Tuning acoustic and mechanical properties of materials for ultrasound phantoms and smart substrates for cell cultures.

Materials with tailored acoustic properties are of great interest for both the development of tissue-mimicking phantoms for ultrasound tests and smart scaffolds for ultrasound mediated tissue engineering and regenerative medicine. In this study, we assessed the acoustic properties (speed of sound, acoustic impedance and attenuation coefficient) of three different materials (agarose, polyacrylamide and polydimethylsiloxane) at different concentrations or cross-linking levels and doped with different concentrations of barium titanate ceramic nanoparticles. The selected materials, besides different mechanical features (stiffness from few kPa to 1.6MPa), showed a wide range of acoustic properties (speed of sound from 1022 to 1555m/s, acoustic impedance from 1.02 to 1.67MRayl and attenuation coefficient from 0.2 to 36.5dB/cm), corresponding to ranges in which natural soft tissues can fall. We demonstrated that this knowledge can be used to build tissue-mimicking phantoms for ultrasound-based medical procedures and that the mentioned measurements enable to stimulate cells with a highly controlled ultrasound dose, taking into account the attenuation due to the cell-supporting scaffold. Finally, we were able to correlate for the first time the bioeffect on human fibroblasts, triggered by piezoelectric barium titanate nanoparticles activated by low-intensity pulsed ultrasound, with a precise ultrasound dose delivered. These results may open new avenues for the development of both tissue-mimicking materials for ultrasound phantoms and smart triggerable scaffolds for tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: This study reports for the first time the results of a systematic acoustic characterization of agarose, polyacrylamide and polydimethylsiloxane at different concentrations and cross-linking extents and doped with different concentrations of barium titanate nanoparticles. These results can be used to build tissue-mimicking phantoms, useful for many ultrasound-based medical procedures, and to fabricate smart materials for stimulating cells with a highly controlled ultrasound dose. Thanks to this knowledge, we correlated for the first time a bioeffect (the proliferation increase) on human fibroblasts, triggered by piezoelectric nanoparticles, with a precise US dose delivered. These results may open new avenues for the development of both tissue-mimicking phantoms and smart triggerable scaffolds for tissue engineering and regenerative medicine.

Speed of sound in rubber-based materials for ultrasonic phantoms.

PURPOSE: In this work we provide measurements of speed of sound (SoS) and acoustic impedance (Z) of some doped/non-doped rubber-based materials dedicated to the development of ultrasound phantoms. These data are expected to be useful for speeding-up the preparation of multi-organ phantoms which show similar echogenicity to real tissues. METHODS: Different silicones (Ecoflex, Dragon-Skin Medium) and polyurethane rubbers with different liquid (glycerol, commercial detergent, N-propanol) and solid (aluminum oxide, graphene, steel, silicon powder) inclusions were prepared. SoS of materials under investigation was measured in an experimental setup and Z was obtained by multiplying the density and the SoS of each material. Finally, an anatomically realistic liver phantom has been fabricated selecting some of the tested materials. RESULTS: SoS and Z evaluation for different rubber materials and formulations are reported. The presence of liquid additives appears to increase the SoS, while solid inclusions generally reduce the SoS. The ultrasound images of realized custom fabricated heterogeneous liver phantom and a real liver show remarkable similarities. CONCLUSIONS: The development of new materials' formulations and the knowledge of acoustic properties, such as speed of sound and acoustic impedance, could improve and speed-up the development of phantoms for simulations of ultrasound medical procedures.

Intraoperative bowel cleansing tool in active locomotion capsule endoscopy.

Capsule endoscopy (CE) can be considered an example of "disruptive technology" since it represents a bright alternative to traditional diagnostic methodologies. If compared with traditional endoscopy, bowel cleansing procedure in CE becomes of greater importance, due to the impossibility to intraoperatively operate on unclean gastrointestinal tract areas. Considering the promising results and benefits obtained in the field of CE for gastrointestinal diagnosis and intervention, the authors approached the bowel cleansing issue with the final aim to propose an innovative and easy-to-use intraoperative cleansing system to be applied to an active locomotion softly-tethered capsule device, already developed by the authors. The system, that has to be intended as an additional tool for intraoperatively cleansing procedure of the colonic tract, is composed by a flexible tube with a metallic deflector attached to the distal end; it can be headed to the target area through the capsule operating channel. Performances of the colonoscopic capsule and intraoperative cleansing capabilities were successfully confirmed both in an in-vitro and ex-vivo experimental session. The innovative intraoperative cleansing system demonstrated promising results in terms of water injection, colonic wall cleansing procedure and subsequent water suction, thus guaranteeing to reduce the risk of inadequate visualization of the mucosa in endoscopic procedures.

Magnetic air capsule robotic system: proof of concept of a novel approach for painless colonoscopy.

BACKGROUND: Despite being considered the most effective method for colorectal cancer diagnosis, colonoscopy take-up as a mass-screening procedure is limited mainly due to invasiveness, patient discomfort, fear of pain, and the need for sedation. In an effort to mitigate some of the disadvantages associated with colonoscopy, this work provides a preliminary assessment of a novel endoscopic device consisting in a softly tethered capsule for painless colonoscopy under robotic magnetic steering. METHODS: The proposed platform consists of the endoscopic device, a robotic unit, and a control box. In contrast to the traditional insertion method (i.e., pushing from behind), a "front-wheel" propulsion approach is proposed. A compliant tether connecting the device to an external box is used to provide insufflation, passing a flexible operative tool, enabling lens cleaning, and operating the vision module. To assess the diagnostic and treatment ability of the platform, 12 users were asked to find and remove artificially implanted beads as polyp surrogates in an ex vivo model. In vivo testing consisted of a qualitative study of the platform in pigs, focusing on active locomotion, diagnostic and therapeutic capabilities, safety, and usability. RESULTS: The mean percentage of beads identified by each user during ex vivo trials was 85 ± 11%. All the identified beads were removed successfully using the polypectomy loop. The mean completion time for accomplishing the entire procedure was 678 ± 179 s. No immediate mucosal damage, acute complications such as perforation, or delayed adverse consequences were observed following application of the proposed method in vivo. CONCLUSIONS: Use of the proposed platform in ex vivo and preliminary animal studies indicates that it is safe and operates effectively in a manner similar to a standard colonoscope. These studies served to demonstrate the platform's added advantages of reduced size, front-wheel drive strategy, and robotic control over locomotion and orientation.