Near-Infrared IIb Fluorescence Imaging of Vascular Regeneration with Dynamic Tissue Perfusion Measurement and High Spatial Resolution

Abstract

Real-time optical imaging is a promising approach for visualizing in vivo hemodynamics and vascular structure in mice with experimentally induced peripheral arterial disease (PAD). The application of a novel fluorescence-based all-optical imaging approach in the near-infrared IIb (NIR-IIb, 1500–1700 nm emission) window, for imaging hindlimb microvasculature and blood perfusion in a mouse model of PAD is reported. In phantom studies, lead sulfide/cadmium sulfide (PbS/CdS) quantum dots show better retention of image clarity, in comparison with single-walled nanotube (SWNT) NIR-IIa (1000–1400 nm) dye, at varying depths of penetration. When systemically injected to mice, PbS/CdS demonstrates improved clarity of the vasculature, compared to SWNTs, as well as higher spatial resolution than in vivo microscopic computed tomography. In a mouse model of PAD, NIR-IIb imaging of the ischemic hindlimb vasculature shows significant improvement in blood perfusion over the course of 10 days (P < 0.05), as well as a significant increase in microvascular density over the first 7 days after induction of PAD. In conclusion, NIR-IIb imaging of PbS/CdS vascular contrast agent is a useful multifunctional imaging approach for high spatial resolution imaging of the microvasculature and quantification of blood perfusion recovery.