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Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord Region are Associated With Clinical Outcomes in Cervical Spondylotic Myelopathy.

ABSTRACT: STUDY DESIGN:A case-control study. OBJECTIVE:The 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 DATA:MTR 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. METHODS:We 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. RESULTS:Compared with controls, CSM patients had lower anterior cord MTR (38.29 vs. 29.97, ? = -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. CONCLUSION:Anterior 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 EVIDENCE:2.

SUBMITTER: Cloney MB

PROVIDER: S-EPMC6621550 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord Region are Associated With Clinical Outcomes in Cervical Spondylotic Myelopathy.

Cloney Michael Brendan MB Smith Zachary A ZA Weber Kenneth A KA Parrish Todd B TB

Spine 20180501 10

<h4>Study design</h4>A case-control study.<h4>Objective</h4>The aim of this study was to understand the role of magnetization transfer ratio (MTR) in identifying patients with clinically significant myelopathy and disability.<h4>Summary of background data</h4>MTR 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. ...[more]

PMID: 29068880

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Project description:Cervical spondylotic myelopathy (CSM) is a degenerative condition of the spine that caused by static and dynamic compression of the spinal cord. However, the mechanisms of motor and somatosensory conduction, as well as pathophysiological changes at dynamic neck positions remain unclear. This study aims to investigate the interplay between neurophysiological and hemodynamic responses at dynamic neck positions in the CSM condition, and the pathological basis behind. We first demonstrated that CSM patients had more severe dynamic motor evoked potentials (DMEPs) deteriorations upon neck flexion than upon extension, while their dynamic somatosensory evoked potentials (DSSEPs) deteriorated to a similar degree upon extension and flexion. We therefore generated a CSM rat model which developed similar neurophysiological characteristics within a 4-week compression period. At 4 weeks-post-injury, these rats presented decreased spinal cord blood flow (SCBF) and oxygen saturation (SO2) at the compression site, especially upon cervical flexion. The dynamic change of DMEPs was significantly correlated with the change in SCBF from neutral to flexion, suggesting they were more sensitive to ischemia compared to DSSEPs. We further demonstrated significant vascular redistribution in the spinal cord parenchyma, caused by angiogenesis mainly concentrated in the anterior part of the compressed site. In addition, the comparative ratio of vascular densities at the anterior and posterior parts of the cord was significantly correlated with the perfusion decrease at neck flexion. This exploratory study revealed that the motor and somatosensory conductive functions of the cervical cord changed differently at dynamic neck positions in CSM conditions. Compared with somatosensory conduction, the motor conductive function of the cervical cord suffered more severe deteriorations upon cervical flexion, which could partly be attributed to its higher susceptibility to spinal cord ischemia. The uneven angiogenesis and vascular distribution in the spinal cord parenchyma might underlie the transient ischemia of the cord at flexion.

Project description:PURPOSE:This study aims to systematically evaluate the accuracy and precision of pool size ratio (PSR) measurements from quantitative magnetization transfer (qMT) acquisitions using simplified models in the context of assessing injury-associated spatiotemporal changes in spinal cords of non-human primates. This study also aims to characterize changes in the spinal tissue pathology in individual subjects, both regionally and longitudinally, in order to demonstrate the relationship between regional tissue compositional changes and sensorimotor behavioral recovery after cervical spinal cord injury (SCI). METHODS:MRI scans were recorded on anesthetized monkeys at 9.4 T, before and serially after a unilateral section of the dorsal column tract. Images were acquired following saturating RF pulses at different offset frequencies. Models incorporating two pools of protons but with differing numbers of variable parameters were used to fit the data to derive qMT parameters. The results using different amounts of measured data and assuming different numbers of variable model parameters were compared. Behavioral impairments and recovery were assessed by a food grasping-retrieving task. Histological sections were obtained post mortem for validation of the injury. RESULTS:QMT fitting provided maps of pool size ratio (PSR), the relative amounts of immobilized protons exchanging magnetization compared to the "free" water. All the selected modeling approaches detected a lesion/cyst at the site of injury as significant reductions in PSR values. The regional contrasts in the PSR maps obtained using the different fittings varied, but the 2-parameter fitting results showed strong positive correlations with results from 5-parameter modeling. 2-parameter fitting results with modest (>3) RF offsets showed comparable sensitivity for detecting demyelination in white matter and loss of macromolecules in gray matter around lesion sites compared to 5-parameter fitting with fully-sampled data acquisitions. Histology confirmed that decreases of PSR corresponded to regional demyelination around lesion sites, especially when demyelination occurred along the dorsal column on the injury side. Longitudinally, PSR values of injured dorsal column tract and gray matter horns exhibited remarkable recovery that associated with behavioral improvement. CONCLUSION:Simplified qMT modeling approaches provide efficient and sensitive means to detect and characterize injury-associated demyelination in white matter tracts and loss of macromolecules in gray matter and to monitor its recovery over time.

Project description:STUDY DESIGN:Case-control. OBJECTIVE:The aim of this study was to understand the role of high-resolution magnetic resonance (MR) in identifying regional cord volume loss in cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA:Preliminary studies suggest that compression of the ventral region of the cord may contribute disproportionately to CSM symptomology; however, tract-specific data are lacking in the CSM population. The current study is the first to use 3T MR imaging (MRI) images of CSM patients to determine specific volume loss at the level of detail of individual descending white matter tracts. METHODS:Twelve patients with CSM and 14 age-matched were enrolled prospectively and underwent 3-Tesla MRI of the cervical spine. Using the high-resolution images of the spinal cord, straightening and alignment with a template was performed and specific spinal cord tract volumes were measured using Spinal Cord Tool-box version 3.0.7. Modified Japanese orthopedic association (mJOA) and Nurick disability scores were collected in a prospective manner and were analyzed in relation to descending spinal tract volumes. RESULTS:Having CSM was predicted by anterior/posterior diameter, eccentricity of the cord [odds ratio (OR) 0.000000621, P?=?0.004], ventral reticulospinal tract volume (OR 1.167, P?=?0.063), lateral corticospinal tract volume (OR 1.034, P?=?0.046), rubrospinal tract volume (OR 1.072, P?=?0.011), and ventrolateral reticulospinal tract volume (OR 1.474, P?=?0.005) on single variable logistic regression. Single variable linear regression showed decreases in anterior/posterior spinal cord diameter (P?=?0.022), ventral reticulospinal tract volumes (P?=?0.007), and ventrolateral reticulospinal tract volumes (P?=?0.017) to significantly predict worsening mJOA scores. Similarly, decreases in ventral reticulospinal tract volumes significantly predicted increasing Nurick scores (P?=?0.039). CONCLUSION:High-resolution 3T MRI can detect tract-specific volume loss in descending spinal cord tracts in CSM patients. Anterior/posterior spinal cord diameter, ventral reticulospinal tract, ventrolateral reticulospinal tract, lateral corticospinal tract, and rubrospinal tract volume loss are associated with CSM symptoms. LEVEL OF EVIDENCE:2.

Project description:Introduction Degenerative Cervical Myelopathy [DCM] is a slow-motion spinal cord injury. Compression and dynamic compression have been considered disease hallmarks. However, this is likely an oversimplification, as compression is more commonly incidental and has only modest correlation to disease severity. MRI studies have recently suggested spinal cord oscillation could play a role. Research question To determine if spinal cord oscillation could contribute to spinal cord injury in degenerative cervical myelopathy. Material and methods A computational model of an oscillating spinal cord was developed from imaging of a healthy volunteer. Using finite element analysis, the observed implications of stress and strain, were measured in the context of a simulated disc herniation. The significance was bench marked by comparison to a more recognised dynamic injury mechanism; a flexion extension model of dynamic compression. Results Spinal cord oscillation altered both compressive and shear strain on the spinal cord. Following initial compression, compressive strain moves from within the spinal cord to the spinal cord surface, whilst shear strain is magnified by 0.1–0.2, depending on the amplitude of oscillation. These orders of magnitude are equivalent to a dynamic compression model. Discussion and conclusion Spinal cord oscillation could significantly contribute to spinal cord damage across DCM. Its repeated occurrence with every heartbeat, draws parallels to the concept of fatigue damage, which could reconcile differing theories on the origins of DCM. This remains hypothetical at this stage, and further investigations are required. Highlights • Aetiology of Degenerative Cervical Myelopathy is poorly understood• Paradigm based purely on ‘compression’ could be an oversimplification• Analysis of a computational model based on an MRI cervical spine• Loading from cord oscillation was equivalent to that from dynamic compression• Proposes a cause of ‘repetitive microtrauma’ warranting further investigation

Project description:MethodsTwenty patients with CSM and 17 controls were recruited. Clinical scores of modified Japanese Orthopedic Association (mJOA) and Nurick were collected. MRI based compression grades such as cord distortion were assessed. Hand dysfunction was tested using a custom motorized apparatus. Subject's forearm was placed in a cast and positioned such that their metacarpophalangeal (MCP) joint was vertically aligned with the motor shaft. Surface electromyographic sensors were placed on flexor digitorum superficialis (FDS) and extensor digitorum communis muscles. Hyperreflexia was measured as the FDS muscle activation during reflex when the MCP joint was moved from flexion to extension at 300°/sec. Proprioception was quantified as the angle of detection in absence of visual or auditory cues (subjects were blindfolded and given noise-cancelling headphones). Strength was measured as the maximum isometric force at the MCP joint. 2-sample t-test (p<0.05) were performed to assess significant differences in reflexes, proprioception and strength among patients and controls (SPSS software version 24).ResultsPatients reported higher Nurick (1.90±1.0 vs 0±0, p<0.001) and lower mJOA scores (14.3±1.9 vs 18.0±0, p<0.001) as compared to controls. Similarly, patients with CSM had increased reflexes (peak FDS EMG) (0.073±0.096 vs. 0.014±0.010, p = 0.019). Patient proprioception was significantly worse; mean angle of detection was greater than twice as high in patients (9.6± 9.43°) compared to controls (4.0± 2.3°), p = 0.022. MRI based compression ratio (CR) was a significant predictor of hyperreflexia, CR<0.44 resulted in steep increase in reflex activity. Fifteen of the 20 patients who completed follow up testing at 6 months after surgery show substantial clinical improvement in reflexes and proprioceptive angle, while repeated testing in controls were unchanged.ConclusionIn conclusion, hyperreflexia and decline in proprioception are the main drivers of hand disability in patients with CSM. Of multiple scales, only a select few MRI scales (such as compression ratio) were predictive of increased reflexes. The study describes a pre-clinical testing apparatus to quantitatively and objectively assess primary presenting symptoms in CSM. This pilot apparatus has the potential to evaluate treatment efficacy through repeated testing. Objective testing of hand dysfunction can help inform the design of clinically feasible devices, guide MRI biomarker analysis, and improve our understanding of the progression of neurological injury in this patient population.

Dataset Information

Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord Region are Associated With Clinical Outcomes in Cervical Spondylotic Myelopathy.

Publications

Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord Region are Associated With Clinical Outcomes in Cervical Spondylotic Myelopathy.

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