Imaging of Spontaneous Ventriculomegaly and Vascular Malformations in Wistar Rats: Implications for Preclinical Research

Abstract

Wistar rats are widely used in biomedical research and commonly serve as a model organism in neuroscience studies. In most cases when noninvasive imaging is not utilized, studies assume a consistent baseline condition in rats that lack visible differences. While performing a series of traumatic brain injury studies, we discovered mild spontaneous ventriculomegaly in 70/162 (43.2%) of Wistar rats that had been obtained from 2 different vendors. Advanced magnetic resonance (MR) imaging techniques, including MR angiography and diffusion tensor imaging, were utilized to evaluate the rats. Multiple neuropathologic abnormalities, including presumed arteriovenous malformations, aneurysms, cysts, white matter lesion and astrogliosis were found in association with ventriculomegaly. Postmortem micro-CT and immunohistochemical staining confirmed the presence of aneurysms and arteriovenous malformations. Diffusion tensor imaging significant decreases in fractional anisotropy and increases in mean diffusivity, axial diffusivity, and radial diffusivity in multiple white matter tracts (p < 0.05). These results could impact the interpretation, e.g. of a pseudo-increase of axon integrity and a pseudo-decrease of myelin integrity, based on characteristics intrinsic to rats with ventriculomegaly. We suggest the use of baseline imaging to prevent the inadvertent introduction of a high degree of variability in preclinical studies of neurological disease or injury in the Wistar rats.

Radiological–pathological correlation of diffusion tensor and magnetization transfer imaging in a closed head traumatic brain injury model

“…from the corresponding locations matching to the MRI data (see Fig 2E–G) to cover various DAI extents for correlation analysis from all five TBI time points (n = 75) via threshold of the normal staining intensity determined by the control staining. 24 The intraclass correlation coefficient for the IHC quantifications among investigators was >0.9 fulfilling the required minimum for good reliability. The IHC quantification from each investigator was then averaged to represent the percentage of positive fluorescent staining in the 20X images.…”

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

“…All animals underwent MRI before sonication to ensure that rats had normal brain ventricular anatomy (35). Following pFUS+MB, gadolinium (Gd)-enhanced T1-weighted (T1w) images demonstrated contrast enhancement in the frontal lobe demarcating the area that was harvested for molecular and histological analysis at different time points (Fig.…”

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

“…Spontaneous ventriculomegaly was also associated with abnormal vasculature, including aneurysms and arteriovenous malformations. 1 MVM rats had no abnormalities in young adulthood (i.e., skull size or shape) and could not be distinguished phenotypically from the normal rats. However, compared with normal rats, MVM rats have a 20% thinner corpus callosum and significantly increased astrogliosis in the cortex, without significant differences in myelination.…”

“…Spontaneous mild ventriculomegaly (MVM) was previously noted on baseline MR scans of Wistar rats used in a recent TBI study. 1 A total of 43% of the Wistar rats purchased from two dif-ferent vendors had abnormalities in their ventricular and vascular systems in the brain. The patterns of congenital ventriculomegaly included mild to moderate ventricle dilation, scattered intracranial arachnoid cysts (in both gray and white matter), and, more rarely, necrotic paraflocculus and cerebellum.…”

“…However, compared with normal rats, MVM rats have a 20% thinner corpus callosum and significantly increased astrogliosis in the cortex, without significant differences in myelination. 1 The ventriculomegaly brains exhibited significant differences in diffusion tensor imaging (DTI) metrics, which have been reported to be sensitive to diffuse axonal injury (DAI) in TBI patients 2,3 and in experimental studies. 4,5 At baseline, MVM rats have decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in the corpus callosum when compared with normal Wistar rats.…”