BME PhD Proposal Presentation: Owen Papuga
A Compression Model of Vertebral Degeneration and the Development of Bone Marrow Edema
By Owen Papuga
Advisor: Prof. Edward Schwarz
Back pain remains as one of our societyâs greatest burdens, and progress towards our understanding of its etiology, prognosis and appropriate clinical management has been limited by the absence of an animal model. Despite the prevalence of back pain, there is no definitive treatment for this condition. Moreover, the absence of predictable radiographic changes that correlate with painful vs. non-painful structural changes pose the greatest obstacle to progress in the field. Currently clinicians utilize Magnetic Resonance Imaging (MRI) as the most sensitive indicator of degeneration, using criteria developed by Michael Modic 1 in which Modic Type 1 (MT1) MRI changes are associated with chronic low back pain and used to designate those individuals who most likely benefit from surgical intervention.
However, the nature of these Modic changes remains unknown. Thus, to the end of elucidating the cellular and biomechanical changes that lead to MT1 we propose the development of a mouse model utilizing chronically loaded tail vertebrae that closely resembles the radiology and histopathology of vertebral degeneration seen in humans. Our proposed model utilizes an Ilizarov-type device to deliver compressive forces, originally described for the rat, and a novel surface coil for high-resolution (100 μm) contrast enhanced (CE)-MRI developed to characterize bone marrow edema in the mouse knee.
This model will help us better understand the physiological inflammatory response that underlies chronic low back pain by testing the following hypotheses:
- Chronic vertebral loading leads to marrow conversion from adipose rich (yellow) marrow to hematopoietic/vascular (red) marrow that gives rise to MT1-like signal changes.
- The release of loading leads to a reversal in conversion, from hematopoietic/vascular (red) marrow to adipose rich (yellow) marrow giving rise to MT2-Like signal changes.
- Chronic vertebral loading leads to structural changes in bone and cartilage, the geometry and organizational changes that occur can be correlated to the incidence and severity of MT1-Like changes.