Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells.

Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both MBP protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role MBP plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.

Calibration-free parallel transmission of the cervical, thoracic, and lumbar spinal cord at 7T.

PURPOSE: To address the limitations of spinal cord imaging at ultra-high field (UHF) due to time-consuming parallel transmit (pTx) adjustments. This study introduces calibration-free offline computed universal shim modes that can be applied seamlessly for different pTx RF coils and spinal cord target regions, substantially enhancing spinal cord imaging efficiency at UHF. METHODS: A library of channel-wise relative B 1 + $$ {B}_1^{+} $$ maps for the cervical spinal cord (six datasets) and thoracic and lumbar spinal cord (nine datasets) was constructed to optimize transmit homogeneity and efficiency for these regions. A tailored B0 shim was optimized for the cervical spine to enhance spatial magnetic field homogeneity further. The performance of the universal shims was validated using absolute saturation based B 1 + $$ {B}_1^{+} $$ mapping and high-resolution 2D and 3D multi-echo gradient-recalled echo (GRE) data to assess the image quality. RESULTS: The proposed universal shims demonstrated a 50% improvement in B 1 + $$ {B}_1^{+} $$ efficiency compared to the default (zero phase) shim mode. B 1 + $$ {B}_1^{+} $$ homogeneity was also improved by 20%. The optimized universal shims achieved performance comparable to subject-specific pTx adjustments, while eliminating the need for lengthy pTx calibration times, saving about 10 min per experiment. CONCLUSION: The development of universal shims represents a significant advance by eliminating time-consuming subject-specific pTx adjustments. This approach is expected to make UHF spinal cord imaging more accessible and user-friendly, particularly for non-pTx experts.

RF shimming in the cervical spinal cord at 7 T.

PURPOSE: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. METHODS: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. RESULTS: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1 + efficiency, and the vendor-based "patient" and "volume" modes showed the lowest B1 + efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior-inferior axis. CONCLUSION: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.

Repeat it without me: Crowdsourcing the T1 mapping common ground via the ISMRM reproducibility challenge.

PURPOSE: T1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T1 mapping technique, using acquisition details from a seminal T1 mapping paper on a standardized phantom and in human brains. METHODS: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed. RESULTS: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org. CONCLUSION: The T1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T1 variations in vivo.

Spiral volumetric optoacoustic tomography of reduced oxygen saturation in the spinal cord of M83 mouse model of Parkinson's disease.

PURPOSE: Metabolism and bioenergetics in the central nervous system play important roles in the pathophysiology of Parkinson's disease (PD). Here, we employed a multimodal imaging approach to assess oxygenation changes in the spinal cord of the transgenic M83 murine model of PD overexpressing the mutated A53T alpha-synuclein form in comparison with non-transgenic littermates. METHODS: In vivo spiral volumetric optoacoustic tomography (SVOT) was performed to assess oxygen saturation (sO2) in the spinal cords of M83 mice and non-transgenic littermates. Ex vivo high-field T1-weighted (T1w) magnetic resonance imaging (MRI) at 9.4T was used to assess volumetric alterations in the spinal cord. 3D SVOT analysis and deep learning-based automatic segmentation of T1w MRI data for the mouse spinal cord were developed for quantification. Immunostaining for phosphorylated alpha-synuclein (pS129 α-syn), as well as vascular organization (CD31 and GLUT1), was performed after MRI scan. RESULTS: In vivo SVOT imaging revealed a lower sO2SVOT in the spinal cord of M83 mice compared to non-transgenic littermates at sub-100 µm spatial resolution. Ex vivo MRI-assisted by in-house developed deep learning-based automatic segmentation (validated by manual analysis) revealed no volumetric atrophy in the spinal cord of M83 mice compared to non-transgenic littermates at 50 µm spatial resolution. The vascular network was not impaired in the spinal cord of M83 mice in the presence of pS129 α-syn accumulation. CONCLUSION: We developed tools for deep-learning-based analysis for the segmentation of mouse spinal cord structural MRI data, and volumetric analysis of sO2SVOT data. We demonstrated non-invasive high-resolution imaging of reduced sO2SVOT in the absence of volumetric structural changes in the spinal cord of PD M83 mouse model.

Quantifying neurodegeneration of the cervical cord and brain in degenerative cervical myelopathy: A multicentre study using quantitative magnetic resonance imaging.

BACKGROUND AND PURPOSE: Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study. METHODS: We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty-eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada. RESULTS: Remote atrophy was observed in the cervical cord (p = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter (p = 0.014), thalamus (p = 0.001), corpus callosum (p = 0.0001), and cranial corticospinal tract (p = 0.03). R2* was increased in the primary somatosensory cortices (p = 0.008). Sensory impairments were associated with increased iron-sensitive R2* in the thalamus and periaqueductal grey matter in DCM. CONCLUSIONS: Simultaneous assessment of the spinal cord and brain revealed DCM-induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level.

Shimming toolbox: An open-source software toolbox for B0 and B1 shimming in MRI.

PURPOSE: Introduce Shimming Toolbox ( https://shimming-toolbox.org), an open-source software package for prototyping new methods and performing static, dynamic, and real-time B0 shimming as well as B1 shimming experiments. METHODS: Shimming Toolbox features various field mapping techniques, manual and automatic masking for the brain and spinal cord, B0 and B1 shimming capabilities accessible through a user-friendly graphical user interface. Validation of Shimming Toolbox was demonstrated in three scenarios: (i) B0 dynamic shimming in the brain at 7T using custom AC/DC coils, (ii) B0 real-time shimming in the spinal cord at 3T, and (iii) B1 static shimming in the spinal cord at 7T. RESULTS: The B0 dynamic shimming of the brain at 7T took about 10 min to perform. It showed a 47% reduction in the standard deviation of the B0 field, associated with noticeable improvements in geometric distortions in EPI images. Real-time dynamic xyz-shimming in the spinal cord took about 5 min and showed a 30% reduction in the standard deviation of the signal distribution. B1 static shimming experiments in the spinal cord took about 10 min to perform and showed a 40% reduction in the coefficient of variation of the B1 field. CONCLUSION: Shimming Toolbox provides an open-source platform where researchers can collaborate, prototype and conveniently test B0 and B1 shimming experiments. Future versions will include additional field map preprocessing techniques, optimization algorithms, and compatibility across multiple MRI manufacturers.

An 8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla.

The quality of cervical spinal cord images can be improved by the use of tailored radiofrequency (RF) coil solutions for ultrahigh field imaging; however, very few commercial and research 7-T RF coils currently exist for the spinal cord, and in particular, those with parallel transmission (pTx) capabilities. This work presents the design, testing, and validation of a pTx/Rx coil for the human neck and cervical/upper thoracic spinal cord. The pTx portion is composed of eight dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made up of twenty semiadaptable overlapping loops to produce high signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while also being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1 + uniformity, power efficiency, and/or specific absorption rate efficiency. B1 + homogeneity, SNR, and g-factor were evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.

Resting-state brain and spinal cord networks in humans are functionally integrated.

In the absence of any task, both the brain and spinal cord exhibit spontaneous intrinsic activity organised in a set of functionally relevant neural networks. However, whether such resting-state networks (RSNs) are interconnected across the brain and spinal cord is unclear. Here, we used a unique scanning protocol to acquire functional images of both brain and cervical spinal cord (CSC) simultaneously and examined their spatiotemporal correspondence in humans. We show that the brain and spinal cord activities are strongly correlated during rest periods, and specific spinal cord regions are functionally linked to consistently reported brain sensorimotor RSNs. The functional organisation of these networks follows well-established anatomical principles, including the contralateral correspondence between the spinal hemicords and brain hemispheres as well as sensory versus motor segregation of neural pathways along the brain-spinal cord axis. Thus, our findings reveal a unified functional organisation of sensorimotor networks in the entire central nervous system (CNS) at rest.

Brain-spinal cord interaction in long-term motor sequence learning in human: An fMRI study.

The spinal cord is important for sensory guidance and execution of skilled movements. Yet its role in human motor learning is not well understood. Despite evidence revealing an active involvement of spinal circuits in the early phase of motor learning, whether long-term learning engages similar changes in spinal cord activation and functional connectivity remains unknown. Here, we investigated spinal-cerebral functional plasticity associated with learning of a specific sequence of visually-guided joystick movements (sequence task) over six days of training. On the first and last training days, we acquired high-resolution functional images of the brain and cervical cord simultaneously, while participants practiced the sequence or a random task while electromyography was recorded from wrist muscles. After six days of training, the subjects' motor performance improved in the sequence compared to the control condition. These behavioral changes were associated with decreased co-contractions and increased reciprocal activations between antagonist wrist muscles. Importantly, early learning was characterized by activation in the C8 level, whereas a more rostral activation in the C6-C7 was found during the later learning phase. Motor sequence learning was also supported by increased spinal cord functional connectivity with distinct brain networks, including the motor cortex, superior parietal lobule, and the cerebellum at the early stage, and the angular gyrus and cerebellum at a later stage of learning. Our results suggest that the early vs. late shift in spinal activation from caudal to rostral cervical segments synchronized with distinct brain networks, including parietal and cerebellar regions, is related to progressive changes reflecting the increasing fine control of wrist muscles during motor sequence learning.

Vendor-neutral sequences and fully transparent workflows improve inter-vendor reproducibility of quantitative MRI.

PURPOSE: We developed an end-to-end workflow that starts with a vendor-neutral acquisition and tested the hypothesis that vendor-neutral sequences decrease inter-vendor variability of T1, magnetization transfer ratio (MTR), and magnetization transfer saturation-index (MTsat) measurements. METHODS: We developed and deployed a vendor-neutral 3D spoiled gradient-echo (SPGR) sequence on three clinical scanners by two MRI vendors. We then acquired T1 maps on the ISMRM-NIST system phantom, as well as T1, MTR, and MTsat maps in three healthy participants. We performed hierarchical shift function analysis in vivo to characterize the differences between scanners when the vendor-neutral sequence is used instead of commercial vendor implementations. Inter-vendor deviations were compared for statistical significance to test the hypothesis. RESULTS: In the phantom, the vendor-neutral sequence reduced inter-vendor differences from 8% to 19.4% to 0.2% to 5% with an overall accuracy improvement, reducing ground truth T1 deviations from 7% to 11% to 0.2% to 4%. In vivo, we found that the variability between vendors is significantly reduced (p = 0.015) for all maps (T1, MTR, and MTsat) using the vendor-neutral sequence. CONCLUSION: We conclude that vendor-neutral workflows are feasible and compatible with clinical MRI scanners. The significant reduction of inter-vendor variability using vendor-neutral sequences has important implications for qMRI research and for the reliability of multicenter clinical trials.

Rapid simultaneous acquisition of macromolecular tissue volume, susceptibility, and relaxometry maps.

PURPOSE: A major obstacle to the clinical implementation of quantitative MR is the lengthy acquisition time required to derive multi-contrast parametric maps. We sought to reduce the acquisition time for QSM and macromolecular tissue volume by acquiring both contrasts simultaneously by leveraging their redundancies. The joint virtual coil concept with GRAPPA (JVC-GRAPPA) was applied to reduce acquisition time further. METHODS: Three adult volunteers were imaged on a 3 Tesla scanner using a multi-echo 3D GRE sequence acquired at 3 head orientations. Macromolecular tissue volume, QSM, R2∗ , T1 , and proton density maps were reconstructed. The same sequence (GRAPPA R = 4) was performed in subject 1 with a single head orientation for comparison. Fully sampled data was acquired in subject 2, from which retrospective undersampling was performed (R = 6 GRAPPA and R = 9 JVC-GRAPPA). Prospective undersampling was performed in subject 3 (R = 6 GRAPPA and R = 9 JVC-GRAPPA) using gradient blips to shift k-space sampling in later echoes. RESULTS: Subject 1's multi-orientation and single-orientation macromolecular tissue volume maps were not significantly different based on RMSE. For subject 2, the retrospectively undersampled JVC-GRAPPA and GRAPPA generated similar results as fully sampled data. This approach was validated with the prospectively undersampled images in subject 3. Using QSM, R2∗ , and macromolecular tissue volume, the contributions of myelin and iron content to susceptibility were estimated. CONCLUSION: We have developed a novel strategy to simultaneously acquire data for the reconstruction of 5 intrinsically coregistered 1-mm isotropic resolution multi-parametric maps, with a scan time of 6 min using JVC-GRAPPA.

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter.

PURPOSE: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. METHODS: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open-access multicenter data set of the spinal cord MRI (N = 267 participants). RESULTS: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial-volume effects. CONCLUSION: We propose quality assessment criteria and metrics for gray-matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open-source code can serve as a benchmark for future optimization of spinal cord gray-matter imaging protocols.

The Myelin-Weighted Connectome in Parkinson's Disease.

BACKGROUND: Even though Parkinson's disease (PD) is typically viewed as largely affecting gray matter, there is growing evidence that there are also structural changes in the white matter. Traditional connectomics methods that study PD may not be specific to underlying microstructural changes, such as myelin loss. OBJECTIVE: The primary objective of this study is to investigate the PD-induced changes in myelin content in the connections emerging from the basal ganglia and the brainstem. For the weighting of the connectome, we used the longitudinal relaxation rate as a biologically grounded myelin-sensitive metric. METHODS: We computed the myelin-weighted connectome in 35 healthy control subjects and 81 patients with PD. We used partial least squares to highlight the differences between patients with PD and healthy control subjects. Then, a ring analysis was performed on selected brainstem and subcortical regions to evaluate each node's potential role as an epicenter for disease propagation. Then, we used behavioral partial least squares to relate the myelin alterations with clinical scores. RESULTS: Most connections (~80%) emerging from the basal ganglia showed a reduced myelin content. The connections emerging from potential epicentral nodes (substantia nigra, nucleus basalis of Meynert, amygdala, hippocampus, and midbrain) showed significant decrease in the longitudinal relaxation rate (P < 0.05). This effect was not seen for the medulla and the pons. CONCLUSIONS: The myelin-weighted connectome was able to identify alteration of the myelin content in PD in basal ganglia connections. This could provide a different view on the importance of myelination in neurodegeneration and disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cortico-spinal imaging to study pain.

Functional magnetic resonance imaging of the brain has helped to reveal mechanisms of pain perception in health and disease. Recently, imaging approaches have been developed that allow recording neural activity simultaneously in the brain and in the spinal cord. These approaches offer the possibility to examine pain perception in the entire central pain system and in addition, to investigate cortico-spinal interactions during pain processing. Although cortico-spinal imaging is a promising technique, it bears challenges concerning data acquisition and data analysis strategies. In this review, we discuss studies that applied simultaneous imaging of the brain and spinal cord to explore central pain processing. Furthermore, we describe different MR-related acquisition techniques, summarize advantages and disadvantages of approaches that have been implemented so far and present software that has been specifically developed for the analysis of spinal fMRI data to address challenges of spinal data analysis.

Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis.

OBJECTIVE: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1 /T2 relaxometry and proton density mapping in multiple sclerosis. METHODS: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan-rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. RESULTS: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. INTERPRETATION: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination. ANN NEUROL 2020;87:710-724.

Diffusion magnetic resonance imaging reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression.

BACKGROUND AND PURPOSE: Non-myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract-specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM. METHODS: High-resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity. Relationship between the degree of DCM disability, assessed by the modified Japanese Orthopaedic Association scale, and tract-specific microstructural changes in DCM patients was also explored. RESULTS: The study identified diffusion-derived abnormalities in the gray matter, dorsal and lateral tracts congruent with trans-synaptic degeneration and demyelination in chronic degenerative spinal cord compression with more profound alterations in DCM than NMDC. Diffusion metrics were affected in the C3-6 area as well as above the compression level at C3 with more profound rostral deficits in DCM than NMDC. Alterations in lateral motor and dorsal sensory tracts correlated with motor and sensory evoked potentials, respectively, whereas electromyography outcomes corresponded with gray matter microstructure. DCM disability corresponded with microstructure alteration in lateral columns. CONCLUSIONS: Outcomes imply the necessity of high-resolution tract-specific diffusion MRI for monitoring degenerative spinal pathology in longitudinal studies.

7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis.

We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein. Brain imaging at 7 T was used to segment cortical and white matter lesions and 3 T imaging for cortical thickness estimation. Cervical spinal cord lesions were mapped voxel-wise as a function of distance from the inner central canal CSF pool to the outer subpial surface. Similarly, brain white matter lesions were mapped voxel-wise as a function of distance from the ventricular system. Subjects with relapsing-remitting multiple sclerosis showed a greater predominance of spinal cord lesions nearer the outer subpial surface compared to secondary progressive cases. Inversely, secondary progressive participants presented with more centrally located lesions. Within the brain, there was a strong gradient of lesion formation nearest the ventricular system that was most evident in participants with secondary progressive multiple sclerosis. Lesion fractions within the spinal cord grey and white matter were related to the lesion fraction in cerebral white matter. Cortical thinning was the primary determinant of the Expanded Disability Status Scale, white matter lesion fractions in the spinal cord and brain of the 9-Hole Peg Test and cortical thickness and spinal cord grey matter cross-sectional area of the Timed 25-Foot Walk. Spinal cord lesions were localized nearest the subpial surfaces for those with relapsing-remitting and the central canal CSF surface in progressive disease, possibly implying CSF-mediated pathogenic mechanisms in lesion development that may differ between multiple sclerosis subtypes. These findings show that spinal cord lesions involve both grey and white matter from the early multiple sclerosis stages and occur mostly independent from brain pathology. Despite the prevalence of cervical spinal cord lesions and atrophy, brain pathology seems more strongly related to physical disability as measured by the Expanded Disability Status Scale.

Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability.

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

Spatial correspondence of spinal cord white matter tracts using diffusion tensor imaging, fibre tractography, and atlas-based segmentation.

PURPOSE: Neuroimaging provides great utility in complex spinal surgeries, particularly when anatomical geometry is distorted by pathology (tumour, degeneration, etc.). Spinal cord MRI diffusion tractography can be used to generate streamlines; however, it is unclear how well they correspond with white matter tract locations along the cord microstructure. The goal of this work was to evaluate the spatial correspondence of DTI tractography with anatomical MRI in healthy anatomy (where anatomical locations can be well defined in T1-weighted images). METHODS: Ten healthy volunteers were scanned on a 3T system. T1-weighted (1 × 1 × 1 mm) and diffusion-weighted images (EPI readout, 2 × 2 × 2 mm, 30 gradient directions) were acquired and subsequently registered (Spinal Cord Toolbox (SCT)). Atlas-based (SCT) anatomic label maps of the left and right lateral corticospinal tracts were identified for each vertebral region (C2-C6) from T1 images. Tractography streamlines were generated with a customized approach, enabling seeding of specific spinal tract regions corresponding to individual vertebral levels. Spatial correspondence of generated fibre streamlines with anatomic tract segmentations was compared in unseeded regions of interest (ROIs). RESULTS: Spatial correspondence of the lateral corticospinal tract streamlines was good over a single vertebral ROI (Dice's similarity coefficient (DSC) = 0.75 ± 0.08, Hausdorff distance = 1.08 ± 0.17 mm). Over larger ROI, fair agreement between tractography and anatomical labels was achieved (two levels: DSC = 0.67 ± 0.13, three levels: DSC = 0.52 ± 0.19). CONCLUSION: DTI tractography produced good spatial correspondence with anatomic white matter tracts, superior to the agreement between multiple manual tract segmentations (DSC ~ 0.5). This supports further development of spinal cord tractography for computer-assisted neurosurgery.