SBIR Phase I: Development of a novel, high-sensitivity diagnostic for bone disease, enabling early-stage diagnosis and precise monitoring of therapy effects.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase l Project, if successful, is the introduction of a new diagnostic paradigm that can significantly increase the ability of clinicians to diagnose early stage bone pathology resulting from age, osteoarthritis, and cancer therapy. While the current standard of bone care relies on a measurement of overall bone density, this new technology assesses the microstructure within bone, a measure that correlates much more strongly with fracture risk and disease stage. Along with providing an accurate measure of fracture risk, this technology will enable sensitive measure to: 1) target patients for inclusion in therapy trials, and 2) enable monitoring of the efficacy of these therapies towards amelioration of an excruciatingly painful pathology with a dire prognosis (half of people suffering hip fracture never regain their ability to live independently, and are at significantly increased risk of further fractures). As such, the commercial market, driven by pharmaceutical companies and diagnostic equipment manufacturers, is large. While the focus of this SBIR project is to develop a diagnostic for bone disease, the development will inform future application of the diagnostic technology to a large range of diseases for which no non-invasive, early-stage diagnostic currently exists. The proposed project is designed to validate the ability of this new magnetic-resonance based diagnostic to provide a sensitive measure of trabecular bone morphometry parameters, in a clinically relevant environment. Direct measurement of the changes in trabecular bone microarchitecture that are the harbinger of bone disease is outside the capability of current magnetic resonance imaging, resolution being limited by patient motion over the long times needed to generate an image. The new diagnostic will have the ability to acquire the requisite data with immunity to patient motion, increasing resolution significantly, and enabling sensitive measurement of trabecular bone morphometry parameters. Validation of this ability will be through application to a set of 3D-printed phantoms of increasing textural complexity and cadaver vertebrae, with use of a purpose-built apparatus capable of inducing clinically relevant motion profiles during data acquisition. The major focus of this effort is optimization of the acquisition and analysis software so as to achieve the high resolution needed to measure trabecular element width in osteoporotic bone.