Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

Abstract

Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations.

In VivoDiffusion Tensor Imaging in Acute and Subacute Phases of Mild Traumatic Brain Injury in Rats

“…The interpretation of changes in DTI metrics as an indicator of changes in the cellular level, however, is ambiguous. Only a few studies have combined DTI and histology, but only qualitative histologic analysis was applied with no direct link to the DTI metrics (Zhuo et al, 2012;Hylin et al, 2013;Singh et al, 2016;Tu et al, 2017;Herrera et al, 2017).…”

Monocyte depletion attenuates the development of posttraumatic hydrocephalus and preserves white matter integrity after traumatic brain injury

“…For these reasons we sought to employ a rapid and noninvasive approach to assess TBI progression and therapeutic responses following monocyte depletion over the course of TBI. Recent literature has identified ventriculomegaly, also known as posttraumatic hydrocephalus, and its associated cortical thinning as a reliable imaging marker for the progression of TBI in rodent models [ 16 , 17 ]. The incidence of clinically relevant posttraumatic hydrocephalus in brain-injured human patients has been estimated be as high as 45% and the development of posttraumatic hydrocephalus is tightly correlated with clinical outcomes [ 18 – 21 ].…”

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats

“…Other possible confounding factors include the emergence of tissue necrosis [ 1 , 15 ], demyelination [ 12 ] and alterations to the local blood vessel architecture [ 16 ] due to potentially higher intracranial pressure in the adult hydrocephalic rats compared to the juvenile hydrocephalic rats. Further investigations of changes in brain tissue microstructure will likely be useful [ 17 , 18 ] in providing further insight into why in-vivo brain stiffness did not change significantly in the adult hydrocephalic rats with closed skull sutures.…”