title: Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T.
abstract: Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression; therefore, there has been significant clinical interest in studying hippocampal neurochemistry. However, the hippocampus is a challenging region to study using (1) H MRS, hence the use of MRS for clinical research in this region has been limited. Our goal was therefore to investigate the feasibility of obtaining high-quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter-session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consecutive sessions using a standard clinical 3 T MR scanner. Neurochemical profiles were obtained with a short-echo (T(E) = 28 ms) semi-LASER localization sequence from a relatively small (~4 mL) voxel that covered about 62% of the hippocampal volume as calculated from segmentation of T1 -weighted images. Voxel composition was highly reproducible between sessions, with test-retest coefficients of variation (CVs) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal-to-noise ratio (~54 based on the N-acetylaspartate (NAA) methyl peak in non-apodized spectra) and linewidths (~9 Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo-inositol and glutamate with high scan-rescan reproducibility (CV ≤ 6%) and quantification precision (Cramér-Rao lower bound, CRLB < 9%). Four other metabolites, including glutathione and glucose, were quantified with scan-rescan CV below 20%. Therefore, the highly optimized, short-echo semi-LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between-session variation in metabolite concentrations, as well as CRLB, was lower than the between-subject variation of the concentrations for most metabolites, indicating that the method has the sensitivity to detect inter-individual differences in the healthy brain.
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA.|Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Multimodal and Functional Neuroimaging Research Group, Central European Institute of Technology, CEITEC MU, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Bednařík
authors.affiliation: Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Moheet
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Deelchand
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA.|Oxford Centre for Functional MRI of the Brain (FMRIB), John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: Uzay E
authors.initials: UE
authors.lastname: Emir
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Eberly
authors.affiliation: Behavioral and Social Neuroscience Research Group, Central European Institute of Technology, CEITEC MU, Brno, Czech Republic.|First Department of Neurology, Masaryk University and St. Anne's Teaching Hospital, Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Bareš
authors.affiliation: Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Seaquist
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Gülin
authors.initials: G
authors.lastname: Öz
mesh_terms: D000328:Adult; D000465:Algorithms; D001704:Biopolymers / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D001704:Biopolymers
keywords: 3 T; MRS; coefficient of variation; human hippocampus; metabolites; quantification precision; reproducibility; segmentation