Andrew Alexander, PhD – Slide of the Week

Andrew Alexander, PhD - Slide of the Week

Title: Mahalanobis distance tractometry (MaD-Tract) – a framework for personalized white matter anomaly detection applied to TBI

Legend: Patient-specific microstructural anomaly detection with MaD-Tract. These results show skeletonized tracts for a severe Traumatic Brain Injury patient in the top panel with abnormalities shown in red. The segments flagged as abnormal exceed a predetermined abnormality index depicted as the shaded gray area in the MaD plots (lower panel). The distribution of MaD as well as the univariate parameter profiles for the reference group are also shown. For reference, the skeletonized tracts color coded by direction embedded in the T1w volume are shown in the top left and right corners.

Citation: Guerrero-Gonzalez, J. M., Yeske, B., Kirk, G. R., Bell, M. J., Ferrazzano, P. A., & Alexander, A. L. (2022). Mahalanobis distance tractometry (MaD-Tract) – a framework for personalized white matter anomaly detection applied to TBI. NeuroImage, 260, 119475.

Abstract: Imaging-based quantitative measures from diffusion-weighted MRI (dMRI) offer the ability to non-invasively extract microscopic information from human brain tissues. Group-level comparisons of such measures represent an important approach to investigate abnormal brain conditions. These types of analyses are especially useful when the regions of abnormality spatially coincide across subjects. When this is not true, approaches for individualized analyses are necessary. Here we present a framework for single-subject multidimensional analysis based on the Mahalanobis distance. This is conducted along specific white matter pathways represented by tractography-derived streamline bundles. A definition for abnormality was constructed from Wilk’s criterion, which accounts for normative sample size, number of features used in the Mahalanobis distance, and multiple comparisons. One example of a condition exhibiting high heterogeneity across subjects is traumatic brain injury (TBI). Using the Mahalanobis distance computed from the three eigenvalues of the diffusion tensor along the cingulum, uncinate, and parcellated corpus callosum tractograms, 8 severe TBI patients were individually compared to a normative sample of 49 healthy controls. For all TBI patients, the analyses showed statistically significant deviations from the normative data at one or multiple locations along the analyzed bundles. The detected anomalies were widespread across the analyzed tracts, consistent with the expected heterogeneity that is hallmark of TBI. Each of the controls subjects was also compared to the remaining 48 subjects in the control group in a leave-one-out fashion. Only two segments were identified as abnormal out of the entire analysis in the control group, thus the method also demonstrated good specificity.

About the Lab: Alexander’s research focuses on the use of magnetic resonance imaging (MRI) for mapping and measuring the functional and structural organization of the human brain. These techniques are used to investigate the brain in both typically developing individuals and subjects with developmental disorders including autism. Functional MRI (fMRI) is used to assess brain regions associated with cognition and affect and their dysfunctions in these populations. Diffusion tensor MRI (DT-MRI) is used to study the patterns of structural connectivity between brain activity regions. Anatomic imaging methods are used to assess longitudinal structural changes in brain regions. These measurements are ultimately compared with measures of affect, behavior and cognition in specific population groups.

Investigator: Andrew Alexander, PhD

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