Clinical Characterization of Coronary Atherosclerosis With Dual-Modality OCT and Near-Infrared Autofluorescence Imaging

Abstract

Objectives: The authors present the clinical imaging of human coronary arteries in vivo using a multimodality optical coherence tomography (OCT) and near-infrared autofluorescence (NIRAF) intravascular imaging system and catheter.

Background: Although intravascular OCT is capable of providing microstructural images of coronary atherosclerotic lesions, it is limited in its capability to ascertain the compositional/molecular features of plaque. A recent study in cadaver coronary plaque showed that endogenous NIRAF is elevated in necrotic core lesions. The combination of these 2 technologies in 1 device may therefore provide synergistic data to aid in the diagnosis of coronary pathology in vivo.

Methods: We developed a dual-modality intravascular imaging system and 2.6-F catheter that can simultaneously acquire OCT and NIRAF data from the same location on the artery wall. This technology was used to obtain volumetric OCT-NIRAF images from 12 patients with coronary artery disease undergoing percutaneous coronary intervention. Images were acquired during a brief, nonocclusive 3- to 4-ml/s contrast purge at a speed of 100 frames/s and a pullback rate of 20 or 40 mm/s. OCT-NIRAF data were analyzed to determine the distribution of the NIRAF signal with respect to OCT-delineated plaque morphological features.

Results: High-quality intracoronary OCT and NIRAF image data (>50-mm pullback length) were successfully acquired without complication in all patients (17 coronary arteries). The maximum NIRAF signal intensity of each plaque was compared with OCT-defined type, showing a statistically significant difference between plaque types (1-way analysis of variance, p < 0.0001). Interestingly, coronary arterial NIRAF intensity was elevated only focally in plaques with a high-risk morphological phenotype (p < 0.05), including OCT fibroatheroma, plaque rupture, and fibroatheroma associated with in-stent restenosis.

Conclusions: This OCT-NIRAF study demonstrates that dual-modality microstructural and fluorescence intracoronary imaging can be safely and effectively conducted in human patients. Our findings show that NIRAF is associated with a high-risk morphological plaque phenotype. The focal distribution of NIRAF in these lesions furthermore suggests that this endogenous imaging biomarker may provide complementary information to that obtained by structural imaging alone.

Keywords: first-in-human; multimodality imaging; near-infrared fluorescence; optical coherence tomography.

Fig. 1. Coronary segment negative for NIRAF

(A) Angiography of RCA showing non-significant coronary disease over the OCT-NIRAF pullback segment (ps). (B) 2D NIRAF map demonstrating negligible NIRAF signal. (C) Cross sectional OCT-NIRAF image showing normal coronary wall and a calcification (2 o'clock) with no NIRAF signal detected. (D) 3D cutaway rendering of the OCT-NIRAF pullback. Scale bar in (C) equal to 1 mm; scale bar in (B) equal to 5 mm. *, guide-wire shadowing artifact; ●, side-branch.

Fig. 2. OCT-NIRAF imaging of TCFA rupture

(A) Coronary angiogram of LAD and (B) 2D NIRAF map showing a focal region of elevated NIRAF in the ostial LAD. (C, D, E) OCT-NIRAF cross-sections from sites in (B) with elevated NIRAF, revealing subclinical OCT-TCFA fibrous cap rupture. (F) Magnification of a cholesterol crystal below the cap, co-localized with high NIRAF, and (G, H) magnified views of the rupture site. In (G), the rupture site (arrowhead) is covered by a small white luminal thrombus (arrow) and the arrow in (H) points to the site of the thin-cap rupture, demonstrating co-localized and very high focal NIRAF signal. (I) 3D cutaway rendering showing that the highest NIRAF spot appears focally within a large lipid pool (arrow), and the remaining portion of the vessel shows diffuse disease that was negative for NIRAF. Scale bars on OCT images and magnifications are equal to 1 mm and 0.5 mm, respectively; scale bar in (B) is equal to 5 mm. ps, pullback segment; L, lipid; R, rupture site; T, thrombus.

Fig. 3. OCT-NIRAF imaging of in-stent restenosis

(A) Angiography of LCx and (B) 2D NIRAF map. (C) Cross-sectional OCT-NIRAF image, showing a focal site with elevated NIRAF co-localized with stent struts overlying an OCT-delineated fibroatheroma. The arrow in (D) identifies OCT uncovered stent struts, a marker of incomplete stent healing. (E) Cross-sectional image from the distal portion of the stent that is negative for NIRAF, showing in-stent restenosis and non-attenuating OCT tissue suggesting intimal hyperplasia and presence of fibrotic tissue. (F) 3D cutaway rendering illustrating that the highest NIRAF signal is co-localized with mid and proximal stent segment and with the tissue with high OCT signal attenuation (fibroatheroma). Scale bars on OCT images are equal to 1 mm; scale bar on (B) is equal to 5 mm. ps, pullback segment; L, lipid.

Fig. 4. Analysis of maximum NIRAF plaque intensities for different plaque types

Values from normal vessel wall and fibrotic plaques were significantly different from each other (p<0.05), demonstrating a lower signal intensity than that of fibrocalcific plaques (p<0.05). Fibrocalcific plaques and ThCFA showed moderate maximum NIRAF signal intensities that were not significantly different from each other (p=0.65). A higher maximum NIRAF signal was detected from sites of plaque rupture (p<0.05) and TCFA (p<0.05). Whisker lengths are defined as +/−2.7σ, and points are drawn as outliers if outside the range [q1 – w(q3 – q1)] and [q3 + w(q3 – q1)], where q1 and q3 are the 25th and 75th percentiles, respectively.