Mazen Albaghdadi, Zhonglie Piao, Adam Mauskapf, Mohammed Chowdhury, Rami Tzafriri, Elazer Edelman, Guillermo Tearney, Farouc Jaffer. “In vivo Imaging Assessment of Arterial Permeability Using Indocyanine Green: Implications for Optimizing Drug-Coated Balloon Treatment of Atherosclerosis.”
Summary: The efficacy of paclitaxel (PTX) drug-coated balloons (DCBs) in reducing restenosis is limited by Inadequate arterial permeability (AP), yet in vivo approaches for imaging AP in atherosclerosis are limited. We applied intravascular near-infrared fluorescence-optical coherence tomography (NIRF-OCT) molecular imaging of indocyanine green (ICG), a validated approach to assess AP in vivo. We sought to characterize the ability of NIRF-OCT/ICG to detect changes in AP following plaque modification, the impact of DCB on AP over time, and the ability of ICG to serve as a biomarker of PTX uptake.
Methods: Atherosclerosis was induced in New Zealand white rabbits (N=3). At 6wks, rabbits underwent NIRF-OCT imaging following ICG (1mg/kg) injection pre- and post- aortic cutting balloon angioplasty (CBA) to enhance AP, and then the CBA zone was treated with a DCB. At 10wks, NIRF-OCT/ICG was repeated followed by sacrifice. Additional normal rabbits (N=2) underwent aortic CBA followed by ICG injection. Resected aortas were then incubated with fluorescent PTX (10mM; Flutax-2) and aortic tissue sections were examined by fluorescence microscopy (FM).
Results: NIRF-OCT imaging of ICG-measured AP in vivo increased post-CBA vs pre-CBA: 496.7±235.9nM vs. 59.3±48.3nM, P<0.01. CBA-treated vs. non-CBA treated regions also had greater NIRF-OCT detected ICG-measured AP: 307.2±110.6nM vs. 31.1±20.8nM, P=0.01. NIRF-OCT imaging revealed significantly reduced ICG uptake within the DCB-treated aorta at 10 vs. 6 weeks: 142.2±50.7nM vs. 366.3±68.7nM, P=0.05. FM of normal aortic sections demonstrated that PTX deposited in areas of enhanced permeability as evidenced by co-localization of PTX and ICG within the CBA-treated regions.
Conclusion: In vivo AP is augmented by CBA plaque modification and can be quantified using NIRF-OCT/ICG molecular imaging. DCBs may reduce atherosclerotic plaque permeability suggesting the potential for DCBs to biologically stabilize atheroma. Areas of enhanced ICG permeability may facilitate PTX deposition in the artery wall. Translational NIRF molecular imaging may help elucidate mechanisms of DCB efficacy and provide insights into the distribution of arterial PTX distribution following DCB.
Poster presented at ATVB|PVD Scientific Sessions, May 14–16, 2019, Boston, MA.