Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA) and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E), long term shear modulus (η), and time constant (τ) in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research

Acoustic radiation force impulse imaging for differentiation of thyroid nodules

Background: Acoustic Radiation Force Impulse (ARFI)-imaging is an ultrasound-based elastography method enabling quantitative measurement of tissue stiffness. The aim of the present study was to evaluate sensitivity and specificity of ARFI-imaging for differentiation of thyroid nodules and to compare it to the well evaluated qualitative real-time elastography (RTE). Methods: ARFI-imaging involves the mechanical excitation of tissue using acoustic pulses to generate localized displacements resulting in shear-wave propagation which is tracked using correlation-based methods and recorded in m/s. Inclusion criteria were: nodules $5 mm, and cytological/histological assessment. All patients received conventional ultrasound, real-time elastography (RTE) and ARFI-imaging. Results: One-hundred-fifty-eight nodules in 138 patients were available for analysis. One-hundred-thirty-seven nodules were benign on cytology/histology, and twenty-one nodules were malignant. The median velocity of ARFI-imaging in the healthy thyroid tissue, as well as in benign and malignant thyroid nodules was 1.76 m/s, 1.90 m/s, and 2.69 m/s, respectively. While no significant difference in median velocity was found between healthy thyroid tissue and benign thyroid nodules, a significant difference was found between malignant thyroid nodules on the one hand and healthy thyroid tissue (p = 0.0019) or benign thyroid nodules (p = 0.0039) on the other hand. No significant difference of diagnostic accuracy for the diagnosis of malignant thyroid nodules was found between RTE and ARFI-imaging (0.74 vs. 0.69, p = 0.54). The combination of RTE with ARFI did not improve diagnostic accuracy. Conclusions: ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules with high negative predictive value and comparable results to RTE

Anisotropic behaviour of human gallbladder walls

Inverse estimation of biomechanical parameters of soft tissues from non-invasive measurements has clinical significance in patient-specific modelling and disease diagnosis. In this paper, we propose a fully nonlinear approach to estimate the mechanical properties of the human gallbladder wall muscles from in vivo ultrasound images. The iteration method consists of a forward approach, in which the constitutive equation is based on a modified Hozapfel–Gasser–Ogden law initially developed for arteries. Five constitutive parameters describing the two orthogonal families of fibres and the matrix material are determined by comparing the computed displacements with medical images. The optimisation process is carried out using the MATLAB toolbox, a Python code, and the ABAQUS solver. The proposed method is validated with published artery data and subsequently applied to ten human gallbladder samples. Results show that the human gallbladder wall is anisotropic during the passive refilling phase, and that the peak stress is 1.6 times greater than that calculated using linear mechanics. This discrepancy arises because the wall thickness reduces by 1.6 times during the deformation, which is not predicted by conventional linear elasticity. If the change of wall thickness is accounted for, then the linear model can used to predict the gallbladder stress and its correlation with pain. This work provides further understanding of the nonlinear characteristics of human gallbladder

Nonlinear fourth‐order elastic characterization of the cornea using torsional wave elastography

Measuring the mechanical nonlinear properties of the cornea remains challenging due to the lack of consensus in the methodology and in the models that effectively predict its behaviour. This study proposed developing a procedure to reconstruct nonlinear fourth-order elastic properties of the cornea based on a mathematical model derived from the theory of Hamilton et al. and using the torsional wave elastography (TWE) technique. In order to validate its diagnostic capability of simulated pathological conditions, two different groups were studied, non-treated cornea samples (n=7), and ammonium hydroxide (NH4OH) treated samples (n=7). All the samples were measured in-plane by a torsional wave device by increasing IOP from 5 to 25 mmHg with 5 mmHg steps. The results show a nonlinear variation of the shear wave speed with the IOP, with higher values for higher IOPs. Moreover, the shear wave speed values of the control group were higher than those of the treated group. The study also revealed significant differences between the control and treated groups for the Lamé parameter ���� (25.9–6.52 kPa), third-order elastic constant A (215.09–44.85 kPa), and fourth-order elastic constant D (523.5–129.63 kPa), with p-values of 0.010, 0.024, and 0.032, respectively. These findings demonstrate that the proposed procedure can distinguish between healthy and damaged corneas, making it a promising technique for detecting diseases associated with IOP alteration, such as corneal burns, glaucoma, or ocular hypertension

Factors that influence muscle shear modulus during passive stretch

Although elastography has been increasingly used for evaluating muscle shear modulus associated with age, sex, musculoskeletal, and neurological conditions, its physiological meaning is largely unknown. This knowledge gap may hinder data interpretation, limiting the potential of using elastography to gain insights into muscle biomechanics in health and disease. We derived a mathematical model from a widely-accepted Hill-type passive force–length relationship to gain insight about the physiological meaning of resting shear modulus of skeletal muscles under passive stretching, and validated the model by comparing against the ex-vivo animal data reported in our recent work (Koo et al. 2013). The model suggested that resting shear modulus of a slack muscle is a function of specific tension and parameters that govern the normalized passive muscle force–length relationship as well as the degree of muscle anisotropy. The model also suggested that although the slope of the linear shear modulus–passive force relationship is primarily related to muscle anatomical cross-sectional area (i.e. the smaller the muscle cross-sectional area, the more the increase in shear modulus to result in the same passive muscle force), it is also governed by the normalized passive muscle force–length relationship and the degree of muscle anisotropy. Taken together, although muscle shear modulus under passive stretching has a strong linear relationship with passive muscle force, its actual value appears to be affected by muscle’s mechanical, material, and architectural properties. This should be taken into consideration when interpreting the muscle shear modulus values

Magnetic Resonance Elastography of the Brain: from Phantom to Mouse to Man

The overall objective of this study is to develop magnetic resonance elastography: MRE) imaging to better understand brain deformation, brain tissue mechanical properties, and brain-skull interaction in vivo. The findings of this study provide parameters for numerical models of human head biomechanics, as well as data for validation of these models. Numerical simulations offer enormous potential to the study of traumatic brain injury: TBI) and may also contribute to the development of prophylactic devices for high-risk subjects: e.g., military personnel, first-responders, and athletes). Current numerical models have not been adequately parameterized or validated and their predictions remain controversial. This dissertation describes three kinds of MRE experiments, conducted in phantom: physical model), mouse, and man. Phantom studies provide a means to experimentally confirm the accuracy of MRE estimates of viscoelastic parameters in relatively simple materials and geometries. Studies in the mouse provide insight into the dispersive nature of brain tissue mechanical properties at frequencies beyond those that can be measured in humans. Studies in human subjects provide direct measurements of the human brain\u27s response to dynamic extracranial loads, including skull-brain energy transmission and viscoelastic properties

Characterizing anisotropy in fibrous soft materials by MR elastography of slow and fast shear waves

The general objective of this work was to develop experimental methods based on magnetic resonance elastography (MRE) to characterize fibrous soft materials. Mathematical models of tissue biomechanics capable of predicting injury, such as traumatic brain injury (TBI), are of great interest and potential. However, the accuracy of predictions from such models depends on accuracy of the underlying material parameters. This dissertation describes work toward three aims. First, experimental methods were designed to characterize fibrous materials based on a transversely isotropic material model. Second, these methods are applied to characterize the anisotropic properties of white matter brain tissue ex vivo. Third, a theoretical investigation of the potential application of MRE to probe nonlinear mechanical behavior of soft tissue was performed. These studies provide new methods to characterize anisotropic and nonlinear soft materials as well as contributing significantly to our understanding of the behavior of specific biological soft tissues