Menu

 


Download in PDF pdf     
Fiscal Year: FY 2017  Task Last Updated:  03/13/2018 
PI Name: Qin, Yi-Xian  Ph.D. 
Project Title: Portable Quantitative Ultrasound with DXA/QCT and FEA Integration for Human Longitudinal Critical Bone Quality Assessment 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
 (2) Med13:We do not have the capability to implement medical resources that enhance operational innovation for medical needs (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: yi-xian.qin@stonybrook.edu  Fax:  631-632-8577 
PI Organization Type: UNIVERSITY  Phone: 631-632-1481  
Organization Name: SUNY- The State University of New York 
PI Address 1: Orthopaedic Bioengineering Research Laboratory 
PI Address 2: Room 215, Bioengineering Bldg 
PI Web Page:  
City: Stony Brook  State: NY 
Zip Code: 11794-5281  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 09/01/2013  End Date:  05/31/2017 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: End date change to 5/31/2017 per NSBRI submission (Ed., 3/14/18)

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Gelato, Marie  M.D. ( University of Kentucky )
Lin, Wei  Ph.D. ( SUNY- The State University of New York ) 
Grant/Contract No.: NCC 9-58-SMST03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: Project Overview: 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 BMD (bone mineral density) 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 monitor bone alteration in disuse osteopenia, and to integrate ultrasound with DXA for human subject in multiple skeleton sites. In vivo human tests are 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) 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.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: Musculoskeletal decay due to a 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, and the delayed healing of fractures. About 13 to 18 percent of women aged 50 years and older and 3 to 6 percent of men aged 50 years and older have osteoporosis in the US alone. One-third of women over 65 will have vertebral fractures and 90% of women aged 75 and older have radiographic evidence of osteoporosis. Thus, approximately a total of 28 million people suffer from osteoporosis in the United States, with an estimated annual direct cost of over $30 billion to national health programs. Hence, an early diagnosis that can predict fracture risk and result in prompt treatment is extremely important. Ultrasound has also demonstrated its therapeutic potentials to accelerate fracture healing. The objectives of this study are focused on developing a combined diagnostic and treatment ultrasound technology for early prediction of bone disorder and guided acceleration of fracture healing, using SCAN imaging and low-intensity pulse ultrasound. Development of a low mass, compact, noninvasive diagnostic and treatment modality will have great impacts as early diagnostic to prevent bone loss and accelerate fracture healing. This research will address critical questions in the Bioastronauts Roadmap related to non-invasive assessment of the acceleration of age-related osteoporosis and the monitoring of fractures and impaired fracture healing. The results have demonstrated the feasibility and efficacy of SCAN for assessing bone's quality in bone. We have been able to demonstrate that the bone quality is predictable via non-invasive scanning ultrasound imaging in the region of interests (ROI), and to demonstrate the strong correlation between SCAN determined data and microCT identified BMD, structural index, and mechanical modulus. These data have provided a foundation for further development of the technology and the clinical application in this research.

 

Task Progress: Musculoskeletal complications induced by age-related diseases like osteoporosis, and in long-term disuse osteopenia such as a lack of microgravity during extended space missions and long-term bed rest, represent a key health problem. Such a skeletal disorder changes both the structural and strength properties of bone, and the latter plays a critic role in ultimately leading to fracture. Early diagnosis of progressive bone loss or poor bone quality would allow prompt treatment and thus will dramatically reduce the risk of bone fracture. While most of the osteoporotic fractures occur in cancellous bone, non-invasive assessment of trabecular strength and stiffness is extremely important in evaluating bone quality. Ultrasound has also been shown therapeutic potentials to accelerate fracture healing. We are able to develop a SCAN system combined with therapeutic ultrasound capable of generating acoustic images at the regions of interest for identifying the strength of trabecular bone, in which the system is capable of generating non-invasive, high-resolution ultrasound (US) attenuation and velocity maps of bone, and thus determining the relationship between ultrasonic specific parameters and bone mineral density (BMD), and bone strength and bone's physical properties (i.e., stiffness and modulus). The ultrasound resolution and sensitivity are significantly improved by its configuration, compared to the existing technology. The new generation of SCAN devices greatly improves the practical use of ultrasound imaging. The issue of free water in microgravity has been solved by the development of a self-contained transducer tank, which would also allow for the replacement of water with a more ideal liquid such as mineral oil. Additionally, the development of a hand-held scanner requiring only a thin coating of ultrasound gel on the skin greatly improves the mobility of the device as well as allowing for the QUS assessment of additional regions of interest.

 

Bibliography Type: Description: (Last Updated: 08/24/2018) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Hu M, Lam H, Yeh R, Teeratananon M, Qin Y-X. "Comparison of morphological changes of muscle fibers in response to dynamic electrical muscle contraction and dynamic hydraulic stimulation in a rat hindlimb disuse model." Physiol Res. 2017 Jul 18;66(3):519-30. Epub 2017 Feb 28. PubMed PMID: 28248540 , Jul-2017
Articles in Peer-reviewed Journals Uddin SM, Richbourgh B, Ding Y, Hettinghouse A, Komatsu DE, Qin Y-X, Liu CJ. "Chondro-protective effects of low intensity pulsed ultrasound." Osteoarthritis Cartilage. 2016 Nov;24(11):1989-98. Epub 2016 Jun 27. https://doi.org/10.1016/j.joca.2016.06.014 ; PubMed PMID: 27364595; PubMed Central PMCID: PMC5071131 , Nov-2016
Articles in Peer-reviewed Journals Zhang D, Hu M, Chu T, Lin L, Wang J, Li X, Ke HZ, Qin Y-X. "Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse." Bone. 2016 Jun;87:161-8. Epub 2016 Feb 8. https://doi.org/10.1016/j.bone.2016.02.005 ; PubMed PMID: 26868528; PubMed Central PMCID: PMC4862887 [Erratum in: Bone. 2016 Aug;89:86. PMID: 27262889] , Jun-2016
Articles in Peer-reviewed Journals Wu L, Lin L, Qin YX. "Enhancement of cell ingrowth, proliferation, and early differentiation in a three-dimensional silicon carbide scaffold using low-intensity pulsed ultrasound." Tissue Eng Part A. 2015 Jan;21(1-2):53-61. Epub 2014 Jul 24. https://doi.org/10.1089/ten.TEA.2013.0597 ; PubMed PMID: 24935158; PubMed Central PMCID: PMC4293095 , Jan-2015
Articles in Peer-reviewed Journals Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Jiao J, Li X, Qin YX, Puttlitz CM. "An investigation of shock wave therapy and low-intensity pulsed ultrasound on fracture healing under reduced loading conditions in an ovine model." J Orthop Res. 2018 Mar;36(3):921-9. Epub 2017 Aug 11. https://doi.org/10.1002/jor.23666 ; PubMed PMID: 28762588 , Mar-2018
Articles in Peer-reviewed Journals Moonga SS, Qin YX. "MC3T3 infiltration and proliferation in bovine trabecular scaffold regulated by dynamic flow bioreactor and augmented by low-intensity pulsed ultrasound." J Orthop Translat. 2018 Jul;14:16-22. https://doi.org/10.1016/j.jot.2018.02.002 ; PubMed PMID: 30035029; PubMed Central PMCID: PMC6042526 , Jul-2018
Download in PDF pdf     
Fiscal Year: FY 2015  Task Last Updated:  03/13/2018 
PI Name: Qin, Yi-Xian  Ph.D. 
Project Title: Portable Quantitative Ultrasound with DXA/QCT and FEA Integration for Human Longitudinal Critical Bone Quality Assessment 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
 (2) Med13:We do not have the capability to implement medical resources that enhance operational innovation for medical needs (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: yi-xian.qin@stonybrook.edu  Fax:  631-632-8577 
PI Organization Type: UNIVERSITY  Phone: 631-632-1481  
Organization Name: SUNY- The State University of New York 
PI Address 1: Orthopaedic Bioengineering Research Laboratory 
PI Address 2: Room 215, Bioengineering Bldg 
PI Web Page:  
City: Stony Brook  State: NY 
Zip Code: 11794-5281  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 09/01/2013  End Date:  05/31/2017 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: End date change to 5/31/2017 per NSBRI submission (Ed., 3/14/18)

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Gelato, Marie  M.D. ( University of Kentucky )
Lin, Wei  Ph.D. ( SUNY- The State University of New York ) 
Grant/Contract No.: NCC 9-58-SMST03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: Project Overview: 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 BMD (bone mineral density) 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 subjects. 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.

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.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: Musculoskeletal decay due to a 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, and the delayed healing of fractures. About 13 to 18 percent of women aged 50 years and older and 3 to 6 percent of men aged 50 years and older have osteoporosis in the US alone. One-third of women over 65 will have vertebral fractures and 90% of women aged 75 and older have radiographic evidence of osteoporosis. Thus, approximately a total of 24 million people suffer from osteoporosis in the United States, with an estimated annual direct cost of over $20 billion to national health programs. Hence, an early diagnosis that can predict fracture risk and result in prompt treatment is extremely important. Ultrasound has also demonstrated its therapeutic potentials to accelerate fracture healing. The objectives of this study are focused on developing a combined diagnostic and treatment ultrasound technology for early prediction of bone disorder and guided acceleration of fracture healing, using SCAN imaging and low-intensity pulse ultrasound. Development of a low mass, compact, noninvasive diagnostic and treatment modality will have great impacts as early diagnostic to prevent bone loss and accelerate fracture healing. This research will address critical questions in the Bioastronauts Roadmap related to non-invasive assessment of the acceleration of age-related osteoporosis and the monitoring of fractures and impaired fracture healing. The results have demonstrated the feasibility and efficacy of SCAN for assessing bone's quality in bone. We have been able to demonstrate that the bone quality is predictable via non-invasive scanning ultrasound imaging in the ROI, and to demonstrate the strong correlation between SCAN determined data and microCT identified BMD, structural index, and mechanical modulus. These data have provided a foundation for further development of the technology and the clinical application in this research.

 

Task Progress: Musculoskeletal complications induced by age-related diseases like osteoporosis, and in long-term disuse osteopenia such as a lack of microgravity during extended space missions and long-term bed rest, represent a key health problem. Such a skeletal disorder changes both the structural and strength properties of bone, and the latter plays a critic role in ultimately leading to fracture. Early diagnosis of progressive bone loss or poor bone quality would allow prompt treatment and thus will dramatically reduce the risk of bone fracture. While most of the osteoporotic fractures occur in cancellous bone, non-invasive assessment of trabecular strength and stiffness is extremely important in evaluating bone quality. Ultrasound has also been shown therapeutic potentials to accelerate fracture healing. We are able to develop a SCAN system combined with therapeutic ultrasound capable of generating acoustic images at the regions of interest for identifying the strength of trabecular bone, in which the system is capable of generating non-invasive, high-resolution ultrasound (US) attenuation and velocity maps of bone, and thus determining the relationship between ultrasonic specific parameters and bone mineral density (BMD), and bone strength and bone's physical properties (i.e., stiffness and modulus). The ultrasound resolution and sensitivity are significantly improved by its configuration, compared to the existing technology. The new generation of SCAN devices greatly improve the practically use of ultrasound imaging. The issue of free water in microgravity has been solved by the development of a self-contained transducer tank, which would also allow for the replacement of water with a more ideal liquid such as mineral oil. Additionally, the development of a hand-held scanner requiring only a thin coating of ultrasound gel on the skin greatly improves the mobility of the device as well as allowing for the QUS (quantitative ultrasound) assessment of additional regions of interest.

 

Bibliography Type: Description: (Last Updated: 08/24/2018) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Hu M, Tian GW, Gibbons DE, Jiao J, Qin Y-X. "Dynamic fluid flow induced mechanobiological modulation of in situ osteocyte calcium oscillations." Arch Biochem Biophys. 2015 Aug 1;579:55-61. Epub 2015 Jun 1. https://doi.org/10.1016/j.abb.2015.05.012 ; PubMed PMID: 26045248; PubMed Central PMCID: PMC4500666 , Aug-2015
Articles in Peer-reviewed Journals Lin L, Lin W, Qin Y-X. "Enhanced correlation between quantitative ultrasound and structural and mechanical properties of bone using combined transmission-reflection measurement." J Acoust Soc Am. 2015 Mar;137(3):1144-52. https://doi.org/10.1121/1.4906830 ; PubMed PMID: 25786930; PubMed Central PMCID: PMC4368590 , Mar-2015
Articles in Peer-reviewed Journals Qin Y-X, Hu M. "Mechanotransduction in musculoskeletal tissue regeneration: Effects of fluid flow, loading, and cellular-molecular pathways." Biomed Res Int. 2014;2014:863421. https://doi.org/10.1155/2014/863421 ; PubMed PMID: 25215295; PubMed Central PMCID: PMC4151828 , Aug-2014
Articles in Peer-reviewed Journals Uddin SM, Qin Y-X. "Dynamic acoustic radiation force retains bone structural and mechanical integrity in a functional disuse osteopenia model." Bone. 2015 Jun;75:8-17. Epub 2015 Feb 7. https://doi.org/10.1016/j.bone.2015.01.020 ; PubMed PMID: 25661670; PubMed Central PMCID: PMC4387114 , Jun-2015
Articles in Peer-reviewed Journals Wu J, Liu G, Qin Y-X, Meng Y. "Effect of low-intensity pulsed ultrasound on biocompatibility and cellular uptake of chitosan-tripolyphosphate nanoparticles." Biointerphases. 2014 Sep;9(3):031016. https://doi.org/10.1116/1.4895711 ; PubMed PMID: 25280857; PubMed Central PMCID: PMC4241703 , Sep-2014
Download in PDF pdf     
Fiscal Year: FY 2014  Task Last Updated:  03/13/2018 
PI Name: Qin, Yi-Xian  Ph.D. 
Project Title: Portable Quantitative Ultrasound with DXA/QCT and FEA Integration for Human Longitudinal Critical Bone Quality Assessment 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
 (2) Med13:We do not have the capability to implement medical resources that enhance operational innovation for medical needs (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: yi-xian.qin@stonybrook.edu  Fax:  631-632-8577 
PI Organization Type: UNIVERSITY  Phone: 631-632-1481  
Organization Name: SUNY- The State University of New York 
PI Address 1: Orthopaedic Bioengineering Research Laboratory 
PI Address 2: Room 215, Bioengineering Bldg 
PI Web Page:  
City: Stony Brook  State: NY 
Zip Code: 11794-5281  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 09/01/2013  End Date:  05/31/2017 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Gelato, Marie  M.D. ( University of Kentucky )
Lin, Wei  Ph.D. ( SUNY- The State University of New York ) 
Grant/Contract No.: NCC 9-58-SMST03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: Project Overview

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

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: Musculoskeletal decay due to a 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, and the delayed healing of fractures. About 13 to 18 percent of women aged 50 years and older and 3 to 6 percent of men aged 50 years and older have osteoporosis in the US alone. One-third of women over 65 will have vertebral fractures and 90% of women aged 75 and older have radiographic evidence of osteoporosis. Thus, approximately a total of 24 million people suffer from osteoporosis in the United States, with an estimated annual direct cost of over $20 billion to national health programs. Hence, an early diagnosis that can predict fracture risk and result in prompt treatment is extremely important. Ultrasound has also demonstrated its therapeutic potentials to accelerate fracture healing. The objectives of this study are focused on developing a combined diagnostic and treatment ultrasound technology for early prediction of bone disorder and guided acceleration of fracture healing, using SCAN imaging and low-intensity pulse ultrasound. Development of a low mass, compact, noninvasive diagnostic and treatment modality will have great impacts as early diagnostic to prevent bone loss and accelerate fracture healing. This research will address critical questions in the Bioastronauts Roadmap related to non-invasive assessment of the acceleration of age-related osteoporosis and the monitoring of fractures and impaired fracture healing. The results have demonstrated the feasibility and efficacy of SCAN for assessing bone's quality in bone. We have been able to demonstrate that the bone quality is predictable via non-invasive scanning ultrasound imaging in the ROI (reactive oxygen species), and to demonstrate the strong correlation between SCAN determined data and microCT identified BMD, structural index, and mechanical modulus. These data have provided a foundation for further development of the technology and the clinical application in this research.

 

Task Progress: Musculoskeletal complications induced by age-related diseases like osteoporosis, and in long-term disuse osteopenia such as a lack of microgravity during extended space missions and long-term bed rest, represent a key health problem. Such a skeletal disorder changes both the structural and strength properties of bone, and the latter plays a critic role in ultimately leading to fracture. Early diagnosis of progressive bone loss or poor bone quality would allow prompt treatment and thus will dramatically reduce the risk of bone fracture. While most of the osteoporotic fractures occur in cancellous bone, non-invasive assessment of trabecular strength and stiffness is extremely important in evaluating bone quality. Ultrasound has also been shown therapeutic potentials to accelerate fracture healing. We are able to develop a SCAN system combined with therapeutic ultrasound capable of generating acoustic images at the regions of interest for identifying the strength of trabecular bone, in which the system is capable of generating non-invasive, high-resolution ultrasound (US) attenuation and velocity maps of bone, and thus determining the relationship between ultrasonic specific parameters and bone mineral density (BMD), and bone strength and bone's physical properties (i.e., stiffness and modulus). The ultrasound resolution and sensitivity are significantly improved by its configuration, compared to the existing technology. The new generation of SCAN devices greatly improve the practically use of ultrasound imaging. The issue of free water in microgravity has been solved by the development of a self-contained transducer tank, which would also allow for the replacement of water with a more ideal liquid such as mineral oil. Additionally, the development of a hand-held scanner requiring only a thin coating of ultrasound gel on the skin greatly improves the mobility of the device as well as allowing for the QUS (quantitative ultrasound) assessment of additional regions of interest.

 

Bibliography Type: Description: (Last Updated: 08/24/2018) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Hu M, Cheng J, Bethel N, Serra-Hsu F, Ferreri S, Lin L, Qin Y-X. "Interrelation between external oscillatory muscle coupling amplitude and in vivo intramedullary pressure related bone adaptation." Bone. 2014 Sep;66:178-81. Epub 2014 Jun 17. https://doi.org/10.1016/j.bone.2014.05.018 ; PubMed PMID: 24947450; PubMed Central PMCID: PMC4125428 , Sep-2014
Articles in Peer-reviewed Journals Hu M, Qin Y-X. "Dynamic fluid flow stimulation on cortical bone and alterations of the gene expressions of osteogenic growth factors and transcription factors in a rat functional disuse model." Arch Biochem Biophys. 2014 Mar 1;545:154-61. Epub 2014 Jan 30. https://doi.org/10.1016/j.abb.2014.01.021 ; PubMed PMID: 24486201; PubMed Central PMCID: PMC3974629 , Mar-2014
Articles in Peer-reviewed Journals Hu M, Serra-Hsu F, Bethel N, Lin L, Ferreri S, Cheng J, Qin Y-X. "Dynamic hydraulic fluid stimulation regulated intramedullary pressure." Bone. 2013 Nov;57(1):137-41. Epub 2013 Jul 27. https://doi.org/10.1016/j.bone.2013.07.030 ; PubMed PMID: 23895997; PubMed Central PMCID: PMC3832679 , Nov-2013
Articles in Peer-reviewed Journals Hu M, Yeh R, Lien M, Teeratananon M, Agarwal K, Qin Y-X. "Dynamic fluid flow mechanical stimulation modulates bone marrow mesenchymal stem cells." Bone Research. 2013 Mar 29;1(1):98-104. eCollection 2013 Mar. https://doi.org/10.4248/BR201301007 ; PubMed PMID: 26273495; PubMed Central PMCID: PMC4472096 , Mar-2013
Articles in Peer-reviewed Journals Lin L, Oon HY, Lin W, Qin Y-X. "Principal trabecular structural orientation predicted by quantitative ultrasound is strongly correlated with µFEA determined anisotropic apparent stiffness." Biomech Model Mechanobiol. 2014 Oct;13(5):961-71. Epub 2014 Jan 14. https://doi.org/10.1007/s10237-013-0547-3 ; PubMed PMID: 24419558; PubMed Central PMCID: PMC4098036 , Oct-2014
Articles in Peer-reviewed Journals Qin Y-X, Lin W, Mittra E, Xia Y, Cheng J, Judex S, Rubin C, Muller R. "Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound." Acta Astronautica. 2013 Nov;92(1):79-88. http://dx.doi.org/10.1016/j.actaastro.2012.08.032 ; PubMed PMID: 23976803; PubMed Central PMCID: PMC3747567 , Nov-2013
Articles in Peer-reviewed Journals Uddin SM, Qin Y-X. "Enhancement of osteogenic differentiation and proliferation in human mesenchymal stem cells by a modified low intensity ultrasound stimulation under simulated microgravity." PLoS One. 2013 Sep 12;8(9):e73914. eCollection 2013. https://doi.org/10.1371/journal.pone.0073914 ; PubMed PMID: 24069248; PubMed Central PMCID: PMC3772078 , Sep-2013
Articles in Peer-reviewed Journals Uddin SM, Hadjiargyrou M, Cheng J, Zhang S, Hu M, Qin Y-X. "Reversal of the detrimental effects of simulated microgravity on human osteoblasts by modified low intensity pulsed ultrasound." Ultrasound Med Biol. 2013 May;39(5):804-12. Epub 2013 Feb 27. https://doi.org/10.1016/j.ultrasmedbio.2012.11.016 ; PubMed PMID: 23453382; PubMed Central PMCID: PMC3717331 , May-2013
Articles in Peer-reviewed Journals Xu K, Ta D, He R, Qin Y-X, Wang W. "Axial transmission method for long bone fracture evaluation by ultrasonic guided waves: Simulation, phantom and in vitro experiments." Ultrasound Med Biol. 2014 Apr;40(4):817-27. Epub 2014 Jan 13. https://doi.org/10.1016/j.ultrasmedbio.2013.10.019 ; PubMed PMID: 24433749; PubMed Central PMCID: PMC4973576 , Apr-2014
Download in PDF pdf     
Fiscal Year: FY 2013  Task Last Updated:  02/06/2014 
PI Name: Qin, Yi-Xian  Ph.D. 
Project Title: Portable Quantitative Ultrasound with DXA/QCT and FEA Integration for Human Longitudinal Critical Bone Quality Assessment 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
 (2) Med13:We do not have the capability to implement medical resources that enhance operational innovation for medical needs (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: yi-xian.qin@stonybrook.edu  Fax:  631-632-8577 
PI Organization Type: UNIVERSITY  Phone: 631-632-1481  
Organization Name: SUNY- The State University of New York 
PI Address 1: Orthopaedic Bioengineering Research Laboratory 
PI Address 2: Room 215, Bioengineering Bldg 
PI Web Page:  
City: Stony Brook  State: NY 
Zip Code: 11794-5281  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 09/01/2013  End Date:  08/31/2016 
No. of Post Docs:   No. of PhD Degrees:   
No. of PhD Candidates:   No. of Master' Degrees:   
No. of Master's Candidates:   No. of Bachelor's Degrees:   
No. of Bachelor's Candidates:   Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution):  
Grant/Contract No.: NCC 9-58-SMST03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: Skeletal complications, i.e., osteoporosis, induced by microgravity during extended space mission, 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 (e.g., hip, knee, wrist, and heel), to longitudinally monitor bone alteration in disuse osteopenia, and to integrate ultrasound with DXA (dual-energy X-ray absorptiometry), QCT (quantitative computed tomography), and finite element analysis (FEA) for human subject. In vivo human tests will be evaluated at Stony Brook Osteoporosis Center and the Johnson Space Center/University of Texas Medical Branch (JSC/UTMB) bedrest facility. Human cadaver will be used for testing feasibility of identifying bone loss, microstructural and mechanical strength properties. The goals will be achieved by a series of specific aims (S.A.s).

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.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: 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.

 

Task Progress: New project for FY2013.

 

Bibliography Type: Description: (Last Updated: 08/24/2018) Show Cumulative Bibliography Listing