Technical Summary: Non-invasive assessment of trabecular bone strength and density is extremely important in predicting the risk of fracture in space and ground operation. Quantitative ultrasound (QUS) has emerged with the potential to directly detect trabecular bone strength. To overcome the current hurdles such as soft tissue and cortical shell interference, improving the quality of QUS and applying the technology for future clinical applications, this phase of the development of image based SCAN system will concentrate on several main areas: (1) increasing the resolution, sensitivity, and accuracy in diagnosing osteoporosis through confocal acoustics to improve signal/noise ratio, and through extracting surface topology to accurately calculate ultrasound speed of sound; (2) minimizing the scanning time while maintaining reasonable resolution via micro-processor controlled and phased array electronic confocal scanning, e.g., in deep bone tissue scan; (3) developing broadband ultrasound system to measure deep bone tissue density and structural parameters in the critical regions; (4) developing hardware and software interface with flexible ultrasound platform (FUS), and therapeutical ultrasound for acceleration of fracture healing; (5) assessment of the capability of the SCAN system of imaging scan for human wrist and calcaneus for bone density assessment in normal and osteoporosis subjects. The proposed work will develop a portable rapid SCAN system combined with imaging capability, and test its efficacy in human, which will ultimately provide a portable, noninvasive device for bone loss assessment in space.

Earth Applications: Skeletal decay complications are major health problems on Earth, i.e., osteoporosis, and delayed healing of fractures. Development of a low mass, compact, noninvasive diagnostic and treatment technology, i.e., using ultrasound, will have a great potential to prevent and treat bone fracture. Our principal goal is to develop a portable quantitative ultrasound system with therapeutic capability, not only for determination of bone's physical properties, but also for predicting subtle changes of bone during extended flights and diseased condition, which will impact both diagnosis and noninvasive treatment for musculoskeletal disorders. Use of a desktop based non-ionizing bone assessment device has great clinical applications as an in-office quantitative assessment of fracture risk in the general and at-risk populations.

Key findings and milestones: In this study, the team is able to continue development of a scanning confocal acoustic diagnostic combined with therapeutic system capable of generating acoustic images at the regions of interest for identifying the strength of trabecular bone with high-resolution QUS attenuation and velocity maps, and thus determining the relationship between ultrasonic parameters and bone mineral density (BMD), and bone's physical properties, as well as providing treatment for fracture healing. Ultrasound has been used in an OVX (ovariectomy) and femur fracture animal model to mitigate bone loss and acceleration of fracture healing. Phase array transducer and system are built and successfully tested in initial normal control and osteoporotic human subjects in multiple skeletal sites. The team is able to work with TRS Transducers, Inc. for evaluation of a wideband frequency ultrasound transducers in range of 0.5MHz - 7.0MHz, and with GE Research Center for flexible ultrasound platform (FUS) system in system requirement specifics, user-interface software evaluation and 2-D array transducer design. The results have shown that ultrasound can mitigate bone loss and promote fracture healing under disuse osteopenia condition.

Earth Applications: Skeletal decay complications are major health problems on Earth, i.e., osteoporosis, and delayed healing of fractures. Development of a low mass, compact, noninvasive diagnostic and treatment technology, i.e., using ultrasound, will have a great potential to prevent and treat bone fracture. Our principal goal is to develop a portable quantitative ultrasound system with therapeutic capability, not only for determination of bone's physical properties, but also for predicting subtle changes of bone during extended flights and diseased condition, which will impact both diagnosis and noninvasive treatment for musculoskeletal disorders. Use of a desktop based non-ionizing bone assessment device has great clinical applications as an in-office quantitative assessment of fracture risk in the general and at-risk populations.

Technical Summary: Non-invasive assessment of trabecular bone strength and density is extremely important in predicting the risk of fracture in space and ground operation. Quantitative ultrasound (QUS) has emerged with the potential to directly detect trabecular bone strength. To overcome the current hurdles such as soft tissue and cortical shell interference, improving the quality of QUS and applying the technology for future clinical applications, this phase of the development of image based SCAN system will concentrate on several main areas: (1) increasing the resolution, sensitivity, and accuracy in diagnosing osteoporosis through confocal acoustics to improve signal/noise ratio, and through extracting surface topology to accurately calculate ultrasound speed of sound; (2) minimizing the scanning time while maintaining reasonable resolution via micro-processor controlled and phased array electronic confocal scanning, e.g., in deep bone tissue scan; (3) developing broadband ultrasound system to measure deep bone tissue density and structural parameters in the critical regions; (4) developing hardware and software interface with flexible ultrasound platform (FUS), and therapeutical ultrasound for acceleration of fracture healing; (5) development of a micro-gravity capable method of QUS assessment through the removal of open-water coupling; (6) assessment of the capability of the SCAN system of imaging the proximal and distal tibia, elbow, humerus, and femur. The proposed work will develop a portable rapid SCAN system combined with imaging capability, and test its efficacy in human, which will ultimately provide a portable, noninvasive device for bone loss assessment in space.

Key findings and milestones: In this study, the team is able to continue development of a scanning confocal acoustic diagnostic (SCAN) combined with therapeutic system capable of generating acoustic images at the regions of interest for identifying the strength of trabecular bone with high-resolution ultrasound (QUS) attenuation and velocity maps, and thus determining the relationship between ultrasonic parameters and bone mineral density (BMD), and bone's physical properties, as well as providing treatment for fracture healing. Ultrasound has been used in an ovariectomy (OVX) and femur fracture animal model to mitigate bone loss and acceleration of fracture healing. Phase array transducer and system are built and successfully tested in initial control human subjects. The team is able to work with TRS Transducers, Inc. for evaluation of a wideband frequency ultrasound transducers in range of 0.5MHz - 7.0MHz, and with GE Research Center for flexible ultrasound platform (FUS) system in system requirement specifics, user-interface software evaluation, and 2-D array transducer design. The results have shown that ultrasound can mitigate bone loss and promote fracture healing under disuse osteopenia condition.

Skeletal complications, i.e., osteoporosis, induced by microgravity during extended space missions represent a key astronaut health problem. Lack of on-board diagnosis has increased significant risk in astronauts' bone loss during long term space flight. Early diagnosis of such disorders can lead to prompt and optimized treatment that will dramatically reduce the risk of fracture and longitudinal monitoring microgravity and countermeasure effects. Advents in quantitative ultrasound (QUS) techniques provide a method for characterizing the material properties of bone in a manner for predicting both bone mineral density (BMD) and mechanical strength. We have developed a scanning confocal acoustic navigation (SCAN) system capable of generating noninvasive ultrasound images at the site of interest. Both animal and human tests indicated strong correlations between SCAN determined data and microCT determined BMD, and bone strength, as well as monitoring fracture healing with guided ultrasound. The objectives of this study are to develop a portable broadband SCAN for critical skeletal quality assessment, to longitudinally monitoring bone alteration in disuse osteopenia, and to integrate ultrasound with DXA, QCT (quantitative computed tomography), and finite element analysis (FEA) for human subject. In vivo human tests will be evaluated at Stony Brook Osteoporosis Center. Human cadaver and animal samples will be used for testing feasibility of identifying bone loss, microstructural and mechanical strength properties. Development of a noninvasive diagnostic and treatment technology using noninvasive ultrasound with new crystal transducer technology will have a great potential to perform longitudinal measurement of bone alteration and prevent the risk of fracture.

Technical Summary: Non-invasive assessment of trabecular bone strength and density is extremely important in predicting the risk of fracture in space and ground operation. Quantitative ultrasound (QUS) has emerged with the potential to directly detect trabecular bone strength. To overcome the current hurdles such as soft tissue and cortical shell interference, improving the quality of QUS and applying the technology for future clinical applications, this phase of the development of image based SCAN system will concentrate on several main areas: (1) increasing the resolution, sensitivity, and accuracy in diagnosing osteoporosis through confocal acoustics to improve signal/noise ratio, and through extracting surface topology to accurately calculate ultrasound speed of sound; (2) minimizing the scanning time while maintaining reasonable resolution via micro-processor controlled and phased array electronic confocal scanning, e.g., in deep bone tissue scan; (3) developing broadband ultrasound system to measure deep bone tissue density and structural parameters in the critical regions; (4) improvement of functionality of SCAN system from a translational research perspective; (5) development of a micro-gravity capable method of QUS assessment through the removal of open-water coupling; (6) assessment of the capability of the SCAN system of imaging the proximal and distal tibia, elbow, humerus, and femur. The proposed work will develop a portable rapid SCAN system combined with imaging capability, and test its efficacy in human, which will ultimately provide a portable, noninvasive device for bone loss assessment in space.

Earth Applications: Skeletal decay complications are major health problems on Earth, i.e., osteoporosis, and delayed healing of fractures. Development of a low mass, compact, noninvasive diagnostic and treatment technology, i.e., using ultrasound, will have a great potential to prevent and treat bone fracture. Our principal goal is to develop a portable quantitative ultrasound system with therapeutic capability, not only for determination of bone's physical properties, but also for predicting subtle changes of bone during extended flights and diseased condition, which will impact both diagnosis and noninvasive treatment for musculoskeletal disorders. Use of a desktop based non-ionizing bone assessment device has great clinical applications as an in-office quantitative assessment of fracture risk in the general and at-risk populations.

Key findings and milestones: In this study, the teams are able to continue development of a scanning confocal acoustic diagnostic (SCAN) combined with therapeutic system capable of generating acoustic images at the regions of interest for identifying the strength of trabecular bone with high-resolution ultrasound (QUS) attenuation and velocity maps, and thus determining the relationship between ultrasonic parameters and bone mineral density (BMD), and bone's physical properties, as well as providing treatment for fracture healing. Ultrasound has been used in an OVX and femur fracture animal model to mitigate bone loss and acceleration of fracture healing. Phase array transducer and system are built and successfully demonstrated at the National Space Biomedical Research Institute (NSBRI) Capitol Hill Demo in March 2014.

Summary of key findings

• Redesign of portable SCAN mechanical array hardware

• Utilization of a non-water coupling method for region of interest bone imaging implementing polyurethane molded standoffs

• Translation of SCAN device from calcaneus scanning to wrist imaging

• Development of a hand-held SCAN device for assessment of bone quality in the forearm, upper arm, and proximal tibia

• Assessment of frequency specific ultrasound attenuation information in higher frequency (1-7 MHz) signals

• Validation of repeat measure consistency of SCAN device

Summary of deliverables (these deliverables are primarily completed)

• Development of second generation portable SCAN desktop device

• Development of hand-held portable SCAN device

• Skeletal imaging and bone quality assessment of the wrist and hand using an integrated mechanical and electronic SCAN device

• Skeletal imaging of the hand, tibia, and humerus using a hand-held SCAN device

1) To develop a new broadband SCAN system capable of extracting trabecular quantitative ultrasound (QUS) parameters and backscatter images at critical skeletal sites using single crystal material transducer with minimal loss of the acoustic signal and integration with scan technology to provide direct assessment of the risk of osteoporotic bone loss and fracture in the deep tissue. The scanning time will be less than 2 min. The SCAN system will be non-invasive, portable, easy to use, and provide automatic analysis.

2) To evaluate the capability of the broadband SCAN diagnostic system in assessing trabecular bone structural and strength parameters in cadaver subjects with microCT determined microstructure and BMD determined by DXA.

3) To longitudinally assess and correlate the degree of bone loss in osteoporosis clinic, bedrest facility to determine intra-subject bone loss and the relationship to age, gender, and rational effects at critical sites using SCAN, DXA, QCT, and FEA.

4) To determine the ability of quantitative ultrasound in pre- and post-flights, as well as rehabilitation effects for astronauts.

Relevance: Skeletal decay generated by the microgravity environment has greatly impacted the nation's civil space missions and ground operations. Such musculoskeletal complications are also major health problems on Earth, i.e., osteoporosis. Development of a noninvasive diagnostic and treatment technology using noninvasive ultrasound with new crystal transducer technology will have a great potential to perform longitudinal measurement of bone alteration and prevent the risk of fracture. This research will address critical questions in the NASA Human Research Program (HRP) Roadmap related to musculoskeletal disorder of crew health.