The chief manifestation of osteoporosis is the occurrence of fractures. Most osteoporotic fractures occur at skeletal locations rich in trabecular bone. Prevailing among these are the vertebrae, wrist and proximal femur. Hip fractures are the most debilitating among osteoporotic fractures in terms of morbidity and mortality. There is now strong evidence that the loss of bone mass is accompanied by a decline in the trabecular bone net- work's structural integrity. The impaired mechanical competence secondary to gonadal steroid depletion is caused by topological changes in the bone's architectural make-up, chief among which is fenestration of tra becular plates resulting in their conversion to rods and the latter's eventual disruption. Complementing antire- sorptive treatment, new therapies have recently become available to treat the devastating consequences of severe bone loss with bone-forming (i.e. anabolic) drugs. It is not clear, however, whether such therapies are, in fact, able to reverse the disintegration of the trabecular network, and to what extent the structural changes differ from those induced by antiresorptive treatment. In this project we propose to develop novel micro-MRI-based technology suitable to quantify the structural and mechanical consequences of various forms of treatment of patients with metabolic bone disease.
We aim to apply this methodology to patients who are at high risk of fracture and who are treated either with 1-34 parathyroid hormone or alendronate. The overall hypothesis is that the new methodology will provide detailed insight into the structural manifestations of trabecular bone subjected to short-term drug treatment. The project will consist of six specific aims involving the development, integration and evaluation of new methods involving data acquisition and reconstruction, motion correction, cryogenic RF coil technology, image processing and analysis, as well as image-based finite-element modeling of bone mechanical competence. We plan to address these goals in partnership with two external collaborators through subcontracts (Dr. Jarek Wosik, Department of Electrical Engineering, Texas Center for Superconductivity, University of Houston, and Dr. Edward Quo, Department of Biomedical Engineering, Columbia University). Already established Penn-internal partnerships with Dr. Charles Epstein (Department of Mathematics) and Dr. Peter Snyder (Department of Medicine, Division of Endocrinology) will be further expanded and strengthened.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR053156-02
Application #
7126778
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (50))
Program Officer
Lester, Gayle E
Project Start
2005-09-23
Project End
2010-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$617,754
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Magland, Jeremy F; Li, Cheng; Langham, Michael C et al. (2016) Pulse sequence programming in a dynamic visual environment: SequenceTree. Magn Reson Med 75:257-65
Chen, Cheng; Jin, Dakai; Liu, Yinxiao et al. (2016) Trabecular bone characterization on the continuum of plates and rods using in vivo MR imaging and volumetric topological analysis. Phys Med Biol 61:N478-N496
Zhang, Ning; Magland, Jeremy F; Rajapakse, Chamith S et al. (2013) Assessment of trabecular bone yield and post-yield behavior from high-resolution MRI-based nonlinear finite element analysis at the distal radius of premenopausal and postmenopausal women susceptible to osteoporosis. Acad Radiol 20:1584-91
Zhang, Ning; Magland, Jeremy F; Rajapakse, Chamith S et al. (2013) Potential of in vivo MRI-based nonlinear finite-element analysis for the assessment of trabecular bone post-yield properties. Med Phys 40:052303
Wald, Michael J; Magland, Jeremy F; Rajapakse, Chamith S et al. (2012) Predicting trabecular bone elastic properties from measures of bone volume fraction and fabric on the basis of micromagnetic resonance images. Magn Reson Med 68:463-73
Bhagat, Yusuf A; Rajapakse, Chamith S; Magland, Jeremy F et al. (2011) Performance of ?MRI-Based virtual bone biopsy for structural and mechanical analysis at the distal tibia at 7T field strength. J Magn Reson Imaging 33:372-81
Bhagat, Yusuf A; Rajapakse, Chamith S; Magland, Jeremy F et al. (2011) On the significance of motion degradation in high-resolution 3D ?MRI of trabecular bone. Acad Radiol 18:1205-16
Wright, Alexander C; Lemdiasov, Rostislav; Connick, Thomas J et al. (2011) Helmholtz-pair transmit coil with integrated receive array for high-resolution MRI of trabecular bone in the distal tibia at 7T. J Magn Reson 210:113-22
Wald, Michael Jeffrey; Magland, Jeremy Franklin; Rajapakse, Chamith Sudesh et al. (2010) Structural and mechanical parameters of trabecular bone estimated from in vivo high-resolution magnetic resonance images at 3 tesla field strength. J Magn Reson Imaging 31:1157-68
Magland, Jeremy F; Rajapakse, Chamith S; Wright, Alexander C et al. (2010) 3D fast spin echo with out-of-slab cancellation: a technique for high-resolution structural imaging of trabecular bone at 7 Tesla. Magn Reson Med 63:719-27

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