Development of a Bio-tissue Oxygenation Nanophosphor Enabled Sensing (BONES) system for Quantifying Hypoxia in Bone Marrow

项目总结/摘要 已知低氧（缺氧）环境对于维持小的 人体内的成体干细胞数量，如骨髓。这些条件 也被认为使休眠的癌细胞在数年或数十年后存活并转移 原来的肿瘤已经被破坏，骨髓是最重要的原因之一， 癌症转移的常见部位。了解这些条件可以推动 开发用于离体生长干细胞的3D细胞支架，从而减轻 需要骨髓移植，以及开发预防癌症复发的治疗方法。 本计画拟发展第一台定量氧气断层影像系统 名为BONES（生物组织氧合纳米荧光启用传感），以解决关键的 需要低氧（低氧）组织中氧浓度的高分辨率成像 骨髓。该技术是基于X射线发光计算的发展 断层扫描，一种新兴的分子成像技术，能够实现细胞水平 分辨率和高灵敏度。该方法使用x射线激发氧敏感 发射近红外光子的纳米荧光粉，最终实现3D氧气测量， 深入骨髓 由于这项技术需要一个具有x射线专业知识的多学科团队， 专业知识，近红外检测专业知识和量化浓度的算法 和最大限度地减少剂量，这个STTR快速通道建议涉及几个机构， 在各自领域的专业知识。第一阶段为期6个月的项目是一个证明- 一种用于低氧环境下纳米荧光粉的试验板系统的原理演示 溶液并嵌入骨中。建议的第二阶段24个月项目是开发一个 完成了原型系统，并通过实验验证了其性能。

Project Summary/Abstract Low oxygen (hypoxic) environments are known to be important for maintaining the small number of adult stem cells in the human body, such as in bone marrow. These conditions are also believed to enable dormant cancer cells to survive and metastasize years or decades after the original tumor has been destroyed and the reason why bone marrow is one of the most common sites of cancer metastasis. Understanding of these conditions can drive the development of 3D cellular scaffolds for growing stem cells ex vivo, thus reducing the burden on requiring bone marrow transplants, and for developing therapeutics that prevent cancer relapse. This project proposes to develop the first quantitative oxygen tomographic imaging system called BONES (Bio-tissue Oxygenation Nanophosphor Enabled Sensing) to address the critical need for high resolution imaging of oxygen concentrations in hypoxic (low oxygen) tissues such as bone marrow. The technique is based on developments in x-ray luminescence computed tomography, an emerging molecular imaging technique capable of achieving cellular level resolution and high sensitivities. The approach uses x-rays to excite oxygen-sensitive nanophosphors that emit near-infrared photons to finally enable 3D oxygen measurements in deep bone marrow. Because the technique requires a multidisciplinary team with x-ray expertise, nanophosphor expertise, near-infrared detection expertise, and algorithms for quantifying the concentrations and minimizing dose, this STTR fast-track proposal involves several institutions with deep expertise in their respective domains. The proposed Phase I 6-month project is a proof-of- principle demonstration of a breadboard system used on nanophosphors in low oxygen solutions and embedded in bone. The proposed Phase II 24-month project is to develop a complete prototype system and experimentally verify its performance.