SummaryCoronary optical coherence tomography (OCT) has the potential to identify in-stent neoatherosclerosis, which is a possible risk factor for late acute coronary events after drug-eluting stent implantation. The purpose of this study was to investigate differences between mid-term and late in-stent restenosis after stent implantation by quantitative and semiautomated tissue property analysis using OCT. In total, 1063 OCT image frames of 16 lesions in 15 patients were analyzed. This included 346 frames of 6 lesions in late in-stent restenosis, which was defined as restenosis that was not detected at 6 to 12 months but ≥ 12 months after follow-up coronary angiography. Signal attenuation was circumferentially analyzed using a dedicated semiautomated software. Attenuation was assessed along 200 lines delineated radially for analysis of the in-stent restenotic lesions (between the lumen and stent contours). All lines were anchored by the image wire to avoid artifacts resulting from wire location. Stronger signal attenuation at the frame level (2.46 ± 0.78 versus 1.47 ± 0.32, P < 0.001) and higher maximum signal intensity at the lesion level (9.19 ± 0.19 versus 8.84 ± 0.32, P = 0.018) were observed in late in-stent restenotic lesions than in mid-term in-stent restenotic lesions. OCT demonstrated stronger signal attenuation and higher maximum signal intensity in late in-stent restenotic lesions than in mid-term in-stent restenotic lesions, indicating the possibility of neoatherosclerosis. (Int Heart J 2015; 56: 13-17) Key words: Coronary artery disease, Intracoronary imaging, Restenosis, Percutaneous coronary intervention D rug-eluting stent (DES) placement decreases the incidence of mid-term in-stent restenosis. 1) However, late in-stent restenosis is occasionally observed in cases of previous DES implantation.2) Thrombus formation or inflammatory cell proliferation in late in-stent restenotic lesions after DES implantation may indicate a delayed healing process.3) Coronary optical coherence tomography (OCT) has emerged as an effective modality to elucidate the healing process after stent implantation. [4][5][6][7][8] Strong signal attenuation is commonly observed in late in-stent restenotic lesions on OCT.9) One recent study revealed the utility of OCT combined with virtual histology intravascular ultrasound in identifying neoatherosclerosis in late in-stent restenosis after DES implantation.10) Strong signal attenuation on OCT may indicate neoatherosclerosis. 4,11) In addition, macrophage proliferation is indicated by high signal intensity on OCT images. 12) Quantitative evaluation of signal attenuation and intensity may enable identification of neoatherosclerosis after DES implantation. In the present study, we analyzed OCT signal intensity and attenuation for tissue property analysis of in-stent restenotic lesions using a contemporary quantitative analysis system. The purpose of this study was to investigate differences between midterm and late in-stent restenosis by using a quantitative OCT analysis system.