Imaging of spontaneous ventriculomegaly and vascular malformations in Wistar rats: implications for preclinical research.
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 used, 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 (43.2%) of 162 Wistar rats that had been obtained from 2 different vendors. Advanced magnetic resonance (MR) imaging techniques, including MR angiography and diffusion tensor imaging, were used to evaluate the rats. Multiple neuropathologic abnormalities, including presumed arteriovenous malformations, aneurysms, cysts, white matter lesions, and astrogliosis were found in association with ventriculomegaly. Postmortem microcomputed tomography and immunohistochemical staining confirmed the presence of aneurysms and arteriovenous malformations. Diffusion tensor imaging showed 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, for example, 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 neurologic disease or injury in Wistar rats.
From the Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland (T-WT, LCT, RAW, JDL, JAF); Department of Environmental Science, Baylor University, Waco, Texas (DDD); and National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland (JAF).
Tsang-Wei
TW
Tu
L Christine
LC
Turtzo
Rashida A
RA
Williams
Jacob D
JD
Lescher
Dana D
DD
Dean
Joseph A
JA
Frank
D000818:Animals; D035843:Biomedical Research / Q000592:standards*; D005260:Female; D006849:Hydrocephalus / Q000000981:diagnostic imaging* / Q000378:metabolism; D002538:Intracranial Arteriovenous Malformations / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000592:standards; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D055114:X-Ray Microtomography / Q000592:standards