PET: quantification of perfusion and beyond Juhani Knuuti Turku PET Centre University of Turku Turku, Finland Juhani.knuuti@utu.fi 27.8.2012 1
Disclosure: Juhani Knuuti, M.D. Juhani Knuuti, M.D. has financial interests to disclose. Potential conflicts of interest have been resolved. Research Support / Grants Stock/Equity (any amount) Consulting Employment Speakers Bureau / Honoraria None None Lantheus None Philips Research contracts (institutional): Orion Pharma, Turku Imanet Ltd, GE Healthcare, GSK, Merck, Bayer-Schering, Novartis, Lundbeck, Roche; Lantheus 2
Quantification of perfusion? Quantification perfusion defect score Quantification = Measurement of myocardial perfusion in absolute terms (ml/g/min) 27.8.2012 3
Quantification of perfusion? Tracer Imaging protocol Data analysis Implementation of quantitative results into clinical reading Understanding the limitations Convince the clinician that quantitative results are useful and reliable 27.8.2012 4
Joutsiniemi et al (submitted) 27.8.2012 5 Absolute flow or flow reserve?
Quantification of perfusion? Tracer Imaging protocol Data analysis Implementation of quantitative results into clinical reading Understanding the limitations Convince the clinician that quantitative results are useful and reliable 27.8.2012 6
Absolute myocardial blood flow: Interpretation criteria need to be revised Stress 6 5 Range in absolute flow image Range in tracer uptake Measured/modelled flow 4 3 2 1 Abnormal Absolute flow Normal Tracer uptake 0 0 1 2 3 4 5 6 Absolute flow (ml/g/min) 27.8.2012 7
Implementation into clinical decision-making Global flow value/reserve in addition to standard reading of relative images Cutoff values for normal and abnormal global flow/reserve Scaling the images into absolute scale regional/vessel based use of quantitative values Cutoff values for normal and abnormal flow 27.8.2012 8
The estimated probability of significant CAD (stenosis+reduced FFR) by O-15 water PET stress flow 27.8.2012 9
Quantification of myocardial perfusion Which patients will benefit? Balanced 3 vessel or multivessel disease Culprit lesion vs. non-culprit lesion in multi vessel disease Early changes in coronary dysfunction 27.8.2012 10
Challenges and solutions of perfusion imaging Challenge Solution LM disease? Balanced 3 vessel disease? Multivessel disease? Anatomical location? Non-ischemic CAD? Microvascular disease? 27.8.2012 11
Challenges and solutions of perfusion imaging Challenge LM disease Balanced 3 vessel disease Multivessel disease Anatomical location Non-ischemic CAD Microvascular disease Solution Hybrid imaging Quantitation Quantitation Hybrid imaging Hybrid imaging Quantitation/ hybrid imaging 27.8.2012 12
The effect of absolute quantification on clinical interpretation of perfusion images No major difference in clinical interpretation: n=54 (51%) More severe multivessel disease with absolute analysis: n=10 (9%) Heterogenous relative perfusion but normal absolute perfusion: n=36 (34%) Balanced 3-vessel disease with preserved relative perfusion: n=6 (6%) 27.8.2012 13
Absolute quantification in patients with multi-vessel disease 100 % 90 % 80 % 70 % 60 % 50 % 40 % 30 % 20 % 10 % 0 % PPV NPV acc absolute relative 106 patients with 30-70% pretest likelihood of CAD Quantitative hybrid PET/CT imaging vs. invasive angiography with FFR Kajander S, et al 2008 27.8.2012 14
Quantification of perfusion? Tracer Imaging protocol Data analysis Implementation of quantitative results into clinical reading Understanding the limitations Convince the clinician that quantitative results are useful and reliable 27.8.2012 15
Problematic patient groups If no anatomical information is available Patients with heart failure Patients with advanced atherosclerosis but no epicardial obstructive disease Microvascular disease 27.8.2012 16
Limitations If no anatomical information is available Patients with heart failure Patients with advanced atherosclerosis but no epicardial obstructive disease Microvascular disease 27.8.2012 17
Quantification of perfusion? Tracer Imaging protocol Data analysis Implementation of quantitative results into clinical reading Understanding the limitations Convince the clinician that quantitative results are useful and reliable 27.8.2012 18
Case Case LeRe Clinical History - 67-year old male - 3 mo stable exercise associated angina that got more severe - Exercise test Normal exercise capacity ECG normal during stress No symptoms After the test chest pain with st-depressions Turku PET Centre, Finland 27.8.2012 19
CTA+ Adenosine stress perfusion Turku PET Centre, Finland 27.8.2012 20 Case LeRe Clinical Application of PET/CT O 15 -water parametric PET/CT hybrid images Relative scale image
Case Case LeRe RCA LAD CTA Findings Left main severe stenosis Distally in LAD and LCX calcified plaques but not clear stenosis. In RCA distally significant stenosis LCX CTA Turku PET Centre, Finland 27.8.2012 21
CTA+ Adenosine stress perfusion Turku PET Centre, Finland 27.8.2012 22 Case LeRe Clinical Application of PET/CT O 15 -water parametric PET/CT hybrid images 3.5 ml/g/min MBF 1.3 ml/g/min 0.0 ml/g/min
Case 2 LCX CT angiography RCA LAD Case:NYM 27.8.2012 23
Case 2 Case:NYM Anterior view Posterior view Hybrid PET/CT imaging (adenosine stress) 27.8.2012 24
Case 2 Case:NYM Anterior view Scale 0-3.5 ml/min/g Posterior view Hybrid PET/CT imaging (adenosine stress) 27.8.2012 25
Ziadi MC, et al J Nucl Cardiol 2012. 27.8.2012 26
12 unselected examples of relative vs quantitative analysis Relative Absolute Relative Absolute Relative Absolute 27.8.2012 27
Quantitation vs relative analysis of perfusion A Saraste and J Knuuti JNC 2012 27.8.2012 28
Labeled Stem Cell Stem Cell Engraftment Labeled ATR Ligand Labeled ACE Inhibitor ACE Matrix- Metalloproteina se Labeled MMP Ligand Presynaptic Sympathetic Innervation Nerve Terminal Labeled Adrenocept or Ligand Labeled Catecholamin e Analogue Glucose Postsynaptic Adrenergic Receptors ATR Renin- Angiotensin System (RAS) Cardiac Molecular Imaging Targets Mitochondrium Nucleus Reporter Gene Product MMP v 3 Integrin Reporter Gene v 3 Integrin Expression Vector Labeled Integrin Ligand Gene Expression / Reporter Gene Imaging FFA TCA Flux Labeled Reporter Probe Bengel, F. In: Braunwald s eart Disease, 8th Ed. Labeled Glucose Labeled 27.08.2012 Analogue Fatty Acid Labeled 29 Analogue Acetate Labeled Membrane Integrity / Metabolism Annexin Apoptosis / Cell Labeled Antimyosin