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.