Joint-label fusion brain atlases for dementia research in Down syndrome

Abstract

Research suggests a link between Alzheimer's Disease in Down Syndrome (DS) and the overproduction of amyloid plaques. Using Positron Emission Tomography (PET) we can assess the in-vivo regional amyloid load using several available ligands. To measure amyloid distributions in specific brain regions, a brain atlas is used. A popular method of creating a brain atlas is to segment a participant's structural Magnetic Resonance Imaging (MRI) scan. Acquiring an MRI is often challenging in intellectually-imparied populations because of contraindications or data exclusion due to significant motion artifacts or incomplete sequences related to general discomfort. When an MRI cannot be acquired, it is typically replaced with a standardized brain atlas derived from neurotypical populations (i.e. healthy individuals without DS) which may be inappropriate for use in DS. In this project, we create a series of disease and diagnosis-specific (cognitively stable (CS-DS), mild cognitive impairment (MCI-DS), and dementia (DEM-DS)) probabilistic group atlases of participants with DS and evaluate their accuracy of quantifying regional amyloid load compared to the individually-based MRI segmentations. Further, we compare the diagnostic-specific atlases with a probabilistic atlas constructed from similar-aged cognitively-stable neurotypical participants. We hypothesized that regional PET signals will best match the individually-based MRI segmentations by using DS group atlases that aligns with a participant's disorder and disease status (e.g. DS and MCI-DS). Our results vary by brain region but generally show that using a disorder-specific atlas in DS better matches the individually-based MRI segmentations than using an atlas constructed from cognitively-stable neurotypical participants. We found no additional benefit of using diagnose-specific atlases matching disease status. All atlases are made publicly available for the research community.

Highlight: Down syndrome (DS) joint-label-fusion atlases provide accurate positron emission tomography (PET) amyloid measurements.A disorder-specific DS atlas is better than a neurotypical atlas for PET quantification.It is not necessary to use a disease-state-specific atlas for quantification in aged DS.Dorsal striatum results vary, possibly due to this region and dementia progression.

Keywords: Alzheimer's disease; Down syndrome; amyloid; dementia; group atlas; joint label fusion; neurotypical.

FIGURE 1

A flow diagram visualizing the probabilistic atlases’ creation and the alignment of the atlases with the amyloid positron emission tomography (PET) scans. In addition, the diagram shows the comparisons of each of the atlases with the Desikan/Killiany (DKT) individual magnetic resonance imaging (MRI) segmentation (IM) atlas in a leave‐one‐out cross‐validation (LOOCV) paradigm. ANTs, Advanced Normalization Tools; CS‐DS, cognitively stable Down syndrome; CS‐NT, cognitively stable neurotypical; DEM‐DS, dementia Down syndrome; JLF, joint label fusion; MCI‐DS, mild cognitive impairment Down syndrome

FIGURE 2

Mean squared error (MSE) by atlas. A higher percentage of MSE score indicates a worse match between our atlas and the individual magnetic resonance imaging (MRI)‐based FreeSurfer segmentations (IM). Asterisks identify results that are significant at P < .05 after adjusting for the P‐value, whereas “n.s.” indicates non‐significant. CS‐DS, cognitively stable Down syndrome; CS‐NT, cognitively stable neurotypical; DEM‐DS, dementia Down syndrome; MCI‐DS, mild cognitive impairment

FIGURE 3

Bland Altman plots of significant regional differences in average amyloid and the corresponding linear regression model statistics are shown for each region of interest (ROI). Each plot illustrates the relationship between the difference in amyloid measurements on the y‐axis and the average amyloid load on the x‐axis. Regression lines with a positive slope indicate an increasing difference between the two atlases as a function of higher amyloid. Only results from the regression model statistics of ROI that were significant at the P < .05 unadjusted threshold are reported here. A, Results of significant regional differences in average amyloid between diagnosis‐specific group (DSG) and individual magnetic resonance imaging (IM) atlases. B, Results of significant regional differences in average amyloid between cognitively stable Down syndrome (CS‐DS) and IM atlases. C, Results of significant regional differences in average amyloid between cognitively stable neurotypical (CS‐NT) and IM atlases. DEM‐DS, dementia Down syndrome; MCI‐DS, mild cognitive impairment; PET, positron emission tomography