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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?

SUBMITTER: Bednarik P

PROVIDER: S-EPMC4454404 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T.

Bednařík Petr P Moheet Amir A Deelchand Dinesh K DK Emir Uzay E UE Eberly Lynn E LE Bareš Martin M Seaquist Elizabeth R ER Öz Gülin G

NMR in biomedicine 20150422 6

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-quali ...[more]

PMID: 25904240

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Project description:Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214.6 ± 11.6 mg/dL; severe hyperglycemia (severe-HG), 338.9 ± 21.7 mg/dL; control, 137.7 ± 2.6 mg/dL) was induced from postnatal day (P) 3 to P12. On P30, the hippocampal neurochemical profile was determined using in vivo 1 H MR spectroscopy. Dendritic arborization in the hippocampal CA1 region was determined using microtubule-associated protein (MAP)-2 immunohistochemistry. In Experiment 2, continuous hyperglycemia (mean blood glucose 275.3 ± 25.8 mg/dL; control, 142.3 ± 2.6 mg/dL) was induced from P2 to P6 by injecting streptozotocin (STZ) on P2. The mRNA expression of glycogen synthase 1 (Gys1), lactate dehydrogenase (Ldh), glucose transporters 1 (Glut1) and 3 (Glut3) and monocarboxylate transporters 1 (Mct1), 2 (Mct2) and 4 (Mct4) in the hippocampus was determined on P6. In Experiment 1, MRS demonstrated lower lactate concentration and glutamate/glutamine (Glu/Gln) ratio in the severe-HG group, compared with the control group (p < 0.05). Phosphocreatine/creatine ratio was higher in both hyperglycemia groups (p < 0.05). MAP-2 histochemistry demonstrated longer apical segment length, indicating abnormal synaptic efficacy in both hyperglycemia groups (p < 0.05). Experiment 2 showed lower Glut1, Gys1 and Mct4 expression and higher Mct1 expression in the hyperglycemia group, relative to the control group (p < 0.05). These results suggest that hyperglycemia alters substrate transport, lactate homeostasis, dendritogenesis and Glu-Gln cycling in the developing hippocampus. Abnormal neurochemical profile and dendritic structure due to hyperglycemia may partially explain the long-term hippocampus-mediated cognitive deficits in human ELGANs.

Dataset Information

Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3?T.

Publications

Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T.

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