Development and Preclinical Evaluation of A Compact Image-guided Microbeam Radiation Therapy System Public Deposited

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  • March 20, 2019
  • Zhang, Lei
    • Affiliation: College of Arts and Sciences, Department of Applied Physical Sciences, Materials Science Graduate Program
  • Microbeam radiation therapy (MRT) is a novel and experimental cancer treatment modality. It has received increasing emphasis worldwide in recent years due to the demonstrated high therapeutic ratio in preclinical studies. MRT uses arrays of quasi-parallel radiation beams that are up to a few hundred microns wide and separated by several times of its beamwidth. Extensive preclinical experiments conducted at European Synchrotron Radiation Facility and several other national synchrotron facilities have shown that microbeams with doses of several hundreds of grays are well tolerated by healthy brain tissues while causing preferential damage in tumors. As the effort now moves towards large animal and clinical trials, there are eminent needs to develop compact and economically-viable microbeam irradiators for MRT radiobiology research and clinical installation eventually. Our research group has invented the carbon nanotube (CNT) field emission based X-ray source technology and has been dedicated to CNT-based medical device research over the past decade. A laboratory-scale microbeam irradiator has been recently developed with the CNT source array technology. The unique nature of CNT X-ray cathode allows for optimization of the anode focal spot shape and size, and therefore overcomes the obstacles of producing high flux microbeam radiation with conventional X-ray tubes. Preliminary studies have shown that the CNT-based MRT prototype is capable of generating orthovoltage radiation with all essential dosimetric characteristics of microbeam radiation therapy. The goals of this dissertation are to characterize and to optimize the system performance, to implement image guidance for dose delivery, and to evaluate the treatment efficacy in preclinical studies. Characterization of radiation source and dosimetric parameters was performed and described in detail. An on-board imaging system was constructed and integrated with the microbeam irradiating system. Dedicated image-guidance protocols were developed for high accuracy microbeam delivery in small animal models. Therapeutic assessment of brain tumor bearing mice was conducted with the CNT-MRT prototype. Preliminary results included encouraging treatment effects in terms of tumor local control and mean survival time extension. MRT radiobiological evaluations were carried out, for the first time, using a non-synchrotron-based compact radiation source. Additionally, feasibility of delivering multi-arrays of microbeams cross-firing geometry at the brain tumor target was successfully demonstrated facilitated by multi-modality 3D image guidance. The results in this work demonstrate the advantages of CNT-based MRT system as an attractive alternative for microbeam generation and delivery. With continued effort in system development and optimization, this nanotechnology-based compact MRT system could become a powerful research tool that can be installed in a laboratory environment for elucidating the still poorly understood therapeutic mechanism of MRT without the need of synchrotron light sources. The feasibility studies also showed that the CNT-based MRT technology offers a promising pathway for clinical implementation in the near future.
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  • In Copyright
  • Lu, Jianping
  • Yuan, Hong
  • Zhou, Otto
  • Washburn, Sean
  • Tepper, Joel
  • Chang, Sha
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016

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