Long-Term In Vivo Imaging of Viscoelastic Properties of the Mouse Brain after Controlled Cortical Impact

Abstract

Traumatic brain injury (TBI) presents a variety of causes and symptoms, thus making the development of reliable diagnostic methods and therapeutic treatments challenging. Magnetic resonance elastography (MRE) is a technique that allows for a noninvasive assessment of the mechanical properties of soft biological tissue, such as tissue stiffness, storage modulus, and loss modulus. Importantly, by quantifying the changes in the stiffness of tissue that is often associated with disease, MRE is able to detect tissue pathologies at early stages. Recent improvements in instrumentation have allowed for the investigation of small samples with microscopic resolution (μMRE). We hypothesize that μMRE can sensitively detect variations in micromechanical properties in the brain caused by the compressive and shearing forces sustained during TBI. To test this hypothesis, we randomized 13 C57BL mice to receive a controlled cortical impact at a 0.5 mm or 0.75 mm depth, with both sham and naïve mice as controls. Our objective was to propagate mechanical shear waves throughout the brain for in vivo TBI μMRE imaging. The mechanical properties of the injured brain tissue were determined at days 0, 1, 7, and 28 post-injury. For both groups, we observed a significant drop in the stiffness of the impacted region immediately following the injury; the 0.75 mm animals experienced increased tissue softness that lasted longer than that for the 0.5 mm group. Although the shear stiffness, storage modulus, and loss modulus parameters all followed the same trend, the tissue stiffness yielded the most statistically significant results. Overall, this article introduces a transformative technique for mechanically mapping the brain and detecting brain diseases and injury.

Intracranial biomechanics following cortical contusion in live rats

“…In the region of impact, the researchers observed decreases in the stiffness (by 24% or 29%, depending on whether the injury was 0.5 or 0.75 mm deep), storage modulus, and loss modulus at 6 hours, with gradual normalization by 7-28 days. 4 Their numeric values are not directly comparable to our data because their dynamic analysis involved using an oscillatory force. However, the time scale of changes is similar.…”

Tissue structure and inflammatory processes shape viscoelastic properties of the mouse brain

“…In conclusion, these results complement reports of viscoelastic changes detected by MRE in animal models of Alzheimer's disease , Parkinson's disease and stroke , in which neurodegeneration is a principle cause of the MRE alterations. In other models such as demyelination and brain injury , effects on oligodendrocytes or astrocytes are prominent. Nevertheless, all of these models share an inflammatory component, thus understanding the relationship between inflammatory processes and viscoelastic changes remains an important objective, with wide implications.…”

Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury

“…By using a dental drill, a 5-mm craniotomy was performed over the left parietal cortex between the bregma and lambda. The bone flap was removed and injury was made using a Precision Systems and Instrumentation TBI-0310 (Fairfax Station, VA) that administered a 1 mm cortical compression (3 mm impactor diameter, 2.5 m/s velocity, 150  ms duration dwell time) [13]. Sham animals were anesthetized but no CCI.…”