title: Reliable non-invasive measurement of human neurochemistry using proton spectroscopy with an anatomically defined amygdala-specific voxel.
abstract: Given the central role of the amygdala in fear perception and expression and its likely abnormality in affective disorders and autism, there is great demand for a technique to measure differences in neurochemistry of the human amygdala. Unfortunately, it is also a technically complex target for magnetic resonance spectroscopy (MRS) due to a small volume, high field inhomogeneity and a shared boundary with hippocampus, which can undergo opposite changes in response to stress. We attempted to achieve reliable PRESS-localized single-voxel MRS at 3T of the isolated human amygdala by using anatomy to guide voxel size and location. We present data from 106 amygdala-MRS sessions from 58 volunteers aged 10 to 52 years, including two tests of one-week stability and a feasibility study in an adolescent sample. Our main outcomes were indices of spectral quality, repeated measurement variability (within- and between-subject standard deviations), and sensitivity to stable individual differences measured by intra-class correlation (ICC). We present metrics of amygdala-MRS reliability for n-acetyl-aspartate, creatine, choline, myo-Inositol, and glutamate+glutamine (Glx). We found that scan quality suffers an age-related difference in field homogeneity and modified our protocol to compensate. We further identified an effect of anatomical inclusion near the endorhinal sulcus, a region of high synaptic density, that contributes up to 29% of within-subject variability across 4 sessions (n=14). Remaining variability in line width but not signal-to-noise also detracts from reliability. Statistical correction for partial inclusion of these strong neurochemical gradients decreases n-acetyl-aspartate reliability from an intraclass correlation of 0.84 to 0.56 for 7-minute acquisitions. This suggests that systematic differences in anatomical inclusion can contribute greatly to apparent neurochemical concentrations and could produce false group differences in experimental studies. Precise, anatomically-based prescriptions that avoid age-related sources of inhomogeneity and use longer scan times may permit study of individual differences in neurochemistry throughout development in this late-maturing structure.
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, Room T-225 Waisman Center, 1500 Highland Ave, University of Wisconsin-Madison, WI 53705, USA.
authors.forename: Brendon M
authors.initials: BM
authors.lastname: Nacewicz
authors.forename: Lisa
authors.initials: L
authors.lastname: Angelos
authors.forename: Kim M
authors.initials: KM
authors.lastname: Dalton
authors.forename: Ron
authors.initials: R
authors.lastname: Fischer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Anderle
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Alexander
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davidson
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D000679:Amygdala / Q000033:anatomy & histology* / Q000737:chemistry* / Q000254:growth & development; D001923:Brain Chemistry / Q000502:physiology*; D002648:Child; D018728:Entorhinal Cortex / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009448:Neurochemistry / Q000379:methods; D011522:Protons; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D013057:Spectrum Analysis; D055815:Young Adult
chemical_list: D011522:Protons