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Development and demonstration of a single-scan rest/stress method for quantitative MBF measurements in PET

Résumé rédigé par
Directeur de thèse:
Doctorant: Nicolas GUEHL
Unité de recherche UMR_S 678 LABORATOIRE D'IMAGERIE FONCTIONNELLE

Projet

Positron emission tomography (PET) can measure absolute myocardial blood flow (MBF) at rest and during stress using dynamic imaging and appropriate tracer kinetic modeling. PET cardiac rest-stress studies are used in the clinic to diagnose the extent of coronary artery disease (CAD) and monitor the efficacy of its treatment. However, one limitation of these studies is that radioactivity from the rest scan must not affect the stress scan, making it necessary to wait 3 to 5 half lives between studies for sufficient radioactive decay to occur. Short-lived PET radiotracers such as 82Rb-chloride, 13N-ammonia or 15O-water can be used to circumvent this problem but the short half lives of 13N and 15O require an onsite cyclotron; whereas, 82Rb- is obtained from a 82Sr/82Rb generator system that decays with a ~25 day half life. With the advent of new 18F-labeled myocardial flow tracers, it is now possible to use 18F- tracers for accurate MBF quantification. Their moderately long physical half-life (109 min) is sufficient for commercial distribution to clinical centers on an as needed basis and thus does not require the need of on-site cyclotron or generator. However, the physical half-life of 18F is a logistical complication for rest-stress measurements because of the between scan waiting period needed to allow for radioactive decay. To address this issue for moderate to long lived tracers an alternative protocol was proposed and studied by simulation. In the new method rest and stress blood flow is measured using a single scan with two tracer injections and analyzed with a nonstationary kinetic model. The goal of this thesis was to demonstrate the in vivo feasibility of this technique and to improve its practicality for future clinical application. First, we demonstrated the use of this method in a porcine model for standard bull’s eye, segmental analysis using the relatively long-lived flow radiotracer [18F]-Flurpiridaz. We then extended the method and developed a computationally efficient algorithm to provide absolute quantitation at the voxel level. Third, we demonstrated the feasibility of our single-scan rest/stress imaging method in humans with healthy volunteers and patients with CAD using the clinically used radiotracer [13N]-NH3. Lastly, using our pig data we developed a framework for the construction of a 4D multimodal probabilistic atlas to facilitate inter- and intra-subjects comparisons and with an eye toward automated evaluation of MBF measurements. Our results showed that the rest/stress PET imaging procedure, that is normally acquired as two separate scans (separated by several hours, and often on different days), can be compressed into a single scan session with less that 15 minutes of PET data acquisition while still obtaining accurate rest and stress MBF estimations. We obtained good quality MBF maps in a timely manner and the constructed 4D multimodal atlas provided myocardial images in standard size and orientation allowing objective and comparative analysis of MBF maps in an automated way.

Key words: Positrons Emission Tomography, Myocardial Blood Flow, kinetic modeling, rest/stress studies