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 Imaging
SPECT
 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).
SPECT Radiotracers
• 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.
Myocardial Perfusion Imaging
Exercise SPECT
Stress Protocols
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.
SPECT Myocardial Perfusion Imaging
Strengths
• 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
60
40
Cardiac Event Rate
(%)
20
0
0
2
4
6
Reversible Defects (Number)
Ladenheim Ml et al. J Am Coll Cardiol. 1986;7:464.
5
*P < 0.001
3
4
*
Medical Rx
1
2
*
Revasc
0
log Hazard Ratio
6
Magnitude of Jeopardized Myocardium
0
12.5%
25%
32.5%
% Total Myocardium Ischemic SPECT
50%
Hachamovitch R et al. Circulation. 2003;107:2900-2907.
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
SPECT
• Energy: 78-140 KeV
• Attenuation correction:
sometimes
• Stress: exercise,
pharmacologic
• Protocol, start to finish:
2–2/12 hours
• Ventricular function: poststress, rest
PET
• 511 KeV
• Attenuation correction:
always
• Stress: pharmacologic,
exercise in future (F-18)
• Protocol, start to
finish:30–45 minutes
• Ventricular function:
stress, rest
Myocardial Perfusion PET in
Patients with a Non-Diagnostic
SPECT2% (5 pts!!) NonDiagnostic
233 consecutive
pts with a
nondiagnostic
SPECT followed
by MP PET <90
days
Abnormal
25%
Normal
73%
64% were women
Mean BMI 32
Mean age 62 yrs
Bateman. Circ 2003;108:IV-454.
Prevalence of Artifacts: PET vs SPECT
SPECT
PET
P value
No artifact
Minor artifact
19 (17%)
49 (44%)
0.0001
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
1 (1%)
0.32
Major GI uptake
2 (2%)
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
Gould
Demer
Go
Schelbert
Yonekura
Williams
Stewart
Weighted
Avg.
Sensitivity Specificity #
Patients
95%
100%
50
94%
95%
193
93%
78%
202
97%
100%
45
93%
100%
49
98%
93%
146
84%
88%
319
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
Abnormal N-13 perfusion study
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 Disease
Ischemia + Transient Dilatation
PET Perfusion/Metabolic Imaging Protocols
13N-ammonia
82Rb
Transm.
13N-ammonia
82Rb
Rest
Exercise Stress
Pharm.
Dipyridamole
Adenosine
Dobutamine
18F-FDG
Metabolic
Imaging
Quantification of Myocardial Blood Flow
LAO
RAO
Rest
Stress
Arterial Tracer Input Function and Changes in
Myocardial Tracer Concentration
5
4
Activity
Concentration
(cts / pixel / sec)
3
2
Myocardium
1
Arterial Blood
0
0
20
40
60
Time (sec)
80
100
120
Clinical Value Long Term Known
MBF in Kawasaki Disease
p = 0.01
400
(ml/100g/min)
Myocardial Blood Flow
500
300
200
100
0
Rest
Adenosine
Control
n = 10
Rest
Adenosine
Kawasaki
n = 10
Muzik et al, J ACC Vol 28; 3:757-62, 1996
Clinical Value Long Term Known
Therapy MBF Changes in Insulin Resistance
RPP
MBF
P <0.05
Percent Increase
NS
50
50
40
40
P <0.05
SD
30
30
20
20
10
10
0
0
Baseline On Treat Off Treat
Baseline
On Treat
Off Treat
Quinones et al, Ann Int Med 2004:140:700-708
Long Term Prognostic Value PET Perfusion
Added Value of Coronary Flow Reserve
Herzog et al. JACC 2009;54:150-156.
Clinical Role of Quantitative PET
Conditions which cannot be evaluated by "relative" imaging
modalities
•
•
•
•
•
•
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)
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 Study
Chronic 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)
HO
HO
HO
OH
18F
Myocyte FDG Uptake
Normal Myocyte
Ischemic Myocyte
Glucose 6-phosphatase
Glucose 6-phosphatase
FDG
FDG
FDG
FDG-6-P
FDG
FFA
FFA
FFA
FFA
FFA
FFA
FFA
FFA
FFA
FFA
FFA
DGlucose
FDG
Glycolytic
Pathway
Hexokinase
FDG
DGlucose
G6P
FDG
FDG
FDG
FDG
FDG
FDG
DGlucose
FDG-6-P
FDG
FDG
FFA
FFA
X
FDG
FDG
X
Glycolytic
Pathway
Hexokinase
FFA
G6P
DGlucose
Glucose 6-phosphatase
Glucose 6-phosphatase
PET Myocardial Viability
NH3
Stress
FDG
Rest
Fixed
Match
Fixed
Mismatch
Partially
Reversible
Partially
Reversible
Match
Mismatch
PET Viability
Improved symptoms of CHF
Improvement
(%)
200
r=0.87,
SEE=10.8
P<0.001
100
Multivessel CAD
Mean LVEF = 28±6%
0
0
20
18%
40
60
80
Extent mismatch (%LV)
Di Carli M et al, Circulation 1995;92:3436-44.
PET vs Dobutamine Echo
Delta METS (%)
Improved Exercise Tolerance
80
80
60
60
40
40
20
20
0
0
-20
r=0.54
P=0.0001
-40
-60
0
20
40
60
80
100
-20
r=0.005
P=0.92
-40
0
PET viable (%)
20
40
DE viable (%)
Multivessel CAD, mean LVEF = 277%
59% NYHA III or IV
Marwick T et al: J Am Coll Cardiol 33:750, 1999
60
80
The Next Thing is….
Tracking of Genetically Labeled Progenitor Cells by PET
Beeres, S. L.M.A. et al. J Am Coll Cardiol 2007;49:1137-1148
Hybrid PET/CTA: Myocardial Perfusion and
Function
Cardiac
Perfusion
Concurrent Rest
& Peak Stress
Function
Coronary
Calcium
Assessment
CTA
Progression of Atherosclerosis
CT Coronary angiography
SPECT
Endothelial
dysfunction
PET
Severe ischemia
Adapted from Abrams J. N Engl J Med. 2005;352:2524-2533.
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
PET/CT scan protocol
Spiral CT
Corrections:
• scatter
• attenuation
(1-8 min total)
Fused PET/CT
CT
PET
CT
PET
Whole-body PET
(6-40 min total)
Reconstruction:
• FORE + OSEM
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
82
IV Lopressor
Rb
82
Rb
IV Lopressor
Sl NTG
Stress
Scout
CAC/
CTAC
List mode
CTAC
List mode
4 min
5 sec
5 sec
7 min
5 sec
7 min
0:00 min
64-MDCT
CTA
6-9 sec
0:30 min
Effective Radiation Dose for Cardiac PET/CT Studies
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
Relationship of Stress-Induced Ischemia and
Atherosclerosis (CAC)
Distribution of the normal
MPS studies (N=1,119)
Distribution of the ischemic
CAC score
MPS studies (N=76)
0
22%
4%
18 %
1-9
10-99
100-399
25 %
400-999
20 %
11 %
1000
5%
0%
7%
20 %
29 %
39 %
Berman DS et al. J Am Coll Cardiol. 2004;44:923-930.
Prognosis of Cardiac Events by PET-CT
Added Value of CAC
Schenker, M. P. et al. Circulation 2008;117:1693-1700
Hybrid PET/CTA: Myocardial
Perfusion and Function
Kajander, S. et al. Circulation 2010;122:603-613
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
Scenarios in Cardiac PET/CT imaging for
(suspected) Coronary Artery Disease
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
Infarct size measurement
Lautamaki, R. et al. Circ Cardiovasc Imaging 2009;2:299-305
Changes Coming With Hybrid Imaging
Nuclear 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.