arm with a different coil design under fluoroscopic guidance. Packing density calculations and scoring of the angiographic occlusion were made. The models were embedded in epoxy and sectioned through the aneurysm neck and the dome. The sections were imaged and processed to derive the fractional surface area of coil material over the coil free area, a quantitative endpoint representing the percentage of the given region of interest consumed by coils. The SD of the surface area fractions is inversely proportional to the uniformity of coil distribution.ResultsThe novel triangular primary wind design of the Deltapaq achieved a more homogenous distribution of coils within the aneurysm dome compared with the helical and complex microcoil systems (p=0.018). The packing density achieved by the Deltapaq (39.1±1.6%) was significantly higher than the complex (35.2±2.8%) and the helical (32.2±3.3%) coils. Angiographically, aneurysms coiled by the Deltapaq were more likely to obtain a Raymond score of class I.ConclusionEvaluation of emerging coil technologies with respect to treatment durability may be well served by an assessment of their uniformity of distribution within an aneurysm in addition of the traditional packing density and angiographic occlusion scoring methods.

BackgroundAdmission neutrophil-lymphocyte ratio (NLR) is significantly correlated to clinical outcomes in acute ischemic stroke (AIS). We investigated follow-up NLR and temporal changes in NLR after endovascular thrombectomy (EVT) with respect to successful revascularization, clinical outcomes, symptomatic intracranial hemorrhage (sICH) and mortality.MethodsRetrospective analysis of EVT for anterior circulation emergent LVO was performed with both admission (NLR1) and 3–7 day follow-up NLR (NLR2) laboratory data. Patient demographics, National Institutes of Health Stroke Scale (NIHSS) presentations, reperfusion efficacy (modified Thrombolysis in Cerebral Infarction (mTICI) score), sICH, and clinical outcomes (modified Rankin Scale (mRS)) at 90 days were studied. Univariate analyses correlated NLR1, NLR2, and temporal change in NLR (NLR2-NLR1) with successful reperfusion (mTICI ≥2b), favorable outcomes (mRS ≤2), sICH, and mortality. Multivariable logistic regression model evaluated the independent effects of NLR2 on favorable outcomes.Results142 AIS patients with median NIHSS 17 underwent EVT within 24 hours, and met NLR laboratory inclusion criteria. Lower follow-up NLR2 and less temporal change in NLR over 3–7 days, but not admission NLR1, inversely correlated with successful reperfusion (p<0.05) and favorable clinical outcomes (p<0.001). Higher follow-up NLR2 and greater temporal change in NLR was significantly associated with sICH and mortality (p≤0.05). In multivariable logistic regression, lower follow-up NLR2 remained a predictor of favorable outcomes (OR 0.785, p=0.001), independent of age or successful reperfusion.ConclusionsFollow-up NLR is a readily available and modifiable biomarker that correlates with the degree of reperfusion after mechanical stroke thrombectomy. Lower follow-up NLR2 at 3–7 days is associated with successful reperfusion and an independent predictor of favorable clinical outcomes, with reduced risk for sICH and mortality.

Catheter Digital Subtraction Angiography (DSA) is markedly degraded by all voluntary, respiratory, or cardiac motion artifact that occurs during the exam acquisition. Prior efforts directed toward improving DSA images with machine learning have focused on extracting vessels from individual, isolated 2D angiographic frames. In this work, we introduce improved 2D + t deep learning models that leverage the rich temporal information in angiographic timeseries. A total of 516 cerebral angiograms were collected with 8784 individual series. We utilized feature-based computer vision algorithms to separate the database into “motionless” and “motion-degraded” subsets. Motion measured from the “motion degraded” category was then used to create a realistic, but synthetic, motion-augmented dataset suitable for training 2D U-Net, 3D U-Net, SegResNet, and UNETR models. Quantitative results on a hold-out test set demonstrate that the 3D U-Net outperforms competing 2D U-Net architectures, with substantially reduced motion artifacts when compared to DSA. In comparison to single-frame 2D U-Net, the 3D U-Net utilizing 16 input frames achieves a reduced RMSE (35.77 ± 15.02 vs 23.14 ± 9.56, p < 0.0001; mean ± std dev) and an improved Multi-Scale SSIM (0.86 ± 0.08 vs 0.93 ± 0.05, p < 0.0001). The 3D U-Net also performs favorably in comparison to alternative convolutional and transformer-based architectures (U-Net RMSE 23.20 ± 7.55 vs SegResNet 23.99 ± 7.81, p < 0.0001, and UNETR 25.42 ± 7.79, p < 0.0001, mean ± std dev). These results demonstrate that multi-frame temporal information can boost performance of motion-resistant Background Subtraction Deep Learning algorithms, and we have presented a neuroangiography domain-specific synthetic affine motion augmentation pipeline that can be utilized to generate suitable datasets for supervised training of 3D (2d + t) architectures.

The optimal management strategy for unruptured cerebral arteriovenous malformations (AVMs) is controversial since the ARUBA trial (A Randomized trial of Unruptured Brain AVMs). An accurate understanding of the morbidity associated with AVM hemorrhages may help clinicians to formulate the best treatment strategy for unruptured AVMs. To determine the morbidity associated with initial cerebral AVM rupture in patients presenting to tertiary medical centers. Retrospective chart reviews from three tertiary academic medical centers were performed for the period between 2008 and 2014. All patients admitted with intracranial hemorrhage due to untreated AVMs were included in this study. Patient-specific variables, including demographics, imaging characteristics, neurologic examination results, and clinical outcome, were analyzed and recorded. 101 Patients met the inclusion criteria. Admission National Institutes of Health Stroke Scale (NIHSS) scores were 0, 1-9, and ≥10 in 26%, 29%, and 45% of patients, respectively. Hematoma locations were subarachnoid, intraventricular, intraparenchymal, and combined in 5%, 11%, 32%, and 52% of patients, respectively. Deep venous drainage was present in 43% of AVMs; AVM-associated aneurysms were present in 44% of patients. Emergent hematoma evacuations were performed in 37% of patients and 8% of patients died while in hospital. At discharge, of those who survived, NIHSS scores of ≥1 and ≥10 were found in 69% and 23%, respectively. At the 90-day follow-up, 34% had a modified Rankin Scale (mRS) score >2. Patients with admission NIHSS score ≥10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥3 (p<0.05). The morbidity associated with cerebral AVM rupture appeared to be higher in our study than previously reported. Morbidity from AVM rupture should be considered as an important factor, together with variables such as risk of AVM rupture and procedural risk, in determining the optimal treatment strategy for unruptured cerebral AVMs.