Considerations and recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 3—Ex vivo imaging: Data processing, comparisons with microscopy, and tractography

Abstract

Diffusion MRI; Ex vivo; Tractography

Ressonància magnètica de difusió; Ex vivo; Tractografia

Resonancia magnética de difusión; Ex vivo; Tractografía

Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high SNR images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work concludes a three-part series of recommendations and considerations for preclinical dMRI. Herein, we describe best practices for dMRI of ex vivo tissue, with a focus on image pre-processing, data processing, and comparisons with microscopy. In each section, we attempt to provide guidelines and recommendations but also highlight areas for which no guidelines exist (and why), and where future work should lie. We end by providing guidelines on code sharing and data sharing and point toward open-source software and databases specific to small animal and ex vivo imaging.

The authors acknowledge financial support from: the National Institutes of Health (K01EB032898, R01A G057991, R01NS125020, R01EB017230, R01EB019980, R01EB031954, R01CA160620, R01NS109090), the National Institute of Biomedical Imaging and Bioengineering (R01EB031765, R56EB031765), the National Institute on Drug Abuse (P30DA048742), the Secretary of Universities and Research (Government of Catalonia) Beatriu de Pinós postdoctoral fellowship (2020 BP 00117), “la Caixa” Foundation Junior Leader fellowship (LCF/BQ/PR22/11920010), the Research Foundation Flanders (FWO: 12M3119N), the Belgian Science Policy Prodex (Grant ISLRA 2009–1062), the μNEURO Research Center of Excellence of the University of Antwerp, the Institutional research chair in Neuroinformatics (Sherbrooke, Canada), the NSERC Discovery Grant, the European Research Council Consolidator grant (101044180), the Canada Research Chair in Quantitative Magnetic Resonance Imaging [950-230815], the Canadian Institute of Health Research [CIHR FDN-143263], the Canada Foundation for Innovation [32454, 34824], the Fonds de Recherche du Québec - Santé [322736], the Natural Sciences and Engineering Research Council of Canada [RGPIN-2019-07244], the Canada First Research Excellence Fund (IVADO and TransMedTech), the Courtois NeuroMod project, the Quebec BioImaging Network [5886, 35450], the Mila - Tech Transfer Funding Program and the Swiss National Science Foundation (Eccellenza Fellowship PCEFP2_194260), the Wellcome Trust (202788/Z/16/A, 203139/Z/16/Z and 203139/A/16/Z).