Abstract

The insula plays a critical role in many neuropsychological disorders. Research investigating its neurochemistry with magnetic resonance spectroscopy (MRS) has been limited compared with cortical regions. Here, we investigate the within-session and between-session reproducibility of metabolite measurements in the insula on a 3T scanner. We measure N-acetylaspartate + N-acetylaspartylglutamate (tNAA), creatine + phosphocreatine (tCr), glycerophosphocholine + phosphocholine (tCho), myo-inositol (Ins), glutamate + glutamine (Glx), and γ-aminobutyric acid (GABA) in one cohort using a j-edited MEGA-PRESS sequence. We measure tNAA, tCr, tCho, Ins, and Glx in another cohort with a standard short-TE PRESS sequence as a reference for the reproducibility metrics. All participants were scanned 4 times identically: 2 back-to-back scans each day, on 2 days. Preprocessing was done using LCModel and Gannet. Reproducibility was determined using Pearson’s r, intraclass-correlation coefficients (ICC), coefficients of variation (CV%), and Bland–Altman plots. A MEGA-PRESS protocol requiring averaged results over two 6:45-min scans yielded reproducible GABA measurements (CV% = 7.15%). This averaging also yielded reproducibility metrics comparable to those from PRESS for the other metabolites. Voxel placement inconsistencies did not affect reproducibility, and no sex differences were found. The data suggest that MEGA-PRESS can reliably measure standard metabolites and GABA in the insula.

Highlights

  • The insula, a bilateral region of the cerebral cortex, plays a major role in human cognition, interoception, sensorimotor, and socio-emotional processing [1]

  • For MEGA-PRESSeditOFF, two participant datasets were removed from analysis (n = 27) upon screening for excessive movements during the scans, as noted by the MR technologist at the time of scanning and corroborated by the spectral quality check: one dataset had large lipid contamination in the LCModel outputs of the MEGA-PRESSeditOFF spectra for both scans on Day2; the second dataset had one scan with excessive head motion resulting in excessive noise visible on one of the four MEGA-PRESSeditOFF spectra output by LCModel

  • By using the MEGA-PRESS protocol requiring 13.5 min of scan time, we obtain D2D reproducibility metrics for GABA+ that are comparable to the reproducibility metrics we get for standard metabolites with a 3.5-min short-TE PRESS

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Summary

Introduction

The insula, a bilateral region of the cerebral cortex, plays a major role in human cognition, interoception, sensorimotor, and socio-emotional processing [1]. Due to its location deep within the lateral sulcus, the insula had largely been overlooked until recent decades, where technological advances provide new insights on its contribution to neuropathologies. Clinical studies have demonstrated its implication in neuropsychiatric disorders, including addiction, schizophrenia, mood, panic, post-traumatic stress, and obsessive-compulsive disorders [2–9]. The insula has become a subject of interest in addiction research following the discovery that insular damage facilitated smoking cessations [10,11]. One approach to studying the insula involves understanding its neurochemistry. Magnetic Resonance Spectroscopy (MRS) allows non-invasive in-vivo metabolite measurements of a particular brain region. Using MRS, altered metabolite concentrations in the insula were reported in fibromyalgia [12], epilepsy [13–15], schizophrenia [16], anxiety disorders [17], major depression [18], and drug addiction [8]

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