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

开发用于量化骨髓缺氧的生物组织氧化纳米磷传感 (BONES) 系统

• 批准号: 10408542
• 负责人: Wenbing Yun
• 金额: $ 86.65万
• 依托单位: SIGRAY, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408542
• 关键词: 3-Dimensional; Address; Affect; Algorithms; Area; Biomedical Research; Biopsy; Blood Vessels; Bone Marrow; Bone Marrow Transplantation; Cancer Patient; Cancer Relapse; Cells; Chemicals; Chronic Kidney Failure; Clinical; Collaborations; Data; Detection; Development; Disease; Dose; Environment; Fiber; Film; Heterogeneity; Human body; Hypoxia; Image; Imaging Techniques; Institution; Light; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Measures; Metastatic Neoplasm to the Bone; Methods; Microscopy; Modality; Molecular; Monitor; Morphology; Nature; Neoplasm Metastasis; Noise; Organ Transplantation; Oxygen; Penetration; Performance; Phase; Photons; Production; Radiation Dose Unit; Resolution; Roentgen Rays; Sampling; Scanning; Signal Transduction; Site; Small Business Technology Transfer Research; Spatial Design; Surface; System; Techniques; Therapeutic; Thick; Time; Tissues; Visible Radiation; X-Ray Computed Tomography; adult stem cell; base; bone; cancer cell; cancer site; deep learning; deep learning algorithm; denoising; design and construction; detector; high resolution imaging; image processing; image reconstruction; imaging system; improved; insight; luminescence; malignant breast neoplasm; molecular imaging; multidisciplinary; nanophosphor; phosphorescence; pre-clinical; prevent; prototype; quantum; response; scaffold; stem cell growth; stem cells; therapeutic effectiveness; tissue oxygenation; tomography; transmission process; tumor; two-photon

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.

项目概要/摘要 众所周知，低氧（缺氧）环境对于维持小 人体（例如骨髓）中成体干细胞的数量。这些条件是 还被认为能够使休眠的癌细胞在数年或数十年后存活并转移 原来的肿瘤已被破坏，骨髓是最重要的之一 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疗法。 该项目拟开发首个定量氧断层成像系统 称为 BONES（生物组织氧化纳米磷启用传感）来解决关键问题 需要对缺氧（低氧）组织中的氧气浓度进行高分辨率成像，例如 作为骨髓。该技术基于 X 射线发光计算的发展 断层扫描，一种能够实现细胞水平的新兴分子成像技术 分辨率和高灵敏度。该方法使用 X 射线来激发对氧敏感的 发射近红外光子的纳米磷最终能够实现 3D 氧气测量 深入骨髓。 由于该技术需要具有 X 射线专业知识的多学科团队，因此纳米磷光体 专业知识、近红外检测专业知识和量化浓度的算法 并最大限度地减少剂量，这项 STTR 快速通道提案涉及多个具有深入研究的机构 各自领域的专业知识。拟议的第一阶段 6 个月项目是一个证明- 低氧纳米磷光体上使用的面包板系统的原理演示 溶液并嵌入骨中。拟议的为期 24 个月的第二阶段项目是开发一个 完成原型系统并通过实验验证其性能。