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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
Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition.
ContributorsTufail, Yusuf Zahid (Author) / Tyler, William J (Thesis advisor) / Duch, Carsten (Committee member) / Muthuswamy, Jitendran (Committee member) / Santello, Marco (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2011
Description
Noninvasive neuromodulation could help treat many neurological disorders, but existing techniques have low resolution and weak penetration. Ultrasound (US) shows promise for stimulation of smaller areas and subcortical structures. However, the mechanism and parameter design are not understood. US can stimulate tail and hindlimb movements in rats, but not forelimb, for unknown reasons. Potentially, US could also stimulate peripheral or enteric neurons for control of blood glucose.
To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.
No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.
The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.
No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.
The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
ContributorsGulick, Daniel Withers (Author) / Kleim, Jeffrey (Thesis advisor) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Herman, Richard (Committee member) / Helms Tillery, Steven (Committee member) / Arizona State University (Publisher)
Created2015
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
Clarinet multiphonics have become increasingly popular among composers since they were first introduced in the 1950s. However, it is a topic poorly understood by both performers and composers, which sometimes leads to the use of acoustically impossible multiphonics in compositions. Producing multiphonics requires precise manipulations of embouchure force, air pressure, and tongue position. These three factors are invisible to the naked eye during clarinet performance, leading to many conflicting theories about multiphonic production strategies, often based on subjective perception of the performer. This study attempts to observe the latter factor—tongue motion—during multiphonic production in situ using ultrasound. Additionally, a multiphonic catalog containing 604 dyad multiphonics was compiled as part of this study. The author hypothesized that nearly all, if not all, of the multiphonics can be produced using one of four primary production strategies. The four production strategies are: (A) lowering the back of the tongue while sustaining the upper note; (B) raising the back of the tongue while sustaining the upper note; (C) changing the tongue position to that of the lower note while sustaining the upper note; and (D) raising the root of the tongue (a sensation similar to constricting the throat) while sustaining the upper note. To distill production strategies into four primary categories, the author documented his perceived tongue motion over twenty repetitions of playing every multiphonic in the catalog. These perceptions were then confirmed or corrected through ultrasound investigation sessions after every five repetitions. The production strategies detailed in this study are only for finding the correct voicing to produce the multiphonics. The catalog compiled during this study is organized using two different organizational systems: the first uses the traditional method of organizing by pitch; the second uses a fingering-based system to facilitate the ease of finding multiphonics in question, since notated pitches of multiphonics often differ between sources.
ContributorsLiang, Jack Yi Jing (Author) / Gardner, Joshua (Thesis advisor) / Spring, Robert (Thesis advisor) / Caslor, Jason (Committee member) / Creviston, Christopher (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2018
Description
The purpose of this thesis experiment was to design and create an Acoustically Active Cannula (AAC), which is furnished by a piezoelectric crystal placed at its tip that produces an acoustic navigation signal. I tested the functionality of the cannula in vitro and demonstrated its navigational abilities in vivo in anesthetized pigs. This experiment was based upon ultrasound science and technology, and thus some practical experience with conventional (B-mode) and Doppler ultrasound was achieved as well. The results of bench and experimental animal studies indicated proper functionality of the AAC for identification and spatial navigation of its tip with color Doppler ultrasound imaging.
ContributorsShamsa, Kayvan (Author) / Tyler, William (Thesis director) / Belohlavek, Marek (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The purpose of this study was to examine swallowing patterns using ultrasound technology subsequent to the implementation of two therapeutic interventions. Baseline swallow patterns were compared to swallows after implementation of therapeutic interventions common in both feeding therapy (FT) and orofacial myofunctional therapy (OMT). The interventions consist of stimulation of the tongue by z-vibe and tongue pops. Changes in swallowing patterns are described, and similarities of interventions across the two professions are discussed. Ultrasound research in the realm of swallowing is sparse despite having potential clinical application in both professions. In using ultrasound, this study outlines a protocol for utilization of a hand-held probe and reinforces a particular protocol described in the literature. Real-time ultrasound recordings of swallows for 19 adult female subjects were made. Participants with orofacial myofunctional disorder are compared to a group with typical swallowing and differences in swallowing patterns are described. Three stages of the oral phase of the swallow were assigned based on ultrasonic observation of the tongue shape. Analysis involves total duration of the swallow, duration of the three stages in relation to the total duration of the swallow, and the number of swallows required for the bolus to be cleared from the oral cavity. No significant effects of either intervention were found. Swallowing patterns showed a general trend to become faster in total duration subsequent to each intervention. An unexpected finding showed significant changes in the relationship between the bolus preparation stage and the bolus transportation stage when comparing the group classified as having a single swallow and the group classified as having multiple swallows.
ContributorsMckay, Michelle Diane (Author) / Weinhold, Juliet (Thesis director) / Scherer, Nancy (Committee member) / Department of Speech and Hearing Science (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Ultrasound is a sound wave that produces acoustic pressure and is most commonly known as a noninvasive technique for bodily imaging. However, high-intensity focused ultrasound can be used for noninvasive physiotherapy. An example of this the treatment of tumors in the kidneys, as the sound waves of HIFU interacts with tissues in the body. For this thesis, the necessary parameters for ultrasonic stimulation of the central nervous system in rats were characterized.
ContributorsHughes, Brett William (Co-author) / Castel, Nikki (Co-author) / Hillen, Brian (Thesis director) / Helms Tillery, Stephen (Committee member) / Lozano, Cecil (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
Description
Research on /r/ production previously used formant analysis as the primary acoustic analysis, with particular focus on the low third formant in the speech signal. Prior imaging of speech used X-Ray, MRI, and electromagnetic midsagittal articulometer systems. More recently, the signal processing technique of Mel-log spectral plots has been used to study /r/ production in children and female adults. Ultrasound imaging of the tongue also has been used to image the tongue during speech production in both clinical and research settings. The current study attempts to describe /r/ production in three different allophonic contexts; vocalic, prevocalic, and postvocalic positions. Ultrasound analysis, formant analysis, Mel-log spectral plots, and /r/ duration were measured for /r/ production in 29 adult speakers (10 male, 19 female). A possible relationship between these variables was also explored. Results showed that the amount of superior constriction in the postvocalic /r/ allophone was significantly lower than the other /r/ allophones. Formant two was significantly lower and the distance between formant two and three was significantly higher for the prevocalic /r/ allophone. Vocalic /r/ had the longest average duration, while prevocalic /r/ had the shortest duration. Signal processing results revealed candidate Mel-bin values for accurate /r/ production for each allophone of /r/. The results indicate that allophones of /r/ can be distinguished based the different analyses. However, relationships between these analyses are still unclear. Future research is needed in order to gather more data on /r/ acoustics and articulation in order to find possible relationships between the analyses for /r/ production.
ContributorsHirsch, Megan Elizabeth (Author) / Weinhold, Juliet (Thesis director) / Gardner, Joshua (Committee member) / Department of Speech and Hearing Science (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05