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Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction.

ABSTRACT: Mean diffusivity (MD) measured by diffusion tensor imaging can reflect microstructural alterations of the brain's gray matter (GM). Therefore, GM MD may be a sensitive marker of neurodegeneration related to Alzheimer's Disease (AD). However, due to partial volume effects (PVE), differences in MD may be overestimated because of a higher degree of brain atrophy in AD patients and in cases with mild cognitive impairment (MCI). Here, we evaluated GM MD changes in AD and MCI compared with healthy controls, and the effect of partial volume correction (PVC) on diagnostic utility of MD. We determined region of interest (ROI) and voxel-wise group differences and diagnostic accuracy of MD and volume measures between matched samples of 39 AD, 39 MCI and 39 healthy subjects before and after PVC. Additionally, we assessed whether effects of GM MD values on diagnosis were mediated by volume. ROI and voxel-wise group differences were reduced after PVC. When using these ROIs for predicting group separation in logistic models, both PVE corrected and uncorrected GM MD values yielded a poorer diagnostic accuracy in single predictor models than regional volume. For the discrimination of AD patients and healthy controls, the effect of GM MD on diagnosis was significantly mediated by volume of hippocampus and posterior cingulate ROIs. Our results suggest that GM MD measurements are strongly confounded by PVE in the presence of brain atrophy, underlining the necessity of PVC when using these measurements as specific metrics of microstructural tissue degeneration. Independently of PVC, regional MD was not superior to regional volume in separating prodromal and clinical stages of AD from healthy controls.

SUBMITTER: Henf J

PROVIDER: S-EPMC5702878 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction.

Henf Judith J Grothe Michel J MJ Brueggen Katharina K Teipel Stefan S Dyrba Martin M

NeuroImage. Clinical 20171004

Mean diffusivity (MD) measured by diffusion tensor imaging can reflect microstructural alterations of the brain's gray matter (GM). Therefore, GM MD may be a sensitive marker of neurodegeneration related to Alzheimer's Disease (AD). However, due to partial volume effects (PVE), differences in MD may be overestimated because of a higher degree of brain atrophy in AD patients and in cases with mild cognitive impairment (MCI). Here, we evaluated GM MD changes in AD and MCI compared with healthy con ...[more]

PMID: 29201644

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Project description:Accurately measuring the cortical mean diffusivity (MD) derived from diffusion tensor imaging (DTI) at the comprehensive lobe, gyral and voxel level of young, elderly healthy brains and those with Alzheimer's disease (AD) may provide insights on heterogeneous cortical microstructural changes caused by aging and AD. Due to partial volume effects (PVE), the measurement of cortical MD is overestimated with contamination of cerebrospinal fluid (CSF). The bias is especially severe for aging and AD brains because of significant cortical thinning of these brains. In this study, we aimed to quantitatively characterize the unbiased regional cortical MD changes due to aging and AD and delineate the effects of cortical thinning of elderly healthy and AD groups on MD measurements. DTI and T1-weighted images of 14 young, 15 elderly healthy subjects and 17 AD patients were acquired. With the parcellated cortical gyri and lobes from T1 weighted image transformed to DTI, regional cortical MD of all subjects before and after PVE correction were measured. CSF contamination model was used to correct bias of MD caused by PVE. Compared to cortical MD of young group, significant increases of corrected MD for elderly healthy and AD groups were found only in frontal and limbic regions, respectively, while there were significant increases of uncorrected MD all over the cortex. Uncorrected MD are significantly higher in limbic and temporal gyri in AD group, compared to those in elderly healthy group but higher MD only remained in limbic gyri after PVE correction. Cortical thickness was also measured for all groups. The correlation slopes between cortical MD and thickness for elderly healthy and AD groups were significantly decreased after PVE correction compared to before correction while no significant change of correlation slope was detected for young group. It suggests that the cortical thinning in elderly healthy and AD groups is a significant contributor to the bias of uncorrected cortical MD measurement. The established comprehensive unbiased cortical MD profiles of young, elderly healthy subjects and AD patients at the lobe, gyral and voxel level may serve as clinical references for cortical microstructure.

Project description:BACKGROUND:There is increasing interest in improving understanding of the timing and nature of early neurodegeneration in Alzheimer's disease (AD) and developing methods to measure this in vivo. Autosomal dominant familial Alzheimer's disease (FAD) provides the opportunity for investigation of presymptomatic change. We assessed early microstructural breakdown of cortical grey matter in FAD with diffusion-weighted MRI. METHODS:Diffusion-weighted and T1-weighed MRI were acquired in 38 FAD mutation carriers (17 symptomatic, 21 presymptomatic) and 39 controls. Mean diffusivity (MD) was calculated for six cortical regions previously identified as being particularly vulnerable to FAD-related neurodegeneration. Linear regression compared MD between symptomatic and presymptomatic carriers and controls, adjusting for age and sex. Spearman coefficients assessed associations between cortical MD and cortical thickness. Spearman coefficients also assessed associations between cortical MD and estimated years to/from onset (EYO). Across mutation carriers, linear regression assessed associations between MD and EYO, adjusting for cortical thickness. RESULTS:Compared with controls, cortical MD was higher in symptomatic mutation carriers (mean?±?SD CDR?=?0.88?±?0.39) for all six regions (p?<?0.001). In late presymptomatic carriers (within 8.1?years of predicted symptom onset), MD was higher in the precuneus (p?=?0.04) and inferior parietal cortex (p?=?0.003) compared with controls. Across all presymptomatic carriers, MD in the precuneus correlated with EYO (p?=?0.04). Across all mutation carriers, there was strong evidence (p?<?0.001) of association between MD and cortical thickness in all regions except entorhinal cortex. After adjusting for cortical thickness, there remained an association (p?<?0.05) in mutation carriers between MD and EYO in all regions except entorhinal cortex. CONCLUSIONS:Cortical MD measurement detects microstructural breakdown in presymptomatic FAD and correlates with proximity to symptom onset independently of cortical thickness. Cortical MD may thus be a feasible biomarker of early AD-related neurodegeneration, offering additional/complementary information to conventional MRI measures.

Project description:Magnetic resonance imaging (MRI) has become an important tool in the early detection of age-related and neuropathological brain changes. Recent studies suggest that changes in mean diffusivity (MD) of cortical gray matter derived from diffusion MRI scans may be useful in detecting early effects of Alzheimer's disease (AD), and that these changes may be detected earlier than alterations associated with standard structural MRI measures such as cortical thickness. Thus, due to its potential clinical relevance, we examined the genetic and environmental influences on cortical MD in middle-aged men to provide support for the biological relevance of this measure and to guide future gene association studies. It is not clear whether individual differences in cortical MD reflect neuroanatomical variability similarly detected by other MRI measures, or whether unique features are captured. For instance, variability in cortical MD may reflect morphological variability more commonly measured by cortical thickness. Differences among individuals in cortical MD may also arise from breakdowns in myelinated fibers running through the cortical mantle. Thus, we investigated whether genetic influences on variation in cortical MD are the same or different from those influencing cortical thickness and MD of white matter (WM) subjacent to the cortical ribbon. Univariate twin analyses indicated that cortical MD is heritable in the majority of brain regions; the average of regional heritability estimates ranged from 0.38 in the cingulate cortex to 0.66 in the occipital cortex, consistent with the heritability of other MRI measures of the brain. Trivariate analyses found that, while there was some shared genetic variance between cortical MD and each of the other two measures, this overlap was not complete (i.e., the correlation was statistically different from 1). A significant amount of distinct genetic variance influences inter-individual variability in cortical MD; therefore, this measure could be useful for further investigation in studies of neurodegenerative diseases and gene association studies.

Dataset Information

Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction.

Publications

Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction.

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