Dataset Information

Age-Related Modifications of Diffusion Tensor Imaging Parameters and White Matter Hyperintensities as Inter-Dependent Processes.

ABSTRACT: Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-weighted MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans of young adults (n = 19, mean age = 33 SD = 7.4) and two age-matched groups of older adults, one presenting low-level-WMH (n = 20, mean age = 78, SD = 3.2) and one presenting high-level-WMH (n = 20, mean age = 79, SD = 5.4). Older subjects with low-level-WMH presented modifications of DTI parameters in comparison to younger subjects, fitting with the DTI pattern classically described in aging, i.e., Fractional Anisotropy (FA) decrease/Radial Diffusivity (RD) increase. Furthermore, older subjects with high-level-WMH showed higher DTI modifications in Normal Appearing White Matter (NAWM) in comparison to those with low-level-WMH. Finally, in older subjects with high-level-WMH, FA, and RD values of NAWM were associated with to WMH burden. Therefore, our findings suggest that DTI modifications and the presence of WMH would be two inter-dependent processes but occurring within different temporal windows. DTI changes would reflect the early phase of white matter changes and WMH would appear as a consequence of those changes.

SUBMITTER: Pelletier A

PROVIDER: S-EPMC4718031 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Age-Related Modifications of Diffusion Tensor Imaging Parameters and White Matter Hyperintensities as Inter-Dependent Processes.

Pelletier Amandine A Periot Olivier O Dilharreguy Bixente B Hiba Bassem B Bordessoules Martine M Chanraud Sandra S Pérès Karine K Amieva Hélène H Dartigues Jean-François JF Allard Michèle M Catheline Gwénaëlle G

Frontiers in aging neuroscience 20160119

Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-weighted MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans o ...[more]

PMID: 26834625

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Project description:BackgroundThe progression of FLAIR white matter hyperintensities (WMHs) on MRI heralds vascular-mediated cognitive decline. Even before FLAIR WMH progression, adjacent normal appearing white matter (NAWM) already demonstrates microstructural deterioration on diffusion tensor imaging (DTI). We hypothesized that elevated DTI free water (FW) would precede FLAIR WMH progression, implicating interstitial fluid accumulation as a key pathological step in the progression of cerebral small vessel disease.MethodsParticipants at least 3 months after an ischemic stroke or TIA with WMH on MRI underwent serial brain MRIs every 3 months over the subsequent year. For each participant, the WMHs were automatically segmented, serial MRIs were aligned, and a region of WMH penumbra tissue at risk was defined by dilating lesions at any time point and subtracting baseline lesions. Penumbra voxels were classified as either stable or progressing to WMH if they were segmented as new lesions and demonstrated increasing FLAIR intensity over time. Aligned DTI images included FW and FW-corrected fractional anisotropy (FATissue) and mean diffusivity (MDTissue). Logistic regression and area under the receiver-operator characteristic curve (AUC) were used to test whether baseline DTI predicted voxel-wise classification of stable penumbra or progression to WMH while covarying for clinical risk factors.ResultsIn the included participants (n = 26, mean age 71 ± 9 years, 31% female), we detected a median annual voxel-wise WMH growth of 2.9 ± 2.6 ml. Each baseline DTI metric was associated with lesion progression in the penumbra, but FW had the greatest AUC of 0.732 (0.730 - 0.733) for predicting voxel-wise WMH progression pooled across participants.DiscussionBaseline increased interstitial fluid, estimated as FW on DTI, predicted the progression of NAWM to WMH over the following year. These results implicate the presence of FW in the pathogenesis of cerebral small vessel disease progression.

Project description:Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54-92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.

Project description:The NODDI-DTI signal model is a modification of the NODDI signal model that formally allows interpretation of standard single-shell DTI data in terms of biophysical parameters in healthy human white matter (WM). The NODDI-DTI signal model contains no CSF compartment, restricting application to voxels without CSF partial-volume contamination. This modification allowed derivation of analytical relations between parameters representing axon density and dispersion, and DTI invariants (MD and FA) from the NODDI-DTI signal model. These relations formally allow extraction of biophysical parameters from DTI data. NODDI-DTI parameters were estimated by applying the proposed analytical relations to DTI parameters estimated from the first shell of data, and compared to parameters estimated by fitting the NODDI-DTI model to both shells of data (reference dataset) in the WM of 14 in vivo diffusion datasets recorded with two different protocols, and in simulated data. The first two datasets were also fit to the NODDI-DTI model using only the first shell (as for DTI) of data. NODDI-DTI parameters estimated from DTI, and NODDI-DTI parameters estimated by fitting the model to the first shell of data gave similar errors compared to two-shell NODDI-DTI estimates. The simulations showed the NODDI-DTI method to be more noise-robust than the two-shell fitting procedure. The NODDI-DTI method gave unphysical parameter estimates in a small percentage of voxels, reflecting voxelwise DTI estimation error or NODDI-DTI model invalidity. In the course of evaluating the NODDI-DTI model, it was found that diffusional kurtosis strongly biased DTI-based MD values, and so, making assumptions based on healthy WM, a novel heuristic correction requiring only DTI data was derived and used to mitigate this bias. Since validations were only performed on healthy WM, application to grey matter or pathological WM would require further validation. Our results demonstrate NODDI-DTI to be a promising model and technique to interpret restricted datasets acquired for DTI analysis in healthy white matter with greater biophysical specificity, though its limitations must be borne in mind.

Dataset Information

Age-Related Modifications of Diffusion Tensor Imaging Parameters and White Matter Hyperintensities as Inter-Dependent Processes.

Publications

Age-Related Modifications of Diffusion Tensor Imaging Parameters and White Matter Hyperintensities as Inter-Dependent Processes.

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