MRS in mouse models of neurodegenerative diseases

Enormous progress has been made in the last decade towards elucidating the pathogenesis of human neurodegenerative diseases. The successful characterization of pathogenic mutations in several inherited diseases together with genetic engineering enabled the creation of transgenic and knock-in mouse models of human neurodegenerative diseases, such as Huntington's disease (HD), spinocerebellar ataxia (SCA1), early-onset familial Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) (1-4). These mouse models require advanced diagnostic methods to characterize the disease progression and the effectiveness of therapies. In vivo MR spectroscopy (MRS) has the potential to become an invaluable method for a non-invasive monitoring of brain neurochemistry in longitudinal studies using mouse models (5,6). However, 1 H MRS of the mouse brain is technically rather challenging due to the small size of the brain and a strong B 0 inhomogeneity induced in the brain by air/tissue interfaces. The aim of this article is to provide some recommendations to maximize the information content extractable from MRS and increase the reliability of neurochemical data. Neurochemical profiles of various mouse brain regions are significantly different (7), therefore small volumes of interest (VOI = 5 – 10 µL) are necessary to minimize the partial volume effect and to increase the measurement reproducibility and specificity. To keep the total duration of measurement in reasonable limits, high magnetic fields are preferable to compensate for reduced SNR from small VOI by an increased sensitivity at high fields. Increased chemical shift dispersion at high fields is extremely important to resolve overlapped resonances and to simplify strongly coupled spin systems. However, efficient minimization of B 0 inhomogeneity (shimming) is essential to take advantage of increased chemical shift dispersion and to increase the spectral resolution. Successful shimming requires an efficient shimming method and shim system (coils and drivers) strong enough to compensate for the field gradient induced in the brain. These local field gradients are scaled with B 0 and are not linear, therefore strong 2 nd-order shims are required. Shim strengths up to 2000 Hz/cm 2 (47.0 µT/cm 2) for XZ, YZ, Z2 and 1000 Hz/cm 2 (23.5 µT/cm 2) for 2XY and X2Y2 are recommended for mouse spectroscopy at 9.4 T (7). Higher field strengths require even stronger shims. Shimming can be efficiently performed by mapping along projections using the FASTMAP method (8,9) or by 3D B 0 mapping (10). A water linewidth of 10 – 12 Hz is achievable at 9.4T in most brain …