Quantitative MRI and DTI Abnormalities During the Acute Period Following CCI in the Ferret

Abstract

During the acute time period following traumatic brain injury (TBI), noninvasive brain imaging tools such as magnetic resonance imaging (MRI) can provide important information about the clinical and pathological features of the injury and may help predict long-term outcomes. In addition to standard imaging approaches, several quantitative MRI techniques including relaxometry and diffusion MRI have been identified as promising reporters of cellular alterations after TBI and may provide greater sensitivity and specificity for identifying brain abnormalities especially in mild TBI. However, for these imaging tools to be useful, it is crucial to define their relationship with the neurophysiological response to brain injury. Recently, a model of controlled cortical impact (CCI) has been developed in the ferret which has many advantages compared with rodent models (e.g., gyrencephalic cortex and high white matter volume). The objective of this study was to evaluate quantitative MRI metrics in the ferret CCI model, including T2 values and diffusion tensor imaging (DTI) metrics, during the acute time period. Longitudinal quantitative comparisons of in vivo MRI and DTI metrics were evaluated to identify abnormalities and characterize their spatial patterns in the ferret brain. Ex vivo MRI and DTI maps were then compared with histological staining for glial and neuronal abnormalities. The main findings of this article describe T2, diffusivity, and anisotropy markers of tissue change during the acute time period following mild TBI, and ex vivo analyses suggest that MRI and DTI markers are sensitive to subtle cellular alterations in this model. This was confirmed by comparison with immunohistochemistry, also showing altered markers in regions of MRI and DTI change.

Progression of histopathological and behavioral abnormalities following mild traumatic brain injury in the male ferret

“…To consistently select histologic sections from a similar location relative to the CCI lesion, ex vivo MRI scans were performed prior to sectioning, and regions of abnormal diffusion tensor imaging (DTI) values were identified according to previously described imaging findings along with details of image acquisition and processing (Hutchinson et al, 2016;Hutchinson, Schwerin, Avram, Juliano, & Pierpaoli, 2018 …”

Detection and Distinction of Mild Brain Injury Effects in a Ferret Model Using Diffusion Tensor MRI (DTI) and DTI-Driven Tensor-Based Morphometry (D-TBM)

“…It is well known that the interstitial space is reduced with perfusion fixation ( Cragg, 1979 ; Korogod et al, 2015 ) such that the effect of interstitial edema may not be evident in ex vivo diffusion MRI acquisitions. In fact, an initial in vivo study of a subset of ferrets from the current work ( Hutchinson et al, 2016 ) found that diffusivity is increased after mTBI in the ferret, but when the same brain is imaged ex vivo , diffusivity is reduced in the affected region. Thus, cellular alterations from mild damage (e.g., cellularity, beading, gliosis) may be present following mTBI, but masked by the overwhelming influence of interstitial edema in vivo and then unmasked when performing ex vivo DTI.…”

“…Blinding of the researchers was not possible in this study as the ferret data was collected in sequential small groups over several years and the nature of the experiments required researcher familiarity with each animal precluding blinding. DTI from one of the injured brains was included in a previous publication to support in vivo findings in the same animal ( Hutchinson et al, 2016 ). An MRI ferret brain template computed from 8 of the 9 controls included in this study is publicly available ( Hutchinson et al, 2017b ).…”

Mini Review of Controlled Cortical Impact: A Well-Suited Device for Concussion Research

“…Later, CCI was scaled up for use in larger laboratory animals, including nonhuman primates [ 17 ] and swine [ 15 , 16 , 30 , 31 , 32 , 33 ]. Ferret models have recently regained popularity with two new papers published recently [ 34 , 35 ].…”