pet and pet/ct in ischemic heart disease miguel hernandez pampaloni, m.d., ph.d. chief, nuclear...
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PET AND PET/CT IN ISCHEMIC HEART DISEASE
Miguel Hernandez Pampaloni, M.D., Ph.D.Chief, Nuclear Medicine
Assistant Professor of Radiology
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Agenda
• Myocardial perfusion imaging
SPECT
Perfusion PET• Metabolic PET (Viability)• Hybrid Imaging (PET/CT)
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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).
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• 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
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Myocardial Perfusion ImagingExercise SPECT
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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
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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.
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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 (%)
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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
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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.
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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
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Normal73%
Abnormal25%
2% (5 pts!!) Non-Diagnostic
Myocardial Perfusion PET in Patients with a Non-Diagnostic
SPECT
64% were women
Mean BMI 32
Mean age 62 yrs
233 consecutive pts with a
nondiagnostic SPECT followed by MP PET <90
days
Bateman. Circ 2003;108:IV-454.
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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.
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Radiation Exposure (mSv) PET vs SPECT
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Perfusion PET Advantages
• High spatial and temporal resolution.
• Excellent sensitivity.• Accurate depth-independent attenuation correction.
• High contrast resolution.• Quantitative imaging capabilities.
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Myocardial Blood Flow and Radiotracer Uptake
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PET Cardiac Radiotracers
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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
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Freedom From Any Cardiac Events Following Rb-82 Myocardial Perfusion PET
Yoshinaga K et al. J Am Coll Cardiol. 2006;48:1029.
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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
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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
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Abn
orm
al N
-13
perf
usio
n st
udy
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
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Multivessel Disease
Ischemia + Transient Dilatation
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PET Perfusion/Metabolic Imaging Protocols
Transm. Rest ExercisePharm.
Stress
DipyridamoleAdenosineDobutamine
13N-ammonia 82Rb
13N-ammonia
82Rb 18F-FDG
MetabolicImaging
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Quantification of Myocardial Blood Flow
Rest
Stress
LAO
RAO
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Arterial Tracer Input Function and Changes inMyocardial Tracer Concentration
ActivityConcentration
(cts / pixel / sec)Myocardium
Time (sec)
1201008060402000
1
2
3
4
5
Arterial Blood
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Clinical Value Long Term KnownMBF in Kawasaki Disease
Muzik et al, J ACC Vol 28; 3:757-62, 1996
Rest
0
100
My
oc
ard
ial B
loo
d F
low
(ml/1
00g
/min
)
Adenosine
Controln = 10
Kawasakin = 10
200
300
400
500
Rest Adenosine
p = 0.01
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Series1
0
10
20
30
40
50
Series1
0
10
20
30
40
50
SD
NS P <0.05
Pe
rce
nt
Inc
rea
se
RPP
Baseline On Treat Off Treat
MBF
P <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
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Herzog et al. JACC 2009;54:150-156.
Long Term Prognostic Value PET PerfusionAdded Value of Coronary Flow Reserve
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• 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 PET
Conditions which cannot be evaluated by "relative" imaging modalities
Limitations of quantitative PET
• Unpredictable hyperemic response (what is "normal"?)• Computational demands
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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.
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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
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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
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Fixed
Fixed
Partially
Reversible
Partially
Reversible
Match
Mismatch
Stress Rest
FDGNH3
Match
Mismatch
PET Myocardial Viability
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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%
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0 20 40 60 80 100PET viable (%)
De
lta M
ET
S (
%)
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
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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
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Hybrid PET/CTA: Myocardial Perfusion and Function
Cardiac Perfusion
Concurrent Rest & Peak
Stress FunctionCTA
Coronary Calcium
Assessment
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Progression of Atherosclerosis
Adapted from Abrams J. N Engl J Med. 2005;352:2524-2533.
SPECT
PETEndothelial dysfunction
Severe ischemia
CT Coronary angiography
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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
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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
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SPECT Underestimates Disease Burden: Stable CAD
Calcium score: 890
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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.
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Rest-Stress PET Rubidium-82 and CTA Protocol
0:00 min 0:30 min
Scout Stress
5 sec4 min
CAC/CTAC
5 sec
List mode
82 Rb82 Rb
List modeCTAC64- MDCT
CTA
6- 9 sec
IV Lopressor
7 min 7 min
IV LopressorSl NTG
5 sec
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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
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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 %
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Schenker, M. P. et al. Circulation 2008;117:1693-1700
Prognosis of Cardiac Events by PET-CTAdded Value of CAC
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Kajander, S. et al. Circulation 2010;122:603-613
Hybrid PET/CTA: Myocardial Perfusion and Function
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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
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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
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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
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Lautamaki, R. et al. Circ Cardiovasc Imaging 2009;2:299-305
Infarct size measurement
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Changes Coming With Hybrid ImagingNuclear Cardiology Evolution
• PET-CT:
Comprehensive evaluation of CAD
Perfusion
Function
Viability
Vulnerable Plaque Assessment (FDG ?)
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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.