ReviewThe current state-of-the-art of spinal cord imaging: Applications
Introduction
Our ability to research and understand human spinal cord function, its role in pain processing, the effects of traumatic injury or diseases such as multiple-sclerosis, and our understanding of pain processing, is all significantly hampered by the limited accessibility of the spinal cord. In the part I of our two part series we have described the current state-of-the-art of spinal cord imaging, the current greatest challenges, and the greatest needs for future development in order to support non-invasive human spinal cord research (Stroman et al., 2014). The general assumption is that providing increased sensitivity and specificity of spinal cord imaging in the context of well-defined clinical readouts will be instrumental to improve novel approaches in the diagnostic and treatment of spinal cord diseases. The objectives of this paper are to:
- 1)
describe the current state-of-the-art and capabilities of human spinal cord imaging applications;
- 2)
identify the greatest current needs, from a clinical point of view, that will drive forward future development.
In order to achieve these objectives we provide a general overview of two key techniques employed in clinical research, functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI), and then focus on specific applications of spinal cord imaging on four areas: investigations of cervical spondylotic myelopathy (CSM), spinal cord injury (SCI), pain and multiple-sclerosis (MS). Wherever applicable, reference to quantitative imaging methods other than fMRI and DTI, such as magnetic resonance spectroscopy (MRS) and magnetization transfer (MT) imaging, will also be mentioned. Issues related to spatial resolution, registration of subsequently acquired volumes, partial volume effects with the cerebrospinal fluid (CSF), as well as the lack of a standard common template and the effects of physiological noise are still limiting the adoption of many techniques into the clinical setting, confounding quantitative MRI of the spinal cord to research studies. The overall goal of this work is therefore to foster the development of novel and sensitive means of characterizing neural function and cellular structure in clinical populations that can supplement or surpass current methods for patient assessment, serve as clinical trial endpoints, and be used for monitoring of disease progression and efficacy of therapies.
Section snippets
fMRI in the human spinal cord: Applications
A growing number of studies (summarized in Table 1) have been carried out to investigate spinal cord function in response to various sensory stimuli and motor tasks and to characterize the effects of traumatic injury and pathology.
Determining the sensitivity and reliability of spinal cord fMRI is a challenging task in that there is no “gold-standard” method that can be used to verify the results obtained in humans (Stroman et al., 2014). Even studies with animal models (Lawrence et al., 2004,
Spondylotic myelopathy
Spinal cord compression can be caused by various pathological processes such as neoplasms, degenerative changes, inflammatory processes and trauma. Degenerative spine disease is the most common and may have enormous effects on the patients' quality of life (Kara et al., 2011). Progressive compression of the spinal cord due to narrowing of the spinal canal is the main pathophysiology underlying the non-traumatic myelopathy. Early diagnosis and appropriately chosen treatment may prevent further
Spinal cord injury
Improving our ability to assess tissue viability and detect residual neuronal function in the spinal cord, in order to identify and distinguish morphological and functional changes, is key to advancing our capacity for clinical prognosis and management of spinal cord injury patients. A recently published prospective longitudinal study in chronic SCI investigated the motor system, including cervical spinal cord, cranial corticospinal tract (CST) and motor cortex, in particular correlating
Pain
The spinal cord (and brainstem) is the first point in the central nervous system that processes nociceptive signals arriving from the body, and which ultimately may produce a sensation of pain. Functional imaging of the spinal cord aims to record this activity and can help to better understand how these signals are processed and whether altered spinal cord function underlies chronic or neuropathic pain states in humans. Nociceptors, free nerve endings located in skin, muscles and viscera,
Multiple sclerosis
Multiple sclerosis (MS) is the disease that has benefitted mostly from advanced quantitative spinal cord imaging techniques, spanning from cord atrophy measurements, fMRI, DTI and also magnetization transfer ratio (MTR), myelin imaging and proton MRS, as described in this section. Fig. 5 is showing an example of some of these techniques in a patient with MS at cervical level.
Cord lesions in MS are more frequently observed in the cervical than in other regions, are usually peripheral, limited to
Concluding statements
Significant advances in spinal cord imaging methods have been realized in the past decade. The great potential of such methods to support research into basic neuroscience and novel treatment strategies, as well as to improve clinical diagnoses, and the monitoring of treatment and rehabilitation outcomes have been well-demonstrated. The realization of methods to provide the desired research and clinical tools still requires technological development. In part I we reported the greatest technical
Acknowledgments
This work is the result of the efforts of the International Spinal Research Trust and the Wings for Life Spinal Cord Research Foundation to bring together researchers with a common goal of developing non-invasive imaging tools for basic and clinical spinal cord research and to support advances in treatment and rehabilitation. The goal is to speed advances and make these imaging tools more widely available by promoting collaboration between researchers and by identifying the most important
References (151)
- et al.
Tactile-associated recruitment of the cervical cord is altered in patients with multiple sclerosis
NeuroImage
(2008) - et al.
‘Mirror pain’ in the formalin test: behavioral and 2-deoxyglucose studies
Pain
(1993) - et al.
Human brain mechanisms of pain perception and regulation in health and disease
Eur J Pain.
(2005) - et al.
Physiological noise modelling for spinal functional magnetic resonance imaging studies
NeuroImage
(2008) - et al.
Mapping of neural activity produced by thermal pain in the healthy human spinal cord and brain stem: a functional magnetic resonance imaging study
Magn. Reson. Imaging
(2011) Fos, nociception and the dorsal horn
Prog. Neurobiol.
(2005)- et al.
Detection of multiple pathways in the spinal cord using q-ball imaging
NeuroImage
(2008) - et al.
Demyelination and degeneration in the injured human spinal cord detected with diffusion and magnetization transfer MRI
NeuroImage
(2011) - et al.
Cervical spinal cord injection of epidural corticosteroids; comprehensive longitudinal study including multiparametric MRI
Pain
(2012) - et al.
Orientation entropy analysis of diffusion tensor in healthy and myelopathic spinal cord
NeuroImage
(2011)
Activation of the opioidergic descending pain control system underlies placebo analgesia
Neuron
Measurement and characterization of the human spinal cord SEEP response using event-related spinal fMRI
Magn. Reson. Imaging
Single, slice-specific z-shim gradient pulses improve T2*-weighted imaging of the spinal cord
NeuroImage
Combined T2*-weighted measurements of the human brain and cervical spinal cord with a dynamic shim update
NeuroImage
GABA and central neuropathic pain following spinal cord injury
Neuropharmacology
Spinal cord
Curr. Biol.
Rapid semi-automatic segmentation of the spinal cord from magnetic resonance images: application in multiple sclerosis
NeuroImage
Assessment of physiological noise modelling methods for functional imaging of the spinal cord
NeuroImage
Correlation of functional activation in the rat spinal cord with neuronal activation detected by immunohistochemistry
NeuroImage
Comparison of functional activity in the rat cervical spinal cord during alpha-chloralose and halothane anesthesia
NeuroImage
Applying functional MRI to the spinal cord and brainstem
Magn. Reson. Imaging
Spinal-cord MRI in multiple sclerosis
Lancet Neurol.
Simultaneous functional magnetic resonance imaging in the rat spinal cord and brain
Exp. Neurol.
Functional magnetic resonance imaging within the rat spinal cord following peripheral nerve injury
NeuroImage
Functional MRI involving painful stimulation of the ankle and the effect of physiotherapy joint mobilization
Magn. Reson. Imaging
Diffusion tensor imaging reveals regional differences in the cervical spinal cord in amyotrophic lateral sclerosis
NeuroImage
Spatial and temporal aspects of spinal cord and brainstem activation in the formalin pain model
Prog. Neurobiol.
Functional activity mapping of the rat spinal cord during formalin-induced noxious stimulation
Neuroscience
MRI of spinal cord in multiple sclerosis
J. Neuroimaging
Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI
Neurology
In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study
Brain
Associations between cervical cord gray matter damage and disability in patients with multiple sclerosis
Arch. Neurol.
Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis
Magn. Reson. Med.
A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients
J. Neurol. Neurosurg. Psychiatry.
Primary progressive multiple sclerosis: tactile-associated functional MR activity in the cervical spinal cord
Radiology
Tactile-associated fMRI recruitment of the cervical cord in healthy subjects
Hum. Brain Mapp.
Preoperative magnetic resonance imaging is associated with baseline neurological status and can predict postoperative recovery in patients with cervical spondylotic myelopathy
Spine (Phila Pa 1976)
Functional MR imaging of the cervical spinal cord by use of median nerve stimulation and fist clenching
AJNR Am. J. Neuroradiol.
The basis of anisotropic water diffusion in the nervous system — a technical review
NMR Biomed.
A diffusion tensor MRI study of cervical cord damage in benign and secondary progressive multiple sclerosis patients
J. Neurol. Neurosurg. Psychiatry.
Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis
J. Neurol. Neurosurg. Psychiatry
Stimulus site and modality dependence of functional activity within the human spinal cord
J. Neurosci.
Toward accurate diagnosis of white matter pathology using diffusion tensor imaging
Magn. Reson. Med.
Axonal injury detected by in vivo diffusion tensor imaging correlates with neurological disability in a mouse model of multiple sclerosis
NMR Biomed.
Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord: a quantitative pixelwise analysis
J. Neurosci.
Diffusion tensor imaging and fibre tracking in cervical spondylotic myelopathy
Eur. Radiol.
Somatotopy of spinal nociceptive processing
J. Comp. Neurol.
Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study
Mult. Scler.
Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis
Brain
Spinal cord repair in MS: does mitochondrial metabolism play a role?
Neurology
Cited by (159)
Sensitivity and specificity of CEST and NOE MRI in injured spinal cord in monkeys
2021, NeuroImage: Clinical