TESTING INOSITOL HYPOTHESIS IN PATIENTS W/ PROBABLE ALZHEIMER DISEASE

该项目的目的是进一步定义 最近发现的大脑肌醇(Ml)的增加， 这表明肌醇代谢紊乱。肌醇增加 因此，信号可能是阿尔茨海默病的一个新的诊断标志 可通过磁共振测量的疾病(AD) 光谱学。此次合作的目标之一是进一步 确定AD患者肌醇代谢缺陷的酶基因座 利用4T自然丰度~(13)C-MRS直接分析 AD受试者脑内总游离肌醇含量，以排除 甘氨酸对~1H磁共振MI诊断峰的贡献 频谱。临床光谱已在1.5特斯拉使用1H获得 MRS，其中肌醇基本上是3.56ppm的一个显著峰值。 然而，信号变化很小，也同样可能导致 通过增加甘油、甘氨酸或肌醇磷酸酯的共振， 所有这些都在1.5特斯拉的相同化学位移下产生共振。13C 由于甘氨酸具有共振性，因此可以使用MRS来区分这些信号 例如，在一个明显的化学位移上。灵敏度为1.5特斯拉 不允许观察甘氨酸浓度的变化， 通常为1？摩尔/克。最近建立的13C-MRS为4 特斯拉建议，敏感度应该足以定义 无论是甘氨酸、甘油还是磷酸化肌醇 在1.5特斯拉看到的信号变化。我们已经执行了13C 对三名从加州飞过来的病人的研究。这个 结果明确地表明，肌醇在 这些病人。

The aim of this project is to further define the significance of the recently discovered increase in cerebral myo-inositol (ml), suggesting that INOSITOL metabolism is disordered. Increased inositol signal may thus be a newly identified diagnostic marker for Alzheimer disease (AD) that can be measured using magnetic resonance spectroscopy. One of the goals of this collaboration is to further define the enzymatic locus of defective inositol metabolism in AD using natural abundance 13C MRS at 4 Tesla to directly assay total-free inositol content of the brain in AD subjects, to exclude contributions from glycine to the diagnostic peak of mI in the 1H MR spectrum. Clinical spectra have been acquired at 1.5 Tesla using 1H MRS, where myo-inositol is essentially one prominent peak at 3.56 ppm. However, the signal change is small and could equally well be caused by increased glycerol, glycine or myo-inositol phosphate resonances, all of which resonate at the same chemical shift at 1.5 Tesla. 13C MRS can be used to distinguish these signals, since glycine resonates for example at a distinct chemical shift. Sensitivity at 1.5 Tesla does not permit observation of changes in the glycine concentration, which is typically 1?mol/g. The recent establishment of 13C MRS at 4 Tesla suggested that the sensitivity should be sufficient to define whether glycine, glycerol or phosphorylated inositol account for the signal change seen at 1.5 Tesla. We have already performed 13C studies on three patients who were flown over from California. The results demonstrated unequivocally that myo-inositol was elevated in these patients.