Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions

Bergers, Elisabeth; Bot, Joseph C.J.; Groot, C. J. A. De; Polman, C.H.; Nijeholt, Geert J. Lycklama à; Castelijns, Jonas A.; Valk, P. van der; Barkhof, Frederik

doi:10.1212/01.wnl.0000036566.00866.26

Cited by 137 publications

(94 citation statements)

References 18 publications

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“…A complicated pattern of change in diffusivities may occur due to axonal loss [147] or an increase in axonal diameter. This was supported by previous findings in post--mortem MS spinal cord studies which showed areas of T 2 WI hyperintensities [148]. For areas containing crossing fibers, abnormal changes to the FA, AD and RD must be carefully assessed as MS pathology in these areas can produce unexpected results such as an apparent increase in diffusion anisotropy [133].…”

Section: Figure 8 Assessment Of Optic Nerve Degeneration In Eae--micsupporting

confidence: 79%

Current Developments In Mri For Assessing Rodent Models of Multiple Sclerosis

et al. 2014

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MRI is a key radiological imaging technique that plays an important role in the diagnosis and characterization of heterogeneous multiple sclerosis (MS) lesions. Various MRI methodologies such as conventional T 1/T 2 contrast, contrast agent enhancement, diffusion-weighted imaging, magnetization transfer imaging and susceptibility weighted imaging have been developed to determine the severity of MS pathology, including demyelination/remyelination and brain connectivity impairment from axonal loss. The broad spectrum of MS pathology manifests in diverse patient MRI presentations and affects the accuracy of patient diagnosis. To study specific pathological aspects of the disease, rodent models such as experimental autoimmune encephalomyelitis, virus-induced and toxin-induced demyelination have been developed. This review aims to present key developments in MRI methodology for better characterization of rodent models of MS.

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Section: Figure 8 Assessment Of Optic Nerve Degeneration In Eae--micsupporting

confidence: 79%

Current Developments In Mri For Assessing Rodent Models of Multiple Sclerosis

et al. 2014

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“…22,41 Although the sensitivity of spinal cord MR imaging is high, the relation between MR imaging and clinical findings remains poor. As already demonstrated by several brain studies, MR imaging parameters (like T2, T1, but also magnetization transfer ratio) in the spine also correlate better with demyelination than with the axonal disease, [41][42][43] which is the most direct cause of disability in patients with MS.…”

Section: Discussionmentioning

confidence: 61%

Quantitative Cervical Spinal Cord 3T Proton MR Spectroscopy in Multiple Sclerosis

Marliani¹,

Clementi²,

Riccioli³

et al. 2009

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Brain proton MR spectroscopy ( 1 H-MR spectroscopy) is a useful technique for evaluating neuronal/axonal damage and demyelization in multiple sclerosis (MS). Because MS disability is frequently related to spinal cord lesions, potential markers for MS stage differentiation and severity would require in vivo quantification of spinal integrity. However, few spectroscopy studies have investigated cervical disease due to technical difficulties. The present study used 3T 1 H-MR spectroscopy to measure the main metabolites in cervical spinal cord plaques of a group in patients with relapsing-remitting MS (RRMS) and compared them with metabolite measurements in healthy volunteers.

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“…Such technologic advancements offer unprecedented resolution of micron-sized axons (12,16) in the living human brain. We hypothesized that MS lesions on high-gradient-diffusion MR images obtained by using a gradient strength of up to 300 mT/m would show decreased axon density and increased axon diameter, as has been shown in prior histopathologic studies (17)(18)(19). The purpose of this study was to evaluate the ability of high-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m to characterize axonal disease in lesions and normal-appearing white matter (NAWM) in patients …”

Section: Discussionmentioning

confidence: 97%

Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging

Huang¹,

Tobyne²,

Nummenmaa³

et al. 2016

Radiology

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).q RSNA, 2016 Purpose:To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods:In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing-remitting MS and six healthy control subjects underwent diffusion-weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intraaxonal, extra-axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results:MS lesions showed increased mean axon diameter (10.3 vs 7.9 mm in the genu, 10.4 vs 9.3 mm in the body, and 10.6 vs 8.2 mm in the splenium; P , .05) and decreased axon density ([0.48 vs 1.1] 3 10 10 /m 2 in the genu, [0.40 vs 0.70] 3 10 10 /m 2 in the body, and [0.35 vs 1.1] 3 10 10 /m 2 in the splenium; P , .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion:High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM.q RSNA, 2016

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Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions

Abstract: Marked axonal loss occurs in MS spinal cords, largely independent of the degree of signal abnormality on T2-weighted MRI.

Cited by 137 publications

References 18 publications

Current Developments In Mri For Assessing Rodent Models of Multiple Sclerosis

Current Developments In Mri For Assessing Rodent Models of Multiple Sclerosis

Quantitative Cervical Spinal Cord 3T Proton MR Spectroscopy in Multiple Sclerosis

Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging

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