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 Define Target Treatment Planning Background
Accurate &
Optimized
Background
Molecular Imaging
Tumor cells
Biological Character
Physiological
change
Spatial extent
Define Target
Treatment Planning

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
FDG 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