A compact 0.5 T MR elastography device and its application for studying viscoelasticity changes in biological tissues during progressive formalin fixation

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The rheological behavior of biological tissues is sensitively linked to the hierarchy of underlying structures 1. Scale‐invariant properties of rheological constants of cells or tissues can provide insight into the organization of structural elements smaller than the resolution limits of the measurement system 2. On the microscale, rheological constants can be measured by various methods such as cell‐deformation‐based experiments 5 or scanning‐force microscopy 8. Macrorheological methods include oscillatory shear stress rheology 10, dynamic shear tests 11, stress‐relaxation measurements 13, tensile tests 14, and macroindentation 15. Most rheological methods are surface‐based, that is, the mechanical stress is locally applied and the resulting tissue strain is measured at the surface. Dynamic elastography, such as magnetic resonance elastography (MRE) 16, induces and measures shear waves within the bulky tissue—in vivo for diagnostic applications 17 and ex vivo for investigating the basic rheological behavior of soft tissues 10. In general, measurement of intrinsic material properties inside a tissue volume is less susceptible to the geometry, texture, and composition of the sample surface. Several studies have confirmed that MRE of macroscopic samples varies less than surface‐based mechanical tests 18, especially when applied to soft biological tissues 10. This high consistency of MRE raises the prospect of an MRE‐based mechanical test device suitable for use in a wide range of venues from tissue engineering labs to operating rooms. However, today most MRE systems require helium‐cooled superconducting magnets, which limit the dissemination of MRE as a stand‐alone modality for rheological tests.
To establish MRE as a rheometry device dedicated to small biological samples we here present an MRE technique integrated into a 0.5 T‐permanent magnet MRI system. Other than recently reported by Ipek‐Ugay et al. 21, the new compact tabletop MRE features 1) a piezoelectric actuator mounted on the cylindrical sample holder, 2) an integrated high‐power amplifier used for both generating magnetic field gradients and driving the mechanical actuator, and 3) inline cylinder wavefield processing based on Bessel functions 22. Overall, these features allow researchers to operate the device in a widely automated fashion for multifrequency mechanical tests of small cylindrical tissue samples.
The performance of the new compact MRE device is demonstrated in specimens of liver and brain tissues by studying the effect of formalin fixation on mechanical tissue properties. Fixation effects on tissue structures are highly relevant in pathology and transplantation medicine 24 and have never been addressed using the springpot model, which is the most basic two‐parameter powerlaw in rheology and predicts a linear increase of both storage and loss modulus on logarithmic scales 4. We employed this model to analyze rheological properties of soft tissues using mechanical constants frequently reported in MRE studies 10.

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