Positron emission tomography and molecular imaging

Transcription

1 Positron emission tomography and molecular imaging EHH, May, 2010 Juhani Knuuti Turku PET Centre University of Turku Turku, Finland

2 PET Imaging in Medicine MRI CT MRI PET US SPET MEG CT PET MRI MRS PET Physiology PET Metabolism PET SPET PET Drug distribution Receptors Molecular pathways Gene expression Structure

3 Why PET? Unlimited number of natural tracers Quantitative method Very high sensitivity Very high chemical resolution Reasonable good spatial resolution (up to 2 mm) Turku PET Centre

4 Cardiac PET vs SPECT Advantages of PET Faster short-lived tracers allow faster rest and stress studies higher patient throughput Lower radiation dose (O-15-water 1.8 msv, NH3 and 82Rb 2.5 msv) Less image artefacts Routine attenuation correction, no rotating camera heads higher specificity Higher accuracy Higher spatial resolution and heart-to-background ratio improved detection of small perfusion defects higher sensitivity More accurate detection of disease Quantitative technique Higher temporal resolution dynamic imaging absolute quantification Extraction and kinetics of PET agents Hybrid scanners with state of the art multislice CT Versatile method (molecular imaging, plaques, viability with higher sensitivity, monitoring of disease)

5 Image artifacts in SPECT low count breast motion upward creep breast diaphragm

6 Quality control in PET/CT

7 Clinical Cardiac PET Imaging of viability Perfusion imaging Turku PET Centre

8 Ischemic CMP Gated FDG PET, Hybrid FDG-PET + CTA Turku PET Centre

9 Clinical Cardiac PET Imaging of viability Perfusion imaging

10 Measured/modelled flow Quantification of myocardial blood flow: Different kinetics in different tracers O-water N-ammonia Rb 201 Tl 99m Tc-MIBI Absolute flow (ml/g/min)

11 The strengths of cardiac perfusion PET Advantages Quantitative Fast Image artifacts rare Versatile method Functional information High accuracy Smaller radiation burden Limitations Availability Costs? Complex? Less prognostic data of perfusion studies Tracer availability Turku PET Centre

12 Myocardial Perfusion with PET N 13 -ammonia, O 15 -water, Rubidium 82 Measurement in ml/min/g At baseline and during adenosine hyperemia Coronary flow reserve Flow during hyperemia / flow at baseline Coronary resistance Mean blood pressure / flow Subtraction image with O 15 -water and PET Turku PET Centre

13 The accuracy of PET in detection of CAD (relative perfusion) Study N Se (%) Sp (%) Schelbert et al Gould et al Yonekura et al Tamaki et al Demer et al Go et al Williams et al Stewart et al Marwick et al Grover-McKay et al Gupta et al Leuenbacher et al Uchechukwu et al Bateman et al Sampson et al Total ~1300 ~90 ~90

14 PET for Localization of CAD Criteria Accuracy CFR Stress MBF All subjects >50% >70% >90% Normals Muzik et al; JACC / /97

15 82 Rubidium Perfusion Study Stress SA HLA VLA Rest

16 Myocardial Perfusion with PET: Rb-82 Advantages Limitations - Generator based tracer production - Quantitation need clinical validation - Reasonable good image quality - Expensive for small units - Short protocol - Partial volume correction - Retention depends on metabolism -

17 [ 13 N]Ammonia Perfusion Study Stress SA HLA VLA Rest

18 Myocardial Perfusion with PET: N-13-NH3 Advantages Limitations - Good quality perfusion image - Longer half-life, longer protocol - Robust data analysis - Partial volume correction - Measures average flow in tissue - Retention depends on metabolism - Global and regional MBF reproducible - 3-compartment model - Tracer production with cyclotron

19 Myocardial Perfusion with PET: O-15-Water Advantages Limitations - Short protocol - No immediate perfusion image - Freely diffusible ideal tracer - Noisy data - Simple single compartment model - Production requires cyclotron - Partial volume correction - Measures flow in perfuseable tissue - Global and regional MBF reproducible - Easy routine tracer production Continuously working 0-15 water production Disposable sterile components Fully remote controlled tracer injection - PTF may be used as viability marker

20 New perfusion tracers for Cardiac PET? Ga-68-Bapen Nekolla et al ESC2007 Turku PET Centre

21 Analysis of dynamic PET Imaging: Complicated? Carimas TM free software developed by Turku PET Centre Nesterov et al EJNMMI 2009

22 Molecular Imaging in Medicine MRI CT MRI PET US SPET MEG PET MRI MRS PET Physiology PET Metabolism PET SPET PET Drug distribution Receptors Molecular pathways Gene expression Structure Turku PET Centre

23 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 Analogue Metabolism Labeled Fatty Acid Analogue Labeled Acetate Labeled Membrane Integrity / Annexin Apoptosis / Cell Labeled Antimyosin

24 PET: Molecular imaging of metabolic pathways F-18 FTHA O-15 oxygen Turku PET Centre C-11 Lactate

25 Cardiac oxidative metabolism: [ 11 C]Acetate PET RV K mono K mono LV

26 Effect of CRT on global LV efficiency Rest Rest and stress Ukkonen et al Circulation 2003 Sundell et al JACC 2004 Turku PET Centre

27 Visualizing Gene Transfer & Expression: The Principle of Reporter Gene Imaging Reporter Gene Gene Product Reporter Probe Ligands FESP SST-Analogues Receptors D2R SSTR Transporters Na-I-S NET Iodine HED Substrates FIAU FHBG Enzymes HSV1-TK HSV1-sr39TK Vector Reporter Gene

28 Imaging of vulnerable plaque...

29 Plaque rupture: the morphological view normal vulnerable ruptured Rupture Fibrous cap Thrombus M. Davies, 1998 Large lipid core, thin fibrous cap (Cheng et al. 1993) Inflammation: M and Lymphocytes (Lendon 1991, van der Wal 1994)

30 Toolbox of tracers required? Markers of all stages of disease. SR-A&B targets RGD peptides FDG MMP s Factor XIII substrates ndothelin peptides Inducible NOS substrates CD40L PK11195 PPAR gamma Angiogenesis Markers CD36 Apoptosis Markers Z2D3 Ap4a LOX1

31 Imaging of human unstable atherosclerotic plaques? MRI-PET (18F-FDG) Hoppela et al (unpublished) Plaque activity Morphologie Anatomy Turku PET Centre PET CTA

32 Molecular imaging of human coronary plaques wet dream? Main problem Fast techniques that can cope with motion have too low sensitivity for molecular targets The techniques that has enough sensitivity suffer from motion due to long acquisition Solution? Simultaneous gating of both cardiac and respiratory motion

33 Dual gated cardiac PET/CT study in minipig Frozen heart Catheter in LAD with radioactive tip (20 kbq)

34 Imaging of vulnerable plaque: Dual gated hybrid imaging Unstable angina pt. RCA Hybrid FDG PET/CT Dual gating Lipid diet LAD

35 Imaging of vulnerable plaque: Dual gated hybrid imaging Unstable angina pt. Hybrid FDG PET/CT Dual gating Lipid diet PT2