MAGNETIC RESONANCE IMAGING OF THE NEUROLOGICAL EFFECTS OF HYPERTENSION

Sumana Veeravelli , Eriko Yoshimaru, Lan Hoang, Michael Valdez, Alex Alvarez, Carol Barnes, Theodore Trouard

MAGNETIC RESONANCE IMAGING OF THE NEUROLOGICAL EFFECTS OF HYPERTENSION

Hypertension is common problem affecting over 30% of the US population over 20 years of age.  It is well-known that hypertension (HTN) in humans can lead to regional brain atrophy and cognitive decline.  The neurophysiological and cognitive effects of hypertension will become a more significant problem as our population ages. Diffusion tensor imaging (DTI), a completely non-invasive MRI method for investigating white matter, could be a useful tool to evaluate these physiological changes.  Data from DTI images are used to determine the fractional anisotropy (FA) value, a measurement of the restricted diffusion of water in various tissues. This provides a quantitative measure of the integrity of white matter tracts in the brain. This project evaluated the utility of DTI in determining whether rats experiencing long-term hypertension would exhibit reduced FA in white matter, and correlate this with lower behavioral performance. In this study we use Cyp1al transgenic rats which have the cytochrome P450 promoter inserted to up-regulate the expression of the mouse renin (Ren-2) gene. Administration of 0.15% indole-3-carbinol (I3C) to their chow activates the promoter to induce a gradual onset of HTN. I3C augmented diet was initiated at 16 months of age over a 6-week interval to produce a HTN group of Cyp1a1-Ren-2 rats, whereas a control group of transgenic rats received normal chow. Magnetic Resonance Imaging was carried out following a 6 week period on a Bruker 7T BioSpec. DTI was carried out in 1 mm coronal sections (0.3 mm in plane) using a singleshot EPI with diffusion weighting (b = 1000 s/mm2) in 25 non-collinear directions. The region of interest (ROI) analysis of the FA maps indicated a significant difference in the white matter integrity of the corpus callosum between the hypertension and control groups in the study. Lower FA values were associated with diminished behavioral performance. From this work, measurements of FA show potential as non-invasive biomarkers for evaluating the cerebrovascular effects of hypertension during aging. This could aid efforts in the evaluation of new treatments and prevention therapies for the brain changes associated with healthy and pathological aging. (Supported in part by HHMI 52006942)

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