IN-VIVO NONINVASIVE DETERMINATION OF ABNORMAL WATER DIFFUSION IN THE RAT-BRAIN STUDIED IN AN ANIMAL-MODEL FOR MULTIPLE-SCLEROSIS BY DIFFUSION-WEIGHTED NMR IMAGING

In vivo NMR images of the rat brain were obtained using a NMR microsco pe (7 T) from SMIS (England). Four animals were imaged every 3-4 days during a pathological cycle (starting after induction and up to 37 day s) of experimental allergic encephalomyelitis (EAE), an animal model f or multiple sclerosis. The EAE rats were weighted and clinically score d daily. We aimed at measuring the apparent diffusion coefficient (ADC ) or the mean diffusivity [D] with a high accuracy, and within a reaso nable experimental time frame, because of the clinical situation of th e animals. Therefore, we fitted the ADC value from five diffusion-weig hted images-with an experimental time of 17 min/image-and chose to app ly diffusion-sensitizing gradients in a direction intersecting all fib er directions of the external capsule. With this, we also obtained hig h b-values. For the control rats, we obtained a statistical mean value of ADC = (388 +/- 16) 10(-12) m(2)/s for gray matter and a statistica l mean value of [D] of (750 +/- 30) 10(-12) m(2)/s for white matter, m easured in the external capsule. For the EAE rats, no alterations in A DC values of gray matter with increasing clinical scores were observed . Concerning white matter, as determined in the external capsule, ther e were no significant differences in [D] values between controls and E AE rats before clinical signs occurred. However, when clinical signs w ere observed, we could demonstrate a significant positive correlation between the clinical score and the [D] values in the external capsule. As the clinical signs became more severe, we measured a rise in water diffusion (increase in [D]) in the external capsule, which was accomp anied by the occurrence of interstitial edema as revealed by a complem entary histological study.