Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

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.

SCIseg: Automatic Segmentation of T2-weighted Intramedullary Lesions in Spinal Cord Injury.

Purpose: To develop a deep learning tool for the automatic segmentation of T2-weighted intramedullary lesions in spinal cord injury (SCI). Material and Methods: This retrospective study included a cohort of SCI patients from three sites enrolled between July 2002 and February 2023. A deep learning model, SCIseg, was trained in a three-phase process involving active learning for the automatic segmentation of intramedullary SCI lesions and the spinal cord. The data consisted of T2-weighted MRI acquired using different scanner manufacturers with heterogeneous image resolutions (isotropic/anisotropic), orientations (axial/sagittal), lesion etiologies (traumatic/ischemic/hemorrhagic) and lesions spread across the cervical, thoracic and lumbar spine. The segmentations from the proposed model were visually and quantitatively compared with other open-source baselines. Wilcoxon signed-rank test was used to compare quantitative MRI biomarkers (lesion volume, lesion length, and maximal axial damage ratio) computed from manual lesion masks and those obtained automatically with SCIseg predictions. Results: MRI data from 191 SCI patients (mean age, 48.1 years ± 17.9 [SD]; 142 males) were used for model training and evaluation. SCIseg achieved the best segmentation performance for both the cord and lesions. There was no statistically significant difference between lesion length and maximal axial damage ratio computed from manually annotated lesions and those obtained using SCIseg. Conclusion: Automatic segmentation of intramedullary lesions commonly seen in SCI replaces the tedious manual annotation process and enables the extraction of relevant lesion morphometrics in large cohorts. The proposed model segments lesions across different etiologies, scanner manufacturers, and heterogeneous image resolutions. SCIseg is open-source and accessible through the Spinal Cord Toolbox.

Improved inter-subject alignment of the lumbosacral cord for group-level in vivo gray and white matter assessments: A scan-rescan MRI study at 3T.

INTRODUCTION: Magnetic resonance imaging (MRI) enables the investigation of pathological changes in gray and white matter at the lumbosacral enlargement (LSE) and conus medullaris (CM). However, conducting group-level analyses of MRI metrics in the lumbosacral spinal cord is challenging due to variability in CM length, lack of established image-based landmarks, and unknown scan-rescan reliability. This study aimed to improve inter-subject alignment of the lumbosacral cord to facilitate group-level analyses of MRI metrics. Additionally, we evaluated the scan-rescan reliability of MRI-based cross-sectional area (CSA) measurements and diffusion tensor imaging (DTI) metrics. METHODS: Fifteen participants (10 healthy volunteers and 5 patients with spinal cord injury) underwent axial T2*-weighted and diffusion MRI at 3T. We assessed the reliability of spinal cord and gray matter-based landmarks for inter-subject alignment of the lumbosacral cord, the inter-subject variability of MRI metrics before and after adjusting for the CM length, the intra- and inter-rater reliability of CSA measurements, and the scan-rescan reliability of CSA measurements and DTI metrics. RESULTS: The slice with the largest gray matter CSA as an LSE landmark exhibited the highest reliability, both within and across raters. Adjusting for the CM length greatly reduced the inter-subject variability of MRI metrics. The intra-rater, inter-rater, and scan-rescan reliability of MRI metrics were the highest at and around the LSE (scan-rescan coefficient of variation <3% for CSA measurements and <7% for DTI metrics within the white matter) and decreased considerably caudal to it. CONCLUSIONS: To facilitate group-level analyses, we recommend using the slice with the largest gray matter CSA as a reliable LSE landmark, along with an adjustment for the CM length. We also stress the significance of the anatomical location within the lumbosacral cord in relation to the reliability of MRI metrics. The scan-rescan reliability values serve as valuable guides for power and sample size calculations in future longitudinal studies.

Longitudinal motor system changes from acute to chronic spinal cord injury.

BACKGROUND AND PURPOSE: In acute spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals tissue bridges and neurodegeneration for 2 years. This 5-year study aims to track initial lesion changes, subsequent neurodegeneration, and their impact on recovery. METHODS: This prospective longitudinal study enrolled acute SCI patients and healthy controls who were assessed clinically-and by MRI-regularly from 3 days postinjury up to 60 months. We employed histologically cross-validated quantitative MRI sequences sensitive to volume, myelin, and iron changes, thereby reflecting indirectly processes of neurodegeneration and neuroinflammation. General linear models tracked lesion and remote changes in volume, myelin- and iron-sensitive magnetic resonance indices over 5 years. Associations between lesion, degeneration, and recovery (using the Spinal Cord Independence Measure [SCIM] questionnaire and the International Standards for Neurological Classification of Spinal Cord Injury total motor score) were assessed. RESULTS: Patients' motor scores improved by an average of 12.86 (95% confidence interval [CI] = 6.70-19.00) points, and SCIM by 26.08 (95% CI = 17.00-35.20) points. Within 3-28 days post-SCI, lesion size decreased by more than two-thirds (3 days: 302.52 ± 185.80 mm2 , 28 days: 76.77 ± 88.62 mm2 ), revealing tissue bridges. Cervical cord and corticospinal tract volumes transiently increased in SCI patients by 5% and 3%, respectively, accompanied by cervical myelin decreases and iron increases. Over time, progressive atrophy was observed in both regions, which was linked to early lesion dynamics. Tissue bridges, reduced swelling, and myelin content decreases were predictive of long-term motor score recovery and improved SCIM score. CONCLUSIONS: Studying acute changes and their impact on longer follow-up provides insights into SCI trajectory, highlighting the importance of acute intervention while indicating the potential to influence outcomes in the later stages.

Investigation of perfusion impairment in degenerative cervical myelopathy beyond the site of cord compression.

The aim of this study was to determine tissue-specific blood perfusion impairment of the cervical cord above the compression site in patients with degenerative cervical myelopathy (DCM) using intravoxel incoherent motion (IVIM) imaging. A quantitative MRI protocol, including structural and IVIM imaging, was conducted in healthy controls and patients. In patients, T2-weighted scans were acquired to quantify intramedullary signal changes, the maximal canal compromise, and the maximal cord compression. T2*-weighted MRI and IVIM were applied in all participants in the cervical cord (covering C1-C3 levels) to determine white matter (WM) and grey matter (GM) cross-sectional areas (as a marker of atrophy), and tissue-specific perfusion indices, respectively. IVIM imaging resulted in microvascular volume fraction ([Formula: see text]), blood velocity ([Formula: see text]), and blood flow ([Formula: see text]) indices. DCM patients additionally underwent a standard neurological clinical assessment. Regression analysis assessed associations between perfusion parameters, clinical outcome measures, and remote spinal cord atrophy. Twenty-nine DCM patients and 30 healthy controls were enrolled in the study. At the level of stenosis, 11 patients showed focal radiological evidence of cervical myelopathy. Above the stenosis level, cord atrophy was observed in the WM (- 9.3%; p = 0.005) and GM (- 6.3%; p = 0.008) in patients compared to healthy controls. Blood velocity (BV) and blood flow (BF) indices were decreased in the ventral horns of the GM (BV: - 20.1%, p = 0.0009; BF: - 28.2%, p = 0.0008), in the ventral funiculi (BV: - 18.2%, p = 0.01; BF: - 21.5%, p = 0.04) and lateral funiculi (BV: - 8.5%, p = 0.03; BF: - 16.5%, p = 0.03) of the WM, across C1-C3 levels. A decrease in microvascular volume fraction was associated with GM atrophy (R = 0.46, p = 0.02). This study demonstrates tissue-specific cervical perfusion impairment rostral to the compression site in DCM patients. IVIM indices are sensitive to remote perfusion changes in the cervical cord in DCM and may serve as neuroimaging biomarkers of hemodynamic impairment in future studies. The association between perfusion impairment and cervical cord atrophy indicates that changes in hemodynamics caused by compression may contribute to the neurodegenerative processes in DCM.

Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy.

Introduction: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known. Methods: We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle. Results: Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13-0.32) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] and anterior-posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15-0.45) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] remained on low magnitudes comparable to HCs. Conclusion: Increased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function.

Abnormal Resting-State Network Presence in Females with Overactive Bladder.

Overactive bladder (OAB) is a global problem reducing the quality of life of patients and increasing the costs of any healthcare system. The etiology of OAB is understudied but likely involves supraspinal network alterations. Here, we characterized supraspinal resting-state functional connectivity in 12 OAB patients and 12 healthy controls (HC) who were younger than 60 years. Independent component analysis showed that OAB patients had a weaker presence of the salience (Cohen's d = 0.9) and default mode network (Cohen's d = 1.1) and weaker directed connectivity between the fronto-parietal network and salience network with a longer lag time compared to HC. A region of interest analysis demonstrated weaker connectivity in OAB compared to HC (Cohen's d > 1.6 or < -1.6), particularly within the frontal and prefrontal cortices. In addition, weaker seed (insula, ventrolateral prefrontal cortex) to voxel (anterior cingulate cortex, frontal gyrus, superior parietal lobe, cerebellum) connectivity was found in OAB compared to HC (Cohen's d > 1.9). The degree of deviation in supraspinal connectivity in OAB patients (relative to HC) appears to be an indicator of the severity of the lower urinary tract symptoms and an indication that such symptoms are directly related to functional supraspinal alterations. Thus, future OAB therapy options should also consider supraspinal targets, while neuroimaging techniques should be given more consideration in the quest for better phenotyping of OAB.

Magnetic resonance spectroscopy investigation in the right human hippocampus following spinal cord injury.

Objective: Preclinical studies have shown that cognitive impairments following spinal cord injury (SCI), such as impaired spatial memory, are linked to inflammation, neurodegeneration, and reduced neurogenesis in the right hippocampus. This cross-sectional study aims to characterize metabolic and macrostructural changes in the right hippocampus and their association to cognitive function in traumatic SCI patients. Methods: Within this cross-sectional study, cognitive function was assessed in 28 chronic traumatic SCI patients and 18 age-, sex-, and education-matched healthy controls by a visuospatial and verbal memory test. A magnetic resonance spectroscopy (MRS) and structural MRI protocol was performed in the right hippocampus of both groups to quantify metabolic concentrations and hippocampal volume, respectively. Group comparisons investigated changes between SCI patients and healthy controls and correlation analyses investigated their relationship to memory performance. Results: Memory performance was similar in SCI patients and healthy controls. The quality of the recorded MR spectra was excellent in comparison to the best-practice reports for the hippocampus. Metabolite concentrations and volume of the hippocampus measured based on MRS and MRI were not different between two groups. Memory performance in SCI patients and healthy controls was not correlated with metabolic or structural measures. Conclusion: This study suggests that the hippocampus may not be pathologically affected at a functional, metabolic, and macrostructural level in chronic SCI. This points toward the absence of significant and clinically relevant trauma-induced neurodegeneration in the hippocampus.

Coherent, time-shifted patterns of microstructural plasticity during motor-skill learning.

Motor skill learning relies on neural plasticity in the motor and limbic systems. However, the spatial and temporal characteristics of these changes-and their microstructural underpinnings-remain unclear. Eighteen healthy males received 1 h of training in a computer-based motion game, 4 times a week, for 4 consecutive weeks, while 14 untrained participants underwent scanning only. Performance improvements were observed in all trained participants. Serial myelin- and iron-sensitive multiparametric mapping at 3T during this period of intensive motor skill acquisition revealed temporally and spatially distributed, performance-related microstructural changes in the grey and white matter across a corticospinal-cerebellar-hippocampal circuit. Analysis of the trajectory of these transient changes suggested time-shifted cascades of plasticity from the dominant sensorimotor system to the contralateral hippocampus. In the cranial corticospinal tracts, changes in myelin-sensitive metrics during training in the posterior limb of the internal capsule were of greater magnitude in those who trained their upper limbs vs. lower limb trainees. Motor skill learning is associated with waves of grey and white matter plasticity, across a broad sensorimotor network.

Reliability of spinal cord measures based on synthetic T1-weighted MRI derived from multiparametric mapping (MPM).

Short MRI acquisition time, high signal-to-noise ratio, and high reliability are crucial for image quality when scanning healthy volunteers and patients. Cross-sectional cervical cord area (CSA) has been suggested as a marker of neurodegeneration and potential outcome measure in clinical trials and is conventionally measured on T1-weigthed 3D Magnetization Prepared Rapid Acquisition Gradient-Echo (MPRAGE) images. This study aims to reduce the acquisition time for the comprehensive assessment of the spinal cord, which is typically based on MPRAGE for morphometry and multi-parameter mapping (MPM) for microstructure. The MPRAGE is replaced by a synthetic T1-w MRI (synT1-w) estimated from the MPM, in order to measure CSA. SynT1-w images were reconstructed using the MPRAGE signal equation based on quantitative maps of proton density (PD), longitudinal (R1) and effective transverse (R2*) relaxation rates. The reliability of CSA measurements from synT1-w images was determined within a multi-center test-retest study format and validated against acquired MPRAGE scans by assessing the agreement between both methods. The response to pathological changes was tested by longitudinally measuring spinal cord atrophy following spinal cord injury (SCI) for synT1-w and MPRAGE using linear mixed effect models. CSA measurements based on the synT1-w MRI showed high intra-site (Coefficient of variation [CoV]: 1.43% to 2.71%) and inter-site repeatability (CoV: 2.90% to 5.76%), and only a minor deviation of -1.65 mm2 compared to MPRAGE. Crucially, by assessing atrophy rates and by comparing SCI patients with healthy controls longitudinally, differences between synT1-w and MPRAGE were negligible. These results demonstrate that reliable estimates of CSA can be obtained from synT1-w images, thereby reducing scan time significantly.

Dynamics of progressive degeneration of major spinal pathways following spinal cord injury: A longitudinal study.

BACKGROUND: Following spinal cord injury (SCI), disease processes spread gradually along the spinal cord forming a spatial gradient with most pronounced changes located at the lesion site. However, the dynamics of this gradient in SCI patients is not established. OBJECTIVE: This study tracks the spatiotemporal dynamics of remote anterograde and retrograde spinal tract degeneration in the upper cervical cord following SCI over two years utilizing quantitative MRI. METHODS: Twenty-three acute SCI patients (11 paraplegics, 12 tetraplegics) and 21 healthy controls were scanned with a T1-weighted sequence for volumetry and a FLASH sequence for myelin-sensitive magnetization transfer saturation (MTsat) of the upper cervical cord. We estimated myelin content from MTsat maps within the corticospinal tracts (CST) and dorsal columns (DC) and measured spinal cord atrophy by means of left-right width (LRW) and anterior-posterior width (APW) on the T1-weighted images across cervical levels C1-C3. MTsat in the CST and LRW were considered proxies for retrograde degeneration, while MTsat in the DC and APW provided evidence for anterograde degeneration, respectively. Using regression models, we compared the temporal and spatial trajectories of these MRI readouts between tetraplegics, paraplegics, and controls over a 2-year period and assessed their associations with clinical improvement. RESULTS: Linear rates and absolute differences in myelin-sensitive MTsat indicated retrograde and anterograde neurodegeneration in the CST and DC, respectively. Changes in MTsat within the CST and in LRW progressively developed over time forming a gradient towards lower cervical levels by 2 years after injury, especially in tetraplegics (change per cervical level in MTsat: -0.247 p.u./level, p = 0.034; in LRW: -0.323 mm/level, p = 0.024). MTsat within the DC was already decreased at cervical levels C1-C3 at baseline (1.5 months after injury) in both tetra- and paraplegics, while linear decreases in APW over time were similar across C1-C3, preserving the spatial gradient. The relative improvement in light touch score was associated with MTsat within the DC at baseline (rs = 0.575, p = 0.014). CONCLUSION: Rostral and remote to the injury, the CST and DC show ongoing structural changes, indicative of myelin reductions and atrophy within 2 years after SCI. While anterograde degeneration in the DC was already detectable uniformly at C1-C3 early following SCI, retrograde degeneration in the CST developed over time revealing specific spatial and temporal neurodegenerative gradients. Disentangling and quantifying such dynamic pathological processes may provide biomarkers for regenerative and remyelinating therapies along entire spinal pathways.

Hand and face somatotopy shown using MRI-safe vibrotactile stimulation with a novel soft pneumatic actuator (SPA)-skin interface.

The exact somatotopy of the human facial representation in the primary somatosensory cortex (S1) remains debated. One reason that progress has been hampered is due to the methodological challenge of how to apply automated vibrotactile stimuli to face areas in a manner that is: (1) reliable despite differences in the curvatures of face locations; and (2) MR-compatible and free of MR-interference artefacts when applied in the MR head-coil. Here we overcome this challenge by using soft pneumatic actuator (SPA) technology. SPAs are made of a soft silicon material and can be in- or deflated by means of airflow, have a small diameter, and are flexible in structure, enabling good skin contact even on curved body surfaces (as on the face). To validate our approach, we first mapped the well-characterised S1 finger layout using this novel device and confirmed that tactile stimulation of the fingers elicited characteristic somatotopic finger activations in S1. We then used the device to automatically and systematically deliver somatosensory stimulation to different face locations. We found that the forehead representation was least distant from the representation of the hand. Within the face representation, we found that the lip representation is most distant from the forehead representation, with the chin represented in between. Together, our results demonstrate that this novel MR compatible device produces robust and clear somatotopic representational patterns using vibrotactile stimulation through SPA-technology.

Reliability of multi-parameter mapping (MPM) in the cervical cord: A multi-center multi-vendor quantitative MRI study.

MRI based multicenter studies which target neurological pathologies affecting the spinal cord and brain - including spinal cord injury (SCI) - require standardized acquisition protocols and image processing methods. We have optimized and applied a multi-parameter mapping (MPM) protocol that simultaneously covers the brain and the cervical cord within a traveling heads study across six clinical centers (Leutritz et al., 2020). The MPM protocol includes quantitative maps (magnetization transfer saturation (MT), proton density (PD), longitudinal (R1), and effective transverse (R2*) relaxation rates) sensitive to myelination, water content, iron concentration, and morphometric measures, such as cross-sectional cord area. Previously, we assessed the repeatability and reproducibility of the brain MPM data acquired in the five healthy participants who underwent two scan-rescans (Leutritz et al., 2020). This study focuses on the cervical cord MPM data derived from the same acquisitions to determine its repeatability and reproducibility in the cervical cord. MPM matrices of the cervical cord were generated and processed using the hMRI and the spinal cord toolbox. To determine reliability of the cervical MPM data, the intra-site (i.e., scan-rescan) coefficient of variation (CoV), inter-site CoV, and bias within region of interests (C1, C2 and C3 levels) were determined. The range of the mean intra- and inter-site CoV of MT, R1 and PD was between 2.5% and 12%, and between 1.1% and 4.0% for the morphometric measures. In conclusion, the cervical MPM data showed a high repeatability and reproducibility for key imaging biomarkers and hence can be employed as a standardized tool in multi-center studies, including clinical trials.

Optimized multi-echo gradient-echo magnetic resonance imaging for gray and white matter segmentation in the lumbosacral cord at 3 T.

Atrophy in the spinal cord (SC), gray (GM) and white matter (WM) is typically measured in-vivo by image segmentation on multi-echo gradient-echo magnetic resonance images. The aim of this study was to establish an acquisition and analysis protocol for optimal SC and GM segmentation in the lumbosacral cord at 3 T. Ten healthy volunteers underwent imaging of the lumbosacral cord using a 3D spoiled multi-echo gradient-echo sequence (Siemens FLASH, with 5 echoes and 8 repetitions) on a Siemens Prisma 3 T scanner. Optimal numbers of successive echoes and signal averages were investigated comparing signal-to-noise (SNR) and contrast-to-noise ratio (CNR) values as well as qualitative ratings for segmentability by experts. The combination of 5 successive echoes yielded the highest CNR between WM and cerebrospinal fluid and the highest rating for SC segmentability. The combination of 3 and 4 successive echoes yielded the highest CNR between GM and WM and the highest rating for GM segmentability in the lumbosacral enlargement and conus medullaris, respectively. For segmenting the SC and GM in the same image, we suggest combining 3 successive echoes. For SC or GM segmentation only, we recommend combining 5 or 3 successive echoes, respectively. Six signal averages yielded good contrast for reliable SC and GM segmentation in all subjects. Clinical applications could benefit from these recommendations as they allow for accurate SC and GM segmentation in the lumbosacral cord.

Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy.

BACKGROUND AND PURPOSE: The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. METHODS: Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS: The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. CONCLUSIONS: This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression).

Structural MRI Reveals Cervical Spinal Cord Atrophy in the P301L Mouse Model of Tauopathy: Gender and Transgene-Dosing Effects.

In primary tauopathies, the deposition of tau neurofibrillary tangles and threads as well as neurodegenerative changes have been found within the brain and spinal cord. While degenerative changes have been intensively studied in the brain using structural magnetic resonance imaging (MRI), MRI studies investigating the spinal cord are still scarce. In the present study, we acquired ex vivo high resolution structural MRI of the cervical spinal cord of 8.5-9 month old hemizygous and homozygous P301L mice and non-transgenic littermates of both genders. We assessed the total cross-sectional area, and the gray and white matter anterior-posterior width and left-right width that are established imaging marker of spinal cord degeneration. We observed significant tissue-specific reductions in these parameters in female P301L mice that were stronger in homozygous than in hemizygous P301L mice, indicating both an effect of gender and transgene expression on cervical spinal cord atrophy. Moreover, atrophy was stronger in the gray matter than in the white matter. Immunohistochemical analysis revealed neurodegenerative and neuroinflammatory changes in the cervical spinal cord in both the gray and white matter of P301L mice. Collectively, our results provide evidence for cervical spinal cord atrophy that may directly contribute to the motor signs associated with tauopathy.

Simultaneous assessment of regional distributions of atrophy across the neuraxis in MS patients.

BACKGROUND: The ability to assess brain and cord atrophy simultaneously would improve the efficiency of MRI to track disease evolution. OBJECTIVE: To test a promising tool to simultaneously map the regional distribution of atrophy in multiple sclerosis (MS) patients across the brain and cord. METHODS: Voxel-based morphometry combined with a statistical parametric mapping probabilistic brain-spinal cord (SPM-BSC) template was applied to standard T1-weighted magnetic resonance imaging (MRI) scans covering the brain and cervical cord from 37 MS patients and 20 healthy controls (HC). We also measured the cord area at C2-C3 with a semi-automatic segmentation method using (i) the same T1-weighted acquisitions used for the new voxel-based analysis and (ii) dedicated spinal cord phase sensitive inversion recovery (PSIR) acquisitions. Cervical cord findings derived from the three approaches were compared to each other and the goodness to fit to clinical scores was assessed by regression analyses. RESULTS: The SPM-BSC approach revealed a severity-dependent pattern of atrophy across the cervical cord and thalamus in MS patients when compared to HCs. The magnitude of cord atrophy was confirmed by the semi-automatic extraction approach at C2-C3 using both standard brain T1-weighted and advanced cord dedicated acquisitions. Associations between atrophy of cord and thalamus with disability and cognition were demonstrated. CONCLUSION: Atrophy in the brain and cervical cord of MS patients can be identified simultaneously and rapidly at the voxel-level. The SPM-BSC approach yields similar results as available standard processing tools with the added advantage of performing the analysis simultaneously and faster.

A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]: Mechanical Stress, Vulnerability and Time.

STUDY DESIGN: Literature Review (Narrative). OBJECTIVE: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5. METHODS: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework. RESULTS: Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with visualized cord compression show clinical myelopathy, and the amount of cord compression only weakly correlates with disability. We propose that DCM is better represented as a function of several interacting mechanical forces, such as shear, tension and compression, alongside an individual's vulnerability to spinal cord injury, influenced by factors such as age, genetics, their cardiovascular, gastrointestinal and nervous system status, and time. CONCLUSION: Understanding the disease pathobiology is a fundamental research priority. We believe a framework of mechanical stress, vulnerability, and time may better represent the disease as a whole. Whilst this remains theoretical, we hope that at the very least it will inspire new avenues of research that better encapsulate the full spectrum of disease.

Extent of Cord Pathology in the Lumbosacral Enlargement in Non-Traumatic versus Traumatic Spinal Cord Injury.

This study compares remote neurodegenerative changes caudal to a cervical injury in degenerative cervical myelopathy (DCM; i.e., non-traumatic) and incomplete traumatic spinal cord injury (tSCI) patients, using magnetic resonance imaging (MRI)-based tissue area measurements and diffusion tensor imaging (DTI). Eighteen mild-to-moderate DCM patients with sensory impairments (modified Japanese Orthopedic score: 16.2 ± 1.9), 14 incomplete tetraplegic tSCI patients (American Spinal Injury Association Impairment Scale C and D), and 20 healthy controls were recruited. All participants received DTI and T2*-weighted scans in the lumbosacral enlargement (caudal to injury) and at C2/C3 (rostral to injury). MRI readouts included DTI metrics in the white matter (WM) columns and cross-sectional WM and gray matter area. One-way analysis of variance with Tukey's post hoc comparison (p < 0.05) was used to assess group differences. In the lumbosacral enlargement, compared with DCM, tSCI patients exhibited decreased fractional anisotropy in the lateral (tSCI vs. DCM, -11.9%, p = 0.007) and ventral WM column (-8.0%, p = 0.021), and showed a trend toward lower values in the dorsal column (-8.9%, p = 0.068). At C2/C3, compared with controls, fractional anisotropy was lower in both groups in the dorsal (DCM vs. controls, -7.9%, p = 0.024; tSCI vs. controls, -10.0%, p = 0.007) and in the lateral column (DCM: -6.2%, p = 0.039; tSCI: -13.3%, p < 0.001), while tSCI patients had lower fractional anisotropy than DCM patients in the lateral column (-7.6%, p = 0.029). WM areas were not different between patient groups but were lower compared with controls in the lumbosacral enlargement (DCM: -16.9%, p < 0.001; tSCI: -10.5%, p = 0.043) and at C2/C3 (DCM: -16.0%, p < 0.001; tSCI: -18.1%, p < 0.001). In conclusion, mild-to-moderate DCM and incomplete tSCI lead to similar degree of degeneration of the dorsal and lateral columns at C2/C3, but tSCI results in more widespread white matter damage in the lumbosacral enlargement. These remote changes are likely to contribute to the patients' impairment and recovery. DTI is a sensitive tool to assess remote pathological changes in DCM and tSCI patients.