Regional Metabolite T2 in the Healthy Rhesus Macaque Brain at 7T

Since the brain of nonhuman primates is biochemically, morphologically, and functionally similar to its human counterpart, rhesus macaques are increasingly used as advanced models for disease and treatment studies, e.g., in neuroAIDS (1), ischemic stroke (2), and Parkinson's and Huntington's diseases (3). Due to the need for repeated measurements, these studies favor nondestructive means: MRI for morphology and function, and proton MR spectroscopy (1H-MRS) for assessment of neuronal cells, cell energetics, and membrane turnover, through the levels of their surrogate markers, N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) (4,5). Unlike MRI, in which anatomy or contrast can be evaluated visually, 1H-MRS requires measurement of additional parameters for quantitative assessment. While instrumental factors (e.g., static, B0, and radio frequency [RF] field [B1] inhomogeneity) can be handled by field mapping (6), line fitting (7), and internal water referencing (8), molecular environment factors require knowledge of local longitudinal (T1) and transverse (T2) relaxation times (4). Although T1- and T2-weighting can be reduced with long repetition and short echo-times (TR ⪢ T1 and TE ⪡ T2) intermediate- and long-TE spectra are often preferred for their flatter baseline, decreased lipid contamination, and simpler peak structure (4). Consequently, reliable estimation of the metabolites’ T2 values is needed for their accurate quantification, especially at high fields (9,10). MRS in animal models is most relevant if voxels can be assigned to analogous human structures. Given that the ∼80 cm3 macaque brain is 16-fold smaller than the average human's 1250-cm3 brain (11,12), isotropic (1.0 cm)3 voxels in the latter scale to (0.4 cm)3 = 64 μl in the former and since the signal-to-noise-ratio (SNR) depends only on voxel size and acquisition time (13), such resolution favors higher B0s. Unfortunately, the lower RF power available at the higher B0s (typically 5−8 kW at 7T vs. up to 30 kW at 3T) also produce less B1 (half as much at 7T than at 4T) per Watt (14), limiting the power that can be delivered to the coil before voltage breakdown or power deposition (specific absorption rate [SAR]) limits are exceeded, even in animals. A simple way to avoid both issues is to extend the duration of the RF pulses (and consequently the TE) in order to reduce their peak amplitude. The shorter T2s at higher B0, however (15,16), may render such sequences “intermediate” or “long” TE that subject metabolites to unknown T2-weighting (4). Regional in vivo metabolite level variations make three-dimensional (3D) MR spectroscopic imaging (MRSI) the localization method of choice (5). To facilitate correction for the adverse effect of T2-weighting on the accuracy of metabolic quantification we measured the T2s of NAA, Cho, and Cr in several brain regions of four rhesus macaques at 7T with 3D MRSI at 64 μl spatial resolution using a two-point protocol optimized for precision per unit time (17).