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

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pet and pet ct in ischemic heart disease

PET AND PET/CT IN ISCHEMIC HEART DISEASE

Miguel Hernandez Pampaloni, M.D., Ph.D.

Chief, Nuclear Medicine

Assistant Professor of Radiology

agenda
Agenda
  • Myocardial perfusion imaging

SPECT

Perfusion PET

  • Metabolic PET (Viability)
  • Hybrid Imaging (PET/CT)
myocardial perfusion imaging spect
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).
spect radiotracers
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.
stress protocols
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.
slide7

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.
slide8

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 CollCardiol. 1986;7:464.

slide9

6

5

*

Medical Rx

4

log Hazard Ratio

3

*

Revasc

2

1

0

0

12.5%

25%

32.5%

50%

% Total Myocardium Ischemic SPECT

Magnitude of Jeopardized Myocardium

*P < 0.001

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

why pet perfusion
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 vs PET Perfusion

SPECT PET

slide12

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%

Normal

73%

64% were women

Mean BMI 32

Mean age 62 yrs

       Bateman. Circ 2003;108:IV-454.

prevalence of artifacts pet vs spect
Prevalence of Artifacts: PET vs SPECT

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

perfusion pet advantages
Perfusion PET Advantages
  • High spatial and temporal resolution.
  • Excellent sensitivity.
  • Accurate depth-independent attenuation correction.
  • High contrast resolution.
  • Quantitative imaging capabilities.
slide17

Myocardial Blood Flow and

Radiotracer Uptake

slide20

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

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

slide21

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
slide22

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
slide23

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% ostialstenosis

slide24

Multivessel Disease

  • Ischemia + Transient Dilatation
slide25

PET Perfusion/Metabolic Imaging Protocols

13N-ammonia

82Rb

13N-ammonia

82Rb

18F-FDG

Transm.

Rest

Exercise

Pharm.

Stress

Metabolic

Imaging

Dipyridamole

Adenosine

Dobutamine

slide27

Arterial Tracer Input Function and Changes in

Myocardial Tracer Concentration

5

4

3

Activity

Concentration

(cts / pixel / sec)

Myocardium

2

1

Arterial Blood

0

0

20

40

60

80

100

120

Time (sec)

slide28

Clinical Value Long Term Known

MBF in Kawasaki Disease

p = 0.01

500

400

300

Myocardial Blood Flow

(ml/100g/min)

200

100

0

Rest

Adenosine

Rest

Adenosine

Control

n = 10

Kawasaki

n = 10

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

slide29

Clinical Value Long Term Known

Therapy MBF Changes in Insulin Resistance

RPP

MBF

P <0.05

P <0.05

NS

SD

Percent Increase

Baseline

On Treat

Off Treat

Baseline

On Treat

Off Treat

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

slide30

Long Term Prognostic Value PET Perfusion

Added Value of Coronary Flow Reserve

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

slide31

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
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

HO

HO

OH

HO

18F

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)

Cellular membrance integrity

Glucose metabolism

slide34

FDG

FDG

FDG-6-P

FDG

FDG

FDG

FDG

FDG

FDG

FFA

FFA

FDG

FDG

FFA

FFA

FDG

FDG

FFA

FFA

FDG

FDG

FFA

FFA

FDG

FDG

FFA

FFA

FFA

FFA

FFA

FFA

D-Glucose

Myocyte FDG Uptake

Normal MyocyteIschemic Myocyte

Glucose 6-phosphatase

Glucose 6-phosphatase

X

X

FDG-6-P

Glycolytic Pathway

Glycolytic Pathway

Hexokinase

Hexokinase

FFA

G6P

D-Glucose

D-Glucose

D-Glucose

G6P

Glucose 6-phosphatase

Glucose 6-phosphatase

slide35

PET Myocardial Viability

NH3

FDG

Stress

Rest

Fixed

Match

Fixed

Mismatch

Partially Reversible

Match

Partially Reversible

Mismatch

slide36

r=0.87,

SEE=10.8

P<0.001

18%

Extent mismatch (%LV)

PET Viability

Improved symptoms of CHF

Improvement

(%)

Multivessel CAD

Mean LVEF = 28±6%

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

slide37

80

80

60

60

40

40

20

20

0

0

-20

-20

-40

-40

-60

PET vsDobutamine Echo

Improved Exercise Tolerance

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 CollCardiol 33:750, 1999

slide38

The Next Thing is….

Tracking of Genetically Labeled Progenitor Cells by PET

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

slide39

Hybrid PET/CTA: Myocardial Perfusion and Function

Concurrent Rest & Peak Stress Function

Coronary Calcium Assessment

Cardiac Perfusion

CTA

progression of atherosclerosis

PET

Endothelial dysfunction

Severe ischemia

SPECT

Progression of Atherosclerosis

CT Coronary angiography

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

why now
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
slide42

PET/CT scan protocol

  • Corrections:
  • scatter
  • attenuation

Spiral CT

(1-8 min total)

Fused PET/CT

CT

PET

CT

PET

Whole-body PET

(6-40 min total)

  • Reconstruction:
  • FORE + OSEM

CT

PET

why use pet cta
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.
relationship of stress induced ischemia and atherosclerosis cac

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

Distribution of the ischemic MPS studies (N=76)

CAC score

0

5%

22%

4 %

1-9

0 %

10-99

18 %

7 %

100-399

20 %

25 %

400-999

20 %

29 %

1000

11 %

39 %

Relationship of Stress-Induced Ischemia and Atherosclerosis (CAC)

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

slide48

Prognosis of Cardiac Events by PET-CT

Added Value of CAC

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

slide49

Hybrid PET/CTA: Myocardial Perfusion and Function

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

pet and cta complement each other
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
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
slide52

Scenarios in Cardiac PET/CT imaging for

(suspected) Coronary Artery Disease

slide53

Infarct size measurement

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

changes coming with hybrid imaging nuclear cardiology evolution
Changes Coming With Hybrid ImagingNuclear Cardiology Evolution
  • PET-CT:

Comprehensive evaluation of CAD

Perfusion

Function

Viability

Vulnerable Plaque Assessment (FDG ?)

take home message
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.
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