In Vivo Translation of the CIRPI System---Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Zaman, R., Yousufi, S., Chibana, H., Ikeno, F., Long, S. R., Gambhir, S. S., Chin, F. T., McConnell, M. V., Xing, L., Yeung, A. 2019


Introduction: Thin-cap fibro atheroma (TCFA), unstable lesions in coronary artery disease (CAD), that prones to rupture resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphological/biological features make early detection and risk assessment difficult. To overcome this limitation, we tested our newly developed catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system in vivo rabbit abdominal aorta to detect and characterize TCFA. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging (CRI) and photoacoustic tomography (PAT). The CIRPI system was tested in rabbit abdominal aorta in vivo (WHHL, n = 5) and controls (NZW, n = 2). Rabbits were fasted for 6 hours before 5.55*107 Bq 18F-FDG was injected one hour prior to the imaging procedure. The experiment was done under anesthetic. A bare metal stent was implanted in the dorsal abdominal aorta as landmark, followed by the 7F imaging catheters that were advanced up to the proximal stent edge (PSE). Our CIRPI and clinical OCT were performed using pullback and non-occlusive flushing techniques. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540/560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were verified with clinical OCT showing an area of low attenuation filled with lipids within TCFA. PAT image illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. However, 4 WHHL rabbits showed both moderate to severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with the OCT and histochemical analysis. Conclusion: Our novel multi-modality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a pre-clinical rabbit models. This proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, it may enhance the clinical evaluation of TCFA, as well as expand our understanding of CAD.

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