Magnetoencephalography Atlas Viewer for Dipole Localization and Viewing.

Magnetoencephalography (MEG) is a noninvasive neuroimaging technique widely recognized for epilepsy and tumor mapping. MEG clinical reporting requires a multidisciplinary team, including expert input regarding each dipole's anatomic localization. Here, we introduce a novel tool, the "Magnetoencephalography Atlas Viewer" (MAV), which streamlines this anatomical analysis. The MAV normalizes the patient's Magnetic Resonance Imaging (MRI) to the Montreal Neurological Institute (MNI) space, reverse-normalizes MNI atlases to the native MRI, identifies MEG dipole files, and matches dipoles' coordinates to their spatial location in atlas files. It offers a user-friendly and interactive graphical user interface (GUI) for displaying individual dipoles, groups, coordinates, anatomical labels, and a tri-planar MRI view of the patient with dipole overlays. It evaluated over 273 dipoles obtained in clinical epilepsy subjects. Consensus-based ground truth was established by three neuroradiologists, with a minimum agreement threshold of two. The concordance between the ground truth and MAV labeling ranged from 79% to 84%, depending on the normalization method. Higher concordance rates were observed in subjects with minimal or no structural abnormalities on the MRI, ranging from 80% to 90%. The MAV provides a straightforward MEG dipole anatomic localization method, allowing a nonspecialist to prepopulate a report, thereby facilitating and reducing the time of clinical reporting.

Magnetoencephalography (MEG) Data Processing in Epilepsy Patients with Implanted Responsive Neurostimulation (RNS) Devices.

Drug-resistant epilepsy (DRE) is often treated with surgery or neuromodulation. Specifically, responsive neurostimulation (RNS) is a widely used therapy that is programmed to detect abnormal brain activity and intervene with tailored stimulation. Despite the success of RNS, some patients require further interventions. However, having an RNS device in situ is a hindrance to the performance of neuroimaging techniques. Magnetoencephalography (MEG), a non-invasive neurophysiologic and functional imaging technique, aids epilepsy assessment and surgery planning. MEG performed post-RNS is complicated by signal distortions. This study proposes an independent component analysis (ICA)-based approach to enhance MEG signal quality, facilitating improved assessment for epilepsy patients with implanted RNS devices. Three epilepsy patients, two with RNS implants and one without, underwent MEG scans. Preprocessing included temporal signal space separation (tSSS) and an automated ICA-based approach with MNE-Python. Power spectral density (PSD) and signal-to-noise ratio (SNR) were analyzed, and MEG dipole analysis was conducted using single equivalent current dipole (SECD) modeling. The ICA-based noise removal preprocessing method substantially improved the signal-to-noise ratio (SNR) for MEG data from epilepsy patients with implanted RNS devices. Qualitative assessment confirmed enhanced signal readability and improved MEG dipole analysis. ICA-based processing markedly enhanced MEG data quality in RNS patients, emphasizing its clinical relevance.

Spectral fitting strategy to overcome the overlap between 2-hydroxyglutarate and lipid resonances at 2.25 ppm.

PURPOSE: 1 H MRS provides a noninvasive tool for identifying mutations in isocitrate dehydrogenase (IDH). Quantification of the prominent 2-hydroxyglutarate (2HG) resonance at 2.25 ppm is often confounded by the lipid resonance at the same frequency in tumors with elevated lipids. We propose a new spectral fitting approach to separate these overlapped signals, therefore, improving 2HG evaluation. METHODS: TE 97 ms PRESS was acquired at 3T from 42 glioma patients. New lipid basis sets were created, in which the small lipid 2.25-ppm signal strength was preset with reference to the lipid signal at 0.9 ppm, incorporating published fat relaxation data. LCModel fitting using the new lipid bases (Fitting method 2) was conducted along with fitting using the LCModel built-in lipid basis set (Fitting method 1), in which the lipid 2.25-ppm signal is assessed with reference to the lipid 1.3-ppm signal. In-house basis spectra of low-molecular-weight metabolites were used in both fitting methods. RESULTS: Fitting method 2 showed marked improvement in identifying IDH mutational status compared with Fitting method 1. 2HG estimates from Fitting method 2 were overall smaller than those from Fitting method 1, which was because of differential assignment of the signal at 2.25 ppm to lipids. In receiver operating characteristic analysis, Fitting method 2 provided a complete distinction between IDH mutation and wild-type whereas Fitting method 1 did not. CONCLUSION: The data suggest that 1 H MR spectral fitting using the new lipid basis set provides a robust fitting strategy that improves 2HG evaluation in brain tumors with elevated lipids.

Brief mindfulness training increased glutamate metabolism in the anterior cingulate cortex.

Mindfulness meditation has become a promising intervention for promoting health and well-being. Neuroimaging studies have shown its beneficial effects on brain functional activity, connectivity, and structures following months to years of practice. A series of randomized controlled trials indicated that one form of mindfulness meditation, the integrative body-mind training (IBMT) induces brain functional and structural changes in brain regions related to self-control networks such as the anterior cingulate cortex (ACC) after 2-10 h of practice. However, whether IBMT could change brain metabolism in the ACC remains unexplored. Utilizing a noninvasive 3T proton magnetic resonance spectroscopy, our results showed a significant increase in glutamate metabolism in the rostral ACC following 10 h of IBMT, suggesting that brief training not only increases ACC activity and structure, but also induces neurochemical changes in regions of the self-control networks. To our knowledge, this is the first study demonstrating the positive effects on brain metabolism in the ACC following brief intervention, suggesting a potential mechanism and implications of mindfulness meditation in ameliorating disorders such as addiction, depression and schizophrenia, which often involve the dysfunction of self-control networks and glutamatergic system (i.e. lower glutamate metabolism).

Glycine by MR spectroscopy is an imaging biomarker of glioma aggressiveness.

BACKGROUND: High-grade gliomas likely remodel the metabolic machinery to meet the increased demands for amino acids and nucleotides during rapid cell proliferation. Glycine, a non-essential amino acid and intermediate of nucleotide biosynthesis, may increase with proliferation. Non-invasive measurement of glycine by magnetic resonance spectroscopy (MRS) was evaluated as an imaging biomarker for assessment of tumor aggressiveness. METHODS: We measured glycine, 2-hydroxyglutarate (2HG), and other tumor-related metabolites in 35 glioma patients using an MRS sequence tailored for co-detection of glycine and 2HG in gadolinium-enhancing and non-enhancing tumor regions on 3T MRI. Glycine and 2HG concentrations as measured by MRS were correlated with tumor cell proliferation (MIB-1 labeling index), expression of mitochondrial serine hydroxymethyltransferase (SHMT2), and glycine decarboxylase (GLDC) enzymes, and patient overall survival. RESULTS: Elevated glycine was strongly associated with presence of gadolinium enhancement, indicating more rapidly proliferative disease. Glycine concentration was positively correlated with MIB-1, and levels higher than 2.5 mM showed significant association with shorter patient survival, irrespective of isocitrate dehydrogenase status. Concentration of 2HG did not correlate with MIB-1 index. A high glycine/2HG concentration ratio, >2.5, was strongly associated with shorter survival (P < 0.0001). GLDC and SHMT2 expression were detectable in all tumors with glycine concentration, demonstrating an inverse correlation with GLDC. CONCLUSIONS: The data suggest that aggressive gliomas reprogram glycine-mediated one-carbon metabolism to meet the biosynthetic demands for rapid cell proliferation. MRS evaluation of glycine provides a non-invasive metabolic imaging biomarker that is predictive of tumor progression and clinical outcome. KEY POINTS: 1. Glycine and 2-hydroxyglutarate in glioma patients are precisely co-detected using MRS at 3T.2. Tumors with elevated glycine proliferate and progress rapidly.3. A high glycine/2HG ratio is predictive of shortened patient survival.

In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.

PURPOSE: To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS: Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS: The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION: The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.