Abnormal Morphology of Select Cortical and Subcortical Regions in Neurofibromatosis Type 1

Abstract

Purpose To evaluate whether patients with neurofibromatosis type 1 (NF1)-a multisystem neurodevelopmental disorder with myriad imaging manifestations, including focal transient myelin vacuolization within the deep gray nuclei, brainstem, and cerebellum-exhibit differences in cortical and subcortical structures, particularly in subcortical regions where these abnormalities manifest. Materials and Methods In this retrospective study, by using clinically obtained three-dimensional T1-weighted MR images and established image analysis methods, 10 intracranial volume-corrected subcortical and 34 cortical regions of interest (ROIs) were quantitatively assessed in 32 patients with NF1 and 245 age- and sex-matched healthy control subjects. By using linear models, ROI cortical thicknesses and volumes were compared between patients with NF1 and control subjects, as a function of age. With hierarchic cluster analysis and partial correlations, differences in the pattern of association between cortical and subcortical ROI volumes in patients with NF1 and control subjects were also evaluated. Results Patients with NF1 exhibited larger subcortical volumes and thicker cortices of select regions, particularly the hippocampi, amygdalae, cerebellar white matter, ventral diencephalon, thalami, and occipital cortices. For the thalami and pallida and 22 cortical ROIs in patients with NF1, a significant inverse association between volume and age was found, suggesting that volumes decrease with increasing age. Moreover, compared with those in control subjects, ROIs in patients with NF1 exhibited a distinct pattern of clustering and partial correlations. Discussion Neurofibromatosis type 1 is characterized by larger subcortical volumes and thicker cortices of select structures. Most apparent within the hippocampi, amygdalae, cerebellar white matter, ventral diencephalon, thalami and occipital cortices, these neurofibromatosis type 1-associated volumetric changes may, in part, be age dependent. © RSNA, 2018 Online supplemental material is available for this article.

Figure 1:

Flowchart of the process of selection of patients with neurofibromatosis type 1 (NF1). PACS = picture archiving and communication system.

Figure 2:

Representative, A, axial, B, coronal, and, C, sagittal images in the control cohort with overlaid subcortical segmentations. Green = thalamus, yellow = hippocampus, pink = putamen, aqua = caudate, light blue = amygdala, blue = pallidum.

Figure 3:

A–J, Boxplots show significantly larger volumes (*) of the, A, pallidum, B, thalamus, C, hippocampus, D, amygdala, E, ventral diencephalon, F, accumbens, and, G, cerebellar white matter (WM) but not of, H, the putamen, I, the cerebellar cortex (CTX), and, J, the caudate in patients with neurofibromatosis type 1 (NF1) relative to control subjects. Data on the y-axes are z-scores. K, Heat map of β values (in 23 cortical regions of interest with significant differences) from linear models comparing cortical thickness in patients with NF1 and control subjects painted on a pial surface rendering of the brain (from left to right: lateral, medial, dorsal, and ventral views).

Figure 4:

A–J, Scatterplots show differences in volumes (* = significant difference) of the, A, pallidum, B, thalamus, C, hippocampus, D, amygdala, E, ventral diencephalon, F, accumbens, G, cerebellar white matter (WM), H, putamen, I, cerebellar cortex (CTX), and, J, caudate as a function of age in patients with neurofibromatosis type 1 (NF1) relative to control subjects. Data on the y-axes are z-scores. K, L, Heat map of β values (in 22 cortical regions of interest with significant differences) from linear models evaluating age-by-diagnosis interactions in, K, patients with NF1 and, L, control subjects painted on a pial surface rendering of the brain (from left to right: lateral, medial, dorsal, and ventral views).

Figure 5:

A, B, Determination of the number of subcortical volume clusters in, A, patients with neurofibromatosis type 1 (NF1) and, B, control subjects by using a k-means algorithm. There are differences in patterns of subcortical volumes clustering between, C, patients with NF1 and, D, control subjects, showing clear clustering by known anatomic divisions in control subjects but not in patients with NF1. * = Regions with significant differences in size between patients and control subjects. E, F, Determination of the number of cortical thickness clusters in, E, patients with NF1 and, F, control subjects by using a k-means algorithm. G, H, Differences in patterns of cortical thickness clustering between, G, patients with NF1 and, H, control subjects. BSTS = banks of superior temporal sulcus, CACG = caudal anterior cingulate gyrus, CCtx = cerebellar cortex, CMFG = caudal middle frontal gyrus, CWM = cerebellar wh ite matter, DC = diencephalon, ICG = isthmus of cingulate gyrus, IPL = inferior parietal lobule, ITG = inferior temporal gyrus, LOC = lateral occipital cortex, LOFG = lateral orbitofrontal gyrus, MOFG = medial orbitofrontal gyrus, MTG = middle temporal gyrus, PCG = posterior cingulate gyrus, PHG = parahippocampal gyrus, RACG = rostral anterior cingulate gyrus, RMFG = rostral middle frontal gyrus, SFG = superior frontal gyrus, SMG = supramarginal gyrus, SPL = superior parietal lobule, STG = superior temporal gyrus, TTG = transverse temporal gyrus.

Figure 6:

A, B, Heat maps of partial correlation coefficients of all subcortical regions for, A, patients with neurofibromatosis type 1 (NF1) compared with, B, control subjects, controlling for age and sex, show associations between known anatomic divisions in control subjects but not in patients with NF1. C, D, Partial correlation coefficients of cortical and subcortical regions for, C, patients with NF1 compared with, D, control subjects. BSTS = banks of superior temporal sulcus, CACG = caudal anterior cingulate gyrus, CMFG = caudal middle frontal gyrus, DC = diencephalon, ICG = isthmus of cingulate gyrus, IPL = inferior parietal lobule, ITG = inferior temporal gyrus, LOC = lateral occipital cortex, LOFG = lateral orbitofrontal gyrus, MOFG = medial orbitofrontal gyrus, MTG = middle temporal gyrus, PCG = posterior cingulate gyrus, PHG = parahippocampal gyrus, RACG = rostral anterior cingulate gyrus, RMFG = rostral middle frontal gyrus, SFG = superior frontal gyrus, SMG = supramarginal gyrus, SPL = superior parietal lobule, STG = superior temporal gyrus, TTG = transverse temporal gyrus, WM = white matter.