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Imaging the cervical spinal cord and nerve roots in patients with spinal muscular atrophy using diffusion tensor imaging

Kuster, L. (2015) Imaging the cervical spinal cord and nerve roots in patients with spinal muscular atrophy using diffusion tensor imaging.

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Abstract:Rationale Spinal muscular atrophy (SMA) is a disorder characterized clinically by axial and proximal muscle weakness and pathologically by degeneration of α-motor neurons, and is caused by the homozygous deletion of the survival motor neuron (SMN) 1 gene. SMN is important for RNA splicing and axonal transport, but the mechanisms that cause SMA are largely unknown. Reduced connectivity of motor neurons may be an important cause for muscle weakness in SMA. We hypothesize that reduced connectivity can be visualized in the spinal cord by using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Robust biomarkers for SMA severity and disease progression are needed because the relatively slow rate of disease progression has complicated the selection of clinical outcome measures for clinical trials. DTI could be helpful as a biomarker to evaluate efficacy of experimental treatment strategies. The aims of this study were to develop an acquisition protocol to visualize the spinal cord and the descending nerves and to gain more insight into the potential value of DTI as a biomarker for disease severity in SMA patients. Methods We developed, optimized and validated an acquisition protocol for use in an observational cross-sectional pilot study. We included 8 patients with SMA types 2 and 3 and 14 healthy controls, who were scanned with the developed protocol. Two anatomical images and two diffusion weighted images were obtained. DTI data was corrected for subject motion and eddy current induced distortions, and diffusion tensors were calculated according to the weighted linear least squares (WLLS) procedure. Fiber tractography was performed and four diffusion parameters were computed of the cervical nerves (C5-C7): fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Cross sectional areas of the spinal cord and of the grey matter, and diameters of the anterior and posterior nerve roots were measured. Results All diffusion parameters for nerves C5-C7 were significantly lower (FA: p<0.05; MD, AD, RD: p<0.005) in SMA patients than in healthy controls. Anatomical differences were found in grey matter to spinal cord area ratio and in anterior to posterior nerve root diameter ratio between an SMA patient and an age- and gender matched healthy control. Conclusion We showed that it is possible to visualize the anatomical and microstructural properties of the cervical spinal cord and the descending nerve roots. To our knowledge we report the first clinical study that used DTI to investigate the anatomical and microstructural properties of the cervical spinal cord and nerves in patients with SMA. DTI can provide additional unique information regarding the pathophysiological mechanisms of SMA in vivo. This study provides a foundation for further exploration of DTI as a biomarker in SMA. Combining anatomical imaging, DTI and tractography, and correlating diffusion parameters with clinical outcome measures may prove a valuable contribution to better monitor the disease progression and therapeutic effect in SMA patients in the future.
Item Type:Essay (Master)
Clients:
University Medical Center Utrecht, Utrecht, The Netherlands
Faculty:TNW: Science and Technology
Subject:44 medicine, 50 technical science in general
Programme:Technical Medicine MSc (60033)
Link to this item:http://purl.utwente.nl/essays/69489
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