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Monitoring diffuse injury during disease progression in experimental autoimmune encephalomyelitis with on resonance variable delay multiple pulse (onVDMP) CEST MRI.

ABSTRACT: Multiple sclerosis (MS) is an autoimmune disorder that targets myelin proteins and results in extensive damage in the central nervous system in the form of focal lesions as well as diffuse molecular changes. Lesions are currently detected using T1-weighted, T2-weighted, and gadolinium-enhanced magnetic resonance imaging (MRI); however, monitoring such lesions has been shown to be a poor predictor of disease progression. Chemical exchange saturation transfer (CEST) MRI is sensitive to many of the biomolecules in the central nervous system altered in MS that cannot be detected using conventional MRI. We monitored disease progression in an experimental autoimmune encephalomyelitis (EAE) model of MS using on resonance variable delay multiple pulse (onVDMP) CEST MRI. Alterations in onVDMP signal were observed in regions responsible for hindlimb function throughout the central nervous system. Histological analysis revealed glial activation in areas highlighted in onVDMP CEST MRI. onVDMP signal changes in the 3rd ventricle preceded paralysis onset that could not be observed with conventional MRI techniques. Hence, the onVDMP CEST MRI signal has potential as a novel imaging biomarker and predictor of disease progression in MS.

SUBMITTER: Thomas AM

PROVIDER: S-EPMC7767058 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Monitoring diffuse injury during disease progression in experimental autoimmune encephalomyelitis with on resonance variable delay multiple pulse (onVDMP) CEST MRI.

Thomas Aline M AM Xu Jiadi J Calabresi Peter A PA van Zijl Peter C M PCM Bulte Jeff W M JWM

NeuroImage 20191009

Multiple sclerosis (MS) is an autoimmune disorder that targets myelin proteins and results in extensive damage in the central nervous system in the form of focal lesions as well as diffuse molecular changes. Lesions are currently detected using T1-weighted, T2-weighted, and gadolinium-enhanced magnetic resonance imaging (MRI); however, monitoring such lesions has been shown to be a poor predictor of disease progression. Chemical exchange saturation transfer (CEST) MRI is sensitive to many of the ...[more]

PMID: 31605825

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Project description:BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2?months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.

Dataset Information

Monitoring diffuse injury during disease progression in experimental autoimmune encephalomyelitis with on resonance variable delay multiple pulse (onVDMP) CEST MRI.

Publications

Monitoring diffuse injury during disease progression in experimental autoimmune encephalomyelitis with on resonance variable delay multiple pulse (onVDMP) CEST MRI.

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