Diffusion tensor tractography is increasingly used to examine structural connectivity in the brain in various conditions, but its test-retest reliability is understudied. The main purposes of this study were to evaluate 1) the reliability of quantitative measurements of diffusion tensor tractography and 2) the effect on reliability of the number of gradient sampling directions and scan repetition. Images were acquired from ten healthy participants. Ten fiber regions of nine major fiber tracts were reconstructed and quantified using six fiber variables. Intra- and inter-session reliabilities were estimated using intraclass correlation coefficient (ICC) and coefficient of variation (CV), and compared to pinpoint major error sources. Additional pairwise comparisons were made between the reliability of images with 30 directions and NEX 2 (DTI30-2), 30 directions and NEX 1 (DTI30-1), and 15 directions and NEX 2 (DTI15-2) to determine whether increasing gradient directions and scan repetition improved reliability. Of the 60 tractography measurements, 43 showed intersession CV ≤ 10%, ICC ≥ .70, or both for DTI30-2, 40 measurements for DTI30-1, and 37 for DTI15-2. Most of the reliable measurements were associated with the tracts corpus callosum, cingulum, cerebral peduncular fibers, uncinate fasciculus, and arcuate fasciculus. These reliable measurements included factional anisotropy (FA) and mean diffusivity of all 10 fiber regions. Intersession reliability was significantly worse than intra-session reliability for FA, mean length, and tract volume measurements from DTI15-2, indicating that the combination of MRI signal variation and physiological noise/change over time was the major error source for this sequence. Increasing the number of gradient directions from 15 to 30 while controlling the scan time, significantly affected values for all six variables and reduced intersession variability for mean length and tract volume measurements. Additionally, while increasing scan repetition from 1 to 2 had no significant effect on the reliability for DTI with 30 directions, this significantly reduced the upward bias in FA values from all 10 fiber regions and fiber count, mean length, and tract volume measurements from 5-7 fiber regions. In conclusion, diffusion tensor tractography provided many measurements with high test-retest reliability across different fiber variables and various fiber tracts even for images with 15 directions (NEX 2). Increasing the number of gradient directions from 15 to 30 with equivalent scan time reduced variability whereas increasing repetition from 1 to 2 for 30-direction DTI improved the accuracy of tractography measurements.

Background: Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem.Objective: To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome.Design: Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. Setting: Inpatient traumatic brain injury unit. Patients: From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age-and sex-matched controls.Main Outcome Measures: Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale-Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients.Results: At least 1 fiber variable of each region showed diffuse axonal injury-associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale-Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. Conclusion:Diffusion tensor tractography-based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome.

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. Neurology ® 2011;77:818-826 GLOSSARY AB ϭ angular bundle; AF ϭ arcuate fasciculus; CB ϭ cingulum bundle; CC ϭ corpus callosum; CCab ϭ anterior body of the corpus callosum; CCg ϭ genu of the corpus callosum; CCpb ϭ posterior body of the corpus callosum; CCs ϭ splenium of the corpus callosum; CPF ϭ cerebral peduncular fibers; CPpa ϭ cerebral peduncular fibers to the parietal lobes; CVLT-II ϭ California Verbal Learning Test-II; DCA ϭ discriminant correspondence analysis; DTI ϭ diffusion tensor imaging; FA ϭ fractional anisotropy; FB ϭ fornix body; FC ϭ fornix crus; GCS ϭ Glasgow Coma Scale; IFO ϭ inferior fronto-occipital fasciculus; ILF ϭ inferior longitudinal fasciculus; MD ϭ mean diffusivity; PLS ϭ partial least-squares; ROI ϭ region of interest; TAI ϭ traumatic axonal injury; TBI ϭ traumatic brain injury; UF ϭ uncinate fasciculus.Traumatic axonal injury (TAI) is strongly linked to high mortality and morbidity in traumatic brain injury (TBI).1 TAI is progressive with typical occurrence of cytoskeletal disruption within 4 -6 hours postinjury and disconnection of axons between 1 and 7 days.2 Secondary axotomy, which damages brain structur...

BackgroundDiffusion 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.MethodsFrom 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.ResultsFA 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.ConclusionsWhite 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.