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Updated: Aug 1, 2026

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury
Published on: August 14, 2019
DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating
Keith L Main1,2,3, Salil Soman1,4,5, Franco Pestilli6
1War Related Illness and Injury Study Center, Veterans Affairs, Palo Alto Health Care System (VAPAHCS), Palo Alto, CA, United States.
Abstract:
Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.
Insights
Diffusion tensor imaging identifies key white matter tracts for diagnosing mild traumatic brain injury (TBI). The left cingulum and left inferior fronto-occipital fasciculus show promise as TBI biomarkers.
Area of Science:
- Neuroimaging
- Neurology
- Biomarkers
Background:
- Standard MRI is insufficient for mild traumatic brain injury (TBI) diagnosis.
- Diffusion tensor imaging (DTI) offers potential TBI biomarkers in white matter tracts.
- Identifying specific diagnostic tracts is crucial for TBI assessment.
Purpose of the Study:
- To rank white matter fiber tracts based on their ability to differentiate between patients with and without TBI.
- To identify the most diagnostic tracts for TBI using DTI measures.
- To evaluate the utility of receiver operating characteristic (ROC) analysis in TBI biomarker discovery.
Main Methods:
- Acquired DTI data from 109 military veterans (67% with TBI).
- Analyzed 20 fiber tracts per patient using fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity.
- Applied ROC analysis and kappa statistics to determine the most diagnostic tracts, validated with logistic regression.
Main Results:
- ROC analysis identified the left cingulum (LCG) and left inferior fronto-occipital fasciculus (LIF) as most diagnostic.
- Logistic regression confirmed LCG for fractional anisotropy and identified the right anterior thalamic tract (RAT) for other diffusivity measures.
- Bootstrapped ROC analyses provided confidence intervals for sensitivity, specificity, and kappa coefficients.
Conclusions:
- The left cingulum and left inferior fronto-occipital fasciculus are promising diagnostic biomarkers for TBI.
- DTI measures, particularly fractional anisotropy and diffusivity metrics, can help identify TBI-related white matter changes.
- ROC analysis is an effective method for identifying clinically relevant variables in TBI research.
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Traumatic Brain Injury l: Introduction

