A. Verbeni

An innovative adaptive control strategy for sensorized left ventricular assist devices.

Nowadays advanced heart failure is mainly treated through heart transplantation. However, the low availability of donors makes the research of alternative therapies urgent. Continuous-flow left ventricular assist devices (LVADs) are going to assume a more significant role in assisting the failing heart. A recent challenge in clinical practice is the possibility to use LVAD as long-term therapy rather than as a bridge to transplantation. For this reason, more comfortable devices, able to dynamically adapt to the physiological cardiac demand in relation to the patient activity level, are needed in order to improve the life quality of patients with implants. Nevertheless, no control system has been developed yet for this purpose. This work proposes an innovative control strategy for a novel sensorized LVAD, based on the continuous collection of physical and functional parameters coming from implantable sensors and from the LVAD itself. Thanks to the proposed system, both the patient and the LVAD conditions are continuously monitored and the LVAD activity regulated accordingly. Specifically, a Proportional Integrative (PI) and a threshold control algorithms have been implemented, respectively based on flow and pressure feedbacks collected from the embedded sensors. To investigate the feasibility and applicability of this control strategy, an on-bench platform for LVADs sensing and monitoring has been developed and tested.

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

AbstractPurposeIn 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.MethodsDifferent 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.ResultsSoS 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.ConclusionsThe 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.SommarioScopoIn questo lavoro sono riportati i valori di velocità del suono (SoS) e impedenza acustica (Z) di alcune gomme nella loro formulazione originale o con l’aggiunta di sostanze droganti (liquide o solide). Le gomme analizzate sono pensate per lo sviluppo di fantocci (phantom) per tecniche ad ultrasuoni. La conoscenza di questi dati può essere utile per accelerare la preparazione di phantom multi-organo che mostrano ecogenicità simili a quelle dei tessuti reali.MetodiDifferenti siliconi (Ecoflex, Dragon-Skin Medium) e gomme poliuretaniche con diversi dopaggi liquidi (Glicerolo, detergente commerciale, N-Propanolo) e inclusioni solide (Ossido di Alluminio, Grafene, Acciaio, Polvere di Silicio) sono stati preparati. La velocità del suono è stata misurata in un banco di prova sperimentale e l’impedenza acustica (Z) è stata ottenuta moltiplicando la densità e la SoS di ogni materiale. Infine, è stato fabbricato un phantom anatomicamente realistico, inteso a riprodurre un fegato ed alcune sue caratteristiche, selezionando alcuni dei materiali testati.RisultatiLe misure della SoS e di Z di diverse gomme a differenti formulazioni sono riportate. In generale, la presenza di additivi liquidi aumenta la SoS, mentre le inclusioni metalliche la riducono. Le immagini ecografiche del phantom e di un fegato reale mostrano somiglianze significative.ConclusioniLa realizzazione di nuovi materiali e la conoscenza delle proprietà acustiche quali la velocità del suono e l’impedenza acustica può dare un importante contributo per quanto riguarda la realizzazione di phantom per simulazioni di procedure mediche che utilizzano ultrasuoni.

Capsule-based ultrasound-mediated targeted gastrointestinal drug delivery

Diseases which are prevalent in the gastrointestinal (GI) tract, such as Crohns disease, are a topic of increasing concern because diagnosis and specific treatment are difficult and may be ineffective. New techniques are therefore sought after and this paper describes a proof-of-concept tethered capsule for targeted drug delivery (TDD) in the GI tract. The capsule consists of a camera, illumination, a drug delivery channel and an ultrasound (US) transducer. The transducer is described in detail, including a comparison of different piezoceramic materials that has been carried out. It was found that PZ54 (Ferroperm Piezoceramics, Kvistgaard, Denmark) was the most suitable material for our application. When driven at 4 Vpp, the outer diameter 5 mm PZ54 transducer operates at a frequency f = 4.05 MHz providing an acoustic pressure, Pac = 125 kPa, with a beam diameter, BD = 0.75 mm at the focus. Pressures in the range 50 - 300 kPa have been previously reported as suitable for sonoporation, a process vital in many TDD applications, so this is a promising result. Basic functional testing of the capsule was performed by supplying glass microbubbles (MBs) through the drug delivery channel into the US focus, monitored via the onboard camera. It was found that the acoustic radiation forces have a clear influence on the MBs, significantly changing their direction at the US focus. This suggests that drugs may be targeted to specific tissue in the GI tract by the new capsule. The results translate into a capsule configuration with the potential to be clinically and biologically useful.

A Prototype Therapeutic Capsule Endoscope for Ultrasound-mediated Targeted Drug Delivery

The prevalence of gastrointestinal (GI) diseases such as Crohn’s disease, which is chronic and incurable, are increasing worldwide. Treatment often involves potent drugs with unwanted side effects. The technological–pharmacological combination of capsule endoscopy with ultrasound-mediated targeted drug delivery (UmTDD) described in this paper carries new potential for treatment of these diseases throughout the GI tract. We describe a proof-of-concept UmTDD capsule and present preliminary results to demonstrate its promise as an autonomous tool to treat GI diseases.

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.