Longitudinal hippocampal diffusion-weighted imaging and T2 relaxometry demonstrate regional abnormalities which are stable and predict subfield pathology in temporal lobe epilepsy.

OBJECTIVE: High-resolution (1 mm isotropic) diffusion tensor imaging (DTI) of the hippocampus in temporal lobe epilepsy (TLE) patients has shown patterns of hippocampal subfield diffusion abnormalities, which were consistent with hippocampal sclerosis (HS) subtype on surgical histology. The objectives of this longitudinal imaging study were to determine the stability of focal hippocampus diffusion changes over time in TLE patients, compare diffusion and quantitative T2 abnormalities of the sclerotic hippocampus, and correlate presurgical mean diffusivity (MD) and T2 maps with postsurgical histology. METHODS: Nineteen TLE patients and 19 controls underwent two high-resolution (1 mm isotropic) DTI and 1.1 × 1.1 × 1 mm3  T2 relaxometry scans (in a subset of 16 TLE patients and 9 controls) of the hippocampus at 3T, with a 2.6 ± 0.8 year inter-scan interval. Within-participant hippocampal volume, MD and T2 were compared between the scans. Contralateral hippocampal changes 2.3 ± 1.0 years after surgery and ipsilateral preoperative MD maps versus postoperative subfield histopathology were evaluated in eight patients who underwent surgical resection of the hippocampus. RESULTS: Reduced volume and elevated MD and T2 of sclerotic hippocampi remained unchanged between longitudinal scans. Focal regions of elevated MD and T2 in bilateral hippocampi of HS TLE were detected consistently at both scans. Regions of high MD and T2 correlated and remained consistent over time. Volume, MD, and T2 remained unchanged in postoperative contralateral hippocampus. Regional elevations of MD identified subfield neuron loss on postsurgical histology with 88% sensitivity and 88% specificity. Focal T2 elevations identified subfield neuron loss with 75% sensitivity and 88% specificity. SIGNIFICANCE: Diffusion and T2 abnormalities in ipsilateral and contralateral hippocampi remained unchanged between the scans suggesting permanent microstructural alterations. MD and T2 demonstrated good sensitivity and specificity to detect hippocampal subfield neuron loss on postsurgical histology, supporting the potential that high-resolution hippocampal DTI and T2 could be used to diagnose HS subtype before surgery.

White Matter Changes Caused by Mild Traumatic Brain Injury in Mice Evaluated Using Neurite Orientation Dispersion and Density Imaging.

Mild traumatic brain injury (mTBI) is common and can lead to persistent cognitive and behavioral symptoms. Although diffusion tensor imaging (DTI) has demonstrated some sensitivity to changes in white matter following mTBI, recent studies have suggested that more complex geometric models of diffusion, including the neurite orientation dispersion and density imaging (NODDI) model, may be more sensitive and specific. Here, we evaluate microstructural changes in white matter following mTBI using DTI and NODDI in a mouse model, and compare the time course of these changes to behavioral impairment and recovery. We also assess volumetric changes for a comprehensive picture of the structural alterations in the brain and histological staining to identify cellular changes that may contribute to the differences detected in the imaging data. Increased orientation dispersion index (ODI) was observed in the optic tracts of mTBI mice compared with shams. Changes in fractional anisotropy (FA) were not statistically significant. Volume deficits were detected in the optic tract as well as in several gray matter regions: the lateral geniculate nuclei of the thalamus, the entorhinal cortex, and the superior colliculi. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) staining was increased in the optic tracts of mTBI brains, and this staining correlated with ODI values. A transient impairment in working memory was observed, which resolved by 6 weeks, whereas increased ODI, GFAP, and Iba1 persisted to 18 weeks post-injury. We conclude that the optic tracts are particularly vulnerable to damage from the closed-skull impact model used in this study, and that ODI may be a more sensitive metric to this damage than FA. Differences in ODI and in histological measures of astrogliosis, neuroinflammation, and axonal degeneration persist beyond behavioral impairment in this model.