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Research ArticleAdult Brain
Open Access

Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T

E.J. Meyer, I.I. Kirov, A. Tal, M.S. Davitz, J.S. Babb, M. Lazar, D. Malaspina and O. Gonen
American Journal of Neuroradiology December 2016, 37 (12) 2273-2279; DOI: https://doi.org/10.3174/ajnr.A4886
E.J. Meyer
aFrom the Department of Radiology (E.J.M., I.I.K., M.S.D., J.S.B., M.L., O.G.), Center for Advanced Imaging Innovation and Research, Bernard and Irene Schwartz Center for Biomedical Imaging
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I.I. Kirov
aFrom the Department of Radiology (E.J.M., I.I.K., M.S.D., J.S.B., M.L., O.G.), Center for Advanced Imaging Innovation and Research, Bernard and Irene Schwartz Center for Biomedical Imaging
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A. Tal
cDepartment of Chemical Physics (A.T.), Weizmann Institute of Science, Rehovot, Israel.
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M.S. Davitz
aFrom the Department of Radiology (E.J.M., I.I.K., M.S.D., J.S.B., M.L., O.G.), Center for Advanced Imaging Innovation and Research, Bernard and Irene Schwartz Center for Biomedical Imaging
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J.S. Babb
aFrom the Department of Radiology (E.J.M., I.I.K., M.S.D., J.S.B., M.L., O.G.), Center for Advanced Imaging Innovation and Research, Bernard and Irene Schwartz Center for Biomedical Imaging
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M. Lazar
aFrom the Department of Radiology (E.J.M., I.I.K., M.S.D., J.S.B., M.L., O.G.), Center for Advanced Imaging Innovation and Research, Bernard and Irene Schwartz Center for Biomedical Imaging
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D. Malaspina
bDepartment of Psychiatry (D.M.), Institute for Social and Psychiatric Initiatives, New York University School of Medicine, New York, New York
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O. Gonen
aFrom the Department of Radiology (E.J.M., I.I.K., M.S.D., J.S.B., M.L., O.G.), Center for Advanced Imaging Innovation and Research, Bernard and Irene Schwartz Center for Biomedical Imaging
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    Fig 1.

    Upper: Axial (A) and sagittal (B) T1-weighted MR imaging from a 23-year-old male patient (17 in Table 1) superimposed on the 9 × 6 × 2 cm3 (left-right × anteroposterior × inferior-superior) VOI, 16 × 16 cm2 axial CSI FOV (solid and dashed lines), and the hippocampal outline (transparent yellow on A). The yellow arrow in B indicates the level of A, C, and D. Lower left: C, Real part of the 9 × 6 axial (left-right × anteroposterior) 1H spectra matrix from the VOI section shown in A and marked with the solid yellow arrow on B. Spectra within the hippocampus in A are black, while the remaining ones (not included in the analyses) are gray. All are on a common frequency (parts per million) and intensity scale. The 3 spectra in the black frame over the right hippocampus are expanded on the right (D) for greater detail. Note that the hippocampi do not include voxels at the edges of the VOI (that may have relative VOI chemical shift displacement); note also the good SNR and excellent spectral resolution (8.1 ± 3.0 Hz linewidth) from the high spatial resolution (0.5 cm3) voxels. Right: D, The 3 spectra from the solid frame on C (black line) overlaid on the spectral fit (thick gray lines) and the residual (experimental − fit) underneath (thin black line). Note the spectral resolution and fidelity of the fit, reflected by the residual.

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    Fig 2.

    Upper: A, Axial MPRAGE image from a 51-year-old female patient (16 in Table 1) superimposed on the VOI (in yellow). Orange lines show the 9 × 6 voxel CSI grid; voxels that passed the selection criteria to calculate the NAA concentration are highlighted in transparent red. B–D, SPM12-generated WM (B), GM (C), and CSF (D) masks also superimposed on the VOI CSI grid and selected voxels. Note the n ≥ 2 voxels that “passed” the selection criteria described in the “Materials and Methods” section.

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    Fig 3.

    Boxplots showing the first, second (median), and third quartiles; 5th and 95th percentiles (whiskers); and outliers (dots) of the distribution of the bilateral hippocampal NAA, Cr, Cho, and mIns concentrations (millimolar) in the patient (shaded) and control (white) boxes. Numbers of controls and patients included in the analyses for each metabolite, N, are listed. Note that the NAA, Cho, and mIns concentrations do not differ significantly between patients and controls (Table 2), whereas the Cr concentration is 19% higher in the bilateral hippocampi of patients than in controls (arrow).

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    Table 1:

    Demographics for controls and patients

    SubjectStatusAge (yr)/SexDisease Duration (yr)Psychotropic Medication
    1C45/MNANA
    2C31/MNANA
    3C29/FNANA
    4C36/MNANA
    5C43/MNANA
    6C24/FNANA
    7C55/FNANA
    8C26/FNANA
    9C29/FNANA
    10C22/MNANA
    11C31/FNANA
    12P41/M22Fluphenazine
    13P44/F27Quetiapine
    14P43/M18Haloperidol, quetiapine
    15P52/M32Citalopram
    16P51/F15Gabapentin, lithium, ziprasidone
    17P23/M3Risperidone
    18P47/M31Fluoxetine, risperidone, valproic acid, trazodone
    19P44/M26Clozapine, valproic acid
    20P26/M8Ziprasidone
    21P29/F8Bupropion, aripiprazole, fluphenazine
    22P42/F23Ziprasidone, bupropion, eszopiclone
    23P22/M4Clozapine
    24P48/M23Quetiapine
    25P34/M5Risperidone
    26P30/F10Risperidone
    27P49/F31Aripiprazole
    28P51/F35NA
    29P43/F20Aripiprazole, escitalopram, fluphenazine
    30P52/M30Aripiprazole, valproic acid, hydroxyzine, paroxetine, trazodone
    • Note:—NA indicates not applicable; C, controls; P, patients.

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    Table 2:

    Means, number of subjects from whom the data was derived (in parentheses), and P values (from unequal variance t tests) of the absolute NAA, Cr, Cho, and mIns hippocampal GM concentrations and the volumes of the bilateral hippocampi in controls and patientsa

    MetaboliteControlsPatientsP Value
    NAA (mM)8.7 ± 1.2 (n = 11)8.8 ± 1.6 (n = 16).876
    Cr (mM)7.4 ± 1.2 (n = 10)b8.7 ± 2.2 (n = 19)b.035b
    Cho (mM)2.1 ± 0.3 (n = 10)2.3 ± 0.7 (n = 18).189
    mIns (mM)5.2 ± 0.9 (n = 10)6.1 ± 1.5 (n = 12).161
    Volume (cm3)8.4 ± 0.5 (n = 11)b7.5 ± 0.9 (n = 19)b.003b
    • ↵a Note the elevation of Cr and the reduction in volume in patients compared with controls.

    • ↵b Significant difference.

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American Journal of Neuroradiology: 37 (12)
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E.J. Meyer, I.I. Kirov, A. Tal, M.S. Davitz, J.S. Babb, M. Lazar, D. Malaspina, O. Gonen
Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T
American Journal of Neuroradiology Dec 2016, 37 (12) 2273-2279; DOI: 10.3174/ajnr.A4886

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Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T
E.J. Meyer, I.I. Kirov, A. Tal, M.S. Davitz, J.S. Babb, M. Lazar, D. Malaspina, O. Gonen
American Journal of Neuroradiology Dec 2016, 37 (12) 2273-2279; DOI: 10.3174/ajnr.A4886
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