Abstract
Disease in the spinal cord is a major component of disability in multiple sclerosis, yet current techniques of imaging spinal cord injury are insensitive and nonspecific. This study seeks to remove this major impediment to research in multiple sclerosis and other spinal cord diseases by identifying reliable biomarkers of disability progression using diffusion tensor imaging (DTI), a magnetic resonance imaging technique, to evaluate the spinal cord in a model of multiple sclerosis, i.e. the Theiler’s Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD). Mice with TMEV-IDD with varying levels of clinical disease were imaged using a 9.4T small animal MRI scanner. Axial diffusivity, radial diffusivity, and fractional anisotropy were calculated. Disability was assessed periodically using Rotarod assay and data were expressed as a neurological function index. Correlation was performed between DTI measurements and disability scores. TMEV-IDD mice displayed significant increased neurological deficits over time when compared with controls (p<0.0001). Concurrently, the values of fractional anisotropy and axial diffusivity were both decreased compared to controls (both p<0.0001), while radial diffusivity was increased (p<0.0001). Overall, fractional anisotropy changes were larger in white matter than in grey matter and differences were more pronounced in the ventral region. Lower disability scores were associated with decreased fractional anisotropy values measured in the ventral (r = 0.68; p<0.0001) and ventral-lateral (r = 0.70; p<0.0001) regions of the white matter. These data demonstrate that DTI measures of the spinal cord contribute to strengthening the association between neuroradiological markers and clinical disability, and support the use of DTI measures in spinal cord imaging in MS patients.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) and is the most common cause of non-traumatic disability among young adults [1]
Within the group of 18 mice (12 infected with Theiler’s murine encephalomyelitis virus (TMEV) and 6 sham-infected) followed longitudinally, all 12 infected mice were positive for serum anti-TMEV antibodies on day 24 p.i indicating that a TMEV infection had occurred
Levels of serum anti-TMEV antibody were significantly lower in polymerase chain reaction (PCR) negative compared with PCR positive mice on both day 108 and 190 p.i (Fig 3A and Table 1)
Summary
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) and is the most common cause of non-traumatic disability among young adults [1]. Much of the disability that develops in MS patients is thought to be due to disease of the spinal cord, which is almost always involved in MS [5]. Several studies have pointed out that routine MRI of the spinal cord is insensitive and non-specific in monitoring disease progression, as no significant correlation between T2 lesions and MS disability is detected [6, 7]. This lack of reliability of spinal cord imaging in identifying significant disease is a major problem in the clinical management of MS patients.
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