Pranav M. Patel, MD, FACC, FSCAI Chief, Division of Cardiology

Director, Cardiac Cath Lab & CCU University of California, Irvine

Division of Cardiology

Cath Lab Essentials: IVUS & OCT

Different Views of Atherosclerosis

Normal vessel

Minimal CAD

CAD Progression

Artery can compensate for

up to 40% plaque volume

(lumen size remains constant)

Artery at maximum

expansion:

lumen narrows

Severe CAD

Moderate CAD

Glagov S et al, N Engl J Med, 1987.

Glagov Hypothesis and Patient

Type A Luminal obstruction in CAD occurs late

Plaque Severity Vs. Stability

lumen

Small lipid core

Stable Plaque

Severe Stenosis

Unstable Plaque

Mild Stenosis lumen lipid

Thick fibrous cap

Stable Plaque

lumen

small

lipid core

thick fibrous cap

Unstable Plaque

Ruptured Plaque with Thrombosis

thrombus

Large

lipid core

thin fibrous cap

Lipid Core Plaque

Thrombus

Fatal thrombus within a

drug-eluting stent located

over a

lipid core plaque.

Adapted from Nakazawa et al.

Circulation 116, No. 16 page II-628,

Delayed Healing in Acute MI

Coronary Artery Disease

James E. Muller, MD

CEO, InfraReDx, Inc.

Coronary Calcium makes lesion and lumen diameter

difficult to assess

Coronary

CTA

CTA : Positive remodeling (+), Soft plaque (+),

Fibrous plaque (+), Calcification (-)

Motoyama et al. JACC 2007

LAD in ACS

Nissen. Circulation 103 (2001)

IVUS: vessel lumen

95% RCA s/p successful PCI; left system angiographically normal

Nissen. Am J Cardiol 87 (2001)

Diagnose concomitant undiagnosed

disease

“Stable” plaque

with thick fibrous

cap with small

lipid core

“Vulnerable”

plaque with thin

fibrous cap and

large lipid core

Potentially diagnose stable vs. vulnerable plaques

IVUS-derived TCFA:

(i) plaque burden > 40

(ii) the presence of

confluent necrotic core of

>10%, and

(iii) no evidence of an

overlying fibrous cap as

previously described by

Rodriguez-Granillo et al.

J Am Coll Cardiol

2005;46:2038–2042.

Calvert P A et al. Heart 2011;97:A2-A2

Copyright © BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.

(A) Post-mortem histology demonstrated coronary segment with stent struts but no

significant necrotic core.

(B) Co-registered VH-IVUS image showing stent struts mistaken for calcium with necrotic core

artefact

Obaid D R et al. Heart 2012;98:A16-A16

Copyright © BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.

NIR Spectroscopy for VP Detection

Emits near-infrared laser

light inside the artery

Forms an image from

how much is absorbed

Picture of the contents

and dimensions of lipids

in the vessel walls.

Gardner, C. M. et al. J Am Coll Cardiol Img 2008;1:638-648

A NIRS Scan Correlates Well to Histologic Findings in Coronary Artery From an 85-Year-

Old Male With a History of MI

Gardner, C. M. et al. J Am Coll Cardiol Img 2008;1:638-648

A Chemogram From a 45-Year-Old Female Who Died of Anoxia

Clinical Case - What Stent

Length? 57 yr old male with stable

exertional angina

Post Stent

4.0 x 28mm Xience DES

STENT

James E. Muller, MD

CEO, InfraReDx, Inc.

NIRS-IVUS combination

NIRS imaging post

stenting revealed that

the lipid core,

represented by the

yellow on the

Chemogram, was no

longer present

Post-stenting

and no-reflow

Pre-stenting

Intravascular Ultrasound and Optical Coherence

Tomographic Imaging

IVUS Resolution = 150 microns

OCT Resolution = 10 microns

Figure 3. Complete tissue coverage

between the vessel lumen (dark area) and a

half-dozen stent struts (brightest objects) in

this OCT image demonstrate good healing.

(Image courtesy LightLab Imaging.)

Figure 2. OCT highlights in-stent

restenosis in a patient who has just

undergone balloon dilatation. (Image

courtesy LightLab Imaging.)

OCT

Image Orientation

Normal coronary artery

Uniform silhouette

3 layers visible in vessel wall

Data on file at LLI

Imaging catheter

Guidewire shadow

Adventitia

Media

Intima

3

Thin Cap Fibroatheroma

TCFA was defined as a plaque with fibrous cap <65μm thick.

The high resolution of OCT has an ability to identify thin-fibrous cap

clearly even if it is less than 100μm.

Giulio Guagliumi MD

Ospedali Riuniti di Bergamo, Italy

False True

Guidewire Location

False lumen

In pullback imaging,

false lumen diverges

from/joins the true

lumen

With OCT identify what

is the true vessel wall

6

Data on file at LLI

Measurements - Restenosis

Area calculations

% area stenosis

Minimum and maximum

diameter within area

Length calculations

% diameter stenosis

8

Data on file at LLI

Measurement of in-stent restenosis

Vessel Wall Damage

Edge dissection

A disruption of the vessel

luminal surface in the edge

region

Easy to interpret using

cross-sectional and longitudinal

views

10

Data on file at LLI

Image: Columbia Presbyterian Hospital

Neointimal Hyperplasia

In-stent restenosis

Thick layer between stent

struts and lumen

15

Data on file at LLI

Stent struts

Thrombosis

16

Data on file at LLI

Thrombus

Stent struts

Data on file at LLI

Thrombus – Red (Acute)

Thrombus – red

Absorbs near-infrared light

High backscatter on

surface due to signal

attenuation

Appears as a bright mass

Shadow (cannot see

behind it)

17

Data on file at LLI

Red thrombus Data on file at LLI

OCT Characteristics

OCT

Combined strengths of OCT and IVUS

IVUS

OCT

Combined strengths of OCT and IVUS

IVUS

Figure : Morphology of the patient's plaque with IVUS-derived,

thin-capped fibroatheroma

Ramcharitar S et al. (2009) First case of stenting of a vulnerable plaque in the SECRITT I trial—the

dawn of a new era?

Nat Rev Cardiol doi:10.1038/nrcardio.2009.34

Foam

cells

Calcified plaques

Lipid plaque

Two images are better than One

Integrated hybrid OCT/IVUS from Patel-Chen Labs at UCI

inti

ma

low

ultrasound

echo

＊

lipid

pool

US O

CT

＊

Fibrous cap

H&

E

Necrotic

tissue

Foam

cells

Fibrous

cap

Scale bar:0.5mm

＊in US image ultrasound pulse ring down effect and the reflection of catheter sheath.

＊ in OCT image caused by the high back reflection from the interface between the prism and

GRIN lens

Integrated intravascular OCT/US from Patel-Chen Labs at UCI

Intravascular ultrasound (IVUS)

Optical coherence tomography (OCT)

IVUS: (full thickness of plaque) FD-OCT: (cap thickness)

Deep penetration

(5 mm)

No need for

blood clearance

Combined imaging

of Vulnerable Plaque

High resolution

(2-15 μm)

Shallow penetration

(1-2 mm)

Poor resolution

(50-300 μm)

OCT/IVUS: Ideal Combination

The future of intravascular imaging? Elastography allows us to measure

strain patterns in tissues (and vulnerable plaques)

image for the agarose film under ARF from an ultrasound transducer with an AM modulation of 500 Hz, is shown in Fig. 4b. The phase change amplitude averaged over depth is shown in Fig. 4c. The boundary (red arrow) between two sides of the phantom with different concentrations can be clearly visualized in Figs. 4b and 4c.

Fig. 4 (a) OCT intensity image of side-by-side agarose phantom; (b) OCE image with 500 Hz AM modulation ARF excitation; (c) phase amplitude

averaged over the depth of tissue. Red arrow indicates the boundary between two sides of 7% and 3.5% agarose film. Total length: 6 mm [73].

A linear relationship between the voltage applied to the ARF transducer and the phase shift measured is observed (Fig. 5). Since the ARF acting on both sides of the phantom was the same, the ratio of Young’s moduli between two sides can be quantified from the ratio of the measured phase shifts. The ratio of Young’s moduli between the 7% and 3.5% agarose phantom measured by phase shifts is 1:3.06, which is consistent with the value measured using a standard compression test (1:3.17). We also performed 3-D imaging of this phantom (Fig. 6) [73]. The OCT image in Fig. 6a shows no differentiation between two sides of the phantom with different stiffness. However, the 3-D PR-ARF-OCE image (Fig. 6b) clearly delineates the two materials with different stiffness. These preliminary results clearly indicate that PR-ARF-OCE image can be used to quantify mechanical properties of a tissue.

Fig. 5. Axial displacement

vs. pre-amplified voltage to the transducer

Fig. 6. (a) 3D OCT imaging of an agarose tissue mimicking

phantom; (b) PR-ARF-OCE image; (c) fused OCT and PR-ARF-OCE image. The phantom is excited with a 500 Hz square wave modulated ARF. Scale bar: 1 mm

Fig. 7 PR-ARF-OCE image of human coronary

artery. (a) OCT image; (b) PR-ARF-OCE image; (c)

histological image (corresponding to across blue line

location in (a); and (d) close-up view of the

atherosclerotic lesion. Scale bars: 1mm

To demonstrate the potential of this technology in imaging plaque, we have performed preliminary imaging of a section of atherosclerotic human coronary artery with PA-ARF-OCE (Fig. 7) [73]. An OCT intensity image (Fig. 7a) provides a general morphological view of the tissue with no obvious evidence of the presence of atherosclerosis. The region indicated by the white arrow in the ARF-OCE image (Fig. 7b) is characterized by less vibration and therefore represents less elastic and stiffer tissue, such as plaques. The strong vibration representing softer tissue is indicated by yellow arrows. The stiffer tissue, in this case atherosclerotic plaque, is clearly distinguished from the softer (usually normal) tissue area highlighted by brighter colors. This preliminary result clearly shows that PR-ARF-OCE can delineate diseased tissue from normal tissue and has the potential to quantitatively characterize tissue mechanical properties.

3C2 Research Method and Experiment

3C2.1. Design and develop integrated OCT/US/PR-ARF-OCE imaging probe (Aim 1)

(i) Develop US transducers using single crystal composites: A focused ring-shaped US transducer with a small center hole will be fabricated at the lab of Drs. Zhou and Shung at USC, an NIH US Transducer Resource Center. The PMN-PT single crystal composite will be used to fabricate transducers in the frequency range of 30-50 MHz because the composite materials can significantly improve device performance by increasing the effective electromechanical coupling coefficient (k33(eff)) up to 0.9 [92], which is the highest piezoelectric coupling coefficient, as well as reducing the effective dielectric constant and acoustic impedance. An increase in keff will result in greater transducer sensitivity and bandwidth for single crystal transducers. Decreases in the dielectric constant and acoustic impedance will also increase transducer sensitivity by improving impedance match to the electric and acoustic loads on the transducer, which are the most desirable for building miniature

Fig. 8. The schematic diagrams of the ring transducer with

inner hole diameter of 0.4 mm, and outer diameter of 1.0

mm and cross section of focused ring transducer

Z. Chen/P Patel. UC Irvine . Acute radiation force –Optical Coherence elastography

Thanks!

End – questions?