Mireille Rosenberg

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.

OBJECTIVES The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. BACKGROUND Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. METHODS The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. RESULTS Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. CONCLUSIONS This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

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.

Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure

Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.

Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study

BACKGROUND Biopsy surveillance protocols for the assessment of Barretts esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. OBJECTIVE The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. DESIGN A pilot feasibility study. SETTING Massachusetts General Hospital. PATIENTS A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barretts esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. INTERVENTION Volumetric laser endomicroscopy. MAIN OUTCOME MEASUREMENTS Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. RESULTS There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. LIMITATIONS This is a single-center feasibility study with a limited number of patients. CONCLUSION Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01439633.).

Automated segmentation and characterization of esophageal wall in vivo by tethered capsule optical coherence tomography endomicroscopy

Optical coherence tomography (OCT) is an optical diagnostic modality that can acquire cross-sectional images of the microscopic structure of the esophagus, including Barretts esophagus (BE) and associated dysplasia. We developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires high-resolution images of entire gastrointestinal (GI) tract luminal organs. This device has a potential to become a screening method that identifies patients with an abnormal esophagus that should be further referred for upper endoscopy. Currently, the characterization of the OCT-TCE esophageal wall data set is performed manually, which is time-consuming and inefficient. Additionally, since the capsule optics optimally focus light approximately 500 µm outside the capsule wall and the best quality images are obtained when the tissue is in full contact with the capsule, it is crucial to provide feedback for the operator about tissue contact during the imaging procedure. In this study, we developed a fully automated algorithm for the segmentation of in vivo OCT-TCE data sets and characterization of the esophageal wall. The algorithm provides a two-dimensional representation of both the contact map from the data collected in human clinical studies as well as a tissue map depicting areas of BE with or without dysplasia. Results suggest that these techniques can potentially improve the current TCE data acquisition procedure and provide an efficient characterization of the diseased esophageal wall.

Imaging the upper gastrointestinal tract in unsedated patients using tethered capsule endomicroscopy.

Endoscopic examination of the upper gastrointestinal tract is costly, inconvenient, and typically requires that the patient be sedated.1 Standard video endoscopy only provides macroscopic information so small, focal biopsies are excised in order to obtain a microscopic tissue diagnosis. Because there are few reliable visible cues for Barrett’s esophagus and dysplasia, crucial diagnostic regions can be missed. In order to overcome these limitations of endoscopy, we have integrated a microscopic imaging technology into a tethered capsule that can be swallowed. This new method, which we term tethered capsule endomicroscopy, provides microscopic information from the entire esophagus as the pill passes through the GI tract.

Multi-laboratory inter-institute reproducibility study of IVOCT and IVUS assessments using published consensus document definitions.

AIMS The aim of this study was to investigate the reproducibility of intravascular optical coherence tomography (IVOCT) assessments, including a comparison to intravascular ultrasound (IVUS). Intra-observer and inter-observer variabilities of IVOCT have been previously described, whereas inter-institute reliability in multiple laboratories has never been systematically studied. METHODS AND RESULTS In 2 independent laboratories with intravascular imaging expertise, 100 randomized matched data sets of IVOCT and IVUS images were analysed by 4 independent observers according to published consensus document definitions. Intra-observer, inter-observer, and inter-institute variabilities of IVOCT qualitative and quantitative measurements vs. IVUS measurements were assessed. Minor inter- and intra-observer variability of both imaging techniques was observed for detailed qualitative and geometric analysis, except for inter-observer mixed plaque identification on IVUS (κ = 0.70) and for inter-observer fibrous cap thickness measurement reproducibility on IVOCT (ICC = 0.48). The magnitude of inter-institute measurement differences for IVOCT was statistically significantly less than that for IVUS concerning lumen cross-sectional area (CSA), maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters (P < 0.001, P < 0.001, P < 0.001, P = 0.02, P < 0.001, and P = 0.01, respectively). Minor inter-institute measurement variabilities using both techniques were also found for plaque identification. CONCLUSION In the measurement of lumen CSA, maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters by analysts from two different laboratories, reproducibility of IVOCT was more consistent than that of IVUS.

Tethered capsule endomicroscopy: from bench to bedside at a primary care practice

Abstract. Due to the relatively high cost and inconvenience of upper endoscopic biopsy and the rising incidence of esophageal adenocarcinoma, there is currently a need for an improved method for screening for Barrett’s esophagus. Ideally, such a test would be applied in the primary care setting and patients referred to endoscopy if the result is suspicious for Barrett’s. Tethered capsule endomicroscopy (TCE) is a recently developed technology that rapidly acquires microscopic images of the entire esophagus in unsedated subjects. Here, we present our first experience with clinical translation and feasibility of TCE in a primary care practice. The acceptance of the TCE device by the primary care clinical staff and patients shows the potential of this device to be useful as a screening tool for a broader population.

An automatic image processing algorithm for initiating and terminating intracoronary OFDI pullback

Intracoronary optical frequency domain imaging (OFDI) provides high resolution, three-dimensional views of coronary artery microstructure, but requires a non-occlusive saline/contrast purge to displace blood for clear artery views. Recent studies utilized manual pullback initiation/termination based on real-time image observation. Automated pullback initiation/termination by real-time OFDI signal analysis would enable more efficient data acquisition. We evaluate the use of simple imaging parameters to automatically and robustly differentiate between diagnostic-quality clear artery wall (CAW) versus blood-obstructed fields (BOF). Algorithms are tested using intracoronary OCT human data retrospectively and intracoronary OFDI swine and human data prospectively. In prospective analysis of OFDI swine data, the sensitivity and specificity of the ratio of second and first moments (contrast parameter) were 99.6% and 97.2%, respectively. In prospective analysis of OFDI clinical data, the contrast parameter yielded 96.0% sensitivity and 94.5% specificity. Accuracy improved further by analyzing sequential frames. These results indicate the algorithm may be utilized with intracoronary OFDI for initiating and terminating automated pullback and digital data recording.

Clinical Translation of Tethered Confocal Microscopy Capsule for Unsedated Diagnosis of Eosinophilic Esophagitis

Esophagogastroduodenoscopy (EGD) is a widely used procedure, posing significant financial burden on both healthcare systems and patients. Moreover, EGD is time consuming, sometimes difficult to tolerate, and suffers from an imperfect diagnostic yield as the limited number of collected biopsies does not represent the whole organ. In this paper, we report on technological and clinical feasibility of a swallowable tethered endomicroscopy capsule, which is administered without sedation, to image large regions of esophageal and gastric mucosa at the cellular level. To demonstrate imaging capabilities, we conducted a human pilot study (n = 17) on Eosinophilic Esophagitis (EoE) patients and healthy volunteers from which representative cases are presented and discussed. Results indicate that, compared to endoscopic biopsy, unsedated tethered capsule endomicroscopy obtains orders of magnitude more cellular information while successfully resolving characteristic tissue microscopic features such as stratified squamous epithelium, lamina propria papillae, intraepithelial eosinophils, and gastric cardia and body/fundic mucosa epithelia. Based on the major import of whole organ, cellular-level microscopy to obviate sampling error and the clear cost and convenience advantages of unsedated procedure, we believe that this tool has the potential to become a simpler and more effective device for diagnosing and monitoring the therapeutic response of EoE and other esophageal diseases.