Intravascular molecular‐structural imaging with a miniaturized integrated near‐infrared fluorescence and ultrasound catheter

Abstract

Coronary artery disease (CAD) remains a leading cause of mortality and warrants new imaging approaches to better guide clinical care. We report on a miniaturized, hybrid intravascular catheter and imaging system for comprehensive coronary artery imaging in vivo. Our catheter exhibits a total diameter of 1.0 mm (3.0 French), equivalent to standalone clinical intravascular ultrasound (IVUS) catheters but enables simultaneous near-infrared fluorescence (NIRF) and IVUS molecular-structural imaging. We demonstrate NIRF-IVUS imaging in vitro in coronary stents using NIR fluorophores, and compare NIRF signal strengths for prism and ball lens sensor designs in both low and high scattering media.Next, in vivo intravascular imaging in pig coronary arteries demonstrates simultaneous, co-registered molecular-structural imaging of experimental CAD inflammation on IVUS and distance-corrected NIRF images. The obtained results suggest substantial potential for the NIRF-IVUS catheter to advance standalone IVUS, and enable comprehensive phenotyping of vascular disease to better assess and treat patients with CAD. K E Y W O R D Sintravascular endoscopy, intravascular imaging, intravascular ultrasound, near-infrared imaging | INTRODUCTIONHigh-resolution intravascular imaging plays a key role in coronary artery disease (CAD) assessment and in guiding percutaneous coronary intervention. Accordingly,Stephan Kellnberger and Georg Wissmeyer contributed equally.

Accounting for blood attenuation in intravascular near-infrared fluorescence-ultrasound imaging using a fluorophore-coated guidewire

“…The major advantage of this approach is that it accounts for the spatiotemporal variations of intravascular blood attenuation by enabling the estimation of frame-specific blood-attenuation correction factors, overcoming the limitations of previous methods that calculated average corrections factors. 4 , 9 – 11 …”

“…Previous studies utilized the Twersky model for fluorescence signal correction, which is based on a two-term exponential function. 4 , 8 , 10 , 11 In this study, we employ a simplified one-term exponential correction model that we validate for a range of blood attenuation levels by recording NIRF signals from a fluorophore-coated guidewire through different blood concentrations [ Fig. 2(h) ].…”

“… 23 , 24 Light attenuation by blood in intravascular fluorescence imaging was modeled as an exponential function of the distance between the outer wall of catheter sheath and the vessel wall or fluorophore-coated guidewire. 4 , 8 – 11 The NIRF signals of the guidewire were segmented from tissue signals using the coregistered IVUS data.…”

“…Previous works assumed blood attenuation using ex vivo reference measurements or approximate average values estimated in vivo . 4 , 9 – 11 However, such approximations can introduce errors since they do not account for deviations of each patient from the average value employed in the correction model; for example, due to variations of hematocrit, 8 oxygenation state, 12 or fluctuations in blood flow 13 , 14 as a function of vessel type, intravascular location, and pathological state. 15 …”

Dual-modality fluorescence lifetime imaging-optical coherence tomography intravascular catheter system with freeform catheter optics

“…For example, intravascular ultrasound (IVUS) has been widely used in clinics to image the lumens with decent resolution and penetration depth. 4 Intravascular optical coherence tomography (IV OCT) can generate high-resolution structural images at the expense of penetration depth and has been proven valuable tool for cardiovascular diagnostics by providing accurate vessel sizing, identify the presence of atherosclerosis lesions and some of their key features (e.g., extracellular matrix, macrophages, and cholesterol crystals) and assess stent apposition. 5 However, neither of these two techniques are sensitive to change in tissue biochemical property, making it difficult to characterize the plaque composition, a key determinant for plaque behavior and subsequent cardiovascular events.…”