Work-related muscle disorders are a main cause of missed work, globally, and arecostly for public health systems. However, development of musculoskeletal tissue diagnostics is lagging compared to other tissues and organs. Myofascial trigger points (MTP) are unique muscle tissue phenomenon that are challenging to address due to a lack of objective assessment methodology. This study seeks to meet this need by devising a non-invasive, objective methodology for evaluating musculoskeletal tissue following intervention or physical provocation, specific to the anterior forearm region. In Aim 1, current literature on MTP pathophysiology informs a multi-modal assessment approach, including: 1) pain pressure threshold (PPT), 2) power Doppler (PD) ultrasound, 3) strain elastography (SE), and 4) surface electromyography (sEMG). In Aim 2, controlled ultrasound image acquisition and standardization techniques are developed for imaging muscle tissue with PD (Aim 2a) and SE (Aim 2b) . These techniques improved differentiability of vascularity and compliance estimation after physical provocation or intervention. In Aim 3, the multi-modal approach is implemented in a human pilot study (n=34) investigating MTP response to osteopathic manipulative treatment, compared to rest and light exercise. Positive trends and significant changes are detected after OMT and rest. PPT significantly increased after OMT (p = 0.021). Tissue compliance significantly increase after rest (p ≪ 0.0001) and after OMT( p = 0.002). Principal component analysis finds 9 of 13 outcome measures to be salient features of MTP treatment effect. The data suggests high and low responders, yielding insights for improved patient screening and study design for future work. With further optimization and development, this method may be applied to a broad array of clinical scenarios for musculoskeletal tissue evaluation directed towards amelioration of neuromuscular symptoms.

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.

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.

Preliminary studies indicate that the use of dietary menthol may prevent excessive weight gain through the activation of the transient receptor potential melastatin family member 8 (TRPM8) ion channel. It has also been expressed that elevation of the core temperature (Tc) inducing mild hyperthermia via an increase in ambient temperature aids in a marked reduction of the drive to eat and weight gain. While caloric restriction (CR) aims to treat obesity and secondary sicknesses, weight regain is a common result during long term weight maintenance. The goal of these studies was to evaluate and identify if the menthol and mild hyperthermia mechanisms could couple synergistically to reduce or abrogate weight gain. Ambient temperature (Ta) was increased incrementally to identify the threshold in which rodents display mild hyperthermia. Our initial attempts at hyperthermia induction failed because of limitations in the environmental chamber. These trials fail to note a threshold at which elevated Tc is sustained for any period of time. The data suggests an ambient temperature of 36-38 °C would be appropriate to induce a mild hyperthermia. A mild hyperthermia is described as the elevation of Tc 2-3 ° above the hypothalamic set point. To facilitate future hyperthermia studies, an environmental chamber was designed. A wine cooler was converted to withstand the desired temperatures, through the use of heat tape, a proportional controller, and a translucent Plexiglas custom fit door. Beyond leveraging temperature to regulate weight gain, dietary changes including a comparison between standard chow food, high fat diet, and menthol supplemented chow food treatment illustrate a strong likelihood of weight gain variability. In this pilot study, weight gain expression when given a diet supplemented with menthol (1%) showed no statistical significance relative to a high fat diet nor chow food, however, it revealed a trend of reduced weight gain. It is assumed the combination of supplemental menthol and mild hyperthermia induction will exacerbate their effects.

This is a pilot study testing a new indirect calorimeter device. This project was designed to determine the effect of a high fat versus a standard chow diet and age on the energy gap (the difference between energy intake and energy expenditure). Measurements of energy expenditure and oxygen consumption were obtained over a 23-hour period from a group of rats fed a high fat diet and a group of rats fed standard chow diet. The experiments were repeated during an experimental phase for 12 weeks, a phase of caloric restriction for 4 weeks, and a phase of weight regain for 4 weeks. We found energy expenditure and oxygen consumption to decrease in the caloric restriction phase and increase with excessive weight gain. Rats fed a high fat diet and obesity prone rats had a wider energy gap than rats fed a standard chow diet and obesity resistant rats. The caloric restriction phase closed the energy gap between energy expenditure and energy intake for all of the rats. The weight regain phase shifted the rats back into positive energy balance so that the energy intake was greater than the energy expenditure. The rats showed greater weight gain in the weight regain phase than in the experimental phase for all groups of rats. The indirect calorimeter device would require further testing to improve the accuracy of the measurements of respiratory quotient and carbon dioxide production before being used in future clinical research applications. The indirect calorimeter device has the potential to record respiratory quotient and carbon dioxide production.

Abstract Modern imaging techniques for sciatic nerves often use imaging techniques that can clearly find myelinated axons (Group A and Group B and analyze their properties, but have trouble with the more numerous Remak Fibers (Group C). In this paper, Group A and B fibers are analyzed while also analyzing Remak fibers using osmium tetroxide staining and imaging with the help of transmission electron microscopy. Using this method, nerves had various electrical stimuli attached to them and were analyzed as such. They were analyzed with a cuff electrode attached, a stimulator attached, and both, with images taken at the center of the nerve and the ends of them. The number and area taken by the Remak fibers were analyzed, along with the g-ratios of the Group A and B fibers. These were analyzed to help deduce the overall health of the fibers along with vacuolization, and mitochondria available. While some important information was gained from this evaluation, further testing has to be done to improve the myelin detection system, along with analyzing the proper and necessary Remak fibers and the role they play. The research tries to thoroughly look at the necessary material and find a way to use it as a guide to further experimentation with electrical stimuli, and notes the differences found within and without various groups, various points of observation, and various stimuli as a whole. Nevertheless, this research allows a strong look into the benefits of transmission electron microscopy and the ability to assess electrical stimulation from these points.

An improved system for wireless neurostimulation was investigated through the design and development of sub-millimeter piezoelectric devices. The devices build on prior work in the lab, which was limited by device size and required surgical implantation. A method of manufacturing sub-mm devices was developed, and utilized to construct this new design. The device frequency response was characterized and its resonant modes and output voltages determined through a Fast Fourier Transform. The fundamental thickness mode frequency was found to be 15.4MHz with a corresponding 10.25mV amplitude, and a longitudinal resonant frequency of 3.1Mhz with a corresponding 2.2mV amplitude across a 50Ω resistor. The high miniaturization of the device holds promise for future work for creating an injectable, wireless system for the treatment of neurological disorders.

Nerve endings are particularly difficult to target during peripheral nerve block (PNB) procedures, so ultrasound-guided needles are of immense importance to guarantee safe and efficient delivery of the anesthetic to the target nerve. Despite significant progress in needle visualization with ultrasound imaging, there are still several factors that lead to poor needle visibility, the main factor being insertion angle. Introducing cavities and holes in the needle at specific intervals through pitting corrosion may alter the ultrasonic feedback from the sensor, thereby resulting in improved clarity of the reconstructed image. The purpose of this experiment is to investigate the effectiveness of two novel pitting designs on the needle’s visibility under ultrasound. Two different designs and two depths of cut are tested in a 22 factorial that is blocked by insertion angle: a uniform and a non-uniform design. Needles were cut using a Plain Jane and Igor laser cutter and imaged using a GE Logig e BT12 ultrasound imaging machine. Images were compared visually and objectively by using a tool in Photoshop to calculate the luminosity of the needle. Two videos were also taken capturing the difficulty of imaging surgical needles. Results showed that pitting had a major impact on needle visibility at 30° and a marginal impact at 0°. The videos supported these results as it was considerably more difficult to locate the control needle than the experimental needle. This suggests the probe must be in a specific plane with the control needle for it to be visible while the experimental needle is much more lenient. Results from the two depths of cuts showed similar results in that the designs which were cut twice were more visible than their counterparts at 30°. The study showed that pitting has positive effects on needle visibility; it improves visibility by increasing the luminescence of the needle and by decreasing its sensitivity to probe position.

As the rates of anxiety in adults rapidly swell, new and creative treatment methods become increasingly relevant. Individuals with an anxiety disorder may experience challenging symptoms that interfere with daily activities and impede academic and social success. The purpose of this project is to design and engineer a portable heart rate monitor that communicates with an iOS mobile application for use by individuals suffering from anxiety or panic disorders. The proposed device captures the innovation of combining biosensor feedback with new, creative therapy methods on a convenient iOS application. The device is implemented as an Arduino Uno which translates radial pulse information onto an LCD screen from a wristband. Additionally, the iOS portion uses a slow expanding and collapsing animation to guide the user through a calming breathing exercise while displaying their pulse in beats per minute. The user's awareness or his or her ability to control one's own physiological state supports and facilitates an additional form of innovative therapy. The current design of the iOS app uses a random-number generator between 40 to 125 to imitate a realistic heart rate. If the value is less than 60 or greater than 105, the number is printed in red; otherwise the heart rate is displayed in green. Future versions of this device incorporate bluetooth capabilities and potentially additional synchronous methods of therapy. The information presented in this research provides an excellent example of the integrations of new mobile technology and healthcare.