49 research outputs found

    Design of a Small, Affordable Low Intensity Focused Ultrasound Device for Vagus Nerve Stimulation

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    Depression is a serious public health issue that affects more than 300 million people worldwide. While there are antidepressant drugs to alleviate depressive symptoms, 10 – 30% of patients either do not respond or develop a tolerance to these drugs. Researchers have found a correlation between the inflammatory response and treatment-resistant depression (TRD). Blocking this inflammatory pathway with electrical vagus nerve stimulation (VNS) can reduce cytokine levels and depressive symptoms. However, placing an electrical VNS device is invasive, costly, and poses a risk to the vagus nerve. Low intensity focused ultrasound (LIFU) is a novel therapy that is able to both excite and suppress neuronal activity in neurological disorders. However, progression of this research area has been impeded by the size and price of these devices. I designed a 50 x 57 x 76 mm LIFU device that consists of a transducer, matching network, and amplification network. Next, I characterized my LIFU device with 2D intensity maps of the focused ultrasound (FUS) field. My device produced an instantaneous intensity up to 350 mW/cm2. My colleagues and I applied the LIFU device on Sprague-Dawley rats (n=12) for VNS with the primary goal of reducing the inflammatory response. Five out of the eight rats that we analyzed showed a decrease in the cytokine TNF-α. Future work will involve design improvements and more animal studies with varying stimulation parameters. As FUS technology becomes smaller we move closer to wearable devices. As FUS technology becomes more affordable more research groups will have the opportunity to employ this novel therapy to investigate the pathophysiology of neurological disorders

    The Generation and Control of Ultrasonic Waves in Nonlinear Media

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    The objective of this thesis is to utilise modern open-design ultrasound research platforms to develop new and advance several existing techniques that incorporate nonlinear phenomena. Acoustically, nonlinearity refers to changes in speed of sound, attenuation or elasticity that vary with frequency, temperature or pressure. These effects cannot be linearised by the wave equation and require fluid dynamics and elasticity equations to be fully understood. While this is a hindrance and source of error in many areas of ultrasound such as high-intensity focused ultrasound (HIFU) and medical imaging, nonlinearities do have uses in non-destructive guided wave (GW) testing. These effects are influenced greatly by the transducer surface pressure, and so precise control of the excitation is necessary to achieve the desired nonlinear effect, if any, in the medium. In this thesis, aided by the use of two new research platforms, several new ultrasound techniques were developed. It was shown the frequency content in the electrical waveform is pertinent and so distortion must be minimised. This requirement conflicts with several hardware limitations, however. Accordingly, a genetic algorithm was applied to find novel switched waveform designs. It was found to achieve a 2% granularity in amplitude control with harmonic reduction, where existing waveform designs could not produce any. This fine amplitude control is a requirement for array applications. Following this, a technique to control the direction of GWs without knowledge of the waveguide was devised. Recordings of a propagating GW, induced by the first element of an array transducer, were re-transmitted in a recursive fashion. The effect was that the transducer's transmissions constructively interfered with the transverse wave, causing most of the guided wave energy to travel in the direction of the transducer's spatial influence. Experimental results show a 34 dB enhancement in one direction compared with the other. GWs were then applied to bone for two purposes: for assessment of osteoporosis and for measurement of skull properties to assist transcranial therapy. It was shown that existing methods for obtaining dispersion curves are ineffectual due to limitations in the available sampling area. A signal processing scheme was devised to temporally align transverse dispersive waves so that beamforming style techniques could be applied to prove or disprove the existence of certain modes. The technique in combination with multiplication was applied to numerical, ex vivo and in vivo experiments. It was found to improve the contrast of the higher order modes. The technique could improve the reliability of osteoporosis diagnosis with ultrasound, but may also prove useful for acquiring dispersion images in NDT. Numerically the technique was shown to improve the S3 and A3 mode intensity by 6 dB and 13 dB respectively compared with an existing Fourier method. In skull, a relationship was found between the curved therapeutic array geometry and the delay profile necessary to form GWs in skull. Several numerical models were tested and it was shown that the thickness could be obtained from the group velocity. The estimated maximum error using this technique was 0.2 mm. Since the data is co-registered with the therapeutic elements, this method could be used to improve the accuracy of thermal treatments in the brain. Finally, the application of switched excitation for HIFU was considered. To improve on cost, efficiency and size, alternative excitation methods have the potential to replace the linear amplifier circuitry currently used in HIFU. In this final study, harmonic reduction pulse width modulation (HRPWM) was proposed as an algorithmic solution to the design of switched waveforms. Its appropriateness for HIFU was assessed by design of a high power 5 level unfiltered amplifier and subsequent thermal-only lesioning of ex vivo chicken breast. HRPWM produced symmetric, thermal-only lesions that were the same size as their linear amplifier equivalents (p > 0.05). These results demonstrate that HRPWM can minimise HIFU drive circuity size without the need for filters to remove harmonics or adjustable power supplies to achieve array apodisation. Overall it has been shown in this thesis that precise control of the nonlinear wave phenomena can be afforded when using open-platform ultrasound research hardware. The methods described within may reduce the cost and increase the efficacy of future commercial systems

    Ultrasound for Material Characterization and Processing

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    Ultrasonic waves are nowadays used for multiple purposes including both low-intensity/high frequency and high-intensity/low-frequency ultrasound. Low-intensity ultrasound transmits energy through the medium in order to obtain information about the medium or to convey information through the medium. It is successfully used in non-destructive inspection, ultrasonic dynamic analysis, ultrasonic rheology, ultrasonic spectroscopy of materials, process monitoring, applications in civil engineering, aerospace and geological materials and structures, and in the characterization of biological media. Nowadays, it is an essential tool for assessing metals, plastics, aerospace composites, wood, concrete, and cement. High-intensity ultrasound deliberately affects the propagation medium through the high local temperatures and pressures generated. It is used in industrial processes such as welding, cleaning, emulsification, atomization, etc.; chemical reactions and reactor induced by ultrasonic waves; synthesis of organic and inorganic materials; microstructural effects; heat generation; accelerated material characterization by ultrasonic fatigue testing; food processing; and environmental protection. This book collects eleven papers, one review, and ten research papers with the aim to present recent advances in ultrasonic wave propagation applied for the characterization or the processing of materials. Both fundamental science and applications of ultrasound in the field of material characterization and material processing have been gathered

    Imaging Sensors and Applications

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    In past decades, various sensor technologies have been used in all areas of our lives, thus improving our quality of life. In particular, imaging sensors have been widely applied in the development of various imaging approaches such as optical imaging, ultrasound imaging, X-ray imaging, and nuclear imaging, and contributed to achieve high sensitivity, miniaturization, and real-time imaging. These advanced image sensing technologies play an important role not only in the medical field but also in the industrial field. This Special Issue covers broad topics on imaging sensors and applications. The scope range of imaging sensors can be extended to novel imaging sensors and diverse imaging systems, including hardware and software advancements. Additionally, biomedical and nondestructive sensing applications are welcome

    Minimally invasive therapies for the brain using magnetic particles

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    Delivering a therapy with precision, while reducing off target effects is key to the success of any novel therapeutic intervention. This is of most relevance in the brain, where the preservation of surrounding healthy tissue is crucial in reducing the risk of cognitive impairment and improving patient prognosis. Our scientific understanding of the brain would also benefit from minimally invasive investigations of specific cell types so that they may be observed in their most natural physiological environment. Magnetic particles based techniques have the potential to deliver cellular precision in a minimally invasive manner. When inside the body, Magnetic particles can be actuated remotely using externally applied magnetic fields while their position can be detected non-invasively using MRI. The magnetic forces applied to the particles however, rapidly decline with increasing distance from the magnetic source. It is therefore critical to understand the amount of force needed for a particular application. The properties of the magnetic particle such as the size, shape and magnetic content, as well as the properties of the applied magnetic field, can then be tailored to that application. The aim of this thesis was to develop magnetic particle based techniques for precise manipulation of cells in the brain. Two different approaches were explored, utilising the versatile nature of magnetic actuation for two different applications. The first approach uses magnetic nanoparticles to mechanically stimulate a specific cell type. Magnetic particles conjugated with the antibody ACSA-1 would selectively bind to astrocytes to evoke the controlled release of ATP and induce a calcium flux which are used for communication with neighbouring cells. This approach allows for the investigation into the role of astrocytes in localised brain regions using a naturally occurring actuation process (mechanical force) without effecting their natural environment. The second approach uses a millimetre sized magnetic particle which can be navigated through the brain and ablate localised regions of cells using a magnetic resonance imaging system. The magnetic particle causes a distinct contrast in MRI images, allowing for precise detection of its location so that it may be iteratively guided along a pre-determined path to avoid eloquent brain regions. Once at the desired location, an alternating magnetic field can be applied causing the magnetic particle to heat and deliver controllable, well defined regions of cell death. The forces needed for cell stimulation are orders of magnitude less than the forces needed to guide particles through the brain. Chapters 4 and 5 use external magnets to deliver forces in the piconewton range. While stimulation was demonstrated in small animals, scaling up this technique to human proportions remains a challenge. Chapters 6 and 7 use a preclinical MRI system to generate forces in the millinewton range, allowing the particle to be moved several centimetres through the brain within a typical surgical timescale. When inside the scanner, an alternating magnetic field causes the particle to heat rapidly, enabling the potential for multiple ablations within a single surgery. For clinical translation of this technique, MRI scanners would require a dedicated propulsion gradient set and heating coil

    Versatile LCP surface microelectrodes for combining electrophysiology and in vivo two-photon imaging in the murine CNS

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    Neurons and astrocytes are highly interconnected and form a complex cellular network for signal processing in the brain. The electrical activity of neurons and astroglial Ca2+ signals are tightly coupled. Parallel recording of electrical activity and Ca2+ signals can help to identify the molecular mechanisms of neuron-glia communications. In this work, flexible liquid crystal polymer microelectrode arrays for electrical recordings and stimulations during two-photon laser-scanning microscopy (2P-LSM) were developed. The arrays were designed for standard craniotomies used for cortical 2P-LSM in vivo imaging. Being of low weight, thin and flexible, they can be easily positioned between the dura mater and the glass coverslip. Three different designs were constructed: arrays (1) with eight circular electrodes (arranged in a matrix of three by three elements, sparing the center), (2) with sixteen circular electrodes (four by four matrix) and (3) with eight rectangular electrodes (placed in four groups of 2 single sites). The initial contact sites of gold were coated with nanoporous platinum to decrease the impedance of the electrode tissue contacts and to increase the charge transfer capability. The biocompatibility of the electrodes was confirmed by immuno-histochemistry. Electrical recordings and Ca2+-imaging were performed in mice with neuronal or astroglial expression of the genetically encoded Ca2+-sensor GCaMP3. With the sixteen channel electrode arrays, an estimation of the spatially resolved electrical activity pattern within the cranial window could be described. The eight channel arrays were used in studies for simultaneous acquisition of Ca2+ (using 2P-LSM) and electrical signals. In addition, Ca2+ signals could be elicited by electrical stimulation. Using different stimulation intensities and depth of anesthesia, the change of brain activity during transition from anesthetized to awake state was investigated. In addition, the LCP technology was transferred from the cortical to a spinal cord application.Neurone und Astrozyten bilden ein komplexes interagierendes zellulares Netzwerk zur Signalverarbeitung im Gehirn. Dabei sind die elektrische Aktivitäten der Nervenzellen und die Ca2+ Signale der Astrozyten eng aneinander gekoppelt. Parallele Aufzeichnungen der elektrischen Aktivität und der Ca2+ Signale können helfen, die molekularen Mechanismen der Neuron-Glia-Kommunikation zu identifizieren. Innerhalb dieser Arbeit wurden flexible Flüssigkristall-Polymer-Mikroelektrodenarrays für elektrische Aufzeichnungen und Stimulationen für die Zwei-Photonen-Laserscan- Mikroskopie (2P-LSM) entwickelt. Die Elektrodenarrays wurden für Standard-Kraniotomien entwickelt, die für die kortikale in vivo 2P-LSM verwendet werden. Sie sind dünn, flexibel und von geringem Gewicht und können leicht auf der Dura positioniert werden. Drei verschiedene Designs wurden konstruiert: Arrays (1) mit acht runden Elektroden (angeordnet in einer drei mal drei Matrix, ohne die mittlere Elektrode), (2) mit sechzehn kreisförmigen Elektroden (vier mal vier Matrix) und (3) mit acht rechteckigen Elektroden (angeordnet in vier Gruppen von zwei einzelnen Standorten). Die ursprünglichen Elektrodenkontakte aus Gold wurden mit nanoporösem Platin beschichtet, um die Gewebekontaktimpedanz zu verringern und die Ladungsübertragungsfähigkeit zu erhöhen. Die Biokompatibilität der Elektroden immunhistochemisch getestet. Elektrische Aktivität und Ca2+ Signale wurden bei Mäusen mit neuronaler oder astroglialer Expression des Ca2+-Indikators GCaMP3 aufgezeichnet. Mit den sechzehn Kanal-Elektroden-Arrays konnten die elektrische Aktivität entlang der Kortexoberfläche innerhalb der Kraniotomie charakterisiert werden. Die achtkanaligen Arrays wurden zur gleichzeitigen Erfassung von Ca2+ (mit 2P-LSM) und elektrischen Signalen verwendet. Darüber hinaus konnten Ca2+ Signale durch elektrische Stimulation hervorgerufen werden. Mit verschiedenen Stimulationsintensitäten und der Tiefe der Anästhesie (Isofluran) wurde die Veränderung der Hirnaktivität beim Übergang von anästhesiert zu wach beobachtet. Zusätzlich konnte die Flüssigkristall-Polymer -Technologie von der kortikalen auf die spinale Anwendung übertragen werden.- European Union / EUGlia-PhD - European Union / Neurofibre

    Design of Acoustic Lenses for Ultrasound Focusing Applications

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    Tesis por compendio[ES] La focalización de ultrasonidos tiene muchas aplicaciones en una gran variedad de áreas tanto científicas como industriales. Los ultrasonidos focalizados son una de las herramientas principales usada por médicos en todo el mundo para obtener imágenes biomédicas de diferentes tipos de tejidos y órganos de manera no invasiva. En las últimas décadas, el uso de ultrasonidos focalizados de alta intensidad (HIFU, por sus siglas en inglés) ha surgido como una de las técnicas principales para el tratamiento de cáncer mediante la ablación térmica de tumores de manera no invasiva. Además, los ultrasonidos focalizados están emergiendo en los últimos años como uno de los métodos más prometedores para el tratamiento de las enfermedades cerebrales, con la aparición de nuevas técnicas disruptivas como la apertura reversible de la barrera hematoencefálica o la neuromodulación. En entornos industriales, los ultrasonidos son ampliamente utilizados como uno de los métodos principales para la evaluación no destructiva de materiales y estructuras, debido a que las ondas acústicas pueden penetrar en los objetos a distancias donde la luz no puede debido a la elevada absorción y dispersión. En este sentido, diseñar estructuras capaces de focalizar ultrasonidos es de una gran relevancia tanto para la comunidad científica como para los sectores médicos e industriales. Esta tesis presenta nuevos diseños de lentes acústicas capaces de controlar los parámetros principales del haz de ultrasonidos focalizados, proporcionando diferentes tipos de perfiles de focalización adecuados para una gran variedad de aplicaciones y escenarios. En particular, se han diseñado y adaptado al campo de los ultrasonidos las lentes de Fresnel (Fresnel Zone Plates, FZPs), ampliamente utilizadas en el campo de la óptica. Se ha presentado una nueva técnica de modulación espacio-temporal capaz de controlar la posición del foco de ultrasonidos tanto en espacio como en tiempo, aumentando así la versatilidad de este tipo de dispositivos. También se ha demostrado el funcionamiento en el campo de la acústica de nuevos diseños basados en aplicar secuencias binarias a una lente de Fresnel convencional, como las secuencias fractales de Cantor o las secuencias de M-bonacci generalizadas, capaces de modificar las propiedades de focalización de las lentes, incluyendo el número, posición y forma de los focos acústicos. Además, se introduce un nuevo diseño de lentes esféricas rellenas de líquido capaces de generar jets ultrasónicos, con mucho potencial en aplicaciones de imagen de alta resolución en campo cercano. Se ha demostrado que, cambiando el líquido interno de la lente o ajustando el ratio de mezcla entre dos líquidos, se pueden controlar los parámetros principales del jet. Los diseños propuestos en la tesis han sido validados tanto empleando simulaciones numéricas como realizando medidas experimentales, allanando el camino para el uso de este tipo de estructuras en aplicaciones de focalización de ultrasonidos.[CA] La focalització d'ultrasons té moltes aplicacions en moltes àrees científiques i industrials. Els ultrasons focalitzats són una de les eines principals utilitzada per metges a tot el món per obtenir imatges biomèdiques de diferents tipus de teixits i òrgans de manera no invasiva. En les últimes dècades, els ultrasons focalitzats d'alta intensitat (HIFU, per les seues sigles en anglès) han aparegut com una de les tècniques principals per al tractament de càncer mitjançant l'ablació de tumors de manera no invasiva. A més, els ultrasons focalitzats estan emergint en els últims anys com un dels mètodes més prometedors per al tractament de les malalties cerebrals, amb l'aparició de noves tècniques disruptives com l'obertura reversible de la barrera hematoencefàlica o la neuromodulació. En entorns industrials, els ultrasons són àmpliament utilitzats com un dels mètodes principals per a l'avaluació no destructiva de materials i estructures, pel fet que les ones acústiques poden penetrar en els objectes a distàncies on la llum no pot a causa de l'elevada absorció i dispersió. En aquest sentit, dissenyar estructures capaces de focalitzar ultrasons és d'una gran rellevància tant per a la comunitat científica com per als sectors mèdics i industrials. Aquesta tesi presenta nous dissenys de lents acústiques capaços de controlar els paràmetres principals del feix d'ultrasons focalitzats, proporcionant diferents tipus de perfils de focalització adequats per a una gran varietat d'aplicacions i escenaris. En particular, s'han dissenyat i adaptat al camp dels ultrasons les lents de Fresnel (Fresnel Zone Plates, FZPs), àmpliament utilitzades en el camp de l'òptica. S'ha presentat una nova tècnica de modulació espai-temporal capaç de controlar la posició del focus d'ultrasons tant en espai com en temps, augmentant així la versatilitat d'aquest tipus de dispositius. També s'ha demostrat el funcionament en el camp de l'acústica de nous dissenys basats en aplicar seqüències binàries a una lent de Fresnel convencional, com les seqüències fractals de Cantor o les seqüències de M-bonacci generalitzades, capaces de modificar les propietats de focalització de les lents, incloent el nombre, posició i forma dels focus acústics. A més, s'introdueix un nou disseny de lents esfèriques plenes de líquid capaces de generar jets ultrasònics, amb molt potencial en aplicacions d'imatge d'alta resolució en camp proper. S'ha demostrat que, canviant el líquid intern de la lent o ajustant la ràtio de barreja entre dos líquids, es poden controlar els paràmetres principals del jet. Els dissenys proposats en la tesi han estat validats tant emprant simulacions numèriques com realitzant mesures experimentals, aplanant el camí per a l'ús d'aquest tipus d'estructures en aplicacions de focalització d'ultrasons.[EN] Ultrasound focusing has many applications in a wide range of fields. Focused ultrasound is one of the main tools used by doctors all over the world to obtain biomedical images of different kind of tissues non-invasively. In the past decades, high intensity focused ultrasound (HIFU) appeared as one of the fundamental techniques for cancer treatment through non-invasive thermal tumor ablation. In addition, focused ultrasonic waves are recently emerging as one of the main tools to treat brain diseases, with novel disruptive techniques such as blood-brain barrier opening or neuromodulation. In industrial environments, ultrasonic waves are widely employed as one of the primary methods for the non-destructive evaluation (NDE) of materials and structures, as acoustic waves are able to penetrate deep into objects otherwise opaque using optical techniques. In this sense, designing structures capable of focusing ultrasonic waves is of great interest and relevance for the scientific, the industrial, and the biomedical sectors. This thesis devises new designs of acoustic lenses capable of controlling the main parameters of the focused ultrasound beam, achieving different kinds of focusing profiles suitable for a wide variety of scenarios. In particular, Fresnel Zone Plates (FZPs), commonly used in optics, are designed and adapted to the ultrasound domain. A novel spatio-temporal modulation technique capable of controlling the ultrasound focus location in both time and space is presented, increasing the versatility of this kind of devices. New design techniques based on applying a binary sequence to FZPs are also demonstrated, such as Cantor fractal sequences or generalized M-bonacci sequences, which modify the focusing properties of the lens, including the number, location, and shape of the different acoustic foci. In addition, acoustic jets generated by liquid-filled spherical lenses are devised for near-field high resolution imaging, demonstrating their applicability in the ultrasound domain. It is demonstrated that, by changing the inner liquid of the spherical lens or by tuning the mixing ratio between two liquids, the main focal parameters of the ultrasonic jet can be accurately controlled. The proposed designs are validated using both numerical simulations and experimental measurements, paving the way for the use of these kind of structures in focused ultrasound applications.This work would not have been possible without the following funding sources: PAID-01-18 personal FPI grant from Universitat Politècnica de València; Spanish government MINECO TEC2015-70939-R project; Spanish government MICINN RTI2018-100792-B-I00 project; Generalitat Valenciana AICO/2020/139 project.Pérez López, S. (2021). Design of Acoustic Lenses for Ultrasound Focusing Applications [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/179907TESISCompendi
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