MS Thesis Defense: Gretchen Carpenter

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"The Accurate Conversion of Biological Experiments from Cesium Irradiation to X-ray Irradiation: Significance, problems, and the future of experimental radiation research"

Abstract

Pre-clinical small animal irradiation studies, once conducted on Cesium irradiators, are increasingly being performed with x-ray-based irradiators. The transition stems from concerns regarding national security risks, making x-ray irradiators which are compact and easy to operate an enticing alternative. However, questions regarding the relative biological effectiveness between the two sources have revealed a lack of adequate dosimetric characterization of x-ray beams, standardized protocol for dose calibration, and thorough understanding of experimental biological parameters. A literature review conducted on orthovoltage irradiators revealed that there are over 54 different types of beam structures used, a dramatic departure from the one uniform beam structure with cesium sources. The lack of consistency and precise dosimetry has resulted in inaccuracies in dose delivery that reach up to 42% across institutions (Pedersen et al. 2016). The complicated physics associated with calibrating orthovoltage irradiators has been thoroughly investigated and reported in literature through measurements and Monte Carlo simulations. However, these results have not yet been translated into practice, and thus many institutions still rely on antiquated calibration procedures.

This thesis aims to address the communication between experimental radiation researchers and physicists who could calibrate the irradiators. To do so, a thorough literature review of orthovoltage radiation physics and a complete characterization of the orthovoltage irradiator at Dartmouth College were first conducted. Then, anthropomorphic mouse phantoms were developed from µCT scans of mice and were used with radiochromic film to assess the agreement of dose delivered in a mouse with that predicted by standard AAPM Task Group 61 calibrations in large water equivalent phantoms. Ultimately, findings were incorporated into an app that allows researchers to accurately deliver dose. Following dosimetry calibration, 70 female mice were irradiated with cesium gamma rays or equivalent doses of cabinet-based orthovoltage x-rays. The relative biological effectiveness of orthovoltage x-rays was assessed through a variety of biological markers including a CBC, serum chemistry panels, daily mouse activity levels, weight loss, and histopathologic quantification of bone marrow, spleen, liver, and small intestine. We have determined that collaborations between physicists and experimental radiation researchers are essential for facilitating accurate dosimetry and biological assays.

Thesis Committee

• David Gladstone (co-chair)
• Jack Hoopes (co-chair)
• Benjamin Williams
• Chad Gunther (C&C Irradiator Service)

Contact

For more information, contact Thayer Registrar at thayer.registrar@dartmouth.edu.