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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


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%


Current Therapy Oxygen Guided Therapy

Oxygenated tissues do not require high radiation dose

MRI pO2 pO2

A B C

low dose

high dose


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


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


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


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


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


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


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


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)


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


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


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


Acknowledgements

EB002034 CA98575

http://epri.uchicago.edu

Matt Maggio (XRAD225Cx corrections)


Charles C. Pelizzari Radiation delivery expertise

Prof. Howard J. Halpern

oxygen-guided radiation therapy - university of chicago · pdf fileoxygen-guided radiation...

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