Raman spectroscopy and imaging techniques for ionizing radiation research

放射治疗(RT)是全球50%癌症的标准治疗方法。辐射防护(RP)旨在确保公众健康安全，不受包括RT在内的所有来源的电离辐射(IR)的影响。放射治疗和放射治疗的主要目标需要新的工具，以改进对放射生物反应的机械理解，并用于高精度的红外剂量测定。我的研究计划将为RT和RP产生新的基础知识，方法是开发(1)相干拉曼成像，用于了解与RT和RP相关的IR剂量下的放射生物学反应，以及(2)拉曼光谱(RS)技术，以促进RP的生物剂量学和RT的微米级剂量学。相干拉曼成像用于了解RT和RP中的放射生物学响应简介：我之前的DG开发了基于RS和非线性光学显微镜(NLOM)的工具，用于在细胞和组织中进行快速分子指纹和高分辨率化学图谱绘制。这一DG的目的是类似地开发基于NLOM的新技术，包括受激拉曼散射(SRS)成像，以检测与RT和RP相关的剂量的细胞和组织中的放射生物学反应；目前IR研究中缺少此类工具。目的：长期：发展SRS、NLOM成像作为了解细胞和组织中放射生物学反应的工具。短期：(I)开发SRS、NLOM仪器技术，用于2D肿瘤和正常细胞以及3D肿瘤模型的放射生物学研究。(2)开发图像分析技术，以确定SRS、NLOM为基础的放射生物学反应的生物识别器。影响：这项工作将导致对放射生物学反应的机械理解的改进，从而导致优化的RT和RP框架。提高红外吸收剂量学和微米级剂量学的遥感技术介绍：目前，基于生物标志物的生物剂量学技术用于确定吸收的IR剂量，而实验微米级剂量学用于确定微米级分辨率的精确剂量测定，这些技术都有一些局限性。本DG旨在建立在我之前的DG工作的基础上，该DG展示了基于全血的拉曼显微光谱(µRS)的高通量技术和基于具有µRS读数的辐射变色膜(RCFs)的高空间分辨率剂量测量技术。目标：长期：开发基于µRS的高通量血浆生物剂量测量技术和微米级RCFs剂量测量技术。短期：(I)开发测量方案和数据分析，以最大限度地区分对照和辐照血浆的拉曼光谱，并识别RS生物标志物(Ii)开发基于RCFs的2D拉曼图谱的测量和数据分析技术，以构建高分辨率剂量图。影响：这项工作将为RP的现场快速便携式生物剂量测量和复杂RT交付的高精度剂量测量铺平道路。

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.