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Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal neurodegeneration in mild cognitive
Long Xie1,2, Sandhitsu R Das1,3,4, Arun Pilania3,4
1Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract:
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.
Insights
Functional brain imaging during a memory task, using arterial spin labeled perfusion MRI (ASL MRI), can predict Alzheimer's disease progression in mild cognitive impairment (MCI). This method shows promise for identifying patients for clinical trials.
Area of Science:
- Neuroimaging
- Neurology
- Biomarkers
Background:
- Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD), characterized by heterogeneity.
- Identifying biomarkers to predict AD progression in MCI is crucial for therapeutic intervention studies.
- Functional neuroimaging may offer greater sensitivity to early AD-related changes than structural measurements, especially during cognitive tasks.
Purpose of the Study:
- To investigate the predictive value of regional cerebral blood flow (CBF) measured by ASL MRI during a memory-encoding task for the rate of hippocampal atrophy in amnestic MCI patients.
- To compare the predictive capability of task-based CBF with resting-state CBF and structural volumetry.
Main Methods:
- The study included 31 amnestic MCI patients and 42 healthy controls.
- Arterial spin labeled perfusion MRI (ASL MRI) was used to measure regional cerebral blood flow (CBF) both at rest and during a memory-encoding task.
- Structural MRI was performed for volumetry. Both region-of-interest and voxelwise analyses were employed.
Main Results:
- Baseline CBF measurements during the memory task, particularly in the fusiform gyrus, were significantly correlated with the rate of hippocampal atrophy in MCI patients (r=0.56, p=0.003).
- Resting-state ASL MRI and structural volumetry did not show a significant correlation with hippocampal atrophy.
- Resting ASL MRI and volumetry did not provide complementary predictive information when combined.
Conclusions:
- Task-based ASL MRI measurements of CBF are sensitive to early functional changes that predict AD progression in MCI.
- Functional neuroimaging during a cognitive challenge, like ASL MRI during a memory task, enhances the ability to detect subtle abnormalities.
- ASL MRI shows significant utility in stratifying candidates for AD clinical trials.
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