Independent tuning of acoustic and mechanical properties of phantoms for biomedical applications of ultrasound

In this work the preparation of tissue mimicking materials (TMMs) with independently tunable acoustic and elastic properties is reported. Although a large number of hydrogel, synthetic polymer, polysaccharides or other natural based materials have been proposed and used for the realization of TMMs, both for diagnostic and therapeutic applications of ultrasounds, up to today, simulation of acoustic properties was often performed using solid particles, reducing dramatically the transparency and inevitably affecting the homogeneity and the elastic properties of the TMM. By means of concentrated salts solutions and different polysaccharides, an easy method to prepare these TMMs have been developed. This approach would lead to obtain homogenous TMMs with Young modulus ranging over 3 orders of magnitude, i.e. from 2 to 1500 kPa, with independently tunable attenuation properties. An accurate mechanical and acoustic characterization of these TMMs have been performed. Finally, by means of a preliminary trials on protein denaturation induced by a high focused ultrasound transducer in a transparent TMMs with different attenuation values, the mechanism underlying on the formation and propagation of lesion has been investigated. Obtained results suggest that this 'chemical' approach would strongly support in vitro investigations on the open issues related to diagnostic and therapeutic application of ultrasounds

Temperature Increase Dependence on Ultrasound Attenuation Coefficient in Innovative Tissue-mimicking Materials

Although high intensity focused ultrasound beams (HIFU) have found rapid agreement in clinical environment as a tool for non invasive surgical ablation and controlled destruction of cancer cells, some aspects related to the interaction of ultrasonic waves with tissues, such as the conversion of acoustic energy into heat, are not thoroughly understood. In this work, innovative tissue- mimicking materials (TMMs), based on Agar and zinc acetate, have been used to conduct investigations in order to determine a relation between the sample attenuation coefficient and its temperature increase measured in the focus region when exposed to an HIFU beam. An empirical relation has been deduced establishing useful basis for further processes of validations of numerical models to be adopted for customizing therapeutic treatments

Tissue mimicking materials for imaging and therapy phantoms: a review

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development

HIGH INTENSITY FOCUSED ULTRASOUND AND OXYGEN LOAD NANOBUBBLES: TWO DIFFERENT APPROCHES FOR CANCER TREATMENT

The study of applications based on the use of ultrasound in medicine and biology for therapeutic purposes is under strong development at international level and joins the notoriously well-established and widespread use of diagnostic applications [1]. In the past few years, High Intensity Focused Ultrasound (HIFU) has developed from a scientific curiosity to an accepted therapeutic modality. HIFU is a non invasive technique for the treatment of various types of cancer, as well as non-malignant pathologies, by inducing localized hyperthermia that causes necrosis of the tissue. Beside HIFU technology, other innovative therapeutic modalities to treat cancer are emerging. Among them, an extremely innovative technique is represented by oxygen loaded nanobubbles (OLNs): gas cavities confined by an appropriately functionalized coating. This is an oxygenating drugs aimed at re-oxygenation of cancerous tissue. Oxygen deficiency, in fact, is the main hallmark of cancerous solid tumors and a major factor limiting the effectiveness of radiotherapy. In this work, these two approaches to treat tumours are under study from a metrological point of view. In particular, a complete characterization of an HIFU fields regarding power, pressure and temperature is provided while oxygen load nanobubbles are synthesized, characterized and applied in in vitro and in vivo experiments

Strain-rate and temperature dependent material properties of Agar and Gellan Gum used in biomedical applications

partially_open3Agar and Gellan Gum are biocompatible polymers extensively used in several fields of tissue engineering research (e.g. tissue replacement, tissue support, tissue mimicking), due to their mechanical behaviour effectively representative of actual biological tissues. Since mechanical properties of artificial tissues are related to biocompatibility and functionality of medical implants and significantly influence adhesion, growth and differentiation of cells in tissue-engineering scaffolds, an accurate characterization of Young׳s modulus and relaxation time processes is needed. In this study, the strain-rate and temperature dependent material properties of Agarose and one among the numerous kind of Gellan Gum commercially available, known as Phytagel®, have been investigated. Nine hydrogel samples have been realized with different mechanical properties: the first one Agar-based as a reference material, the further eight samples Gellan Gum based in which the effect of dispersed solid particles like kieselguhr and SiC, as enhancing mechanical properties factors, have been investigated as a function of concentration. Stress-strain has been investigated in compression and relaxation time has been evaluated by means of the Kohlrausch-Williams-Watts time decay function. Mechanical properties have been measured as a function of temperature between 20°C and 35°C and at different strain rates, from ~10-3s-1 and ~10-2s-1 (or deformation rate from ~0.01mms-1 to ~0.1mms-1). From experimental data, the combined temperature and strain-rate dependence of hydrogels Young׳s modulus is determined on the basis of a constitutive model. In addition to a dependence of Young׳s modulus on temperature, a remarkable influence of strain-rate has been observed, especially in the sample containing solid particles; in same ranges of temperature and strain-rate, also relaxation time variations have been monitored in order to identify a possible dependence of damping properties on temperature and strain-rate. The result is the impossibility to determine univocally mechanical properties of studied biomaterials without a proper definition of boundary conditions at which they have been obtained.openSchiavi Alessandro; Cuccaro Rugiada; Troia AdrianoSchiavi, Alessandro; Cuccaro, Rugiada; Troia, Adrian

Effects of Compression on the Temperature Distribution of a Tissue-Mimicking Material During High-Intensity Focused Ultrasound (HIFU) Ablation

Local blood flow near a high-intensity focused ultrasound (HIFU) target has been shown to decrease ablation effectiveness and predictability, creating a barrier to clinical use for breast cancer treatment. This study investigated the effects of compression on HIFU ablation of a perfused tissue-mimicking material. Gellan gum-based phantoms, with thermal and acoustic properties similar to those of soft tissue, were ablated with a 1.13 MHz HIFU transducer while being subjected to varying levels of external compression. Phantoms were designed with an embedded 6 mm diameter vessel meant to mimic a thermally significant blood vessel near a breast tumor. The internal temperature profile was measured using T-type thin-wire thermocouples embedded in the phantom along the transverse axis. The temperature distributions on opposing lateral sides of the HIFU focal point were measured to determine the effects of compression on heating symmetry. After heating with 30 W for 30 s, the maximum discrepancy between a pair of thermocouples located 2 mm left and right of centerline, respectively, was 40 °C. This maximum discrepancy was observed at a fluid flow rate of 38 mL/min. With applied compression reducing flow to between 28 mL/min and 25 mL/min, the discrepancy between left and right thermocouples was reduced to as low as 5.7 °C. Numerical predictions revealed an agreement with experimental results in the reduction of heating asymmetry as the flow rate decreased from 40 mL/min to 20 mL/min

Development of acoustic tissue mimicking materials for preclinical ultrasound imaging applications

Many applications of ultrasound test phantoms require that the acoustical properties of the phantom should closely match those of soft tissue. Numerous commercial test phantoms of this type are available for use with clinical ultrasound scanners, which use frequencies up to 20 MHz. However, scanners designed for imaging small animals in preclinical studies, typically operate at much higher frequencies. No commercially available test phantoms exist for use at frequencies above 20 MHz. The aim of this work was to develop a tissue-mimicking-material (TMM) that closely matches the acoustic properties of small animal tissues at high frequencies (HF). Such a material would, therefore, be suitable for ultrasound test phantoms for application with HF ultrasound scanners (20 MHz to 50 MHz). A three-step approach was adopted to address this lack of a suitable HF-TMM. Firstly, verify the acoustic characteristics of the existing IEC agar-based TMM. Secondly, establish the acoustic properties (speed of sound and attenuation coefficient) of small animal tissue at high frequencies. Thirdly, develop a TMM which exhibits, as closely as possible, these small animal tissue acoustic characteristics. A pulse-echo substitution method was used throughout to characterise the materials and the tissue samples. The speed of sound and attenuation coefficient of an IEC agar-based TMM were measured using two different techniques. Initially, a widely used method was tried, where samples are wrapped in film and placed in degassed, deionised water for assessment. The second technique was developed and validated for use in this work. In this method, TMM samples were uncovered (without film) and were both stored and assessed in a TMM preserving fluid. The second method provided up to four times more consistent results. The acoustical properties of the individual components of the IEC agar-based TMM were then measured in order to determine whether the overall attenuation coefficient of the agar TMM was a linear sum of the attenuation coefficients of its component parts. Within experimental uncertainties, this was found to be the case. This is a key observation from which the formulation of an agar TMM, matching the acoustic properties of small animal tissue, can be facilitated. The acoustical properties (speed of sound and attenuation coefficient) of mouse brain, liver, and kidney were measured using a preclinical ultrasound scanner