QUANTITATIVE IN-VIVO H-1 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC IMAGING OF NEURONAL LOSS IN RAT-BRAIN

The aim of this research was to determine whether in vivo nuclear magn etic resonance spectroscopic measurement of N-acetyl aspartate, a neur on specific brain marker, provides a quantitative index of neuronal lo ss. Five rats were injected unilaterally in the corpus striatum with k ainic acid, an analogue of glutamate that causes excitotoxic degenerat ion of intrinsic neurons, and were subjected to nuclear magnetic reson ance imaging and spectroscopic imaging. Measurements of N-acetyl aspar tate were determined in vivo and compared to post mortem nuclear magne tic resonance spectroscopic measures of N-acetyl aspartate and choline acetyl transferase and glutamate decarboxylase activities, biochemica l markers for striatal intrinsic neuronal integrity. Mean per cent neu ronal survival of hemispheres with lesion versus the contralateral hem ispheres measured 72 for glutamate decarboxylase and 71 for N-acetyl a spartate (in vivo), 74 for N-acetyl aspartate (in vitro), and 62 for c holine acetyl transferase, respectively. Our studies in rats have show n that estimates of neuronal loss through nuclear magnetic resonance s pectroscopic measurements of N-acetyl aspartate are equivalent to trad itional neuronal enzyme activity assays. The results unequivocally dem onstrate that N-acetyl aspartate is a valid and sensitive neuronal mar ker with the capability of providing accurate assessments of neuronal loss in vivo.