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- Genre: Masters Thesis
Description
The object of this study is to charac terize the effect of focused ultrasound stimulation (FUS) on the rat ce rvix which has been observed to speed its ripening during pregnancy. Ce rvical ripening is required for successful fetal delivery. Timed-pregnant Sprague-Dawley rats (n=36) were used. On day 14 of gestation, the FUS system was placed on the body surface of the rat over the cervix and ultrasound energy was applied to cervix for variable times up to 1 hour in the control group, the FUS system was placed on rats but no energy was applied. Daily measurement of cervix light-induced florescence (LIF, photon counts of collagen x-bridge fluorescence) were made on days 16 of gestation and daily until spont-aneous delivery (day22) to estimate changes in cervical ripening. We found that pulses of 680 KHz ultrasound at 25 Hertz, 1 millisecond pulse duration at 1W/cm^2 applied for as little as 30 minutes would immediately afterwards show the cervix to hav e ripened to the degree seen just before delivery on day 22. Delivery times, fetal weights and viability were unaffected in the FUS-treated animals.
ContributorsLuo, Daishen (Author) / Towe, Bruce C (Thesis advisor) / Wang, Xiao (Committee member) / Caplan, Michael (Committee member) / Arizona State University (Publisher)
Created2012
Description
Peripheral Vascular Disease (PVD) is a debilitating chronic disease of the lower extremities particularly affecting older adults and diabetics. It results in reduction of the blood flow to peripheral tissue and sometimes causing tissue damage such that PVD patients suffer from pain in the lower legs, thigh and buttocks after activities. Electrical neurostimulation based on the "Gate Theory of Pain" is a known to way to reduce pain but current devices to do this are bulky and not well suited to implantation in peripheral tissues. There is also an increased risk associated with surgery which limits the use of these devices. This research has designed and constructed wireless ultrasound powered microstimulators that are much smaller and injectable and so involve less implantation trauma. These devices are small enough to fit through an 18 gauge syringe needle increasing their potential for clinical use. These piezoelectric microdevices convert mechanical energy into electrical energy that then is used to block pain. The design and performance of these miniaturized devices was modeled by computer while constructed devices were evaluated in animal experiments. The devices are capable of producing 500ms pulses with an intensity of 2 mA into a 2 kilo-ohms load. Using the rat as an animal model, a series of experiments were conducted to evaluate the in-vivo performance of the devices.
ContributorsZong, Xi (Author) / Towe, Bruce (Thesis advisor) / Kleim, Jeffrey (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2014
Description
There is a strong medical need and important therapeutic applications for improved wireless bioelectric interfaces to the nervous system. Multichannel devices are desired for neural control of robotic prosthetics that interface to remaining nerves in limb stumps of amputees and as alternatives to traditional wired arrays used in for some types of brain stimulation. This present work investigates a new approach to ultrasound-powering of implantable microelectronic devices within the tissue that may better support such applications. These devices are of ultra-miniature size that is enabled by a wireless technique. This study investigates two types of ultrasound-powered neural interfaces for multichannel sensory feedback in neurostimulation. The piezoceramics lead zirconate titanate (PZT) ceramic and polyvinylidene fluoride (PVDF) polymer were the primary materials used to build the devices. They convert ultrasound to electricity that when rectified by a diode produce a current output that is neuro stimulatory to peripheral nerve or the neurons in the brain. Multichannel devices employ a form of spatial multiplexing that directs focused ultrasound towards localized and segmented regions of PVDF or PZT that allows independent channels of nerve actuation. Different frequencies of ultrasound were evaluated for best results. Firstly, a 2.25 MHz frequency signal that is reasonably penetrating through body tissue to an implant several centimeters deep and also a 5 MHz frequency more suited to application for actuation of devices within a less than a centimeter of nerve. Results show multichannel device performance to have a complex inter-relationship with frequency, size and thickness, angular incidence, channel separations, and number of folds (layers connected in series and parallel). The output electrical port impedances of PVDF devices were examined in relationship to that of stimulating electrodes and tissue interfaces. Miniature multichannel devices were constructed using an unreported method of employing state of the art laser cutting systems. The results show that PVDF based devices have advantages over PZT, because of better acoustic coupling with tissue, known better biocompatibility, and better separation between multiple channels. However, the PZT devices proved to be better overall in terms of compactness and higher outputs for a given ultrasound power level.
ContributorsNanda Kumar, Yashwanth (Author) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2015
Description
The use of a non-invasive form of energy to modulate neural structures has gained wide spread attention because of its ability to remotely control neural excitation. This study investigates the ability of focused high frequency ultrasound to modulate the excitability the peripheral nerve of an amphibian. A 5MHz ultrasound transducer is used for the study with the pulse characteristics of 57msec long train burst and duty cycle of 8% followed by an interrogative electrical stimulus varying from 30μsecs to 2msecs in pulse duration. The nerve excitability is determined by the compound action potential (CAP) amplitude evoked by a constant electrical stimulus. We observe that ultrasound's immediate effect on axons is to reduce the electrically evoked CAP amplitude and thereby suppressive in effect. However, a subsequent time delayed increased excitability was observed as reflected in the CAP amplitude of the nerve several tens of milliseconds later. This subsequent change from ultrasound induced nerve inhibition to increased excitability as a function of delay from ultrasound pulse application is unexpected and not predicted by typical nerve ion channel kinetic models. The recruitment curve of the sciatic nerve modified by ultrasound suggests the possibility of a fiber specific response where the ultrasound inhibits the faster fibers more than the slower ones. Also, changes in the shape of the CAP waveform when the nerve is under the inhibitive effect of ultrasound was observed. It is postulated that these effects can be a result of activation of stretch activation channels, mechanical sensitivity of the nerve to acoustic radiation pressure and modulation of ion channels by ultrasound.
The neuromodulatory capabilities of ultrasound in tandem with electrical stimulation has a significant potential for development of neural interfaces to peripheral nerve.
The neuromodulatory capabilities of ultrasound in tandem with electrical stimulation has a significant potential for development of neural interfaces to peripheral nerve.
ContributorsChirania, Sanchit (Author) / Towe, Bruce (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2016
Description
The blood-brain-barrier (BBB) is a significant obstacle for treating many neurological disorders. Bubble-assisted focused ultrasound (BAFUS) medicated BBB disruption is a promising technology that enables the delivery of large drug doses at targeted locations across the BBB. However, the current lack of an in vitro model of this process hinders the full understanding of BAFUS BBB disruption for better translation into clinics. In this work, a US-transparent organ-on-chip device has been fabricated that can be critical for the in vitro modeling of the BAFUS BBB disruption. The transparency of the device window to focused ultrasound (FUS) was calculated theoretically and demonstrated by experiments. Nanobubbles were fabricated, characterized by cryogenic transmission electron microscopy (cryo-TEM), and showed bubble cavitation under FUS. Human colorectal adenocarcinoma (Caco-2) cells were used to form a good cellular barrier for BAFUS barrier disruption, as suggested by the measured permeability and transepithelial electrical resistance (TEER). Finally, barrier disruption and recovery were observed in BAFUS disrupted US-transparent organ-on-chips with Caco-2 barriers, showing great promise of the platform for future modeling BAFUS BBB disruption in vitro.
ContributorsAkkad, Adam Rifat (Author) / Gu, Jian (Thesis advisor) / Nikkhah, Mehdi (Thesis advisor) / Belohlavek, Marek (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2022
Description
Neural tissue is a delicate system comprised of neurons and their synapses, glial cells for support, and vasculature for oxygen and nutrient delivery. This complexity ultimately gives rise to the human brain, a system researchers have become increasingly interested in replicating for artificial intelligence purposes. Some have even gone so far as to use neuronal cultures as computing hardware, but utilizing an environment closer to a living brain means having to grapple with the same issues faced by clinicians and researchers trying to treat brain disorders. Most outstanding among these are the problems that arise with invasive interfaces. Optical techniques that use fluorescent dyes and proteins have emerged as a solution for noninvasive imaging with single-cell resolution in vitro and in vivo, but feeding in information in the form of neuromodulation still requires implanted electrodes. The implantation process of these electrodes damages nearby neurons and their connections, causes hemorrhaging, and leads to scarring and gliosis that diminish efficacy. Here, a new approach for noninvasive neuromodulation with high spatial precision is described. It makes use of a combination of ultrasound, high frequency acoustic energy that can be focused to submillimeter regions at significant depths, and electric fields, an effective tool for neuromodulation that lacks spatial precision when used in a noninvasive manner. The hypothesis is that, when combined in a specific manner, these will lead to nonlinear effects at neuronal membranes that cause cells only in the region of overlap to be stimulated. Computational modeling confirmed this combination to be uniquely stimulating, contingent on certain physical effects of ultrasound on cell membranes. Subsequent in vitro experiments led to inconclusive results, however, leaving the door open for future experimentation with modified configurations and approaches. The specific combination explored here is also not the only untested technique that may achieve a similar goal.
ContributorsNester, Elliot (Author) / Wang, Yalin (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2022
Description
The field of non-invasive neurostimulation techniques offer promising avenues for the treatment of various neurological and psychiatric disorders such as Parkinson's disease, migraines, chronic pain, and epilepsy. The proposed work is a novel technique for the production of high-end ultrasonic forces by interaction of gigahertz electromagnetic radiations for the purpose of neural modulation. These ultrasonic forces are created in dielectric materials such as cell membranes by the electrostrive effect, providing a potential new neurotherapeutic technique. The ability for this technique to provide neurostimulatory effects was investigated using in vitro studies of neuronal cultures and in vivo studies on sciatic nerves. Direct exposure of E18 rat cortical neurons to these EM radiations demonstrated changes in cellular membrane potential, suggesting effects could be potentially similar to direct electrical stimulation. An exploration of neuromodulatory effects to rat sciatic nerves indicates exposure produces changes to peak-to-peak muscular response. These findings suggest promising results for this new potential neuromodulation modality.
ContributorsDagher, Michael Jonathan (Author) / Muthuswamy, Jitendran (Thesis advisor) / Towe, Bruce (Committee member) / Sridharan, Arati (Committee member) / Aberle, James (Committee member) / Arizona State University (Publisher)
Created2023
Description
Bioimpedance measurements have been long used for monitoring tissue ischemia and blood flow. This research employs implantable microelectronic devices to measure impedance chronically as a potential way to monitor the progress of peripheral vascular disease (PVD). Ultrasonically powered implantable microdevices previously developed for the purposes of neuroelectric vasodilation for therapeutic treatment of PVD were found to also allow a secondary function of tissue bioimpedance monitoring. Having no structural differences between devices used for neurostimulation and impedance measurements, there is a potential for double functionality and closed loop control of the neurostimulation performed by these types of microimplants. The proposed technique involves actuation of the implantable microdevices using a frequency-swept amplitude modulated continuous waveform ultrasound and remote monitoring of induced tissue current. The design has been investigated using simulations, ex vivo testing, and preliminary animal experiments. Obtained results have demonstrated the ability of ultrasonically powered neurostimulators to be sensitive to the impedance changes of tissue surrounding the device and wirelessly report impedance spectra. Present work suggests the potential feasibility of wireless tissue impedance measurements for PVD applications as a complement to neurostimulation.
ContributorsCelinskis, Dmitrijs (Author) / Towe, Bruce (Thesis advisor) / Greger, Bradley (Committee member) / Sadleir, Rosalind (Committee member) / Arizona State University (Publisher)
Created2015