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.
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.
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