Mapping of Hippocampal pH and Neurochemicals from in vivo Multi-Voxel 31P Study in Healthy Normal Young Male/Female, Mild Cognitive Impairment, and Alzheimer's Disease
Issue title: Predictive Biomarkers for Alzheimer's Disease using State-of-the-Art Brain Imaging Techniques
Affiliations: [a] Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Centre, Gurgaon, India | [b] Department of Neurology, All Indian Institute of Medical Sciences, New Delhi, India
Correspondence:
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Correspondence to: Dr. Pravat K. Mandal, Adjunct Associate Professor, Department of Radiology, Johns Hopkins Medicine, Baltimore, MD, USA and Additional Professor, National Brain Research Centre, India. E-mails: pravat.mandal@gmail.com or pmandal4@jhmi.edu.
Abstract: Magnetic resonance spectroscopy (MRS) plays an important role in the understanding of membrane and energy metabolism. The outcome of MRS experiments helps to derive important cellular conditions (e.g., intracellular pH, energy, membrane metabolism, etc.), which are directly related to neuronal health. We present a novel multi-voxel 31P MRS imaging experimental scheme along with an advanced 31P signal processing technique to determine the pH and neurochemicals from both hippocampal areas in shorter time (13.2 min) for subjects (e.g. healthy young male/female, mild cognitive impairment (MCI) and Alzheimer's disease (AD)). Significant (p = 0.005) decrease of phosphomonoester (PME) and increase of phosphodiester (PDE) (p < 0.001), γ-ATP (0.008), and PCr (p = 0.001) levels in the left hippocampus of AD patients (n = 6) compared to the control subjects (n = 12) were found based on post-hoc ANOVA. On the other hand, in the right hippocampus, decrease in PME (p = 0.008) and increase in PDE (p < 0.001) were significant between AD patients and controls. In case of AD subjects, pH in the left hippocampus is increased towards alkaline side compared to MCI but did not reach statistical significance level. The pH (left hippocampus) in AD is found to be negatively correlated (r = −0.829, p = 0.042) with PCr level (left hippocampus) in AD subjects. In the left hippocampus, the increase in pH to alkaline range (in normal aging, pH is decreased to acidic range) along with statistically significant increments of PCr, γ-ATP, and PDE as well as decrease of PME in AD subjects provide extremely crucial clinical information, which can be used as biomarker for AD and potentially aid in the diagnosis.
