Research On Mechanical Characterization Of Brain Tissue Using Micro/nanoindentation Testing

Brain tissue is not only one of the most extraordinary sophisticated but also the most sensitive and vulnerable parts of the human anatomy.External loading will induce stress/strain in the brain tissue,and may lead to temporary or permanent brain damage and dysfunction when the stress/strain range exceeds the limiting value.In China,traumatic brain injury(TBI)caused by external impact is an important cause of death,and has become a severe problem of public health.On the other hand,mechanical properties of brain have noticeable effect on brain development and disorders(such as tumor growth,hydrocephalus,etc.).Accordingly,the reaserch of brain menchanical behavior could provide important theoretical foundations in the field of basic life science,such as neurodevelopment and brain injury,but be of guiding significance to the development of more effective assessment,prevention and therapeutics.Compared with most macroscale mechanical testing techniques,such as tention,compression,and shear,the indentation testing,as a non/micro-invasive technique,could achieve region-specific mapping of materials inhomogeneity without restriction of tissue morphology,and therefore is considered as an ideal method for mechanical characterization of biological tissue.However,compared with the traditional indentation technique based on engineering materials,biological indentation technique,especially in the field of soft biomaterials such as brain tissue,is still in its infancy in terms of testing methods and data analysis.In this thesis,based on the self-made instrument and aiming at the special mechanical parameters of brain tissue,a biological indentation testing system with the functions of electric field loading and macro-/micro-scale characterization switching is developed.Based on the traditional indentation testing techniques and constitutive characteristics of(soft)biological materials,the key techniques and methods in the process of biological indentation testing are summarized.By means of a series of brain indentation tests,the differences of brain mechanical properties under different conditions and different tissue regions are evaluated,and the relationship betweent brain mechanical properties and underlying microstructural composition is analyzed.The main research work of this thesis is as follows:(1)The research status of mechanical characterization of brain tissue and the development of related testing technology are reviewed,as well as the nanoindentation thory and the constitutive characteristics of brain tissue are summarized.The key techniques and methods of biological indentation testing in terms of tip selection,parameter optimization,and data processing are concluded.Further,the module composition and mechanical structure of the biological indentation system used in this thesis is introduced,and the driving and detecting elements in the testing system are calibrated.The reliability and accuracy of data acquisition of biological indentation system are tested based on hydrogels indentation testing.(2)Macro-indentaion tests of brain tissue are conducted.(1)The effects of different hemispheres on the mechanical properties of brain tissue are studied.The results show that there is no significant difference in mechanical properties between left and right brain hemispheres.(2)The effects of different regions on the mechanical properties of brain tissue are investigated.The brain tissue is devided into three regions: anterior,middle,and posterior.By comparing different regional indentation results of brain tissue,the differences in the mechanical properties of brain tissue in different regions are found: the moludus of posterior region are lower,and of anterior region are higher.(3)The influences of different experimental parameters on brain mechanical properties are addressed.As a viscoelastic material,the properties of brain tissue depend on the strain rate by definition.However most efforts focus on the aspect of velocity in the field of brain indentation,rather than strain rate.By introducing the indentation strain rate as a reference,the effect of indentation strain rate on brain response that correlates with indenter diameters,depths of indentation and velocities is revealed.The mechanical behavior of brain tissue is found to be strain rate-dependent: with an increase strain rate,the brain tissue has higher shear modulus,and shows more viscous and responds more quickly.(3)The effect of electric fields on brain indentation response is investigated,and the mechanism is analyzed.Aiming at some therapies involving brain stimulation with electrical fields,such as deep brain stimulation(DBS),the effect of electric fields on brain tissue is assessed by using electric field loading module in biological indentation testing system.The brain tissue is found to be softened at a higher electric field level and less viscous,and substantially responds more quickly with an increase in electric field.Through resistance,thermal,and morphological analysis during testing,the relationship between brain mechanical behavior and electrical fields is analyzed: It is speculated that the oxidation–reduction(redox)reactions occurring at the tissue–electrode interface and/or the alteration in intrinsic molecular structure within brain tissue result in permanent changes in brain tissue biomechanics.(4)Mechanical characterization of brain tissue at different length scales.Here,multi-scale indentation-relaxation tests are performed using diffenrent length scale indenters(macro-and microscale)to address mechanical heterogeneity of brain tissue.This study reveals the multi-scale mechanical heterogeneity of brain tissue: the instantaneous modulus measured at the microscale are obviously larger than the value obtained at the macroscale.Additionally,the time-dependent response derived from experiments at a relatively smaller(?m)length scale turns to have a less time-spending decay and higher equilibrium shear modulus.The individual contributions of the microstructural components to the mechanical heterogeneity are discussed from the cell to the tissue level:The contribution of the internal white matter in the case of macro-indentation is more significant owing to the higher indentation depth.White matter contains more cell nuclei in cellular component as well as more lipids and proteoglycans in extracellular component than gray matter.Cells are the softest components of brain tissue,and therefore weak the brain strength.The proteoglycans can bind water molecules and will slowly drain during relaxation,which leads to more significant time-dependent behavior of brain tissue.