Matching ex vivo MRI With Iron Histology: Pearls and Pitfalls

Iron levels in the brain can be estimated using newly developed specific magnetic resonance imaging (MRI) sequences. This technique has several applications, especially in neurodegenerative disorders like Alzheimer's disease or Parkinson's disease. Coupling ex vivo MRI with histology allows neuroscientists to better understand what they see in the images. Iron is one of the most extensively studied elements, both by MRI and using histological or physical techniques. Researchers were initially only able to make visual comparisons between MRI images and different types of iron staining, but the emergence of specific MRI sequences like R2^* or quantitative susceptibility mapping meant that quantification became possible, requiring correlations with physical techniques. Today, with advances in MRI and image post-processing, it is possible to look for MRI/histology correlations by matching the two sorts of images. For the result to be acceptable, the choice of methodology is crucial, as there are hidden pitfalls every step of the way. In order to review the advantages and limitations of ex vivo MRI correlation with iron-based histology, we reviewed all the relevant articles dealing with the topic in humans. We provide separate assessments of qualitative and quantitative studies, and after summarizing the significant results, we emphasize all the pitfalls that may be encountered.