Neurodegenerative disorders include Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and multiple sclerosis. Selective neuronal loss or necrosis is also associated with disorders such as schizophrenia, ischemia, cancer, and stroke. Reduced levels of NAA are also associated with mesial temporal lobe epilepsy.
A dicarboxylic acid found almost exclusively in neurons, N-acetylaspartic acid (NAA) is endogenously localized in the cytoplasm. Formed in the presence of acetyl CoA and a membrane-bound enzyme from brain or spinal cord, NAA is the amino acid or amino acid derivative found in highest concentration in the brain, except for glutamic acid. NAA appears to be metabolically inert in adults and may function as an anion or to effect behavioral changes. The level of NAA correlates with neuronal health. Mapping levels and distribution of NAA in a brain is a noninvasive measure of neuronal density, which is useful in the study, staging, and diagnosis of disorders relating to neuronal injury, loss, or degeneration.
Conventional magnetic resonance spectroscopic imaging (MRSI), or chemical shift imaging (CSI), has been used to map NAA. See, for example, Brown et al., Proc. Natl. Acad. Sci. (USA) 79:3523-3526 (1982), and Maudsley et al., J. Magn. Reson. 51:147-152 (1983). Spatial and spectral information can be acquired simultaneously by using a time-varying, periodic magnetic field gradient wave form during the data acquisition (Echo Planar-CSI or EPCSI). Mansfield, Magn. Reson. Med. 1:370-386 (1984). Other approaches include acquiring data from different slices in the brain, and using multiple echoes. Duyn et al., Radiology 188:277-282 (1993) and Spielman et al., J. Magn. Reson. Imaging 2:253-262, (1992).
These methods provide an NAA map of 16.times.16 or 32.times.32 pixels, the latter requiring about 17 minutes by conventional CSI/MRSI techniques. A 256.times.64 image would take a minimum of 4.5 hours. EP-CSI can acquire a 32.times.32.times.16 matrix in a 17 minute scan with degraded spectral resolution. EP-CSI requires post-processing algorithms even more complicated than conventional CSI/MRSI. The acquired data is manipulated and reconstructed with the aid of custom software and a skilled operator.