Tuesday Seminar 24 th , Dec, 2013 Radiological Physics Lab, Seoul national university

1. An Introduction to Molecular Imaging in Radiation Oncology :A report by the AAPM Working Group on Molecular Imaging in Radiation Oncology(WGMIR) Tuesday Seminar 24th, Dec, 2013 Radiological Physics Lab, Seoul national university Seongmoon Jung

3. Outline • Introduction • Molecular Imaging Modalities and Techniques • Molecular Imaging Challenges in Clinical Radiation Oncology • Conclusion

4. Introduction • Definition “ Directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic, therapeutic applications.” – Radiological Society of North America(2005) “ The visualization, characterization, and measurement of biological processes at the molecular and cellular levels in human and other living things……” – Society of Nuclear Medicine(2007)

5. Introduction • Background

6. Introduction • Interest to the radiation oncology community - Imaging of biological tumor characteristics Such as presence of hypoxia, proliferation rate - diagnosis, radiation treatment, evaluation in the molecular manner

7. Molecular Imaging Modalities and Techniques

8. Molecular Imaging Modalities and Techniques • 5 devices for molecular imaging • PET • SPECT • MRI • Optical imaging • Ultrasound

9. Molecular Imaging Modalities and Techniques • PET – (1) Basic Principle • Simultaneous detection of annihilation X-rays ( two 511 KeV) of a positron - coincident event - random(false) event - scatter event • Positron emitting Radionuclides(Short half life) + biological tracer molecule(Ligand) to localize in vivo in tissues

10. Molecular Imaging Modalities and Techniques • PET – (2) Spatial Resolution • The finite positron range - depends on the radioisotope, the type of tissue • Noncolinearity of the annihilation photons • Pet scanner itself (detector size)

11. Molecular Imaging Modalities and Techniques • PET – (3) application in oncology • FDG to image metabolically active, increased glycolysis - presence of tumor, inflammation • Cerebral blood flow using 15O H2O, tumor hypoxia with 18F fluoromisonidazole, cell proliferation with 11C thymidine • The hybrid PET-CT

12. PET – (4) application in oncology

13. Molecular Imaging Modalities and Techniques B. SPECT –(1) basic principle • Detection of gamma decay X-rays by radiolabeled agents • Gamma emitting radioisotopes + Ligand (99mTc, 111In, 67Ga, 131I, 201Tl ) • Detector called the Anger gamma camera rotated around the object 3 or 6 degree, 120 or 60 projection data mathematically reconstruction

14. Molecular Imaging Modalities and Techniques B. SPECT – (2) Compared to PET • Disadvantage - Using a collimator reduction of sensitivity - Less radiation event poorer spatial resolution • Advantage - Multiple radiotracers can be administered and detected - Relatively long half life radioisotopes slow biological processes - Availability for research even at labs far away from cyclotron facilities

15. Molecular Imaging Modalities and Techniques B. SPECT – (3) application in oncology • A number of radiolabeled tracer for specific tumors • In early work, pre- & post- optimization of lung treatment plans also in brain tumor and malignant lymphoma • Different organs or functions monitored simultaneously • Hybrid SPECT-CT in oncology, cardiology and neuropsychiatry

16. B. SPECT – (3) application in oncology

17. Molecular Imaging Modalities and Techniques C. MRI – (1) Basic Principle • The origin of signal is the magnetic dipole moment - External magnetic field(B0) - RF coil - Gradient coil • Signals (SNR, signal-to-noise ratio) - T1, T2, T2* relaxation time

18. Molecular Imaging Modalities and Techniques C. MRI – (2) Four types of MR • MRSI • Perfusion MRI • Diffusion MRI • Functional MR(fMRI)

19. Molecular Imaging Modalities and Techniques C. MRI – (3) fMRI & MRSI application • MRSI detect, quantify, differentiate neo-plastic disease processes in the brain, breast and prostate - By changes of N-acetylaspartate(NAA) choline lactate, creatine citrate • fMRI - Using BOLD (blood oxygen level-dependent) contrast Relative concentration of deoxyhemoglobin and oxyhemoglobin

20. C. MRI – (3) fMRI , MRSI application

21. Molecular Imaging Modalities and Techniques D. Optical Imaging – (1) Basic Principle • Detection of visible and infrared photons transmitted through biological tissues • Short penetration depth - In vitro measurements - Surface in vivo of small animals

22. Molecular Imaging Modalities and Techniques D. Optical Imaging – (2) Four types • Bioluminescence • Fluorescence – GFP • Diffuse optical tomography(DOT) • Optical coherence tomography(OCT)

24. Molecular Imaging Modalities and Techniques E. Ultrasound • Development of ultrasound - Characterization of tissues through Spectral analysis - Enhancing image quality by the use of specialized contrast agents • High spatial resolution, real-time imaging • But poor image quality

25. Molecular Imaging Modalities and Techniques E. Ultrasound • Contrast Agent, Microbubbles - Small gas-filled bubbles(1~10μm diameter, 10~200nm shell thickness) - Provide contrast due to echogenicity of its gas or shell - Attachment of antibodies, peptides, ligands • Application - Blood vessel detection - Assessment of perfusion and vascular delivery of drugs - Detection of inflammation and angiogenesis of tumors

27. Summary

28. Summary

29. Molecular Imaging Challenges in Clinical Radiation Oncology • A.Spatial scale in molecular imaging • Image quality • Biologic structure definition and response • Biological modeling & application for treatment planning and response assessment

30. Molecular Imaging Challenges in Clinical Radiation Oncology • Spatial scale in molecular imaging • Spatial scale covers 4 orders of magnitude presents challenges with respect to integrating such data into a clinical radiation treatment system • Although resolution is improving due to technological advantages, fundamental physical limits exist

31. Molecular Imaging Challenges in Clinical Radiation Oncology B. Imaging Quality • It depends on a number of complex interacting factors including - the physical processes affecting the signal - origination(depth and surrounding tissues) - spatial & temporal resolution - noise ….. • Each modality requires specialized QA and quality control - individual calibration or QA for each patient • Standardized phantoms, QA tests and benchmark data for various lesion locations would be valuable for future work

32. Molecular Imaging Challenges in Clinical Radiation Oncology • Biologic structure definition and response • Challenges in radiation treatment • Image transmission • Registration of multimodality images • Image interpretation • Composition of the target and critical volumes from a set of multimodality image

33. Molecular Imaging Challenges in Clinical Radiation Oncology • Biologic structure definition and response • Accurate image interpretation is required - Experts - Software tools • Even above challenges are accepted, the clinical use of molecular images is still challenged by the needs to define a target volume • Biological target volumes for multimodality image sets will not be congruent in size or shape • Temporal effects must also be addressed when defining the target

34. Molecular Imaging Challenges in Clinical Radiation Oncology D. Biological modeling & application for treatment planning and response assessment • Predicted models based on biological data from molecular images provide information to therapeutic decisions and prognoses • Standardized image acquisition and processing techniques required To routinely use in biological modeling of radiation dose response

35. Conclusion • Molecular imaging is not only imaging a specific cell or molecular dimensional objects, but also imaging their molecular or biological processes • High resolution anatomical imaging + high sensitivity molecular imaging can achieve volumetric tumor characterization and quantitative modeling of tissue irradiation • For the clinical application - accurate registration - clinical interpretation of data - target definition - image quality • Great challenges and opportunities for collaborations through the convergence of molecular biology, diagnostic radiology, radiation oncology, physics, imaging science, chemistry, and other fields

36. Discussion & Question Thank you for your attention !

38. MRI