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Ronel Veksler

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2 papers

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YNICL Journal 2020 Journal Article

Blood-brain barrier imaging as a potential biomarker for bipolar disorder progression

Lyna Kamintsky
Kathleen A. Cairns
Ronel Veksler
Chris Bowen
Steven D. Beyea
Alon Friedman
Cynthia Calkin

Bipolar disorder affects approximately 2% of the population and is typically characterized by recurrent episodes of mania and depression. While some patients achieve remission using mood-stabilizing treatments, a significant proportion of patients show progressive changes in symptomatology over time. Bipolar progression is diverse in nature and may include a treatment-resistant increase in the frequency and severity of episodes, worse psychiatric and functional outcomes, and a greater risk of suicide. The mechanisms underlying bipolar disorder progression remain poorly understood and there are currently no biomarkers for identifying patients at risk. The objective of this study was to explore the potential of blood-brain barrier (BBB) imaging as such a biomarker, by acquiring the first imaging data of BBB leakage in bipolar patients, and evaluating the potential association between BBB dysfunction and bipolar symptoms. To this end, a cohort of 36 bipolar patients was recruited through the Mood Disorders Clinic (Nova Scotia Health Authority, Canada). All patients, along with 14 control subjects (matched for sex, age and metabolic status), underwent contrast-enhanced dynamic MRI scanning for quantitative assessment of BBB leakage as well as clinical and psychiatric evaluations. Outlier analysis has identified a group of 10 subjects with significantly higher percentages of brain volume with BBB leakage (labeled the "extensive BBB leakage" group). This group consisted exclusively of bipolar patients, while the "normal BBB leakage" group included the entire control cohort and the remaining 26 bipolar subjects. Among the bipolar cohort, patients with extensive BBB leakage were found to have more severe depression and anxiety, and a more chronic course of illness. Furthermore, all bipolar patients within this group were also found to have co-morbid insulin resistance, suggesting that insulin resistance may increase the risk of BBB dysfunction in bipolar patients. Our findings demonstrate a clear link between BBB leakage and greater psychiatric morbidity in bipolar patients and highlight the potential of BBB imaging as a mechanism-based biomarker for bipolar disorder progression.

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YNIMG Journal 2019 Journal Article

Combining white matter diffusion and geometry for tract-specific alignment and variability analysis

Itay Benou
Ronel Veksler
Alon Friedman
Tammy Riklin Raviv

We present a framework for along-tract analysis of white matter (WM) fiber bundles based on diffusion tensor imaging (DTI) and tractography. We introduce the novel concept of fiber-flux density for modeling fiber tracts’ geometry, and combine it with diffusion-based measures to define vector descriptors called Fiber-Flux Diffusion Density (FFDD). The proposed model captures informative features of WM tracts at both the microscopic (diffusion-related) and macroscopic (geometry-related) scales, thus enabling improved sensitivity to subtle structural abnormalities that are not reflected by either diffusion or geometrical properties alone. A key step in this framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tracts enable meaningful inter-subject comparisons and group-wise statistical analysis. Moreover, we show that the FMM alignment can be generalized in a straight forward manner to a single-shot co-alignment of multiple fiber bundles. The proposed alignment technique is shown to outperform a well-established, commonly used DTI registration algorithm. We demonstrate the FFDD framework on the Human Connectome Project (HCP) diffusion MRI dataset, as well as on two different datasets of contact sports players. We test our method using longitudinal scans of a basketball player diagnosed with a traumatic brain injury, showing compatibility with structural MRI findings. We further perform a group study comparing mid- and post-season scans of 13 active football players exposed to repetitive head trauma, to 17 non-player control (NPC) subjects. Results reveal statistically significant FFDD differences (p-values<0. 05) between the groups, as well as increased abnormalities over time at spatially-consistent locations within several major fiber tracts of football players.

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