Functional Magnetic Resonance Spectroscopy of Lactate in Alzheimer Disease: A Comprehensive Review of Alzheimer Disease Pathology and the Role of Lactate.

ABSTRACT: Functional 1H magnetic resonance spectroscopy (fMRS) is a derivative of dynamic MRS imaging. This modality links physiologic metabolic responses with available activity and measures absolute or relative concentrations of various metabolites. According to clinical evidence, the mitochondrial glycolysis pathway is disrupted in many nervous system disorders, especially Alzheimer disease, resulting in the activation of anaerobic glycolysis and an increased rate of lactate production. Our study evaluates fMRS with J-editing as a cutting-edge technique to detect lactate in Alzheimer disease. In this modality, functional activation is highlighted by signal subtractions of lipids and macromolecules, which yields a much higher signal-to-noise ratio and enables better detection of trace levels of lactate compared with other modalities. However, until now, clinical evidence is not conclusive regarding the widespread use of this diagnostic method. The complex machinery of cellular and noncellular modulators in lactate metabolism has obscured the potential roles fMRS imaging can have in dementia diagnosis. Recent developments in MRI imaging such as the advent of 7 Tesla machines and new image reconstruction methods, coupled with a renewed interest in the molecular and cellular basis of Alzheimer disease, have reinvigorated the drive to establish new clinical options for the early detection of Alzheimer disease. Based on the latter, lactate has the potential to be investigated as a novel diagnostic and prognostic marker for Alzheimer disease.

Prediction of Normal Tissue Complication Probability (NTCP) After Radiation Therapy Using Imaging and Molecular Biomarkers and Multivariate Modelling.

The aim of this study was to design a predictive radiobiological model of normal brain tissue in low-grade glioma following radiotherapy based on imaging and molecular biomarkers. Fifteen patients with primary brain tumors prospectively participated in this study and underwent radiation therapy. Magnetic resonance imaging (MRI) was obtained from the patients, including T1- and T2-weighted imaging and diffusion tensor imaging (DTI), and a generalized equivalent dose (gEUD) was calculated. The radiobiological model of the normal tissue complication probability (NTCP) was performed using the variables gEUD; axial diffusivity (AD) and radial diffusivity (RD) of the corpus callosum; and serum protein S100B by univariate and multivariate logistic regression XLIIIrd Sir Peter Freyer Memorial Lecture and Surgical Symposium (2018). Changes in AD, RD, and S100B from baseline up to the 6 months after treatment had an increasing trend and were significant in some time points (P-value < 0.05). The model resulting from RD changes in the 6 months after treatment was significantly more predictable of necrosis than other univariate models. The bivariate model combining RD changes in Gy40 dose-volume and gEUD, as well as the trivariate model obtained using gEUD, RD, and S100B, had a higher predictive value among multivariate models at the sixth month of the treatment. Changes in RD diffusion indices and in serum protein S100B value were used in the early-delayed stage as reliable biomarkers for predicting late-delayed damage (necrosis) caused by radiation in the corpus callosum. Current findings could pave the way for intervention therapies to delay the severity of damage to white matter structures, minimize cognitive impairment, and improve the quality of life of patients with low-grade glioma.

Early Detection of Radiation-Induced Injury and Prediction of Cognitive Deficit by MRS Metabolites in Radiotherapy of Low-Grade Glioma.

PURPOSE: To compare the sensitivity of MRS metabolites and MoCA and ACE-R cognitive tests in the detection of radiation-induced injury in low grade glioma (LGG) patients in early and early delayed postradiation stages. METHODS: MRS metabolite ratios of NAA/Cr and Cho/Cr, ACE-R and MoCA cognitive tests, and dosimetric parameters in corpus callosum were analyzed during RT and up to 6-month post-RT for ten LGG patients. RESULTS: Compared to pre RT baseline, a significant decline in both NAA/Cr and Cho/Cr in the corpus callosum was seen at the 4th week of RT, 1, 3, and 6-month post-RT. These declines were detected at least 3 months before the detection of declines in cognitive functions by ACE-R and MoCA tools. Moreover, NAA/Cr alterations at 4th week of RT and 1-month post-RT were significantly negatively correlated with the mean dose received by the corpus callosum, as well as the corpus callosum 40 Gy dose volume, i.e., the volume of the corpus callosum receiving a dose greater than 40 Gy. CONCLUSION: MRS-based biomarkers may be more sensitive than the state-of-the-art cognitive tests in the prediction of postradiation cognitive impairments. They would be utilized in treatment planning and dose sparing protocols, with a specific focus on the corpus callosum in the radiation therapy of LGG patients.