NOTE: Extended to 10/31/2013 per NSBRI (Ed., 2/22/2013)

In this period, the technology development of a new generation of the SCAN device is significantly advanced as a portable device to access the bone quality at wrist and heel sites, and to use ultrasound for guided treatment for controlled bone fracture. A demo of the technology was performed at the new National Space Biomedical Research Institute (NSBRI) headquarters in April of 2012. A combined mechanical and electrical array scan modality has been initiated and achieved, which can complete the SCAN time at the particular skeletal site less in than 2 minutes. The new development is capable of generating non-invasive, high-resolution quantitative ultrasound (QUS) attenuation and velocity maps of bone for determining the relationship between ultrasonic specific parameters and bone mineral density (BMD) and bone's physical properties (i.e., stiffness). Several example studies were briefly described.

1) Developing a SCAN system for bone quality assessment: A real time rapid acoustic mapping system is developed for evaluation of bone density, structural and mechanical properties, and defect using a patented technology developed in the Principal Investigator's lab. Phased arrays using a linear array of elements, emitted with different delays, generate a focal ultrasonic beam in X-direction by controlled programming. Combined mechanical scanning will be performed in the Y-direction. Such design greatly reduces scan time (less than 30 sec) and maintains resolution and image quality. Beams are generated and received with the use of focal laws, in which software models the programs to spatially control confocal points and scanning. Setup of pulse wizards will be controlled by a house designed 16-bit microprocessor. Phased array transducers will be designed and built with 120 linear elements with the frequency range of 0.5~2.5 MHz. Each phase of excitation is approximately 2 micros. Each focal point will take approximately 0.1 ms. A 2-D electro-mechanic scanning region may take about 20 sec. Thus, the influences of soft tissue, cortical bone, and irregular shape surfaces can be greatly reduced. In this confocal scanning mode, ultrasound parameters, i.e., broadband ultrasound attenuation (BUA) and ultrasound-UV, can generate a spatial acoustic map at the region of interest.

2) Noninvasive prediction of bone internal and principal structural orientation using SCAN: Bone has the ability to adapt its structure in response to the mechanical environment as defined as Wolff's Law. The alignment of trabecular structure is intended to adapt to the particular mechanical milieu applied to it. Due to the absence of normal mechanical loading, it will be extremely important to assess the anisotropic deterioration of bone during the extreme conditions, i.e., long term space mission and disease orientated disuse, to predict risk of fractures. In this work, 7 bovine trabecular bone balls were used for rotational ultrasound measurement around 3 anatomical axes to elucidate the ability of ultrasound to identify trabecular orientation. By comparing to the mean intercept length (MIL) tensor obtained from µCT, the angle difference of the prediction by UV was 4.45 , while it resulted in 11.67 angle difference between direction predicted by µCT and the prediction by Achilles tendon thickness (ATT). This result demonstrates the ability of ultrasound as a non-invasive measurement tool for the principal structural orientation of the trabecular bone.

3) Development of mechano-electronic array SCAN imaging for bone quality assessment: New hardware and software are developed to synchronize mechanical fine scan with electrical phase delay scan, and sequential data transaction. Computer algorithms are designed to perform data analysis and imaging forming. An accelerated continuous scan mode is further designed and built including rapid A/D (amplitude-dependent) data acquisition, microprocessor control synchronizing (for scanning, transmit signal, and A/D trigger), and control algorithm. A high-resolution ultrasound image array with 0.5 mm resolution results in scan times of less than 2 minutes is achieved in the region of interest (ROI).

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. Developed prototype of SCAN is successfully used in the bedrest subjects and clinical test (Stony Brook University). A fast scan mode (~2.5 min) and a surface topology mapping technology using scanning ultrasound are developed and capable of determining calcaneus bone thickness accurately and hence enhancing the accuracy of UV measurement. Ultrasound treatment for progressive bone loss is also initiated in this year's research.

NOTE: Extended to 10/31/2013 per NSBRI (Ed., 2/22/2013)

Several studies were conducted:

1) Development of electronic array SCAN for bone imaging. The objective for this project is to develop computer-controlled phase delay and sequence of acoustic excitation energy for electronic focusing in the 3-D object. An accelerated continuous scan mode is further designed and built including rapid A/D data acquisition, microprocessor control synchronizing (for scanning, transmit signal, and A/D trigger) and control algorithm. A high-resolution ultrasound image array with 60x60 (mm2) and 0.5 mm resolution results in scan times of less than 2.5 minutes in the region of interest (ROI).

2) Development of SCAN for multi-site quantitative ultrasound measurement. The team is continuing to develop an image based SCAN technology for enhanced diagnostic readings at multiple anatomical sites, e.g., wrist region for distal radius and ulna. A soft contact transducer holder was designed to provide acoustic coupling free of water. The design was validated using 2D SCAN imaging system, and evaluated with its performance at the distal radius. Strong correlation between H2O and gel coupling (R2=0.89), and high repeatability (95%) were observed at the tested site. Results indicated that there was an excellent relationship between ultrasound imaging and microradiographic image. These data demonstrated feasibility of ultrasound imaging in multiple critical skeletal sites, i.e., wrist.

3) Characterization of cortical bone fracture with SCAN and longitudinal acoustic velocity. The objectives of this study were to evaluate the cortical fracture gap size using quantitative ultrasound imaging, and the longitudinal ultrasound velocity in bone to predict the fracture gap size. Strong correlations were observed between ultrasound and X-ray images in fracture size (R2=0.91). High correlation was found between gap size and the longitudinal velocity from 4000 m/s to 3000 m/s for 0-5 mm gaps (R2=0.93). These results suggest that ultrasound is capable to predict bone fracture, and provide useful information for longitudinal assessment of complications, such as non-union fracture, and for evaluating healing.

4) Improving ultrasound sensitivity with phase cancellation method. Phase cancellation in ultrasound due to large receiver size has been proposed as a contributing factor to the inaccuracy of estimating broadband ultrasound attenuation (BUA). In vitro ultrasound measurements were conducted on 54 trabecular bone samples (harvested from sheep femurs) in a confocal configuration with a focused transmitter and synthesized focused receivers of different aperture sizes. Phase sensitive (PS) and phase insensitive (PI) detections were performed. The results indicate that the receiver aperture size used in the confocal configuration with PI detection should at least equal the aperture of the transmitter to capture most of the energy redistributed by the interference and diffraction from the trabecular bone.

5) Mitigation of bone loss using guided therapeutic ultrasound in osteopenia. The objective of this project is to evaluate the capability of guided ultrasound in generating dynamic mechanical signal to inhibit bone loss in an estrogen deficient model of osteopenia. Specimen specific, voxel based, finite element (FE) models (E=18GPa & v=0.3), were generated using µCT image data and 1% axial compressive strain was simulated using a nonlinear FE solver (ABAQUS). US treatment significantly increased BVF compared to OVX controls for the 100mW/cm2 treated group. This study suggests that there exists a minimum intensity threshold below which US in less effective at maintaining bone's microstructural and mechanical characteristics. The paper is published in BONE.

6) Acceleration of fracture healing in vivo in a disuse animal model using guided ultrasound. Long duration microgravity not only induces bone loss, but also increases risk of fracture. The aim of this project is to evaluate the potentials of low-intensity guided therapeutic ultrasound on acceleration of fracture healing under delayed union model using hindlimb suspension (HLS) rats. The results have revealed that 6% less bone volume was observed in HLS alone group than the normal fracture (i.e., normal non-HLS condition). Ultrasound treatment on HLS fracture accelerated the healing with significant higher bone volume (25% than the HLS alone group. These data imply that guided ultrasound can speed up the healing and mineralization in the fracture callus, while disuse may delay the fracture healing.

In this year's research, the team is continuing the development of a new generation of the prototype SCAN system to access the bone quality at multiple skeletal sites, and use ultrasound to detect bone fracture. A combined mechanical and electrical array scan modality has been initiated, which can complete the SCAN time at the particular skeletal site less in than 2.5 minutes. The new development is capable of generating non-invasive, high-resolution quantitative ultrasound (QUS) attenuation and velocity maps of bone for determining the relationship between ultrasonic specific parameters and bone mineral density (BMD) and bone's physical properties (i.e., stiffness). The team has achieved several milestones:

1) Continuing development of SCAN for multi-site quantitative ultrasound measurement. The objective of this project is to develop an image based SCAN technology for enhanced diagnostic readings at multiple anatomical sites, e.g., wrist region for distal radius and ulna. Strong correlation between H2O and gel coupling (R2=0.89), and high repeatability (95%) were observed at the tested site. Results indicated that there was an excellent relationship between ultrasound imaging and microradiographic image.

2) Characterization of cortical bone fracture with SCAN and longitudinal acoustic velocity. A real-time scanning confocal ultrasound image was developed to evaluate bone defect and bone loss. The objectives of this study were to evaluate the cortical fracture gap size using quantitative ultrasound imaging, and the longitudinal ultrasound velocity in bone to predict the fracture gap size. Strong correlations were observed between ultrasound and X-ray images in fracture size (R2=0.91). These results suggest that ultrasound is capable to predict bone fracture, and provide useful information for longitudinal assessment of complications, such as non-union fracture, and for evaluating healing.

3) Continuing development of electronic SCAN with array ultrasound transducer. To develop computer-controlled phase delay and sequence of acoustic excitation energy for electronic focusing in the 3-D object, an accelerated continuous scan mode is designed and built including rapid A/D data acquisition, microprocessor control synchronizing (for scanning, transmit signal, and A/D trigger) and control algorithm. A high-resolution 2-D ultrasound image array with 60x60 (mm2) and 0.5 mm resolution results in scan times of less than 2.5 minutes in the region of interest (ROI), i.e., in calcaneus, wrist, and knee. 4) Guided low-energy therapeutic ultrasound in an OVX rat model of osteopenia. The objective of this project is to evaluate the capability of therapeutic ultrasound in mitigation of bone loss in an estrogen deficient model of osteopenia. US treatment significantly increased BVF compared to OVX controls for the 100mW/cm2 treated group. This study suggests that there exists a minimum intensity threshold below which US in less effective at maintaining bone's microstructural and mechanical characteristics.

5) Bone fracture healing using low-energy guided ultrasound. The aim of this project is to evaluate the potentials of low-intensity guided therapeutic ultrasound on acceleration of fracture healing under delayed union model (femur) using hindlimb suspension (HLS) rats. The results have revealed that 6% less bone volume was observed in HLS alone group than the normal fracture (i.e., normal non-HLS condition). Ultrasound treatment on HLS fracture accelerated the healing with significant higher bone volume (25%) than the HLS alone group.

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 Bioastronautics 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 µCT 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.

In this year’s research, the research team is continuing in development of a new generation of the prototype of scanning confocal acoustic navigation (SCAN) system to access the bone quality at the multiple skeletal sites, and use ultrasound to detect bone fracture. A combined mechanical and electrical array scan modality has been initiated, which can complete the SCAN time at the particular skeletal site less than 2.5 minutes. The new development is capable of generating non-invasive, high-resolution quantitative ultrasound (QUS) attenuation and velocity maps of bone for determining the relationship between ultrasonic specific parameters and bone mineral density (BMD) and bone’s physical properties (i.e., stiffness). Several studies were conducted.

(1) Multi-Site Quantitative Ultrasound Scanner for Osteoporosis Diagnostics - Evaluated at the Distal Radius. The objective of this study was to provide validation of the new mechanical setup for the 2D scanning confocal acoustic diagnostic (SCAD) system, and evaluate its performance at the distal radius.

(2) Non-invasive assessment of long bone fracture and its potential healing process using quantitative ultrasound.

In this study, we evaluated a hypothesis that the ultrasonic velocity drop is dependent on the fracture gap size. A three transducers ultrasound system was setup to measure fracture gap size. This was verified by both experiment and mathematical simulation.

(3) Mediation of Bone Loss with Ultrasound Induced Dynamic Mechanical Signals in an OVX Rat Model of Osteopenia.

This study tests the hypothesis that an ultrasound generated dynamic mechanical signal can inhibit bone loss in an estrogen deficient model of osteopenia.

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 SCAD 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 Bioastronautics Roadmap related to non-invasive assessment of the acceleration of age-related osteoporosis and the monitoring of fractures and impaired fracture healing.