Computer Aided Clinical Trials for Implantable Cardiac Devices

In this effort we investigate the design and use of physiological and device models to conduct pre-clinical trials to provide early insight in the design and execution of the actual clinical trial. Computer models of physiological phenomena like cardiac electrical activity can be extremely complex. However, when the purpose of the model is to interact with a medical device, then it becomes sufficient to model the measurements that the device makes, e.g. the intra-cardiac electrograms (EGMs) that an Implantable Cardioverter Defibrillator (ICD) measures. We present a probabilistic generative model of EGMs, capable of generating exemplars of various arrhythmias. The model uses deformable shape templates, or motifs, to capture the variability in EGM shapes within one EGM channel, and a cycle length parameter to capture the variability in cycle length in one EGM channel. The relation between EGM channels, which is essential for determining whether the current arrhythmia is potentially fatal, is captured by a time-delayed Markov chain, whose states model the various combinations of (learned) motifs. The heart model is minimally parameterized and is learned from real patient data. Thus the statistics of key features reflect the statistics of a real cohort, but the model can also generate rare cases and new combinations from the inferred probabilities. On the device end, algorithms for signal sensing, detection and discrimination for major ICD manufacturers have been implemented both in simulation and on hardware platforms. The generated arrhythmia episodes are used as input to both the modeled ICD algorithms and real ICDs as part of a Computer Aided Clinical Trial (CACT). In a CACT, a computer model simulates the inputs to the device (such as a new, investigational ICD), and the device’s performance is evaluated. By incorporating these results into the appropriate statistical framework, the Computer Aided Clinical Trial results can serve as regulatory evidence when planning and executing an actual clinical trial. We demonstrate this by conducting a mock trial similar to the 2005-2010 RIGHT trial which compared the discrimination algorithms from two major ICD manufacturers. The results of the CACT clearly demonstrate that the failed outcome of the RIGHT trial could have been predicted and provides statistical support for deeper results that could have been captured prior to the trial

Wireless tissue palpation: Head characterization to improve tumor detection in soft tissue

For surgeons performing open procedures, the sense of touch is a valuable tool to directly access buried structures and organs, to identify their margins, detect tumors, and prevent undesired cuts. Minimally invasive surgical procedures provide great benefits for patients; however, they hinder the surgeon's ability to directly manipulate the tissue. In our previous work, we developed a Wireless Palpation Probe (WPP) to restore tissue palpation in Minimally Invasive Surgery (MIS) by creating a real-time stiffness distribution map of the target tissue. The WPP takes advantage of a field-based magnetic localization algorithm to measure its position, orientation, and tissue indentation depth, in addition to a barometric sensor measuring indentation tissue pressure. However, deformations of both the tissue and the silicone material used to cover the pressure sensors introduce detrimental nonlinearities in sensor measurements. In this work, we calibrated and characterized different diameter WPP heads with a new design allowing exchangeability and disposability of the probe head. Benchtop trials showed that this method can effectively reduce error in sensor pressure measurements up to 5% with respect to the reference sensor. Furthermore, we studied the effect of the head diameter on the device's spatial resolution in detecting tumor simulators embedded into silicone phantoms. Overall, the results showed a tumor detection rate over 90%, independent of the head diameter, when an indentation depth of 5 mm is applied on the tissue simulator

Component based design of a drug delivery capsule robot

Since the introduction of Wireless Capsule Endoscopy (WCE) researchers have started exploring the design space of Medical Capsule Robots (MCRs): embedded micro-systems that can operate autonomously within the human body and can diagnose, prevent, monitor, and cure diseases. Although the research in the area of MCRs is an active topic and has grown exponentially, current devices provide only limited functionalities because their design process is expensive and time consuming. To open this research field to a wider community and, at the same time, create better designs through advanced tool support, in our previous works we presented a design environment for the rapid development of MCRs. In this paper, this environment was adopted to design a Drug Delivery Capsule (DDC) based on a coil-magnet-piston mechanism. The force of the coil acting on the magnetic piston and the drug release profile were modeled and assessed on bench-top with a maximum relative error below 5%. Then, in vivo trials were performed to validate the DDC functionality with a scheduled drug release profile for a 5 h and 24 min procedure. The resulting design environment template is available open source for further development of drug delivery applications as well as to serve as guideline in prototyping novel MCRs addressing other clinical needs

Wireless Tissue Palpation: head characterization to improve tumor detection in soft tissue

Abstract For surgeons performing open procedures, the sense of touch is a valuable tool to directly access buried structures and organs, to identify their margins, detect tumors, and prevent undesired cuts. Minimally invasive surgical procedures provide great benefits for patients; however, they hinder the surgeon's ability to directly manipulate the tissue. In our previous work, we developed a Wireless Palpation Probe (WPP) to restore tissue palpation in Minimally Invasive Surgery (MIS) by creating a real-time stiffness distribution map of the target tissue. The WPP takes advantage of a field-based magnetic localization algorithm to measure its position, orientation, and tissue indentation depth, in addition to a barometric sensor measuring indentation tissue pressure. However, deformations of both the tissue and the silicone material used to cover the pressure sensors introduce detrimental nonlinearities in sensor measurements. In this work, we calibrated and characterized different diameter WPP heads with a new design allowing exchangeability and disposability of the probe head. Benchtop trials showed that this method can effectively reduce error in sensor pressure measurements up to 5 % with respect to the reference sensor. Furthermore, we studied the effect of the head diameter on the devices spatial resolution in detecting tumor simulators embedded into silicone phantoms. Overall, the results showed a tumor detection rate over 90 %, independent of the head diameter, when an indentation depth of at 5 mm is applied on the tissue simulator

ARTICLE IN PRESS G Model

a b s t r a c t For surgeons performing open procedures, the sense of touch is a valuable tool to directly access buried structures and organs, to identify their margins, detect tumors, and prevent undesired cuts. Minimally invasive surgical procedures provide great benefits for patients; however, they hinder the surgeon's ability to directly manipulate the tissue. In our previous work, we developed a Wireless Palpation Probe (WPP) to restore tissue palpation in Minimally Invasive Surgery (MIS) by creating a real-time stiffness distribution map of the target tissue. The WPP takes advantage of a field-based magnetic localization algorithm to measure its position, orientation, and tissue indentation depth, in addition to a barometric sensor measuring indentation tissue pressure. However, deformations of both the tissue and the silicone material used to cover the pressure sensors introduce detrimental nonlinearities in sensor measurements. In this work, we calibrated and characterized different diameter WPP heads with a new design allowing exchangeability and disposability of the probe head. Benchtop trials showed that this method can effectively reduce error in sensor pressure measurements up to 5% with respect to the reference sensor. Furthermore, we studied the effect of the head diameter on the device's spatial resolution in detecting tumor simulators embedded into silicone phantoms. Overall, the results showed a tumor detection rate over 90%, independent of the head diameter, when an indentation depth of 5 mm is applied on the tissue simulator

Design and Development of a Scanning Tunneling Microscope

ABSTRACT This work consists of the design and implementation of an Scanning Tunneling Microscope based on a totally digital feedback loop control and different Z and X-Y stages. Chapter I illustrates the tunneling current physics which Scanning Tunneling System is based on: after a short history remarking of its previous system, a brief description of STM is given. Then STM operative modes are explained. The state of the art of STM products complete this introductory chapter. Chapter II describes the piezoelectric effect since it was discovered, until the most recent studies, integrated by a brief mathematic description. Piezoelectric scanner are then analyzed: tripod, bimorph tube scanner and at least the piezo stack actuator which our design is based on. Two possible driver solutions: a piezo stack actuator is then illustrated. First one is the voltage multiplier based on a Dickson Charge Pump, second one is a voltage amplifier adopted in this system. Chapter III describes all developed system Hardware: MCU board, user interface, tunneling current measure and sample bias board, Z scanner and X Y stage. Developed system firmware is described in chapter IV; it manages all the electronic and the linear stepper motor controller. A manual coarse approach, an electrically controlled approach and all the scanning functions moving the STM tip over sample surface have been designed. PC firmware has been developed with C function for X86 processor, MCU firmware is based on C18 for PIC18 MCU and includes both C and Assembly instructions. Developed C functions are then illustrated in this chapter together with all the algorithm necessary to manage STM operations. Chapter V illustrates results, limitations and future developments of this STM system. RIASSUNTO ANALITICO Questo lavoro di tesi consiste nello sviluppo dell' hardware e del software di un microscopio a scansione di corrente tunnel basato su un controllo in retroazione completamente digitale e stadi traslazionali X-Y e Z tra di loro separati. Il primo capitolo illustra la fisica della corrente tunnel, il funzionamento e le modalità operatie del microscopio. Infine, per concludere il capitolo, viene presentato lo stato dell'arte. Il secondo capitolo descrive l'effetto piezoelettico dalla sua scoperta fino ai più recenti studi. Sono quindi analizzate alcune tipologie di scanner: il tripod, il bimorph e il piezo tubo. Viene quindi analizzato il funzionamento del piezo stack su cui si basa il nostro sistema. Sono quindi presentate due possibili soluzioni di driver per gli attuatori piezo stack: la prima si basa su di una pompa di carica, la seconda su di un amplificatore push pull. Nel terzo capitolo viene presentato l'hardware del sistema: la scheda per il microcontrollore, quella di misura della corrente tunnel e di polarizzazione della punta del sistema. Vengono quindi trattate le schede di comunicazione con il controller del motore lineare. Il software ed il firmware del sistema sono quindi presentati nel quarto capitolo. Sono quindi descritte le funzionalità sviluppate: l'avvicinamento manuale della punta al campione, l'avvicinamento controllato e l'avvicinamento controllato fine. Viene quindi presentato il software di controllo in retroazione digitale e le funzioni di scansione. Il software è stato sviluppato in C per architetture X86 mentre il firmware del microcontrollore in C18 ed assempler. Sempre in questo capitolo vengono infine presentate le funzioni sviluppate. Il quinto capitolo infine illustra i risultati ottenuti e gli sviluppi futuri