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Steven D. Beyea

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4 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 2011 Journal Article

Functional mapping in the corpus callosum: A 4T fMRI study of white matter

Jodie R. Gawryluk
Ryan C.N. D'Arcy
Erin L. Mazerolle
Kimberly D. Brewer
Steven D. Beyea

Introduction The idea of fMRI activation in white matter (WM) is controversial. Our recent work has used two different approaches to investigate whether there is evidence for WM fMRI. The first approach used words and faces to elicit interhemispheric transfer activation in the posterior corpus callosum (Sperry task). The second approach used checkerboard stimuli to elicit similar activation in the anterior corpus callosum (Poffenberger task). Using these different tasks, it has been possible to detect WM activation in different regions. In the current study, we report the results of a critical experiment: demonstrating that callosal activation can be experimentally manipulated within the same set of individuals. Methods All subjects completed both the Sperry and Poffenberger tasks. Functional MRI data were acquired at 4T, using an asymmetric spin echo spiral sequence. Data were analyzed with FSL using a model-based approach. Analyses focused on group and individual activations in WM. Results and discussion Corpus callosum activation was elicited for both tasks, with activation varying according to task type. A statistical contrast of the two tasks revealed posterior callosal activation for the Sperry task and anterior callosal activation for the Poffenberger task. The Sperry task showed activation in the isthmus and middle body of the corpus callosum at the group level and in 100% of subjects. The Poffenberger task showed activation in the genu and middle body of the corpus callosum at the group level and in 94% of subjects. The WM activation replicated prior results, with the additional strength of functional mapping within the same group of individuals.

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YNIMG Journal 2010 Journal Article

Confirming white matter fMRI activation in the corpus callosum: Co-localization with DTI tractography

Erin L. Mazerolle
Steven D. Beyea
Jodie R. Gawryluk
Kimberly D. Brewer
Chris V. Bowen
Ryan C.N. D'Arcy

Recently, functional magnetic resonance imaging (fMRI) activation has been detected in white matter, despite the widely-held belief that fMRI activation is restricted to gray matter. The objective of the current study was to determine whether the regions of white matter fMRI activation were structurally connected to the functional network in gray matter. To do this, we used fMRI-guided tractography to evaluate whether tracts connecting regions of gray matter fMRI activation were co-localized with white matter fMRI activation. An established interhemispheric transfer task was employed to elicit activation in the corpus callosum. Diffusion tensor imaging (DTI) tractography was used to determine the existence of tracts that connected regions of gray matter fMRI activation to regions of activation in the corpus callosum. Corpus callosum activation was detected in the majority of participants. While there was individual variability in the location of corpus callosum activation, activation was commonly observed in the callosal mid-body, isthmus/splenium, or both. Despite the variability, gray matter fMRI-guided tractography identified tracts that were co-localized with corpus callosum fMRI activation in all instances. In addition, callosal activation had tracts to bilateral gray matter fMRI activation for 7/8 participants. The results confirmed that the activated regions of the corpus callosum were structurally connected to the functional network of gray matter regions involved in the task. These findings are an important step towards establishing the functional significance of white matter fMRI, and provide the foundation for future work combining white matter fMRI and DTI tractography to study brain connectivity.

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YNIMG Journal 2009 Journal Article

Optimizing the detection of white matter fMRI using asymmetric spin echo spiral

Jodie R. Gawryluk
Kimberly D. Brewer
Steven D. Beyea
Ryan C.N. D'Arcy

The majority of functional magnetic resonance imaging (fMRI) studies restrict their focus to gray matter regions because this tissue is highly perfused relative to white matter. However, an increasing number of studies are reporting fMRI activation in white matter. The current study had two objectives: 1) to evaluate whether it is possible to detect white matter fMRI activation and 2) to determine whether certain MRI contrast mechanisms are more sensitive to white matter activation (i. e. , BOLD contrast- versus T 2-weighting). Data were acquired from a 4 T MRI using an asymmetric spin echo spiral sequence (ASE spiral). This technique collected three images with equal BOLD contrast weighting and increasing T 2-weighting. An interhemispheric transfer task was used to elicit activation in the corpus callosum. White matter fMRI activation was examined for the averaged ASE spiral data and for each image separately. Callosal activation was present in all subjects as well as in the group analysis. Analyses revealed that increasing T 2 contrast improved sensitivity as measured by percent signal change. The results suggest that it is possible to detect white matter activation in fMRI and that ASE spiral showed increasing sensitivity to this activation as a function of T 2-weighting. The findings provide further support for the investigation of white matter fMRI.

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