Cardiac Positron Emission Tomography

Cardiac Positron Emission

Tomography

Department ofNuclear Medicine

Department of Nuclear MedicineAsan Medical Center

University of Ulsan College of Medicine

Dae Hyuk Moon, MD

Advanced Cardiology… Anatomy to Physiology

PET-CT Fusion… Better Coronary Artery Disease Assessment

CAI – Vessel Tracking Perfusion


Cardiac PET• Perfusion imaging• Cardiac metabolism• Pre & Post synaptic autonomous nervous system• Other cardiac receptors• Atherosclerotic plaque characterization• Angiogenesis• Hypoxia• Cardiac transgenic expression• Cell therapy


Advantage: Cardiac PET over SPECT

• Higher spatial resolution

• Higher temporal resolution

• Quantitation of myocardial flow

• Assessment of myocardial metabolism


Clinical Issues in Cardiac PET

• More expensive than other methods

• Blunted ratio of cost-effectiveness

PET must demonstrate a complementary and optimally unique clinical role in comparison to less costly and more readily available conventional imaging methods and modalities.


ACC/AHA/ASNC GuidelineCardiac Radionuclide Imaging, 2003

• Acute Syndrome

• Chronic Syndrome: Vasodilator stress myocardial perfusion PETDx and risk stratification of pts with an intermediate or high LH of CAD

Equivocal myocardial perfusion SPECT (I) To identify the extent, severity, & location of ischemia as the initial diagnostic test in patients who are unable to exercise, or able to exercise but have LBBB or electronically-paced rhythm (IIa)

• Heart Failure: Perfusion plus PET FDG imaging

Predicting improvement in LV function after revasc (I)Predicting improvement in HF symptoms after revasc (IIa)Predicting improvement in natural history after revasc (I)


ACC/AHA Guideline for PET• Chronic Stable Angina, 2002

• Chronic Heart Failure, 2001 Coronary revascularization: Pts with CAD, angina, and HF (I, A)Noninvasive imaging: known CAD, no angina, candidate for

revasc to detect ischemia & viability (IIa, C)Noninvasive imaging: define the likelihood of CAD in pts with

LV dysfunction (IIb, C)

• Coronary Artery Bypass Graft Surgery, 2002CABG: 2 VD (LAD), LV dysfunction or ischemia (I)PCI or CABG: 1 or 2 VD, large viable, or high risk on imaging (I)PCI or CABG: 1 or 2 VD, mod viable & ischemic on imaging (IIa)

• Percutaneous Coronary Intervention, 2001PCI: large viable myocardium or myocardial ischemia (I)


[18F]FDG PET covered by Medicare in US, 2003

• Diagnosis, staging and restaging of lymphoma and lung, head and neck, esophageal, melanoma and colorectal cancer

• Staging & restaging of breast, and thyroid cancer

• Presurgical evaluation of refractory epilepsy

• Assessing myocardial viability A positive myocardial perfusion imaging study when clinical evidence is

mixed. The decision to perform revascularization is based on theprobability that improved systolic function that can occur with viable myocardium. FDG PET likely detects tissue that will not respond well to revascularization when SPECT is positive and FDG is negative.


FDG PET To Assess Viability

• Regional Function

• Global LV Function

• Symptom and Performance

• Prognosis

• Impact on Patient Management

Prediction of Improvement after Revascularization


• Myocardial perfusion: N-13 ammonia, Rb-82 chloride, O-15 water

• Myocardial metabolism: F-18 FDG, C-11 palmitate, C-11 acetate

Positron Emitters used for Cardiac PET imaging


Myocardial Perfusion, FDG Uptake, and Contraction in Relation to Tissue Classification

Contraction Perfusion FDG Uptake

Normal myocardium N N N

Repetitive stunning ↓ N N or ↑

Hibernation ↓ ↓/↓↓ N or ↑

Transmural scar ↓ ↓↓ ↓↓

Nontransmural scar ↓ ↓ ↓

N, normal; ↓, decreased; ↓↓, severely decreased; ↑, increased.

Bax et al. Semin Nucl Med 2000;30:281-98.


• 12/male

• 1 year ago, Kawasaki’s disease/Coranary aneurysm• Recurrent chest pain

Viability: SN and SP for the Different Imaging Techniques(based on weighted mean values from available studies)

No. of Sens SpecPts (%) 95% CI 99% CI (%) 95% CI 99% CI

Tc-99m MIBI 207 83 78-87 77-89 69 63-74 61-76

LDDE 448 84 82-86 81-87 81 79-84 79-84

Tl-201 reinjection 209 86 83-89 82-90 47 43-51 42-52

F-18 FDG PET 332 88 84-91 83-92 73 69-77 69-77

Tl-201 rest-redistribution 145 90 87-93 86-94 54 49-60 48-61

Bax et al. J Am Coll Cardiol 1997;30:451-60.


Declining specificity in viability studies

• Segments with nontransmural infarction or remodelling:Not necessarily improve in function after revascularizationNot necessarily improve in function after revascularization

• The time of follow-up may be too early.

• Irreversible structural changes in long standing hibernation

• The adequacy of revascularization

• Patient selection bias: "true-negative" segments will not be included in the analysis.

• Other benefit: LV remodeling, ventricular arrhythmia, MIDepartment ofNuclear Medicine

• Inclusion of severe LV dysfunction?

• Varying metabolic conditions

• Different imaging protocol

• Not uniform viability criteria

Limitations of the available viability data


Summary of 20 FDG PET Studies with Functional Follow-up Post Revascularisation

Authors Perfusion tracer Analysis Viability criteria Metabolic conditions

Baer None Semi-quantitative ≥50% of Maximun FDG uptake Oral glucoseCarrel 82Ru NA Mismatch FastingGerber NH3 Semi-quantitative Mismatch ClampGropler 11C-acetate Semi-quantitative Mismatch, FDG > 2SD normal Oral glucoseKitsiou NH3 Semi-quantitative ≥65% of normal FDG uptake Oral glucoseKnuuti Tl-201/MIBI Semi-quantitative Mismatch, normalised FDG uptake Oral glucoseLucignani MIBI Visual Mismatch FastingMaes NH3 Absolute quantification Mismatch, nl ClampMarwick Ru-82 Semi-quantitative Mismatch, nl Oral glucoseFath-Ordoubadi None Absolute quantification rMGU ClampPagano None Absolute quantification rMGU ≥ 0.25 μmol min-1 g-1 ClampPaolini MIBI Visual Mismatch FastingSchoder NH3 Semi-quantitative Mismatch Oral glucoseTamaki NH3 Semi-quantitative Mismatch FastingTamaki NH3 Semi-quantitative Mismatch FastingTamaki NH3 Semi-quantitative Mismatch FastingTillisch NH3 Semi-quantitative Mismatch, nl Oral glucoseVom Dahl NH3 Visual Mismatch, nl Oral glucoseVom Dahl MIBI Semi-quantitative Mismatch, nl Oral glucoseWolpers 11C-acetate Absolute quantification Mismatch Oral glucose

Knuuti , et al. Eur J Nucl Med 2002;29:1257-66.Department ofNuclear Medicine

Allman et al. J Am Coll Cardiol 2002;39:1151-8.

Myocardial Viability Testing & Impact of RevascularizationPrognosis in Pt with CAD and LV dysfunction: A meta-analysis

Survival of pts with viable myocardium: Revasc. > Medical tx?

Viability assessment improve selection of pts for revasc?

Improved outcomes after revasc are related to improved LV function?


Limitations of the available prognosis data• No randomized controlled trials

• Retrospective studies: selection biases

• Small sample size, short f/u period, low event rate

• No standardized criteria for viability

• Limitation of binary grouping: viable vs non

• No standardized medical therapy

• Heterog. pts: CAD, Sx, HF, prior revasc, women

• Different type and completeness of revasc

• Lack of postrevasc study for completeness of revascDepartment ofNuclear Medicine

Successful Viability Outcomes Study Design

• Randomized-controlled trial ideally (or large prospective cohort study).• Large sample size.• Follow-up for at least 5 years.• Adequate power to detect clinically significant differences in mortality.• Stricter inclusion criteria: EF ≤ 40% and epicardial vessels or major

branches with stenosis ≥ 70% on recent CAG (within 6 m).• Use of accurate viability criteria: analysis of ≥ 17 segments, use of

Cox modeling or ROC curves to establish cutoff for significant viability.• Use of both medical and revascularization groups (PCI and CABG),

with analysis using Kaplan-Meier and Cox-adjusted survival curves.• Analysis of baseline characteristics btw subjects undergoing viability

and those not to establish magnitude of referral bias or adjust study design to eliminate large differences.

• Identification of the prevalence of viability in a large cohort of patients irrespective of treatment received.

• Recruitment of more women and minorities. Department ofNuclear Medicine

Unresolved issues• Prospective randomized trialrandomized trial with long-term clinical, perfusion and function

follow-up: Difficult because clinicians already accept "viability study”

• Require confirmation in larger serieslarger series: small number of patients with hard events

• Extent of mismatchof mismatch with PET to suggest good outcome from revasclularization

• Time course of recoverycourse of recovery after revascularization relative to preop index of perfusion and contractile reserve

• Outcome of patients with extensive regions of viable myocardiumcome of patients with extensive regions of viable myocardium by PET that lack contractile reserve

• LV volume measurementvolume measurement adds additional discriminatory value?

• Relationship between tissue viability and changes in LV geometrytissue viability and changes in LV geometry

• Limited data in women and patients with diabetes


Targets for Atherosclerosis ImagingNecrotic core, Fibrous cap, Calcium, Inflammatory activity

Histopathology of Plaque Progression

PET: Smooth muscle cells, Macrophage, Lipid Core


ImagingAtheroscleroticPlaque InflammationWith FDG PET

[3H]DGAutoradiography

Rudd et al, Circulation2002;105:2708-11.


Imaging Large Vessel Arteritis with [18F]-FDG PET

M/81 recurrent fever

Circulation 2003;107:923, & Heart 2003;89:e9.

F/27 Takayasu’s arteritiswith LM stenosis


Inubushi et al. Circulation 2003;107:326-32.

PET Reporter Gene Expression Imaging in Rat Myocardium

Ad-CMV-HSV1-sr39tk IM injection and [18F]-FHBG PET imaging


Bioluminescence and PET: Cardiac Cell TransplantationRats receiving cardiomyoblast expressing HSV1-sr39tk

A: Optical imaging, BC: MicroPET with [18F]-FHBG and [13N]-NH3

Wu et al. Circulation 2003;108:1302-5.Department ofNuclear Medicine

Herreros J, et al. Eur Heart J 2003;24:2012-20.

13N Ammonia 18F FDG 13N Ammonia 18F FDGBaseline Follow-up

Cultured Skeletal Muscle-derived Stem Cells in Infarction


Health & Medicine

Cardiac Positron Emission Tomography