Quantitative Molecular MRI of Intervertebral Disc Degeneration

Degeneration of the intervertebral disc (IVD) is the most common cause of back-related disability among North American adults. Low-back-pain and associated disability costs the United States more than 100 billion dollars annually in health care expenditures and reduced productivity. The mechanism of IVD degeneration, especially its biomolecular aspect, is poorly understood in an in vivo setting. Thus there is increasingly a need for the non-invasive diagnosis and quantification of IVD degeneration. MRI is a non-invasive imaging modality capable of producing contrast sensitive to biomolecules. Therefore, the primary objective of this dissertation research project is to develop MRI techniques capable of non-invasive quantification of IVD biomolecular composition in vivo. We further developed three MRI techniques specifically for IVD imaging. Magnetization transfer (MT) MRI, T1ρ MRI and sodium MRI were first separately validated of their specificities for IVD biomolecular components. In doing so, we concluded that MT MRI is sensitive to IVD collagen content, T1ρ MRI is indicative of IVD osmotic pressure, and sodium MRI is sensitive to IVD proteoglycan (PG) content. Next, we applied all three techniques to human subjects in vivo. Due to the inherently low signal-to-noise ratio (SNR) efficiency of sodium MRI, we engineered a custom radio-frequency (RF) surface coil for sodium MRI of human lumbar spine on a 7 T MRI scanner. Cross-correlation of the MT MRI, T1ρ MRI and sodium MRI data with the corresponding Pfirrmann grade revealed that the relative collagen density of IVD increases with degeneration, the IVD osmotic pressure decreases with degeneration, and the IVD PG content decreases with degeneration. By establishing that in vivo MT MRI, T1ρ MRI and sodium MRI can be used to quantify multiple IVD biomolecular characteristics non-invasively, we open up the possibility to conduct longitudinal studies on human subjects as they undergo IVD degeneration. The combination of MT MRI, T1ρ MRI and sodium MRI provides scientists and clinicians with the diagnostic tool to improve our understanding of IVD degeneration, which could benefit future treatment and prognosis of IVD degeneration