Development of pH-Weighted Magnetic Resonance Imaging in the Spinal Cord: Application in Degenerative Cervical Myelopathy

Abstract

Degenerative cervical myelopathy (DCM) is a degenerative disease of the spinal cord that can lead to neurological dysfunction. It has been hypothesized that ischemia and hypoxia in the spinal cord at the site of compression could impact functional recovery after decompression surgery. Unfortunately, direct in-vivo quantification of hypoxia and ischemia in the spine has been limited in humans. Magnetic resonance imaging (MRI) can be utilized to measure hypoxia indirectly in soft tissue. Specifically, chemical exchange saturation transfer (CEST) is an MRI contrast that can be derived from the transfer of magnetization from selectively excited endogenous protons to bulk water protons. This exchange process is pH-dependent and can be exploited to produce a pH-weighted CEST contrast called amine/amide concentration independent detection (AACID). Hypoxia can decrease the pH of tissue. For the first time in DCM patients, the severity of spinal cord compression was correlated with functional brain activity changes, suggesting that hypoxic injury in the spinal cord may contribute to cortical reorganization in the motor areas of the brain. The results from this study provided the motivation for this thesis to develop three-dimensional (3D) AACID CEST pH-weighted MRI at the clinically relevant field strength of 3.0T in the healthy brain and spinal cord and then to demonstrate the feasibility of pH-weighted imaging in the spinal cord of DCM patients. Furthermore, the reproducibility of spinal cord AACID CEST MRI was quantified and found to have the greatest reproducibility at the center of the 3D volume when incorporating a B1-inhomogeneity correction. In conclusion, this dissertation demonstrates the process of developing a 3D pH-weighted CEST MRI contrast at the clinically relevant field strength of 3.0T in the cervical spinal cord. This work includes initially exploring how the severity of cord compression affects brain functional activity, optimizing the CEST sequence at 3.0T, evaluating the reproducibility of the AACID measurement in both the healthy brain and cervical spinal cord and initial utilization in the spinal cord of people with DCM. This dissertation lays the groundwork to determine if hypoxia is occurring in the spinal cord of DCM patients and if it is a measure of neurological outcome