Tracking sensory system atrophy and outcome prediction in spinal cord injury

Grabher, Patrick; Callaghan, Martina F.; Ashburner, John; Weiskopf, Nikolaus; Thompson, Alan J.; Curt, Armin; Freund, Patrick

doi:10.1002/ana.24508

Cited by 85 publications

(119 citation statements)

References 71 publications

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“…This indicates a correlation between the MT saturation and the transfer term, and, thus, the macromolecular fraction. The sensitivity of the MPM‐based MT saturation metric to myelination has been demonstrated in neuroscientific [Callaghan et al, ; Dick et al, ; Sereno et al, ] and clinical research studies [Freund et al, ; Grabher et al, ].…”

Section: Methodsmentioning

confidence: 99%

Four in vivo g‐ratio‐weighted imaging methods: Comparability and repeatability at the group level

Ellerbrock

Mohammadi

2017

Human Brain Mapping

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A recent method, denoted in vivo g-ratio-weighted imaging, has related the microscopic gratio, only accessible by ex vivo histology, to noninvasive MRI markers for the fiber volume fraction (FVF) and myelin volume fraction (MVF). Different MRI markers have been proposed for g-ratio weighted imaging, leaving open the question which combination of imaging markers is optimal. To address this question, the repeatability and comparability of four g-ratio methods based on different combinations of, respectively, two imaging markers for FVF (tract-fiber density, TFD, and neurite orientation dispersion and density imaging, NODDI) and two imaging markers for MVF (magnetization transfer saturation rate, MT, and, from proton density maps, macromolecular tissue volume, MTV) were tested in a scan-rescan experiment in two groups. Moreover, it was tested how the repeatability and comparability were affected by two key processing steps, namely the masking of unreliable voxels (e.g., due to partial volume effects) at the group level and the calibration value used to link MRI markers to MVF (and FVF). Our data showed that repeatability and comparability depend largely on the marker for the FVF (NODDI outperformed TFD), and that they were improved by masking. Overall, the g-ratio method based on NODDI and MT showed the highest repeatability (90%) and lowest variability between groups (3.5%). Finally, our results indicate that the calibration procedure is crucial, for example, calibration to a lower g-ratio value (g 5 0.6) than the commonly used one (g 5 0.7) can change not only repeatability and comparability but also the reported dependency on the FVF imaging marker. Hum Brain Mapp 39:24-41, 2018.V C 2017 Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 99%

Four in vivo g‐ratio‐weighted imaging methods: Comparability and repeatability at the group level

Ellerbrock

Mohammadi

2017

Human Brain Mapping

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“…In summary, neurodegeneration in CSM, although different in causation, disease onset and progression trajectory, 3 resembles the pathophysiological processes of antero-and retrograde degeneration observed after spinal cord injury. 38,46,47 …”

Section: Journal Of Neurotraumamentioning

confidence: 99%

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Grabher

Mohammadi

Dávid

et al. 2017

Journal of Neurotrauma

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Remote grey matter pathology has been suggested rostral to the compression site in cervical spondylotic myelopathy (CSM). We used computational neuroimaging to assess in-vivo the extent and functional relevance of neurodegeneration in ventral and dorsal horns above the site of compression in the cervical cord of CSM patients. Twenty patients with CSM and eighteen healthy subjects underwent a high-resolution structural and diffusion MRI protocol at vertebra C2/C3. Patients received comprehensive clinical assessments. T2*-weighted data were used to segment the cross-sectional area of the grey matter into the ventral and dorsal horns. Within the ventral and dorsal horns mean diffusivity (MD) and fractional anisotropy (FA) derived from diffusion tensor imaging data determined the underlying microstructural integrity. Finally, the relationships between neurodegeneration occurring in the grey and white matter and clinical impairment were investigated. Patients suffered from mild to moderate CSM with mainly sensory impairment. The cross-sectional area of the ventral horns was not reduced (p=0.863) when compared to controls, but MD was increased (p=0.045). Greater increases in MD within the ventral horn were associated with white matter diffusivity changes (increased MD: p=0.013; decreased FA: p=0.028) within the lateral corticospinal tract. In contrast, dorsal horn cross-sectional area was reduced by 16.0% (p<0.001) without alterations in diffusivity indices when compared to controls. No associations between neurodegeneration and clinical impairment were evident. Grey matter atrophy and microstructural changes are evident remote to the compression site in CSM patients. Prior to marked motor impairment, pathophysiological changes in the ventral horns (e.g. motoneurons) related to white matter changes within the corticospinal tract. Thus, neuroimaging biomarkers of cord grey matter integrity reveal focal neurodegeneration prior to marked clinical impairment and thus could serve as predictors of ensuing impairment in CSM patients. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. AbstractRemote grey matter pathology has been suggested rostral to the compression site in cervical spondylotic myelopathy (CSM). We therefore assessed neurodegeneration in the grey matter ventral and dorsal horns.Twenty patients with CSM and eighteen healthy subjects underwent a high-...

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“…Investigations applying qMRI restricted to a set of regions-of-interest reported progressive volume loss in the internal capsule of SCI patients paralleled by myelin reduction at 12 months post-injury compared to baseline (Freund et al, 2013). Using the same technique in the very same cohort, the authors observed also myelin reduction in thalamus, cerebellum and brainstem in the same period of time (Freund et al, 2013;Grabher et al, 2015). These combined morphometry and tissue property findings in the early injury phase contrast with the absence of volume differences when comparing sub-acute (duration <1 year) and chronic (duration >1 year) patients with complete motor SCI (Chen et al, 2017).…”

Section: Introductionmentioning

confidence: 89%

“…One of the well-established methods -voxel-based morphometry (VBM), was used to monitor local grey matter volume changes following SCI to deliver conflicting results ranging from lack of SCI related brain anatomy changes (Crawley et al, 2004) to evidence about profound sensorimotor cortex reorganization (Jurkiewicz et al, 2006;Wrigley et al, 2009a;Henderson et al, 2011;Freund et al, 2013). More recent reports demonstrate grey matter loss in nonmotor areas including anterior cingulate gyrus, insula, orbitofrontal gyrus, prefrontal cortex and thalamus (Wrigley et al, 2009b;Grabher et al, 2015;Chen et al, 2017). One of the potential reasons for the reported controversial findings is the fact that these studies pooled together patients with incomplete and complete SCI (Crawley et al, 2004;Jurkiewicz et al, 2006;Chen et al, 2017) not taking into account potential impact of differences in the time span since injury (Grabher et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…More recent reports demonstrate grey matter loss in nonmotor areas including anterior cingulate gyrus, insula, orbitofrontal gyrus, prefrontal cortex and thalamus (Wrigley et al, 2009b;Grabher et al, 2015;Chen et al, 2017). One of the potential reasons for the reported controversial findings is the fact that these studies pooled together patients with incomplete and complete SCI (Crawley et al, 2004;Jurkiewicz et al, 2006;Chen et al, 2017) not taking into account potential impact of differences in the time span since injury (Grabher et al, 2015). The non-quantitative character of the used T1-weighted MRI protocols represents another source for differences between studies.…”

Section: Introductionmentioning

confidence: 99%

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Brain tissue properties and morphometry assessment after chronic complete spinal cord injury

Hug

Bernini

Wang

et al. 2019

Preprint

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There is much controversy about the potential impact of spinal cord injury (SCI) on brain's anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ) we performed statistical analyses of grey matter volume and parameter maps indicative for brain's myelin, iron and free tissue water content in complete SCI patients (n=14) and healthy individuals (n=14). Our whole-brain analysis showed significant white matter volume loss in the rostral and dorsal part of the spinal cord consistent with Wallerian degeneration of proprioceptive axons in the lemniscal tract in SCI subjects, which correlated with spinal cord atrophy assessed with quantification of the spinal cord cross-sectional area at cervical level.The latter finding suggests that Wallerian degeneration of the lemniscal tract represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical ultrastructural/histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in the brain representing remote changes in the course of chronic SCI could not be confirmed with conventional VBM or VBQ statistical analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.

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Tracking sensory system atrophy and outcome prediction in spinal cord injury

Cited by 85 publications

References 71 publications

Four in vivo g‐ratio‐weighted imaging methods: Comparability and repeatability at the group level

Four in vivo g‐ratio‐weighted imaging methods: Comparability and repeatability at the group level

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Brain tissue properties and morphometry assessment after chronic complete spinal cord injury

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