1. PET AND PET/CT IN ISCHEMIC HEART DISEASE
Miguel Hernandez Pampaloni, M.D., Ph.D.
Chief, Nuclear Medicine
Assistant Professor of Radiology

2. Agenda Myocardial perfusion imaging SPECT Perfusion PET
Metabolic PET (Viability)
Hybrid Imaging (PET/CT)

3. 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).

4. 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.

5. Myocardial Perfusion Imaging Exercise SPECT
arrow

6. Stress Protocols Exercise Pharmacologic
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.

7. 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.

8. Relationship between Extent of Ischemia and Cardiac Events60 40
Cardiac Event Rate (%) 20 2 4 6
Reversible Defects (Number)
Ladenheim Ml et al. J Am Coll Cardiol. 1986;7:464.

9. Magnitude of Jeopardized Myocardium
log Hazard Ratio 1 2 3 4 5 6
% Total Myocardium Ischemic SPECT
12.5%
25%
32.5%
50%
Medical Rx
Revasc *
*P < 0.001
Hachamovitch R et al. Circulation. 2003;107:

10. 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.

11. SPECT vs PET Perfusion SPECT PET 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

12. Myocardial Perfusion PET in Patients with a Non-Diagnostic SPECT
2% (5 pts!!) Non-Diagnostic
233 consecutive pts with a nondiagnostic SPECT followed by MP PET <90 days
Abnormal
25%
Put in the comparison differences
Normal
73%
64% were women
Mean BMI 32
Mean age 62 yrs
       Bateman. Circ 2003;108:IV-454.

13. Prevalence of Artifacts: PET vs SPECT
P value
No 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
5 (4%)
0.0002
Significant GI uptake
46 (41%)
6 (5%)
Major GI uptake
1 (1%)
Bateman TM et al. J Nucl Cardiol. 2006;13(1):24-33.

14. Radiation Exposure (mSv) PET vs SPECT

15. Perfusion PET Advantages
High spatial and temporal resolution.
Excellent sensitivity.
Accurate depth-independent attenuation correction.
High contrast resolution.
Quantitative imaging capabilities.
At the end

17. Myocardial Blood Flow and
Radiotracer Uptake

18. PET Cardiac Radiotracers

19. PET Perfusion for Detecting Myocardial Ischemia
Author
Sensitivity
Specificity
# Patients
Gould
95%
100% 50
Demer
94%
193 Go
93%
78%
202
Schelbert
97% 45
Yonekura 49
Williams
98%
146
Stewart
84%
88%
319
Weighted Avg.
93% +/- 8
92% +/- 5
766
This sensitivity & specificity chart is a compilation of studies from various authors using both Rb-82 & N-13 Ammonia.2
2. Nuclear Medicine Self-Study Program III: Nuclear Medicine Cardiology. Botvinik, EH, Ed. 1998: Society of Nuclear Medicine, Reston, VA.

20. Yoshinaga K et al. J Am Coll Cardiol. 2006;48:1029.
Freedom From Any Cardiac Events Following Rb-82 Myocardial Perfusion PET
Yoshinaga K et al. J Am Coll Cardiol. 2006;48:1029.

21. 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
This slide enumerates the important descriptors of a normal ECG-gated rest and peak stress Rb-82 PET scan after dipyridamole stress.

22. N13-Ammonia PET Images

23. 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
This slide enumerates the important descriptors of a normal ECG-gated rest and peak stress Rb-82 PET scan after dipyridamole stress.

24. 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

25. Ischemia + Transient Dilatation
Multivessel Disease
Ischemia + Transient Dilatation
The peak stress images show a uniform distribution of Rb-82 to all regions except for the inferior and inferolateral walls. That region shows a severe defect with normalized uptake in the rest images.
Note that the LV cavity is larger at peak stress than at rest; the TID ratio is quantitated at This is frequently observed with PET in the presence of ischemia, even when this involves only a single coronary territory. With SPECT, TID is seen infrequently, and usually indicates multivessel CAD. The difference presumably is because PET stress images are acquired during hyperemia, while SPECT images are acquired late after hyperemia has resolved.
The reversible perfusion defect is severe in its intensity, and involves a moderately large amount of contiguous lateral and inferior myocardium extending from the base of the left ventricle to the apex. Because the anterolateral wall is spared, this defect is most likely in the distribution of a large obtuse marginal vessel, rather than the proximal left circumflex itself.

26. PET Perfusion/Metabolic Imaging Protocols
13N-ammonia
82Rb
13N-ammonia
82Rb
18F-FDG
Transm.
Rest
Exercise
Pharm.
Stress
Metabolic
Imaging
Dipyridamole
Adenosine
Dobutamine

27. Quantification of Myocardial Blood Flow
Rest
LAO
Stress
RAO

28. Arterial Tracer Input Function and Changes in
Myocardial Tracer Concentration 5 4 3
Activity
Concentration
(cts / pixel / sec)
Myocardium 2 1
Arterial Blood 20 40 60 80
100
120
Time (sec)

29. Clinical Value Long Term Known
MBF in Kawasaki Disease
p = 0.01
500
400
300
Myocardial Blood Flow
(ml/100g/min)
200
100
Rest
Adenosine
Rest
Adenosine
Control
n = 10
Kawasaki
n = 10
Muzik et al, J ACC Vol 28; 3:757-62, 1996

30. Clinical Value Long Term Known
Therapy MBF Changes in Insulin Resistance
RPP
MBF NS
P <0.05
P <0.05 SD
Percent Increase
Baseline
On Treat
Off Treat
Baseline
On Treat
Off Treat
Quinones et al, Ann Int Med 2004:140:

31. Long Term Prognostic Value PET Perfusion
Added Value of Coronary Flow Reserve
Herzog et al. JACC 2009;54:

32. 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

33. 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:

34. 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)
Cellular membrance integrity
Glucose metabolism OH HO
18F

35. Myocyte FDG Uptake Normal Myocyte Ischemic Myocyte X X Hexokinase
Glucose 6-phosphatase
Glucose 6-phosphatase X X
FDG-6-P
FDG
FDG
FDG-6-P
FFA
Glycolytic Pathway
Glycolytic Pathway
Hexokinase
Hexokinase
FFA
FFA
G6P
D- Glucose
D- Glucose
G6P
D- Glucose
D- Glucose
Glucose 6-phosphatase
Glucose 6-phosphatase

36. PET Myocardial Viability
NH3
FDG
Stress
Rest
Fixed
Match
Fixed
Mismatch
Partially Reversible
Match
Partially Reversible
Mismatch

37. Improved symptoms of CHF
PET Viability
Improved symptoms of CHF
Extent mismatch (%LV)
r=0.87,
SEE=10.8
P<0.001
Improvement
(%)
Multivessel CAD
Mean LVEF = 28±6%
18%
Di Carli M et al, Circulation 1995;92:

38. PET vs Dobutamine Echo Improved Exercise Tolerance Delta METS (%)80 20
-20
-40
-60 40 60 80 20
-20
-40 40 60
Delta METS (%)
r=0.54
P=0.0001
r=0.005
P=0.92
PET viable (%)
DE viable (%)
Multivessel CAD, mean LVEF = 277% 59% NYHA III or IV
Marwick T et al: J Am Coll Cardiol 33:750, 1999

39. The Next Thing is….
Tracking of Genetically Labeled Progenitor Cells by PET
3 x 106 endothelial progenitor cells transfected with the sodiumiodide symporter gene were injected intramyocardially in a healthy rat. After injection of N-13 ammonia, homogeneous myocardial perfusion is shown in grayscale on the top. Perfusion images are overlayed with images of reporter-gene expression (bottom). obtained after injection of I-124 sodiumiodide (red/yellow). Regional accumulation of the reporter probe depicts presence of viable transplanted cells at the injection site in the lateral wall. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.
Beeres, S. L.M.A. et al. J Am Coll Cardiol 2007;49:

40. Hybrid PET/CTA: Myocardial Perfusion and Function
Concurrent Rest & Peak Stress Function
Cardiac Perfusion
Coronary Calcium Assessment
CTA

41. Progression of Atherosclerosis
CT Coronary angiography
SPECT
PET
Endothelial dysfunction
Severe ischemia
Adapted from Abrams J. N Engl J Med. 2005;352:

42. 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

43. 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

44. SPECT Underestimates Disease Burden: Stable CAD
Calcium score: 890

45. 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.

46. Rest-Stress PET Rubidium-82 and CTA Protocol
0:00 min
0:30 min

47. 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
MSCT
Calcium Scoring
CT angiography
CT based PET attenuation correction

48. Relationship of Stress-Induced Ischemia and Atherosclerosis (CAC)
Distribution of the normal MPS studies (N=1,119)
1-9
10-99
1000
Distribution of the ischemic MPS studies (N=76)
CAC score 5%
0 %
7 %
20 %
29 %
39 %
22%
4 %
18 %
25 %
20 %
11 %
Berman DS et al. J Am Coll Cardiol. 2004;44:

49. Prognosis of Cardiac Events by PET-CT
Added Value of CAC
Schenker, M. P. et al. Circulation 2008;117:

50. Hybrid PET/CTA: Myocardial Perfusion and Function
A 57-year-old man with atypical chest pain during exertion. A, CT reconstructions show significant stenoses in the LAD, RCA, and a small intermediate branch (IM). LCx was nonstenosed. Yellow dotted line denotes motion artifacts in the RCA. B, Hybrid volume-rendered image. Stress myocardial perfusion was reduced only in the area supplied by the LAD. C, ICA with quantitative analysis showed significant 73% luminal narrowing in the LAD. Other vessels were not stenosed.
A 63-year-old man with positive family history. Good performance, atypical chest pain, and 2-mm ST depression in the ECG at the exercise test. In hybrid images, stress myocardial perfusion was reduced in most regions (green and blue). However, both CT and ICA showed normal coronary arteries, indicating possible microvascular disease.
Kajander, S. et al. Circulation 2010;122:

51. 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

52. 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

53. Scenarios in Cardiac PET/CT imaging for
(suspected) Coronary Artery Disease
PET
CTA
Diagnosis
Potential Strategy
Normal
No CAD
Discharge
Abnormal
Non-significant CAD
Medical Tx & Follow-up
Significant CAD
Medical Tx & Consider Cath
Coronary microvascular dysfunction
Risk Profile Modification & Consider Antianginal Tx

54. Infarct size measurement
Representative midventricular short-axis slices of CT delayed enhancement (left), resting PET perfusion (measured by N-13 ammonia, NH3) and metabolism (measured by FDG) (right), and PET-CT fusion (middle) in animals studied in the chronic and acute phases
Representative midventricular short-axis slices of CT delayed enhancement (left), resting PET perfusion (measured by N-13 ammonia, NH3) and metabolism (measured by FDG) (right), and PET-CT fusion (middle) in animals studied in the chronic and acute phases after myocardial infarction. Images of chronic infarction show transmural delayed enhancement in anteroseptal wall, associated with a perfusion/metabolism matched defect on PET. Images of acute infarction show a no-reflow phenomenon in anteroseptal wall, associated with reduced perfusion but enhanced metabolism (mismatch) on PET.
Lautamaki, R. et al. Circ Cardiovasc Imaging 2009;2:

55. Changes Coming With Hybrid Imaging Nuclear Cardiology Evolution
PET-CT:
Comprehensive evaluation of CAD
Perfusion
Function
Viability
Vulnerable Plaque Assessment (FDG ?)

56. 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.