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There is an ever-increasing demand for new imaging methods that can provide additional information about the coronary wall to better characterize and stratify high-risk plaques, and to guide interventional and pharmacologic management of patients with coronary artery disease. While there are a number of imaging modalities that facilitate the assessment of coronary artery pathology, this review paper focuses on intravascular optical imaging modalities that provide information on the microstructural, compositional, biochemical, biomechanical, and molecular features of coronary lesions and stents. The optical imaging modalities discussed include angioscopy, optical coherence tomography, polarization sensitive-optical coherence tomography, laser speckle imaging, near-infrared spectroscopy, time-resolved laser induced fluorescence spectroscopy, Raman spectroscopy, and near-infrared fluorescence molecular imaging. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in the evaluation of the coronary artery in the future. [Copyright &y& Elsevier]

Background: Random biopsy esophageal surveillance can be subject to sampling errors, resulting in diagnostic uncertainty. Optical frequency domain imaging (OFDI) is a high-speed, 3-dimensional endoscopic microscopy technique. When deployed through a balloon-centering catheter, OFDI can automatically image the entire distal esophagus (6.0 cm length) in approximately 2 minutes. Objective: To test a new platform for guided biopsy that allows the operator to select target regions of interest on an OFDI dataset, and then use a laser to mark the esophagus at corresponding locations. The specific goals include determining the optimal laser parameters, testing the accuracy of the laser marking process, evaluating the endoscopic visibility of the laser marks, and assessing the amount of mucosal damage produced by the laser. Design: Experimental study conducted in 5 swine in vivo. Setting: Massachusetts General Hospital. Main Outcome Measurements: Success rate, including endoscopic visibility of laser marks and accuracy of the laser marking process for selected target sites, and extent of the thermal damage caused by the laser marks. Results: All of the laser-induced marks were visible by endoscopy. Target locations were correctly marked with a success rate of 97.07% (95% confidence interval, 89.8%-99.7%). Thermal damage was limited to the superficial layers of the mucosa and was observed to partially heal within 2 days. Limitations: An animal study with artificially placed targets to simulate pathology. Conclusions: The study demonstrates that laser marking of esophageal sites identified in comprehensive OFDI datasets is feasible and can be performed with sufficient accuracy, precision, and visibility to guide biopsy in vivo. [Copyright &y& Elsevier]

Background: Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution. Objective: The goal of this study was to demonstrate large-area SECM in upper GI tissues and to determine whether the images contain microstructural information that is useful for pathologic diagnosis. Design: A feasibility study. Setting: Gastrointestinal Unit, Massachusetts General Hospital. Patients: Fifty biopsy samples from 36 patients undergoing routine EGD were imaged by SECM, in their entirety, immediately after their removal. Results: The microstructure seen in the SECM images was similar to that seen by histopathology. Gastric cardia mucosa was clearly differentiated from squamous mucosa. Gastric fundic/body type mucosa showed more tightly packed glands than gastric cardia mucosa. Fundic gland polyps showed cystically dilated glands lined with cuboidal epithelium. The presence of intraepithelial eosinophils was detected with the cells demonstrating a characteristic bilobed nucleus. Specialized intestinal metaplasia was identified by columnar epithelium and the presence of goblet cells. Barrett''s esophagus (BE) with dysplasia was differentiated from specialized intestinal metaplasia by the loss of nuclear polarity and disorganized glandular architecture. Limitations: Ex vivo, descriptive study. Conclusions: Large-area SECM images of gastroesophageal biopsy samples enabled the visualization of both subcellular and architectural features of various upper GI mucosal types and were similar to the corresponding histopathologic slides. These results suggest that the development of an endoscopic SECM probe is merited. [Copyright &y& Elsevier]

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 (∼7-μm axial resolution, ∼30-μm 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. [Copyright &y& Elsevier]

Background: Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas. Objective: The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (∼6.0 cm) in patients. Design: A pilot feasibility study. Setting: Massachusetts General Hospital. Patients: Twelve patients undergoing routine EGD. Results: Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion. Limitations: Inability to obtain direct correlation of OFDI data and histopathologic diagnoses. Conclusions: Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses. [Copyright &y& Elsevier]