Longitudinal changes of structural connectivity in traumatic axonal injury

Abstract

Objectives: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome.

Methods: The participants were 28 patients with mild to severe traumatic axonal injury and 20 age- and sex-matched healthy control subjects. Neuroimaging was obtained 0-9 days postinjury for acute scans and 6-14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used.

Results: Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients' long-term outcome. Acute tractography measurements were able to predict patients' learning and memory performance; chronic measurements also determined performance on processing speed and executive function.

Conclusions: Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients' long-term outcome.

Figure 1. Representative fiber tracking results

The reconstructed fiber tracts are overlaid on the images with minimum diffusion. The colors are assigned for the purpose of demarcating the fiber tracts and do not represent the principal diffusion direction as it is in the diffusion tensor imaging color-coded map. AB = angular bundle; AF = arcuate fasciculus; CB = cingulum bundle; CC = corpus callosum; CPF = cerebral peduncular fibers; IFO = inferior fronto-occipital fasciculus; ILF = inferior longitudinal fasciculus; UF = uncinate fasciculus.

Figure 2. Observations and group boundaries in the discriminant correspondence analysis (DCA) space

(A) Group boundaries. (B) Patients' progression on the DCA map from the acute to chronic stage of injury. The origins of arrows show the patients' positions at the acute stage of injury, and the terminations show their positions at the chronic stage. The colors of arrows indicate the group that the patients were assigned to in DCA at the chronic stage of traumatic brain injury (TBI). NC = normal control; TBIa = patients with acute TBI; TBIc = patients with chronic TBI.

Figure 3. Partial least-squares regression predicted and actual scores of California Verbal Learning Test (CVLT) long delay recall

The jackknife procedure was used to make the predictions using (A) acute measurements and (B) chronic measurements.