1 / 62

Ronald Boellaard r.boellaard@vumc.nl

Molecular Imaging using Positron Emission Tomography: Assessment of (neuro-)receptor changes with PET. Ronald Boellaard r.boellaard@vumc.nl. Even voorstellen (mini CV). Ronald Boellaard Huidige functie: klinisch fysicus en UHD bij de afdeling Nucleaire Geneeskunde, VUmc, A’dam

aislin
Download Presentation

Ronald Boellaard r.boellaard@vumc.nl

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Molecular Imaging using Positron Emission Tomography:Assessment of (neuro-)receptor changes with PET Ronald Boellaard r.boellaard@vumc.nl

  2. Even voorstellen (mini CV) • Ronald Boellaard • Huidige functie: klinisch fysicus en UHD bij de afdeling Nucleaire Geneeskunde, VUmc, A’dam • Vooropleiding:- VWO (Gym-β), 1987- Exp.Natuurkunde (en Biologie), 1994- AIO/promovendus op het NKI (afdeling RT) , 1998- opleiding klin.fys. Op VUmc, 2001- klin.fys./UHD op VUmc – tot heden • Klinische of Medische Fysica = toegepaste fysica

  3. Presentation • General introduction NM and PET • Physics and principles of PET- general introduction- overview of (neuro-receptor) tracers- positron emission and coincidence detection • PET pharmacokinetic analysis- principles of kinetic modelling- generation of parametric images • SPM example of assessment of (neuro-) receptor change

  4. Physiology Imaging Emission Tomography Biochemistry Quantification Pharmacokinetics Flexibility NM & Positron Emission Tomography

  5. The spectrum of medical imagingJones, 1996 Structure/anatomy X-ray/CT/MRI Physiology US, SPECT, PET, MRI/S Metabolism PET, MRS Drug distribution PET Molecular pathways PET Molecular targets PET, SPECT

  6. Clinical Applications • Oncology • Cardiology • Neurology / Psychiatry • Pneumology • Nephrology ......

  7. Very basic principle of nuclear medicine and PET • Inject radiopharmaceutical (single photon or positron emitter labelled to a drug) • Use gamma or PET camera to:- evaluate distribution of radiopharmaceutical at some time after injection- evaluatie uptake, retention and washout of radiopharmaceutical = dynamic or kinetic information

  8. I. Qualitative analysis of PET studies“qualitative/visual inspection” Examples of FDG whole body scans Purpose: staging, unknown primary

  9. II. Semi-quantitative analysis of PET studies“standard uptake values (SUV)” regions of interest analysis: Average uptake (Bq/cc) in e.g. tumor SUV is the uptake of a radiopharmaceutical, normalised to the injected dose and body weight (or lean body mass or body surface area etc) Purpose: diagnosis (benign/malignant), prognosis, response monitoring, definition of RT treatment volumes,…

  10. Department of Nuclear Medicine and PET Researchlocation ‘hospital’ RDS 111 15O-cyclotron CTI / Siemens HR+ PET scanner

  11. Department of Nuclear Medicine and PET Researchlocation ‘Radionuclide Centre’ GMP lab with 6 hot cells HRRT PET scanner

  12. The High Resolution Research Tomograph (HRRT) PET scanner • 8 panel detector heads • 60.000 LSO crystals • 1 crystal = 2.1 x 2.1 x 7.5 mm • 1 billion lines of response • Cs-137 singles transmission • 3D only, no septa • Only 10 scanners in the world (up to now 4 operational)

  13. Figure A: HR+, 7 mm resolution Figure A: HR+, 7 mm resolution Figure A: HR+, 7 mm resolution Figure B: HRRT, 2.5 mm resolution Figure B: HRRT, 2.5 mm resolution Figure B: HRRT, 2.5 mm resolution HRRT upcoming protocols: Clinical Comparison with HR+: A STUDY IN NORMAL SUBJECTS USING THE TRACERS [11C]RACLOPRIDE, [11C]FLUMAZENIL AND [18F]FP-b-CIT.

  14. HRRT upcoming protocols: Clinical Comparison with HR+: A STUDY IN NORMAL SUBJECTS USING THE TRACERS [11C]RACLOPRIDE, [11C]FLUMAZENIL AND [18F]FP-b-CIT.

  15. Isotope production Nuclear reactions t1/2 18F (p,n) 110 min 11C (p,a) 20 min 13N (p,a) 10 min 15O (p,n) 2 min

  16. GMP- LAB

  17. Current Tracers [11C] [11C]Flumazenil central type benzodiazepine receptor (R)-[11C]PK11195 activated microglia [11C]Raclopride D2/D3 (R) -[11C]Verapamil PgP in BBB [11C]R116301 NK1 receptor [11C] PIB amyloid

  18. Current Tracers [18F] [18F]FP-CIT dopamine transporter [18F]MPPF 5HT1a receptor [18F]FDDNP amyloid [18F]FLT proliferation [18F]Proline aminoacid [18F]FDG glucose metabolism

  19. Current Tracers[15O] [15O]H2O perfusion [15O]O2 oxygen consumption [15O]CO blood volume OXYGEN EXTRACTION FRACTION

  20. Presentation • General introduction NM and PET • Physics and principles of PET- principles- overview of (neuro-receptor) tracers- positron emission and coincidence detection • PET pharmacokinetic analysis- principles of kinetic modelling- generation of parametric images • SPM example of assessment of (neuro-) receptor change

  21. Positron emission positron annihilates with electron 511 keV fotonen Annihilation produces 2 photons of 511 keV which are sent out in opposite directions

  22. Positron emission detection Positron emission tomography is based on the simultaneous (coincidence) detection of both annihilation photons

  23. PET radio-nuclide: positron emitter -> 2 photons acquisition: coincidence-detection coincidence processor

  24. ImageReconstruction Projections PET image reconstruction PET scanner acquires projection reconstruction of activity distribution in patient

  25. Filtered Backprojection Iterative Reconstruction PET Image reconstruction

  26. Results patients (2)Example images, early frame, poor statistics, ‘fully converged’ FBP NAW-OSEM WLS-nn SP-OS-(W)LS

  27. Presentation • General introduction NM and PET • Physics and principles of PET- principles- overview of (neuro-receptor) tracers- positron emission and coincidence detection • PET pharmacokinetic analysis- principles of kinetic modelling- generation of parametric images • SPM example of assessment of (neuro-) receptor change

  28. Tracer Model: Mathematical description of the fate of the tracer in the human body, in particular in the organ under study Purpose: To quantify functional entities given the distribution of Radioactivity (over time) Method: Divide possible distribution of tracer in a limited number of discrete compartments Tracer Kinetic Modelling

  29. Brain FDG uptake as function of time T=0 T=60min

  30. pharmacokinetic modelling Parametric image representing binding of tracer in tissue Dynamic scan Purpose: generation of image representing distribution of PET pharmacokinetic parameter: glucose consumption, DNA synthesis, perfusion etc etc.

  31. Uptake, retention and washout of radiopharmaceutical • Used radiopharm. (=tracer) • Supply of tracer in arterial blood (= input function) • “Physiology” of tumor/organ, which can be quantified using a PET-pharmacokinetic model Shape and amplitude of time activity curve depends on:

  32. Dynamic PET scanspharmacokinetic analysis • dynamic scans consist of 20 to 40 sequential acquisitions during a 60 min period • dynamic scans provide info on the variation of the activity(=pharmaceutical) in an organ/tumor as function of time • dyn. scans are made to study and quantify the “functional or physiological” behaviour of the organ of interest (glucose and oxygen consumption, blood flow, blood volume, neuroreceptor density)

  33. Bolustoediening bij dyn. (Ex) scans Bolus injector Veneuze inspuiting Loodpot met activiteit Bloodsampler waste pomp detector PET scan

  34. Analysis of dynamic PET scansInput function Input function also needs to be corrected for metabolites and plasma/blood ratio’s

  35. Example of Two Tissue Compartment Model PET Tissue Blood Free Bound (or metabolized or trapped)

  36. k3 K1 Ca Cf Cb k4 k2 Analyse van dynamische PET scanskinetische analyse • Quantitative value of a • pharmacokinetic • parameter, such as: • glucose comsumption • Perfusion • DNA synthesis • Hypoxia

  37. Overview of ‘common’ pharmacokinetic models Plasma input models • Single tissue compartment model (1TC-R) • Single tissue compartment model (1TC-Ir) • Irreversible two tissue compartment model (2TC-Ir) • Reversible two tissue compartment model (2TC-R) Reference tissue input models • Simplified reference tissue model • Full reference tissue model

  38. Reversible single tissue compartment model with plasma input PET Tissue K1 Blood k2 K1=E x F, E=extraction and F=flow=perfusion Vd= K1/k2 = volume of distribution

  39. Irreversible single tissue compartment model with plasma input PET Tissue K1 Blood K1=E x F, E=extraction and F=flow=perfusion

  40. Irreversible two tissue compartment model with plasma input PET Tissue k3 K1 Blood Free Bound/ metabolized/ trapped k2 K1=E x F, E=extraction and F=flow=perfusion Ki= K1 x k3/(k2+k3)

  41. Reversible two tissue compartment model with plasma input PET Tissue k3 K1 Blood Free Bound k4 k2 K1=E x F, E=extraction and F=flow=perfusion BP=k3/k4 (sum of specific and ‘slow’ non-specific binding Vd= K1/k2 x (1+BP)

  42. Reference tissue models A reference tissue time activity curve (TAC) is used as input in stead of plasma input R1=K1/k2=K1’/k2’=relative flow distribution BP=k3/k4=‘specific’ binding

  43. Presentation • Physics and principles of PET- general introduction- overview of (neuro-receptor) tracers- positron emission and coincidence detection • PET pharmacokinetic analysis- principles of kinetic modelling- generation of parametric images • SPM example of assessment of (neuro-) receptor change

  44. Parametric pharmacokinetic modelling Parametric image representing binding of tracer in tissue Dynamic scan Purpose: generation of image representing distribution of PET pharmacokinetic parameter: glucose consumption, DNA synthesis, perfusion etc etc.

  45. PET pharmacokinetic parametric methods • Parametric=pixelwise=voxelwise, i.e. calculation/modeling is performed per pixel/voxel • A 3D PET image (volume) consists of ~106 voxels • Ergo, parametric methods need to be fast • Most parametric methods use ‘tricks’ to gain computational speed (linearisation,basis function method, (multi-) linear plots) • Parametric methods are fast calculations performed for each voxel (independently).

  46. Parametric kinetic modelling(1) basis function and linear methodsBlood flow model example K1 Cb, Cp Ct k2

  47. Theory • 2 solutions for differential equation: • convolution: • linearization:

More Related