Validating Quantitative MRI for the Study of Brain Microstructure

A direct link between tissue microstructure and its magnetic properties need to be established. Although ex vivo tissue in combination with histology is helpful in specific contexts (e.g. detection of amyloid plaques in Alzheimer’s in small tissue speciments) a more general use requires adaptation to high field and characterization of the fixation process per se.

We performed whole brain MRI of ex vivo samples, and found that the dielectric properties of the fixative deteriorated B1+ homogeneity at 9.4T[1]. Alternative fixative agents with improved properties were developed [2]. Interestingly, quantitative MRI was helpful to characterize the fixation process, and could serve as a marker to assure reproducible results in future validation studies.

The quality of ex vivo MRI at 3T using a conventional fixative was superior to 9.4T owing to the dielectric properties of the agent [1]. Improvements could be achieved through the use of additives and more in vivo like dielectric properties (below).

Depth dependence of R2*-kinetics during immersion fixation with different fixatives. The spatial location of different tissue depths is shown in a sagittal slice through the pig brain hemisphere (A) with corresponding curves fitted to the experimental data (B). At increasing depths, maximum R2* is reached at later timepoints, indicating the turning point when autolysis is stopped by the incoming fixative. For each tissue depth, we determined the square-root-of the time, t=DMAX*24 [hours] at which maximum R2* was reached. Plotting these two parameters yielded the Medawar coefficient K, depth=K√t , characterizing the fixation process.


Hagberg GE., Shiozawa T, Mirkes C, Engelmann J, Bause J, Hirt B, Scheffler K.:
MRI of whole brain formalin-fixed samples at 9.4T: influence of the fixation agent and its dielectric properties on image quality.
Proc Intl Soc Mag Reson Med. 2018;26:3310.
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