Traumatic brain injury (TBI) has a high incidence of long-term morbidity. Manganese-enhanced MRI (MEMRI) provides high contrast structural and functional detail of the brain in-vivo. The study utilized serial MEMRI scanning in the fluid percussion injury (FPI) rat's model to assess long-term changes in the brain following TBI. Rats underwent a left-sided craniotomy and a 3.5 atmosphere FPI pulse (n = 23) or sham procedure (n = 22). MEMRI acquisition was performed at baseline, 1 day, 1 month, and 6 months after FPI. Volume changes and MnCl(2) enhancement were measured blindly using region-of-interest analysis and the results analyzed with repeated measures MANOVA. Compared to the shams, FPI animals showed a progressive decrease in brain volume from 1 (right, p = 0.02; left, p = 0.008) to 6 months (right, p = 0.04; left, p = 0.006), with progression over time (F = 7.16, p = 0.00018). Similar changes were found in the cortex and the hippocampus. Conversely, the ventricular volume was increased at 1 (p = 0.02) and 6 months (p = 0.003), with progression over time (F = 7.27, p = 0.0001). There were no differences in thalamic or amygdalae volumes. The severity of the early neuromotor deficits and the T2 signal intensity of the subacute focal lesion were highly predictive of the severity of the long-term hippocampal decrease, and the former was also associated with the degree of neuronal sprouting. Differential MnCl(2) enhancement occurred only in the dentate gyrus at 1 month on the side of trauma (p = 0.04). Progressive functional and structural changes occur in specific brain regions post-FPI. The severity of the neuromotor deficit and focal signal changes on MRI subacutely post-injury are predictive of severity of these long-term neurodegenerative changes.

Purpose:To report the detection of structural and functional biological changes in living animals using small animal in vivo MRI that complements traditional ex vivo histological techniques. We report the development and validation of the application of large deformation high dimensional mapping (HDM-LD) segmentation for the hippocampus in the rat. Materials and Methods:High resolution volumetric T2 weighted MRI images were acquired at 4.7 Tesla from six male in-breed nonepileptic Wistar rats. Two HDM-LD segmentations of the hippocampus (automated 1 and automated 2) were compared with the manual segmentations of two investigators who independently segmented the hippocampi (manual 1 and manual 2). Results:The mean overlap for the hippocampi between automated 1 and automated 2 for the right hippocampi was 94.4% (SD 1.0) and for the left hippocampi was 94.3% (SD 2.5), while the mean overlap between automated 1 and manual 1 for the right hippocampi was 91.4% (SD 1.3) and for the left hippocampi was 91.9% (SD 1.4). Mean values for absolute differences for comparisons of all the segmentations were the following: automated 1 versus automated 2, 3.2% (SD 1.0); manual 1 versus manual 2 6.82% (SD 5.22); automated 1 versus manual 1 13.0% (SD 1.8).Conclusion: HDM-LD can be applied to obtain accurate and reproducible three-dimensional segmentations of the hippocampus from rat MR images. HDM-LD will be a useful tool for investigations of hippocampal structural changes in vivo in rat models of human disease.

A series of novel oxazolo[3,2-a]pyrazolo [1,5-d]pyrazin-5-ones were synthesized by the reaction of ethyl 3-aryl-1-(2-oxo-2-arylethyl)-1H-pyrazole-5-carboxylate derivatives and aminoethanol under microwave-assisted one-step and solvent-free conditions.