Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers.
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ABSTRACT:
SUBMITTER: Cohen-Adad J
PROVIDER: S-EPMC8368310 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spinal cord atrophy is a well-known biomarker in multiple sclerosis (MS) and other diseases. It is measured by segmenting the spinal cord on an MRI image and computing the average cross-sectional area (CSA) over a few slices. Introduced about 25 years ago, this procedure is highly sensitive to the quality of the segmentation and is prone to rater-bias. Recently, fully-automated spinal cord segmentation methods, which remove the rater-bias and enable the automated analysis of large populations, have been introduced. A lingering question related to these automated methods is: How reliable are they at detecting atrophy? In this study, we evaluated the precision and accuracy of automated atrophy measurements by simulating scan-rescan experiments. Spinal cord MRI data from the open-access spine-generic project were used. The dataset aggregates 42 sites worldwide and consists of 260 healthy subjects and includes T1w and T2w contrasts. To simulate atrophy, each volume was globally rescaled at various scaling factors. Moreover, to simulate patient repositioning, random rigid transformations were applied. Using the DeepSeg algorithm from the Spinal Cord Toolbox, the spinal cord was segmented and vertebral levels were identified. Then, the average CSA between C3-C5 vertebral levels was computed for each Monte Carlo sample, allowing us to derive measures of atrophy, intra/inter-subject variability, and sample-size calculations. The minimum sample size required to detect an atrophy of 2% between unpaired study arms, commonly seen in MS studies, was 467 +/- 13.9 using T1w and 467 +/- 3.2 using T2w images. The minimum sample size to detect a longitudinal atrophy (between paired study arms) of 0.8% was 60 +/- 25.1 using T1w and 10 +/- 1.2 using T2w images. At the intra-subject level, the estimated CSA, observed in this study, showed good precision compared to other studies with COVs (across Monte Carlo transformations) of 0.8% for T1w and 0.6% for T2w images. While these sample sizes seem small, we would like to stress that these results correspond to a "best case" scenario, in that the dataset used here was of particularly good quality and the model for simulating atrophy does not encompass all the variability met in real-life datasets. The simulated atrophy and scan-rescan variability may over-simplify the biological reality. The proposed framework is open-source and available at https://csa-atrophy.readthedocs.io/.
| S-EPMC8503570 | biostudies-literature
Project description:PurposeValidation of quantitative MR measures for myelin imaging in the postmortem multiple sclerosis spinal cord.MethodsFour fixed spinal cord samples were imaged first with a 3T clinical MR scanner to identify areas of interest for scanning, and then with a 7T small bore scanner using a multicomponent-driven equilibrium single-pulse observation of T1 and T2 protocol to produce apparent proton density, T1 , T2 , myelin water, intracellular water, and free-water fraction maps. After imaging, the cords were sectioned and stained with histological markers (hematoxylin and eosin, myelin basic protein, and neurofilament protein), which were quantitatively compared with the MR maps.ResultsExcellent correspondence was found between high-resolution MR parameter maps and histology, particularly for apparent proton density MRI and myelin basic protein staining.ConclusionHigh-resolution quantitative MRI of the spinal cord provides biologically meaningful measures, and could be beneficial to diagnose and track multiple sclerosis lesions in the spinal cord.
| S-EPMC9208576 | biostudies-literature
Project description:ObjectiveThe clinicoradiologic paradox, or disconnect between clinical and radiologic findings, is frequently encountered in multiple sclerosis (MS), particularly in the spinal cord (SC), where lesions are expected to cause clinical impairment. We aimed to assess whether quantitative diffusion tensor and magnetization transfer imaging measures in the SC can distinguish MS cases of comparable lesion burdens with high and low disability.MethodsOne hundred twenty-four patients with MS underwent 3-T cervical SC MRI and were categorized into 4 subgroups according to SC lesion count and disability level. Regions of interest circumscribed the SC cross-section axially between C3 and C4. Cross-sectional area, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (?(?)), parallel diffusivity (?(?)), and magnetization transfer ratio (MTR) were calculated. Differences between patient subgroups were assessed using t tests and linear regression.ResultsFA, MD, ?(?), ?(?), MTR, and SC cross-sectional area were more abnormal in the high- vs low-disability subgroup of patients with low lesion counts (p < 0.05). MRI measures (except ?(?) and MTR) were more abnormal in the high- vs low-disability subgroup of patients with high lesion counts (p < 0.05). In age- and sex-adjusted comparisons of high- vs low-disability subgroups, all MRI measures retained differences in the low-lesion subgroup, except ?(?), whereas only FA, MD, and ?(?) retained differences in the high-lesion subgroup.ConclusionsIn this cross-sectional study of patients with MS, quantitative MRI reflects clinically relevant differences beyond what can be detected by conventional MRI. Our findings support the utility of quantitative MRI in clinical settings, where accurate measurement of disease burden is becoming increasingly critical for assessing treatment efficacy.
| S-EPMC3589285 | biostudies-literature
Project description:To assess relationships between spinal cord MRI (SC-MRI) and retinal measures, and to evaluate whether these measures independently relate to clinical disability in multiple sclerosis (MS).One hundred two patients with MS and 11 healthy controls underwent 3-tesla brain and cervical SC-MRI, which included standard T1- and T2-based sequences and diffusion-tensor and magnetization-transfer imaging, and optical coherence tomography with automated segmentation. Clinical assessments included visual acuity (VA), Expanded Disability Status Scale, MS functional composite, vibration sensation threshold, and hip-flexion strength. Regions of interest circumscribing SC cross-sections at C3-4 were used to obtain cross-sectional area (CSA), fractional anisotropy (FA), perpendicular diffusivity (??), and magnetization transfer ratio. Multivariable regression assessed group differences and SC, retinal, and clinical relationships.In MS, there were correlations between SC-CSA, SC-FA, SC-??, and peripapillary retinal nerve fiber layer (pRNFL) (p = 0.01, p = 0.002, p = 0.001, respectively) after adjusting for age, sex, prior optic neuritis, and brain atrophy. In multivariable clinical models, when SC-CSA, pRNFL, and brain atrophy were included simultaneously, SC-CSA and pRNFL retained independent relationships with low-contrast VA (p = 0.04, p = 0.002, respectively), high-contrast VA (p = 0.06, p = 0.008), and vibration sensation threshold (p = 0.01, p = 0.05). SC-CSA alone retained independent relationships with Expanded Disability Status Scale (p = 0.001), hip-flexion strength (p = 0.001), and MS functional composite (p = 0.004).In this cross-sectional study of patients with MS, correlations exist between SC-MRI and retinal layers, and both exhibit independent relationships with clinical dysfunction. These findings suggest that the SC and optic nerve reflect ongoing global pathologic processes that supplement measures of whole-brain atrophy, highlighting the importance of combining measures from unique compartments to facilitate a thorough examination of regional and global disease processes that contribute to clinical disability in MS.
| S-EPMC4336102 | biostudies-other
Project description:Multi-parametric quantitative MRI (qMRI) of the spinal cord is a promising non-invasive tool to probe early microstructural damage in neurological disorders. It is usually performed in vivo by combining acquisitions with multiple signal readouts, which exhibit different thermal noise levels, geometrical distortions and susceptibility to physiological noise. This ultimately hinders joint multi-contrast modelling and makes the geometric correspondence of parametric maps challenging. We propose an approach to overcome these limitations, by implementing state-of-the-art microstructural MRI of the spinal cord with a unified signal readout in vivo (i.e. with matched spatial encoding parameters across a range of imaging contrasts). We base our acquisition on single-shot echo planar imaging with reduced field-of-view, and obtain data from two different vendors (vendor 1: Philips Achieva; vendor 2: Siemens Prisma). Importantly, the unified acquisition allows us to compare signal and noise across contrasts, thus enabling overall quality enhancement via multi-contrast image denoising methods. As a proof-of-concept, here we provide a demonstration with one such method, known as Marchenko-Pastur (MP) Principal Component Analysis (PCA) denoising. MP-PCA is a singular value (SV) decomposition truncation approach that relies on redundant acquisitions, i.e. such that the number of measurements is large compared to the number of components that are maintained in the truncated SV decomposition. Here we used in vivo and synthetic data to test whether a unified readout enables more efficient MP-PCA denoising of less redundant acquisitions, since these can be denoised jointly with more redundant ones. We demonstrate that a unified readout provides robust multi-parametric maps, including diffusion and kurtosis tensors from diffusion MRI, myelin metrics from two-pool magnetisation transfer, and T1 and T2 from relaxometry. Moreover, we show that MP-PCA improves the quality of our multi-contrast acquisitions, since it reduces the coefficient of variation (i.e. variability) by up to 17% for mean kurtosis, 8% for bound pool fraction (myelin-sensitive), and 13% for T1, while enabling more efficient denoising of modalities limited in redundancy (e.g. relaxometry). In conclusion, multi-parametric spinal cord qMRI with unified readout is feasible and provides robust microstructural metrics with matched resolution and distortions, whose quality benefits from multi-contrast denoising methods such as MP-PCA.
| S-EPMC7378937 | biostudies-literature
Project description:INTRODUCTION:Quantitative longitudinal magnetic resonance imaging and spectroscopy (MRI/S) is used to assess progress of brain disorders and treatment effects. Understanding the significance of MRI/S changes requires knowledge of the inherent technical and physiological consistency of these measurements. This longitudinal study examined the variance and reproducibility of commonly used quantitative MRI/S measurements in healthy subjects while controlling physiological and technical parameters. METHODS:Twenty-five subjects were imaged three times over 5 days on a Siemens 3T Verio scanner equipped with a 32-channel phase array coil. Structural (T1, T2-weighted, and diffusion-weighted imaging) and physiological (pseudocontinuous arterial spin labeling, proton magnetic resonance spectroscopy) data were collected. Consistency of repeated images was evaluated with mean relative difference, mean coefficient of variation, and intraclass correlation (ICC). Finally, a "reproducibility rating" was calculated based on the number of subjects needed for a 3% and 10% difference. RESULTS:Structural measurements generally demonstrated excellent reproducibility (ICCs 0.872-0.998) with a few exceptions. Moderate-to-low reproducibility was observed for fractional anisotropy measurements in fornix and corticospinal tracts, for cortical gray matter thickness in the entorhinal, insula, and medial orbitofrontal regions, and for the count of the periependymal hyperintensive white matter regions. The reproducibility of physiological measurements ranged from excellent for most of the magnetic resonance spectroscopy measurements to moderate for permeability-diffusivity coefficients in cingulate gray matter to low for regional blood flow in gray and white matter. DISCUSSION:This study demonstrates a high degree of longitudinal consistency across structural and physiological measurements in healthy subjects, defining the inherent variability in these commonly used sequences. Additionally, this study identifies those areas where caution should be exercised in interpretation. Understanding this variability can serve as the basis for interpretation of MRI/S data in the assessment of neurological disorders and treatment effects.
| S-EPMC5607538 | biostudies-literature
Project description:We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity.
| S-EPMC4889527 | biostudies-literature
Project description:Introduction: Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Methods: Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally. Results: Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content. Conclusion: In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA in vivo and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort.
| S-EPMC8039452 | biostudies-literature
Project description:Study designA case-control study.ObjectiveThe aim of this study was to understand the role of magnetization transfer ratio (MTR) in identifying patients with clinically significant myelopathy and disability.Summary of background dataMTR is a quantitative measure that correlates with myelin loss and neural tissue destruction in a variety of neurological diseases. However, the usefulness of MTR in patients with cervical spondylotic myelopathy (CSM) has not been examined.MethodsWe prospectively enrolled seven CSM patients and seven age-matched controls to undergo magnetic resonance imaging (MRI) of the cervical spine. Nurick, Neck Disability Index (NDI), and modified Japanese Orthopedic Association (mJOA) scores were collected for all patients. Clinical hyperreflexia was tested at the MCP joint, using a six-axis load cell. Reflex was simulated by quickly moving the joint from maximum flexion to maximum extension (300°/second). Anterior, lateral, and posterior cord MTR measurements were compared with clinical outcomes.ResultsCompared with controls, CSM patients had lower anterior cord MTR (38.29 vs. 29.97, Δ = -8.314, P = 0.0022), and equivalent posterior cord (P = 0.2896) and lateral cord (P = 0.3062) MTR. Higher Nurick scores were associated with lower anterior cord MTR (P = 0.0205), but not lateral cord (P = 0.5446) or posterior cord MTR (P = 0.1222). Lower mJOA was associated with lower anterior cord MTR (P = 0.0090), but not lateral cord (P = 0.4864) or posterior cord MTR (P = 0.4819). There was no association between NDI and MTR of the anterior (P = 0.4351), lateral (P = 0.7557), or posterior cord (P = 0.9171). There was a linear relationship between hyperreflexia and anterior cord MTR (slope = -117.3, R = 0.6598, P = 0.0379), but not lateral cord (P = 0.1906, R = 0.4511) or posterior cord (P = 0.2577, R = 0.3957) MTR.ConclusionAnterior cord MTR correlates with clinical outcomes as measured by mJOA index, Nurick score, and quantitative hyperreflexia, and could play a role in the preoperative assessment of CSM.Level of evidence2.
| S-EPMC6621550 | biostudies-literature
Project description:Traumatic spinal cord injury (SCI) is a common and devastating condition. In the absence of effective validated therapies, there is an urgent need for novel methods to achieve injury stabilization, regeneration, and functional restoration in SCI patients. Ultrasound is a versatile platform technology that can provide a foundation for viable diagnostic and therapeutic interventions in SCI. In particular, real-time perfusion and inflammatory biomarker monitoring, focal pharmaceutical delivery, and neuromodulation are capabilities that can be harnessed to advance our knowledge of SCI pathophysiology and to develop novel management and treatment options. Our review suggests that studies that evaluate the benefits and risks of ultrasound in SCI are severely lacking and our understanding of the technology's potential impact remains poorly understood. Although the complex anatomy and physiology of the spine and the spinal cord remain significant challenges, continued technological advances will help the field overcome the current barriers and bring ultrasound to the forefront of SCI research and development.
| S-EPMC8889947 | biostudies-literature