Diffusion MRI approaches for investigating microstructural complexity in a rat model of traumatic brain injury

Abstract

Our study explores the potential of conventional and advanced diffusion MRI techniques including diffusion tensor imaging (DTI), and single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD) to investigate complex microstructural changes following severe traumatic brain injury in rats at a chronic phase. Rat brains after sham-operation or lateral fluid percussion (LFP) injury were scanned ex vivo in a 9.4 T scanner. Our region-of-interest-based approach of tensor-, and SS3T-CSD derived fixel-, 3-tissue signal fraction maps were sensitive to changes in both white matter (WM) and grey matter (GM) areas. Tensor-based measures, such as fractional anisotropy (FA) and radial diffusivity (RD), detected more changes in WM and GM areas as compared to fixel-based measures including apparent fiber density (AFD), peak FOD amplitude and primary fiber bundle density, while 3-tissue signal fraction maps revealed distinct changes in WM, GM, and phosphate-buffered saline (PBS) fractions highlighting the complex tissue microstructural alterations post-trauma. Track-weighted imaging demonstrated changes in track morphology including reduced curvature and average pathlength distal from the primary lesion in severe TBI rats. In histological analysis, changes in the diffusion MRI measures could be associated to decreased myelin density, loss of myelinated axons, and increased cellularity, revealing progressive microstructural alterations in these brain areas five months after injury. Overall, this study highlights the use of combined conventional and advanced diffusion MRI measures to obtain more precise insights into the complex tissue microstructural alterations in chronic phase of severe brain injury.

ComBating inter‐site differences in field strength: harmonizing preclinical traumatic brain injury MRI data

“…Values were harmonized across sites to investigate longitudinal changes to the ipsilateral and contralateral CC following TBI-an interhemispheric fiber bundle particularly vulnerable to injury, 52 including following lateral FPI. 11,12,29,48,[53][54][55][56] We found that TBI was associated with reduced FA in both the ipsilateral and contralateral CC, consistent with previous findings 11,26,47,48,56,57 and likely reflecting a loss of myelinated axons. 9,47,55 Consistent with this, we also observed a significant effect of injury on ipsilateral CC susceptibility values, with increased susceptibility in the ipsilateral CC at 28 days after injury likely reflecting decreased myelin content.…”

“…11,12,29,48,[53][54][55][56] We found that TBI was associated with reduced FA in both the ipsilateral and contralateral CC, consistent with previous findings 11,26,47,48,56,57 and likely reflecting a loss of myelinated axons. 9,47,55 Consistent with this, we also observed a significant effect of injury on ipsilateral CC susceptibility values, with increased susceptibility in the ipsilateral CC at 28 days after injury likely reflecting decreased myelin content. 9 In the ipsilateral CC, changes in ADC depended on the time after injury.…”

“…Whether this is a true biological effect or an artifact introduced by Com-Bat harmonization is unclear; however, reduced FA in the contralateral CC has been observed in this injury model previously. 26,29,47,48 Although ComBat harmonization also improved the Bland-Altman plot for QSM values, we did not observe a main effect of site on the unharmonized data. This is consistent with previous studies showing good reproducibility for clinical QSM data acquired at field strengths of 1.5 and 3 T 49,50 and 3 and 7 T, 42 and phantom data acquired at field strengths from 1.5 to 9.4 T. 51 In addition to the analysis of mean CC values, we also performed TBSS analyses to explore the effect of ComBat harmonization throughout the whole brain.…”

White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma

“…Other investigations also showed that white matter atrophy was associated with elevated MD and reduced FA 46 . Consistent with the findings of Chary and colleagues 56 , the ic in TBI rats during the chronic phase exhibited a decrease in FA, a decrease in AD, an increase in RD, and an increase in MD, which can be attributed to microstructural changes, such as the loss of myelinated axons and/or the accumulation of iron deposits. However, their findings in the CCs region partially align with our results, showing a decrease in FA, an increase in RD, and an increase in MD.…”

White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury

“…It is often assumed that lower fractional anisotropy values may correspond to a reduction of the white matter microstructural integrity. 71 However, emerging evidence suggests that higher fractional anisotropy and axial diffusivity values can be attributed to factors such as cytotoxic edema during the acute phase following injury 72 , 73 , 74 as well as glial scarring and a manifestation of recovery and/or compensation in the chronic phase, 69 , 72 , 74 , 75 , 76 or simply in the voxels with less fiber crossings. In these conditions, the interpretation of higher fractional anisotropy values as solely indicative of increased white matter integrity may not hold true.…”