TITLE: DEVELOPMENT OF A PHOTOACOUSTIC QUANTITATIVE ULTRASOUND (PAQUS) DEVICE FOR CLINICAL USE Abstract: Osteoporosis is a major public health threat with significant physical, psychosocial, and financial consequences. Technologies that can facilitate population screening, early diagnosis and, more importantly, highly sensitive therapeutic assessment are crucial for achieving optimal management of osteoporosis. Clinically available diagnostic technologies for osteoporosis rely on either X-rays or ultrasound (US) to assess bone mass. Although representing the integrated effects of osteoclast and osteoblast activity and the appearance of altered skeletal structure, these standard clinical techniques have no or limited sensitivity to the real-time cellular activities and physiological properties in bone, resulting in a delay of information relayed to the clinician. Therefore, there is a clear and urgent need to develop alternate methodologies that add diagnostic imaging power using instruments that are cost-effective and accessible for wide-spread use. To fill this long-standing gap in technology, the objective of this program is to develop and commercialize an innovative and cost-effective device for early and accurate diagnosis and treatment monitoring of human osteoporosis. By combining our recently invented photoacoustic (PA) bone assessment techniques with more established quantitative ultrasound (QUS), the proposed PAQUS device can measure a group of biomarkers, including bone mass and bone microstructure, as well as chemical and functional properties which can then be combined with established biomarkers from QUS, such as speed of sound (SOS), broadband ultrasonic attenuation (BUA), and stiffness, to achieve more comprehensive assessment of bone health. In the last two years, sponsored by the Phase I SBIR project, the feasibility of PA assessment of human bone health has been rigorously validated. Experiments conducted in vivo on the calcaneus bones of 20 females (10 healthy volunteers and 10 subjects with osteoporosis) demonstrated that by performing spectral analysis of light-induced acoustic signals from a calcaneus bone over a broad optical spectrum, both chemical and micro-structural information in the bone can be obtained in a non-invasive and non-ionizing manner. Encouraged by the successful Phase I study, we now propose to further develop and commercialize this highly translational PAQUS technique in Phase II, aiming at a comprehensive and objective validation of the overall performance of PAQUS, and to prepare the device for FDA approval. To achieve this goal, three Specific Aims are proposed. Aim 1: Refine and optimize PAQUS method and establish testing phantoms; Aim 2: Develop clinical PAQUS system; and Aim 3: Perform pre-market field evaluation and collect reference data on a minimum of 150 individuals as a representative sampling based on the FDA’s publication “Bone Sonometers - Class II Special Controls Guidance for Industry and ...