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. 2023 Jul;44(7):768-775.
doi: 10.3174/ajnr.A7894. Epub 2023 Jun 22.

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

P Ravanfar  1   2 , W T Syeda  3 , R J Rushmore  2   4   5 , B Moffat  6 , A E Lyall  2   7   8 , A H Merritt  3 , G A Devenyi  9   10 , M M Chakravarty  9   10   11 , P Desmond  12 , V L Cropley  3 , N Makris  2   4 , M E Shenton  2   7   13   8 , A I Bush  14 , D Velakoulis  3   15 , C Pantelis  3   16 , M Walterfang  3   15
Affiliations

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

P Ravanfar et al. AJNR Am J Neuroradiol. 2023 Jul.

Abstract

Background and purpose: While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls.

Materials and methods: A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses.

Results: We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity.

Conclusions: Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.

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Figures

FIG 1.
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.
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.
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.
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.
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.
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