Synopsis

Keywords: Neuroinflammation, Preclinical

Clinicians are curious about preclinical MRI and interested in the opportunities that preclinical models of neurodegenerative diseases grant in terms of manipulation and investigating therapeutic strategies. Here, we review the fundamental principles of preclinical neuroimaging that clinicians should be aware of prior to embarking on basic research experimentation.

Clinical Significance

Clinicians are curious about preclinical MRI and interested in the opportunities that preclinical models of neurodegenerative diseases grant in terms of manipulation and investigating therapeutic strategies. However, preclinical MRI is highly experimental, particularly at ultra high-fields where brain MR sequences and analysis methods must often be developed in-house. Here, we review the fundamental principles of preclinical neuroimaging that clinicians should be aware of prior to embarking on basic research experimentation.

Fundamental Principles

· The size of a mouse’s brain compared to a human brain – signal: to noise ratio is completely different and, therefore, more difficult with a mouse.

· Rodent brain anatomy is different to the human brain. Eg. Does the disease or neuronal circuitry that you are wanting to investigate exist in the rodent? If it does not, how reliable are your model and your potential preclinical findings?

· Mice need anaesthesia – must be maintained at a degree that allows regular breathing pattern avoiding irregularities, which will contribute to artefacts, particularly on diffusion tensor imaging (DTI MRI).

· Head positioning is everything – when it comes to shimming. If head is not positioned perfectly symmetrically, everything else is mostly a waste of time.

· Powerful (expensive) gradients! Sequences must be designed carefully!

· Use the RF pulse wisely in order not to overheat the subject or blow out the gradients!

· Preclinical scanners are open systems and experimental machines as opposed to routine clinical scanners

· Make your own surface coils and test them on the subject straight away – 31P!

· You can do brain surgery on the animal, suture them up and immediately place them in the scanner for imaging.

· Accurate Data analysis methods for rodent imaging are not as abundant or as accurate as in clinical neuroimaging – using human neuroimaging analysis methods does not work!

· We image at ultra high-field: 7 T, 9.4 T, 11.7 T +/- cryocoils, 14 T and 21 T

· The higher you go in strength of magnetic field, the more the problem with inhomogeneity issues and artefacts. Thus, sequence design and animal stability (breathing) are key.

· Transmit-receive coils (eg cryocoil) require expertise due to inhomogeneity issues.

· State of the art ultra high-field scanners do not come with MRI sequences developed for the mouse brain and must be developed and optimised by the MR physicist. Taking a 9.4 T brain MRI sequence for an 11.7 T will not work optimally! Taking a clinical MRI sequence will definitely not work!

· Preclinical MRI is able to do the manipulations and cutting-edge experimentation that clinical MRI cannot do. Preclinical findings can be advantageously translated to the clinic. Eg. Diagnostic cerebral malaria protocols.

· Ultra high-field magnets are notorious for quenching! Gas, electricity, water supplies must be diligently monitored and kept stable.

Acknowledgements

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References

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