Inter-Subject Variability of Axonal Injury in Diffuse Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading cause of cognitive morbidity worldwide for which reliable biomarkers are needed. Diffusion tensor imaging (DTI) is a promising biomarker of traumatic axonal injury (TAI); however, existing studies have been limited by a primary reliance on group-level analytic methods not well suited to account for inter-subject variability. In this study, 42 adults with TBI of at least moderate severity were examined 3 months following injury and compared with 35 healthy controls. DTI data were used for both traditional group-level comparison and subject-specific analysis using the distribution-corrected Z-score (DisCo-Z) approach. Inter-subject variation in TAI was assessed in a threshold-invariant manner using a threshold-weighted overlap map derived from subject-specific analysis. Receiver operator curve analysis was used to examine the ability of subject-specific DTI analysis to identify TBI subjects with significantly impaired processing speed in comparison with region of interest-based fractional anisotropy (FA) measurements and clinical characteristics. Traditional group-wise analysis demonstrated widespread reductions of white matter FA within the TBI group (voxel-wise p < 0.05, corrected), despite relatively low consistency of subject-level effects secondary to widespread variation in the spatial distribution of TAI. Subject-specific mapping of TAI with the DisCo-Z approach was the best predictor of impaired processing speed, achieving high classification accuracy (area under the curve [AUC] = 0.94). In moderate-to-severe TBI, there is substantial inter-subject variation in TAI, with extent strongly correlated to post-traumatic deficits in processing speed. Significant group-level effects do not necessarily represent consistent effects at the individual level. Better accounting for inter-subject variability in neurobiological manifestations of TBI may substantially improve the ability to detect and classify patterns of injury.
1 Department of Radiology, Hospital of the University of Pennsylvania , Philadelphia, Pennsylvania.
Jeffrey B
JB
Ware
2 Moss Rehabilitation Research Institute , Philadelphia, Pennsylvania.
Tessa
T
Hart
2 Moss Rehabilitation Research Institute , Philadelphia, Pennsylvania.
John
J
Whyte
2 Moss Rehabilitation Research Institute , Philadelphia, Pennsylvania.
Amanda
A
Rabinowitz
3 Department of Neurology, Hospital of the University of Pennsylvania , Philadelphia, Pennsylvania.
John A
JA
Detre
2 Moss Rehabilitation Research Institute , Philadelphia, Pennsylvania.|4 Department of Physiology, Pharmacology, and Neuroscience, City University of New York School of Medicine , New York, New York.
Junghoon
J
Kim
D000328:Adult; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D020833:Diffuse Axonal Injury / Q000150:complications / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
cognitive function; diffusion tensor imaging; traumatic axonal injury; traumatic brain injury