Raman spectroscopy and imaging techniques for ionizing radiation research

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Radiation therapy (RT) is a standard treatment for ~50% of cancers worldwide. Radiation protection (RP) aims to ensure public health safety from exposure to ionizing radiation (IR) arising from all sources including RT. Major goals in RT and RP require new tools for improved mechanistic understanding of radiobiological response, and for high precision IR dosimetry. My research program will generate new basic knowledge for RT and RP by developing (1) Coherent Raman imaging for use in the understanding of radiobiological response at IR doses relevant to RT and RP and, (2) Raman spectroscopy (RS) techniques to advance bio-dosimetry for RP and micron-scale dosimetry for RT. Coherent Raman imaging for understanding the radiobiological response in RT and RP Introduction: My previous DG has developed tools based on RS and Non-Linear Optical Microscopy (NLOM) for rapid molecular fingerprinting and high-resolution chemical mapping in cells and tissue. The aim of this DG is to similarly develop novel techniques based on NLOM including Stimulated Raman Scattering (SRS) imaging to detect the radiobiological response in cells and tissue at doses relevant to RT and RP; such tools are currently missing in IR research. Objectives: Long term: To develop SRS, NLOM imaging as a tool for understanding the radiobiological response in cells and tissue. Short term: (I) to develop the SRS, NLOM instrumentation techniques for radiobiological studies in 2D cancer and normal cells, and 3D tumor models. (II) to develop image analysis techniques to determine SRS, NLOM-based bio-identifiers of radiobiological response. Impact: This work will result in improved mechanistic understanding of radiobiological response thus leading to optimized RT and RP frameworks. RS techniques to advance bio-dosimetry and micron-scale dosimetry of IR Introduction: Current techniques in bio-dosimetry for determining absorbed IR dose based on biological markers, and in experimental micron-scale dosimetry for determining the accurate dose determination at micron-scale resolution, have several limitations. This DG aims to build on the work in my previous DG that demonstrated a high-throughput technique based on Raman micro-spectroscopy (µRS ) of whole blood and a high spatial resolution dosimetry technique based on radiochromic films (RCFs) with µRS readout. Objectives: Long term: To develop µRS based techniques for high-throughput bio-dosimetry of blood plasma, and for micron-scale dosimetry of RCFs. Short term: (I) to develop the measurement protocols and data analytics to maximize discrimination between Raman spectra of control and irradiated blood plasma in addition to identifying RS biomarkers (II) to develop measurement and data analysis techniques based on 2D Raman mapping of RCFs for constructing high resolution dose maps. Impact: This work will pave the path for rapid in-field portable bio-dosimetry for RP and for high accuracy dose measurements of complex RT deliveries.