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Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease.

ABSTRACT: Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early stage HD subjects and 41 age- and gender-matched healthy controls. We found profound yet heterogeneous CBF reductions in the cortex, extending to the sensorimotor, paracentral, inferior temporal and lateral occipital regions, with sparing of the neighboring postcentral gyrus, insula and medial occipital areas. As expected, CBF in subcortical regions was also profoundly reduced, and to a similar degree. Unexpectedly, however, the association between CBF reductions and regional atrophy was complex, the two being directly associated in certain areas but not with others. In contrast, CBF was associated with performance on the Stroop, suggesting a potentially important role for alterations in CBF in cognitive deficits in HD. The work described here may have broad-reaching implications for our understanding of HD pathogenesis, progression and emerging therapies.

SUBMITTER: Chen JJ

PROVIDER: S-EPMC3787075 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease.

Chen J Jean JJ Salat David H DH Rosas H Diana HD

NeuroImage 20110916 2

Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early stage HD subjects and 41 ...[more]

PMID: 21945790

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Project description:BACKGROUND:Several small cross-sectional studies have investigated cerebrospinal fluid (CSF) flow dynamics in multiple sclerosis (MS) patients and have reported mixed results. Currently, there are no longitudinal studies that investigate CSF dynamics in MS patients. OBJECTIVE:To determine longitudinal changes in CSF dynamics measured at the level of aqueduct of Sylvius (AoS) in MS patients and matched healthy controls (HCs). MATERIALS AND METHODS:Forty (40) MS patients and 20 HCs underwent 3T MRI cine phase contrast imaging with velocity-encoded pulse-gated sequence at baseline and 5-year follow-up. For atrophy determination, MS patients underwent additional high-resolution 3D T1-weighted imaging. Measures of AoS cross-sectional area (CSA), average systolic and diastolic velocity peaks, maximal systolic and diastolic velocity peaks and average CSF flow rates were determined. Brain atrophy and ventricular CSF (vCSF) expansion rates were determined. Cross-sectional and longitudinal changes were derived by analysis of covariance (ANCOVA) and paired repeated tests. Confirmatory general linear models were also performed. False discovery rate (FDR)-corrected p-values lower than 0.05 were considered significant. RESULTS:The MS population demonstrated significant increase in maximal diastolic peak (from 7.23 to 7.86 cm/s, non-adjusted p = 0.037), diastolic peak flow rate (7.76 ml/min to 9.33 ml/min, non-adjusted p = 0.023) and AoS CSA (from 3.12 to 3.69 mm2, adjusted p = 0.001). The only differentiator between MS patients and HCs was the greater AoS CSA (3.58 mm2 vs. 2.57 mm2, age- and sex-adjusted ANCOVA, p = 0.045). The AoS CSA change was associated with vCSF expansion rate (age- and sex-adjusted Spearman's correlation r = 0.496, p = 0.019) and not with baseline nor change in maximal velocity. The expansion rate of the vCSF space explained an additional 23.8% of variance in change of AoS CSA variance when compared to age and sex alone (R2 = 0.273, t = 2.557, standardized ? = 0.51, and p = 0.019). CONCLUSION:MS patients present with significant longitudinal AoS enlargement, potentially due to regional atrophy changes and ex-vacuo expansion of the aqueduct.

Project description:UnlabelledQuantification of β-amyloid (Aβ) in vivo is often accomplished using the distribution volume ratio (DVR), based on a simplified reference tissue model. We investigated the local relationships between DVR and cerebral blood flow (CBF), as well as relative CBF (R1), in nondemented older adults.MethodsFifty-five nondemented participants (mean age, 78.5 y) in the Baltimore Longitudinal Study of Aging underwent (15)O-H2O PET CBF and dynamic (11)C-PiB PET. (15)O-H2O PET images were normalized and smoothed using SPM. A simplified reference tissue model with linear regression and spatial constraints was used to generate parametric DVR images. The DVR images were regressed on CBF images on a voxel-by-voxel basis using robust biologic parametric mapping, adjusting for age and sex (false discovery rate, P = 0.05; spatial extent, 50 voxels). DVR images were also regressed on R1 images, a measure of the transport rate constant from vascular space to tissue. All analyses were performed on the entire sample, and on high and low tertiles of mean cortical DVR.ResultsVoxel-based analyses showed that increased DVR is associated with increased CBF in the frontal, parietal, temporal, and occipital cortices. However, this association appears to spare regions that typically show early Aβ deposition. A more robust relationship between DVR and CBF was observed in the lower tertile of DVR, that is, negligible cortical Aβ load, compared with the upper tertile of cortical DVR and Aβ load. The spatial distributions of the DVR-CBF and DVR-R1 correlations showed similar patterns. No reliable negative voxelwise relationships between DVR and CBF or R1 were observed.ConclusionRobust associations between DVR and CBF at negligible Aβ levels, together with similar spatial distributions of DVR-CBF and DVR-R1 correlations, suggest that regional distribution of DVR reflects blood flow and tracer influx rather than pattern of Aβ deposition in those with minimal Aβ load. DVR-CBF associations in individuals with a higher DVR are more likely to reflect true associations between patterns of Aβ deposition and CBF or neural activity. These findings have important implications for analysis and interpretation of voxelwise correlations with external variables in individuals with varying amounts of Aβ load.

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Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease.

Publications

Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease.

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