Development and validation of a constitutive growth model for brain tissue characterising brain alterations in space and time

大脑作为中枢神经系统的一部分，可能是最复杂的生物系统，它经历了重大的变化，特别是在其生长阶段。由于这些复杂性，无论是在宏观和微观层面上，以及相关的困难，在实验取样，有不足的实验研究。此外，对脑组织进行的与年龄相关的机械研究也是非常罕见的。然而，为了更好地了解大脑在生长过程中的机械特性和功能，并能够开发和验证数值模型，这样的实验是必不可少的。这种模型在预测准确性方面的性能特别取决于所识别的材料参数的质量。本研究项目的目标是开发和验证一种表征哺乳动物大脑在空间和时间上的改变的脑组织组成性生长模型。这一目标将通过实验、建模和模拟的密切相互作用分四步实现。实验将在猪脑组织上进行，显示出与人脑相似的微观结构和机械特性。建模的一个基本要求是方法开发（I），以进行适当的组织水平实验。由于灰质和白色组织将单独取样，因此组织标本相对较小。这意味着，在这个项目中计划的轴向，双轴向和三轴向实验，显微镜下的微机械测量设置必须开发，构建和验证。这些测量将使我们能够准确地测量脑组织的轴向、双轴向和三轴向行为（II）。为了研究神经发育对机械性能的影响，将在不同年龄收集大脑样本。在第三步中，将通过免疫组织学研究确定大脑的微观结构以及宏观几何形状（III）。由此产生的细胞密度、髓鞘含量和组织微观结构将直接为模型开发和验证提供信息（IV）。

The brain, as a part of the central nervous system is probably the most complex biological system, which undergoes significant changes, especially during its growth phase. Because of these complexities, both, at the macroscopic and microscopic level, and the associated difficulties in experimental sampling, there are insufficient experimental investigations. In addition, age-related, mechanical investigations on brain tissue, which were also carried out spatially resolved, are extremely rare. However, such experiments are essential in order to better understand the mechanical properties and functions of the brain during growth and to be able to develop and validate numerical models. The performance of such models in terms of predictive accuracy depends particularly on the quality of the identified material parameters.The objective of this research project is the development and validation of a constitutive growth model for brain tissue that characterises alterations of the mammalian brain both, in space and time. This goal will be achieved in four steps through a close interplay of experiment, modelling, and simulation. Experiments will be performed on porcine brain tissue, displaying similar microstructural and mechanical properties as the human brain. An essential requirement for the modelling is the method development (I) to perform appropriate tissue-level experiments. Since grey and white matter tissue will be sampled individually, the tissue specimens are relatively small. This implies that for the axial, biaxial, and triaxial experiments planned within this project, micromechanical measurement setups under a microscope have to be developed, constructed, and verified. These measurements will allow us to accurately characterise the axial, biaxial, and triaxial behaviour of brain tissue (II). To examine the influence of neurodevelopment on the mechanical properties, brain samples will be collected at different ages. In a third step, the microstructure as well as the macroscopic geometry of the brain will be determined by means of immunohistological investigations (III). The resulting cell density, myelin content, and tissue microstructure will directly inform the model development and validation (IV).