Overview

A Scanning Confocal Acoustic Diagnostic System for Noninvasively Assessing Bone Quality

Principal Investigator:
Yi-Xian Qin, Ph.D.

Organization:
Stony Brook University - State University of New York

The bone loss resulting from extended missions in zero gravity represents a serious problem for astronaut health, both during flight and upon return to Earth’s gravity. Early diagnosis of bone loss would enable prompt treatment and dramatically reduce the risk of injury to astronauts. Yet currently, the principal method used to diagnose bone disease only provides a 2-dimensional representation of bone mineral density but not its physical properties. To resolve this, Dr. Yi-Xian Qin is developing a scanning acoustic diagnostic system which uses ultrasound to determine bone quality and serve as a diagnostic tool for assessing both density and strength of bone. The real-time, high-resolution, portable bone imaging device will be used in flight to monitor bone loss and can be used to determine subtle changes in density and strength of the skeleton, e.g., the risk of fracture. Since musculoskeletal disorders like osteoporosis and delayed healing of fractures have become a major societal problem affecting approximately 25 million people in the United States, this device holds promise for use on Earth as well as in space.

NASA Taskbook Entry

Technical Summary

The bone loss which parallels extended space missions represents a serious threat to astronaut health, both during flight and on return to gravitational fields. Early diagnosis of osteoporosis would enable prompt treatment and thus dramatically reduce the risk of fracture. Currently, the principal method used to diagnose osteoporosis is dual-energy X-ray absorptiometry (DEXA), which provides a two-dimensional representation of bone mineral density (BMD), but not bone's physical properties. Recent advances in quantitative ultrasound have enabled a true characterization of bone quality, including both BMD and mechanical strength. We have developed a scanning confocal acoustic diagnostic (SCAD) system capable of generating acoustic images at the regions of interest. The objectives of this study are to develop an unique diagnostic modality for noninvasively evaluating human bone mineral density and stiffness. In particular, we will aim to improve the resolution, to shorten the ultrasound scanning time (e.g., < 5 minutes), to validate image-based characterization of bones physical properties with true bone quality as based on material testing, and to initiate human subject testing. In essence, this next phase of research will focus on developing the SCAD prototype as a real-time, high-resolution and portable bone image modality for determining bone quality. A series of four interrelated specific aims are proposed to achieve the goals.

Specific Aims
The aims of the study are to develop and establish the efficacy of a real-time SCAD system for assessing bone status, to identify the complexity of surface morphology, and to correlate image based parameter to bone quality.

Develop a rapid SCAD system capable of generating high-resolution acoustic images for trabecular structural and strength properties in the region of interest.
Develop the system capable of extracting trabecular broadband ultrasound attenuation and ultraviolet images at multiple skeletal sites (i.e., calcaneus, wrist and knee), providing evaluation of loss and fracture risk.
Evaluate the capability of the SCAD system in testing bone structure and strength in cadavers by microtomography determined microstructure, nanoindentor tested integrity and modulus.
Correlate the degree of osteoporosis and disuse osteopenia in humans to determine the relationship to age, gender, degree of bone loss and rational effects at region of interest using SCAD and DXA.

The SCAD system was further developed in this research period. The new system is capable of generating noninvasive, high-resolution quantitative ultrasound (QUS) attenuation and velocity maps of bone, and thus determining the relationship between ultrasonic determined parameters and BMD, bone strength and bone physical properties (i.e., stiffness and modulus). The ultrasound resolution and sensitivity are significantly improved in this new configuration. Several milestones were achieved.

Project Milestones

Improvement of scanning speed by computer chip, hardware design, time sequence and control in the software design. The goal was to accelerate the bone scan with reduced time and incorporate with identifying 3D surface topology of bone for accurate calculation of ultrasound wave velocity and attenuation. The hardware and programming were successfully developed, in which the scan time for 80 x 80 pixel region of confocal ultrasound was reduced to 5 minutes with all the surface topology information. The irregular surfaces of calcaneus can be clearly depicted using surface mapping. SCAD parameters were highly correlated to BMD, bone volume fraction and bone modulus.
Bone surface topology mapping and its role in trabecular bone quality assessment using scanning confocal ultrasound. The goal was to identify 3D surface topology of bone for accurate calculation of ultrasound wave velocity. The irregular surfaces of calcaneus can be clearly depicted using surface mapping, and SCAD parameters were highly correlated to BMD, bone volume fraction and bone modulus.
Automatic region of interests based on the ultrasound broad band attenuation. This feature is capable of determining ultrasonic parameters through bone more accurately and automatically with a friendly user-device interface, which can be easily incorporated into future in vivo clinical application.
Explore the capability of ultrasound assessment for bone quality in bed-rest subjects. QUS provides a method for characterizing the quality of bone noninvasively. The team continues to conduct the study for longitudinal assessment of bone mass and quality for bed-rest subjects. The performance of a scanning confocal QUS system was evaluated in a 90-day microgravity analog study with the comparison to standard DXA in localized regions of interest, e.g., calcaneus. The subject pool included 11 disuse (control) and 18 disuse plus vibration (low-magnitude, high-frequency treatment) subjects at University of Texas Medical Branch in Galveston, Texas. QUS scanning for the calcaneus region showed a unique pattern in the acoustic images. Strong correlation was observed between pooled broadband ultrasound attenuation (BUA) in the heel region and pooled whole body BMD (determined by the DXA), R2=0.7. Longitudinally, subtle changes were significantly predicted by the ultrasound wave velocity (UV) measurements at 0, 60, and 90 days, in which 1.5 percent UV reduction in 60 days bed rest. These results suggested that BMD is one of the major contributors for bone loss in the skeleton, and QUS could be used to longitudinally monitor bone loss in the bed-rest environment.
Initiation of SCAD assessment in large and critical bone sites, e.g., proximal femur. These works will help refine a noninvasive diagnosis for bone loss and may potentiate the development of a flight instrument for the precise determination of bone quality during extended space missions.

Earth Applications

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 women over 65 will have vertebral fractures and 90 percent of women aged 75 and older have radiographic evidence of osteoporosis. Thus, approximately 24 million people suffer from osteoporosis in the United States, with an estimated annual direct cost of more than $18 billion to national health programs. Hence, an early diagnosis that can predict fracture risk and result in prompt treatment is extremely important.

Development of a low mass, compact, noninvasive diagnostic tool (i.e., ultrasound bone quality detector) will have a great impact as an early diagnostic to prevent bone fracture. This research addressed the NASA Human Research Program's risks map related to noninvasive 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 scanning confocal acoustic diagnostic (SCAD) ultrasound for assessing bone quality. We have been able to demonstrate that bone quality is predictable via noninvasive scanning ultrasound imaging in the region of interest and demonstrate the strong correlation between SCAD determined data and microtomography identified bone mineral density, structural index and mechanical modulus. These data have provided a foundation for further development of the technology and the clinical application in this research.

Our principal goal is to continue the development and evaluation of the SCAD system for ground-based determination of physical properties of bone, for determining even subtle changes in bone during extended flights, and for early diagnosis of osteoporosis and prediction of fracture risks.

This project's funding ended in 2008