Abstract

Magnetic resonance imaging (MRI) is the most important paraclinical tool for assessing drug response in multiple sclerosis (MS) clinical trials. As such, MRI has also been widely used in preclinical research to investigate drug efficacy and pathogenic aspects in MS animal models. Keeping track of all published preclinical imaging studies, and possible new therapeutic approaches, has become difficult considering the abundance of studies. Moreover, comparisons between studies are hampered by methodological differences, especially since small differences in an MRI protocol can lead to large differences in tissue contrast. We therefore provide a comprehensive qualitative overview of preclinical MRI studies in the field of neuroinflammatory and demyelinating diseases, aiming to summarize experimental setup, MRI methodology, and risk of bias. We also provide estimates of the effects of tested therapeutic interventions by a meta-analysis. Finally, to improve the standardization of preclinical experiments, we propose guidelines on technical aspects of MRI and reporting that can serve as a framework for future preclinical studies using MRI in MS animal models. By implementing these guidelines, clinical translation of findings will be facilitated, and could possibly reduce experimental animal numbers.

Highlights

  • A growing number of large cooperatives, including the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Human Connectome Project (HPC) (Petersen et al, 2010; Van Essen et al, 2013) aim to standardize reporting on neuroimaging in humans

  • Through a meta-analysis, we investigated the efficacy of assessed therapeutic approaches using Magnetic resonance imaging (MRI) outcome measures and histological measures of disease activity in multiple sclerosis (MS) animal models

  • A search string for MS animal models and MRI was used in conjunction with an animal filter

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Summary

Introduction

A growing number of large cooperatives, including the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Human Connectome Project (HPC) (Petersen et al, 2010; Van Essen et al, 2013) aim to standardize reporting on neuroimaging in humans. Whereas standardized reporting on neuroimaging in clinical research — including the use of magnetic resonance imaging (MRI) as a fundamental tool in diagnosis and monitoring of multiple sclerosis (MS) — has received much attention, no such attempts have been made in preclinical neuroimaging research. This gap is surprising since MRI is widely used in preclinical research to screen for drug efficacy and to investigate pathogenic aspects in animal models, especially in MS animal models, in which both inflammatory and demyelinating pathology are readily detectable using MRI. Keeping track of the abundance of preclinical MS neuroimaging studies so far published has proven difficult

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