HYBRID INTRAVASCULAR IMAGING Hector M GarciaGarcia MD MSc

HYBRID INTRAVASCULAR IMAGING Hector M. Garcia-Garcia MD, MSc, Ph. D, FESC, FACC Director, Angio and IVUS/NIRS corelab Chairman, Clinical Event Committee Confidential 2016

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Outline • IVUS and OCT combined catheters • Scanning fiber endoscope

Hybrid Imaging –IVUS/OCT 1. PROS: Excellent resolution (10 -20 um) enables more accurate visualization and reconstruction of luminal , strut and plaque morphology. 2. CONS: Limited penetration… 1. IVUS 1. PROS: Excellent penetration depth through blood and soft tissue, enabling estimation of vessel dimension, remodeling and plaque burden 2. CONS: Limited soft tissue contrast and resolution (>100 um)

Hybrid Imaging –IVUS/OCT The gray lines OCT signal through the optic fiber, blue lines signify electrical signals and red lines signify the trigger signals through electric wires. Schematic of IVUS-OCT imaging system and signal transmission system. (b) OCT and IVUS images obtained (c) The imaging catheter. Li. J, Ma. T et al

COMBINED IVUS-OCT CATHETERS Probe Size Probe Arrangement Probe Characteristics Image depth Image Axial resolution Frame Rate Technical Limitations Histological evidence 7. 2 Fr First reported Side by Side IVUS: 40 MHz OCT: 1310 nm NA IVUS: 38 um OCT: 8 um 1/s Large catheter size Poor image In vitro feasibility study in rabbit aorta 4 Fr (1 m long hybrid catheter) Side by side 90° apart IVUS: 42. 5 MHz OCT: 1325 nm OCT: 1 mm within tissue NA 5/s Increased artefacts/moderate image quality Low frame rate Poor co-registration in the case of NURD Qualitative validation in human cadavers First coplanar hybrid IVUS-OCT catheter to image human coronary atherosclerosis. 3. 6 Fr Sequential arrangement -2 mm apart. IVUS: 35 MHz OCT: NA IVUS: 4. 5 mm OCT: NA IVUS: 60 um OCT: 8 um 20/s Large catheter size Inaccurate registration of IVUS and OCT Feasibility study in human cadaver and in vivo in the aorta of the rabbit Back to back IVUS: 45 MHz OCT: NA NA NA 10/s Low image acquisition rate Feasibility study in human and swine cadavers NA NA 100/s None Feasibilty in preclinical in-vivo models 2. 7 Fr Plus fluorescence imaging for plaque characterization Built to minimize loss of coregistration caused by cardiac motion during pullback 3 Fr Co-linear ultrasound and optical beams Optics reside within the ultrasound transducer to IVUS: 40 MHz OCT: 1320 nm

COMBINED IVUS-OCT CATHETERS Catheterization and Cardiovascular Interventions 81: 494– 507 (2013)

COMBINED IVUS-OCT CATHETERS The hybrid IVUS-OCT catheter has the potential to harness the complementary advantages of both modalities and significantly improve the ability to better characterize plaques.

Outline • IVUS and OCT combined catheters • Scanning fiber endoscope

Scanning fiber endoscope excites tissues by blue, green and red lasers Savastano L. E. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017) Garcia-Garcia H. M. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017)

Scanning fiber endoscope excites tissues by blue, green and red lasers Backscattered (reflectance) light and fluorescent signal is collected by a ring of optical fibers located in the periphery of the scanner housing and shaft Savastano L. E. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017) Garcia-Garcia H. M. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017)

Scanning fiber endoscope excites tissues by blue, green and red lasers Savastano et al. demonstrated the first use of a novel multimodal endoscope technology to collect laser-induced reflectance and fluorescence simultaneously and perform structural and biological evaluation of atherosclerosis. Savastano L. E. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017) Garcia-Garcia H. M. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017)

Scanning fiber endoscope excites tissues by blue, green and red lasers Ulcerated Plaque: Punched-out lesion with irregular elevated borders at the carotid bifurcation on white-light system (k), red reflectance (l), and reflectance with green (m) and blue (n) channels. Note the speckled pattern in the crater of the ulcer with multiple irregular dots of strong autofluorescence in a background of very low autofluorescence [>75 points of difference in color-coded bar chart of pixel values of a line traced in (o), better appreciated in pseudocolor images (q)]. Histological Savastano L. E. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017) analysis of axial cut at the bifurcation reveals an atherosclerotic plaque [Movat’s Garcia-Garcia H. M. , et al. Nature Biomedical Engineering 1, Article number: 0023 (2017) stain, (r)] with necrotic debris, some of which appears calcified, and fibrin (s), with

Multimodal laser-based angioscopy: Conclusions 1. First intra-arterial forward-viewing device capabe of generate real time structural, chemical and biological images of the vascular surface. 2. Feasibility for in vivo endovascular endoscopy in an animal model with medium-sized arteries. 3. Potential to become a new platorm for research, diagnosis, prognosis and perhaps image-guided local therapy in cardiovascular disease.