Medical Physics (a Peacefull activity!) Thanks to Nuclear Physics ….

1. Medical Physics(a Peacefull activity!) Thanks to Nuclear Physics …. Yves Lemoigne, ESI-Archamps (near Geneva) European School of Medical Physics (ESMP) Note for this presentation: - Slides with green background concern mainly ESMP organisation • Slides with yellow background concern mainly Medical Physics taught during the School (within other topics taught in Archamps…)

3. ESMP=6 weeks: 3 Imaging, 3 RT

4. - Help to diagnosis (anatomical imaging and functional imaging) : MRI, Echography, X-ray Radiology, SPECT & PET… - Radiotherapy: tele- and Brachy-therapy (with X-rays, inserted radioactive products, protons & Ions beams..) Since More than 50 years Physics is a great help to Medicine and Biomedical research : Chicago University Now: (X-rays) Future: Protons / Ions

5. Medical Physics & Nuclear Physics They have clear links : Because techniques used in MP are directly coming from Nuclear Physics : Ex : Particle accelerators for Radiotherapy (electrons, protons, ions…) or radiotracer production EX : sealed sources used in Brachytherapy EX : Radiotracers with PET (SPECT) cameras The case of PET will be developped here

6. Basic principles for Medical IMAGING CT-Scan X-ray imaging is “trans- missionimaging” and is used mainly for “anatomy” imaging” Nuclear medicine is “emission imaging” and is used for “functional Imaging” (i.e. how this is Working as function of time)More powerful for oncology PET-Scan

7. Precise Medical Imaging is now compulsory for Radiotherapy BEFORE and AFTER Radiotherapy BEFORE:- Diagnosis - Input for Treatment plannings (accuracy…) Needed TPS If available Future…. • AFTER:- Treatment results

8. Tumor siteX-rays IMXT Protons Oesoph. & stomach 0.15 0.11 0.00 Colon 0.15 0.07 0.00 Breast 0.00 0.00 0.00 Lung 0.07 0.07 0.01 Thyroid 0.18 0.06 0.00 Bone & soft tissue 0.03 0.02 0.01 Leukemia 0.07 0.05 0.03 All 0.75 0.43 0.05 Compared to X-rays 1 0.6 0.07 • AFTER: - Treatment results 3D whole-body PET imaging BEFORE AFTER Estimated absolute yearly rate (%) of 2nd cancer

9. Radio tracers can be used to label the chemical molecule we would like to follow inside the patient body. Positrons emitters more used in PET are : F18(110mn), C11 (20 mn), (in research :N13(10 mn), O15(2mn)….). They allow to see metabolism, while X-ray scan or MRI are better to see the anatomy Nuclear medicine (imaging of metabolism using molecules labeled with an appropriate radioisotope) is therefore not in competition, but in complement of imaging techniques such as X-ray, X-ray scan or MRI (Magnetic Resonance Imaging).

10. Complementarity of imaging devices Example of brain tumor : Nuclear Magnetic Resonance Positron-electron annihilation X-rays MRI CT PET Modest accuracy but good for functionnal imaging (very good sensitivity) : because their abnormal metabolism tumor are avid of glucose which emits photon from e+e-annihilation if radiotracer have been injected previously Excellent accuracy but specific only in some cases (could give functional imaging) : detects resonance of atom nucleus Good accuracy for anatomical imaging (Only density is measured) Complementarity :- CT-PET devices are available (Bodygraph-Siemens…)- MRI-PET could be available soon for Small-Animal-PET camera only (Biomedical research only) Specification of the GTV

11. PETcameras for IMAGING Image fusion (CT + PET) Positron Emission Tomography (PET) is one form of radio- pharmaceutical diagnosis. It is a powerful technique whose development owes Nuclear Research. Due to its good sensitivity, PET allows disease-related changes in tissues and organs could be detected long before serious symptoms set in. “Standard “is now CT+PET devices

12. PET CAMERA : a child of Nuclear Physics Matter – Antimatter annihilation e+ e- => g g Becauseitsprinciple : e+ e- => g g

13. Take care of Scale : 1 meter 15 meters ! Versus PET camera Nuclear Physics (detector @ CERN) gdetectors in circle around Colliding point of the two beams In principle : Particlebeam Particlebeam Positron Radio-Tracer Emitter inside the body e+ e- => g gat 1024 KeV e+ e- => g g + … because higher energy (100000000 KeV !) Size and cost are different ! Realisation: In Hospitals … In Research centers (CERN, Geneva)

14. Medical imaging / Nuclear Physics : Similar techniques Inside a PET camera(here CPET from Philips) in 90’s Scintillators + PM’s Nuclear Physiscs research (ex: CMS exp @ CERN) have replaced photomultipliers (PM) by Avalanche Photodiode (APD). Medical imaging begins to do the same (ex: Lab-PET)

15. Why PET camera are powerful … From Y. Yongen (IBA) Great selectivity due to the 3 conditions we are demanding:-1- detect g with Energy selection ≈ 511 KeV-2- detect two g in sharp timecoincidence (≈10 nanosecond)-3- detect twog in opposite directions (within a few degres) Coincidence detection in a PET scanner

16. Medical Physics &Nuclear Physics PET Photon detectors are done like several Nuclear Physics detectors. Typically : Crystals, PM, gantry, electronic chains and controllers, computer interfaces, hard discs or tapes for mass storage, displays devices…

17. A PET needs a complex environment… Chemistry, Bio-Chemistry, Physics, mathema-tics, computing and… medicine. A cyclotron to produce radioactive tracers (F18, C11..) is needed not too far… Previously only availablein big centres (USA, UE…). With modern transport facilities, a regional centrecould supply hospitals in a 1500 km radius (about)… PET camera for biomedical research can use “generator” Ge68 - Ga68 => e+ (not for human use)

18. All these techniques are studied during the three first weeks of ESMP (111 hours) with some of the best experts from Belgium, France, Germany, Italy, Nether-lands, Switzerland, USA…. ESMP organisation + One week of Medical computing Simulation / modelling of Physics and/or Live systems, Networks,Tools for computer simulation (GEANT4, EGS5…), Image reconstruc- tion algoritms, Data compression and processing…

19. Then ESMP students study the sophisticated techniques of tumors killing by use of radiations (External sources for Radiotherapy, internal sources for brachytherapy)= 74 h or teletherapy or curiethérapie Modern Radiotherapy is more and more obliged to use accurate medical imaging of previous ESMP weeks (Role of Treatment Planning Systems)

20. External radiation therapy refers to radiation applied externally to the body using a beam of high-energy x-rays (or proton / light ion beams) to kill tumor cells (also called Tele-Therapy). Internal radiation therapy refers to the use of small radioactive seeds implanted in the tumor tissue. The seeds emit radiation over a period of time to kill tumor cells (Brachytherapy or Curiethérapie).

21. In Teletherapylinear accelerators dominate In the world radiation oncologists use 10 000 electron linacs delivering X-ray beams. The planning of RadioTherapy treatment has been revolutionized by the ability to delineate tumors. • To irradiate only the tumour oncologists use : • collimator homothetic to tumor shape (Blocks) • Multi-Leaf Collimator (static) : Conformal RT • Dynamic MLC (position varyingduring the irradiation). Driven by computer, it’s IMRT (Intensity Modulated Radiation Therapy) IMRT is an advanced RT technique to treat tumor and to spare surrounding tissue from doses above tolerances. Screen Blocks or Hight-tailored computing applications are needed to perform optimisation and treatment simulation (treatment planning) Often limitations due to availibility of experienced medical personnel (time consuming technique)… High-level education needed…. (ESMP provides it) 21

22. CENTRAL ROLE OF TPS REGISTRATION CT-SCAN MRI or / and PET • external contours • densities • anatomical structures • anatomical structures BEAM DEFINITION TREATMENT PLANNING SYSTEM • beam data library OPTIMISATION • Dose distribution • Dose-Volume Histograms • Biological indices • Reconstructed radiographs(DRR) • Field shapeor • Position of leaves • Treatment parameters • Treatment time(monitor units) SIMULATOR and/or ELECTRONIC PORTAL IMAGING BLOCK CUTTING DEVICE or MLC VERIFIY AND RECORD SYSTEM ACCELERATOR

23. Specification of the GTV Nuclear Magnetic Resonance X-rays Positron-electron annihilation MRI CT PET Kneschaurek, 2002 Impact of the imaging method on the Tumor Volume definition Recall Summary Volumes and Margins[ICRU-50 Supplement of rules definitions] PTV ITV CTV GTV Specification of the GTV

24. In case of deep tumor, it is better to use “several” beams, all converging to the tumor, to avoid excessive dose irradiation of heathly tissuesaround Beam 1 TargetVolume X-ray Beam Proton beam@PSI Beam 2 Beam 3 “Simplest” way : Rotate the accelerator or the patient

25. "Conventional" Planning Inverse Planning Treated Volume Treated Volume TargetVolume TargetVolume OAR OAR OAR = Organ At Risk (for instance Spinal Cord) which is compulsory to protect from high dose. Inverse Planning

26. Modern RT technique :Intensity Modulated Radio-Therapy (Dose Intensity is driven by computer following the previously treatment planning calculating – only if precise imaging taken before) Clinical Example

27. Courtesy of IBA Accelerators for Hadrontherapy:developed first in physics labs They are used routinely in hospitals Hadron Therapy Around 9000 of the 17000 accelerators operating in the World today are used for medicine. Very few ( less than 50) are hadron (P or light Ions) accelerators. (Future ? Next slide : why they are better despite higher cost: the Bragg peak)

28. Protons and ions spare healthy tissues 27 cm tumour target charged hadron beam that loses energy in matter X rays Photons Protons protons or carbon ions linac cobalt 60 proton tail light ion (carbon) httt://global.mitsubishielectric.com/bu/particlebeam/index_b.html 200 MeV - 1 nA protons 4800 MeV – 0.1 nA carbon ions which can control radioresistant tumours Archamps - 17.11.08 – U.Amaldi 28 28

29. Photon IMRT Photon Proton Scattering technique : Low dose outside Conventional Radiotherapy:Important dose outside the tumor IMRT = Intensity Modulated Radio Therapy:still non negligable doseoutside the tumor Particle Therapy: Comparing Proton & photon Conventional RT Y.Yongen (IBA)

30. PT center under operation Courtesy Janet Sisterson & PTCOG Proton Therapy is growing rapidly!

31. Hadron therapy owe very much to Nuclear Research Centres experience for accelerators, beam transport, detectors… A Proton therapy system is a complex system, filling a Hospital building. The treatment rooms are larger and complex (gantries), The total investment is around 100 M€, about half for the equipment, A Proton facility can treat 1500 patients/year mainly for special cases (Proximity organ-at-risk tumors, radioresistive tumor, children tumor…) Hadron facilities providing protons and carbon ions are more costly…. Example of IBA Proton Therapy System

32. The accelerators used today in hadrotherapy are “circular” SYNCHROTRONS 6-9 metres SYNCHROTRONS 18-25 metres Teletherapywith protons (200-250 MeV) CYCLOTRONS (Normal or SC) OR 4-5 metres Teletherapy with carbon ions (4800 MeV = 400 MeV/u) Archamps - 17.11.08 - UA 32 32

33. LET > 20 keV/μm = 200 MeV/cm =40 eV/(2 nm) Production of many unreparable localized double strand breaks and clustered damages DNA- double strand Effect of ΔE/Δx = LET Why light Ions (C12) are better than protons (photons): 2 nm size

34. Accelerators for protontherapy LOMA-LINDA :since 1992 : first Hospital-basedProton therapy centre 2005 : 160 sessions per day

35. In the world protontherapy has already treated 55'000 patients. carbon ion therapy has already treated 4500 patients (Japan, RFA) Close Future : CNAO in Italy The synchrotron (proton and C12 ions ): beams ready in summer 2009 25 m synchrotron and 3 treatment rooms Other centres in progress: Germany (Heidelberg, Marburg)France (Lyon, Caen, Orsay), USA, China, India… Concepts directly transferred from Nuclear Physics Reasearch centres (CERN, DESY, Fermilab…)

36. A new concept: Cyclinac=Cyclotron+ Linac for Image Guided HadronTherapy 2 Modules tested at LNS, Catania, Italy This project would allow radio-tracer production cyclotrons to be transformed at raisonable cost in hadrontherapy facility : A real breakthrough ! now in Microcosm at CERN

37. Example of Prostate cancer A few words about Brachytherapy :Local Eradication of a Tumor by Radioactive Implants Real advantage in case of tumor on moving organs (ab-domen)… Note the spectacu-lar progress when seeds are implanted under Magnetic Resonance Imaging (Geneva) Brachytherapy

38. Last Part of ESMP : RADIOPROTECTION in Medical PhysicsPublic (and media) are very concerned by this topic !

39. Origin of participants involved in EUROPEAN SCHOOL OF MEDICAL PHYSICS MORE THAN 1000 STUDENTS WENT IN ARCHAMPS-GENEVA SINCE THE SETTING UP OF THE SCHOOL IN EUROPE…. * . * … And IN The WORLD EGYPT (as 6 other neighbouring countries) is eligible to a subsidy from NATO Scientific Department in the frame of the “South Mediterranean Dialogue group of countries” Medical Physicists (or students in MP) can contact the secretariat : filiz.zilif@yahoo.com ESMP is known by all European countries (and farer…)

40. Please, Visit our website :www.cur-archamps.fr/esi Or the EFOMP website : www.efomp.org For further information and application form for ESMP 2009 (deadline : June 2009) School activities are on bothsides of the border :- French side : Archamps- Swiss side : Genevabut as Switzerland recently joined the “schengen System”, only one visa is needed !!

41. As a Conclusion-1 : Correlations between Physics & Medicine (from Nobel Prize Robert Hofstadter, Stanford University in 1983)still true

42. Key Areas for Biomedicine In conclusion, there is no doubt that the contribution of Medical Physics (and thus Nuclear Physics) is not negligible in the better efficiency of Medicine during the past decades. This is why a high level education in Medical Physics, done by first class experts deeply involved in this science branch, is absolutely compulsory. CONCLUSION-2 The 50-year tenure of Nuclear Physics in Medicine and Biology has coincided with some of the most important developments in oncology and radiological science, including the introduction of artificial radioactivity, computers and 3D imaging into medicine. These events have profoundly influenced the development of Medicine Fundamental breakthroughs in physics are continuing to yield new medical technologies for identifying and treating a range of diseases. 18.11.2006 ESMP 2006

43. Further information : www.cur-archamps.fr/esi or www.efomp.org