Challenge: The underlying causes of Alzheimer’s disease (AD) remain poorly understood, and only few dynamic biomarkers are available to monitor responses for experimental therapies. Neuroimaging methods such as structural magnetic resonance imaging (MRI) can detect brain atrophy, but slow changes during disease progression cannot be measured during the timeframe of clinical trials, while functional MRI (fMRI) methods are not yet fully adapted for quantitative measurements. Moreover, positron emission tomography (PET) requires repetitive exposures to radiation, which is also not compatible with the duration of clinical trials.
Solution: The multidisciplinary research team developed a novel MRI technology allowing a rapid and non-invasive imaging of oxidative metabolism in the human brain. Their approach, termed QUO2 (Quantitative O2) MRI, follows the brain consumption of oxygen with superior spatial resolution, sensitivity and, more importantly, without radiation exposure.
Achievements/Impact: This technology was first tested in healthy participants to assess its accuracy and reliability. QUO2 MRI data acquisition was based on arterial spin-labeling (ASL) with a multi-echo imaging readout performed on 34 AD patients and 37 healthy controls. As a result, dynamic image recordings of brain perfusion and blood oxygenation through controlled administrations of inhaled carbon dioxide or enriched oxygen was obtained. Image processing software yielded quantitative maps of cerebral blood flow, vascular reactivity, and oxygen consumption. Datasets were further analyzed, demonstrating the ability of the QUO2 MRI method to detect parietotemporal patterns of hypoperfusion and hypometabolism, that are typical of AD, and previously detectable only with radiotracer methods. The resulting non-invasive and non-radioactive technology could thus be used as a biomarker to diagnose and stratify AD patients at an earlier stage and to follow disease progression, characterizing vascular and metabolic deficits in patient cohorts under consideration for clinical drug trials.
| Principal Investigator: Richard Hoge Montreal Neurological Institute and Hospital |
| Co-investigators Pierre Bellec, Sylvie Belleville, Julien Doyon, Ouri Monchi Montreal Neurological Institute and Hospital Yan Deschaintre Centre Hospitalier de l’Université de Montréal (CHUM) Serge Gauthier McGill University Douglas Arnold NeuroRx Research |
| Completed Project |
| $ 1,412,000 / 3 years |
| Supported by CQDM through: – AstraZeneca – Merck – Pfizer – MEI – BL-NCE |
| And by a co-funding partner: – Mitacs |
