1] Commissariat à l'Energie Atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center, Centre National de la Recherche Scientifique, Unité de Recherche Associée, Fontenay-aux-Roses Cedex, France [2] Institut de Myologie, Laboratoire de RMN, Paris, France.
J Cereb Blood Flow Metab. 2012 May;32(5):771-9. doi: 10.1038/jcbfm.2012.15. Epub 2012 Feb 29.
Early diagnosis and follow-up of neurodegenerative diseases are often hampered by the lack of reliable biomarkers. Neuroimaging techniques like magnetic resonance spectroscopy (MRS) offer promising tools to detect biochemical alterations at early stages of degeneration. Intracellular pH, which can be measured noninvasively by (31)P-MRS, has shown variations in several brain diseases. Our purpose has been to evaluate the potential of MRS-measured pH as a relevant biomarker of early degeneration in Huntington's disease (HD). We used a translational approach starting with a preclinical validation of our hypothesis before adapting the method to HD patients. (31)P-MRS-derived cerebral pH was first measured in rodents during chronic intoxication with 3-nitropropionic acid (3NP). A significant pH increase was observed early into the intoxication protocol (pH=7.17±0.02 after 3 days) as compared with preintoxication (pH=7.08±0.03). Furthermore, pH changes correlated with the 3NP-induced inhibition of succinate dehydrogenase and preceded striatum lesions. Using a similar MRS approach implemented on a clinical MRI, we then showed that cerebral pH was significantly higher in HD patients (n=7) than in healthy controls (n=6) (7.05±0.03 versus 7.02±0.01, respectively, P=0.026). Altogether, both preclinical and human data strongly argue in favor of MRS-measured pH being a promising biomarker for diagnosis and follow-up of HD.
早期诊断和跟踪神经退行性疾病通常受到缺乏可靠生物标志物的阻碍。磁共振波谱（MRS）等神经影像学技术提供了有前途的工具，可以在变性的早期阶段检测生物化学变化。细胞内 pH 值可以通过 (31)P-MRS 进行非侵入性测量，在几种脑部疾病中已经显示出了变化。我们的目的是评估 MRS 测量的 pH 值作为亨廷顿病（HD）早期变性的相关生物标志物的潜力。我们采用了一种转化方法，首先在临床前验证了我们的假设，然后将该方法应用于 HD 患者。在慢性 3-硝基丙酸（3NP）中毒期间，我们首先在啮齿动物中测量了 (31)P-MRS 衍生的脑 pH 值。与中毒前相比（pH=7.08±0.03），在中毒早期观察到 pH 值显著升高（pH=7.17±0.02，在第 3 天）。此外，pH 值变化与 3NP 诱导的琥珀酸脱氢酶抑制相关，并且早于纹状体损伤。然后，我们使用类似的 MRS 方法在临床 MRI 上实施，结果表明 HD 患者的脑 pH 值明显高于健康对照组（n=7 与 n=6，分别为 7.05±0.03 与 7.02±0.01，P=0.026）。总而言之，临床前和人体数据都强烈支持 MRS 测量的 pH 值作为 HD 诊断和随访的有前途的生物标志物。
