Magnetic resonance imaging of the cervical spinal cord in spinal muscular atrophy

Abstract

ObjectiveIn this study we investigated the potential value of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in characterizing changes in the cervical spinal cord and peripheral nerve roots in vivo in patients with spinal muscular atrophy (SMA).MethodsWe developed an MRI protocol with 4 sequences to investigate the cervical spinal cord and nerve roots on a 3 Tesla MRI system. We used 2 anatomical MRI sequences to investigate cross-sectional area (CSA) at each spinal segment and the diameter of ventral and dorsal nerve roots, and two diffusion tensor imaging (DTI) techniques to estimate the fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD) in 10 SMA patients and 20 healthy controls.ResultsThere were no significant differences in CSA (p > .1), although an 8.5% reduction of CSA in patients compared to healthy controls was apparent at segment C7. DTI data showed a higher AD in grey matter of patients compared to healthy controls (p = .033). Significantly lower MD, AD and RD values were found in rostral nerve roots (C3-C5) in patients (p < .045).ConclusionsWe showed feasibility of an advanced 3 T MRI protocol that allowed differences to be determined between patients and healthy controls, confirming the potential of this technique to assess pathological mechanisms in SMA. After further development and confirmation of findings in a larger sample, these techniques may be used to study disease course of SMA in vivo and evaluate response to survival motor neuron (SMN) augmenting therapy.

Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

“…Our measurements of the CSA of SC, GM, and VH are in line with the known degeneration of αMN caused by SMA. In agreement with previous studies ( 28 , 29 ), we did not detect pathological alterations of diffusion parameters in the WM of SMA patients. Conversely, we documented an increase of GM FA and a slight reduction of RD, while AD and MD were unchanged.…”

“…We found a clear difference in total CSA of the SC between SMA patients and HCs at TP3, in substantial agreement with previous studies ( 27 – 29 ). SMA patients showed a smaller CSA than HCs, with the largest discrepancy being observed in correspondence of the cervical vertebrae.…”

“…Advanced techniques such as magnetization transfer (MT) and diffusion tensor imaging (DTI) of the SC can be used for in vivo quantification of possible pathology-related microstructural changes occurring within the SC (26). qMRI of the cervical SC has been recently applied in three recent cross-sectional studies focusing on pediatric and adult SMA patients not under therapy (27)(28)(29). El Mendili et al (27) reported a significant cord atrophy gradient with a more evident reduction of SC CSA between C3 and C6 levels of adult SMA patients compared to HCs; Querin et al (28) investigated both WM and GM, showing a significant reduction of the CSA of both total SC and GM (but not of WM) at each cervical level (from C2 to C7) in adult untreated SMA patients (SMA 3a, 3b, and 4); finally, in the third study, both pediatric and adult SMA patients (type 2 and 3) showed lower SC CSA values than HCs, though the difference was not statistically significant (29).…”

“…qMRI of the cervical SC has been recently applied in three recent cross-sectional studies focusing on pediatric and adult SMA patients not under therapy (27)(28)(29). El Mendili et al (27) reported a significant cord atrophy gradient with a more evident reduction of SC CSA between C3 and C6 levels of adult SMA patients compared to HCs; Querin et al (28) investigated both WM and GM, showing a significant reduction of the CSA of both total SC and GM (but not of WM) at each cervical level (from C2 to C7) in adult untreated SMA patients (SMA 3a, 3b, and 4); finally, in the third study, both pediatric and adult SMA patients (type 2 and 3) showed lower SC CSA values than HCs, though the difference was not statistically significant (29). Two of the studies mentioned above also explored the diffusion properties of SC in SMA: Stam et al (29) reported significantly higher axial diffusivity (AD) in the GM of SMA patients than HCs, while Querin et al (28) found preserved diffusion properties of SC WM.…”

“…El Mendili et al ( 27 ) reported a significant cord atrophy gradient with a more evident reduction of SC CSA between C3 and C6 levels of adult SMA patients compared to HCs; Querin et al ( 28 ) investigated both WM and GM, showing a significant reduction of the CSA of both total SC and GM (but not of WM) at each cervical level (from C2 to C7) in adult untreated SMA patients (SMA 3a, 3b, and 4); finally, in the third study, both pediatric and adult SMA patients (type 2 and 3) showed lower SC CSA values than HCs, though the difference was not statistically significant ( 29 ). Two of the studies mentioned above also explored the diffusion properties of SC in SMA: Stam et al ( 29 ) reported significantly higher axial diffusivity (AD) in the GM of SMA patients than HCs, while Querin et al ( 28 ) found preserved diffusion properties of SC WM. However, to date and to the best of our knowledge, there are no imaging studies that longitudinally describe the natural evolution of SC features in SMA patients or the effects of treatment on SC properties measured by qMRI over time.…”