Milen Shishkov

Characterization of Human Atherosclerosis by Optical Coherence Tomography

Background—High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 &mgr;m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. Methods and Results—OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, &kgr;=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (&kgr; values of 0.88 and 0.91, respectively). Conclusions—Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.

Visualization of Coronary Atherosclerotic Plaques in Patients Using Optical Coherence Tomography: Comparison With Intravascular Ultrasound

OBJECTIVES The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.

In Vivo Characterization of Coronary Atherosclerotic Plaque by Use of Optical Coherence Tomography

Background—The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution (≈10 μm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. Methods and Results—Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non–ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying ≥2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively (P=0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 μm, respectively (P=0.034). The frequency of thin-cap fibroatheroma (defined by lipid-rich plaque with cap thickness ≤65 μm) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group (P=0.012). No procedure-related complications occurred. Conclusions—OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations.

Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography

Background—Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of ≈10 &mgr;m. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. Methods and Results—OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density (r =0.84, P <0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density (r =−0.56, P <0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing >10% CD68 staining. Conclusions—The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients.

Evaluation of intracoronary stenting by intravascular optical coherence tomography

Background: Conventional contrast cineangiography and intravascular ultrasound (IVUS) provide a limited definition of vessel microstructure and are unable to evaluate dissection, tissue prolapse, and stent apposition on a size scale less than 100 μm. Objective: To evaluate the use of intravascular optical coherence tomography (OCT) to assess the coronary arteries in patients undergoing coronary stenting. Methods: OCT was employed in patients having percutaneous coronary interventions. Images were obtained before initial balloon dilatation and following stent deployment, and were evaluated for vessel dissection, tissue prolapse, stent apposition, and stent asymmetry. IVUS images were obtained before OCT, using an automatic pull back device. Results: 42 stents were imaged in 39 patients without complications. Dissection, prolapse, and incomplete stent apposition were observed more often with OCT than with IVUS. Vessel dissection was identified in eight stents by OCT and two by IVUS. Tissue prolapse was identified in 29 stents by OCT and 12 by IVUS; the extent of the prolapse (mean (SD)) was 242 (156) μm by OCT and 400 (100) μm by IVUS. Incomplete stent apposition was observed in seven stents by OCT and three by IVUS. Irregular strut separation was identified in 18 stents by both OCT and IVUS. Conclusions: Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS.

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging

OBJECTIVES We present the first clinical experience with intracoronary optical frequency domain imaging (OFDI) in human patients. BACKGROUND Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (approximately 7-microm axial resolution, approximately 30-microm transverse resolution), cross-sectional images of the coronary wall. Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments. OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates. The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge. METHODS Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment. Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s. After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered. RESULTS Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 3.0 to 7.0 cm at pullback rates ranging from 5 to 20 mm/s. A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia. There were no complications of the OFDI procedure. CONCLUSIONS Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients. Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease.

Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo

Advancing understanding of human coronary artery disease requires new methods that can be used in patients for studying atherosclerotic plaque microstructure in relation to the molecular mechanisms that underlie its initiation, progression and clinical complications, including myocardial infarction and sudden cardiac death. Here we report a dual-modality intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo using a combination of optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging. By providing simultaneous molecular information in the context of the surrounding tissue microstructure, this new catheter could provide new opportunities for investigating coronary atherosclerosis and stent healing and for identifying high-risk biological and structural coronary arterial plaques in vivo.

Spectrally encoded miniature endoscopy

A method for performing miniature endoscopy with a high number of resolvable points is presented. This approach, spectrally encoded endoscopy (SEE), uses a broad-bandwidth light source and a diffraction grating to simultaneously detected the reflectivity at multiple points along a transverse line within the sample. As opposed to images from miniature optical fiber bundle endoscopes, the number of resolvable points in SEE images is dependent on the spectral width and the groove density of the diffraction grating. We acquired images of a human finger in vivo, using a 550-mu;m -diameter SEE system to demonstrate the feasibility of this technique.

Porcine coronary imaging in vivo by optical coherence tomography.

OBJECTIVE A high-resolution coronary artery imaging modality has the potential to address important diagnostic and management problems in cardiology. Optical coherence tomography (OCT) is a promising new optical imaging technique with a resolution of approximately 10 microm. The purpose of this study was to use a new OCT catheter to demonstrate the feasibility of performing OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in vivo. METHODS AND RESULTS Normal coronary arteries, intimal dissections, and stents were imaged in five swine with OCT and compared with intravascular ultrasound (IVUS). In the normal coronary arteries, visualization of all of the layers of the vessel wall was achieved with a saline flush, including the intima which was not identified by IVUS. Following dissection, detailed layered structures including intimal flaps, intimal defects, and disruption of the medial wall were visualized by OCT. IVUS failed to show clear evidence of intimal and medial disruption. Finally, the microanatomic relationships between stents and the vessel walls were clearly identified only by OCT. CONCLUSIONS In this preliminary experiment, we have demonstrated that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents is feasible, and allows identification of clinically relevant coronary artery morphology with high-resolution and contrast.