The past 10 years have seen a rapid increase in the use of diffusion tensor imaging to identify biomarkers of traumatic brain injury (TBI). Although the literature generally indicates decreased anisotropic diffusion at more chronic injury periods and in more severe injuries, considerable debate remains regarding the direction (i.e., increased or decreased) of anisotropic diffusion in the acute to semi-acute phase (here defined as less than 3 months post-injury) of mild TBI (mTBI). A systematic review of the literature was therefore performed to (1) determine the prevalence of different anisotropic diffusion findings (increased, decreased, bidirectional, or null) during the semi-acute injury phase of mTBI and to (2) identify clinical (e.g., age of injury, post-injury scan time, etc.) and experimental factors (e.g., number of unique directions, field strength) that may influence these findings. Results from the literature review indicated 31 articles with independent samples of semi-acute mTBI pati...

Diffusion tensor imaging findings in semi-acute mild traumatic brain injury.

Fear-potentiated startle during extinction is associated with white matter microstructure and functional connectivity.

This study examines how injury mechanisms and early neuroimaging and clinical measures impact white matter (WM) fractional anisotropy (FA), mean diffusivity (MD), and tract volumes in the chronic phase of traumatic brain injury (TBI) and how WM integrity in the chronic phase is associated with different outcome measures obtained at the same time. Diffusion tensor imaging (DTI) at 3 T was acquired more than 1 year after TBI in 49 moderate-to-severe-TBI survivors and 50 matched controls. DTI data were analyzed with tract-based spatial statistics and automated tractography. Moderate-to-severe TBI led to widespread FA decreases, MD increases, and tract volume reductions. In severe TBI and in acceleration/deceleration injuries, a specific FA loss was detected. A particular loss of FA was also present in the thalamus and the brainstem in all grades of diffuse axonal injury. Acute-phase Glasgow Coma Scale scores, number of microhemorrhages on T2*, lesion volume on fluid-attenuated inversion recovery, and duration of posttraumatic amnesia were associated with more widespread FA loss and MD increases in chronic TBI. Episodes of cerebral perfusion pressure 20 mmHg nor acute-phase Rotterdam CT scores were associated with WM changes. Glasgow Outcome Scale Extended scores and performance-based cognitive control functioning were associated with FA and MD changes, but self-reported cognitive control functioning was not. In conclusion, FA loss specifically reflects the primary injury severity and mechanism, whereas FA and MD changes are associated with objective measures of general and cognitive control functioning.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jnr.23534

White matter microstructure in chronic moderate-to-severe traumatic brain injury: impact of acute-phase injury-related variables and associations with outcome measures

To evaluate the clinical utility of quantitative diffusion tensor tractography (DTT) and tractography-based core analysis (TBCA) of the cingulum by defining the reproducibility, normal values, and findings in traumatic brain injury (TBI). Eighty patients with TBI and normal routine MRI and 78 controls underwent MRI at 3T. To determine reproducibility, 12 subjects were scanned twice. Superior (SC) and inferior (IC) cingulum were analyzed separately by DTT (fractional anisotropy (FA) thresholds 0.15 and 0.30). TBCA was performed from volumes defined by tractography with gradually changed FA thresholds. FA values were correlated with clinical and neuropsychological data. The lowest coefficient of variation was obtained at DTT threshold 0.30 (2.0 and 2.4 % for SC and IC, respectively), but in proportion to standard deviations of normal controls, the reproducibility of TBCA was better in SC and similar to that of DTT in IC. In patients with TBI, volume reduction with loss of peripheral fibers was relatively common; mean FA was mostly normal in these tractograms. The frequency of FA reductions (>2 SD) was in DTT smaller than in TBCA, in which FA decrease was present in 42 (13.1 %) of the 320 measurements. Central FA values in SC predicted visuoperceptual ability, and those in left IC predicted cognitive speed, language, and communication ability (p < 0.05). Tractography-based measurements have sufficient reproducibility for demonstration of severe abnormalities of the cingulum. TBCA is preferential for clinical FA analysis, because it measures corresponding areas in patients and controls without inaccuracies due to trauma-induced structural changes.

Diffusion tensor tractography-based analysis of the cingulum: clinical utility and findings in traumatic brain injury with chronic sequels

Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor imaging (DTI) sequence suitable for clinical magnetic resonance imaging (MRI) protocols was evaluated. DTI of 15 subjects was used to analyze intra-rater and inter-rater reproducibility. Another 10 subjects underwent MRI twice for assessment of between-scan reliability. Ten long association tracts were defined by fiber tracking using inclusion and exclusion regions of interest (ROIs). Whole-tract analysis and tractography-based core analysis were performed, and the effect of fractional anisotropy (FA 0.15/0.30) and turning angle threshold (27°/60°) on reproducibility was evaluated. Additionally, ROI measurements were performed in the core of the tracts. For the tract-based methods, intra-rater and inter-rater reliabilities of FA and mean diffusivity (MD) measurements were excellent. Between-scan reproducibility was good or excellent in 127 of 130 of the measurements. There was no systematic difference in the reproducibility of the FA, MD, and volume measurements depending on the FA or turning angle threshold. For the cross-sectional ROI measurements, reliability showed large variation from poor to excellent depending on the tract. Compared with the commonly used cross-sectional core ROI method, the tract-based analyses seem to be a more robust way to identify and measure white matter tracts of interest, and provide a novel reproducible tool to perform core analysis.

/pdf/reproducibility-of-tract-based-and-region-of-interest-dti-2nl68gcpjc.pdf

Reproducibility of Tract-based and Region-of-Interest DTI Analysis of Long Association Tracts.

Purpose
To demonstrate the sensitivity of quantitative diffusion tensor tractography to traumatic injury of the uncinate fasciculus (UF), and to evaluate the effect of volume changes on the accuracy of quantitative analysis

Materials and Methods
Diffusion tensor imaging (DTI) was performed at 3 T for 110 patients with traumatic brain injury (TBI) and 60 control subjects Volume, mean diffusivity (MD), and mean fractional anisotropy (FA) of the UF were measured by means of tractography The influence of FA threshold on mean FA values was determined and the values were further related to the tract volume

Results
In patients with TBI, 16% of the volumes and 29% of the FA values were decreased and 25% of the MD values were increased (>2 SD from the mean of controls) Small tracts (6% of trajectories) often had normal mean FA, but low volume-related FA values Large UFs often had decreased mean FA values, but normal volume-related central values (3% of trajectories)

Conclusion
Posttraumatic FA and MD changes and volume reductions are common in the tractography of UF Trauma-induced volume changes can cause misleading whole-tract mean FA values Therefore, additional volume-based analysis of the central part is beneficial for clinical assessment J Magn Reson Imaging 2013;38:46–53 © 2012 Wiley Periodicals, Inc

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.23901

Olli M. Oksaranta

Papers

Diffusion tensor tractography of the uncinate fasciculus: Pitfalls in quantitative analysis due to traumatic volume changes