Non-invasive evaluation of left ventricular afterload, part 2 : arterial pressure-flow and pressure-volume relations in humans

The mechanical load imposed by the systemic circulation to the left ventricle is an important determinant of normal and abnormal cardiovascular function. Left ventricular afterload is determined by complex time-varying phenomena, which affect pressure and flow patterns generated by the pumping ventricle. Left ventricular afterload is best described in terms of pressure-flow relations, allowing for quantification of various components of load using simplified biomechanical models of the circulation, with great potential for mechanistic understanding of the role of central hemodynamics in cardiovascular disease and the effects of therapeutic interventions. In the second part of this tutorial, we review analytic methods used to characterize left ventricular afterload, including analyses of central arterial pressure-flow relations and windkessel modeling (pressure-volume relations). Conceptual descriptions of various models and methods are emphasized over mathematical ones. Our review is aimed at helping researchers and clinicians obtain and interpret results from analyses of left ventricular afterload in clinical and epidemiological settings

Progress Towards a Multi-Modal Capsule Endoscopy Device Featuring Microultrasound Imaging

Current clinical standards for endoscopy in the gastrointestinal (GI) tract combine high definition optics and ultrasound imaging to view the lumen superficially and through its thickness. However, these instruments are limited to the length of an endoscope and the only clinically available, autonomous devices able to travel the full length of the GI tract easily offer only video capsule endoscopy (VCE). Our work seeks to overcome this limitation with a device (“Sonopill”) for multimodal capsule endoscopy, providing optical and microultrasound (μUS) imaging and supporting sensors1. μUS transducers have been developed with multiple piezoelectric materials operating across a range of centre frequencies to study viability in the GI tract. Because of the combined constraints of μUS imaging and the low power / heat tolerance of autonomous devices, a hybrid approach has been taken to the transducer design, with separate transmit and receive arrays allowing multiple manufacturing approaches to maximise system efficiency. To explore these approaches fully, prototype devices have been developed with PVDF, high-frequency PZT and PMN-PT composites, and piezoelectric micromachined ultrasonic transducer arrays. Test capsules have been developed using 3D printing to investigate issues including power consumption, heat generation / dissipation, acoustic coupling, signal strength and capsule integrity. Because of the high functional density of the electronics in our proposed system, application specific integrated circuits (ASICs) have been developed to realise the ultrasound transmit and receive circuitry along with white-light and autofluorescence imaging with single-photon avalanche detectors (SPADs). The ultrasound ASIC has been developed and the SPAD electronics and optical subsystem have been validated experimentally. The functionality of various transducer materials has been examined as a function of frequency and ultrasound transducers have been developed to operate at centre frequencies in the range 15 - 50 MHz. Ex vivo testing of porcine tissue has been performed, generating images of interest to the clinical community, demonstrating the viability of the Sonopill concept

Detection of breast cancer with electrical impedance mammography

Electrical Impedance Tomography (EIT) is a medical imaging technique that reconstructs internal electrical conductivity distribution of a body from impedance data that is measured on the body surface, and Electrical Impedance Mammography (EIM) is the technique that applies EIT in breast cancer detection. The use of EIM for breast cancer identification is highly desirable because it is a non-invasive and low-cost imaging technology. EIM has the potential in detecting early stage cancer, however there are still challenges that hindering EIM to be provided as a routine health care system. There are three major groups of obstacles. One is the hardware design, which includes the selection of electronic components, electrode-skin contacting methods, etc. Second is theoretical problems such as electrode configurations, image reconstruction and regularization methods. Third is the development of analysis methods and generation of a cancerous tissue database. Research reported in this thesis strives to understand these problems and aims to provide possible solutions to build a clinical EIM system. The studies are carried out in four parts. First the functionalities of the Sussex Mk4 EIM system have been studied. Sensitivity of the system was investigated to find out the strength and weakness of the system. Then work has been made on image reconstruction and regularization methods in order to enhance the system’s endurance to noise, also to balance the reconstruction conductivity distribution throughout the reconstructed object. Then a novel cancer diagnosis technique was proposed. It was developed based on the electrical property of human breast tissue and the behaviour or systematic noise, to provide repeatable results for each patient. Finally evaluation has been made on previous EIM systems to find out the major problems. Based on sensitivity analysis, an optimal combined electrode configuration has been proposed to improve sensitivity. The system has been developed and produced meaningful clinical images. The work makes significant contributions to society. This novel cancer diagnosis method has high accuracy for cancer identification. The combined electrode configuration has also provided flexibilities in the designing of current driving and voltage receiving patterns, thus sensitivity of the EIM system can be greatly improved

A Dual-Beam Irradiation Facility for a Novel Hybrid Cancer Therapy

In this paper we present the main ideas and discuss both the feasibility and the conceptual design of a novel hybrid technique and equipment for an experimental cancer therapy based on the simultaneous and/or sequential application of two beams, namely a beam of neutrons and a CW (continuous wave) or intermittent sub-terahertz wave beam produced by a gyrotron for treatment of cancerous tumors. The main simulation tools for the development of the computer aided design (CAD) of the prospective experimental facility for clinical trials and study of such new medical technology are briefly reviewed. Some tasks for a further continuation of this feasibility analysis are formulated as well.Comment: 18 pages, 3 tables, 8 figures, 50 reference

NASA contributions to - Cardiovascular monitoring

NASA contributions to cardiovasular monitorin

Applications of Graphene Quantum Dots in Biomedical Sensors

Due to the proliferative cancer rates, cardiovascular diseases, neurodegenerative disorders, autoimmune diseases and a plethora of infections across the globe, it is essential to introduce strategies that can rapidly and specifically detect the ultralow concentrations of relevant biomarkers, pathogens, toxins and pharmaceuticals in biological matrices. Considering these pathophysiologies, various research works have become necessary to fabricate biosensors for their early diagnosis and treatment, using nanomaterials like quantum dots (QDs). These nanomaterials effectively ameliorate the sensor performance with respect to their reproducibility, selectivity as well as sensitivity. In particular, graphene quantum dots (GQDs), which are ideally graphene fragments of nanometer size, constitute discrete features such as acting as attractive fluorophores and excellent electro-catalysts owing to their photo-stability, water-solubility, biocompatibility, non-toxicity and lucrativeness that make them favorable candidates for a wide range of novel biomedical applications. Herein, we reviewed about 300 biomedical studies reported over the last five years which entail the state of art as well as some pioneering ideas with respect to the prominent role of GQDs, especially in the development of optical, electrochemical and photoelectrochemical biosensors. Additionally, we outline the ideal properties of GQDs, their eclectic methods of synthesis, and the general principle behind several biosensing techniques.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

Investigation of undesired errors relating to the planar array system of electrical impedance mammography for breast cancer detection

Breast cancer in women continues to be one of the leading causes of death in the world. Since the exact causes are not completely known, the most important approach is to reduce this mortality by early detection and treatment. Although the current detection techniques for breast cancer such as X-ray mammography provide useful informationfor diagnosis; development of a new imaging technique using non-ionising radiation is highly desirable in order to detect breast cancer at an early stage and overcome current limitations, such as age-dependent sensitivity. Electrical Impedance Mammography (EIM) provides a new solution to break through the current limitation for early cancer detection. The focus of this thesis is to investigate the current fourth generation Sussex EIM system. This system implements the EIM technique by examination of the tissueresponse to a multi-frequency injected current. The Sussex Mk4 system is discussed indetail followed by system hardware modelling. The hardware modelling includes both analogue and digital components. The analogue part includes modelling of the voltage to current converter (V-I) and analogue multiplexer while the digital section consists of modelling the signal generation, measurement and demodulating components. In the analogue section, bandwidth limitation due to the current source and the analogue multiplexer’s configuration is also the prime focus of investigation along with the proposal to overcome it. Possible factors affecting the system performance and signal quality are also part of the research. In this section, possible factors are characterized and discussed in detail on the basis of external and internal sources of possible errors along with predictable and unpredictable noise sources. External sources of error artefacts introduced by the patients and their movements while scanning are most likely to affect the image reconstruction. Predictable and unpredictable causes may introduce frequency dependent noise whereas internal sources, which can be also be classified as systematic errors, degrade system performance due to electronic circuit design, configuration, stray capacitance and cable connections. Further, comprehensive investigation is performed on the in-vivoun desired voltage threshold levels which come hand-in-hand with the methods to mitigate the possible factors responsible for them. A comprehensive study and analysis is also carried out to determine what ratio of electrode blockage can affect the acquired raw data and how this may compromise reconstruction. Techniques for fast detection of any such occurrences are also discussed

SU-8 microprobes for biomedical applications

152 p. : il.[ES]La presente tesis doctoral aborda el diseño, fabricación, encapsulado, y caracterización de microagujas de SU-8 para aplicaciones médicas. En la actualidad existe una amplia variedad de agujas para el registro, estimulación y dispensado de drogas, pero se han observado algunas limitaciones en relación a su diseño y material estructural utilizados. En este trabajo se han desarrollado microagujas basadas en la tecnología de SU-8 como alternativa a las agujas actuales. Primeramente se diseñan las agujas para cada tipo de aplicación, después se determinan los procedimientos de fabricación y finalmente se desarrollan los encapsulados para conectar la aguja miniaturizada con el exterior macroscópico. La aplicación de las agujas se ha centrado en dos campos biomédicos: 1) la monitorización de órganos tal como el riñón, y 2) el registro de la actividad neuronal, añadiendo la posibilidad de realizar dispensado de drogas de forma simultánea. El primer objetivo es crear microagujas que causen el menor daño posible en el tejido biológico. Las mediciones eléctricas que se llevan a cabo para conocer el estado real del tejido pueden resultar modificadas, debilitadas o destruidas si las células que constituyen el tejido han sido previamente dañadas. En este trabajo, se desarrollan microagujas basadas en la tecnología MEMS (micro electromechanical systems) para evitar daños profundos en el tejido y poder así realizar mediciones fidedignas. La tecnología MEMS integra elementos y dispositivos eléctricos, mecánicos y electrónicos miniaturizados, los cuales están basados en la industria consolidada de los Circuitos Integrados (IC). Generalmente, las dimensiones de los elementos basados en MEMS son de entre 1 y 100 micras y los dispositivos pueden variar entre 20 micras y 1 milímetro. Las técnicas base de esta tecnología son la deposición de materiales en láminas, la fotolitografía y el grabado. El silicio es el material más utilizado para crear los múltiples dispositivos MEMS, sin embargo, su rigidez y fragilidad ha motivado el estudio de otros materiales tales como los polímeros. En esta tesis se ha utilizado el polímero SU-8 como material estructural debido a sus propiedades favorables para la fabricación de microagujas. Además, la fabricación de microagujas con este polímero permite el uso de procesos de bajo coste. Esta fotoresina presenta una baja absorción a la luz UV, posibilitando exposiciones uniformes en función del espesor del polímero. Así, se obtienen perfiles verticales y un buen control dimensional para toda la estructura. Además, estudios recientes muestran una adecuada biocompatibilidad del polímero SU-8. El segundo objetivo es obtener la más alta relación señal-ruido posible en las mediciones eléctricas. Para ello se han integrado microelectrodos en las agujas y se ha estudiado la constitución física, la configuración espacial y los tratamientos superficiales de los mismos. Un determinado diseño para cada aplicación y la modificación de las técnicas de fabricación han dado como resultado una óptima capacidad sensora de los electrodos. Así, se ha demostrado su uso a través de la monitorización de episodios de isquemia y reperfusión en riñón de rata. En cuanto a las aplicaciones neuronales, se han registrado potenciales de acción con una amplitud de hasta 400-500 ¿V en hipocampo de rata. Además, se ha demostrado que los microelectrodos son capaces de discriminar diferentes fuentes neuronales. Todos estos resultados han demostrado la versatilidad del polímero para crear dispositivos sensores con aplicación en diversas áreas biomédicas. El último objetivo de esta tesis ha sido integrar canales microfluídicos en la aguja para poder dispensar drogas en aplicaciones neuronales y como resultado, detectar cambios en la actividad neuronal. Finalmente, se han llevado a cabo los primeros experimentos fluídicos in vivo en hipocampo de rata como prueba de concepto. Se dispensan 0.5 ¿l de una disolución de kainato y a continuación se registra un incremento en la actividad neuronal. Los resultados preliminares han demostrado la funcionalidad de la aguja para dispensar y monitorizar de forma simultánea aunque se tienen que realizar más experimentos y optimizar el protocolo experimental para verificar el buen funcionamiento de la aguja. En estos momentos, se están realizando más experimentos neuronales para llegar a establecer la tecnología desarrollada en esta tesis