Faculty Bibliography

Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high SNR images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work concludes a three-part series of recommendations and considerations for preclinical dMRI. Herein, we describe best practices for dMRI of ex vivo tissue, with a focus on image pre-processing, data processing, and comparisons with microscopy. In each section, we attempt to provide guidelines and recommendations but also highlight areas for which no guidelines exist (and why), and where future work should lie. We end by providing guidelines on code sharing and data sharing and point toward open-source software and databases specific to small animal and ex vivo imaging.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Sex steroid hormones have been demonstrated to affect the immune system in multiple sclerosis (MS), and puberty may trigger MS activity. We aimed to evaluate the association between menarche and disease course in pediatric MS through comparison of relapse rates across premenarche, perimenarche, and postmenarche periods. METHODS:This is a retrospective analysis of a prospectively followed female cohort with pediatric-onset MS in the US Network of Pediatric MS Centers database. Perimenarche was considered the period from 1 year before to 1 year after the estimated menarche date based on menarche integer age. Relapses were collected prospectively. Negative binomial and repeated-measures Cox regression models were used to assess the association of pubertal development stage with relapse rate, adjusted for race, body mass index, and disease-modifying therapy (DMT). RESULTS:< 0.001). DISCUSSION/CONCLUSIONS:Onset of puberty may be a time of increase in disease activity and may require consideration of a change in therapeutic approach. Menarche age was used as a surrogate for puberty, and future studies measuring sex steroid hormones may be informative.

IMPORTANCE/UNASSIGNED:Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves. OBJECTIVE/UNASSIGNED:To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024. EXPOSURE/UNASSIGNED:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presence of LC and participant-reported symptoms. RESULTS/UNASSIGNED:A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

BACKGROUND:The diagnosis and treatment of tumors often depend on molecular-genetic data. However, rapid and iterative access to molecular data is not currently feasible during surgery, complicating intraoperative diagnosis and precluding measurement of tumor cell burdens at surgical margins to guide resections. METHODS:Here, we introduce Ultra-Rapid droplet digital PCR (UR-ddPCR), a technology that achieves the fastest measurement, to date, of mutation burdens in tissue samples, from tissue to result in 15 min. Our workflow substantially reduces the time from tissue biopsy to molecular diagnosis and provides a highly accurate means of quantifying residual tumor infiltration at surgical margins. FINDINGS/RESULTS: = 0.995). CONCLUSIONS:The technology and workflow developed here enable intraoperative molecular-genetic assays with unprecedented speed and sensitivity. We anticipate that our method will facilitate novel point-of-care diagnostics and molecularly guided surgeries that improve clinical outcomes. FUNDING/BACKGROUND:This study was funded by the National Institutes of Health and NYU Grossman School of Medicine institutional funds. Reagents and instruments were provided in kind by Bio-Rad.

Seizures occur in 20-45% of patients with cerebral arteriovenous malformations (AVMs) and can potentially influence their quality of life. Some studies have suggested risk factors influencing their development, but the evidence is limited to small cohorts. To analyze seizure presentation and factors influencing seizure development in patients with cerebral AVMs using a multi-institutional consortium. Retrospective multicenter registry from multiple centers in North America and Europe of patients aged 1 to 89 years who had undergone any intervention for brain AVMs between January 2010 and December 2023. Demographics, functional assessment (modified Rankin Scale; mRS), and AVM characteristics, were evaluated to assess for relationship with seizures using a multivariate generalized linear mixed-effects model. 1,005 AVM patients were analyzed; the median age was 42, 73% had a baseline mRS ≤ 2. The median nidus size was 2.2 cm, and most AVMs were Spetzler-Martin grade II (37%). Seizure was the presenting symptom in 237 patients (24%). After adjusting for significant variables, patient-specific factors associated with seizures were younger age (OR 0.99, CI95% 0.98-1), male sex (OR 1.65, CI95% 1.18-2.30), and smoking history (OR 1.69, CI95% 1.17-2.44). AVM-specific factors associated with seizures included rupture status (OR 0.42, CI95% 0.30-0.61); eloquent cortex (OR 1.61, CI95% 1.13-2.29); frontal (OR 1.54, CI95% 1.01-2.35), temporal (OR 1.93, CI95% 1.26-2.96) and parietal (OR 1.71 CI95% 1.08-2.71) location; larger nidal size (OR = 1.23, CI95% 1.08-1.39), and superficial draining vein location (OR 1.86, CI95% 1.15-3.01). In this multicenter consortium, after controlling for significant variables, the incidence of AVM-related seizures was associated with younger age, male sex, smoking history, larger AVMs, eloquent locations, and AVMs in the frontal, temporal, and parietal cortices. Conversely, rupture status, deep venous drainage, and cerebellar locations were negatively associated with seizures.

PURPOSE/UNASSIGNED:People with blindness and low vision (pBLV) face challenges in navigating. Mobility aids are crucial for enhancing independence and safety. This paper presents an electronic travel aid that leverages a haptic-based, higher-order sensory substitution approach called Virtual Whiskers, designed to help pBLV navigate obstacles effectively, efficiently, and safely. MATERIALS AND METHODS/UNASSIGNED:Virtual Whiskers is equipped with a plurality of modular vibration units that operate independently to deliver haptic feedback to users. Virtual Whiskers features two navigation modes: open path mode and depth mode, each addressing obstacle negotiation from different perspectives. The open path mode detects and delineates a traversable area within an analyzed field of view and then guides the user in the most traversable direction with adaptive vibratory feedback. Depth mode assists users in negotiating obstacles by highlighting spatial areas with prominent obstacles; haptic feedback is generated by re-mapping proximity to vibration intensity. We recruited 10 participants with blindness or low vision for user testing of Virtual Whiskers. RESULTS/UNASSIGNED:Both approaches reduce hesitation time (idle periods) and decrease the number of cane contacts with objects and walls. CONCLUSIONS/UNASSIGNED:Virtual Whiskers is a promising obstacle negotiation strategy that demonstrates great potential to assist with pBLV navigation.

INTRODUCTION/UNASSIGNED:The impact of multiple feeding arteries on clinical outcomes of cerebral arteriovenous malformations (AVMs) is not well understood. This study aims to compare outcomes between AVMs with multiple versus single feeding arteries. PATIENTS AND METHODS/UNASSIGNED:Data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium were analyzed. Propensity score matching (PSM) was used to balance cohorts. Subgroup analysis was conducted for ruptured and unruptured AVMs and different treatment options, and multivariable logistic regression was applied to assess the impact of feeding artery origin. RESULTS/UNASSIGNED: = 0.002). DISCUSSION AND CONCLUSION/UNASSIGNED:AVMs with a single feeding artery were more likely to present with rupture, but no significant differences in obliteration rates or complications were observed between the groups after PSM. These findings suggest that while the number of feeding arteries may influence the initial presentation, it does not appear to impact overall treatment success or patient prognosis. Further prospective studies are needed to confirm these findings.

Curbs separate the edge of raised sidewalks from the street and are crucial to locate in urban environments as they help delineate safe pedestrian zones from dangerous vehicular lanes. However, the curbs themselves are also significant navigation hazards, particularly for people who are blind or have low vision (pBLV). The challenges faced by pBLV in detecting and properly orienting themselves for these abrupt elevation changes can lead to falls and serious injuries. Despite recent advancements in assistive technologies, the detection and early warning of curbs remains a largely unsolved challenge. This paper aims to tackle this gap by introducing a novel, multi-faceted sensory substitution approach hosted on a smart wearable; the platform leverages an RGB camera and an embedded system to capture and segment curbs in real time and provide early warning and orientation information. The system utilizes a YOLOv8 segmentation model which has been trained on our custom curb dataset to interpret camera input. The system output consists of adaptive auditory beeps, abstract sonifications, and speech, which convey curb distance and orientation. Through human-subjects experimentation, we demonstrate the effectiveness of the system as compared to the white cane. Results show that our system can provide advanced warning through a larger safety window than the cane, while offering nearly identical curb orientation information. Future enhancements will focus on expanding our curb segmentation dataset, improving distance estimations through advanced 3D sensors and AI-models, refining system calibration and stability, and developing user-centric sonification methods to cater for a diverse range of visual impairments.

BACKGROUND:Arteriovenous malformations (AVMs) are complex vascular anomalies with a high risk of hemorrhage and neurological deficits, especially when located in eloquent brain regions. The eloquence of an AVM location is a critical factor in the treatment planning, influencing both the risk of complications and long-term functional outcomes. This study aims to compare outcomes between eloquent and non-eloquent AVMs. METHODS:This multicenter, retrospective study utilized data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium. Patients with eloquent and non-eloquent AVMs were compared on baseline characteristics, angiographic outcomes, and functional outcomes using the modified Rankin Scale (mRS). Propensity score weighting (IPTW) was applied to adjust for confounding variables. RESULTS:The study included 1,013 patients, with 498 (49.2%) AVMs located in eloquent regions and 515 (50.8%) in non-eloquent regions. In unadjusted analysis, eloquent AVMs had lower complete obliteration rates (67.6% vs. 79.5%, OR: 0.53, 95% CI: 0.39-0.72, p < 0.001) and higher complication rates (24.5% vs. 19.0%, OR: 1.38, 95% CI: 1.02-1.86, p = 0.03) compared to non-eloquent AVMs. After IPTW adjustment, eloquent AVMs continued to show significantly higher odds of overall complications (OR: 1.68, 95% CI: 1.12-2.52, p = 0.01) and symptomatic complications (OR: 1.77, 95% CI: 1.12-2.80, p = 0.01). Secondary analysis within the eloquent group indicated that embolization was linked to an elevated risk of complications. Surgery and radiosurgery showed comparable functional outcomes at last follow-up and complications rates with higher complete obliteration rates in surgery. CONCLUSION/CONCLUSIONS:AVMs in eloquent brain areas present higher risks of complications and lower obliteration rates, emphasizing the need for cautious, individualized treatment planning. Within the eloquent group, embolization increased the risk of complications, while surgery and radiosurgery showed comparable functional outcomes at last follow-up and complication rates with higher complete obliteration rates in surgery. These findings highlight the importance of location in AVM management and support further research focusing on comparing treatment strategies for AVMs in eloquent brain areas.