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Neuroimage Clin. 2017 May 16;15:348-358. doi: 10.1016/j.nicl.2017.05.009. eCollection 2017.

Application of calibrated fMRI in Alzheimer's disease.

Lajoie I1,2,3, Nugent S2,3,4, Debacker C2,3,5, Dyson K2,3,6, Tancredi FB7, Badhwar A2,8, Belleville S2,9, Deschaintre Y10,11, Bellec P2,8, Doyon J2,9, Bocti C12, Gauthier S13, Arnold D3,4, Kergoat MJ2,14, Chertkow H2,4,15, Monchi O2,4,13,16, Hoge RD1,2,3,4.

Author information

Département de Pharmacologie et physiologie, Université de Montréal, Montreal, QC, Canada.
Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Montreal, QC, Canada.
Montreal Neurological Institute, Montreal, QC, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Department of Psychiatry, McGill University, Montreal, QC, Canada.
Department of Physiology, McGill University, Montreal, QC, Canada.
Departamento de Radiologia, Centro de Pesquisa em Imagem, Hospital Israelita Albert Einstein, São Palo, SP, Brazil.
Department of Computer Science and Operations Research, Université de Montréal, Montreal, QC, Canada.
Département de Psychologie, Université de Montréal, Montreal, QC, Canada.
Département de Neurosciences, Université de Montréal, Montreal, QC, Canada.
Service de neurologie, Département de Médecine, CHUM Notre-Dame, Montréal, QC, Canada.
Division de Neurologie, Faculté de Médecine et des Sciences de la Santé & Research Centre on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada.
McGill Center for Studies in Aging, Douglas Mental Health Research Institute, Montreal, QC, Canada.
Département de Médecine, Université de Montréal, Montreal, QC, Canada.
Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.


Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO2). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO2 values fell within the range from previous studies using positron emission tomography (PET) with 15O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO2 can be imaged with 15O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function.


Alzheimer's disease; BOLD calibration constant; Calibrated fMRI; Cerebral blood flow; Cerebrovascular reactivity; Oxidative metabolism; Oxygen extraction fraction

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