Longitudinal inter- and intra-individual human brain metabolic quantification over 3 years with proton MR spectroscopy at 3 T.

The longitudinal repeatability of proton MR spectroscopy ((1) H-MRS) in the healthy human brain at high fields over long periods is not established. Therefore, we assessed the inter- and intra-subject repeatability of (1) H-MRS in an approach suited for diffuse pathologies in 10 individuals, at 3T, annually for 3 years. Spectra from 480 voxels over 360 cm(3) (∼30%) of the brain, were individually phased, frequency-aligned, and summed into one average spectrum. This dramatically increases metabolites' signal-to-noise-ratios while maintaining narrow linewidths that improve quantification precision. The resulting concentrations of the N-acetylaspartate, creatine, choline, and myo-inositol are: 8.9 ± 0.8, 5.9 ± 0.6, 1.4 ± 0.1, and 4.5 ± 0.5 mM (mean ± standard-deviation). the inter-subject coefficients of variation are 8.7%, 10.2%, 10.7%, and 11.8%; and the longitudinal (intra-subject) coefficients of variation are lower still: 6.6%, 6.8%, 6.8%, and 10%, much better than the 35%, 44%, 55%, and 62% intra-voxel coefficients of variation. The biological and nonbiological components of the summed spectra coefficients of variation had similar contributions to the overall variance.

Multivoxel proton MR spectroscopy used to distinguish anterior cingulate metabolic abnormalities in patients with schizophrenia.

PURPOSE: To test the hypothesis that anterior cingulate cortex (ACC) subregions in patients with schizophrenia are metabolically different from those in healthy control subjects. MATERIALS AND METHODS: This institutional review board-approved study was HIPAA compliant, and all participants provided written informed consent. Twenty-two patients with schizophrenia (13 male, nine female; 39.4 years ± 10.6 [standard deviation]) and 11 age- and sex-matched control subjects (seven male, four female; 35.5 years ± 10.7) underwent magnetic resonance (MR) imaging and three-dimensional 3-T voxel proton MR spectroscopy to measure absolute rostral and caudal ACC N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) concentrations. Exact Mann-Whitney test was used to compare patient data with control data, paired-sample Wilcoxon signed rank test was used to compare subregions within groups, and receiver operating characteristic curve analysis was used to assess sensitivity and specificity in diagnosis of schizophrenia. RESULTS: There were no significant metabolic differences between patients and control subjects or between ACC subregions in control subjects. In patients, rostral ACC NAA and Cr concentrations were significantly lower than those in caudal ACC (6.2 mM ± 1.3 vs 7.1 mM ± 1.3, P < .01; 5.7 mmol/L ± 1.4 vs 6.3 mmol/L ± 1.6, P < .01; respectively); however, this did not hold true for Cho concentrations (1.7 mmol/L ± 0.5 vs 1.8 mmol/L ± 0.5). For individual differences between caudal and rostral measurements, only NAA in patients was different from that in control subjects (0.9 mmol/L ± 1.3 vs -0.1 mmol/L ± 0.5, P < .01), enabling prediction of schizophrenia with 68% sensitivity and 91% specificity, for a difference of more than 0.4. CONCLUSION: Significant differences between caudal and rostral NAA concentration are found in ACC of patients with schizophrenia but not in ACC of healthy control subjects, indicating that neuronal density or integrity differences between ACC subregions may be characteristic of the disease.

In vivo 7 Tesla imaging of the dentate granule cell layer in schizophrenia.

PURPOSE: The hippocampus is central to the pathophysiology of schizophrenia. Histology shows abnormalities in the dentate granule cell layer (DGCL), but its small size (~100 µm thickness) has precluded in vivo human studies. We used ultra high field magnetic resonance imaging (MRI) to compare DGCL morphology of schizophrenic patients to matched controls. METHOD: Bilateral hippocampi of 16 schizophrenia patients (10 male) 40.7 ± 10.6 years old (mean ± standard deviation) were imaged at 7 Tesla MRI with heavily T2*-weighted gradient-echo sequence at 232 µm in-plane resolution (0.08 µL image voxels). Fifteen matched controls (8 male, 35.6 ± 9.4 years old) and one ex vivo post mortem hippocampus (that also underwent histopathology) were scanned with same protocol. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from "not discernible" to "easily visible, appearing dark gray or black") and mean left and right DGCL scores were compared using a non-parametric Mann-Whitney test. RESULTS: MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings in patients (3.2 ± 1.0 and 3.5 ± 1.2) were not statistically different from those of controls (3.9 ± 1.1 and 3.8 ± 0.8), but patients had a trend for lower right DGCL score (p = 0.07), which was significantly associated with patient diagnosis (p = 0.05). The optimal 48% sensitivity and 80% specificity for schizophrenia were achieved with a DGCL rating of ≤2. CONCLUSION: Decreased contrast in the right DGCL in schizophrenia was predictive of schizophrenia diagnosis. Better utility of this metric as a schizophrenia biomarker may be achieved in future studies of patients with homogeneous disease subtypes and progression rates.