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Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease.

ABSTRACT: White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. We explored the relationship between baseline DTI characteristics of the thalamus, caudate, and putamen, and the volume and subsequent accrual of WMHs over a 4-year period in 56 community-dwelling older (⩾75 years) individuals. Baseline thalamic fractional anisotropy (FA) was an independent predictor of WMH accrual. WMH accrual also correlated with baseline lacune count and baseline WMH volume, the latter showing the strongest predictive power, explaining 27.3% of the variance. The addition of baseline thalamic FA in multivariate modeling increased this value by 70%, which explains 46.5% of the variance in WMH accrual rate. Thalamic FA might serve as a novel predictor of cerebral small-vessel disease progression in clinical settings and trials. Furthermore, our findings point to the possibility of a causal relationship between thalamic damage and the accrual of WMHs.

SUBMITTER: Cavallari M

PROVIDER: S-EPMC4126092 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease.

Cavallari Michele M Moscufo Nicola N Meier Dominik D Skudlarski Pawel P Pearlson Godfrey D GD White William B WB Wolfson Leslie L Guttmann Charles R G CR

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20140514 8

White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. W ...[more]

PMID: 24824915

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Project description:IntroductionDiffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. At higher b-values, diffusion-signal decay becomes bi-exponential, suggesting the presence of two, unrestricted and restricted, water pools. Theoretical work suggests that semi-permeable cellular membrane rather than the presence of two physical compartments is the cause. The permeability-diffusivity (PD) parameters measured from bi-exponential modeling may offer advantages, over traditional DTI-FA, in identifying WM deficits in schizophrenia.MethodsImaging was performed in N = 26/26 patients/controls (age = 20-61 years, average age = 40.5 ± 12.6). Imaging consisted of fifteen b-shells: b = 250-3800 s/mm(2) with 30 directions/shell, covering seven slices of mid-sagittal corpus callosum (CC) at 1.7 × 1.7 × 4.6 mm. 64-direction DTI was also collected. Permeability-diffusivity-index (PDI), the ratio of restricted to unrestricted apparent diffusion coefficients, and the fraction of unrestricted compartment (Mu) were calculated for CC and cingulate gray matter (GM). FA values for CC were calculated using tract-based-spatial-statistics.ResultsPatients had significantly reduced PDI in CC (p ? 10(- 4)) and cingulate GM (p = 0.002), while differences in CC FA were modest (p ? .03). There was no group-related difference in Mu. Additional theoretical-modeling analysis suggested that reduced PDI in patients may be caused by reduced cross-membrane water molecule exchanges.ConclusionPDI measurements for cerebral WM and GM yielded more robust patient-control differences than DTI-FA. Theoretical work offers an explanation that patient-control PDI differences should implicate abnormal active membrane permeability. This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients.

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Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease.

Publications

Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease.

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