Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study.

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.

Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities.

Despite early antiviral treatment, herpes simples virus encephalitis (HSVE) still remains a life-threatening sporadic disease with high mortality and morbidity. In patients and in experimental disease, chronic progressive magnetic resonance imaging (MRI) abnormalities have been found even after antiviral therapy. Secondary autoimmune-mediated and not directly virus-mediated mechanisms might play a key role for the outcome of disease. This study aimed to evaluate a possible beneficial effect of a therapy of acyclovir and corticosteroids versus acyclovir only. In a mouse model of HSVE (intranasal inoculation with 10(5) pfu [plaque-forming units] of HSV-1 strain F), a long-term MRI study was realized. Cranial MRI was performed serially at days 2, 7, 14, 21, 60, and 180 in different therapy groups: 1, saline; 2, acyclovir; 3, acyclovir, subsequently methylprednisolone; 4, sham-infected with saline. Brain viral load peaked at day 7 to decline thereafter to a low baseline value. Viral load in group 1 was significantly higher than in animals with antiviral therapy. In group 4, no viral DNA was detectable. Viral load did not differ significantly between acyclovir and acyclovir/corticosteroid-treated groups, suggesting that the use of corticosteroids in addition to acyclovir does not increase viral burden. MRI findings in untreated and acyclovir-treated animals revealed chronic progressive changes. In contrast, there was a significant reduction of the severity of long-term MRI abnormalities in acyclovir/corticosteroid-treated animals. With respect to abnormal MRI findings, this study demonstrates a clear beneficial effect of an acyclovir and corticosteroid therapy without influencing brain viral load.