Deep learning for fast and robust medical image reconstruction and analysis

Medical imaging is an indispensable component of modern medical research as well as clinical practice. Nevertheless, imaging techniques such as magnetic resonance imaging (MRI) and computational tomography (CT) are costly and are less accessible to the majority of the world. To make medical devices more accessible, affordable and efficient, it is crucial to re-calibrate our current imaging paradigm for smarter imaging. In particular, as medical imaging techniques have highly structured forms in the way they acquire data, they provide us with an opportunity to optimise the imaging techniques holistically by leveraging data. The central theme of this thesis is to explore different opportunities where we can exploit data and deep learning to improve the way we extract information for better, faster and smarter imaging. This thesis explores three distinct problems. The first problem is the time-consuming nature of dynamic MR data acquisition and reconstruction. We propose deep learning methods for accelerated dynamic MR image reconstruction, resulting in up to 10-fold reduction in imaging time. The second problem is the redundancy in our current imaging pipeline. Traditionally, imaging pipeline treated acquisition, reconstruction and analysis as separate steps. However, we argue that one can approach them holistically and optimise the entire pipeline jointly for a specific target goal. To this end, we propose deep learning approaches for obtaining high fidelity cardiac MR segmentation directly from significantly undersampled data, greatly exceeding the undersampling limit for image reconstruction. The final part of this thesis tackles the problem of interpretability of the deep learning algorithms. We propose attention-models that can implicitly focus on salient regions in an image to improve accuracy for ultrasound scan plane detection and CT segmentation. More crucially, these models can provide explainability, which is a crucial stepping stone for the harmonisation of smart imaging and current clinical practice.Open Acces

Piezoelectric energy harvesting utilizing metallized poly-vinylidene fluoride (PVDF)

The primary objective of the enclosed thesis was to identify and develop a viable concept for an autonomous sensor system that could be implemented onto the surface of a road. This was achieved by an analysis of combinations of materials, sensing methods, power sources, microsystems, energy storage options, and wireless data transmission systems; the sub-systems required for an autonomous sensor. Comparison of sensing methods for the application of an on-road, autonomous sensor yielded a piezoelectric material as the ideal choice. A 52μm thin film of poly- vinylidene fluoride (PVDF) was chosen and coated with Ag electrodes on both sides.This was due to many constraints imposed by the intended environment including: physical, electrical, thermal, and manufacturing characteristics. One major hurdle in providing an autonomous sensor is the power source for the sensing, encoding, and transmission of data. Research involved determining the option best suited for providing a power source for the combination of sensors and wireless telemetry components. An energy budget of 105μJ was established to determine an estimate of energy needed to wirelessly transmit data with the selected RF transmitter. Based on these results, several candidates for power sources were investigated, and a piezoelectric energy harvesting system was identified to be the most suitable. This is an ideal case as the sensor system was already based on a piezoelectric material as the sensing component. Thus, a harvesting circuit and the sensor can be combined into one unit, using the same material. By combining the two functions into a single component, the complexity, cost and size of the unit are effectively minimized. In order to validate the conclusions drawn during this sensor system analysis and conceptual research, actual miniaturized systems were designed to demonstrate the ability to sense and harvest energy for the applications in mind. This secondary aspect of the research was a proof-of-concept, developing two prototype energy harvesting/sensing systems. The system designed consisted of a PVDF thin film with a footprint of 0.2032 m x 0.1397m x 52μm. This film was connected to an energy-harvesting prototype circuit consisting of a full-wave diode bridge and a storage capacitor. Two prototypes were built and tested, one with a 2.2μF capacitor, the other with a 0.1mF capacitor. The film was first connected to an oscilloscope and impulsed in an open circuit condition to determine the sensor response to a given signal. Secondly, the energy harvesting circuits were tested in conjunction with the film to test the energy supply component of the system. Lastly, the film and both energy-harvesting systems underwent full scale testing on a road using a vehicle as the stimulus. Both systems showed excellent rectification of the double polarity input with an evident rise in voltage across the capacitor, meaning energy was harvested. Typical results from the tests yielded 600-800mV across the 2.2μF capacitor, harvesting only a few μJ of energy. The 0.1mF capacitor system yielded approximately 4V per vehicle axle across the capacitor, harvesting 400-800μJ of energy. This equates to 4-8 times the required energy for wireless data transmission of the measurement data, which was estimated by other research groups to be on the order of 105μJ for the given system, and therefore proves the concept both, for bench-top and full-scale on-road experiments under controlled laboratory conditions

High-throughput large-area plastic nanoelectronics

Large-area electronics (LAE) manufacturing has been a key focus of both academic and industrial research, especially within the last decade. The growing interest is born out of the possibility of adding attractive properties (flexibility, light weight or minimal thickness) at low cost to well-established technologies, such as photovoltaics, displays, sensors or enabling the realisation of emerging technologies such as wearable devices and the Internet of Things. As such there has been great progress in the development of materials specifically designed to be employed in solution processed (plastic) electronics, including organic, transparent metal oxide and nanoscale semiconductors, as well as progress in the deposition methods of these materials using low-cost high-throughput printing techniques, such as gravure printing, inkjet printing, and roll-to-roll vacuum deposition. Meanwhile, industry innovation driven by Moore’s law has pushed conventional silicon-based electronic components to the nanoscale. The processes developed for LAE must strive to reach these dimensions. Given that the complex and expensive patterning techniques employed by the semiconductor industry so far are not compatible with LAE, there is clearly a need to develop large-area high throughput nanofabrication techniques. This thesis presents progress in adhesion lithography (a-Lith), a nanogap electrode fabrication process that can be applied over large areas on arbitrary substrates. A-Lith is a self-alignment process based on the alteration of surface energies of a starting metal electrode which allows the removal of any overlap of a secondary metal electrode. Importantly, it is an inexpensive, scalable and high throughput technique, and, especially if combined with low temperature deposition of the active material, it is fundamentally compatible with large-area fabrication of nanoscale electronic devices on flexible (plastic) substrates. Herein, I present routes towards process optimisation with a focus on gap size reduction and yield maximisation. Asymmetric gaps with sizes below 10 nm and yields of > 90 % for hundreds of electrode pairs generated on a single substrate are demonstrated. These large width electrode nanogaps represent the highest aspect ratio nanogaps (up to 108) fabricated to date. As a next step, arrays of Schottky nanodiodes are fabricated by deposition of a suitable semiconductor from solution into the nanogap structures. Of principal interest is the wide bandgap transparent semiconductor, zinc oxide (ZnO). Lateral ZnO Schottky diodes show outstanding characteristics, with on-off ratios of up to 106 and forward current values up to 10 mA for obtained upon combining a-Lith with low-temperature solution processing. These unique devices are further investigated for application in rectifier circuits, and in particular for potential use in radio frequency identification (RFID) tag technology. The ZnO diodes are found to surpass the 13.56 MHz frequency bernchmark used in commercial applications and approach the ultra-high frequency (UHF) band (hundreds of megahertz), outperforming current state of the art printed diodes. Solution processed fullerene (C60) is also shown to approach the UHF band in this co-planar device configuration, highlighting the viability of a-Lith for enabling large-area flexible radio frequency nanoelectronics. Finally, resistive switching memory device arrays based on a-Lith patterned nanogap aluminium symmetric electrodes are demonstrated for the first time. These devices are based either on empty aluminium nanogap electrodes, or with the gap filled with a solution-processed semiconductor, the latter being ZnO, the semiconducting polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) or carbon nanotube/polyfluorene blends. The switching mechanism, retention time and switching speed are investigated and compared with published data. The fabrication of arrays of these devices illustrates the potential of a-Lith as a simple technique for the realisation of large-area high-density memory applications.Open Acces

Engineering mechanobiology: the bacterial exclusively-mechanosensitive ion channel MscL as a future tool for neuronal stimulation technology

The development of novel approaches to stimulate neuronal circuits is crucial to understand the physiology of neuronal networks, and to provide new strategies to treat neurological disorders. Nowadays, chemical, electrical or optical approaches are the main exploited strategies to interrogate and dissect neuronal circuit functions. However, although all these methods have contributed to achieve important insights into neuroscience research field, they all present relevant limitations for their use in in-vivo studies or clinical applications. For example, while chemical stimulation does not require invasive surgical procedures, it is difficult to control the pharmacokinetics and the spatial selectivity of the stimulus; electrical stimulation provides high temporal bandwidth, but it has low spatial resolution and it requires implantation of electrodes; optical stimulation provides subcellular resolution but the low depth penetration in dense tissue still requires the invasive insertion of stimulating probes. Due to all these drawbacks, there is still a strong need to develop new stimulation strategies to remotely activate neuronal circuits as deep as possible. The development of remote stimulation techniques would allow the combination of functional and behavioral studies, and the design of novel and minimally invasive prosthetic approaches. Alternative approaches to circumvent surgical implantation of probes include transcranial electrical, thermal, magnetic, and ultrasound stimulation. Among v these methods, the use of magnetic and ultrasound (US) fields represents the most promising vector to remotely convey information to the brain tissue. Both magnetic and low-intensity US fields provide an efficient mean for delicate and reversible alteration of cells and tissues through the generation of local mechanical perturbations. In this regard, advances in the mechanobiology research field have led to the discovery, design and engineering of cellular transduction pathways to perform stimulation of cellular activity. Furthermore, the use of US pressure fields is attracting considerable interest due to its potential for the development of miniaturized, portable and implantation-free US stimulation devices. The purpose of my PhD research activity was the establishment of a novel neuronal stimulation paradigm adding a cellular selectivity to the US stimulation technology through the selective mechano-sensitization of neuronal cells, in analogy to the well-established optogenetic approach. In order to achieve the above mentioned goal, we propose the cellular overexpression of mechanosensitive (MS) ion channels, which could then be gated upon the application of an US generated pressure field. Therefore, we selected the bacterial large conductance mechanosensitive ion channel (MscL), an exclusively-MS ion channel, as ideal tool to develop a mechanogenetic approach. Indeed, the MscL with its extensive characterization represents a malleable nano-valve that could be further engineered with respect to channel sensitivity, conductance and gating mechanism, in order to obtain the desired biophysical properties to achieve reliable and efficient remote mechanical stimulation of neuronal activity. In the first part of the work, we report the development of an engineered MscL construct, called eMscL, to induce the heterologous expression of the bacterial protein in rodent primary neuronal cultures. Furthermore, we report the structural and functional characterization of neuronal cells expressing the eMscL channel, at both single-cell and network levels, in order to show that the functional expression of the engineered MscL channel induces an effective vi neuronal sensitization to mechanical stimulation, which does not affect the physiological development of the neuronal itself. In the second part of the work, we report the design and development of a water tank-free ultrasound delivery system integrated to a custom inverted fluorescence microscope, which allows the simultaneous US stimulation and monitoring of neuronal network activity at single resolution. Overall, this work represents the first development of a genetically mechanosensitized neuronal in-vitro model. Moreover, the developed US delivery system provides the platform to perform high-throughput and reliable investigation, testing and calibration of the stimulation protocols. In this respect, we propose, and envisage in the near future, the exploitation of the engineered MscL ion channel as a mature tool for novel neuro-technological applications