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Title

Correlating Microstructural Properties to Macroscopic Shear Mechanics to Improve the Understanding of Tissue Biomechanics

Creator

Cahoon, Stacey Marie

Date

2023

Description

Understanding tissue biomechanics is of interest for modeling organ injury from external loads, development of tissue surrogate materials, and...
Show moreUnderstanding tissue biomechanics is of interest for modeling organ injury from external loads, development of tissue surrogate materials, and creating new biomarkers for disease. Probing the response of soft tissue in shear can provide information on histopathology, provided a methodology exists that connects the macroscopic mechanical properties with cell-level properties. Two of the available methods to measure the macroscopic shear viscoelastic properties of soft tissue are oscillatory shear rheometry and ultrasound shear wave elastography (SWE). Due to its accuracy, rheometry is the gold standard, but it is destructive, requires excised homogeneous samples, and can only be applied ex-vivo. SWE is an emerging non-invasive imaging technique which requires validation, ostensibly by comparing with rheometry. Histology is the gold standard for providing morphological information on the cell level, which can determine tissue pathology. The challenge is to connect the macroscopic mechanical metrics derived from SWE and rheometry to the tissue microstructure. To address this challenge, mathematical models can be used that employ multiple, judiciously chosen measurements of macroscopic shear properties and histology to estimate intrinsic mechanical properties at the cell level.A class of homogeneous and composite lipid phantoms mimicking the mechanical properties of brain white matter were fabricated to test a novel stereotactic system and an optimized SWE imaging protocol. The shear stiffness measurements obtained with SWE on the whole phantom were validated with rheometry performed on a series of samples made with the same material as the phantoms. The same procedure was applied to porcine brain white matter excised from fresh whole brains (n=3). Cylindrical cores were extracted from the corpus callosum area, sliced into discs and microscopic sections were subsequently removed for histology. Good agreement was found between the SWE and rheometry measurements of shear stiffness, which generally increases with the level of compressive prestress. Immunofluorescence was used to stain separately the axon neurofilaments and myelin sheaths, and digital image analysis of the confocal microscopy images allowed the estimation of axon volume fraction and axon-to-myelin ratio in the corpus callosum. Using these metrics and a composite mechanical model, a connection between the macroscopic shear measurements and the viscoelastic properties of axon and glia matrix was made for porcine brain tissue. Similarly, rheometry was used to measure the macroscopic properties of decellularized porcine myocardium extracellular matrix (ECM) in two different fiber locations, and for three different fiber orientations. The mechanical properties were found to be dependent upon fiber location, but not on fiber orientation. Since collagen is a primary supportive structure for the ECM, several microscopic slices were probed with immunofluorescence to compute the collagen I and collagen IV volume fractions. Another mechanical model was employed to establish a connection between the macroscopic properties and the mechanical properties of the collagen matrix in decellularized porcine myocardial ECM.This dissertation highlights the use and integration of three different experimental techniques (rheometry, ultrasound SWE, and histology) to correlate key microstructural properties of soft, fibrous tissues (ex-vivo healthy porcine brain white matter and myocardium ECM) with macroscopic shear mechanics. The consideration of the effect of compressive prestress is noteworthy. The reported baseline data for the tissues under shear loading and prestress are pertinent to the physiological function of these tissues, and therefore constitute preliminary data and a necessary first step before a systematic study of the biomechanics of the same tissues in vivo is performed.
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