MEDICAL PHYSICS SCIENCE TEACHERS WORKSHOP 2010

1. MEDICAL PHYSICS SCIENCE TEACHERS WORKSHOP 2010 Kathy Willowson K.Willowson@physics.usyd.edu.au Institute of Medical Physics, Sydney University Department of Nuclear Medicine, Royal North Shore Hospital

2. Ultrasound, Radiology, MRI, Nuclear Medicine Diagnostic Imaging Particle transport and interaction with matter Instrumentation – detection, image formation Image analysis – qualitative, quantitative Key areas in medical physics

3. Ultrasound, Radiology, MRI, Nuclear Medicine Diagnostic Imaging Particle transport and interaction with matter Instrumentation – detection, image formation Image analysis – qualitative, quantitative Mechanisms of dose absorption Treatment planning – xRT, SIRT, radioimmunotherapy… Therapy and Dosimetry Radiation safety Key areas in medical physics

4. Today’s workshop • Comparison of diagnostic imaging techniques • Functional vs Anatomical imaging • Radionuclides for therapy • Dosimetry: Calculating dose to organs during • diagnostic and therapeutic studies • Dosimetry and radiation safety: putting dose in • perspective • Quantitative PET in the treatment of cancer

5. Function vs Structure Portable, cheap Real time No radiation No contrast agent Multi-planar imaging Evaluate blood flow Cysts vs solid structures

6. Function vs Structure Portable, cheap Real time No radiation No contrast agent Multi-planar imaging Evaluate blood flow Cysts vs solid structures Poor quality Experience needed Only shows anatomy Difficult for obese Deep lying structures Can’t see through bone/air

7. Function vs Structure Portable, cheap Real time No radiation No contrast agent Multi-planar imaging Evaluate blood flow Cysts vs solid structures Poor quality Experience needed Only shows anatomy Difficult for obese Deep lying structures Can’t see through bone/air No toxic contrast No radiation V good resolution Exquisite detail in soft tissue fMRI

8. Function vs Structure Portable, cheap Real time No radiation No contrast agent Multi-planar imaging Evaluate blood flow Cysts vs solid structures Poor quality Experience needed Only shows anatomy Difficult for obese Deep lying structures Can’t see through bone/air Expensive Claustrophobia Mag field safety Lengthy exams Less detail in bone No toxic contrast No radiation V good resolution Exquisite detail in soft tissue fMRI

9. Function vs Structure Anatomical detail All structures Readily available Fast

10. Function vs Structure Radiation dose May use contrast Artifacts from metal, obese patients Anatomical only Anatomical detail All structures Readily available Fast

11. Function vs Structure Radiation dose May use contrast Artifacts from metal, obese patients Anatomical only Anatomical detail All structures Readily available Fast Functional images See early changes Can delineate between active tumour and scarring WB scanning Quantitative

12. Function vs Structure Radiation dose May use contrast Artifacts from metal, obese patients Anatomical only Anatomical detail All structures Readily available Fast Functional images See early changes Can delineate between active tumour and scarring WB scanning Quantitative Radiation dose Little anatomy Limited resolution Need specific tracers

13. Function vs Structure

14. Function vs Structure

15. Function vs Structure

16. Function vs Structure WB functional imaging shows abnormal uptake in 3 areas. The large focus is clearly off-centre and probably a soft tissue mass

17. Function vs Structure

18. Function vs Structure

19. Function vs Structure

20. Physics of Nuclear Medicine • The tracer principle: Radioactive isotopes have the same chemical properties as non-radioactive isotopes of the same element. They differ only in the number of neutrons in their atoms which leads to different stabilities. Unstable nuclei gain stability by radioactive decay, which results in the emission of different types of particles. When introduced to the body, a radioactive isotope will behave in the same way that its non-radioactive counterpart would. • As a radioactive isotope participates in a certain physiological process in the body, it will emit radiation particles – allows us to image the process as it occurs.

21. Physics of Nuclear Medicine • Tissue specificity: Specific tissues in the body will accumulate specific substances. Labelling one of these substances with a radioactive isotope leads to information on certain tissues or organs of interest. • EXAMPLE - the Thyroid gland: The thyroid removes Iodine from the blood and traps it, where it is processed and used to create thyroid hormones. When we inject I-123 into the blood, it behaves as any isotope of Iodine, and is taken up by thyroid tissue. However, it also emits gamma radiation which can be detected and used to analyse whether or not the thyroid is functioning correctly.

22. Physics of Nuclear Medicine • Radioactive isotopes can emit different types of radiation: gamma rays, x-rays, positrons, electrons (beta), alphas… • Radioactivity used for imaging must escape the body

23. head Physics of Nuclear Medicine Single Photon Emission Computed Tomography (SPECT) detects gamma rays emitted by a radioisotope in the body Positron Emission Tomography (PET) detects gamma rays created by a positron emitting radioisotope

24. Physics of Nuclear Medicine • Radioactive isotopes can emit different types of radiation: gamma rays, x-rays, positrons, electrons (beta), alphas… • Radioactivity used for imaging must escape the body • Radioactivity used for therapy must be contained in the body • Alpha and Beta particles are ideal for therapy because they are heavy and slow – do a lot of damage in a localised area

25. Radionuclide Therapy Alpha particles can irradiate tissues with cellular dimensions, are very effective due to their high LET and can kill cells even in a hypoxic environment Beta particles can irradiate multi-cellular dimensions

26. Advantages of Radionuclide Therapy • Systemic treatment: Eliminates primary tumour and other sites of metastasis that have spread through the body – even if they are yet to be detected with diagnostic imaging • Beta’s have the additional feature of the “bystander effect” – they will kill adjacent tumour cells, even if these cells lack the specific tumour-associated antigen or receptor

27. Treatment of Thyroid Cancer • I-131 is a beta and gamma emitter • Patient takes a capsule of liquid I-131 which is absorbed through the gut into the bloodstream, before concentrating in thyroid tissue • Due to its specificity, very large doses can be given • Beta particles mean very localised damage • Gamma particles mean it can also be used to image distribution of uptake • Systemic treatment – targets ALL thyroid tissue cells – even those that have metastasized elsewhere

28. Treatment of Thyroid Cancer Normal uptake in gut, bladder and salivary glands Uptake in remaining cancerous thyroid tissue Uptake at sites of metastases

29. Treatment of Thyroid Cancer • The body will naturally distribute/take-up 131I • It will also naturally excrete 131I (body fluids – urine) • The PHYSICAL half life of 131I ~ 8 days • The BIOLOGICAL half life is much faster (10-15 hours) • After a therapeutic dose of 131I, about 75% is excreted in 24hrs • The 131I trapped by thyroid tissue is much slower to leave • This uptake/excretion is used to model how much activity should be given to a particular patient • Slow excretion of the remainder = radiation safety issues

30. Treatment of Thyroid Cancer • Beta emitter: • Contamination through body fluids can easily occur • Patient must not vomit in first 24hrs • Flush toilet twice and obey good hygeine practice (wash hands well, use separate bathroom if possible) • Do not prepare food for others • Gamma emitter: • Distance / Time for visitors is important • Discharge limit = 9mSv/hr at 2m or 25mSv/hr at 1m • Transport after discharge must be arranged with a family member / carer (NOT public transport)

31. Treatment of Thyroid Cancer FOR 1 WEEK AFTER DISCHARGE: • Avoid being around members of the public for extended periods of time (transport, cinema, shopping centres) • Sleep alone • Keep extra distance with family members FOR 2 WEEKS AFTER DISCHARGE: • Keep additional distance and only spend short periods of time with children and pregnant women • Delay return to work for this additional week if working with children

32. Selective Internal Radiation Therapy • SIRT involves selective uptake of a radionuclide at the site of disease, usually by “force” • SIR-Spheres: resin microspheres labeled with 90Y • 90Y is a pure beta emitter – ideal for therapy if we can get the microspheres at the site of disease (liver) • Millions of the radioactive microspheres (~30mm in diameter) are injected through a catheter inserted into the hepatic artery • Become concentrated in the microvasculature of the tumour and deliver a very high/localised dose

33. Selective Internal Radiation Therapy

34. Selective Internal Radiation Therapy • Important questions for therapy: • - How much activity do we administer? • - What dose does the tumour receive? • - What dose is given to healthy tissue? • - Is this acceptable/can it be improved? • - What is the risk associated with this dose?

35. Total amount of energy emitted by the source organ x the fraction of that energy absorbed in the target organ Absorbed Dose in the target organ = Mass of the target organ Selective Internal Radiation Therapy How is dose related to activity?

36. Selective Internal Radiation Therapy Where à = cumulated activity (the sum of all transitions occurring in the source organ over the residence time) S = the fraction of energy emitted by the source that is absorbed per unit mass of the target

37. Selective Internal Radiation Therapy • This equation is deceptively simple • Must also consider dose from multiple source organs (summation) • Cumulated activity relies on the “effective half life” (Teff) of the activity which must be modeled based on physical half life and biological clearance:

38. Selective Internal Radiation Therapy Longer “half life” (both physical and biological) = Larger area under time activity curve = Larger cumulated activity = Larger dose

39. Selective Internal Radiation Therapy S = fraction of energy emitted by the source that s absorbed by the target Units = Gy.MBq-1.sec-1 where Gy (Gray) = absorbed dose S values range from simple approximations (whole organ irradiated uniformly) to complex calculations (voxel dose kernels for convolution) Published S value for 90Y in the liver (average mass = 1910g) for an adult male = 7.83x10-5 mGy/MBq-sec

40. Selective Internal Radiation Therapy PROBLEM: What is the absorbed dose to the liver from a SIRT involving 1800MBq of 90Y? Assume all the implanted activity remains in the liver and is uniformly distributed. ANSWER: D = Ã.S Ã = 1.443. f.A(0).T(eff) = 1.443.(1800).T(1/2) 90Y has a half life of 64 hours (230400 sec) Ã = 5.98x10-8 MBq.sec D = 46.9 Gy

41. The concept of dose • Absorbed dose (D): The energy deposited by ionizing radiation per unit mass (all types of radiation), measured in Grays (Gy). 1Gy=1J/kg

42. The concept of dose • Absorbed dose (D): The energy deposited by ionizing radiation per unit mass (all types of radiation), measured in Grays (Gy). 1Gy=1J/kg • Equivalent dose (H): The absorbed dose scaled by a radiation weighting factor (wR) to take into account the type of radiation and how much damage it causes, measured in Sieverts (Sv). X-rays/g-rays/e- have a weighting factor of 1 (1Gy=1Sv), a-particles have a weighting factor of 20. Therefore 1mGy of alpha rad has the same biological effectiveness of 20mGy of x-rays.

43. The concept of dose • Effective dose (E): Takes into account the weighting factor of a given tissue (wT) as opposed to whole body irradiation, measured in units of Sieverts (Sv) (=equiv dose to tissue * tissue weighting factor). The gonads have the highest weighting factor (0.2) as they are the most sensitive to radiation, whilst skin is least sensitive (0.01) (total sum of weighting factors across all tissues = 1). Allows for comparison of radiation of different types to different regions

44. The concept of dose

45. The concept of dose PROBLEM: What is the effective dose to the liver from a SIRT involving 1800MBq of 90Y? Assume all the implanted activity remains in the liver and is uniformly distributed. ANSWER: D = Ã.S = 46.9 Gy = 0.05(46.9 * 1) = 2.4 Sv

46. The concept of dose Is an effective dose of 2.4Sv / absorbed dose of 47Gy acceptable? • Tumour dose -> 100Gy, healthy tissue doses ->??? • Dose measures should be interpreted very carefully • They are useful in the development of new treatments/drugs and to compare existing treatments • Play an important role in assessing risk vs benefit

47. The concept of dose • Background radiation living in Sydney ~ 2mSv/year • Dose limit for radiation workers = 20mSv/year (50mSv in US) • Dose limit to public = 1mSv/year • Chest x-ray <0.05mSv / Mammogram ~ 0.5mSv • Return flight Sydney/London ~ 0.1mSv • Nuc med studies ~ 1-10 mSv / x-ray CT studies ~ 1-20mSv • Evidence for small increases in human cancer above 100mSv (acute exposure, or 200mSv chronic) • Release of 131I cancer patients = 10mSv/hour at 1m

48. The concept of dose • Be careful how you interpret dose!!! • Age at exposure plays an important role • Dose calculations have adopted the Linear No Threshold model, which assumes a linear relationship between exposure and risk • There is no evidence to support this model for doses < 0.2Sv • Some predict that the biological effect below a threshold dose may in fact be reduced • Acute vs chronic exposure also plays a part

49. PET SUV – response to therapy • Medical physics plays an important role in nuclear medicine for the evaluation and staging of disease, and monitoring response to therapy • The quantitative nature of PET allows for direct comparison of uptake across different patients, or in the same patient at different time points • Standardised Uptake Value: • SUV = Concentration (MBq/kg) • Injected activity (MBq) / Body weight (kg)

50. PET SUV – response to therapy • SUV readings can be affected by: Recent chemotherapy, uncontrolled glucose levels (diabetics), leanness of the body, length of fasting prior to test, inflammation/infection, resolution… • Commonly used to indicate benign from malignant lesions: Normal tissue has an SUV=1.0. Lesions with an SUV > 2.5 are likely to be malignant, however lower SUVs can still be malignant • Used in staging and to look at response to therapy, and in comparison of treatment regimes across a patient cohort