Virtual Histology:From Theory to Vulnerable Plaque Detection

Shaoliang Chen MD

Nanjing First Hospital

Nanjing Cardiovascular Hospital

Acute coronary syndrome (ACS) commonly results from rupture of thin-cap fibroatheroma (TCFA), and occasionally results from erosion or calcified nodules.

Pathological features of TCFA are the presence of thin fibrous cap (<65μm) and a large lipid core.

Bruke AP et al. N Eng J Med.1997;336:1276-1282Falk E, et al. Circulation. 1995; 92: 657-671Virmani R, et al. Arterioscler Thromb Vasc Biol.2000; 20: 1262

IVUS – Listening through walls

LumenLumen

Lipid

VesselVessel

US signalUS signal

BackscatteredBackscatteredsignal or RF datasignal or RF data

BackscatteredBackscatteredsignal or RF datasignal or RF data

From Conventional IVUS imaging toFrom Conventional IVUS imaging toRadiofrequency Signal ProcessingRadiofrequency Signal Processing

• Conventional IVUS images are derived from the Conventional IVUS images are derived from the envelope of the RadioFrequency signal recorded by envelope of the RadioFrequency signal recorded by the US transducerthe US transducer

• More information can be derived from the processing More information can be derived from the processing of the raw RF signal itself for:of the raw RF signal itself for:

tissue characterizationtissue characterization evaluation of mechanical properties evaluation of mechanical properties assessment of flowassessment of flow

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5-150

-100

-50

0

50

100

150

bloodblood

wallwall

cathetercatheter

Virtual histology IVUS (VH-IVUS) uses amplitude and frequency of echoes

Especially, Necrotic Core component is knownto related to plaque vulnerability.

VH- IVUS differentiates coronaryplaque into 4 types

Frequency

Amplitude

“Conventional” IVUS Assessment of

Patients Presenting with ACS

Echolucent Plaque=Vulnerable Plaque?

Echolucent Plaque and VH

Echolucent Plaque and VH(n=53)

VH Phenotype of Echolucent Lesion

Echolucent Zone Adjacend of Echolucent Zone

Yang AHA 2008

Plaque Classification

1. “ Adaptive Intimal Thickening ”Plaque comprised of nearly allfibrous tissue (<5% of fibrofatty,calcification and/or NC plaque).

2. Pathological Intimal Thickening” –Mainly mixture of fibrous, fibrofatty(>5%), and necrotic core and somecalcified tissue <5%.

Plaque Classification“Fibro-Atheroma” – Fibrotic cap and significantNecrotic Core (confluent NC >5% of total plaquevolume) in fibrotic and/or fibrofatty tissue

It will very likely be that the most important goal is todifferentiate the FibroAtheroma plaque types from theother three plaque types during assessments of highrisk lesions for rupture.

Definition of thin-cap fibroatheroma (TCFA) by VH-IVUS

In at least 3 consecutive frames,(1)Percent Necrotic Core area to plaque area> 10%without evident overlying fibrous component(2)Percent plaque area to vessel area > 40%

Rodriguez-Granillo et al. J Am Coll Cardiol ,2005; 46:2038-42

Not only volume of NC, but also extent of NC contact with lumen are important.

Measurement of angle of NC contact with lumen (NCCL) wasperformed by a MATLABTM at Thoraxcenter, Erasmus MC, byDr. Garcia-Garcia HM.

Overall NC 31.1%Blue area;major NCCL, 28.3%purple plus blue areaTotal NCCL, 30.5%

Red line;angle of the major NCCL, 9°White and red line;angle of the total NCCL, 35°

Sawada T, Shite J et al Eur Heart J 2008; 29:1136-46

By necrotic core angle contact with lumen,VH-IVUS may estimate thin fibrous cap.However, IVUS can not visualize surface

fibrous cap due to limited resolution >100μm.

Thin-Cap FibroAtheroma (TCFA)

Courtesy of Renu Virmani

VH is entirely dependent on drawing accurate borders

Is VH-TCFA really vulnerable?

Recent MI Culprit lesion

Distal

Prox

Acute Plaque Rupture79 years old maleUnstable, DM (type II), hypertension, lipid disorder, prior MIVH IVUS; TCFA with three layers

52-yo Male with Abn Nuc Scan (DB)

Pre-interventionPost-intervention(Peak CK-MB releasemeasured 21.2 ng/ml)

Global VH-IVUS Registry

Serial VH Evaluation

Case ExamplesBaseline

TCFA TCFA TCFA PIT

Follow-upThCFA Fibrotic TCFA TCFA

Changes of plaque morphology

TCFA n=20

ThCFA n=93

PITn=62

65%10%

25%

90%

3%1%6%

71%

10%

Fibrotic/fibrocalcific plaques did not change.

Kubo T, JACC in press

Changes at MLA site

Plaque Area Lumen Area

Serial VH in Patients After Stenting:DES vs BMS

Kubo ACC2008

Serial VH of DESBaseline Follow-up

Stented segment

Reference segment

Serial VH of BMSBaseline Follow-up

Stented segment

Reference segment

Abutting Necrotic Core to the Lumen

* p<0.05Kubo ACC2008

The PROSPECT Trial700 pts with ACS

UA (with ECGΔ) or NSTEMI or STEMI >24o

1-2 vessel CAD undergoing PCIat up to 40 sites in U.S., Europe

PCI of culprit lesion(s)Successful and uncomplicated

Metabolic S.• Waist circum• Fast lipids• Fast glu• HgbA1C• Fast insulin• Creatinine

Biomarkers• Hs CRP• IL-6• sCD40L• MPO• TNFα• MMP9• Lp-PLA2• others

Formally enrolled

PI: Gregg W. StoneSponsor: Abbott Vascular; Partner: Volcano

3-vessel imaging post PCICulprit artery, followed by

non-culprit arteries

3-vessel imaging post PCICulprit artery, followed by

non-culprit arteries

PROSPECT MethodologyIVUS/VH Core Lab Analysis

Lesions are classified into 5 main sub-typesbased on VH composition

PROSPECT: Acute MI

PROSPECT: Acute MI

MLA: 6.1 mm2

PROSPECT: Baseline FeaturesN = 697

PROSPECT: Imaging SummaryLength of coronary arteries analyzed

PROSPECT: Imaging SummaryNon culprit angio and IVUS lesions

(LM, P/MLAD, PLCX and P/M/DRCA only)

PROSPECT: Imaging SummaryNon culprit angio and IVUS lesions

(LM, P/MLAD, PLCX and P/M/DRCA only)

PROSPECT: Imaging SummaryPer pt incidence of

IVUS lesions with MLA <4.0 mm2

PROSPECT: Imaging SummaryPresence of ≥1 VH lesion

subtypes (2765 lesions in 614 pts)

PROSPECT: Imaging Summary

Per patient incidence of VH-TCFAs

Longitudinal sections from 50 autopsy pts10.9 meters examined from 148 coronary arteries

44% of pts had ≥1 TCFA (range 0 - 6)Mean 0.46 TCFAs/pt

(0.55 vs. 0.38 in pts dying of CV ds. vs. other)- 1.21/pt in hearts with ruptured plaques -

Cheruvu PK et al. JACC 2007;50:940–9