Brain preservation technique could lead to unreliable autopsies

For the first time, scientists have conducted neutron scattering  experiments on brain tissue. They have found that formaldehyde preservation is not as reliable as initially thought, as it significantly affects the process of water diffusion.

These findings are the first stage in the Institut Laue-Langevin-based group’s research where neutrons are used to understand the movement of cellular water within brain tissue. Water movement forms the basis of diffusion magnetic resonance imaging (dMRI) which is used in analysis of several brain pathologies.

Lead research Dr Francesca Natali said: “This is the first evidence that water diffusion, a key process in the modelling and diagnosis of brain pathologies is significantly affected by common tissue sample preservation techniques.”

Cellular water is the major constituent of our bodies and its content varies in brain regions depending on their specific composition. As this water plays a key role in cell regulation, its distribution is an accurate indicator of cellular structure as it interacts with different tissue components such as membranes and nerve fibres.

dMRI and other imaging techniques rely on water diffusion as a contrast method to reveal and characterise various brain pathologies, such as ischaemia and tumours on the micron scale. But concerns over the impact of preservation processes used for imaging on the brain’s fundamental structural and compositional properties have reduced confidence in dMRI as an accurate technique.

To address these concerns, the researchers compared the behaviour of cellular water in ex vivo bovine tissue preserved using two common preservation techniques: chemical fixation with formaldehyde and cryopreservation. The samples were investigated using incoherent quasi-elastic neutrons scattering (QENS) experiments carried out on the high-resolution IN5 spectrometer at the ILL.

Neutrons are an ideal probe for investigating biological materials at the atomic scale because they  have an ability to ‘see’ the effects of biological processes on a scale 10,000 times smaller than dMRI. They also produce no damaging radiation effects and can accurately map any changes in the samples over time.

The researchers discovered that water movement was significantly reduced in the samples preserved with formaldehyde. This effect may be due to cross-links between proteins which trap free water and reduce its mobility.

“With this new understanding of the impacts of preservation techniques, the team’s neutron scattering can begin to investigate at the atomic scale the conditions that lead to these autoimmune diseases and any potential treatments,” Dr Francesca Natali told Laboratory News.