Table 4.

DTI Studies with Different DTI Severities Including Mild

First Author	Year	Type of Study [time post-injury]	Magnet	Subjects (N, gender, age)	DTI Analysis Method and Dependent Measures	Brain Region(s)	Main Finding(s)
Huisman	2004	Acute <7 days.	1.5T	Patients: 20 patients (15M, 5F; mean age 31). [GCS 4–15]. Controls: 15 healthy subjects with a matching age distribution (mean age 35).	Analysis and Methods: ROI Analysis. Dependent Measures: FA, ADC.	Posterior limb of the internal capsule (bilaterally) and the splenium of the CC. Measurements in the thalamus and putamen served as internal references.	FA values were significantly reduced in the internal capsule. FA values were significantly correlated with GCS and Rankin scores for the internal capsule and splenium. ADC values were significantly reduced within the splenium. Correlation between FA and clinical markers was better than that for the ADC values. ADC of the internal capsule was not correlated with the GCS and Rankin scores.
Salmond	2006	Chronic > 6 months.	3T	Patients: 16 patients (13M, 3F; mean age 32) [Median GCS 7, range 3–13]. Controls: 16 controls [12M, 3F; mean age 34].	Analysis and Methods: Voxel based analysis. Dependent Measures: FA, MD.	Maps of FA and MD were calculated from the diffusion-weighted images.	Major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes showed bilateral decreases in FA. Increases in MD were found in widespread areas of the cortex. A positive correlation was found between MD and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex.
Benson	2007	Acute to Chronic. Variable from days to years (mean 35.3 months, range 3 days to 15 years).	1.5T	Patients: 20 patients (13M, 7F; mean age 35.5) [GCS 3–15]. 6 mTBI and 14 moderate/severe TBI All CT+ except N=3 mTBI. Controls: 14 age-matched controls (mean age 27.5).	Analysis and Methods: White matter whole-brain FA histogram parameters. Dependent Measures: FA, Kurtosis, Skewness.	Whole-brain analysis using histogram shape parameters.	White matter whole-brain FA histograms showed a decrease in FA in TBI patients with no overlap between patient and controls. Histogram shape parameters correlated with each other and with admission GCS and PTA. Mean FA was the best predictor of PTA duration (r=−.64) and GCS (−.47). 40% of PTA variance in ADC was accounted for by FA. Most of the FA decrease was likely accounted for by increased diffusion in the short axis dimension, reflecting dysmyelination and axonal swelling. The correlation of injury severity with changes in FA suggests a role for DTI in early diagnosis and prognosis of TBI.
Kumar	2009	Acute. 5–14 days.	1.5T	Patients: 83 patients [62M, 21F; mean age 34.25]. 26 mTBI [GCS 13–15, mean 14.5]. 57 moderate TBI [GCS 9–12]. All were positive for clinical findings on CT at injury. Controls: 33 age- and sex-matched controls (22M, 11F; mean age 32.1).	Analysis and Methods: ROI. Dependent Measures: FA, RD, MD, AD.	CC (divided into 7 segments).	Decreased FA in genu in mTBI compared to moderate TBI, and in both TBI groups compared with controls. Decreased FA in splenium in moderate TBI compared to controls. Decreased MD in moderate TBI compared to controls. Increased RD in genu and splenium in mTBI and moderate TBI compared to controls. Increased RD in midbody CC in moderate TBI compared to controls. Decreased AD in genu in moderate TBI compared to controls. Poor neuropsychological outcome at 6-months was associated with DT abnormalities in the CC.
Levin	2010	Chronic. Post-injury interval 871.5 days.	3T	Patients: 37 veterans (mean age 31.5) with mild or moderate TBI [GCS not provided]. 5 had positive findings on clinical MRI. Controls: 15 veterans without a history of TBI or exposure to blast (mean age 31.4), including 7 subjects with extracranial injury (mean post-injury interval 919.5 days), and 8 who were uninjured.	Analysis and Methods: Tractography, standard single-slice ROI measurement, and voxel-based analysis. Manually-traced ROIs on a slice-by-slice basis, and quantitative fiber tractography to assess white matter integrity Dependent Measures: FA, ADC	Non-tractography ROI protocols included the total CC (including genu, body, splenium, and total), and the right and left anterior and posterior limbs of the internal capsule.	No group differences in FA and ADC were found. However, FA of the left and right posterior internal capsule and left corticospinal tract positively correlated with total words consistently recalled. ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent.
Hartikainen	2010	Acute. 3 weeks.	1.5T	Patients: 18 patients (6M, 12F; 11 asymptomatic and 7 symptomatic; mean age 43) with mild and moderate TBI. All moderate subjects had positive findings on clinical CT or MRI. Controls: None.	Analysis and Methods: ROI Dependent Measures: FA, ADC	Thalamus, internal capsule, centrum semiovale, and mesencephalon.	Symptomatic patients had higher FA and lower ADC in the mesencephalon then asymptomatic patients. None of the other FA or ADC measurements were significantly different between symptomatic and asymptomatic patients.
Little	2010	Chronic. ≥12 months.	3T	Patients: 12 patients with mTBI (mean age 31.2). 12 moderate to severe TBI (mean age 33.3) Severity was based on duration of Loss of Consciousness and Post-Traumatic Amnesia. 4 mTBI and 9 moderate to severe patients had positive findings on MRI or CT. Controls: 12 age- and education-matched controls (mean age 30.8).	Analysis and Methods: ROI. Dependent Measures: FA.	12 ROIs in cortical and CC structures and 7 subcortical ROIs (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei).	TBI patients showed reductions in FA in the anterior and posterior corona radiata, forceps major, the body of CC, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. FA from cortico-cortico and CC ROIs did not account for significant variance in neuropsychological function. However, FA from the thalamic seed voxels did account for variance in executive function, attention, and memory.
Singh	2010	Acute to Chronic. Mean ~1 month.	1.5T	Patients: 12 patients (mean age 28) with mild to moderate brain injuries (loss of consciousness for <1 h) primarily due to falls, assault or traffic accidents. Controls: 10 age-matched volunteers (mean age 27). No evidence of neurological disease on MR imaging.	Analysis and Methods: ROI analysis. Dependent Measures: FA, MD, AD, RD.	Differences in the FA maps between each TBI subject and the control group were computed in a common space using a t-test, transformed back to the individual TBI subject’s head space, and then thresholded to create ROIs that were used to sort tracts from the control group and the individual TBI subject. Tract counts for a given ROI in each TBI subject were compared to group mean for the same ROI in order to quantify the impact of injury along affected pathways. The same procedure was used to compare the TBI group to the control group in a common space.	Within TBI subjects affected pathways included hippocampal/ fornix, inferior fronto-occipital, inferior longitudinal fasciculus, CC (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study.
Brandstack	2011	Acute. Mean 7 days	1.5T	Patients: 22 patients (GCS 6–15) admitted to the emergency department for TBI. On clinical MRI 7 were negative for findings, 15 showed cortical contusions or traumatic axonal injury. Controls: 14 healthy subjects.	Analysis and Methods: ROI analysis. Dependent Measures: ADC.	Measurements were performed at 46 different locations including bilateral cortical, subcortical and deep brain structures.	TBI patients with and without visible lesions did not show any differences in ADC values but both groups differed from the controls in several cortical and deep brain regions. Increased ADC values were common in TBI groups but decreased ADC values were relatively uncommon. Regional ADC values and the number of abnormal regions did not correlate with either GCS or GOS (Glasgow outcome scale)-E scores.
Ljungqvist	2011	Acute. Within 11 days and at 6 months post-injury.	1.5T	Patients: 8 patients with TBI (4M, 4F; mean age 36.4) [GCS 3–14]. All patients were CT negative. Controls: 6 controls (3M, 3F; mean age 33.1).	Analysis and Methods: ROI analysis. Dependent Measures: FA, Trace, AD, RD.	Polygonal ROIs were manually placed in the CC.	Patients showed a reduction in FA in the corpus callosum in the acute phase compared to controls. There was no significant change in AD, RD, or Trace. At 6 months, a significant reduction in FA and a significant increase in Trace and AD in patients compared to controls.
Yurgelun-Todd	2011	Not reported.	3T	Patients: 15M veterans with TBI (mild, moderate and severe according to The Ohio State University - TBI Identification Method). Controls: 17M controls: 10 civilians, 6 veterans.	Analysis and Methods: ROI analysis. Dependent Measures: FA, MD.	ROIs for major white matter tracts were created for the genu and the cingulum using the Johns Hopkins University White Matter Labels Atlas.	TBI patients showed a decrease in FA values in the left cingulum, and left and total genu compared to controls. The TBI group showed greater impulsivity Total and right cingulum FA positively correlated with current suicidal ideation and measures of impulsivity.

Key: M=Male; F=Female; GCS=Glasgow Coma Scale; CC=Corpus Callosum; ADC=Apparent Diffusion Coefficient; FA=Fractional Anisotropy; MD=Mean Diffusivity; RD=Radial Diffusivity; AD=Axial Diffusivity; ROI=Region of Interest.

This table presents findings derived from Diffusion Tensor Imaging (DTI), including: Trace, Mean Diffusivity (MD), Fractional Anisotropy (FA), Axial Diffusivity (AD), Radial Diffusivity (RD), and Mean Kurtosis (MK). In studies where non-DTI diffusion weighted imaging (DWI) was also presented, we include the main measure, Apparent Diffusion Coefficient (ADC). In the description of the subjects, we provide, when available, the Glascow Coma Scale (GCS) score, Loss of Consciousness (LOC) duration, and Posttraumatic Amnesia (PTA) duration. Acute is defined as under 1 month, subacute is defined as >1 month but greater than 6 months, and chronic is defined as >6 months.