Tract-Specific Diffusion MRI in Degenerative Cervical Spinal Cord Compression

Ing. Jan VALOŠEK

Doctoral thesis

Abstract:

The aim of this PhD thesis is to advance the diffusion magnetic resonance imaging (MRI) in different stages of degenerative spinal cord compression. We strive to optimize both the acquisition protocol as well as the processing analysis pipeline to provide markers sensitive to microstructural damage in patients with non-myelopathic degenerative cervical spinal cord compression (NMDC), a condition that precedes the degenerative cervical myelopathy (DCM), which is the most common cause of non-traumatic spinal cord dysfunction. First, the thesis describes basic principles of MRI as well as diffusion MRI, introduces spinal cord anatomy and degenerative spinal cord compression, defines the current challenges of spinal cord MRI and details their potential solutions. Next, clinical and electrophysiological assessments of spinal cord compression are discussed and predictors of progression from non myelopathic compression to symptomatic degenerative cervical myelopathy are reviewed. After this introduction, aims of the thesis are stated, including the studies addressing them. Second, materials and methods together with results of two original research articles are described in detail. In the first article, optimized multi-shell diffusion protocol based on reduced field-of-view technique was proposed and its reproducibility and clinical useability in both healthy controls as well as NMDC patients was examined. In the second manuscript, we employed tract-specific analysis of microstructural metrics derived from conventional DTI and multi-compartment ball-and-sticks diffusion models on a large cohort of NMDC and DCM patients relative to healthy controls. We detected changes in diffusion markers in the dorsal and lateral tracts as well as the gray matter at the level of compression and rostrally pointing to demyelination, trans synaptic degeneration and Wallerian degeneration. The depicted changes were more severe in symptomatic DCM patients than in NMDC patients and were mirrored by abnormalities in clinical scale and electrophysiological measures. Importantly, we demonstrated, for the first time, the utility of multi-compartment ball-and-sticks model in spinal cord imaging. Lastly, the discussion elaborates on contribution of the above-mentioned findings as well as the findings published within several other related manuscripts to the current scientific knowledge, discuss the limitations and outline future directions of our research. In conclusion, this PhD thesis demonstrated that high resolution tract specific dMRI is a sensitive microstructural marker of SC alterations and offers new opportunities for longitudinal trials aiming to provide early predictors of progression from NMDC to symptomatic DCM.

Abstract:

The aim of this PhD thesis is to advance the diffusion magnetic resonance imaging (MRI) in different stages of degenerative spinal cord compression. We strive to optimize both the acquisition protocol as well as the processing analysis pipeline to provide markers sensitive to microstructural damage in patients with non-myelopathic degenerative cervical spinal cord compression (NMDC), a condition that precedes the degenerative cervical myelopathy (DCM), which is the most common cause of non-traumatic spinal cord dysfunction. First, the thesis describes basic principles of MRI as well as diffusion MRI, introduces spinal cord anatomy and degenerative spinal cord compression, defines the current challenges of spinal cord MRI and details their potential solutions. Next, clinical and electrophysiological assessments of spinal cord compression are discussed and predictors of progression from non myelopathic compression to symptomatic degenerative cervical myelopathy are reviewed. After this introduction, aims of the thesis are stated, including the studies addressing them. Second, materials and methods together with results of two original research articles are described in detail. In the first article, optimized multi-shell diffusion protocol based on reduced field-of-view technique was proposed and its reproducibility and clinical useability in both healthy controls as well as NMDC patients was examined. In the second manuscript, we employed tract-specific analysis of microstructural metrics derived from conventional DTI and multi-compartment ball-and-sticks diffusion models on a large cohort of NMDC and DCM patients relative to healthy controls. We detected changes in diffusion markers in the dorsal and lateral tracts as well as the gray matter at the level of compression and rostrally pointing to demyelination, trans synaptic degeneration and Wallerian degeneration. The depicted changes were more severe in symptomatic DCM patients than in NMDC patients and were mirrored by abnormalities in clinical scale and electrophysiological measures. Importantly, we demonstrated, for the first time, the utility of multi-compartment ball-and-sticks model in spinal cord imaging. Lastly, the discussion elaborates on contribution of the above-mentioned findings as well as the findings published within several other related manuscripts to the current scientific knowledge, discuss the limitations and outline future directions of our research. In conclusion, this PhD thesis demonstrated that high resolution tract specific dMRI is a sensitive microstructural marker of SC alterations and offers new opportunities for longitudinal trials aiming to provide early predictors of progression from NMDC to symptomatic DCM.

Keywords

diffusion magnetic resonance imaging, spinal cord compression, degenerative cervical myelopathy

Language used: English

Date on which the thesis was submitted / produced: 20. 4. 2022

Thesis defence

• Supervisor: prof. Ing. MUDr. Petr Hluštík, Ph.D.

Palacký University Olomouc

Faculty of Medicine and Dentistry

Doctoral programme / field:
Neurosciences / Neurosciences