Characterization of perfused and sectioned liver tissue in a full indentation cycle using a visco-hyperelastic model.

Realistic modeling of biologic material is required for optimizing fidelity in computer-aided surgical training and assistance systems. The modeling of liver tissue has remained challenging due to its nonlinear viscoelastic properties and high hysteresis of the stress-strain relation. While prior studies have described the behavior of liver tissue during the loading status (in elongation, compression, or indentation tests) or unloading status (in stress relaxation or creep tests), a hysteresis curve with both loading and unloading processes was incompletely defined. We seek to use a single material model to characterize the mechanical properties of liver tissue in a full indentation cycle ex vivo perfused and then sectioned. Based on measurements taken from ex-vivo perfused porcine livers, we converted force-displacement curves to stress-strain curves and developed a visco-hyperelastic constitutive model to characterize the liver's mechanical behavior at different locations under various rates of indentation (1, 2, 5, 10, and 20 mm/s). The proposed model is a mixed visco-hyperelastic model with up to 6 coefficients. The normalized root mean square standard deviations of fitted curves are less than 5% and 10% in low (<0.05) and high strain (>0.3) conditions respectively.

Effects of Low Intensity Focused Ultrasound on Liposomes Containing Channel proteins.

The ability to reversibly and non-invasively modulate region-specific brain activity in vivo suggests Low Intensity Focused Ultrasound (LIFU) as potential therapeutics for neurological dysfunctions such as epilepsy and Parkinson's disease. While in vivo studies provide evidence of the bioeffects of LIFU on neuronal activity, they merely hint at potential mechanisms but do not fully explain how this technology achieves these effects. One potential hypothesis is that LIFU produces local membrane depolarization by mechanically perturbing the neuronal cell membrane, or activating channels or other proteins embedded in the membrane. Proteins that sense mechanical perturbations of the membrane, such as those gated by membrane tension, are prime candidates for activating in response to LIFU and thus leading to the neurological responses that have been measured. Here we use the bacterial mechanosensitive channel MscL, which has been purified and reconstituted in liposomes, to determine how LIFU may affect the activation of this membrane-tension gated channel. Two bacterial voltage-gated channels, KvAP and NaK2K F92A channels were also studied. Surprisingly, the results suggest that ultrasound modulation and membrane perturbation does not induce channel gating, but rather induces pore formation at the membrane protein-lipid interface. However, in vesicles with high MscL mechanosensitive channel concentrations, apparent decreases in pore formation are observed, suggesting that this membrane-tension-sensitive protein may serve to increase the elasticity of the membrane, presumably because of expansion of the channel in the plane of the membrane independent of channel gating.

Vibroacoustographic System for Tumor Identification.

Oral and head and neck squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. The primary management of OSCC relies on complete surgical resection of the tumor. Margin-free resection, however, is difficult given the devastating effects of aggressive surgery. Currently, surgeons determine where cuts are made by palpating edges of the tumor. Accuracy varies based on the surgeon's experience, the location and type of tumor, and the risk of damage to adjacent structures limiting resection margins. To fulfill this surgical need, we contrast tissue regions by identifying disparities in viscoelasticity by mixing two ultrasonic beams to produce a beat frequency, a technique termed vibroacoustography (VA). In our system, an extended focal length of the acoustic stress field yields surgeons' high resolution to detect focal lesions in deep tissue. VA offers 3D imaging by focusing its imaging plane at multiple axial cross-sections within tissue. Our efforts culminate in production of a mobile VA system generating image contrast between normal and abnormal tissue in minutes. We model the spatial direction of the generated acoustic field and generate images from tissue-mimicking phantoms and ex vivo specimens with squamous cell carcinoma of the tongue to qualitatively demonstrate the functionality of our system. These preliminary results warrant additional validation as we continue clinical trials of ex vivo tissue. This tool may prove especially useful for finding tumors that are deep within tissue and often missed by surgeons. The complete primary resection of tumors may reduce recurrence and ultimately improve patient outcomes.

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.

Ultrasound-stimulated vibro-acoustography for high-resolution differentiation based on viscoelastic properties of tissue mimicking phantoms.

In the absence of an imaging technique that provides imagery of diseased tissue with high diagnostic accuracy and contrast, surgeons must often excise excess healthy tissue surrounding neoplasms to ensure complete removal of malignant tissues. Additional approaches that are commonly used in the detection of tumor regions include palpation and conventional ultrasound to locate the affected area. However, these techniques suffer from limitations such as minimal specificity and lack of depth penetration. Lack of specificity results in the production of unclear diseased tissue regions, and therefore fails to offer surgeons a reliable and accurate image guidance tool. The proposed work provides an alternative diagnostic modality termed ultrasound-stimulated vibro-acoustography (USVA) that aims to generate detailed images characterized by viscoelastic properties of tissues. We demonstrate selective imaging using phantom tissue samples of polyvinyl alcohol (PVA) that are altered and arranged into unique geometries of varying elastic topology. Determining the precision and sensitivity of the USVA imaging system in identifying boundary regions as well as intensity ranges associated with tissue phantom targets will provide additional important information to allow for a non-invasive tool to distinguish diseased tissues from normal tissues in an in vivo setting.

An L-section DC electric field switchable bulk acoustic wave solidly mounted resonator filter based on Ba0.5Sr0.5TiO3.

This paper reports on the modeling, fabrication, and experimental results of a voltage switchable barium strontium titanate solidly mounted resonator filter at 6 GHz. The filter insertion loss was measured to be -4.26 dB and the return loss to be -13.5 dB. The 3-dB bandwidth was measured to be 72 MHz and the quality factor was calculated to be 83. The data were collected at a dc bias voltage of 10 V. Temperature data were also collected, and the filter demonstrated a 0.71-dB increase in insertion loss and a 7-MHz decrease in center frequency with increase in temperature.