Elucidating sources of contrast in quantitative brain MRI  Short lay paragraph

Magnetic Resonance Imaging (MRI) is a type of scan that uses strong magnetic fields and radio waves to produce detailed images of the inside of the body. It is routinely applied to image the human brain.

The characterisation of one particular type of tissue in the brain, the white matter, is important for diagnosing disease (such as Multiple Sclerosis).

While MRI is very good in depicting lesions in the brain (referred to as "qualitative assessment"), clinicians are now interested in quantitative information, such as length or volume of brain cells, to provide a more refined diagnosis. But the microstructure of white matter is complex, which makes it challenging to interpret the MRI images in an accurate and quantitative manner. 

Plan of work and impact of our studies

We plan to study the relationship between a specific imaging contrast and the orientation of white matter bundles using the orientation of the main magnetic field provided by the MRI system. We particularly aim to investigate why this contrast is more anisotropic (that is, it displays different properties when measured in different directions) in one compartment (i.e. myelin – an insulating layer around nerves) than in another compartment of brain tissue (i.e. inside the axons, or nerve fibres).

We will use a mouse model of demyelination (i.e. where the insulating layer around the nerves has been reduced or removed) to study this in more detail. We will compare our in vivo imaging findings to ex vivo MR images (i.e. where the brain has been excised and chemically preserved), and ultimately to histology (the microscopic study of cells and tissues), increasing the resolution of the imaging technique at each step. 

Three Rs

Replacement

Given the difficulties in interpreting MRI images, we need to study the relationship between imaging findings and anatomical features in an animal model, such as the mouse, where we can easily compare our MRI findings with histology. This would not be possible in humans. Histology can then be related to the MRI images in a novel way by spanning a range from nanometer to millimeter.

Reduction

This is a defined project on two relatively small groups of animals. One will be fed with a cuprizone-supplemented diet for a short period of time to prevent permanent brain damage and to minimise the occurrence of clinical symptoms. The other group will serve as a control. A non-invasive imaging technique will be used in vivo to investigate the research question.

Refinement

The proposed experimental design (i.e. manipulation with the cuprizone model) together with the cutting-edge MRI and electron-microscopy technologies used in the study will generate extremely valuable multimodal datasets of the same organ that are novel.

The combination of imaging approaches will provide complementary information to gain a deeper understanding of the biophysical origins of differences in the estimated MRI parameters. They will ultimately enhance the interpretation of quantitative MRI, which can be translated back to patients in the clinical setting.