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Research ArticleAdult Brain
Open Access

Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study

P. Ravanfar, W.T. Syeda, R.J. Rushmore, B. Moffat, A.E. Lyall, A.H. Merritt, G.A. Devenyi, M.M. Chakravarty, P. Desmond, V.L. Cropley, N. Makris, M.E. Shenton, A.I. Bush, D. Velakoulis, C. Pantelis and M. Walterfang
American Journal of Neuroradiology July 2023, 44 (7) 768-775; DOI: https://doi.org/10.3174/ajnr.A7894
P. Ravanfar
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
bPsychiatry Neuroimaging Laboratory (P.R., R.J.R., A.E.L., N.M., M.E.S.)
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  • ORCID record for P. Ravanfar
W.T. Syeda
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
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R.J. Rushmore
bPsychiatry Neuroimaging Laboratory (P.R., R.J.R., A.E.L., N.M., M.E.S.)
eCenter for Morphometric Analysis (R.J.R., N.M.), Massachusetts General Hospital, Charlestown, Massachusetts
fDepartment of Anatomy and Neurobiology (R.J.R.), Boston University School of Medicine, Boston, Massachusetts
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B. Moffat
gMelbourne Brain Centre Imaging Unit (B.M.), Department of Radiology, University of Melbourne, Parkville, Victoria, Australia
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A.E. Lyall
bPsychiatry Neuroimaging Laboratory (P.R., R.J.R., A.E.L., N.M., M.E.S.)
cDepartment of Psychiatry (A.E.L., M.E.S.)
hDepartment of Psychiatry (A.E.L., M.E.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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  • ORCID record for A.E. Lyall
A.H. Merritt
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
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G.A. Devenyi
iCerebral Imaging Center (G.A.D., M.M.C.), Douglas Research Centre, Montreal, Quebec, Canada
jDepartments of Psychiatry (G.A.D., M.M.C.)
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M.M. Chakravarty
iCerebral Imaging Center (G.A.D., M.M.C.), Douglas Research Centre, Montreal, Quebec, Canada
jDepartments of Psychiatry (G.A.D., M.M.C.)
kBiomedical Engineering (M.M.C.), McGill University, Montreal, Quebec, Canada
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P. Desmond
lDepartments of Radiology (P.D.)
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V.L. Cropley
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
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N. Makris
bPsychiatry Neuroimaging Laboratory (P.R., R.J.R., A.E.L., N.M., M.E.S.)
eCenter for Morphometric Analysis (R.J.R., N.M.), Massachusetts General Hospital, Charlestown, Massachusetts
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M.E. Shenton
bPsychiatry Neuroimaging Laboratory (P.R., R.J.R., A.E.L., N.M., M.E.S.)
cDepartment of Psychiatry (A.E.L., M.E.S.)
dDepartment of Radiology (M.E.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
hDepartment of Psychiatry (A.E.L., M.E.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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A.I. Bush
nMelbourne Dementia Research Centre (A.I.B.)
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D. Velakoulis
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
mNeuropsychiatry (D.V., M.W.), Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
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C. Pantelis
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
oThe Florey Institute of Neuroscience and Mental Health (C.P.), The University of Melbourne, Parkville, Victoria, Australia
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M. Walterfang
aFrom Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
mNeuropsychiatry (D.V., M.W.), Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
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  • FIG 1.
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    FIG 1.

    Between-group comparison of volume in the ROIs. In the Tukey boxplots, the middle line of each box indicates the median, upper and lower boundaries of the boxes show the upper and lower quartiles, respectively; the upper and lower whiskers show the maximum and minimum data points; and the cross signs indicate the mean in each group. Filled triangles represent data points from patients with NPC who were not taking miglustat. Error bars indicate SDs. L indicates left; R, right.

  • FIG 2.
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    FIG 2.

    Voxelwise between-group comparison of QSM. A, Lightbox axial view with 4-mm section spacing. The yellow-red spectrum indicates clusters with higher QSM, and the blue-to-light blue spectrum shows clusters with lower QSM values in the NPC group compared with healthy controls. B, A visualization of the thalamus with clusters that show significant between-group QSM difference. Red and blue indicate higher and lower QSM in the NPC group compared with the control group, respectively. Clusters with increased QSM in NPC, depicted in red, are in the posterior part of the thalamus, consistent with the anatomic location of the pulvinar nucleus.

  • FIG 3.
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    FIG 3.

    Representative QSM images from control and NPC groups. Colored lines mark the borders of segmentations labels: green, putamen; brown, caudate nucleus; red, thalamus; blue, globus pallidus.

  • FIG 4.
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    FIG 4.

    ROI-based between-group comparison of mean QSM values. In the Tukey boxplots, the middle line of each box indicates the median, upper, and lower boundaries of the boxes and shows the upper and lower quartiles, respectively; the upper and lower whiskers show the maximum and minimum data points; and the cross signs indicate the mean in each group. Filled triangles represent data points from patients with NPC who were not taking miglustat. Error bars indicate SDs in the entire control and NPC groups. In the thalamus, patients with NPC who were not taking miglustat had higher mean QSM values than those who were prescribed miglustat. L indicates left; R, right.

  • FIG 5.
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    FIG 5.

    Pearson correlation between volume and QSM in the brain regions that showed a difference in volume or QSM values between groups. Cells containing correlation coefficients are color-coded according to the value of the correlation coefficient. Blue indicates negative correlation, and red indicates positive correlation. Color intensities correspond to the value of the coefficient.

Tables

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    Table 1:

    Demographic description and comparison of the study population

    Control (n = 14)NPC (n = 10)P Value
    Age (mean) (SD) (yr)32.6 (9.2)33.1 (12.1).92
    Sex (male/female)6:84:6.89
    Iturriaga score (mean) (SD)NA9.1 (3)NA
    NUCOG (mean) (SD)NA63.9 (18)NA
    SOFAS (mean) (SD)NA42 (22.7)NA
    Miglustat doseNA7 Patients taking 200 mg TIDNA
    • Note:—NA indicates not applicable; TID, 3 times per day.

    • View popup
    Table 2:

    ROI-based between-group comparison of mean QSM values with age and ROI volume as covariates

    ROIControl (Mean) (SD) (ppb)NPC (Mean) (SD) (ppb)FDR-Adjusted P ValueEffect Size (η2p)
    Putamen
     Left17 (5)17.01 (9).560.03
     Right15.6 (3.5)15.8 (7.4).790.003
    Caudate
     Left22.6 (3.4)22 (7.7).560.02
     Right22.2 (4.3)20.4 (5.9).630.01
    Globus pallidus
     Left81.3 (20.8)95.1 (23).560.06
     Right84.9 (16.6)102.7 (19.5).510.12
    Thalamus
     Left2.4 (4)2.2 (6.1).310.1
     Right1.5 (3.5)1 (6.2).560.04
    Hippocampus
     Left–1.6 (2.2)–8.2 (3.6).100.3
     Right–1.9 (2.1)–5.7 (3.3).040.2
    • Note:—ppb indicates parts per billion; FDR, false detection rate

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American Journal of Neuroradiology: 44 (7)
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P. Ravanfar, W.T. Syeda, R.J. Rushmore, B. Moffat, A.E. Lyall, A.H. Merritt, G.A. Devenyi, M.M. Chakravarty, P. Desmond, V.L. Cropley, N. Makris, M.E. Shenton, A.I. Bush, D. Velakoulis, C. Pantelis, M. Walterfang
Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study
American Journal of Neuroradiology Jul 2023, 44 (7) 768-775; DOI: 10.3174/ajnr.A7894

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Brain Iron in Niemann-Pick Type C: 7T Study
P. Ravanfar, W.T. Syeda, R.J. Rushmore, B. Moffat, A.E. Lyall, A.H. Merritt, G.A. Devenyi, M.M. Chakravarty, P. Desmond, V.L. Cropley, N. Makris, M.E. Shenton, A.I. Bush, D. Velakoulis, C. Pantelis, M. Walterfang
American Journal of Neuroradiology Jul 2023, 44 (7) 768-775; DOI: 10.3174/ajnr.A7894
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