Proton MR Spectroscopic Imaging of Rhesus Macaque Brain In Vivo at 7T

Insights into the pathogenesis of neurological disorders and the subsequent development of therapies for them may require preclinical trials in nonhuman primates whose brain anatomy, cellular composition, biochemistry, and physiology is similar to their human counterpart. Indeed, such models are used to study Parkinson's and Huntington's diseases (1,2), ischemic stroke (3), and neuroAIDS (4,5) among others. These models have shown similar metabolic changes to those in analogous regions of the human brain, making their use critical to our understanding of basic disease mechanisms and response to therapy. Such models may be particularly suitable to test therapeutic strategies using stem cell transplantation, trophic factors, and gene therapy (3,6). Compared with smaller animals, however, the cost and complexity of experiments in nonhuman primates severely restrict the number that can be used. Serial studies, therefore, favor nondestructive methods, such as MRI and proton MR spectroscopy/spectroscopic imaging (1H-MRS/MRSI). The latter modality allows assessment of neuronal cells, cell energetics, membrane turnover, gliosis, and glycolysis through their respective surrogate markers, N-acetylaspartate (NAA) (7), creatine (Cr) (8), choline (Cho), myo-inositol (mI), and lactate levels (9). Furthermore, since in vivo 1H-MRS has shown variable metabolic changes among different brain regions, 3D MRSI variants are clearly the technology of choice (10,11). These constraints combined with the much smaller primate brain require proportionally higher spatial resolution than the 1−8 cm3 common in humans (12,13) in order to resolve several analogous structures in the same scan. Additionally, they should be short enough to complete all the tests on an unharmed anesthetized animal. In this study, we report for the first time a 3D multi-voxel 1H-MRSI at 0.05 cm3 spatial resolution over ≈25% of the rhesus macaque brain with a 25-min acquisition time at 7T. The goal is to demonstrate that the above points are addressable with current state-of-the-art hardware, technology, and techniques.