plaque characterization and perfusion

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1 Plaque Characterization: Non-Calcified, Calcified, Partially Calcified Is that all CT can do? Suhny Abbara, MD Associate Professor, Harvard Medical School Director Cardiac Imaging Fellowship, Massachusetts General Hospital [email protected] Disclosures Medical Advisory Board Member Partners Imaging Perceptive Informatics Magellan Healthcare Consultant / Editing / Authoring (honoraria/options): Amirsys, Inc. Research Agreement/Funding BD Medical Bracco Diagnostics Member, Board of Directors (unpaid) Certification Board of Cardiovascular CT (CBCCT) Society of Cardiovascular Computed Tomography (SCCT) Iodinated Contrast not FDA approved for cardiac CT Life History of Atheromas Peter Libby. Nature 2002 (420): 868-874 Acute MI Remodeling index: D p D n “Vulnerable Plaque” Narula et al. Nature clinical practice cardiovascular medicine. 2008 (5)S2. Ruptured Plaque Vulnerable Plaque Characteristics of Vulnerable Plaques Plaque area Necrotic Core • Inflammation Spotty Calcification Positive Remodelling Vasa Vasorum • Hemorrhage Ulceration / Intraplaque Dye Penetation Plaque Detection & Area / Volume Quantification

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Page 1: Plaque Characterization and Perfusion

1

Plaque Characterization: Non-Calcified, Calcified, Partially Calcified

Is that all CT can do?

Suhny Abbara, MD

Associate Professor, Harvard Medical School

Director Cardiac Imaging Fellowship, Massachusetts General Hospital

[email protected]

Disclosures

• Medical Advisory Board Member – Partners Imaging

– Perceptive Informatics

– Magellan Healthcare

• Consultant / Editing / Authoring (honoraria/options):– Amirsys, Inc.

• Research Agreement/Funding– BD Medical

– Bracco Diagnostics

• Member, Board of Directors (unpaid)– Certification Board of Cardiovascular CT (CBCCT)

– Society of Cardiovascular Computed Tomography (SCCT)

Iodinated Contrast not FDA approved for cardiac CT

Life History of Atheromas

Peter Libby. Nature 2002 (420): 868-874

Acute MI

Remodeling index:

Dp

Dn

“Vulnerable Plaque”

Narula et al. Nature clinical practice cardiovascular medicine. 2008 (5)S2.

Ruptured Plaque

Vulnerable Plaque

Characteristics of Vulnerable Plaques

• Plaque area

• Necrotic Core

• Inflammation

• Spotty Calcification

• Positive Remodelling

• Vasa Vasorum

• Hemorrhage

• Ulceration / Intraplaque Dye Penetation

Plaque Detection&

Area / Volume Quantification

Suhny
Typewriter
Cardiac Function and Perfusion
Page 2: Plaque Characterization and Perfusion

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83 segments in 22 patients Sensitivity plaque per segment: 94% (all)

16-slice CT 53% (non-calcified)

Achenbach et al, Circulation 2003

58 vessels in 37 patients Sensitivity plaque detection: 85% (all)

16-slice CT 82% (non-calcified)

Leber et al, JACC 2004

36 vessels in 19 patients Sensitivity plaque detection: 90% (all)

64-slice CT 83% (non-calcified)

Leber et al, JACC 2006

685 segments in 45 patients Interobserver agreement: 93% (κ = 0.85)

16-slice CT (375 ms rotation)

Ferencik et al, JACC 2006

Coronary Plaque Detection: CT vs. IVUS

Courtesy Maros Ferencik

Partially Calcified

Plaque Calcification Types

Spotty calcificationNon calcified plaque

Calcified plaque Coarse calcification

Ex vivo

Coronary Arteries16 slice CT

Wall area

Ferencik et al. Radiology 2006

Measurements of Plaque Size

R = 0.67

Luminal area R = 0.92 Plaque area R = 0.55

* Moselewski et al. AJC 2004

In vivo:Plaque area

CT vs. IVUS“2D”

* Bamberg

Achenbach et al, Circulation 2004 Schepis et al, Heart 2010

Plaque volume

24 ± 35 mm3 vs. 43 ± 60 mm3

Plaque volume

89 ± 66 mm3 vs. 90 ± 73 mm3

In vivo: Plaque volume CT vs. IVUS “3D”

Courtesy Maros Ferencik

r=0.8, P<0.001

Remodeling Index

Page 3: Plaque Characterization and Perfusion

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Achenbach et al, JACC 2004

Remodeling Index

Coronary plaque characteristics in ACS and stable AP patients (n = 27)

Hoffmann et al, JACC 2006 Courtesy M. Ferencik, MGH

Culprit Lesions

in ACS (n=14)

Lesions in

SAP (n=13)p-value

Outer vessel area at

stenosis (mm2)21.2±7.0 15.6±10.5 0.01

Luminal area at

stenosis (mm2)3.7±1.6 2.1±1.4 0.18*

Plaque area (mm2) 17.5±5.9 13.5±10.7 0.02*

Degree of stenosis (%) 79.8±7.2 82.7±9.7 0.79*

RI 1.4±0.3 1.2±0.3 0.04

Plaque Volume / Remodeling Index

Prognostic Value?

Motoyama et al. JACC Vol. 54, No. 1, 2009 :49–57

Semi-quantitative Plaque Burden - Prognosis

0-5 vs. >5 of segments with plaque present

Min JK et al. JACC, 2007

N= 1127

All causemortality

<=5 SegmentsN=949

>5 SegmentsN=178

Low Attenuation Plaque

Napkin Ring Sign

Plaque Attenuation vs. IVUS

Motoyama. Circulation Journal Vol.71, 2007

Page 4: Plaque Characterization and Perfusion

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19 DEPARTMENT OF RADIOLOGY

Napkin-ring Sign: CT signature of high-risk coronary plaques?

Maurovich-Horvat P et al. JACCimg 2010 . Courtesy of CL Schlett, U Hoffmann

Cross Sections of a Coronary Plaque (Late Fibroatheroma)

Non-calcified plaque with a napkin-ring sign:

Low CT attenuation core (22.0 to 31.0 HU) &

Outer rim of high CT attenuation (35.0 to 76.0 HU).

Non-contrast enhanced CTA Contrast enhanced CTA Histopathology

Semiautomatic 3D Plaque Volume / Attenuation

Quantification

Voros S, et al. JACC-Intv 2011;4:198–208

Low Attenuation Plaque (LAP) Metrics

Prognostic Value?

Motoyama et al. JACC Vol. 54, No. 1, 2009 :49–57

ACS within

12 monthsNo ACS

Plaque Disruption

Ulceration and Intraplaque Dye Penetration

“Disrupted Plaques “

Madder, et al. Circ Cardiovasc Imaging. 2011; 4(2):105-13. Features of disrupted plaques by cCTA: correlates with invasively proven complex lesions.

ACP, CAC=0

CAC=0 Intraplaque Dye Penetration

Plaque Inflammation

Page 5: Plaque Characterization and Perfusion

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Potential Targets for Plaque Imaging

Libby et al. J Nucl Med May 2010; 51 (S1):33S-37

Molecular Imaging of Plaque Inflammation

Narula et al. Nature clinical practice cardiovascular medicine. 2008; (5)S2.

18F-FDG uptake indicates high cellular metabolic activity

� plaque inflammation

Stent for ACS. Inflammation

suggests culprit lesion was inflamed.Ahmed Tawakol, MGH

Indirect Plaque Inflammation Marker

Burdo, Lo, Abbara, Wei, Dorn, Preffer, Rosenberg, Subramanian, Tawakol, Williams, Grinspoon. The Journal of Infectious Diseases 2011. In Press.

Soluble CD163 (Monocyte/Macrophage Activation Marker)

is Associated with Noncalcified Coronary Plaque in HIV Patients

sCD163 levels correlated with # coronary segments with noncalcified plaque (r=0.23, p=0.02),

but not with # segments with calcified plaque nor Agatston calcium score.

Hyafil, Cornily, Rudd, Machac, Feldman, Fayad. JNuclMed June 2009;50(6): 959-65

Molecular Imaging of Inflammation -MDCT

• N1177 = iodinated nanoparticles dispersed with surfactant

• accumulate in macrophages

• atherosclerotic rabbit modelNative 2h post N1177

18F-FDG PET

3h post injection

Aortic enhancement N1177 + CT

Native 2h post N1177

Hyafil, Cornily, Rudd, Machac, Feldman, Fayad. JNuclMed June 2009;50(6): 959-65

Molecular Imaging of Inflammation - N1177

Immunohistochemistry

Axial slice corresponding to intense enhancement at N1177 CT

Strong macrophage infiltration

Axial slice corresponding to low enhancement at N1177 CT

Weak macrophage infiltration

Non-Calcified, Calcified, Partially Calcified

Is That All CT Can Do?

No CT can do much more:

• Positive Remodeling

• Area and Volume

• Low Attenuation

• Napkin Ring Sign

• Spotty calcification

• Ulceration and Intraplaque Dye Penetration

• Inflammation

Page 6: Plaque Characterization and Perfusion

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Non-Calcified, Calcified, Partially Calcified

Is That All CT Can Do?

But there are a few things CT cannot do:

• Identify “Thin Cap” in TCFA

• Intraplaque hemorrhage

• Vasa Vasorum

• Plaque Erosion

• Predict MACE vs. Asymptomatic Ruptures

Cardiac Function

Background

• Every retrospectively gated Coronary MDCT raw

dataset contains information about ventricular &

valvular function and myocardial perfusion

• Functional analysis requires additional

reconstruction of multiphasic datasets

• Perfusion analysis may be performed via post-

processing of the coronary CTA dataset (average weighted 5-10mm MPR)

Ventricular

Function

Multiple cardiac phases in one spatial location � cine images

Volumetric Ejection Fraction Calculation

• 4D workstation

• Threshold volumetric lumen detection

• Manual reference of mitral valve plane

Page 7: Plaque Characterization and Perfusion

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Wall ThickeningEF by 64-slice MDCT vs. SPECT

Bland-Altman Plot

Abbara S, Chow BJ, Pena A, et al. Assessment of left ventricular function with 16- and 64-slice multi-detector computed tomography. Eur J Radiol. 2008 Sep;67(3):481-6.

4D CT Ventriculogram Dyskinesia in LAD Territory � acute MI

Abbara S, Soni AV, Cury RC. Evaluation of cardiac function and valves by multidetector row computed tomography. Semin Roentgenol. 2008 Apr;43(2):145-53

Akinesia in RCA Territory - acute MI Regional Wall Motion Assessment

17 segment AHA classification – Cirquera et al. Circulation

apical

mid

base

Page 8: Plaque Characterization and Perfusion

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Regional Wall Motion Assessment

17 segment AHA classification

Navigating 4D Datasets

Navigating 4D Datasets

Comprehensive cCT analysis for ACS

• 102 patients, 34 AMI

• analyzed for myocardial perfusion defect (vs. SPECT & biomarkers), regional wallmotion defects (vs. TTE), and global LV function (vs TTE)

Cury RC, et al. Comprehensive assessment of myocardial perfusion defects, regional wall motion, and left ventricular function by using 64-section multidetector CT. Radiology. 2008 Aug;248(2):466-75.

Regional Wall Motion (RWM) - MDCT vs. TTE

Agreement between RWM by MDCT and:

• Clinical assessment of

AMI territory �K=0.82

• TTE (4-point scale, 17 myocardial

segments) � K=0.79Perfect agreement in 96% of segments (1664 out of 1734)

Cury RC, et al. Comprehensive assessment of myocardial perfusion defects, regional wall motion, and left ventricular function by using 64-section multidetector CT. Radiology. 2008 Aug;248(2):466-75.

54♂ 3 h substernal pain, pain relief after nitronegative 1st Troponin / CK-MB - non-diagnostic EKG

Page 9: Plaque Characterization and Perfusion

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54♂ 3 h substernal pain, pain relief after nitro

negative 1st Troponin / CK-MB - non-diagnostic EKG

RCALAD Occlusion

Functional Information from Cardiac CT

Perfusion Defect

RV

LV

54♂ 3 h substernal pain, pain relief after nitro

negative 1st Troponin / CK-MB - non-diagnostic EKG

Myocardial Akinesis

± LV thrombus

Culprit Lesion in LAD

Perfusion

Page 10: Plaque Characterization and Perfusion

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Hoffmann, U. et al. Radiology 2004;231:697-701

Porcine Infarct ModelLAD surgically ligated � non reperfusion infarct

Hoffmann, U. et al. Radiology 2004;231:697-701

Single phase

MDCT

TTC stained

gross pathology

Attenuation in infarcted area significantly lower than in normally perfused myocardium. p<0.01

Hoffmann, U. et al. Radiology 2004;231:697-701

Perfusion Imaging MRI vs. MDCT vs. Pathology

Mahnken Europ Rad 2005

MDCTMulti Phase

MRI

TTC stained

gross pathology

Single Perfusion Phase May Suffice

George et al. Investigative radiology (2007)

Acute MI

Nieman, Abbara, Cury et al, AHA 2005

Infarct size r = 0.73

MDCT DE-MRI

Page 11: Plaque Characterization and Perfusion

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Acute LAD Infarct Acute LCX Infarct

Delayed EnhancementMRI - DE CT perfusionCT - DE

Mahnken, JACC 2005

CT MRI

FIRST PASS

DELAYED

ENHANCEMENT

Microvascular Obstruction

Nieman et al.

N=21, 18male, 60 +/- 13 years

STEMI within 5days

MRI � FP, DE and CT � FP, DE

FP Perfusion

Defect Size

DE Microvascular

Obstruction Size

Page 12: Plaque Characterization and Perfusion

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Ruzsics, Lee, Powers, Flohr, Costello, Schoepf. Circulation 2008;117:1244-1245

Dual-energy CTIodine maps

80kV 140kV Dual Energy

Acute vs. chronic MI

Chronic MIChronic Infarct with Aneurysm

CT MRI

Contrast bolus60-80 cc

@ 4 cc/sec

AdenosinePerfusion

CT Scan

~5 minuteRecovery period

Contrast bolus60-80 cc

@ 4 cc/sec

Resting CTA

~10 minuteDelay

Delayed

CT

Stress/Rest Perfusion CT

Scan protocol, order, gating variations

Courtesy Brian Ghoshharjha, MGH

Stress Rest Delayed

Coregistered short-axis image sets

Stress Agent

Contrast

CT Procotol

Image Analysis

Courtesy Brian Ghoshharjha, MGH

Page 13: Plaque Characterization and Perfusion

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Blankstein, Okada, Ghoshhajra et al. In: Abbara, Walker. CardioVascular Images of the MGH

MGH Stress Perfusion CT ExperienceN=34; BMI 30.4+/-5

Stress perfusion CT, radionuclide imaging (MPI), conventional angiography

sens spec (cath >=50%)

pCT 79 80

MPI 67 83

sens spec (cath >=50% AND MPI defect)

pCT 79 80

12.7mSv average dose (stress,rest, AND delayed enhancement)

Blankstein et al.JACC, September 2009 15;54(12):1072-84

Mochizuki T, Radiology, Ehime Univ School of Med

ST (%)

Systolic Thickening

Systolic Thickening

hypohypo

StenosisStenosis

Tl SPECT

hypohypo

StenosisStenosis

MDCT

Courtesy Dr.

Thank you!

[email protected]

Thank you!