Simultaneous assessment of carotid plaque inflammation and micro-calcification with dual-tracer 18F-FDG:18F-NaF PET-MR imaging: a clinical feasibility study

Objectives: Simultaneous PET-MR has recently been introduced as a multi-parametric cardiovascular imaging framework of potentially high clinical value, thanks to its unique capability of combining i) the superior vessel wall anatomical features characterization of MRI, together with ii) the PET in-vivo progress quantification of critical molecular mechanisms in atherosclerosis. Moreover, a range of PET tracers has been independently employed to investigate the association of atherosclerosis disease with specific molecular processes in plaques, such as inflammation with 18F-Fluorodeoxyglucose (18F-FDG) or micro-calcification with 18F-sodium fluoride (18F-NaF). In this study we introduce the concept of a novel dual-tracer cardiovascular PET-MR imaging framework to expand the clinical potential of current PET-MR protocols by combining 18F-FDG and 18F-NaF plaque imaging in a single dynamic PET-MR scan of a standard of care total dosage. Thus, we aim at the co-registered in-vivo imaging of inflammation and micro-calcification processes in carotid plaques to enable parallel evaluations of any potential correlations between their activity progress and response to therapy at different stages of atherosclerosis.

Methods: A 90min dynamic human carotid dual-tracer PET-MR scan is proposed involving: a) the initial administration of half of the standard-of-care amount of weight-regulated 18F-FDG dosage, b) the start of a PET-MR scan at 80min post 18F-FDG injection, c) the administration of 18F-NaF of the same dosage amount at 90min post 18F-FDG injection and, d) the completion of PET/MR acquisition at 170min post 18F-FDG injection. The dynamic PET acquisition is conducted without interruption on list-mode to allow reconstruction of any time segments. The MR protocol component begins with a 2-point Dixon MR sequence, from which 4 tissue classes (air, lungs, fast and water) were manually segmented for enhanced MR-based PET attenuation correction, followed by a 3D time-of-flight non-contrast enhanced carotid MR angiography and a series of diagnostic black blood T1, T2 and proton density sequences over the same set of 2D transaxial slices covering the right and left carotids bifurcation sections. Subsequently, the net 18F-FDG PET images for the first 10min of scan data are independently reconstructed and, assuming sufficient 18F-FDG kinetics stability, the decay-corrected net 18F-FDG SUV image is linearly extrapolated to the last 10min scan period. Finally, it is subtracted from the cocktail 18F-FDG:18F-NaF PET SUV image, after the latter is normalized according to the combined dosage and decay-corrected, to quantitatively estimate the net 18F-NaF SUV uptake.

Results: Dynamic imaging of the 90min PET-MR data was conducted with the proposed 18F-FDG:18F-NaF protocol on a patient subject, followed by regional quantitative analysis in left and right carotid wall bifurcation points and proximal common carotids lumen. The results demonstrated a relatively high and stable net 18F-FDG PET signal in both carotids after 80min of 18F-FDG circulation, therefore permitting the reliable extrapolation of the decay-corrected net 18F-FDG signal distribution for later times. In addition, the last 10min of the scan, corresponding to 70-80min window after 18F-NaF injection the total cocktail signal is dynamically stabilized thereby suggesting a total dual-tracer PET scan time of 90min is sufficient for the imaging of sufficient 18F-NaF plaque uptake.

Conclusion: Dual-tracer 18F-FDG:18F-NaF PET/MR imaging facilitates the co-registered in-vivo clinical evaluation of the activity progress and treatment response of both inflammation and micro-calcification mechanisms in carotid plaques thereby permitting the systematic in-depth study of their potential correlation during the course of atherosclerosis. Research Support: This work was supported by NIH/NHLBI R01HL071021 grant.