BACKGROUND & PURPOSE Precision Medicine is an approach to disease diagnosis, treatment and prevention which relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of this study is to assess the inter-site variability after harmonization of a high angular resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) multisite study. MATERIALS AND METHODS Diffusion MRI was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology (NIST) and from the brain of a traveling volunteer on thirteen 3T MR scanners representing three major vendors (General Electric, Philips and Siemens). Means of the DTI parameters and their coefficients of variation (CoVs) across scanners were calculated for each DTI metric and white matter tract. RESULTS For the NIST diffusion phantom, the CoV of apparent diffusion coefficient (ADC) across the 13 scanners was < 3.8% for a range of diffusivities from 0.4 to1.1×10−6 mm2/s. For the volunteer, the CoVs across scanners of the 4 primary DTI metrics, each averaged over the entire white matter skeleton, were all < 5%. In individual white matter tracts, large central pathways showed good reproducibility with the CoV consistently below 5%. However, smaller tracts showed more variability with the CoV of some DTI metrics reaching 10%. CONCLUSION The results suggest the feasibility of standardizing DTI across 3T scanners from different MR vendors in a large-scale neuroimaging research study.

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Fundamental questions remain unanswered about the longitudinal impact of blast-plus-impact complex traumatic brain injuries (TBI) from wars in Iraq and Afghanistan. This prospective, observational study investigated measures of clinical outcome in US military personnel evacuated to Landstuhl Regional Medical Center (LRMC) in Germany after such "blast-plus" concussive TBIs. Glasgow Outcome Scale-Extended assessments completed 6-12 months after injury indicated a moderate overall disability in 41/47 (87%) blast-plus TBI subjects and a substantial but smaller number (11/18, 61%, p=0.018) of demographically similar US military controls without TBI evacuated for other medical reasons. Cognitive function assessed with a neuropsychological test battery was not different between blast-plus TBI subjects and controls; performance of both groups was generally in the normal range. No subject was found to have focal neurological deficits. However, 29/47 (57%) of blast-plus subjects with TBI met all criteria for post-traumatic stress disorder (PTSD) versus 5/18 (28%) of controls (p=0.014). PTSD was highly associated with overall disability; 31/34 patients with PTSD versus 19/31 patients who did not meet full PTSD criteria had moderate to severe disability (p=0.0003). Symptoms of depression were also more severe in the TBI group (p=0.05), and highly correlated with PTSD severity (r=0.86, p<0.0001). Thus, in summary, high rates of PTSD and depression but not cognitive impairment or focal neurological deficits were observed 6-12 months after concussive blast-plus-impact complex TBI. Overall disability was substantially greater than typically reported in civilian non-blast concussive ("mild") patients with TBI, even with polytrauma. The relationship between these clinical outcomes and specific blast-related aspects of brain injuries versus other combat-related factors remains unknown.