Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

source: © 2010 Journal of Biomedical Optics

New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.  [Read more…]

Fig 1. Catheter prototype for intravascular sensing of NIR fluorescence signals. (a) The NIRF catheter consists of a 0.36-mm∕0.014-in. floppy radiopaque tip with a maximum outer diameter of 0.48mm∕0.019in.. The arrow highlights the focal spot (40±15μm) for the 90-deg arc-sensing catheter at a distance of 2±1mm (arrow). (b) Phantom experiment to measure NIR light attenuation in the presence of whole blood. Plaque (P) consists of 1% Intralipid plus India ink 50ppm plus AF750 (an NIR fluorochrome, concentration 300nmol∕L); tissue (T: fibrous cap) consists of polyester casting resin plus titanium dioxide plus India ink; a container (gray shaded area) was filled with fresh rabbit blood or saline. The catheter was immersed in fresh rabbit blood and positioned at variable distance (D) from a fluorescent phantom representing the plaque (P). To mimic the presence of a fibrous cap, a solid tissue phantom of thickness T was interposed between the plaque and the lumen. (c) Plot of detected NIRF signal as a function of distance D in presence of blood compared to saline, showing only modest attenuation by blood. Inset, fluorescence signal decay in saline at distance of up to 10mm. (d) Plot of the detected NIRF signal in blood in the presence of a tissue phantom (T) of thickness 500μm shows modest NIRF signal attenuation (<35%) vs the case in (c) where T=0. Reproduced by permission from Ref. 22.

Marcella A. Calfon, Claudio Vinegoni, Vasilis Ntziachristos, Farouc A. Jaffer, “Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques,” J. of Biomedical Optics, 15(1), 011107 (2010)