Relating tissue properties of post-mortem brain to time from death using magnetic resonance elastography

Introduction:: The mechanical properties of brain tissue play an important role in the construction of computational models for simulating traumatic brain injury (TBI), which is a significant health care problem affecting over 2.5 million people in the United States annually. Mechanical testing, such as tissue indentation, has been performed on animal models and post-mortem human surrogates (PMHS) to characterize brain stiffness. Those techniques, however, require removal of the brain or portions of the skull, thereby altering the properties. Non-invasive techniques, such as magnetic resonance elastography (MRE), have been developed and are increasingly used to measure the tissue properties of the brain in vivo. MRE has shown differences in properties between neuroanatomical regions and sensitivity to aging, neurological disorders, and brain function [1, 2]. MRE incorporates mechanical wave propagation and motion-sensitive magnetic-field gradients to record the harmonic displacements of soft tissue in phase images, which are then used to estimate tissue properties. In biomechanical studies of TBI, experimental models in living subjects under high loading are not possible due to ethical concerns. Such experiments are therefore applied to PMHS, which can exhibit different properties from that of in vivo tissue. It is therefore important to understand the mechanical properties of PMHS brain tissue and how it evolves after death. In this study, we performed MRE on a cadaver head over the span of a month to investigate the change in tissue properties. These measurements can be used in combination with experimental data to build and validate computational models of TBI.


Materials and Methods:: A PMHS cadaver head was obtained within 48 hours of death through the State of Anatomy board, Baltimore, Maryland. The neck was sealed at extraction to preserve fluid in the intracranial cavity. The head was stored at 4⁰C in between scanning sessions to limit tissue degradation. Before scanning, it was removed from refrigeration to allow it time to reach room temperature. During the MRE experiment, the head was placed on a soft “pillow” driver attached to a pneumatic actuator system (Resoundant Inc., Rochester, MN, USA) that applied an excitation in the anterior-posterior (AP) direction (shown in Figure 1a). Using a single-shot echoplanar imaging (EPI) sequence [1], MRE displacement data were acquired for three separate scans at 30, 50, and 70 Hz, with 2.5 mm isotropic imaging resolution and whole-brain coverage (240 × 240 × 120 mm³). All imaging data were acquired on a Siemens 1.5 T Aera scanner with a 20-channel head/neck coil at 2, 7, 14, 21, and 30 days after death.

From the acquired images, brain tissue material properties were estimated using Nonlinear Inversion, a finite element-based optimization approach [3]. Considering brain tissue as heterogeneous and viscoelastic solids, the storage modulus, G′, and the loss modulus, G″, representing the elastic and viscous behavior of tissue, respectively, were estimated. Shear modulus represented by G* = G′ + iG″ was also calculated. Here, we focus on shear stiffness μ = 2|G*|²/(|G*| + G′) and damping ratio ξ = G″/2G′, which summarize the behavior of the materials.


Results, Conclusions, and Discussions:: For each frequency, the properties were estimated using the magnitude and phase images from MRE experiments (Shown in Figure 1b, c). Representative regional distributions of damping ratio and shear stiffness for 70Hz are shown in Figure 2. The estimated storage modulus and loss modulus were (6.8±2.8 kPa and 1.13±0.3 kPa) at day 2 and (8.3±6.0 kPa and 1.25±0.4kPa) at day 30, respectively. Both shear stiffness and damping ratio at day 2 were 7.0±3.0kPa and 0.1088±0.01. These values are higher than those found in healthy adults, possibly due to the subject being older (91 years old) and deterioration of tissue after death. An increase in tissue properties was found over time (Figure 3). More specifically, storage modulus and shear stiffness were increased by 23% and 24%, respectively, at day 30 compared to day 2. This suggests that the elastic behavior of brain tissue becomes stiffer over time in the cadaver head. In addition, an increase in damping ratio (29%) suggests that the relative viscous behavior is also increased in cadaver brain.

In conclusion, we investigated the change in tissue properties of the brain after death by using MRE on PMHS over a month. The results suggest that the brain tissue gets stiffer over time. In addition, our results showed that the increase in stiffness is more due to the increase in elastic properties of tissue than viscous properties. These changes likely occur due to the degradation of the tissue and should be considered when attempting to use PMHS to inform computational models of TBI.

Our study has some limitations. The results showed a global mean value of respective parameters over the entire brain. A regional comparison of tissue properties can provide us more insights on change in properties across different types of tissue in the brain. A comparative MRE study between cadaver head and the living human brain could also be performed to investigate the change in tissue properties in brain over time.


Acknowledgements (Optional): : This work was partially supported by NINDS grant U01-NS112120, the Department of Defense in the Center for Neuroscience and Regenerative Medicine, the intramural research program of the NIH and an NIH Bench-to-Bedside grant. The authors have no conflicts of interest to disclose. The opinions and assertions expressed herein are those of the author(s) and do not reflect the official policy or position of the Henry M. Jackson Foundation, the Uniformed Services University of the Health Sciences or the Department of Defense.


References (Optional): : 1. Hiscox et. al. 2016, Phys. Med. Biol. 61 R401.
2. Bayly et al. 2021 Ann Biomed Eng 49, 2677–2692.
3. M. McGarry et al., 2013 IEEE Trans. Med. Imaging, vol. 32, no. 10, pp. 1901–1909.