1. POSTER 2 7:17 – 7:24 Validation of Novel Combined IVUS/OCT Catheter using Ex-Vivo Samples: Qualitative Examination of Human Cadaver Specimens Presenter: Jonathan Toma Authors: Jonathan Toma, MD, FRCPC; Brian Li, MD, BASc; Natasha Alvez-Kotsev, PhD; Mark Harduar, BEng, MASc; Jill Weyers, PhD; Andrew Lim; Peter Faure; Anna Zavodni, MD, FRCPC; Jagdish Buthany, MBBS, MS, FRCPC; Brian Courtney MD, MSEE, FRCPC

2. Validation of Novel Combined IVUS-OCT Catheter using Ex-Vivo Samples: Qualitative Examination of Human Cadaver Specimens A custom-built, rotational, 3 French, hybrid IVUS-OCT catheter was used during the experiment for purposes of image acquisition. The imaging head contained a 40 MHz ultrasound transducer, and an embedded OCT fiber-optic imaging cable to generate coincidental imaging beams (Fig 1). The coaxial imaging setup allows the images to be inherently co-registered. The imaging assembly was housed in a custom-built microcatheter sheath, and rotated / pulled longitudinally by the use of a custom torque cable. The rotational and pullback speeds could be manually controlled by the operator, however pullback rates of 0.5 and 1.0 mm / second were most often chosen. The operator could also manually control the following settings: ultrasound frequency, signal gain, frame rate, and OCT mirror length. Common defaults for these parameters were often employed. Images were acquired and stored using custom software developed by Conavi Medical Technologies Inc™ on their imaging console. Images could be processed and reviewed using their proprietary imaging software (Snowy Owl™). Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) serve as invaluable tools in the cardiac catheterization laboratory for the assessment of coronary vessel wall pathology. Intravascular ultrasound in capable of penetrating both blood and soft tissue in real-time, at imaging depths of 5-7 mm, with a resolution of 80-200 micrometers (μm). It is capable of delineating the three major vessel wall layers (intima, media, adventitia) at any position in the coronary vascular tree, and does not require the use of contrast media to improve tissue characterization. While the lack of contrast media, and depth of penetration are major advantages of IVUS, soft tissue contrast is unfortunately poor, and IVUS suffers from imaging artifacts, such as ring-down artifacts closer to the transducer sheath and reflections from the catheter sheath. The ultrasound transducer is unfortunately also incapable of penetrating through calcifications, which leads to acoustic shadowing artifacts with IVUS. The presence of such artifacts, however, is highly sensitive for the presence of calcification. Optical coherence tomography uses an infrared spectrum source of light to obtain tomographic images in a smaller field-of-view compared to IVUS (1-2 mm compared to 5-7 mm) [2]. The spatial resolution of OCT is however 5-10 times greater than IVUS (10-20 μm vs. 80-200 μm), with greatly improved soft tissue characterization. OCT provides superior imaging of lipid-rich plaques, and calcifications are delineated with sharply-defined borders [3]. Unfortunately, in clinical scenarios, OCT is often limited by its lack of imaging depth, tissue penetration, and the requirement for contrast use to clear blood from the imaging field. In this study, we present the results of a novel combined IVUS-OCT catheter in explanted human cadaver coronary specimens. Results Background: Intravascular imaging technologies have proven to be invaluable tools in assessing coronary vessel pathology in the cardiac catheterization laboratory. The use of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging techniques have well-known individual strengths, however few studies have presented the benefits of their combined use [1]. In this study, we present the results of a novel IVUS- OCT catheter used in ex-vivo samples of human cadavers. Methods: A custom-built, rotational, 3-French, hybrid IVUS-OCT imaging catheter was used for image acquisition. A 40 MHz ultrasound transducer at the tip of the catheter contains an embedded OCT fiber optic cable to generate coincident imaging beams (Fig 1). The combined catheter is capable of obtaining simultaneous co-registered IVUS and OCT images in a single pullback. Explanted human cadaver heart specimens were obtained from the pathology laboratory at University Health Network (UHN). Ethics approval for tissue collection and image acquisition were obtained from the Sunnybrook Research Institute and UHN. The specimens were perfused in a formalin solution prior to imaging. Samples of major epicardial coronary vessels were excised from the explanted hearts. Simultaneous IVUS and OCT images were acquired from the samples immersed in saline solution. Pathology slides were prepared with hemotoxylin/eosin (H&E) staining at UHN. Results: Six explanted coronary samples were excised from two human autopsy specimens. Cross-sectional IVUS-OCT images were obtained from the length of each sample. Two to six representative cross-sections per vessel were processed for histological examination using H&E staining. Anatomic features observed in the vessel by IVUS, OCT, and histology, including the luminal border, plaque morphology, and the presence of calcification, were compared qualitatively. As seen in Figure 2, the calcium content of an atheroma can be easily appreciated on OCT, and confirmed by area of acoustic shadowing by IVUS. As seen in Figure 3, the vessel wall architecture, and characteristics of plaque outside the visual range of OCT are well appreciated by IVUS. Conclusions: In a series of explanted human cadaver coronaries, IVUS and OCT served as complimentary imaging modalities, and their combined use contributed to a more detailed understanding of vessel wall pathology, as compared with histology. Jonathan Toma, MD, FRCPC 1 ; Brian Li, MD, BASc 1,2 ; Natasha Alves-Kotzev, PhD 1 ; Mark Harduar, BEng, MASc 2 ; Jill Weyers, PhD 1 ; Andrew Lim 1,3 ; Peter Faure, PA 4 ; Anna Zavodni, MD, FRCPC 1 ; Jagdish Butany, MBBS, MS, FRCPC 4 ; Brian Courtney MD, MSEE, FRCPC 1,2 1. Sunnybrook Health Sciences Centre, University of Toronto; 2. Conavi Medical Technologies Inc, Toronto, ON; 3. Division of Engineering Science, University of Toronto; 4. University Health Network, University of Toronto Ethics approval for tissue collection and image acquisition were obtained from the Sunnybrook Research Institute (SRI) and University Health Network (UHN). Ex-vivo heart specimens were obtained from the pathology department at UHN through Dr. Jagdish Butany. Two ex-vivo human specimens were obtained for the purpose of our experiment. Explanted hearts were obtained on the day of autopsy, and perfused in a formalin solution for 30 minutes prior to transportation to Sunnybrook. The explanted hearts underwent cardiac CT imaging at Sunnybrook (not presented in this abstract) prior to coronary vessel dissection as part of our research protocol. The major epicardial coronary vessels were excised from the explanted heart by manual dissection. A total of six 10-20 cm coronary sections were obtained form the two cadaver samples. Intracoronary imaging was performed on the excised samples using a custom combined IVUS-OCT catheter, provided by Conavi Medical Technologies™. Images were acquired while the samples were immersed in a room-temperature saline solution. Histology slides were prepared by the pathology department at UHN, using hemotoxylin /eosin (H&E) staining. Histology slides were catalogued according to their anatomic position and were compared to the corresponding IVUS-OCT images using vessel wall landmarks. Co-registered IVUS and OCT images were acquired from the six explanted coronary samples. The images were compared to corresponding histology sections prepared by the UHN pathology department. Features such as lipid-rich plaque, lumen contour, and the presence of calcification close to the imaging catheter were well-appreciated by OCT imaging (Fig 2, left). The imaging findings correlated well with these features in the corresponding histology sections. The presence of lesion calcification was confirmed by the presence of acoustic shadowing by IVUS (Fig 2, right). IVUS demonstrated superior imaging depth as expected compared to OCT. It was useful in delineating the full vessel layer architecture (Fig 3, bottom right), and vessel wall details beyond the range of OCT. This was especially evident in larger vessel sections (>3 mm), and details found in the vessel wall furthest away form the imaging probe (Fig 3, 10 o’clock). Both IVUS and OCT images acquired during pullback were diagnostic quality, and suffered only minimally from common imaging artifacts, such as non-uniform rotational distortion (NURD). Since the imaging probes were co-linear, there was no image processing required to obtain co-registered tomographic images. Several benefits of a combined IVUS-OCT imaging probe are demonstrated in our cadaver study. Although this represents a limited sample-size, the initial result of this study, and other small imaging studies performed by Drs. Courtney and Li are promising. In the near future, this work will be further validated by in-vivo human clinical trails. The combined imaging catheter is capable of acquiring either modality (IVUS, or OCT) alone if required by the operator. This is especially useful in cases requiring repeated intravascular imaging runs where the operator would prefer to limit contrast exposure by using IVUS alone for several runs. A potential major application of the combined imaging catheter will be in the placement of bioresorbable scaffolds (BVS), which require both wide field-of-view images for appropriate vessel sizing, and high resolution images of the individual struts to confirm approximation of the stent to the vessel wall. Abstract References: 1.Li, BH, et al. Catheterization and Cardiovascular Interventions. 2013. 81 (3):494-507. 2.Sawada T, et al. European Heart Journal 2008; 29(9):1136-1146. 3.Kubo T, et al. Journal of American College of Cardiology. 2007; 50:933–9. Disclosure: Conavi Medical Technologies Inc™ is the licensee of patent applications related to this abstract: Significant ownership interest: B.K. Courtney Modest Ownership interest: B.H. Li Employment: As indicated in author affiliations. The imaging devices used in this study are investigational and not approved for human use. Materials and Methods Continued Fig 1: Imaging core of a 3F hybrid IVUS / OCT catheter. The 40-MHz transducer at the tip is capable of obtaining IVUS images, while the circular optical lens protruding through the surface of the ultrasound transducer (top) provides intrinsically co-registered OCT images (bottom). The novel combined IVUS-OCT catheter presented in our study is capable of obtaining simultaneous co-registered IVUS and OCT images in a single-pullback, and combines the strength of each imaging modality. The high-resolution OCT imaging probe is capable of acquiring high-resolution near-field images with excellent soft tissue contrast. The full depth of the vessel wall, including all three vessel wall layers, as well as details beyond the range of OCT are visualized concurrently by IVUS. The complimentary imaging information provided by the two modalities enhances the operators understanding of vessel wall pathology, as seen in our study compared to corresponding histology sections. Fig 2: Coronary vessel cross-section by IVUS (right) and OCT (left) highlights the difference in imaging a calcified lesion (7-9 o’clock). OCT demonstrates high-resolution characterization of the calcified plaque, while IVUS is limited by corresponding acoustic shadowing. The presence of acoustic shadowing, however, confirms the calcium-content of the plaque. Fig 3: Histology section with hemotoxylin /eosin (H&E) staining (left), and corresponding OCT (top right) and IVUS (bottom right). Calcified coronary plaque in the mid-vessel wall appreciated by the presence of acoustic shadowing by IVUS (bottim right, 9-11 o’clock). Calcified lesion unfortunately out of range of OCT probe sat on the adjacent wall. The lesion is best appreciated by a combined imaging approach. Features ≥ 3 mm from the OCT probe are underappreciated due to imaging signal loss. Results Conclusions Discussion Introduction Materials and Methods IVUS Transducer OCT Light Source