Many of the diseases affecting today's aging population involve the degeneration of critical skeletal elements, causing chronic pain and loss of mobility. Clearly there is a need to better understand the basics of skeletal biology and its disease pathologies. While skeletal changes during bone development (in children) or bone degeneration (in the elderly) can be studied with X-ray based techniques, these studies measure the mineral content alone and expose healthy subjects to ionizing radiation. What is required is an analytical technique that can non-invasively evaluate the changes that occur in skeletal tissues during skeletogenesis, fracture healing, bone growth into orthopaedic implants, and in response to pharmaceutical interventions. This application proposes a strategy whereby nuclear magnetic resonance (NMR) imaging can be used as a novel non-invasive, non-ionizing means of assessing vertebrate bone formation and repair, providing new measures of these processes and circumventing the invasive and ionizing character of current approaches. This objective will be achieved through the application of the following specific aims: 1) To investigate the efficacy of NMR imaging as a tool for assessing bone formation in a model system based on a hollow fiber bioreactor (HFBR) seeded with primary osteoblast cells; 2) To employ X-ray microtomography (XMT) to establish the ranges of mineral densities for which quantitative NMR parametric maps can be used as surrogate measures of mineral content during bone formation in a HFBR; 3) To employ FT-IR microspectroscopy to establish the range of collagen concentrations for which quantitative NMR maps of the magnetization transfer (MT) effect can be used as a surrogate measure of collagen content for bone formed in a HFBR; and 4) To apply quantitative NMR indices to monitor how collagen and mineral contents change during the bone formation process in a calvarial organ culture system. Our studies, if successful, will yield quantitative, surrogate measures, which can be applied spatially and temporally to monitor the efficacy of different orthopaedic biomaterials, growth factors, bioreactors designs, and mechanical loading conditions on the bone formation process in vitro. Our studies will also yield a novel, non-invasive approach to osteogenesis studies in vivo. ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Biology Development and Disease Study Section (SBDD)
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Lester, Gayle E
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American Registry of Pathology, Inc.
United States
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Chesnick, Ingrid E; Centeno, Jose A; Todorov, Todor I et al. (2011) Spatial mapping of mineralization with manganese-enhanced magnetic resonance imaging. Bone 48:1194-201
Chesnick, Ingrid E; Fowler, Carol B; Mason, Jeffrey T et al. (2011) Novel mineral contrast agent for magnetic resonance studies of bone implants grown on a chick chorioallantoic membrane. Magn Reson Imaging 29:1244-54
Chesnick, Ingrid E; Mason, Jeffrey T; Giuseppetti, Anthony A et al. (2008) Magnetic resonance microscopy of collagen mineralization. Biophys J 95:2017-26
Chesnick, Ingrid E; Avallone, Francis A; Leapman, Richard D et al. (2007) Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and FTIR microspectroscopy. Bone 40:904-12
Chesnick, Ingrid E; Todorov, Todor I; Centeno, Jose A et al. (2007) Manganese-enhanced magnetic resonance microscopy of mineralization. Magn Reson Imaging 25:1095-104
Potter, Kimberlee; Sweet, Donald E; Anderson, Paul et al. (2006) Non-destructive studies of tissue-engineered phalanges by magnetic resonance microscopy and X-ray microtomography. Bone 38:350-8