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LOCAL VISCOELASTIC PROPERTIES OF SOFT ANISOTROPIC FIBROUS TISSUE
Title
LOCAL VISCOELASTIC PROPERTIES OF SOFT ANISOTROPIC FIBROUS TISSUE
Creator
Gallo, Nicolas Remy
Date
2020
Description
The current aging population, with more than 80 million "baby boomers", will present a steep medical challenge for our society in a...
Show moreThe current aging population, with more than 80 million "baby boomers", will present a steep medical challenge for our society in a foreseeable future. Half of the adults over 85 years old are predicted to be diagnosed with Alzheimer's disease by 2050. With healthcare cost reaching over 700 billion dollars in the United States, early detection of Alzheimer's disease (AD) and other co-existing neurodegenerative diseases is crucial to improve the recovery odds in patients and to decrease individual care cost. This work seeks to tackle this problem by proposing a novel computational framework toward improving the measurement of shear visco-elastic properties of brain white matter (WM), which vary with age. These measurements practically represent the effective (average) response of many cells and are typically obtained by using rheology or elastography. Although the former is direct, the latter requires the solution of an inverse problem based on a priori mechanical tissue model. The mechanical anisotropy of WM has previously not been fully explored although many inconsistencies have been reported in brain MRE experiments. To account for these inconsistencies a transversely isotropic constitutive model for the brain WM is proposed to interpret prior experiments involving 7 young and 4 older healthy men. By employing a novel inversion scheme, we report the local variation of the effective transverse and axial shear moduli in two well aligned WM structures (corpus callosum: CC; and cortical spinal tract: CST) for both the young and old cohort of healthy subjects part of the study. This work reports statistically significant changes in local regional variation of the transverse modulus across the CC for the young cohort. In the older cohort, the trend was similar yet not statistically significant. A novel candidate biomarker, the shear anisotropy metric, defined as the ratio of the transverse and axial shear moduli, found statistically significant local regional variation across the CC but not in the CST. Healthy aging was observed to decrease both transverse and axial in both CC and CST, although the variation was significant only for the CC. Finally, in an effort to understand the cause of effective transverse mechanical properties variation in WM with aging, the connection between effective and intrinsic contribution of WM cellular constituents is established. The intrinsic mechanical contributions of axons and glial matrix are separated by fitting the estimates of the effective shear moduli to a microscopic composite fiber model of myelinated axons embedded in the glial matrix. This work provides a method to establish a baseline for healthy brain mechanical properties thus promising to increase the specificity of MRE toward early diagnosis of neurodegenerative diseases. Additional oscillating disc rheology experiments with decellularized porcine myocardium, and the fabrication of a stable heterogeneous phantom matching the mechanical, diffusional and electrical properties of the WM provide foundational knowledge for due development and validation of MRE methodologies employed in other tissues.
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