MR Elastography shows Increased Stiffness of Brain Tissue with Applied Pre-Strain

Introduction:: Traumatic brain injury (TBI) is a neuropathology caused by blunt or blast impact to the skull and brain, which affects approximately 70 million people each year¹. Despite extensive research, many questions regarding the damage mechanisms involved with TBI remain unanswered, and based on the complex injury mechanisms, limited treatment options are available. Computational models, which play a fundamental role in TBI analysis, require physiologically relevant mechanical properties as input parameters. Using magnetic resonance elastography (MRE)² we can determine properties such as the stiffness and damping ratio, by phase-encoding mechanical waves as they propagate through the tissue of interest². Traditional in vivo MRE is limited to characterization of linear viscoelastic properties of brain tissue³ with induced strains on the order of approximately 10^-4 to 10^-3. However, tissue damage from TBI involves significant strain beyond its linear elastic range which is associated with permanent damage and disruption of typical brain function⁴. Experiments analyzing mechanical properties with greater strains and strain rates are required for accurately modeling injury events associated with TBI, though they are unable to be safely performed in vivo. Here we implement a method for performing MRE with increased levels of applied compressive pre-strain in a phantom system with ex vivo bovine brain tissue to develop a better understanding of tissue properties for TBI modeling.


Materials and Methods:: Fresh calf bovine brain samples were purchased through a local butcher and cut to approximately 8 x 8 cm² sections using a square metal slicer. These samples were then encapsulated in a 0.65 wt.% agarose phantom and placed at 4°C overnight to gel. Agar was used as an encapsulation material to assist with wave penetration and minimize boundary conditions during mechanical property estimation. MRE data was collected on room temperature tissue-agar phantoms using a 60 slice EPI sequence with 2.5 mm³ isotropic resolution on a Siemens 3T Prisma MRI scanner and a 20-channel head coil. Vibrations were generated at 75 Hz using a commercial driver system (Resoundant, Rochester, MN). Pre-strain was applied through incremental axial compression using a custom-made, MR-compatible device (Figure 1), which applies compression by turning a knob to lower a plate onto the sample. Each 360° turn lowered the compression plate by 0.98 mm, which was used with the original phantom height to calculate compressive strain. Viscoelastic property maps of stiffness were estimated from MRE displacement images using a nonlinear inversion algorithm (NLI)⁵ at each compression state.


Results, Conclusions, and Discussions:: Following baseline, five compression states were achieved with strain values of 0.70%, 1.40%, 2.09%, 3.49%, and 4.88%. Regions of interest corresponding to the brainstem and cerebellum were segmented using MRE magnitude images, and stiffness values were averaged for each region. Figure 2A displays stiffness maps across each of the six states of compression where a general stiffness increase is observed across both regions (outlined in Figure 2B). Maps illustrating the ratio of stiffness with baseline at different compressions are shown in Figure 2C, where values of zero show no change and values of one indicate a 100% increase or doubling in stiffness. Figure 2D plots the relationship between applied strain and apparent stiffness for both regions of interest. As the phantoms were compressed the apparent stiffness of the brainstem increased by 30.7% while the cerebellum stiffness increased by 24.0% (Figure 2D).



MRE was used to observe the relationship between applied pre-strain and viscoelastic properties through incremental compression. The novel compression device designed for this analysis achieved five stages of compression ranging from baseline (0%) to our highest applied strain value of approximately 5%. Our preliminary results show that as compressive pre-strain is applied the stiffness of bovine brain tissue increases across regions with a larger increase in stiffness observed in the brainstem as compared to the cerebellum. Future work seeks to expand on this technique to characterize the nonlinear viscoelastic properties of bovine and human cadaveric brain tissue at expected TBI-inducing strain levels.


Acknowledgements (Optional): : U01-NS112120

References (Optional): : [1] Wiles, M.D., J Anesth, 2022; [2] Bayly, P.V., Ann Biomed Eng, 2021; [3] Upadhyay, K., J R Soc Interface, 2022; [4] Boulet, T., J Neurosci Methods, 2011; [5] McGarry, M.D.J., Med Phys, 2012.