Mijailovic Aleksandar S, Galarza Sualyneth, Raayai-Ardakani Shabnam, Birch Nathan P, Schiffman Jessica D, Crosby Alfred J, Cohen Tal, Peyton Shelly R, Van Vliet Krystyn J
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Chemical Engineering, University of Massachusetts-Amherst, Amherst, MA, 01003, USA.
J Mech Behav Biomed Mater. 2021 Feb;114:104168. doi: 10.1016/j.jmbbm.2020.104168. Epub 2020 Oct 26.
Changes in the elastic properties of brain tissue have been correlated with injury, cancers, and neurodegenerative diseases. However, discrepancies in the reported elastic moduli of brain tissue are persistent, and spatial inhomogeneities complicate the interpretation of macroscale measurements such as rheology. Here we introduce needle induced cavitation rheology (NICR) and volume-controlled cavity expansion (VCCE) as facile methods to measure the apparent Young's modulus E of minimally manipulated brain tissue, at specific tissue locations and with sub-millimeter spatial resolution. For different porcine brain regions and sections analyzed by NICR, we found E to be 3.7 ± 0.7 kPa and 4.8 ± 1.0 kPa for gray matter, and white matter, respectively. For different porcine brain regions and sections analyzed by VCCE, we found E was 0.76 ± 0.02 kPa for gray matter and 0.92 ± 0.01 kPa for white matter. Measurements from VCCE were more similar to those obtained from macroscale shear rheology (0.75 ± 0.06 kPa) and from instrumented microindentation of white matter (0.97 ± 0.40 kPa) and gray matter (0.86 ± 0.20 kPa). We attributed the higher stiffness reported from NICR to that method's assumption of a cavitation instability due to a neo-Hookean constitutive response, which does not capture the strain-stiffening behavior of brain tissue under large strains, and therefore did not provide appropriate measurements. We demonstrate via both analytical modeling of a spherical cavity and finite element modeling of a needle geometry, that this strain stiffening may prevent a cavitation instability. VCCE measurements take this stiffening behavior into account by employing an incompressible one-term Ogden model to find the nonlinear elastic properties of the tissue. Overall, VCCE afforded rapid and facile measurement of nonlinear mechanical properties of intact, healthy mammalian brain tissue, enabling quantitative comparison among brain tissue regions and also between species. Finally, accurate estimation of elastic properties for this strain stiffening tissue requires methods that include appropriate constitutive models of the brain tissue response, which here are represented by inclusion of the Ogden model in VCCE.
脑组织弹性特性的变化已与损伤、癌症和神经退行性疾病相关联。然而，报道的脑组织弹性模量存在差异，且空间不均匀性使诸如流变学等宏观测量的解释变得复杂。在此，我们引入针诱导空化流变学（NICR）和体积控制腔扩张（VCCE），作为在特定组织位置以亚毫米空间分辨率测量最少受操纵脑组织的表观杨氏模量E的简便方法。对于通过NICR分析的不同猪脑区域和切片，我们发现灰质和白质的E分别为3.7±0.7 kPa和4.8±1.0 kPa。对于通过VCCE分析的不同猪脑区域和切片，我们发现灰质的E为0.76±0.02 kPa，白质的E为0.92±0.01 kPa。VCCE的测量结果与宏观剪切流变学（0.75±0.06 kPa）以及白质（0.97±0.40 kPa）和灰质（0.86±0.20 kPa）的仪器化微压痕测量结果更为相似。我们将NICR报道的较高刚度归因于该方法基于新胡克本构响应假设的空化不稳定性，该假设未捕捉到大应变下脑组织的应变强化行为，因此未提供合适的测量结果。我们通过球形腔分析建模和针几何形状的有限元建模均证明，这种应变强化可能会阻止空化不稳定性。VCCE测量通过采用不可压缩的单参数奥格登模型来考虑这种强化行为，以找到组织的非线性弹性特性。总体而言，VCCE能够快速简便地测量完整健康哺乳动物脑组织的非线性力学特性，实现脑组织区域之间以及物种之间的定量比较。最后，对于这种应变强化组织的弹性特性进行准确估计需要采用包含脑组织响应适当本构模型的方法，在此通过在VCCE中纳入奥格登模型来体现。
