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 microscope (7 T) from SMIS (England). Four animals were imaged every 3–4 days during a pathological cycle (starting after induction and up to 37 days) of experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis. The EAE rats were weighted and clinically scored daily. We aimed at measuring the apparent diffusion coefficient (ADC) or the mean diffusivity 〈D〉 with a high accuracy, and within a reasonable experimental time frame, because of the clinical situation of the animals. Therefore, we fitted the ADC value from five diffusion-weighted images—with an experimental time of 17 min/image—and chose to apply diffusion-sensitizing gradients in a direction intersecting all fiber directions of the external capsule. With this, we also obtained high b-values. For the control rats, we obtained a statistical mean value of ADC = (388 ± 16) 10−12 m2/s for gray matter and a statistical mean value of 〈D〉 of (750 ± 30) 10−12 m2/s for white matter, measured in the external capsule. For the EAE rats, no alterations in ADC values of gray matter with increasing clinical scores were observed. Concerning white matter, as determined in the external capsule, there were no significant differences in 〈D〉 values between controls and EAE rats before clinical signs occurred. However, when clinical signs were 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 accompanied by the occurrence of interstitial edema as revealed by a complementary histological study.