Near-Infrared Autofluorescence in Atherosclerosis Associates With Ceroid and Is Generated by Oxidized Lipid-Induced Oxidative Stress.

[Figure: see text].

Histopathological correlation of near infrared autofluorescence in human cadaver coronary arteries.

BACKGROUND AND AIMS: Prior coronary optical coherence tomography (OCT)-near infrared auto-fluorescence (NIRAF) imaging data has shown a correlation between high-risk morphological features and NIRAF signal intensity. This study aims to understand the histopathological origins of NIRAF in human cadaver coronary arteries. METHODS: Ex vivo intracoronary OCT-NIRAF imaging was performed on coronary arteries prosected from 23 fresh human cadaver hearts. Arteries with elevated NIRAF were formalin-fixed and paraffin-embedded. Microscopic images of immunostained Glycophorin A (indicating intraplaque hemorrhage) and Sudan Black (indicating ceroid after fixation) stained slides were compared with confocal NIRAF images (ex. 635 nm, em. 655-755 nm) from adjacent unstained slides in each section. Different images from the same section were registered via luminal morphology. Confocal NIRAF-positive 45° sectors were compared to immunohistochemistry and colocalization between NIRAF and intraplaque hemorrhage or ceroid was quantified by Manders' overlap and Dice similarity coefficients. RESULTS: Thirty-one coronary arteries from 14 hearts demonstrated ≥1.5 times higher NIRAF signal than background, and 429 sections were created from them, including 54 sections (12.6%) with high-risk plaques. Within 112 confocal NIRAF-positive 45° sectors, 65 sectors (58.0%) showed both Glycophorin A-positive and Sudan Black-positive, while 7 sectors (6.3%) and 40 sectors (33.6%) only showed Glycophorin A-positive or Sudan black-positive, respectively. A two-tailed McNemar's test showed that Sudan Black more closely corresponded to confocal NIRAF than Glycophorin A (p < 1.0 × 10-6). NIRAF was also found to spatially associate with both Glycophorin A and Sudan Black, with stronger colocalization between Sudan Black and NIRAF (Manders: 0.19 ± 0.15 vs. 0.13 ± 0.14, p < 0.005; Dice: 0.072 ± 0.096 vs. 0.060 ± 0.090, p < 0.01). CONCLUSIONS: As ceroid associates with oxidative stress and intraplaque hemorrhage is implicated in rapid lesion progression, these results suggest that NIRAF provides additional, complementary information to morphologic imaging that may aid in identifying high-risk coronary plaques via translatable intracoronary OCT-NIRAF imaging.

Clinical outcomes of low-intensity area without attenuation and cholesterol crystals in non-culprit lesions assessed by optical coherence tomography.

BACKGROUND AND AIMS: Pathologists have shown that intraplaque hemorrhage contributes to plaque destabilization and is frequently co-located with cholesterol crystals (CC). Optical coherence tomography (OCT)-detected low-intensity area without attenuation (LIA) may represent intraplaque hemorrhage. We aimed to examine the prevalence and impact of OCT-detected LIA + CC in untreated non-culprit lesions (NCLs) on subsequent major adverse cardiac events (MACE). METHODS: OCT imaged NCLs in the culprit vessel in the patients who underwent OCT-guided percutaneous coronary intervention were included. An NCL was a lesion with >90° of diseased arc (≥0.5 mm intimal thickness), length ≥2 mm, and >5 mm away from stent edge. CC was defined as a thin linear region of high intensity. NCL-related MACE includes cardiac death, myocardial infarction, or ischemia-driven revascularization attributed to NCLs. RESULTS: We included 735 NCLs in 566 patients with 2.5 ± 0.7 years follow-up. The prevalence of concomitant LIA with CC (LIA + CC) was 15.5% (114/735). Three-year NCL-related MACE rate was 2.9% (20 events) at a lesion level and 15.6% (78 events) at a patient level. Untreated NCLs with LIA + CC had an increased risk for NCL-MACE (adjusted hazard ratio [HR] 3.09, 95% confidence interval [CI] 1.27-7.50, p = 0.01) along with thin-cap fibroatheroma (adjusted HR 4.38, 95% CI 1.44-13.30, p < 0.01) and minimum lumen area <3.5 mm2 (adjusted HR 5.33, 95% CI 1.94-14.62, p < 0.01). Patients having ≥1 untreated NCL with LIA + CC had an increased risk for NCL-MACE (adjusted HR 1.95, 95% CI 1.19-3.19, p < 0.01). CONCLUSIONS: An OCT-detected LIA + CC in an NCL was associated with subsequent NCL-MACE.

Sex differences in the outcomes of stent implantation in mini-swine model.

Sex-related differences have been noted in cardiovascular anatomy, pathophysiology, and treatment responses, yet we continued to drive evaluation of vascular device development in animal models without consideration of animal sex. We aimed to understand sex-related differences in the vascular responses to stent implantation by analyzing the pooled data of endovascular interventions in 164 Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation, 68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES implantation). Histomorphological parameters were evaluated from vascular specimens at 3-365 days after stent implantation and evaluated values were compared between female and male groups. While neointima formation at all times after implantation was invariant to sex, statistically significant differences between female and male groups were observed in injury, inflammation, adventitial fibrosis, and neointimal fibrin deposition. These differences were observed independently, i.e., for different procedure types and at different follow-up timings. Only subtle temporal sex-related differences were observed in extent and timing of resolution of inflammation and fibrin clearance. These subtle sex-related differences may be increasingly important as interventional devices meld novel materials that erode and innovations in drug delivery. Erodible materials may act differently if inflammation has a different temporal sequence with sex, and drug distribution after balloon or stent delivery might be different if the fibrin clearance speaks to different modes of pharmacokinetics in male and female swine.

Vessel centerline reconstruction from non-isocentric and non-orthogonal paired monoplane angiographic images.

PURPOSE: Three-dimensional reconstruction of a vessel centerline from paired planar coronary angiographic images is critical to reconstruct the complex three-dimensional structure of the coronary artery lumen and the relative positioning of implanted devices. In this study, a new vessel centerline reconstruction method that can utilize non-isocentric and non-orthogonal pairs of angiographic images was developed and tested. METHODS: Our new method was developed in in vitro phantom models of bifurcated coronary artery with and without stent, and then tested in in vivo swine models (twelve coronary arteries). This method was also validated using data from six patients. RESULTS: Our new method demonstrated high accuracy (root mean square error = 0.27 mm or 0.76 pixel), and high reproducibility across a broad imaging angle (20°-130°) and between different cardiac cycles in vitro and in vivo. Use of this method demonstrated that the vessel centerline in the stented segment did not deform significantly over a cardiac cycle in vivo. In addition, the total movement of the isocenter in each image could be accurately estimated in vitro and in vivo. The performance of this new method for patient data was similar to that for in vitro phantom models and in vivo animal models. CONCLUSIONS: We developed a vessel centerline reconstruction method for non-isocentric and non-orthogonal angiographic images. It demonstrated high accuracy and good reproducibility in vitro, in vivo, and in clinical setting, suggesting that our new method is clinically applicable despite the small sample size of clinical data.

Constraining OCT with Knowledge of Device Design Enables High Accuracy Hemodynamic Assessment of Endovascular Implants.

BACKGROUND: Stacking cross-sectional intravascular images permits three-dimensional rendering of endovascular implants, yet introduces between-frame uncertainties that limit characterization of device placement and the hemodynamic microenvironment. In a porcine coronary stent model, we demonstrate enhanced OCT reconstruction with preservation of between-frame features through fusion with angiography and a priori knowledge of stent design. METHODS AND RESULTS: Strut positions were extracted from sequential OCT frames. Reconstruction with standard interpolation generated discontinuous stent structures. By computationally constraining interpolation to known stent skeletons fitted to 3D 'clouds' of OCT-Angio-derived struts, implant anatomy was resolved, accurately rendering features from implant diameter and curvature (n = 1 vessels, r2 = 0.91, 0.90, respectively) to individual strut-wall configurations (average displacement error ~15 µm). This framework facilitated hemodynamic simulation (n = 1 vessel), showing the critical importance of accurate anatomic rendering in characterizing both quantitative and basic qualitative flow patterns. Discontinuities with standard approaches systematically introduced noise and bias, poorly capturing regional flow effects. In contrast, the enhanced method preserved multi-scale (local strut to regional stent) flow interactions, demonstrating the impact of regional contexts in defining the hemodynamic consequence of local deployment errors. CONCLUSION: Fusion of planar angiography and knowledge of device design permits enhanced OCT image analysis of in situ tissue-device interactions. Given emerging interests in simulation-derived hemodynamic assessment as surrogate measures of biological risk, such fused modalities offer a new window into patient-specific implant environments.

Vascular Response to Experimental Stent Malapposition and Under-Expansion.

Up to 80% of all endovascular stents have malapposed struts, and while some impose catastrophic events others are inconsequential. Thirteen stents were implanted in coronary arteries of seven healthy Yorkshire pigs, using specially-designed cuffed balloons inducing controlled stent malapposition and under-expansion. Optical coherence tomography (OCT) imaging confirmed that 25% of struts were malapposed (strut-wall distance

The Deformation Rate of Smooth Muscle Cells in Vessel Walls After Short-Duration Heating Dilatation in a Porcine Model Ex Vivo and In Vivo.

We have proposed a novel short-duration thermal angioplasty with uniform temperature distribution. Although the dilatation mechanism of our short-duration heating dilatation was reported in our previous study, the influences on smooth muscle cells (SMCs) are not sufficiently understood. We studied the influences on SMCs in terms of shape change and discussed the relationship between the SMCs' shape change and dilatation mechanism ex vivo and in vivo. We found that the SMCs were fixed in the stretched condition after our short-duration heating dilatation both ex vivo and in vivo. The deformation rate of SMCs' shape, measured by the cells' nuclei, was increased with rising balloon maximum temperature (T(balloon)), and the same tendency was observed for the arterial dilatation rate. We hypothesize that the SMCs were fixed in the stretched condition because the arterial dilatation with our short-duration heating dilatation was performed without any plastic deformations of the vessel wall, causing the vessel wall itself to be stretched. We also prospect that the reasons for the positive correlation between the deformation rate of SMCs' shape and T(balloon) are that (i) the area heated over 60 °C was expanded with rising T(balloon), and (ii) the arterial dilatation rate was also increased with rising T(balloon).

Characteristics of smooth muscle cells' shape and proliferation rate in novel short-term thermal angioplasty ex vivo and in vitro.

We investigated the influences on the smooth muscle cells of temporally heated arterial walls in both ex vivo and in vitro study to determine the optimum heat parameter of novel short-term thermal angioplasty, Photo-thermo Dynamic Balloon Angioplasty (PTDBA). Arterial heating dilatation was performed by the prototype PTDBA balloon ex vivo. We found that the smooth muscle cells in the vessel wall were stretch-fixed after the heating dilatation ex vivo. The stretch-fixing rate of these cells was increased with the temperature rise in the balloon of PTDBA from 60 °C to 70 °C. We measured the proliferation rate of the stretch-fixed smooth muscle cells, which were extracted from porcine arteries, on specially designed culture equipment in vitro. It was observed that the proliferation rate was inhibited at 20 % stretching compared to 10 % stretching. We think the stretch-fixing of the smooth muscle cells might not be harmful for PTDBA performances.

The laser driven short-term heating balloon catheter: Relation between the chronic neointimal hyperplasia formation and thermal damage to arterial smooth muscle cells.

We proposed a novel laser-driven short-term heating angioplasty to realize restenosis-suppressive angioplasty for peripheral artery disease. In this study, we investigated the chronic intimal hyperplasia formation after the short-term heating dilatation in vivo, as well as the thermal damage calculation on arterial smooth muscle cells (SMCs). The prototype short-term heating balloon catheter with 5.0, 5.5, 6.0 mm φ in balloon diameter and 25 mm in balloon length were employed. The short-term heating dilatation was performed in porcine iliac arteries with dilatation conditions of 75°C (N=4) and 65°C (N=5) as peak balloon temperature, 18 ± 4s as heating duration, 3.5 atm as balloon dilatation pressure. Four weeks after the balloon dilatation, the balloon-dilated artery segments were extracted and were stained with HE and picrosirius red for histological observation. In the case of 75°C as the peak balloon temperature, neointimal hyperplasia formation was significantly reduced. In this case, the SMCs density in the artery media measured from the HE-stained specimen was 20% lower than that in the reference artery. According to the thermal damage calculation, it was estimated that the SMCs lethality in artery media after the short-term heating angioplasty was 20% in the case of 75°C as the peak balloon temperature. We demonstrated that the short-term heating dilatation reduced the number of SMCs in artery media. We think this SMCs reduction might contribute to the suppression of chronic neointimal hyperplasia.