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Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study.

ABSTRACT: We examined differences in cerebral blood flow (CBF) measured by Arterial Spin Labeled perfusion MRI (ASL MRI) across the continuum from cognitively normal (CN) older adults to mild Alzheimer's Disease (AD) using data from the multi-site Alzheimer's Disease Neuroimaging Initiative (ADNI). Measures of CBF, in a predetermined set of regions (meta-ROI), and hippocampal volume were compared between CN (n = 47), patients with early and late Mild Cognitive Impairment [EMCI (n = 32), LMCI (n = 35)], and AD (n = 15). Associations between these measures and disease severity, assessed by Clinical Dementia Rating scale sum of boxes (CDR SB), were also assessed. Mean meta-ROI CBF was associated with group status and significant hypoperfusion was observed in LMCI and AD relative to CN. Hippocampal volume was associated with group status, but only AD patients had significantly smaller volumes than the CN. When examining the relationship between these measures and disease severity, both were significantly associated with CDR SB and appeared to provide independent prediction of status. In light of the tight link between CBF and metabolism, ASL MRI represents a promising functional biomarker for early diagnosis and disease tracking in AD and this study is the first to demonstrate the feasibility in a multi-site context in this population. Combining functional and structural measures, which can be acquired in the same scanning session, appears to provide additional information about disease severity relative to either measure alone.

SUBMITTER: Wang Z

PROVIDER: S-EPMC3777751 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study.

Wang Ze Z Das Sandhitsu R SR Xie Sharon X SX Arnold Steven E SE Detre John A JA Wolk David A DA

NeuroImage. Clinical 20130430

We examined differences in cerebral blood flow (CBF) measured by Arterial Spin Labeled perfusion MRI (ASL MRI) across the continuum from cognitively normal (CN) older adults to mild Alzheimer's Disease (AD) using data from the multi-site Alzheimer's Disease Neuroimaging Initiative (ADNI). Measures of CBF, in a predetermined set of regions (meta-ROI), and hippocampal volume were compared between CN (n = 47), patients with early and late Mild Cognitive Impairment [EMCI (n = 32), LMCI (n = 35)], an ...[more]

PMID: 24179814

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Project description:BackgroundQuantitative transport mapping (QTM) of blood velocity, based on the transport equation has been demonstrated higher accuracy and sensitivity of perfusion quantification than the traditional Kety's method-based cerebral blood flow (CBF). This study aimed to investigate the associations between QTM velocity and cognitive function in Alzheimer's disease (AD) using multiple post-labeling delay arterial spin labeling (ASL) MRI.MethodsA total of 128 subjects (21 normal controls (NC), 80 patients with mild cognitive impairment (MCI), and 27 AD) were recruited prospectively. All participants underwent MRI examination and neuropsychological evaluation. QTM velocity and traditional CBF maps were computed from multiple delay ASL. Regional quantitative perfusion measurements were performed and compared to study group differences. We tested the hypothesis that cognition declines with reduced cerebral blood perfusion with consideration of age and gender effects.ResultsIn cortical gray matter (GM) and the hippocampus, QTM velocity and CBF showed decreased values in the AD group compared to NC and MCI groups; QTM velocity, but not CBF, showed a significant difference between MCI and NC groups. QTM velocity and CBF showed values decreasing with age; QTM velocity, but not CBF, showed a significant gender difference between male and female. QTM velocity and CBF in the hippocampus were positively correlated with cognition, including global cognition, memory, executive function, and language function.ConclusionThis study demonstrated an increased sensitivity of QTM velocity as compared with the traditional Kety's method-based CBF. Specifically, we observed only in QTM velocity, reduced perfusion velocity in GM and the hippocampus in MCI compared with NC. Both QTM velocity and CBF demonstrated a reduction in AD vs. controls. Decreased QTM velocity and CBF in the hippocampus were correlated with poor cognitive measures. These findings suggest QTM velocity as potential biomarker for early AD blood perfusion alterations and it could provide an avenue for early intervention of AD.

Project description:Mild cognitive impairment (MCI) is considered a prodromal stage of Alzheimer's disease (AD), but is also recognized to be a heterogeneous condition. Biomarkers that predict AD progression in MCI are of clinical significance because they can be used to better identify appropriate candidates for therapeutic intervention studies. It has been hypothesized that comparing to structural measurements, functional ones may be more sensitive to early disease abnormalities and the sensitivity could be further enhanced when combined with cognitive task, a "brain stress test." In this study, we investigated the value of regional cerebral blood flow (CBF), measured by arterial spin labeled perfusion MRI (ASL MRI) during a memory-encoding task, in predicting the estimated rate of hippocampal atrophy, an established marker of AD progression. Thirty-one amnestic MCI patients (20 male and 11 female; age: 70.9?±?6.5 years, range from 56 to 83?years; mini mental status examination: 27.8?±?1.8) and 42 normal control subjects (13 male and 29 female; age: 70.6?±?8.8 years, range from 55 to 88?years; mini mental status examination: 29.1?±?1.2) were included in this study. We compared the predictive value of CBF during task to CBF during rest and structural volumetry. Both region-of-interest and voxelwise analyses showed that baseline CBF measurements during task (strongest effect in fusiform gyrus, region-of-interest analysis statistics: r?=?0.56, p?=?.003), but not resting ASL MRI or structural volumetry, were correlated with the estimated rate of hippocampal atrophy in amnestic MCI patients. Further, stepwise linear regression demonstrated that resting ASL MRI and volumetry did not provide complementary information in prediction. These results support the notion that physiologic measures during a cognitive challenge may increase the ability to detect subtle functional changes that predict progression. As such, ASL MRI could have important utility in stratifying candidates for AD treatment trials.

Project description:BackgroundVascular dysfunction, including cerebral hypoperfusion, plays an important role in the pathogenesis and progression of Alzheimer's disease (AD), independent of amyloid and tau pathology. We established an AD-related perfusion pattern (ADRP) measured with arterial spin labeling (ASL) MRI using multivariate spatial covariance analysis.MethodsWe obtained multimodal MRI including pseudo-continuous ASL and neurocognitive testing in a total of 55 patients with a diagnosis of mild to moderate AD supported by amyloid PET and 46 normal controls (NCs). An ADRP was established from an identification cohort of 32 patients with AD and 32 NCs using a multivariate analysis method based on scaled subprofile model/principal component analysis, and pattern expression in individual subjects was quantified for both the identification cohort and a validation cohort (23 patients with AD and 14 NCs). Subject expression score of the ADRP was then used to assess diagnostic accuracy and cognitive correlations in AD patients and compared with global and regional cerebral blood flow (CBF) in specific areas identified from voxel-based univariate analysis.ResultsThe ADRP featured negative loading in the bilateral middle and posterior cingulate and precuneus, inferior parietal lobule, and frontal areas, and positive loading in the right cerebellum and bilateral basal areas. Subject expression score of the ADRP was significantly elevated in AD patients compared with NCs (P < 0.001) and showed good diagnostic accuracy for AD with area under receiver-operator curve of 0.87 [95% CI (0.78-0.96)] in the identification cohort and 0.85 in the validation cohort. Moreover, there were negative correlations between subject expression score and global cognitive function and performance in various cognitive domains in patients with AD. The characteristics of the ADRP topography and subject expression scores were supported by analogous findings obtained with regional CBF.ConclusionsWe have reported a characteristic perfusion pattern associated with AD using ASL MRI. Subject expression score of this spatial covariance pattern is a promising MRI biomarker for the identification and monitoring of AD.

Dataset Information

Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study.

Publications

Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study.

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