Degeneration of intervertebral discs is associated with low back pain, which affects a large proportion of the U.S. population. Treatments for back pain, such as therapeutics (e.g., growth factors) to alter cell function and biological implants aimed at modifying symptoms and the morphology of intervertebral discs are topics of active investigation at present. The cartilaginous endplate (CEP), which is a part of the intervertebral disc and is situated between the avascular disc proper and the bony vertebral body, plays an important role in the function and homeostasis of the disc. Vascular canals are found in calcified portions of the CEP and facilitate the supply of nutrients to the disc. Past studies have noted structural and compositional changes such as thinning and calcification of cartilage with aging and these may change the transport properties of the endplate. Such changes may lead to subsequent disc degeneration, and ultimately back pain. Additionally, hindered transport through the CEP may render biologic treatment options ineffective, if cells do not receive sufficient concentration of the active agent. Non-invasive evaluation of cartilaginous endplate, and its association with disc degeneration, is likely to be of critical importance in selecting patients for various treatments, as well as in understanding disc degeneration. The long-term goal of our study is to evaluate changes in the cartilaginous endplates of the disc using novel magnetic resonance imaging (MRI) approaches. The overall hypothesis is that ultra short time-to-echo (UTE) MR imaging will be sensitive to abnormal changes in structure, composition and transport properties of the cartilaginous endplate (CEP) of human spine, and that abnormalities will be associated with disc degeneration. The UTE sequence captures short T2 signals intrinsic to the CEP, parts of which are invisible using conventional sequences. I propose to perform UTE MRI on experimentally prepared CEP samples to determine the structural and compositional basis underlying the signal change, and use these findings to help understand signal changes seen in abnormal endplates. Transport properties of normal and abnormal cartilaginous endplates will be correlated with UTE MRI signals, to establish the functional basis of fluid transfer with and without loading. Lastly, the association between UTE MRI signals and disc degeneration will be assessed. The proposed research will provide a non-invasive means of evaluating disease of the cartilaginous endplates of human spines and increase our understanding of the relationship between UTE MRI appearances, endplate structure, composition, and function. This is likely to be useful for early intervention in treatment of disc degeneration and selection of patients suitable for biological therapy.

Public Health Relevance

Cartilaginous endplates of intervertebral discs play important role in normal function and nutrition of the disc proper. The proposed research will establish a novel technique for MR imaging of cartilaginous endplates, not possible using conventional techniques, and associate imaging findings with biomechanical and transport properties of the endplate, for a better understanding of pathogenesis of disc degeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR059764-03
Application #
8274445
Study Section
Special Emphasis Panel (ZAR1-CHW (M3))
Program Officer
Lester, Gayle E
Project Start
2010-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$120,159
Indirect Cost
$8,479
Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Bae, Won C; Biswas, Reni; Statum, Sheronda et al. (2014) Sensitivity of quantitative UTE MRI to the biomechanical property of the temporomandibular joint disc. Skeletal Radiol 43:1217-23
Geiger, Daniel; Bae, Won C; Statum, Sheronda et al. (2014) Quantitative 3D ultrashort time-to-echo (UTE) MRI and micro-CT (?CT) evaluation of the temporomandibular joint (TMJ) condylar morphology. Skeletal Radiol 43:19-25
Bae, Won C; Biswas, Reni; Chen, Karen et al. (2014) UTE MRI of the Osteochondral Junction. Curr Radiol Rep 2:35
Bae, Won C; Statum, Sheronda; Zhang, Zhao et al. (2013) Morphology of the cartilaginous endplates in human intervertebral disks with ultrashort echo time MR imaging. Radiology 266:564-74
Bae, Won C; Chen, Peter C; Chung, Christine B et al. (2012) Quantitative ultrashort echo time (UTE) MRI of human cortical bone: correlation with porosity and biomechanical properties. J Bone Miner Res 27:848-57
Biswas, Reni; Bae, Won; Diaz, Eric et al. (2012) Ultrashort echo time (UTE) imaging with bi-component analysis: bound and free water evaluation of bovine cortical bone subject to sequential drying. Bone 50:749-55
Sanal, Hatice T; Bae, Won C; Pauli, Chantal et al. (2011) Magnetic resonance imaging of the temporomandibular joint disc: feasibility of novel quantitative magnetic resonance evaluation using histologic and biomechanical reference standards. J Orofac Pain 25:345-53
Bae, Won C; Masuda, Koichi (2011) Emerging technologies for molecular therapy for intervertebral disk degeneration. Orthop Clin North Am 42:585-601, ix
Kokabi, Nima; Bae, Won; Diaz, Eric et al. (2011) Ultrashort TE MR imaging of bovine cortical bone: the effect of water loss on the T1 and T2* relaxation times. Magn Reson Med 66:476-82
Buck, Florian M; Bae, Won C; Diaz, Eric et al. (2011) Comparison of T1rho measurements in agarose phantoms and human patellar cartilage using 2D multislice spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot techniques at 3 T. AJR Am J Roentgenol 196:W174-9

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