High-Speed Intravascular Near-infrared Fluorescence-Ultrasound Imaging In Vivo

Objective: The combination of near-infrared fluorescence (NIRF) with intravascular ultrasound (IVUS) has shown promising applications for imaging atherosclerosis in ex vivo human arteries and in vivo animal models. However, long acquisition times, rotational distortion causing inconsistent image quality and poor catheter durability have hampered clinical translation. Technical limitations have included motor drive unit (MDU) instability, and catheter designs with a single-layer drive shaft and long rigid length of the distal tip. Methods: Herein, we present an improved, next-generation NIRF-IVUS system by integrating an aluminum v-block-based high-speed MDU and 3.0 French (∅ = 1.0mm) catheter with a dual-layer drive shaft and reduced rigid tip length. We show a sixfold increase in imaging speed (30 FPS, 6 mm/s pullback) mirroring speed capabilities of standalone, commercial IVUS imaging. Results: In phantoms, we find that key NIRF-IVUS specifications like co-registration, rotational stability and NIRF resolution/sensitivity are preserved. Furthermore, we demonstrate that NIRF-IVUS molecular imaging of cathepsin protease activity can highlight stent-induced arterial inflammation independent of imaging speed, in rabbits in vivo. We calculate similar (not significant, p = 0.65) NIRF target-to-background ratios (TBRs) in stented tissue areas at low-speed (1.88) and high-speed (2.00) imaging. Finally, in vivo NIRF-IVUS imaging of FDA-approved indocyanine green detects early-stage plaques in rabbit aorta not visible on standalone IVUS. Similar NIRF TBRs are calculated in low-speed (4.13) and high-speed (4.08) pullbacks. Conclusion and Significance: Our study demonstrates that NIRF-IVUS can highlight key pathobiological markers of atherosclerosis beyond standalone IVUS at clinical imaging speeds, further supporting the clinical translation of the NIRF-IVUS technology.