Coronary optical frequency domain imaging (OFDI) for in vivo evaluation of stent healing: comparison with light and electron microscopy

Abstract

Aims: Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial approximately 10-20 microm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.

Methods and results: Twenty stents were implanted into 10 pigs and coronary OFDI was performed after 1, 3, 10, 14, and 28 days. Neointimal thickness as detected by OFDI correlated closely with neointimal thickness as measured by LM (r = 0.90, P < 0.01). The comparison of stent strut coverage as detected by OFDI and SEM analysis revealed an excellent agreement (r = 0.96, P < 0.01). In particular, stents completely covered by OFDI analysis were also completely covered by SEM analysis. All incompletely covered stents by OFDI were also incompletely covered by SEM. Analyses of fibrin-covered stent struts suggested that these may rarely be detected as uncovered stent struts by OFDI. Importantly, optical density measurements revealed a significant difference between fibrin- and neointima-covered coronary stent struts [0.395 (0.35-0.43) vs. 0.53 (0.47-0.57); P < 0.001], suggesting that differences in optical density provide information on the type of stent strut coverage. The sensitivity and specificity for detection of fibrin vs. neointimal coverage was evaluated using receiver-operating characteristic analysis.

Conclusion: The present study demonstrates that OFDI is a highly promising tool for accurate evaluation of coronary stent strut coverage, as supported by a high agreement between OFDI and light and electron microscopic analysis. Furthermore, our data indicate that optical density measurements can provide additional information with respect to the type of stent strut coverage, i.e. fibrin vs. neointimal coverage. Therefore, coronary OFDI analysis will provide important information on the biocompatibility of coronary stents.

Figures

Figure 1

Representative corresponding images of scanning electron microscopy (SEM) and optical frequency domain imaging (OFDI) analysis of the same stent segment. (A) Overview in SEM; (B) details of the side-branch in SEM; (C) overview in OFDI; (D–G) sequential OFDI images showing covered and uncovered stent struts corresponding to the marked positions in the electron microscopy image in (B); (F) shows one strut covered (upper) and one strut blank (lower) as seen on the SEM image as well.

Figure 2

Different characteristics of stent strut coverage at different time points after stent implantation, i.e. fibrin- vs. neointima-covered stent struts. (A) Fibrin at Day 3 in scanning electron microscopy (SEM) and optical frequency domain imaging (OFDI), where a low intensity of stent strut coverage can be seen (A‴′); (B) neointima at Day 10 in SEM and OFDI, where stent strut coverage with higher intensity when compared with fibrin can be observed; (C) neointima at Day 28 in SEM and OFDI, where a high intensity of stent strut coverage is present (is, intensity of strut; it, intensity of tissue).

Figure 3

Assessment of the optical density of the optical frequency domain imaging (OFDI) images of stent strut coverage—differences between fibrin vs. neointimal stent strut coverage. (A) Densitometric analysis of OFDI images with histologically approved fibrin- and neointima-covered stent struts (medians with interquartile ranges); (B) receiver-operating characteristic curve of data presented in (A); (C) densitometric analysis of the development of neointimal coverage of stents at different time points after stent implantation.

Figure 4

Relation of measurements of neointimal thickness between light microscopic (LM) and optical frequency domain imaging (OFDI) analysis on Days 10–28 after coronary stent implantation. Dot plot (A) and log transformation of Bland–Altman plot (B; red lines = limit of agreements) are shown demonstrating the agreement between neointimal thickness measurements obtained by light microscopy and OFDI analysis.

Figure 5

Corresponding images of light microscopic (LM) and optical frequency domain imaging (OFDI) analysis of neointima measurements. The image wire and the guide wire shadow have been marked in OFDI (white) and on their corresponding sites in LM (black), matching pairs were found as positions of LM images in the stent were known and positions of OFDI images could be calculated from the number of images between start and end of the stent. (A) Day 3, one strut on OFDI is hidden behind the guide wire shadow, one is hidden behind the image wire shadow (indicated by asterisks); (B) Day 14, again, one strut is hidden behind the guide wire shadow in the OFDI image (asterisks); (C) Day 28 LM vs. OFDI, all struts are visible in OFDI and LM images, measurement of neointimal thickness is marked in red.