Assessment of functional magnetic resonance imaging as a tool to detect neuronal activity in the spinal cord.

摘要

Functional Magnetic Resonance Imaging (fMRI) is an indirect, non-invasive tool that has been used to detect areas of neuronal activity in the brain during a stimulus or task. Regions of activity are identified based on a hemodynamic effect. Coupling between the metabolic demands of neuronal activity and the hemodynamic response results in localized increases in blood oxygenation as the areas of activity receive a much larger supply of oxygenated blood than is needed. Oxyhemoglobin and deoxyhemoglobin have different magnetic susceptibilities therefore the localized increases in blood oxygenation are detectable by fMRI. More recently, the technique has been developed for use in the spinal cord. Spinal cord imaging is subject to more confounds than brain imaging. Examples of additional problems include motion due to respiration and the flow of cerebral spinal fluid (CSF). For these reasons the technique must be verified by comparison with "gold standards" in order to demonstrate that spinal fMRI can detect regions of neuronal activity.; In Chapter 2, a chronic experimental model for fMRI imaging of the rat spinal cord is described. This section is critical for later parts of the thesis as well as future studies as currently, alpha-chloralose is the most commonly used anesthetic during animal fMRI studies. Recovery of the animal is not possible therefore limiting experimental design. The areas of functional activity in the cervical spinal cord were compared in alpha-chloralose and halothane anesthetized rats during electrical forepaw stimulation. The expression of c-fos, a known marker of neuronal activity, was used to observe the regions of the spinal cord in which activity was observed. Correspondence between functional activity and c-fos expression was found in the rostral-caudal direction. The results indicate that halothane anesthesia can be used during animal spinal fMRI studies.; In Chapter 3, the fMRI response in the rat spinal cord to different intensities of thermal stimuli is characterized. A comparison between alpha-chloralose and halothane anesthesia was also repeated in order to confirm our previous findings that halothane could be used for animal spinal fMRI. The most striking results demonstrate that the intensity of stimulation could be identified by the magnitude of the percentage signal change observed. Regardless of type of anesthesia, greater percentage signal change was observed during noxious thermal stimulation as compared to innocuous thermal stimulation. Results confirmed that functional activity could be observed in the rat spinal cord under halothane anesthesia. As in Chapter 2, c-fos expression was used to verify the presence and identify the rostral-caudal distribution of neuronal activity.; Finally, we have used local field potentials to localize areas of neuronal activity and compare to areas of functional activity identified by fMRI in the rat lumbar spinal cord during electrical stimulation of the hind paw. Generally, fMRI revealed a similar rostral-caudal distribution of active pixels compared to the distribution of negative local field potentials. The correlation within the slices was limited, however, the two measurements were not taken simultaneously therefore a direct site-to-site match between active pixels and negative local field potentials may not be possible. Further work is needed to investigate the causes of disagreement between the two techniques that is observed in some areas. Electrophysiology reveals neuronal activity within the deeper layers of the cord and on the contralateral side. This provides a better assessment of spinal fMRI than the comparison to c-fos labeling alone. This work advances our understanding of what the functional maps obtained by spinal fMRI represent. In turn, a better understanding of spinal fMRI will help further the acceptance of the technique as a useful clinical tool for assessing pathological conditions of the spinal cord.