Diffusion-weighted MRI in neurodegenerative and psychiatric animal models: Experimental strategies and main outcomes

Preclinical MRI approaches constitute a key tool to study a wide variety of neurological and psychiatric illnesses, allowing a more direct investigation of the disorder substrate and, at the same time, the possibility of back-translating such findings to human subjects. However, the lack of consensus on the optimal experimental scheme used to acquire the data has led to relatively high heterogeneity in the choice of protocols, which can potentially impact the comparison between results obtained by different groups, even using the same animal model. This is especially true for diffusion-weighted MRI data, where certain experimental choices can impact not only on the accuracy and precision of the extracted biomarkers, but also on their biological meaning. With this in mind, we extensively examined preclinical imaging studies that used diffusion-weighted MRI to investigate neurodegenerative, neurodevelopmental and psychiatric disorders in rodent models. In this review, we discuss the main findings for each preclinical model, with a special focus on the analysis and comparison of the different acquisition strategies used across studies and their impact on the heterogeneity of the findings.SDS was supported by the European Research Council through a Marie Skłodowska-Curie Individual Fellowship (Grant #749506) and by the Generalitat Valenciana through a Subvencion a la Excelencia de Juniors Investigadores (SEJI/2019/038). AE was supported by La Caixa-Severo Ochoa predoctoral fellowship from Obra Social La Caixa. All authors also acknowledge financial support from the Spanish State Research Agency through the Severo Ochoa Program for Centres of Excellence in R&D (SEV- 2017-0723).Peer reviewe