PROJECT 3

There currently exists no practical and reliable technique for prevention or reversal of osteoporosis (bone loss) that occurs due to prolonged exposure to less than Earth's gravity. Without practical and effective measures to counter the debilitating effects of bone loss, astronauts may not be able to function normally upon return to Earth's gravity after extended survival in non-terrestrial (space, Moon, Mars) environments. Although countermeasures to space deconditioning have been developed (ergometer, treadmill, "Penguin" suit, and lower body negative pressure), these measures do not completely solve the muscle atrophy and bone loss problem, nor are they particularly efficient strategies. My NASA EPSCoR research focuses on preservation of skeletal function by determining optimal ways to use proven techniques (resistive exercise) and by developing novel mechanical assessment and stimulation therapies (including broadband acoustic and impulsive mechanical excitation).

My previous research on musculoskeletal adaptation has identified constant resistance (isoinertial) exercise and mechanical stimulation at specific frequencies as essential elements for prevention and maintenance of muscle mass and bone mass, respectively. This work has resulted in a theory which can be used to predict skeletal mass changes in altered activity and gravity environments, and has led to the development of a patented instrument that can be tuned and used to mechanically stimulate the skeleton and to simultaneously quantify skeletal stiffness and changes in skeletal stiffness following long-term inactivity, exercise and space-flight. One key aspect of the proposed research will examine the effect of load intensity, duration and postural effects of resistive exercise in order to gain insight into the musculoskeletal remodeling response. I am currently collaborating with Dr. James Jordan, M.D. who has patented a methodology/technology dubbed "Resist-Stance" that targets a broad spectrum of exercise, cross-training and rehabilitation applications. The Resist-Stance methodology utilizes a cycle ergometer and emphasizes relatively low RPM, while targeting greater resistance as work effort increases. This methodology differs from conventional harnessed treadmill and horizontal cycling exercise methods, in that the Resist-Stance methodology emphasizes simultaneous activation of the entire musculoskeletal system by promoting a standing cycling posture. Dr. Jordan and I are currently working to adapt the existing standing cycle ergometer for closed kinetic chain exercise and rehabilitation in space. The design will simulate gravitational, centripetal and centrifugal forces on all musculoskeletal units and intersegmental joints. Simultaneous activation of the entire musculoskeletal system should produce an efficient exercise prescription during long duration space missions. A controlled clinical trial that prospectively quantifies changes in musculoskeletal strength is under development.

Another portion of my musculoskeletal countermeasures research focuses on assessment of bone stiffness using non-invasive mechanical stimulation (impedance) and broadband ultrasound techniques. In collaboration with Activator Methods, Inc. and the OrthoLogic Corp, both of Phoenix, Arizona, I have developed a non-invasive impulse-based mechanical impedance technique for quantifying the structural stiffness of the musculoskeleton. During the past few months, custom MatLab-based software analysis and vibration simulation programs have been written to efficiently perform non-invasive, frequency-dependent mechanical stiffness assessments of the musculoskeleton. The ability to characterize the frequency-dependent mechanical stiffness of the musculoskeletal system may prove to be a particular effective method to prospectively assess musculoskeletal changes associated with the aforementioned exercise countermeasures. During the past year, I have also teamed up with Dr. Junru Wu (Physics) and together we have developed an "acoustic microscope" that can be used to non-destructively evaluate spatial variations (20 micron resolution) in the transverse and longitudinal mechanical properties of trabecular bone. This information is being used to provide precise material property descriptions of trabecular bone for use in fully three-dimensional, large scale finite element models of trabecular bone structures. During the past semester (Fall 1999), two Belgian computer science graduate students worked in my musculoskeletal research laboratory and greatly extended the capabilities of an existing analytical and numerical analysis program dubbed "Trabecular Bone Morphology and Analysis System" or TBMAS. This program currently performs 2D and 3D morphological analysis of serial image data sets. TBMAS can import image arrays from any data source (including computed tomography, magnetic resonance imaging, histologic data sets) and produces a volumetric mathematical description of the data set. A new feature added to of the program is the capability to generate brick-element and tetrahedral-element meshes that can be exported commercial finite element analysis systems. I am currently using Cosmos/M to process data arrays with up to 1 million degrees of freedom, and the resulting models are being used to simulate gravity and activity-induced changes in skeletal density, stiffness and strength. Current work also focuses on developing an efficient method to map acoustic microscope-determined spatial variations in trabecular bone mechanical properties with the finite element mesh models.

Ties and collaboration with NASA researchers at JSC - Dr. Laurie Webster II (Space Biomedical Research Institute), Dr. Michael Greenisen (Director, Exercise Physiology Lab), Dr. Linda Shackelford (Director, Bone and Mineral Research Laboratory), Suzanne Schneider (Research Physiologist, Exercise Physiology Lab), Stuart Lee (Exercise Physiologist & Wyle Contractor, Exercise Physiology Lab) have been established over the past several years. As part of my NASA EPSCoR project, I am working to establish closer ties with one or more of these NASA researchers as well as Vermont-based and national strategic enterprises involved in musculoskeletal rehabilitation. I am in the process of recruiting a Ph.D. level graduate student who can facilitate the above research and ultimately hope to recruit a post-doctoral research fellow to further assist with my exercise countermeasures research development and ties to NASA centers and researchers.

Dr. Tony S. Keller, Principal Investigator for this project, is currently Associate Professor of Mechanical Engineering at the University of Vermont and Director of the Musculoskeletal Research Laboratory (MRL). He has a joint appointment in the Department of Orthopaedics & Rehabilitation, and has established research collaborations with NASA and other national and international musculoskeletal biomechanics research groups. His research interests focus on computational and experimental biomechanics of the musculoskeletal system and areas of expertise include: experimental mechanics, stress analysis, image analysis and implant design. He has several patents which focus on assessment and treatment of osteoporosis using a novel form of mechanical stimulation.

REFERENCES

1. A Three-Dimensional Finite Element Scheme to Investigate the Apparent Mechanical Properties of Trabecular Bone. R. Saxena, T.S. Keller and J.M. Sullivan. Computer Methods in Biomechanics and Biomedical Engineering, 2:285-294, 1999.

2. In Vivo Transient Vibration Analysis of the Normal Human Thoraco-Lumbar Spine. T.S. Keller, C.J. Colloca, A.W. Fuhr. J Manipulative Physiol Ther., in press.

3. Mechanical Impedance of the Human Lower Thoracic and Lumbar Spine Exposed to In Vivo Posterior-Anterior Manipulative Thrusts. C.J. Colloca, T.S. Keller, D.E. Selzer, and A.W. Fuhr, Submitted to 12th Conference of the European Society of Biomechanics, Dublin, Ireland, August 27-30, 2000.

4. Dynamic Response of the Human Lumbar Spine: A 5 DOF Lumped Parameter Time and Frequency Domain Model. T.S. Keller and C.J. Colloca, Submitted to 12th Conference of the European Society of Biomechanics, Dublin, Ireland, August 27-30, 2000.