Clinical MR Unit, Huntington Medical Research Institutes, Pasadena, CA, USA.
Neuropsychiatr Dis Treat. 2011;7:495-9. doi: 10.2147/NDT.S23721. Epub 2011 Aug 24.
We applied (13)C magnetic resonance spectroscopy (MRS), a nonradioactive, noninvasive brain imaging technique, to quantify the oxidation of [1-(13)C] acetate in a conventional clinical magnetic resonance imaging (MRI) scanner in five consecutive elderly subjects at various clinical stages of Alzheimer's disease (AD) progression. [1-(13)C] acetate entered the brain and was metabolized to [5-(13)C] glutamate and glutamine, as well as [1-(13)C] glutamate and glutamine, and the final glial oxidation product, (13)C bicarbonate, at a linear rate. Calculation of the initial slope was similar in a single subject, examined twice, 1 month apart (test-re-test 8%). Mean rate of cerebral bicarbonate production in this elderly group was 0.040 ± 0.01 (n = 5). Assuming that the rate of conversion of acetate to bicarbonate is a reflection of glial metabolic rate and that glial metabolic rate is a surrogate marker for 'neuroinflammation', our preliminary results suggest that [1-(13)C] MRS may provide biomarkers for diseases, believed to involve microglia and other cells of the astrocyte series. Among these is AD, for which novel drugs which ameliorate the damaging effects of neuroinflammation before symptoms of dementia appear, are in advanced development. The value of (13)C MRS as an early, noninvasive biomarker may lie in the conduct of cost-effective clinical trials.
我们应用(13)C 磁共振波谱(MRS),一种非放射性、非侵入性的脑成像技术,在常规临床磁共振成像(MRI)扫描仪中定量测定 5 例连续的、处于不同阿尔茨海默病(AD)进展临床阶段的老年患者[1-(13)]乙酸的氧化。[1-(13)]乙酸进入大脑并被代谢为[5-(13)]谷氨酸和谷氨酰胺,以及[1-(13)]谷氨酸和谷氨酰胺,以及最终的神经胶质氧化产物(13)碳酸氢盐,以线性速率。在相隔 1 个月的两次检查中,单个患者的初始斜率计算相似(测试-测试 8%)。在这个老年组中,大脑碳酸氢盐生成的平均速率为 0.040±0.01(n=5)。假设乙酸转化为碳酸氢盐的速率反映了神经胶质代谢率,并且神经胶质代谢率是“神经炎症”的替代标志物,我们的初步结果表明[1-(13)]MRS 可能为疾病提供生物标志物,这些疾病被认为涉及小胶质细胞和星形胶质细胞系列中的其他细胞。其中包括 AD,目前正在开发新型药物,这些药物在痴呆症状出现之前可以改善神经炎症的破坏性影响。(13)C MRS 作为早期、非侵入性生物标志物的价值可能在于进行具有成本效益的临床试验。