PET AND PET/CT IN ISCHEMIC HEART DISEASE

Miguel Hernandez Pampaloni, M.D., Ph.D.Chief, Nuclear Medicine

Assistant Professor of Radiology

Agenda

• Myocardial perfusion imaging SPECT Perfusion PET• Metabolic PET (Viability)• Hybrid Imaging (PET/CT)

Myocardial Perfusion ImagingSPECT

Indications• Detects presence/location/extent of myocardial

ischemia in patients with R/O ACS.• Risk stratification after ACS.• Identify fixed defects, evaluate EF and viability.• CP with abnormal EKG’s.• Equivocal ETT.• Inability to exercise (pharmacological stress).

• Isotopes• Thallium-201 or Technetium-99m compounds.

• Both assess LV function and ischemia• Isotopes taken up by viable myocardial cells in quantities proportional to perfusion.

• Well perfused regions appear brighter.

SPECT Radiotracers

Myocardial Perfusion ImagingExercise SPECT

Exercise• Pt walks on treadmill with increasing speed/incline.

• Goal = increase myocardial oxygen demand (MVO2)– CAD: the increased demand exceeds supply = ischemia

• Advantages: flexible protocols.• Disadvantages: pt must be able to achieve 85% of maximal HR.

Pharmacologic• dobutamine = increases HR, BP, contractility; mimics exercise.

• Coronary vasodilators – dipyridamole and adenosine.

» Flow mismatch; diseased dilated arteries get less flow

• Sensitivities and specificities comparable to exercise stress.

Stress Protocols

SPECT Myocardial Perfusion ImagingStrengths

• Extensively validated, useful for cost-effective risk stratification & patient management.

• Widely available – outpatient settings.• Standardized protocols.• Excellent procedural and clinical utilization guidelines published by professional medical societies.

• 27 accepted clinical indications.

Relationship between Extent of Ischemia and Cardiac Events

Ladenheim Ml et al. J Am Coll Cardiol. 1986;7:464.

20

40

60

00 2 4 6

Reversible Defects (Number)

Cardiac Event Rate (%)

log

Haz

ard

Rat

io

01

23

45

6

% Total Myocardium Ischemic SPECT

0 12.5% 25% 32.5% 50%

Medical Rx

Revasc*

*

*P < 0.001

Hachamovitch R et al. Circulation. 2003;107:2900-2907.

Magnitude of Jeopardized Myocardium

Why PET Perfusion?

• Obesity and poor quality studies, SPECT.

• Dosing• Attenuation correction

• Image clarity.• Improved diagnostic accuracy, lower false positive.

• Identification of multivessel ischemia.

• Rapid acquisition: impaired patients.

• Lower radiation burden.

SPECT vs PET Perfusion

• Energy: 78-140 KeV• Attenuation correction: sometimes• Stress: exercise, pharmacologic• Protocol, start to finish: 2–2/12 hours• Ventricular function: post-stress, rest

• 511 KeV• Attenuation correction: always• Stress: pharmacologic, exercise in future (F-18)• Protocol, start to finish:30–45 minutes• Ventricular function: stress, rest

SPECT PET

Normal73%

Abnormal25%

2% (5 pts!!) Non-Diagnostic

Myocardial Perfusion PET in Patients with a Non-Diagnostic

SPECT

64% were womenMean BMI 32Mean age 62 yrs

233 consecutive pts with a

nondiagnostic SPECT followed by MP PET <90

days

       Bateman. Circ 2003;108:IV-454.

Prevalence of Artifacts: PET vs SPECT

SPECT PET P valueNo artifact 19 (17%) 49 (44%) 0.0001

Minor artifact 26 (23%) 28 (25%) 0.75

Significant artifact 64 (57%) 33 (29%) 0.0003

Major artifact 3 (3%) 2 (2%) 0.32

No GI uptake 45 (40%) 100 (89%) <0.001

Minor GI uptake 19 (17%) 5 (4%) 0.0002

Significant GI uptake 46 (41%) 6 (5%) <0.001

Major GI uptake 2 (2%) 1 (1%) 0.32

Bateman TM et al. J Nucl Cardiol. 2006;13(1):24-33.

Radiation Exposure (mSv) PET vs SPECT

Perfusion PET Advantages

• High spatial and temporal resolution.

• Excellent sensitivity.• Accurate depth-independent attenuation correction.

• High contrast resolution.• Quantitative imaging capabilities.

Myocardial Blood Flow and Radiotracer Uptake

PET Cardiac Radiotracers

PET Perfusion for Detecting Myocardial Ischemia

Author Sensitivity Specificity # Patients

Gould 95% 100% 50Demer 94% 95% 193Go 93% 78% 202Schelbert 97% 100% 45Yonekura 93% 100% 49Williams 98% 93% 146Stewart 84% 88% 319Weighted Avg.

93% +/- 8 92% +/- 5 766

Freedom From Any Cardiac Events Following Rb-82 Myocardial Perfusion PET

Yoshinaga K et al. J Am Coll Cardiol. 2006;48:1029.

Characteristics of a Normal Myocardial Perfusion PET Study

• Uniform distribution of tracer, independent of gender• LV cavity at peak stress equal to/smaller than at rest • Uniform and normal wall thickness and thickening• Uniform and normal regional wall motion• Peak stress LVEF > rest LVEF

Characteristics of an Abnormal Myocardial Perfusion PET Study

• Decrease in regional tracer uptake at peak stress

• LV cavity at peak stress larger than at rest • Frequent regional contraction abnormality

(stunning) at peak stress• Peak stress LVEF < rest LVEF

Abn

orm

al N

-13

perfu

sion

stu

dy

72 year old man with peripheral vascular disease.

Coronary arteriography:•LAD: 60% ostial and 80% mid vessel stenoses•LCX: 90% proximal stenosis and occluded OM•RCA: 90% ostial stenosis

Multivessel DiseaseIschemia + Transient Dilatation

PET Perfusion/Metabolic Imaging Protocols

Transm. Rest ExercisePharm.

Stress

DipyridamoleAdenosineDobutamine

13N-ammonia 82Rb

13N-ammonia

82Rb 18F-FDG

MetabolicImaging

Quantification of Myocardial Blood Flow

Rest

Stress

LAO

RAO

Arterial Tracer Input Function and Changes inMyocardial Tracer Concentration

ActivityConcentration

(cts / pixel / sec)Myocardium

Time (sec)

1201008060402000

1

2

3

4

5

Arterial Blood

Clinical Value Long Term KnownMBF in Kawasaki Disease

Muzik et al, J ACC Vol 28; 3:757-62, 1996

Rest0

100

Myo

card

ial B

lood

Flo

w(m

l/100

g/m

in)

Adenosine

Controln = 10

Kawasakin = 10

200

300

400

500

Rest Adenosine

p = 0.01

Series10

10

20

30

40

50

Series10

10

20

30

40

50

SD

NS P <0.05

Perc

ent I

ncre

ase

RPP

Baseline On Treat Off Treat

MBFP <0.05

Baseline On Treat Off Treat

Clinical Value Long Term KnownTherapy MBF Changes in Insulin Resistance

Quinones et al, Ann Int Med 2004:140:700-708

Herzog et al. JACC 2009;54:150-156.

Long Term Prognostic Value PET PerfusionAdded Value of Coronary Flow Reserve

• Extent and significance of multivessel disease• Pharmacologic therapy and life style modifications• Detection of preclinical and early CAD• Microvascular disease (endothelial disfunction)• Evaluation of procedural outcome (PTCA)• Hemodynamic significance of CAD (coronary steal

syndrome, collaterals)• Myocardial regeneration• Ventricular remodeling (the discussion of which

would require two more hours)

Clinical Role of Quantitative PETConditions which cannot be evaluated by "relative" imaging modalities

Limitations of quantitative PET• Unpredictable hyperemic response (what is "normal"?)• Computational demands

Why Is PET More Suitable to Follow Pro/Regression of CAD

• Coronary blood flow is a function of the arterial radius raised to the fourth power

• Small changes in diameter not measurable by anatomic imaging are magnified into much larger changes in blood flow that are readily quantifiable by PET

• Changes in PET perfusion can be seen in 40–90 days after intense risk factor treatment is begun

Gould KL. J Nucl Cardiol. 2005;12:625-638.

Viability PET StudyChronic LVEF Dysfunction

• Traditionally the gold standard• Two sets of resting images to detect viable

and hibernating myocardium:• Perfusion image (usually with N-13 ammonia or

rubidium-82)• Glucose metabolic image (with F-18

fluorodeoxyglucose = FDG)

OH

HO

HO

HO

18F

Myocyte FDG UptakeNormal Myocyte Ischemic

Myocyte

Glucose 6-phosphatase

Hexokinase

Glucose 6-phosphatase

G6P D-Glucose

Glycolytic Pathway

D-Glucose

X

FFA

Glucose 6-phosphatase

Hexokinase

Glucose 6-phosphatase

FDG-6-P

G6P

Glycolytic Pathway

D-Glucose

XFDGFDG

D-Glucose

FDG-6-P

FDG

FDGFDG

FDGFDG

FDGFDG

FDG

FDG

FDG

FDG

FDGFDG

FDG

FFA FFA

FFA

FFA

FFA

FFA

FFA

FFA

FFA

FFA

FFA FFA

FFA FFA

Fixed

Fixed

Partially Reversible

Partially Reversible

Match

Mismatch

Stress Rest

FDGNH3

Match

Mismatch

PET Myocardial Viability

Impr

ovem

ent

(%)

Di Carli M et al, Circulation 1995;92:3436-44.

0

100

200

0 20 40 60 80Extent mismatch (%LV)

r=0.87,SEE=10.8P<0.001

PET ViabilityImproved symptoms of CHF

18%

Multivessel CADMean LVEF = 28±6%

0 20 40 60 80 100PET viable (%)

Del

ta M

ETS

(%)

r=0.54P=0.0001

PET vs Dobutamine EchoImproved Exercise Tolerance

Marwick T et al: J Am Coll Cardiol 33:750, 1999

DE viable (%)

80

20

0

-20

-40

-60

40

60

Multivessel CAD, mean LVEF = 277%59% NYHA III or IV

0 20 40 60 80

r=0.005P=0.92

80

20

0

-20

-40

40

60

Beeres, S. L.M.A. et al. J Am Coll Cardiol 2007;49:1137-1148

The Next Thing is….Tracking of Genetically Labeled Progenitor Cells by PET

Hybrid PET/CTA: Myocardial Perfusion and Function

Cardiac Perfusion

Concurrent Rest & Peak

Stress FunctionCTA

Coronary Calcium

Assessment

Progression of Atherosclerosis

Adapted from Abrams J. N Engl J Med. 2005;352:2524-2533.

SPECT

PETEndothelial dysfunction

Severe ischemia

CT Coronary angiography

Why Now? Availability of PET cameras: oncology Availability of Radiopharmaceutical Improvement in acquisition protocols Improvement in cardiac processing Ability to do ECG-gated imaging Improvement in cardiac display

Spiral CT

Whole-body PET

(1-8 min total)

(6-40 min total)

Corrections:• scatter• attenuation

Fused PET/CT

PET

CT

PET/CT scan protocol

Reconstruction:• FORE + OSEM

CT PET

CT PET

SPECT Underestimates Disease Burden: Stable CAD

Calcium score: 890

Why use PET/CTA ?• Non invasive.• Offer high diagnostic accuracy.• Monitor the course of disease.• Allow quantification of myocardial blood flow and

coronary reserve.• Able to detect early functional abnormalities.• Able to monitor consequences of lifestyle

modifications.

Rest-Stress PET Rubidium-82 and CTA Protocol

0:00 min 0:30 min

Scout Stress

5 sec4 min

CAC/CTAC5 sec

List mode

82 Rb 82 Rb

List modeCTAC 64- MDCT CTA

6- 9 sec

IV Lopressor

7 min 7 min

IV LopressorSl NTG

5 sec

Study Effective Radiation (mSv)

PET

F-18 FDG (370 MBq) 7.0

N-13 NH3 rest/stress (2X 550 MBq) 2.2

Rb82 rest/stress (2 x 740 MBq) 3.6

H2O-15 rest/stress (2 x 740 MBq) 1.4

Transmission Ge-68 rod source 0.08-0.13

MSCT

Calcium Scoring 0.7-6.2

CT angiography 3.7-13.0

CT based PET attenuation correction 0.23-5.66

Effective Radiation Dose for Cardiac PET/CT Studies

Relationship of Stress-Induced Ischemia and Atherosclerosis (CAC)

Berman DS et al. J Am Coll Cardiol. 2004;44:923-930.

Distribution of the normal MPS studies (N=1,119)

0

1-9

10-99

100-399

400-999

1000

Distribution of the ischemic MPS studies (N=76)CAC score

5%

0 %

7 %

20 %

29 %

39 %

22%

4 %

18 %

25 %

20 %

11 %

Schenker, M. P. et al. Circulation 2008;117:1693-1700

Prognosis of Cardiac Events by PET-CTAdded Value of CAC

Kajander, S. et al. Circulation 2010;122:603-613

Hybrid PET/CTA: Myocardial Perfusion and Function

PET and CTA Complement Each Other

• Calcium (blooming)• Stents• Limited spatial resolution, <1.5-mm vessels• Overestimation of stenosis• Positive predictive value MDCT ~50%• Clinical outcomes data• Preclinical disease

Abnormal CT Angiography: Limited Positive Predictive Value

Discordance Between Noninvasively Determined Anatomic and Functional Measures of Atherosclerosis

• Percent stenosis a moderate descriptor of coronary resistance– Stenosis difficult to estimate with soft plaque

• Coronary vasodilator reserve integrates coronary epicardial and microvascular function

• Balanced ischemia (MPI)• Artifacts (MPI)• Noncoronary causes of myocardial damage

PET CTA Diagnosis Potential Strategy

Normal Normal No CAD Discharge

Normal Abnormal Non-significant CAD

Medical Tx & Follow-up

Abnormal Abnormal Significant CAD Medical Tx & Consider Cath

Abnormal Normal Coronary microvascular dysfunction

Risk Profile Modification & Consider Antianginal Tx

Scenarios in Cardiac PET/CT imaging for (suspected) Coronary Artery Disease

Lautamaki, R. et al. Circ Cardiovasc Imaging 2009;2:299-305

Infarct size measurement

Changes Coming With Hybrid ImagingNuclear Cardiology Evolution

• PET-CT: Comprehensive evaluation of CAD Perfusion Function Viability Vulnerable Plaque Assessment

(FDG ?)

Take Home Message

• Information derived from CT and PET is complementary for the evaluation of CAD.

• Promising new 18F-labelled myocardial perfusion tracers are under development and will likely increase use cardiac PET as a routine diagnostic tool.

• Absolute quantification of myocardial blood flow by dynamic PET has contributed to an improved understanding of the pathophysiology of CAD. It characterizes patients without evidence of regional, visually detectable perfusion heterogeneity.

• The potential of PET to introduce tracers targeting biologic and molecular mechanisms relevant to cardiac disease and therapy is basically unlimited. PET has the potential to take a central role as a diagnostic tool in personalised, molecular cardiovascular medicine of the future.