Pulse-Echo Ultrasound for Quantitative Measurements of Two Uncorrelated Elastic Parameters.

OBJECTIVE: This paper describes the relationship between elastic tissue properties and strain and presents an initial investigation of pulse-echo ultrasound to measure two uncorrelated elastic parameters in tissue-mimicking phantoms. The two elastic parameters are the shear modulus, related to deformation of shape, and what we in the paper define as the nonlinear compressibility, related to deformation of volume. METHODS: We prepared tissue-mimicking phantoms containing lesions of variable shear modulus and variable nonlinear compressibility. An in-house framework for shear wave imaging was developed using ultrasound radiation force at 4.5 MHz to induce shear waves and plane wave imaging with pulses in a frequency band centered around 12.5 MHz to track the shear waves. For measurements of nonlinear compressibility, co-propagating dual-frequency pulse complexes at 0.7 MHz and 14 MHz were applied. Algorithms were implemented on a Verasonics Vantage ultrasound scanner and a custom-made multi-frequency ultrasound transducer was used. Mechanical indentation measurements were performed to validate ultrasound measurements of the shear modulus. For the nonlinear compressibility, ultrasound measurements were compared to results derived from the literature. RESULTS: We found good agreement in elasticity results from ultrasound measurements and mechanical indentation as well as when comparing with results derived from the literature. CONCLUSION: Results of the current investigation were promising. We plan patient studies involving thyroid lesions and liver steatosis to explore whether measurements of elastic parameters related both to shape deformation and volume deformation are useful in clinical practice.

Macro-indentation testing of soft biological materials and assessment of hyper-elastic material models from inverse finite element analysis.

Mechanical characterization of hydrogels and ultra-soft tissues is a challenging task both from an experimental and material parameter estimation perspective because they are much softer than many biological materials, ceramics, or polymers. The elastic modulus of such materials is within the 1 - 100 kPa range, behaving as a hyperelastic solid with strain hardening capability at large strains. In the current study, indentation experiments have been performed on agarose hydrogels, bovine liver, and bovine lymph node specimens. This work reports on the reliable determination of the elastic modulus by indentation experiments carried out at the macro-scale (mm) using a spherical indenter. However, parameter identification of the hyperelastic material properties usually requires an inverse finite element analysis due to the lack of an analytical contact model of the indentation test. Hence a comprehensive study on the spherical indentation of hyperelastic soft materials is carried out through robust computational analysis. Neo-Hookean and first-order Ogden hyperelastic material models were found to be most suitable. A case study on known anisotropic hyperelastic material showed the inability of the inverse finite element method to uniquely identify the whole material parameter set.

Potential of computational models in personalized treatment of obstructive sleep apnea: a patient-specific partial 3D finite element study.

The upper airway experiences mechanical loads during breathing. Obstructive sleep apnea is a very common sleep disorder, in which the normal function of the airway is compromised, enabling its collapse. Its treatment remains unsatisfactory with variable efficacy in the case of many surgeries. Finite element models of the upper airway to simulate the effects of various anatomic and physiologic manipulations on its mechanics could be helpful in predicting surgical success. Partial 3D finite element models based on patient-specific CT-scans were undertaken in a pilot study of 5 OSA patients. Upper airway soft tissues including the soft palate, hard palate, tongue, and pharyngeal wall were segmented around the midsagittal plane up to a width of 2.5 cm in the lateral direction. Simulations of surgical interventions such as Uvulopalatopharyngoplasty (UPPP), maxillo-mandibular advancement (MMA), palatal implants, and tongue implants have been performed. Our results showed that maxillo-mandibular advancement (MMA) surgery of 1 cm improved the critical closing pressure by at least 212.2%. Following MMA, the best improvement was seen via uvulopalatopharyngoplasty (UPPP), with an improvement of at least 19.12%. Palatal and tongue implants also offered a certain degree of improvement. Further, we observed possible interacting mechanisms that suggested simultaneous implementation of UPPP and tongue stiffening; and palatal and tongue stiffening could be beneficial. Our results suggest that computational modeling is a useful tool for analyzing the influence of anatomic and physiological manipulations on upper airway mechanics. The goal of personalized treatment in the case of OSA could be achieved with the use of computational modeling.

Evaluation of a multi-scale discrete fiber model for analyzing arterial failure.

So far, the prevalent rupture risk quantification of aortic aneurysms does not consider information of the underlying microscopic mechanisms. Uniaxial tension tests were performed on imaged aorta samples oriented in circumferential and longitudinal directions. To account for local heterogeneity in collagen fiber architecture, SHG imaging was performed on tissues at several locations prior to mechanical testing. This enabled the quantification of micro-scale information including organization of collagen fibers using relevant probability density functions. Two different modeling approaches are presented in this study for the sake of comparison. A multi-scale mechanical model was developed using this micro-structural information with collagen fibers as main components. accounting for non-affine fiber kinematics. Simultaneously, an embedded element model that accounts for affine fiber kinematics was developed in Abaqus using the same micro-structural information. Numerical simulations emulating uniaxial tension experiments were performed on the developed models. Global mechanical response of both models agreed well with the experimental data, although leading to mismatched material properties. The models present a rudimentary yet better than before representation of structure based description of aortic-tissue failure mechanics. reinforcing the importance of structural organization of micro-scale constituents and their kinematics in determining tissue failure.

Region- and layer-specific investigations of the human menisci using SHG imaging and biaxial testing.

In this paper, we examine the region- and layer-specific collagen fiber morphology via second harmonic generation (SHG) in combination with planar biaxial tension testing to suggest a structure-based constitutive model for the human meniscal tissue. Five lateral and four medial menisci were utilized, with samples excised across the thickness from the anterior, mid-body, and posterior regions of each meniscus. An optical clearing protocol enhanced the scan depth. SHG imaging revealed that the top samples consisted of randomly oriented fibers with a mean fiber orientation of 43.3 o . The bottom samples were dominated by circumferentially organized fibers, with a mean orientation of 9.5 o . Biaxial testing revealed a clear anisotropic response, with the circumferential direction being stiffer than the radial direction. The bottom samples from the anterior region of the medial menisci exhibited higher circumferential elastic modulus with a mean value of 21 MPa. The data from the two testing protocols were combined to characterize the tissue with an anisotropic hyperelastic material model based on the generalized structure tensor approach. The model showed good agreement in representing the material anisotropy with a mean r 2 = 0.92.

Microstructure and mechanics of the bovine trachea: Layer specific investigations through SHG imaging and biaxial testing.

The trachea is a complex tissue made up of hyaline cartilage, fibrous tissue, and muscle fibers. Currently, the knowledge of microscopic structural organization of these components and their role in determining the tissue's mechanical response is very limited. The purpose of this study is to provide data on the microstructure of the tracheal components and its influence on tissue's mechanical response. Five bovine tracheae were used in this study. Adventitia, cartilage, mucosa/submucosa, and trachealis muscle layers were methodically cut out from the whole tissue. Second-harmonic generation(SHG) via multi-photon microscopy (MPM) enabled imaging of collagen fibers and muscle fibers. Simultaneously, a planar biaxial test rig was used to record the mechanical behavior of each layer. In total 60 samples were tested and analyzed. Fiber architecture in the adventitia and mucosa/submucosa layer showed high degree of anisotropy with the mean fiber angle varying from sample to sample. The trachealis muscle displayed neat layers of fibers organized in the longitudinal direction. The cartilage also displayed a structure of thick mesh-work of collagen type II organized predominantly towards the circumferential direction. Further, mechanical testing demonstrated the anisotropic nature of the tissue components. The cartilage was identified as the stiffest component for strain level < 20% and hence the primary load bearing component. The other three layers displayed a non-linear mechanical response which could be explained by the structure and organization of their fibers. This study is useful in enhancing the utilization of structurally motivated material models for predicting tracheal overall mechanical response.

A computational model for understanding the micro-mechanics of collagen fiber network in the tunica adventitia.

Abdominal aortic aneurysm is a prevalent cardiovascular disease with high mortality rates. The mechanical response of the arterial wall relies on the organizational and structural behavior of its microstructural components, and thus, a detailed understanding of the microscopic mechanical response of the arterial wall layers at loads ranging up to rupture is necessary to improve diagnostic techniques and possibly treatments. Following the common notion that adventitia is the ultimate barrier at loads close to rupture, in the present study, a finite element model of adventitial collagen network was developed to study the mechanical state at the fiber level under uniaxial loading. Image stacks of the rabbit carotid adventitial tissue at rest and under uniaxial tension obtained using multi-photon microscopy were used in this study, as well as the force-displacement curves obtained from previously published experiments. Morphological parameters like fiber orientation distribution, waviness, and volume fraction were extracted for one sample from the confocal image stacks. An inverse random sampling approach combined with a random walk algorithm was employed to reconstruct the collagen network for numerical simulation. The model was then verified using experimental stress-stretch curves. The model shows the remarkable capacity of collagen fibers to uncrimp and reorient in the loading direction. These results further show that at high stretches, collagen network behaves in a highly non-affine manner, which was quantified for each sample. A comprehensive parameter study to understand the relationship between structural parameters and their influence on mechanical behavior is presented. Through this study, the model was used to conclude important structure-function relationships that control the mechanical response. Our results also show that at loads close to rupture, the probability of failure occurring at the fiber level is up to 2%. Uncertainties in usually employed rupture risk indicators and the stochastic nature of the event of rupture combined with limited knowledge on the microscopic determinants motivate the development of such an analysis. Moreover, this study will advance the study of coupling microscopic mechanisms to rupture of the artery as a whole.