John J. Kotyk

Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging.

Using magnetic resonance diffusion tensor imaging (DTI), the present study investigates changes in both gray and white matter in the APPsw transgenic mouse (Tg2576), a model of beta-amyloid plaque deposition associated with Alzheimers disease (AD). DTI analyses were performed in cross-sectional groups of transgene-positive and -negative mice at 8, 12, 16, and 18 months of age to assess the magnitude of water diffusion in gray matter (i.e., Tr(D)) and changes in diffusion in white matter that may be indicative of axonal degeneration (i.e., reduced water diffusion parallel to axonal tracts, lambda(||)) and myelin degradation (i.e., increased water diffusion perpendicular to axonal tracts, lambda(perpendicular)). No appreciable changes in gray or white matter were observed between the APPsw and the age-matched control mice at 8 months of age. Reduced Tr(D) and lambda(||) were observed in gray and white matter, respectively, for the APPsw mice at ages greater than 8 months, which coincides with the time period when appreciable amyloid plaque accumulation was confirmed by ex vivo histopathological studies. The decreases in lambda(||) suggest the presence of axonal injury in multiple white matter tracts of APPsw mice. Unlike lambda(||), lambda(perpendicular) was unaltered between control and APPsw mice in most white matter tracts. However, in the corpus collosum (CC), lambda(perpendicular) increased at 16 and 18 months of age, suggesting the possibility of myelin damage in the CC at these later ages. This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues.

Evaluation of white matter integrity in ex vivo brains of amyloid plaque-bearing APPsw transgenic mice using magnetic resonance diffusion tensor imaging

Magnetic resonance diffusion tensor imaging (DTI) was used to examine the integrity of midline white matter tracts in APPsw (Tg2576) transgenic mice, a mouse-model of cerebral amyloid deposition. Ex vivo DTI was performed on formalin-fixed brains from APPsw and age-matched transgene-negative control mice at the ages of 12, 15, and 17 months. The characteristics of water diffusion in six midline white matter tracts were quantified using four metrics: relative anisotropy (RA), mean diffusivity, axial diffusivity, and radial diffusivity. Two-way ANOVA analyses indicated a significant main effect of transgene on RA in the corpus callosum (CC) and ventral hippocampal commissure (VHC), due to small reductions (2-6%) in RA in APPsw mice relative to age-matched control mice. However, these reductions were not significant at any specific age group and were not progressive with increasing age. The other diffusion metrics exhibited no significant differences between APPsw and control mice in the CC and VHC, nor did any of the diffusion metrics exhibit significant differences between APPsw and control mice in other midline white matter tracts (anterior commissure, posterior commissure, fornix, and dorsal fornix). Overall, these results indicate that white matter integrity, as measured by ex vivo DTI, is predominately unaltered in formalin-fixed brains from amyloid plaque-bearing APPsw mice.

Quantitative imaging of cartilage morphology at 3.0 Tesla in the presence of gadopentate dimeglumine (Gd-DTPA).

MRI‐based cartilage morphometry was previously validated in the absence of gadopentate dimeglumine (Gd‐DTPA). However, Gd‐DTPA is required for compositional (proteoglycan) imaging using delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC). Therefore, the effect of Gd‐DTPA on cartilage morphometry was studied. A total of 165 female participants (67 with and 98 without osteoarthritis [OA]) were imaged at 3.0 Tesla before and 2 hr after intravenous Gd‐DTPA injection. Flip angles in post‐Gd‐DTPA scans varied between 12° and 35°. Cartilage volume and thickness of post‐ vs. pre‐Gd‐DTPA scans showed intraclass correlation coefficients (ICCs) of 0.85 ≥ r ≥ 0.95, mean differences between –2.1% and +1.1%, and standard deviations (SDs) of differences between 4.7% and 9.2%. Mixed‐effect models found no consistent impact of flip angle and OA status on post‐ vs. pre‐Gd‐DTPA differences. Accurate morphological measurements of cartilage can be obtained after Gd‐DTPA injection, allowing compositional and morphological imaging to be combined into one session. Magn Reson Med 58:402–406, 2007.