Intravascular Fluorescence Molecular Imaging of Atherosclerosis

Abstract

Optical molecular imaging using near-infrared fluorescence (NIRF) light is an emerging high-resolution imaging approach to image a wide range of molecular and cellular species in vivo. Imaging using NIR wavelengths (650-900 nm) enables deeper photon penetration into tissue and reduced tissue autofluorescence, resulting in higher sensitivity to detect exogenously administered NIR fluorophores (injectable molecular imaging agents). Greater imaging depth of several centimeters is further achievable in the NIR window as blood absorption is as an order of magnitude lower than in the visible range. Furthermore, as optical imaging is routinely performed in the cardiac catheterization laboratory (e.g., optical coherence tomography), intravascular NIRF offers a promising translational approach for clinical coronary and peripheral arterial imaging. To this point, the first human intravascular NIRF imaging study recently demonstrated the ability to detect NIR autofluorescence in patients with coronary atherosclerosis. This study provides a foundation for targeted intravascular NIRF molecular imaging studies in coronary patients. In this chapter, we detail system engineering, imaging agents and translational applications of intravascular NIRF molecular imaging.

Keywords: Atherosclerosis; Drug-coated balloon; Imaging; Inflammation; Intravascular ultrasound; Near-infrared fluorescence; Optical coherence tomography; Peripheral arterial disease.

FIGURE 1:. Jablonski diagram of the fluorescence mechanism

A photon is absorbed causing the molecule to move to an excited electronic state (blue line). The molecule loses some energy to heat as it moves to the lowest excited state (green). A photon is spontaneously emitted allowing the molecule to return to the ground state (red line).

FIGURE 2:

Molar extinction coefficients of oxy- (red)/deoxy- (blue)- haemoglobin over a large spectral range

FIGURE 3:

Dual-modality intravascular NIRF-OCT imaging system and catheter (reproduced from reference[18] with permission)

FIGURE 4:

Wavelength-swept laser (reproduced from reference [18] with permission)

FIGURE 5:

NIRF console and rotary junction (reproduced from reference [18] with permission)

FIGURE 6:

Dual-modality NIRF-OCT catheter. (reproduced from reference [18] with permission)

FIGURE 7:

High-resolution NIRF-OCT imaging. (reproduced from reference [19] with permission)

FIGURE 8:. Experimental Study Design

All 25 rabbits received 1.0% high-cholesterol diet (HCD) 2 weeks before aorta balloon injury, and for 4 weeks thereafter, followed by normal chow for the final 4 weeks. At 4 weeks after balloon injury, rabbits were intravenously injected with ProSense VM110 (400 nmol/kg). Rabbits underwent in vivo multimodal survival near-infrared fluorescence–optical coherence tomography (NIRF-OCT), intravascular ultrasound (IVUS), and x-ray angiography 24 h later. Then animals randomly underwent drug-coated balloon percutaneous transluminal angioplasty (DCB-PTA) (n = 10), PTA (n = 10), or sham-PTA (n = 5) therapy. Four weeks later at week 10, multimodal imaging NIRF-OCT and IVUS imaging were repeated, followed by sacrificed and ex vivo fluorescence imaging, as well as RNA and histopathological analysis. FRI = fluorescence reflectance imaging; IHC = immunohistochemistry; qPCR= quantitative polymerase chain reaction. Reproduced by permission from reference [22]

FIGURE 9:. Experimental Study Design

Paclitaxel drug-coated balloons (DCBs) reduce restenosis, but their overall safety has recently raised concerns. The work highlighted in this chapter hypothesized that DCBs could lessen inflammation and reduce plaque progression. Using 25 rabbits with cholesterol feeding- and balloon injury-induced lesions, DCB-percutaneous transluminal angioplasty (PTA), plain PTA, or sham-PTA (balloon inserted without inflation) was investigated using serial intravascular near-infrared fluorescence-optical coherence tomography and serial intravascular ultrasound. In these experiments, DCB-PTA reduced inflammation and plaque burden in non-obstructive lesions compared with PTA or sham-PTA. These findings indicated the potential for DCBs to serve safely as regional anti-atherosclerosis therapy (as evidenced in Figure 5). Reproduced by permission from reference [22]