Evaluating tissue injury in cervical spondylotic myelopathy with spinal cord MRI: a systematic review.

PURPOSE: Cervical Spondylotic Myelopathy (CSM) is a degenerative condition that leads to loss of cervical spinal cord (CSC) integrity. Various spinal cord Magnetic Resonance Imaging (MRI) methods can identify and characterize the extent of this damage. This systematic review aimed to evaluate the diagnostic, biomarker, and predictive utilities of different spinal cord MRI methods in clinical research studies of CSM. The aim was to provide a comprehensive understanding of the progress in this direction for future studies and effective diagnosis and management of CSM. METHODS: A comprehensive literature search was conducted on PubMed and EMBASE from 2010 to 2022 according to PRISMA guidelines. Studies with non-human subjects, less than 3T magnetic field strength, non-clinical design, or not quantitatively focusing on the structural integrity of CSC were excluded. The extracted data from each study included demographics, disease severity, MRI machine characteristics, quantitative metrics, and key findings in terms of diagnostic, biomarker, and predictive utilities of each MRI method. The risk of bias was performed using the guide from AHRQ. The quality of evidence was assessed separately for each type of utility for different MRI methods using GRADE. RESULTS: Forty-seven studies met the inclusion criteria, utilizing diffusion-weighted imaging (DTI) (n = 39), magnetization transfer (MT) (n = 6), MR spectroscopy (n = 3), and myelin water imaging (n = 1), as well as a combination of MRI methods (n = 12). The metric fractional anisotropy (FA) showed the highest potential in all facets of utilities, followed by mean diffusivity. Other promising metrics included MT ratio and intracellular volume fraction, especially in multimodal studies. However, the level of evidence for these promising metrics was low due to a small number of studies. Some studies, mainly DTI, also reported the usefulness of spinal cord MRI in mild CSM. CONCLUSIONS: Spinal cord MRI methods can potentially facilitate the diagnosis and management of CSM by quantitatively interrogating the structural integrity of CSC. DTI is the most promising MRI method, and other techniques have also shown promise, especially in multimodal configurations. However, this field is in its early stages, and more studies are needed to establish the usefulness of spinal cord MRI in CSM.

Spinal cord imaging markers and recovery of standing with epidural stimulation in individuals with clinically motor complete spinal cord injury.

Spinal cord epidural stimulation (scES) is an intervention to restore motor function in those with severe spinal cord injury (SCI). Spinal cord lesion characteristics assessed via magnetic resonance imaging (MRI) may contribute to understand motor recovery. This study assessed relationships between standing ability with scES and spared spinal cord tissue characteristics at the lesion site. We hypothesized that the amount of lateral spared cord tissue would be related to independent extension in the ipsilateral lower limb. Eleven individuals with chronic, clinically motor complete SCI underwent spinal cord MRI, and were subsequently implanted with scES. Standing ability and lower limb activation patterns were assessed during an overground standing experiment with scES. This assessment occurred prior to any activity-based intervention with scES. Lesion hyperintensity was segmented from T2 axial images, and template-based analysis was used to estimate spared tissue in anterior, posterior, right, and left spinal cord regions. Regression analysis was used to assess relationships between imaging and standing outcomes. Total volume of spared tissue was related to left (p = 0.007), right (p = 0.005), and bilateral (p = 0.011) lower limb extension. Spared tissue in the left cord region was related to left lower limb extension (p = 0.019). A positive trend (p = 0.138) was also observed between right spared cord tissue and right lower limb extension. In this study, MRI measures of spared spinal cord tissue were significantly related to standing outcomes with scES. These preliminary results warrant future investigation of roles of supraspinal input and MRI-detected spared spinal cord tissue on lower limb motor responsiveness to scES.

Evaluation of Intra- and Interscanner Reliability of MRI Protocols for Spinal Cord Gray Matter and Total Cross-Sectional Area Measurements.

BACKGROUND: In vivo quantification of spinal cord atrophy in neurological diseases using MRI has attracted increasing attention. PURPOSE: To compare across different platforms the most promising imaging techniques to assess human spinal cord atrophy. STUDY TYPE: Test/retest multiscanner study. SUBJECTS: Twelve healthy volunteers. FIELD STRENGTH/SEQUENCE: Three different 3T scanner platforms (Siemens, Philips, and GE) / optimized phase sensitive inversion recovery (PSIR), T1 -weighted (T1 -w), and T2 *-weighted (T2 *-w) protocols. ASSESSMENT: On all images acquired, two operators assessed contrast-to-noise ratio (CNR) between gray matter (GM) and white matter (WM), and between WM and cerebrospinal fluid (CSF); one experienced operator measured total cross-sectional area (TCA) and GM area using JIM and the Spinal Cord Toolbox (SCT). STATISTICAL TESTS: Coefficient of variation (COV); intraclass correlation coefficient (ICC); mixed effect models; analysis of variance (t-tests). RESULTS: For all the scanners, GM/WM CNR was higher for PSIR than T2 *-w (P < 0.0001) and WM/CSF CNR for T1 -w was the highest (P < 0.0001). For TCA, using JIM, median COVs were smaller than 1.5% and ICC >0.95, while using SCT, median COVs were in the range 2.2-2.75% and ICC 0.79-0.95. For GM, despite some failures of the automatic segmentation, median COVs using SCT on T2 *-w were smaller than using JIM manual PSIR segmentations. In the mixed effect models, the subject was always the main contributor to the variance of area measurements and scanner often contributed to TCA variance (P < 0.05). Using JIM, TCA measurements on T2 *-w were different than on PSIR (P = 0.0021) and T1 -w (P = 0.0018), while using SCT, no notable differences were found between T1 -w and T2 *-w (P = 0.18). JIM and SCT-derived TCA were not different on T1 -w (P = 0.66), while they were different for T2 *-w (P < 0.0001). GM area derived using SCT/T2 *-w versus JIM/PSIR were different (P < 0.0001). DATA CONCLUSION: The present work sets reference values for the magnitude of the contribution of different effects to cord area measurement intra- and interscanner variability. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:1078-1090.

Spinal cord multi-parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival. METHODS: Forty-nine ALS patients were recruited and clinical data were collected. Patients were scored on the Revised ALS Functional Rating Scale and manual muscle testing. They were followed longitudinally to assess survival. The cervical SC was imaged using the 3 T MRI system. Cord volume and cross-sectional area (CSA) at each vertebral level were computed. Diffusion tensor imaging metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model. RESULTS: On building a multivariate Cox regression model with clinical and MRI parameters, fractional anisotropy, magnetization transfer ratio and CSA at C2-C3, C4-C5, C5-C6 and C6-C7 vertebral levels were significant. Moreover, the hazard ratio calculated for CSA at the C3-C4 and C5-C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had a hazard ratio very close to 1. CONCLUSIONS: It is suggested that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, confirmation of the results in bigger independent cohorts of patients is warranted.

Nineteen-channel receive array and four-channel transmit array coil for cervical spinal cord imaging at 7T.

PURPOSE: To design and validate a radiofrequency (RF) array coil for cervical spinal cord imaging at 7T. METHODS: A 19-channel receive array with a four-channel transmit array was developed on a close-fitting coil former at 7T. Transmit efficiency and specific absorption rate were evaluated in a B1 (+) mapping study and an electromagnetic model. Receive signal-to-noise ratio (SNR) and noise amplification for parallel imaging were evaluated and compared with a commercial 3T 19-channel head-neck array and a 7T four-channel spine array. The performance of the array was qualitatively demonstrated in human volunteers using high-resolution imaging (down to 300 µm in-plane). RESULTS: The transmit and receive arrays showed good bench performance. The SNR was approximately 4.2-fold higher in the 7T receive array at the location of the cord with respect to the 3T coil. The g-factor results showed an additional acceleration was possible with the 7T array. In vivo imaging was feasible and showed high SNR and tissue contrast. CONCLUSION: The highly parallel transmit and receive arrays were demonstrated to be fit for spinal cord imaging at 7T. The high sensitivity of the receive coil combined with ultra-high field will likely improve investigations of microstructure and tissue segmentation in the healthy and pathological spinal cord.

Spinal cord MRI activity in multiple sclerosis: Predictive value for relapses and impact on treatment decisions.

INTRODUCTION: Emerging evidence suggests the prognostic value of spinal cord (SC) pathology in multiple sclerosis (MS). However, the 2021 MAGNIMS-CMSC-NAIMS guidelines don't recommend routine SC MRI for disease monitoring. This study investigates the frequency of new asymptomatic and isolated SC lesions, exploring their potential to predict clinical activity and guide treatment decisions. METHODS: We enrolled relapsing-remitting MS (RRMS) patients who underwent brain and SC MRI at baseline and after 12 months. New, enlarged, or gadolinium-enhanced (Gd+) lesions on MRI were considered disease activity markers. Clinical relapses and treatment changes observed 3 months after the 12-month MRI were analyzed using regression analysis, evaluating their association with worsening SC findings. RESULTS: A total of 201 RRMS patients (56 males, 27.9%, mean age 42.5 ± 12.1 years, mean EDSS 2.7 ± 1.9) were included. Isolated worsening of T2 lesion burden in the SC occurred in 16 patients (8%), and 12 (6%) had Gd + lesions. Among patients without brain MRI activity (n = 138), regression analysis revealed a significant association between new Gd + SC lesions and clinical relapses within 3 months of the 12-month MRI (p = 0.024). Worsening SC findings (p = 0.021) and SC lesion enhancement (p = 0.046) emerged as key factors influencing disease-modifying therapy changes within 3 months in these patients. Notably, even without clinical symptoms, worsening SC findings significantly predicted treatment changes (p = 0.003). CONCLUSION: Our findings highlight the independent value of SC MRI findings in MS monitoring. Importantly, isolated and asymptomatic SC worsening significantly impacted treatment decisions.

The added value of spinal cord lesions to disability accrual in multiple sclerosis.

Spinal cord MRI is not routinely performed for multiple sclerosis (MS) monitoring. Here, we explored whether spinal cord MRI activity offers any added value over brain MRI activity for clinical outcomes prediction in MS. This is a retrospective, monocentric study including 830 MS patients who underwent longitudinal brain and spinal cord MRI [median follow-up 7 years (range: < 1-26)]. According to the presence (or absence) of MRI activity defined as at least one new T2 lesion and/or gadolinium (Gd) enhancing lesion, each scan was classified as: (i) brain MRI negative/spinal cord MRI negative; (ii) brain MRI positive/spinal cord MRI negative; (iii) brain MRI negative/spinal cord MRI positive; (iv) brain MRI positive/spinal cord MRI positive. The relationship between such patterns and clinical outcomes was explored by multivariable regression models. When compared with the presence of brain MRI activity alone: (i) Gd + lesions in the spine alone and both in the brain and in the spinal cord were associated with an increased risk of concomitant relapses (OR = 4.1, 95% CI 2.4-7.1, p < 0.001 and OR = 4.9, 95% CI 4.6-9.1, p < 0.001, respectively); (ii) new T2 lesions at both locations were associated with an increased risk of disability worsening (HR = 1.4, 95% CI = 1.0-2.1, p = 0.05). Beyond the presence of brain MRI activity, new spinal cord lesions are associated with increased risk of both relapses and disability worsening. In addition, 16.1% of patients presented asymptomatic, isolated spinal cord activity (Gd + lesions). Monitoring MS with spinal cord MRI may allow a more accurate risk stratification and treatment optimization.

The independent contribution of brain, spinal cord and gadolinium MRI in treatment decision in multiple sclerosis: A population-based retrospective study.

BACKGROUND: Spinal cord and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can provide additional information to brain MRI to determine prognosis of multiple sclerosis (MS). However, the real-world impact of routine use of brain MRI with spinal cord and/or Gd sequences is unknown. Our aim was to evaluate the effect of brain, spinal cord and Gd MRI on treatment decisions in MS. METHODS: In this 2015-2020 population-based study, we performed a retrospective analysis on MS patients resident in the Campania Region (South Italy), with disease modifying treatment (DMT) prescription (n = 6,161). DMTs were classified as platform (dimethyl fumarate, glatiramer acetate, interferon-beta, peg-interferon-beta, teriflunomide), or high-efficacy (alemtuzumab, cladribine, fingolimod, natalizumab, ocrelizumab). We evaluated the association between binary MRI variables and switch from platform to high-efficacy DMT using multivariable logistic regression. RESULTS: The likelihood of switch from platform to high-efficacy DMT was 47% higher when including post-Gd acquisitions to brain and/or spinal cord MRI, 59% higher when including spinal cord acquisitions to brain MRI, and 132% higher when including any MRI compared with no MRI (all p < 0.05). The likelihood of switch to high-efficacy DMT decreased over time from treatment start. CONCLUSION: Our results show that spinal cord and Gd MRI acquisitions can provide relevant information to influence subsequent treatment decisions, especially in early treatment phases, compared with stand-alone brain MRI.

Comparison of spinal magnetic resonance imaging and classical clinical factors in predicting motor capacity in amyotrophic lateral sclerosis.

BACKGROUND: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors. METHODS: Spinal multimodal MRI was performed shortly after diagnosis in 41 ALS patients and 12 healthy participants as part of a prospective multicenter cohort study, the PULSE study (NCT00002013-A00969-36). Motor capacity was assessed using ALSFRS-R scores. Multiple stepwise linear regression models were constructed to predict motor capacity at 3 and 6 months from diagnosis, based on clinical variables, structural MRI measurements, including spinal cord cross-sectional area (CSA), anterior-posterior, and left-to-right cross-section diameters at vertebral levels from C1 to T4, and diffusion parameters in the lateral corticospinal tracts (LCSTs) and dorsal columns. RESULTS: Structural MRI measurements were significantly correlated with the ALSFRS-R score and its sub-scores. And as early as 3 months from diagnosis, structural MRI measurements fit the best multiple linear regression model to predict the total ALSFRS-R (R2 = 0.70, p value = 0.0001) and arm sub-score (R2 = 0.69, p value = 0.0002), and combined with DTI metric in the LCST and clinical factors fit the best multiple linear regression model to predict leg sub-score (R2 = 0.73, p value = 0.0002). CONCLUSIONS: Spinal multimodal MRI could be promising as a tool to enhance prognostic accuracy and serve as a motor function proxy in ALS.

Automated Classification of Intramedullary Spinal Cord Tumors and Inflammatory Demyelinating Lesions Using Deep Learning.

Accurate differentiation of intramedullary spinal cord tumors and inflammatory demyelinating lesions and their subtypes are warranted because of their overlapping characteristics at MRI but with different treatments and prognosis. The authors aimed to develop a pipeline for spinal cord lesion segmentation and classification using two-dimensional MultiResUNet and DenseNet121 networks based on T2-weighted images. A retrospective cohort of 490 patients (118 patients with astrocytoma, 130 with ependymoma, 101 with multiple sclerosis [MS], and 141 with neuromyelitis optica spectrum disorders [NMOSD]) was used for model development, and a prospective cohort of 157 patients (34 patients with astrocytoma, 45 with ependymoma, 33 with MS, and 45 with NMOSD) was used for model testing. In the test cohort, the model achieved Dice scores of 0.77, 0.80, 0.50, and 0.58 for segmentation of astrocytoma, ependymoma, MS, and NMOSD, respectively, against manual labeling. Accuracies of 96% (area under the receiver operating characteristic curve [AUC], 0.99), 82% (AUC, 0.90), and 79% (AUC, 0.85) were achieved for the classifications of tumor versus demyelinating lesion, astrocytoma versus ependymoma, and MS versus NMOSD, respectively. In a subset of radiologically difficult cases, the classifier showed an accuracy of 79%-95% (AUC, 0.78-0.97). The established deep learning pipeline for segmentation and classification of spinal cord lesions can support an accurate radiologic diagnosis. Supplemental material is available for this article. © RSNA, 2022 Keywords: Spinal Cord MRI, Astrocytoma, Ependymoma, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Deep Learning.

Seropositive neuromyelitis optica spectrum disorder in Emirati patients: A case series.

OBJECTIVE: To describe clinical and radiological characteristics of seropositive neuromyelitis optica (NMO) in Emirati patients. While epidemiology of seropositive NMO in Abu Dhabi has been reported in a previous paper, its clinical and MRI profiles among Emirati patients have not been previously fully investigated. METHODS: In our case series, we describe clinical and MRI characteristics of 5 Emirati patients with NMO, consecutively admitted at Cleveland Clinic Abu Dhabi, a major tertiary hospital in Abu Dhabi, United Arab Emirates. RESULTS: Patients were all females, mean age of onset (SD) was 41 (11) years, and 67% had autoimmune comorbidities. Most patients initially presented with acute myelitis (80%) while 20% got optic neuritis. Mean (SD) number of further relapses after onset was 3 (1) and mean (SD) disease duration was 12 (11) years. At MRI, apparent longitudinal extensive transverse myelitis was present in all patients affecting mostly the central gray matter of the cervical cord but extending as well to the thoracic portion. Furthermore, seropositive NMO related brain lesions were also observed. CONCLUSIONS: Our work provides valuable information regarding seropositive NMO with the potential to increase recognition of this disorder in Abu Dhabi and confirms NMO findings described in the other populations with this disorder. Further research is needed to advance clinical and MRI characterization of seronegative NMO in the region.

Spinal Cord Imaging Markers and Recovery of Volitional Leg Movement With Spinal Cord Epidural Stimulation in Individuals With Clinically Motor Complete Spinal Cord Injury.

Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

The spinal and cerebral profile of adult spinal-muscular atrophy: A multimodal imaging study.

Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging. METHODS: Twenty-five type III and IV adult SMA patients and 25 age-matched healthy controls were enrolled in a spinal cord and brain imaging study. Structural measures of grey and white matter involvement and diffusion parameters of white matter integrity were evaluated at each cervical spinal level. Whole-brain and region-of-interest analyses were also conducted in the brain to explore cortical thickness, grey matter density and tract-based white matter alterations. RESULTS: In the spinal cord, considerable grey matter atrophy was detected between C2-C6 vertebral levels. In the brain, increased grey matter density was detected in motor and extra-motor regions of SMA patients. No white matter pathology was identified neither at brain and spinal level. CONCLUSIONS: Adult forms of SMA are associated with selective grey matter degeneration in the spinal cord with preserved white matter integrity. The observed increased grey matter density in the motor cortex may represent adaptive reorganisation.

A case of Susac syndrome with cervical spinal cord involvement on MRI.

We describe a typical case presentation of Susac syndrome with a novel MRI finding of cervical spinal cord involvement. A 25-year-old, 14-week gestation white woman presented with two episodes of encephalopathy, responsive to steroids, with abnormal brain magnetic resonance imaging (MRI) concerning for Susac syndrome. Further studies confirmed the clinical triad of encephalopathy, branch retinal artery occlusions and hearing loss pathognomonic for Susac syndrome. Cervical spine MRI demonstrated two focal areas of high-signal abnormality at C2 and C3. We provide a brief review of Susac syndrome, data regarding pregnancy in this rare syndrome, and discuss how this unique observation may assist in the medical management of such cases and contribute to the understanding of the underlying pathophysiology.