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

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.Project Narrative 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. Local oxygen microenvironments and changes to oxygen tensions over only tens of micrometers are known to be important for maintaining stem cell growth and are suspected to also enable cancer metastases, but are poorly understood because there are no methods with the resolution and sensitivity required. The proposed solution will finally enable 3D oxygen measurements in deep bone marrow based on a newly developed technique called x- ray luminescence computed tomography (XLCT) and oxygen-sensitive nanophosphors for 10 to 100 µm imaging of oxygen concentrations.