József Varga Introduction to UCLEAR MEDICIE Department of uclear Medicine University of Debrecen 2011. UCLEAR MEDICIE uclear Medicine: Manuals Required reading: Taylor A., Alazraki., and Schuster D.M.: A Clinician's Guide to uclear Medicine (2nd Edition) The Society of uclear Medicine, Reston, 2006 ISB: 0972647872 Link to English reference manual: http://www.auntminnie.com/index.asp?sec=ref&sub=ncm Lectures in English: http://www.nmc.dote.hu/nmt_eng/oktatas_e.htm In Hungarian: http://www.nmc.dote.hu/nmtk/index.html Book: A ukleáris Medicina Tankönyve (Szerk. Szilvási I.; B+V Kiadó, 2002, 2010) Medical & biological applications of radionuclides 2 1924: Principle of radiotracer applications: Medical applications (nuclear medicine) Research applications (nuclear medicine) Changing an atom in a molecule for its radioisotope will not change its chemical and biological behaviour significantly. Consequence: the movement, distribution, concentration of the molecule can be measured with radiation detectors. György HEVESY (1885-1966) 1943 obel Laureate in Chemistry for his work on the use of isotopes as tracers in the study of chemical processes Diagnostics Therapy 3 4 In vivo imaging In vivo non-imaging In vitro Application of diagnostic methods for research Molecular imaging Combination of analitical laboratory methods with radiotracer technique Fields of uclear Medicine: 1. In vitro concentration measurements Fields of uclear Medicine: 2. In vivo imaging A. With gamma emitters ( single photon ) 1960: Yalow and Berson developed a radioassay for measuring Insulin concentration from plasma samples (saturation analysis) 1957: Anger camera RIA: radioimmunoassay (competitive protein binding; the ligand is labeled) IRMA: immunoradiometric assay ( sandwich assay) RSALY YALW (1921-) 1977 obel Laureate in Medicine for the development of radioimmunoassays of peptide hormones Principle: many photomultiplier tubes see the same large scintillation crystal; an electronic circuit decodes the coordinates of each event Hal Anger (Berkeley) with his positron camera Developer of the scintillation camera 5 6 2. In vivo imaging B. With positron emitters ( kétfotonos ) Early 70-s: PET Principle: Two 511 kev photons resulting from annihilation fly in opposite directions. Their coincident detection determines the line of annihilation. Michel M. Ter-Pogossian, Mallinckrodt Institute Michael E. Phelps, UCLA Selecting the radionuclide for imaging For external detection: electromagnetic radiation can be used! Gamma emitters gamma energy: 80-400 kev (if lower: attenuated inside the patient if higher: low detection sensitivity) Characteristic X-ray (following K-capture) 7 8 e - X-ray γ Positron emitters annihilation radiation: 2 511 kev C-11-13 -15 F-18
Producing artificial radioactive material Radionuclides in uclear Medicine, UK 2003/04 In nuclear reactors (high neutron flux) Using accelerators (circular: cyclotron) expensive! Kr-81m; 6.1% Cr-51; 3.8% R therapy Tl-201; 2.4% Gamma imaging I-131; 2.3% F-18; 1.5% C-14; 1.2% Tc-99m; 79.5% Ernest Lawrence (Berkeley) inventor of the cyclotron Egyéb; 1.3% generator Filter Air filter Lead shielding Alumina column 11 The role of a collimator IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Crystal 10 1. Collimator 2. Crystal: ai (Tl) 3. Photomultiplier tubes 4. Impulses 5. Anger circuit 6. X, Y coordinates 7. Good events 8. Memory scope 9. Analog-digital converters 10. Computer Eluent Detector Anger (gamma) camera Evacuated vial PET imaging In-111; 0.4% 9 99Mo-99mTc Xe-133; 0.8% I-123; 0.7% Stanley Livingstone and Ernest Lawrence with their 8 MeV cyclotron (1935) Matrix circuit Differential discriminator 12 Introductiontouclear Medicine 14 PET: Concept Lead collimator Photomultipliers + preamplifiers To form an image from the detected photons, the direction of movements should be known The collimator lets through only the photons that move perpendicularly to its plane Source: Freek Beekman et al., Utrecht 13 Fields of uclear Medicine: 3. Therapy with Medical imaging unsealed radiactive preparations Principle: Beta-emitting radiopharmaceuticals go directly to the cells or tissue to be destroyed or deactivated Very specific radiopharmaceuticals are needed Unsealed preparation: ne that mixes in the patients body on a molecular level (e.g. after intravenous injection) Source: What is uclear Medicine? (SM) 15 16
United ations Scientific Committee on the Effects of Atomic Radiations Targets and tools of medical imaging Average of health-care level I, 1991-96 (USCEAR) Brachytherapy Teletherapy Radionuclide therapy Therapy Diagnosis uclear imaging Interventional Angiography CT X-ray, medical X-ray, dental 1 17 19 10 100 1 000 10 000 100 000 umber of procedures / million population 1 000 000 18 20 Functional vs. structural imaging: Low-grade recidive glioma (FDG) PET Center, Debrecen Emission imaging: Study types Detection sensitivity of imaging techniques Static: Imaging technique UH CT Gamma camera PET MRI MRS Concentration of tracer / contrast material (mol/kg body mass) 10-3 10-3 10-9- 10-12 10-9- 10-12 10-5 10-5 Imaging an equilibrium distribution Dynamic: Series of images following the accumulation / metabolic pathways / secretion of a radiopharmaceutical Whole body: Static images connected Tomographic: Single Photon Emission Computed Tomography (SPECT) Positron Emission Tomography (PET) Source: G. von Schulthess, University Hospital, Zürich 21 22 Example: Static image Thyroid scintigram without and with filtering Spot images Whole body bone scintigram RAW image 23 Metz-filtered 24
Different molecules have different distribution Positive scintigram: Toxic nodular goiter Malignant thyroid tumor Decreased activity with pertechnetate higher uptake is abnormal here 99mTc-Pertechnetate 99mTc-MIBI Increased MIBI accumulation 25 Information from dynamic studies Examples: Dynamic studies Time-activity curves from regions Kidney Esophagus 26 Parametric images Calculate a parameter of the time-activity curve for each pixel Gated blood pool Image series utline Regions of Interest Display with pseudo-colors Create timeactivity curves from the RIs 27 SPECT: Single Photon Emission Computed Tomography 28 Gamma cameras Generally 360 arc For the heart: 180 Images at 3-6 (30-120 projections) Calculation of distributions in transaxial slices Reslicing along the organ (transversal, coronal, sagittal) 29 Backprojection Projections utilized: Browser view 1 16 3 32 30 3 dimensional cine display 4 64 31 32
PET - advantages Brain receptor imaging PET ligands for imaging various receptor systems [F-18] fluoro-2deoxy-glucose Coincidence detection at 180 : - higher sensitivity - better signal/noise ratio Easier attenuation correction (sum of the two paths inside = body thickness) More physiologic radiopharmaceuticals (C-11, -13, -15, F-18) Dynamic tomography is possible (simultaneous acquisition from all projections) [C-11]-flumazenil (benzodiazepinereceptor) * [C-11]-b-CPPIT (dopamine transporter) [C-11]-raclopride (dopamine D 2 receptor) [F-18]-memantin (MDA-receptor) [C-11]-Mc5652 (serotonin transporter) H2 H H H H3C H Ph H CH2CH3 FH2C Cl CH3 F H CH2 CH3 H F SCH3 Cl CH3 Cl H CH3 Source: G. von Schulthess, University Hospital, Zürich 33 ur PET is growing up 34 Structure without function is a corpse; function without structure is a ghost From P. Vernon, GE 35 Functional and morphological imaging: CT, MR functional information structural / morphological information significant partial volume effect better resolution higher noise CT: high patient dose attenuation and scatter degrades images MR: inhomogeneous image, geometric distortion (due to magnetic field inhomogeneity) 36 Hybrid devices Complementary roles PET & SPECT PET & CT or SPECT &CT on the same gantry Subsequent imaging, while the patient lies in the same position SPECT/CT 37 Hybrid imaging, step 1: CT 38 Hybrid imaging, step 2: Emission 39 40
History: tomography 1895: X-ray (Röntgen) 1958: Gamma camera (Hal Anger) 1962: Emission reconstruction tomography (David Kuhl) 1971: CT (Godfrey Hounsfield) CT image reconstruction (Allan M. Cormack) 197~: PET (Michel Ter-Pogossian) 1976: SPECT camera (John Keyes) Brain SPECT camera (Ronald Jaszczak) 1992: SPECT/CT, attenuation correction with CT (T. F. Lang, Bruce H. Hasegawa) 2000: PET-CT (Ron utt, David Townsend) 2008: Human PET/MRI Why to use hybrid devices? 1. To integrate anatomical with functional information: Localization Correction for partial volume effect 2. Attenuation correction Faster (shorter imaging time) More acurate (less noisy) CT!!! 41 42 Attenuation correction of SPECT Tumor localization for radiation therapy Uncorrected (filtered backprojection) Attenuation map Corrected (S-EM) Source: M. King et al. 43 44 Effective doses (msv) SPECT M, UK 2003/04 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% Myocardial perfusion ; 15.0% Brain perfusion HMPA; 0.7% 25 Bone Phosphates; 29.0% Lung perfusion MAA; 14.0% (msv) 20 15 10 Scintigraphy Hybrid Complicated radiological Simple X-ray Planar gamma camera Lung ventillation ; 11.3% Kidney, dynamic ; 5.3% Kidney, static DMSA; 4.3% Inflammation HMPA; 1.2% Thyroid Pertechnetate; 1.6% 5 0 Thyroid Stat. kidney Dyn. kidney (DTPA) Dyn. kidney (MAG3) Myocard.perf. (stress+rest) Brain perfusion Bone Lung perf. Hepatobiliary Inflammation (Ga) Myocard. SPECT/CT (stress+rest) FDG+LR-CT FDG+HR CT Intravenous Pyelogram Barium swallow Barium meal CT head CT chest CT abdomen CT pelvis CT (head or chest) PTCA (heart study) Coronary angiogram Mammogram Lumbar spine series Thoracic spine series Cervical spine series Skull (PA or AP) Chest (PA and lateral) Thoracic spine (AP) Lumbar spine (AP) Abdomen Pelvis or hips Cardiac wall motion Tc-rbc; 1.5% Thyroid therapy I-131; 1.5% Tumor metabolism FDG; 1.3% 45 46 Therapy PET onimaging ther PET ; 0.4% GFR Cr-51 EDTA; 3.4% Helicobacter Pylori C-14 urea; 1.0%