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

2. No disclosures

3. Outline
IVUS and OCT combined catheters
Scanning fiber endoscope

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

5. 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

6. COMBINED IVUS-OCT CATHETERS
Probe Size
Probe Arrangement
Probe Characteristics
Image depth
Image Axial resolution
Frame Rate
Technical Limitations
Histological
evidence
7.2Fr
First reported
Side by Side
IVUS: 40 MHz
OCT: 1310nm NA
IVUS: 38um
OCT: 8um
1/s
Large catheter size
Poor image
In vitro feasibility study in rabbit aorta
4Fr
(1m long hybrid catheter)
Side by side 90° apart
IVUS: 42.5 MHz
OCT: 1325nm
OCT: 1mm
within tissue
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.
3.6Fr
Sequential arrangement
-2mm apart.
IVUS: 35 MHz
OCT: NA
Plus fluorescence imaging for plaque characterization
IVUS: 4.5mm
IVUS: 60um
20/s
Inaccurate registration of IVUS and OCT
Feasibility study in human cadaver and in vivo in the aorta of the rabbit
2.7Fr
Back to back
IVUS: 45MHz
Built to minimize loss of co-registration caused by cardiac motion during pullback
10/s
Low image acquisition rate
Feasibility study in human and swine cadavers
3Fr
Co-linear ultrasound and optical beams
Optics reside within the ultrasound transducer to facilitate miniaturization, while the IVUS and OCT beams travel in the same direction
OCT: 1320nm
100/s
None
Feasibilty in pre-clinical in-vivo models

7. COMBINED IVUS-OCT CATHETERS
Pathological intimal thickening. (A) Histology—Movat’s pentachrome. (B) Histology—Hematoxylin and Eosin. (C) Intravascular ultrasound image (IVUS). (D) Optical coherence tomography (OCT). Histology (A,B) demonstrates thickening of the intima with distinct layers. IVUS (C) depicts concentric thickening while optical coherence tomography (D) demonstrates homogenous, signal rich region consistent with circumferential intimal hyperplasia. The relatively good signal penetration with OCT (over 500 lm deep) around the entire circumference is consistent with the absence of lipid pools near the luminal surface. Brian H Li et al
(A &D) Luminal shape consistency and plaque location when compared to histology and micro-CT images.(B) IVUS was able to penetrate the full thickness of the vessel wall, except in regions with extensive calcification.
(C) Higher resolution and contrast shown on OCT over IVUS, while OCT signal penetration through tissue was limited to approximately 1 mm. Furthermore, the OCT system used in this experiment was configured such that it could only image objects that were between 0.75 and 2.0 mm from the center of the catheter without producing aliasing artifacts.
Catheterization and Cardiovascular Interventions 81:494–507 (2013)

8. COMBINED IVUS-OCT CATHETERS
Pathological intimal thickening. (A) Histology—Movat’s pentachrome. (B) Histology—Hematoxylin and Eosin. (C) Intravascular ultrasound image (IVUS). (D) Optical coherence tomography (OCT). Histology (A,B) demonstrates thickening of the intima with distinct layers. IVUS (C) depicts concentric thickening while optical coherence tomography (D) demonstrates homogenous, signal rich region consistent with circumferential intimal hyperplasia. The relatively good signal penetration with OCT (over 500 lm deep) around the entire circumference is consistent with the absence of lipid pools near the luminal surface. Brian H Li et al
(A &D) Luminal shape consistency and plaque location when compared to histology and micro-CT images.(B) IVUS was able to penetrate the full thickness of the vessel wall, except in regions with extensive calcification.
(C) Higher resolution and contrast shown on OCT over IVUS, while OCT signal penetration through tissue was limited to approximately 1 mm. Furthermore, the OCT system used in this experiment was configured such that it could only image objects that were between 0.75 and 2.0 mm from the center of the catheter without producing aliasing artifacts.
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.

9. Outline
IVUS and OCT combined catheters
Scanning fiber endoscope

10. 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)

11. 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)

12. 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)

13. 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 analysis of axial cut at the bifurcation reveals an atherosclerotic plaque [Movat’s stain, (r)] with necrotic debris, some of which appears calcified, and fibrin (s), with highly heterogenous autofluorescence signal on confocal microscopy (t). Ruptured Plaque with Intraluminal Thrombus: Left subclavian artery (SCA) and left vertebral artery (VA) of a man with a large left-sided stroke [brain MRI, (u)] secondary to artery-to-artery embolic occlusion of distal left vertebral artery and basilar artery [arrows in anteroposterior cerebral angiogram, (v)]. Computed tomographic angiography showed atherosclerotic plaque at origin of the vertebral artery, associated with extensive luminal defect likely caused by thrombus [arrow, (w)]. At time of autopsy, left subclavian artery and vertebral artery were harvested and multimodal endovascular scanning fiber angiography was performed. A sub-occlusive lesion with preserved reflectance and minimal fluorescence was found to extend distally into vertebral artery (x-z). Histological analysis revealed an organized chronic intraluminal thrombus associated with a complicated plaque [Movat’s pentachrome, (a’) and insert (b’)], with significant intraplaque vascularization, commonly resulting from organized thrombus/hemorrhage. The thrombus has very low autofluorescence on confocal microscopy in comparison with the underlying fibroatheroma (c’). Scanning fiber angiography analysis of distal vertebral artery revealed an occlusive lesion with negligible reflectance and autofluorescence (d’-e’) corresponding to acute intraluminal thrombus (f’) with absent fluorescence signal in confocal microscopy (g’). In the boxplot ANOVA model for log-transformed fluorescent target-to-background ratio comparison between different pathological diagnoses, all diagnoses had target-to-background ratios <0 except ulcerated plaque (h’).
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)

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