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Background: Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome., Methods: Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation., Results: Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores., Conclusions: In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance.

Background: Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI., Methods: From a prospective TBI outcomes database, 11 patients who underwent acute (≤7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation., Results: FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 ± 0.02 vs. 0.55 ± 0.11, p < 0.05) and inferior longitudinal fasciculus (0.54+/-0.07 vs. 0.49+/-0.07, p < 0.01). Acute correlations between FA and DRS score were variable: higher FA in the body (R = -0.78, p = 0.02) and splenium (R = -0.83, p = 0.003) of the corpus callosum was associated with better outcomes (i.e. lower DRS scores), whereas higher FA in the genu of the corpus callosum (R = 0.83, p = 0.02) corresponded with worse outcomes (i.e. higher DRS scores). In contrast, in the subacute period higher FA in the splenium correlated with better outcomes (R = -0.63, p < 0.05) and no inverse correlations were observed., Conclusions: White matter FA declined during the acute-to-subacute stages of TBI. Variability in acute FA correlations with outcome suggests that the optimal timing of DTI for TBI prognostication may be in the subacute period.

Traumatic brain injury (TBI) commonly results in residual memory difficulties. Such deficits are amenable to cognitive rehabilitation, but optimal selection of rehabilitation interventions remains a challenge. We hypothesized that diffusion tensor imaging (DTI) could be used to predict which individuals were likely to benefit from a specific memory rehabilitation intervention. Thirty-seven individuals with TBI, of all severities, first underwent DTI scanning, along with 18 matched controls. Participants with TBI then attended a 12-session memory intervention emphasizing internal memory strategies (I-MEMS). Primary outcome measures (HVLT, RBMT) were collected at the time of DTI scanning, and both immediately and one month post-therapy. In contrast to typical neuroimaging analysis, fractional anisotropy (FA) was used to predict long-term outcome scores, adjusting for typical predictors (injury severity, age, education, time since injury, pretest score). FA of the parahippocampal white matter was a significant negative predictor of HVLT, while the anterior corpus callosum, left anterior internal capsule, and right anterior corona radiata were negative predictors of RBMT outcome. The importance of these predictors rivaled those of pretest scores. Thus, FA measures may provide substantial predictive value for other cognitive interventions as well. The reason why higher FA was associated with less successful response to cognitive intervention remains unclear and will require further study.