Title

A PRECLINICAL STUDY OF RADIATION-INDUCED LUNG TOXICITY WHEN IRRADIATING IN A STRONG MAGNETIC FIELD

Author ORCID Identifier

orcid.org/0000-0003-0221-4603

Date of Graduation

8-2017

Document Type

Dissertation (PhD)

Program Affiliation

Medical Physics

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Laurence E. Court

Committee Member

David S. Followill

Committee Member

Adam D. Melancon

Committee Member

Christine B. Peterson

Committee Member

Julianne M. Pollard-Larkin

Committee Member

Ramesh C. Tailor

Abstract

The purpose of this work was to evaluate the effect of a strong, transverse magnetic field on the severity of radiation-induced lung damage in mice. This data can be used to support the safe clinical implementation of MRI-guided radiation therapy systems.

Monte Carlo simulations and EBT3 film measurements were used to determine an irradiator and magnetic field strength that would produce magnetic-field-induced dose perturbations in mice that were comparable to those seen in human simulations. We developed an irradiation scheme for C57L/J mice, which included irradiating mice to the whole thorax in a 3D-printed holder with parallel-opposed Co-60 beams. We developed non-invasive assays for evaluating the extent of radiation-induced lung injury, including a respiratory rate measurement technique and techniques for measuring lung damage on cone-beam CTs. We showed that these assays were correlated to survival, the ultimate predictor of radiation-induced lung injury.

The mice were irradiated to 9.0, 10.0, 10.5, 11.0, 12.0, or 13.0 Gy between the poles of an electromagnet in a 1.5 T field (n=60) or 0 T field (n=60). Twenty control mice did not receive radiation. Survival, respiratory rate measurements, and free-breathing cone-beam CT measurements (lung density and healthy lung volume) were used to assess the severity of radiation-induced pneumonitis.

Cox regression showed that dose was a much higher predictor of survival than magnetic field strength. The presence of a transverse 1.5 T field during irradiation had little to no effect on survival for each of the dose groups. The 1.5 T field did, however, have an effect on the severity of radiation-induced lung injury, as measured by respiratory rate, lung density, and lung volume.

The results of these studies suggest that it is possible to reduce magnetic-field-induced dose perturbations by using parallel-opposed fields, and in this case the impact of a strong, transverse magnetic field on survival would be expected to be insignificant. However, our results also suggest that there could be some impact on the severity of radiation-induced lung damage, though that impact is likely small.

Keywords

MRIgRT, dose perturbations, mice, radiation-induced pneumonitis, MCNP6, magnetic-field-induced dose effects, MRI-guided radiation therapy

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