An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication.

Pathophysiological changes in the white and gray matter resulting from spinal cord injury can be revealed by magnetic resonance imaging (MRI) techniques that provides sensitive markers of macro-and microstructural integrity with important histological correlates. This review highlights spinal cord pathology in traumatic spinal cord injury (tSCI) and in non-traumatic spinal cord injury (i.e. degenerative cervical myelopathy (DCM)), detected by means of cross-sectional area measurements and spinal cord diffusion tensor imaging (DTI), and outlines the current trends and future directions.Cord MRI findings in these pathologies have provided important insights into the pathophysiological processes not just at the focal injury site, but also rostral and caudal to the spinal injury. Interestingly, although tSCI and DCM have different etiologies, they show similar magnitudes of remote tissue specific cord pathology, which suggests similar secondary degenerative mechanisms in tSCI and DCM.Advanced quantitative MRI protocols sensitive to tissue specific cord pathology have the potential to enhance current diagnosis and, more importantly, predict outcome in patients with traumatic and non-traumatic spinal cord injury. It is a promising area of research ripe for further study.

Agenesis of the corpus callosum (AgCC) is a congenital condition associated with wide-ranging emotional and social impairments often overlapping with the diagnostic criteria for autism. Mapping functional connectivity in the acallosal brain can help identify neural correlates of the deficits associated with this condition, and elucidate how congenital white matter alterations shape the topology of large-scale functional networks. By using resting-state BOLD functional magnetic resonance imaging (rsfMRI), here we show that acallosal BTBR T+tpr3tf/J (BTBR) mice, an idiopathic model of autism, exhibit impaired intra-hemispheric connectivity in fronto-cortical, but not in posterior sensory cortical areas. We also document profoundly altered subcortical and intra-hemispheric connectivity networks, with evidence of marked fronto-thalamic and striatal disconnectivity, along with aberrant spatial extension and strength of ipsilateral and local connectivity. Importantly, inter-hemispheric tracing of monosynaptic connections in the primary visual cortex using recombinant rabies virus confirmed the absence of direct homotopic pathways between posterior cortical areas of BTBR mice, suggesting a polysynaptic origin for the synchronous rsfMRI signal observed in these regions. Collectively, the observed long-range connectivity impairments recapitulate hallmark neuroimaging findings in autism, and are consistent with the behavioral phenotype of BTBR mice. In contrast to recent rsfMRI studies in high functioning AgCC individuals, the profound fronto-cortical and subcortical disconnectivity mapped suggest that compensatory mechanism may not necessarily restore the full connectional topology of the brain, resulting in residual connectivity alterations that serve as plausible substrates for the cognitive and emotional deficits often associated with AgCC.

In this prospective study, we made an unbiased voxel-based analysis to investigate above-stenosis spinal degeneration and its relation to impairment in patients with cervical spondylotic myelopathy (CSM). Twenty patients and 18 controls were assessed with high-resolution MRI protocols above the level of stenosis. Cross-sectional areas of grey matter (GM), white matter (WM), and posterior columns (PC) were measured to determine atrophy. Diffusion indices assessed tract-specific integrity of PC and lateral corticospinal tracts (CST). Regression analysis was used to reveal relationships between MRI measures and clinical impairment. Patients showed mainly sensory impairment. Atrophy was prominent within the cervical WM (13.9%, p = 0.004), GM (7.2%, p = 0.043), and PC (16.1%, p = 0.005). Fractional anisotropy (FA) was reduced in the PC (−11.98%, p = 0.006) and lateral CST (−12.96%, p = 0.014). In addition, radial (+28.47%, p = 0.014), axial (+14.72%, p = 0.005), and mean (+16.50%, p = 0.001) diffusivities were increased in the PC. Light-touch score was associated with atrophy (R2 = 0.3559, p = 0.020) and FA (z score 3.74, p = 0.003) in the PC, as was functional independence and FA in the lateral CST (z score 3.68, p = 0.020). This study demonstrates voxel-based degeneration far above the stenosis at a level not directly affected by the compression and provides unbiased readouts of tract-specific changes that relate to impairment.

The adequacy of a histopathological diagnosis of bovine spongiform encephalopathy (BSE) based exclusively on observations of neuroparenchymal vacuolation in three specific neuroanatomic nuclei was tested by using a standard coronal section of medulla oblongata cut at the obex. The agreement between the observations and the definitive histopathological diagnosis was assessed in each of 684 bovine brains - 563 confirmed cases of BSE, 20 with changes which did not diagnose BSE conclusively and 101 in which the lesions of BSE were not detected. When the assessment was confined to the solitary tract nucleus and the spinal tract nucleus of the trigeminal nerve a positive result was obtained in 99.6 per cent of confirmed cases of BSE and only 1 per cent of brains in which lesions of BSE were not detected gave a false positive result. Thus an initial examination of the single section, together with an examination of representative areas of the rest of the brain when no unequivocal lesion was found, provided a satisfactory method for the routine diagnosis of BSE.

ObjectiveTo investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury.MethodsA 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome.ResultsNeurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence.ConclusionOur results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo transsynaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.

This study aimed to compare macrostructural and microstructural neurodegenerative changes remote from a cervical spinal cord injury in traumatic spinal cord injury (tSCI) and degenerative cervical myelopathy (DCM) patients using quantitative magnetic resonance imaging (MRI). Twenty-nine tSCI patients, 20 mild/moderate DCM patients, and 22 healthy controls underwent a high-resolution MRI protocol at the cervical cord (C2/C3). High-resolution T2*-weighted and diffusion-weighted scans provided data to calculate tissue-specific cross-sectional areas of the spinal cord and tractspecific diffusion indices of cord white matter, respectively. Regression analysis determined associations between neurodegeneration and clinical impairment. tSCI patients showed more impairment in upper limb strength and manual dexterity when compared with DCM patients. While macrostructural MRI measures revealed a similar extent of remote cord atrophy at cervical level, microstructural measures (diffusion indices) were able to distinguish more pronounced tract-specific neurodegeneration in tSCI patients when compared with DCM patients. Tract-specific neurodegeneration was associated with upper limb impairment. Despite clinical differences between severely impaired tSCI compared with mildly affected DCM patient, extensive cord atrophy is present remotely from the focal spinal cord injury. Diffusion indices revealed greater tract-specific alterations in tSCI patients. Therefore, diffusion indices are more sensitive than macrostructural MRI measures as these are able to distinguish between traumatic and non-traumatic spinal cord injury. Neuroimaging biomarkers of cervical cord integrity hold potential as predictors of recovery and might be suitable biomarkers for interventional trials both in traumatic and non-traumatic SCI.

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.