Most osteoporotic fractures occur at skeletal locations rich in cancellous (trabecular) bone. The most widely used criterion for risk assessment is bone mineral density (BMD). However, it is well known that BMD is not a satisfactory predictor of fracture risk. Indeed, there is now compelling theoretical, experimental and clinical evidence for the role of architecture as an additional predictor of the bone's mechanical competence. During the past cycles of this project we have shown both in the laboratory and in patient studies that magnetic resonance micro-imaging (mu-MRI), in conjunction with image analysis, can predict the trabecular bone's mechanical behavior and clinical outcome, respectively. In preliminary work we have conceived a new approach toward a complete quantification of cancellous bone architecture based on three-dimensional digital topological analysis and have shown that this techniques accurately describes the conversion of trabecular plates to rods, a process well known to occur during aging and, in particular, in osteoporosis. Paralleling these developments we have made significant progress in data acquisition, processing and analysis, which improved both sensitivity and precision of mu-MRI to the extent that longitudinal studies are now feasible. During the next phase of the project we propose (i) to further develop and evaluate digital topological analysis and additional structural analysis tools; (ii) to determine the precision of the mu-MRI-derived topological and scale parameters in specimens and representative patients; (iii) to assess the sensitivity of the method to detect architectural changes during early menopause in a pilot project involving women treated with estrogen and their controls; (iv) to compare sensitivity and precision of mu-MRI with DEXA and p-QCT. The overall hypothesis to be tested is that mu-MRI-based cancellous bone structural analysis is sensitive and reproducible and capable of detecting changes in cancellous bone architecture as they occur over time, either as a result of normal changes or in response to treatment. The long-term goal of the work proposed is to establish """"""""virtual bone biopsy,"""""""" analogous to physical bone biopsy, by three-dimensional architectural analysis of mu-MRI data collected in vivo, as a means to follow patients longitudinally, either as a method for assessing osteoporosis risk or for evaluating treatment efficacy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR041443-10
Application #
6655098
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Lester, Gayle E
Project Start
1993-01-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
10
Fiscal Year
2003
Total Cost
$367,363
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
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
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) 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
Sundberg, John P; McElwee, Kevin J; Carroll, Joseph M et al. (2011) Hypothesis testing: CTLA4 co-stimulatory pathways critical in the pathogenesis of human and mouse alopecia areata. J Invest Dermatol 131:2323-4
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
Wehrli, Felix W; Rajapakse, Chamith S; Magland, Jeremy F et al. (2010) Mechanical implications of estrogen supplementation in early postmenopausal women. J Bone Miner Res 25:1406-14
Rajapakse, Chamith S; Magland, Jeremy F; Wald, Michael J et al. (2010) Computational biomechanics of the distal tibia from high-resolution MR and micro-CT images. Bone 47:556-63
Magland, Jeremy F; Jones, Catherine E; Leonard, Mary B et al. (2009) Retrospective 3D registration of trabecular bone MR images for longitudinal studies. J Magn Reson Imaging 29:118-26

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