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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.


  • 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 CollCardiol. 1986;7:464.


    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


    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 SPECT of Artifacts: PET vs SPECT

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


    Radiation exposure msv pet vs spect
    Radiation Exposure ( SPECTmSv) PET vs SPECT


    Perfusion pet advantages
    Perfusion PET Advantages SPECT

    • High spatial and temporal resolution.

    • Excellent sensitivity.

    • Accurate depth-independent attenuation correction.

    • High contrast resolution.

    • Quantitative imaging capabilities.


    Myocardial Blood Flow and SPECT

    Radiotracer Uptake




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

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


    Characteristics of a Normal Perfusion PET 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 Perfusion PET 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 Perfusion PET

    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


    • Multivessel Perfusion PET Disease

    • Ischemia + Transient Dilatation


    PET Perfusion/Metabolic Imaging Protocols Perfusion PET

    13N-ammonia

    82Rb

    13N-ammonia

    82Rb

    18F-FDG

    Transm.

    Rest

    Exercise

    Pharm.

    Stress

    Metabolic

    Imaging

    Dipyridamole

    Adenosine

    Dobutamine


    Quantification of Myocardial Blood Flow Perfusion PET

    Rest

    LAO

    Stress

    RAO


    Arterial Tracer Input Function and Changes in Perfusion PET

    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)


    Clinical Value Long Term Known Perfusion PET

    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


    Clinical Value Long Term Known Perfusion PET

    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


    Long Term Prognostic Value PET Perfusion Perfusion PET

    Added Value of Coronary Flow Reserve

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


    Clinical Role of Quantitative Perfusion PETPET

    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 Perfusion PET

    • 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 Perfusion PET

    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


    FDG Perfusion PET

    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


    PET Myocardial Viability Perfusion PET

    NH3

    FDG

    Stress

    Rest

    Fixed

    Match

    Fixed

    Mismatch

    Partially Reversible

    Match

    Partially Reversible

    Mismatch


    r Perfusion PET=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.


    80 Perfusion PET

    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


    The Next Thing is… Perfusion PET.

    Tracking of Genetically Labeled Progenitor Cells by PET

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


    Hybrid PET/CTA: Myocardial Perfusion and Function Perfusion PET

    Concurrent Rest & Peak Stress Function

    Coronary Calcium Assessment

    Cardiac Perfusion

    CTA


    Progression of atherosclerosis

    PET Perfusion 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? Perfusion PET

    • 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 Perfusion PET

    • 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


    Spect underestimates disease burden stable cad

    Calcium score: 890 Perfusion PET

    SPECT Underestimates Disease Burden: Stable CAD


    Why use pet cta
    Why use PET/CTA ? Perfusion PET

    • 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 Perfusion PET

    0:30 min

    Rest-Stress PET Rubidium-82 and CTA Protocol



    Relationship of stress induced ischemia and atherosclerosis cac

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

    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.


    Prognosis of Cardiac Events by PET-CT Perfusion PET

    Added Value of CAC

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


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


    Pet and cta complement each other
    PET and CTA Complement Each Other Perfusion PET

    • 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


    Scenarios in Cardiac PET/CT imaging for Functional Measures of Atherosclerosis

    (suspected) Coronary Artery Disease


    Infarct size measurement Functional Measures of Atherosclerosis

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


    Changes coming with hybrid imaging nuclear cardiology evolution
    Changes Coming With Hybrid Imaging Functional Measures of AtherosclerosisNuclear Cardiology Evolution

    • PET-CT:

      Comprehensive evaluation of CAD

      Perfusion

      Function

      Viability

      Vulnerable Plaque Assessment (FDG ?)


    Take home message
    Take Home Message Functional Measures of Atherosclerosis

    • 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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