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Oxygen-guided radiation therapy
Boris Epel Dept. Radiation and Cellular Oncology, University of Chicago Center for EPR Imaging in vivo Physiology
Outline
• Introduction ▫ Oxygen as a biomarker - The impact of tumor
oxygenation on radiation therapy • Imaging large objects ▫ Oxygen images with 1.2 mm spatial resolution and
1 torr pO2 accuracy ▫ Image registration with MRI / CT
• Development of hypoxia-targeted radiation therapy for small animals with sub- millimeter precision
EPR Oxygen Imaging Workshop 2017, Chicago
Oxygen and radiation treatment
Tumors with low oxygenation levels are resistant to
radiation and chemotherapy.
Hypoxia induces changes
in cell sensitivity to
radiation cytotoxicity.
Hypoxia threshold 10 torr
3
EPR Oxygen Imaging Workshop 2017, Chicago
Rockwell, S. Manual de Radiotherapia Oncologia. Yale University; New Haven CT: 1989. Principios de radiobiologia
Barnett GC, West CML, Dunning AM, et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nature reviews Cancer. 2009;9(2):134-142. doi:10.1038/nrc2587.
HF10=0%
EPR Oxygen Imaging Workshop 2017, Chicago
Current Therapy Oxygen Guided Therapy
Oxygenated tissues do not require high radiation dose
MRI pO2 pO2
A B C
low dose
high dose
EPR Oxygen Imaging Workshop 2017, Chicago
Getting ready to human imaging
T1 Sequences with Reduced SAR
τ τ T
Inversion recovery (IRESE)
T τ τ
Stimulated Echo (SE)
Pulse Seque
nce
T1 Error of T1
Transmitted
power IRESE 5.9
µs 0.29 µs 0.42 W
SE 5.8 µs 0.38 µs 0.05 W
We use IRESE sequence for preclinical imaging due to higher precision and accuracy Stimulated echo sequence allows to reduce average transmitted power by a factor of 8
EPR Oxygen Imaging Workshop 2017, Chicago
Time resolved Oxygen Imaging
0 5 10 15 20 2530
35
40
45
50
55
60
N image
0 5 10 15 20 2510
15
20
25
30
35
40
N image
0 5 10 15 20 250
5
10
15
20
25
N image
1 3
2
1
2
3
pO2 [torr]
Spontaneous fluctuations of pO2 in tissues
60
0
What is more relevant for therapy: static or acute
hypoxia ? What is the relevant time
frame for oxygen imaging ?
Key Problem: FDA Approval
• Instrumentation • Spin probe
• See Lecture 9
Imaging large objects
Surface coils and large magnets EPR Oxygen Imaging Workshop 2017, Chicago
• Large objects will require surface coils rather than volume resonators
• We have developed bimodal surface coil that can be applied to superficial tumors imaging
• We have large magnets capable to accommodate a human
Localization of objects in large magnet
EPR Oxygen Imaging Workshop 2017, Chicago
Rigid body
Surface coil
Vicra
𝒓𝒓𝟎𝟎
Advance methods of image composition
mm
190 µm per voxel
mm
Effective bandwidth
Imager bandwidth
Large object
High resolution
75 mm
Seifi, P., et al., Medical Physics, 2010. 37(10): p. 5412-5420.
13
Multi-B ESE leaves no instrumental restrictions on object size and image resolution
EPR Oxygen Imaging Workshop 2017, Chicago
Large Animal Imaging – Rabbit EPROI
• Large size 4 cm VX-2 tumor located on the leg of a New Zealand white rabbit
• Localized delivery of spin probe. 27 Ga arterial catheter was installed in the femoral artery feeding the tumor-bearing leg of the rabbit
• 170 mg/kg for the first injection and 170 mg/kg/h continuous infusion
• Intravenous injections to mice requires 800 mg/kg injection
• For humans the dose reduction will be even larger
EPR Oxygen Imaging Workshop 2017, Chicago
Rabbit EPROI
• The study involved volume 52 mm resonator
• Continuous wave and pulse EPR oxygen imaging were tested
• Image duration: 45 min for CW and 13 min for pulse imaging
• Similar results were obtained • Pulse images show considerable
advantage both in acquisition speed and pO2 precision
CW
CW
Pulse
Pulse
MRI
EPR Oxygen Imaging Workshop 2017, Chicago
Radiation delivery with sub-millimeter accuracy
Oxygen image-guided radiation therapy EPR Oxygen Imaging Workshop 2017, Chicago
EPR and MRI compatible animal bed
The 25 mm bed
• Diameter: 19 mm and 25 mm • Technology: 3D printing, SLA, Accura Xtreme White 200 • Compatibility: Bruker 9.T MRI, EPR imager, animal CT
The 19 mm bed with wide tail
Radiation protocol: 5 beam conformal radiation protocol
EPR Oxygen Imaging Workshop 2017, Chicago
The beam’s eye view (BEV) apertures are produced by projection of all target voxels along the beam direction onto the radiation block plane
Source, port1
port 3
port 2
port 4
port 5
Fused deposition modelling 3D printer and GMASS Tungsten infused filament
EPR Oxygen Imaging Workshop 2017, Chicago
Fused deposition modelling: 1 – nozzle ejecting molten material, 2 – deposited material (printed part), 3 – controlled movable table
lead
GMASS
Half-depth is 4x smaller as compared to lead
Radiation blocks and holder EPR Oxygen Imaging Workshop 2017, Chicago
Comparison of radiation delivery methods (geometric approximation)
EPR Oxygen Imaging Workshop 2017, Chicago
Red curves show delivery histogram, ideally 100% of volume should receive full dose. Blue curves show radiation delivery for non-targeted areas. The area below this curve should be as small as possible.
Spherical volume radiation delivery
5 field conformal radiation delivery
Target is missed
Non-target is irradiated
Validation of the radiation delivery
EPR Oxygen Imaging Workshop 2017, Chicago
Radiation Phantom
Posts that hold The phantom together
Radiation films
22.5 mm
1mm
Contours –calculated profiles
0.4 mm precision is estimated
Figure 2. Dataset: IMRT_45_experiment
EPR Oxygen Imaging Workshop 2017, Chicago
Conclusion
We developed unique preclinical image-guided technology for delivery radiation with sub-millimeter precision • Unique radiation beam spatial resolution better than 0.4 mm • Enabling technology for animal radiation tests • Potential for dose compensation • Relatively fast • Low cost
This technology may be suitable as a low cost substitution of conventional intensity modulated radiation machines
EPR Oxygen Imaging Workshop 2017, Chicago
Acknowledgements
EB002034 CA98575
http://epri.uchicago.edu
Matt Maggio (XRAD225Cx corrections)
EPR Oxygen Imaging Workshop 2017, Chicago
Charles C. Pelizzari Radiation delivery expertise
Prof. Howard J. Halpern