Brain and Human Body Modelling 2021

This open access book describes modern applications of computational human modelling to advance neurology, cancer treatment, and radio-frequency studies including regulatory, safety, and wireless communication fields. Readers working on any application that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest models and techniques available to assess a given technology’s safety and efficacy in a timely and efficient manner. This is an Open Access book

Brain and Human Body Modelling 2021

This open access book describes modern applications of computational human modelling to advance neurology, cancer treatment, and radio-frequency studies including regulatory, safety, and wireless communication fields. Readers working on any application that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest models and techniques available to assess a given technology’s safety and efficacy in a timely and efficient manner. This is an Open Access book

Vibration

Studies on hand-transmitted vibration exposure, biodynamic responses, and biological effects were conducted by researchers at the Health Effects Laboratory Division (HELD) of the National Institute for Occupational Safety and Health (NIOSH) during the last 20 years. These studies are systematically reviewed in this report, along with the identification of areas where additional research is needed. The majority of the studies cover the following aspects: (i) the methods and techniques for measuring hand-transmitted vibration exposure; (ii) vibration biodynamics of the hand-arm system and the quantification of vibration exposure; (iii) biological effects of hand-transmitted vibration exposure; (iv) measurements of vibration-induced health effects; (iv) quantification of influencing biomechanical effects; and (v) intervention methods and technologies for controlling hand-transmitted vibration exposure. The major findings of the studies are summarized and discussed.CC999999/ImCDC/Intramural CDC HHSUnited States/2021-01-18T00:00:00Z34414357PMC83715621023

Stepper microactuators driven by ultrasonic power transfer

Advances in miniature devices for biomedical applications are creating ever-increasing requirements for their continuous, long lasting, and reliable energy supply, particularly for implanted devices. As an alternative to bulky and cost inefficient batteries that require occasional recharging and replacement, energy harvesting and wireless power delivery are receiving increased attention. While the former is generally only suited for low-power diagnostic microdevices, the latter has greater potential to extend the functionality to include more energy demanding therapeutic actuation such as drug release, implant mechanical adjustment or microsurgery. This thesis presents a novel approach to delivering wireless power to remote medical microdevices with the aim of satisfying higher energy budgets required for therapeutic functions. The method is based on ultrasonic power delivery, the novelty being that actuation is powered by ultrasound directly rather than via piezoelectric conversion. The thesis describes a coupled mechanical system remotely excited by ultrasound and providing conversion of acoustic energy into motion of a MEMS mechanism using a receiving membrane coupled to a discrete oscillator. This motion is then converted into useful stepwise actuation through oblique mechanical impact. The problem of acoustic and mechanical impedance mismatch is addressed. Several analytical and numerical models of ultrasonic power delivery into the human body are developed. Major design challenges that have to be solved in order to obtain acceptable performance under specified operating conditions and with minimum wave reflections are discussed. A novel microfabrication process is described, and the resulting proof-of-concept devices are successfully characterized.Open Acces

Advances in materials strategies, circuit designs, and informatics for wearable, flexible and stretchable electronics with medical and robotic applications

The future of medical electronics should be flexible, stretchable and skin-integrated. While modern electronics become increasing smaller, faster and energy efficient, the designs remain bulky and rigid due to materials and processing limitations. The miniaturization of health monitoring devices in wearable form resembles a significant progress towards the next-generation medical electronics. However, there are still key challenges in these wearable electronics associated with medical-grade sensing precision, reliable wireless powering, and materials strategy for skin-integration. Here, I present a series of systematic studies from materials strategies, circuit design to signal processing on skin-mounted electronic wearable devices. Several types of Epidermal Electronic Systems (EES) develop applications in dermatology, cardiology, rehabilitation, and wireless powering. For skin hydration measurement, fundamental studies of electrode configurations and skin-electrode impedance reveal the optimal sensor design. Furthermore, wireless operation of hydration sensor was made possible with direct integration on skin, and on porous substrates that collect and analyze sweats. Additionally, I present an epidermal multi-functional sensing platform that could provide a control-feedback loop through electromyogram and current stimulation; and a mechano-acoustic device that could capture vibrations from muscle, heart, and throat as diagnostic tools or human-machine interface. I developed a modularized epidermal radio-frequency energy transfer epidermal device to eliminate batteries and power cables for wearable electronics. Finally, I present a clinical study that validates a commercialized ESS on patients with nerve disorders for electromyography monitoring during peripheral nerve and spinal cord surgeries

Aerospace Medicine and Biology. A continuing bibliography with indexes

This bibliography lists 244 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1981. Aerospace medicine and aerobiology topics are included. Listings for physiological factors, astronaut performance, control theory, artificial intelligence, and cybernetics are included

Influence of transdermal current flow in tDCS-induced cutaneous adverse events

Significant contributors to the broad application of transcranial direct current stimulation (tDCS) are portability, ease-of-use, and tolerability; with adverse events limited to transient and mild cutaneous sensations (e.g. perception of burning, itching, and tingling) and erythema. However, the fundamental questions remain about the mechanism of transdermal current flow during transcranial electrical stimulation, including tDCS. Example of previously unexplained questions in tDCS include: 1) the relationship between tDCS-induced skin reddening (erythema) profile and local current density profile predicted by the model; 2) the source of burning sensation during tDCS and whether it is related to an actual skin heating; 3) the role of skin multi-layers and ultrastructures (blood vessels, sweat glands, and hair follicles) in current flow. The finite element modeling (FEM) of current flow using simplified tissue geometries predict higher current density at the electrode edge, but the experimental evidences for the cutaneous effects of tDCS (skin heating or skin reddening) are unclear. Prior skin models of cutaneous current flow lacked anatomical details that will a priori be expected to govern current flow patterns. In this dissertation we address the aforementioned questions by: first quantifying tDCS-induced skin erythema profile alongside FEM predicting local current density profile; then assess the extent of skin heating during tDCS, including the role of joule heating, and relate temperature increase (if any) to burning sensation; and finally develop a realistic skin model to address the role of complex skin tissue layers and ultrastructures in current flow. In the first study, we conclude that the tDCS-induced skin reddening profile is diffuse, higher in active stimulation than sham stimulation, and does not occur at the electrode edges suggesting two alternate hypothesis: 1) skin reddening profile is not related to local current density; and 2) skin current density is relatively uniform, so prior FEM models are incorrect. Next, we conduct phantom measurement suggesting no significant temperature increase due to joule heat as expected at the skin during tDCS. The in vitro human skin temperature measurement suggests that independent of tDCS polarity, temperature increases by about 1oC; an increase during tDCS that is less than the cooling produced following a room-temperature sponge application during the set-up. We conclude that any incremental temperature increase by tDCS may reflect vascular flare response due to current flow, cannot exceed the core body temperature, and is more than the offset by sponge-material coolness, thus, the sensation of skin “burning” during tDCS is not related to an actual increase in temperature. In the final study, we develop a detailed multi-layer skin model including sweat glands, hair follicles, and vasculature, and assess the role of multi-layers and ultrastructures in current flow. The FEM analysis predict that sweat glands eliminates localized current density around the electrode edges, and blood vessels uniformly distribution current across the modeled vasculature under the electrode. We expect that a current flow and bioheat model of such a detailed skin would increase the uniformity of current density and temperature predicted at the skin - consistent with the experimental measurement of skin reddening and skin heating

Noninvasive Thrombolysis Using Histotripsy Pulsed Ultrasound Cavitation Therapy.

Histotripsy is a noninvasive ultrasound therapy that utilizes short, high-amplitude, focused ultrasound pulses to mechanically reduce targeted tissue structures to liquid debris by acoustic cavitation. In this work, the physical mechanisms of histotripsy and its application as a method of thrombolysis were investigated. Cavitation activity which causes tissue breakdown during histotripsy was studied by high-speed photography. It was found that cavitation clouds form due to scattering of shock waves in a focused ultrasound pulse from individual inertial cavitation bubbles. The scattered shock is a large tensile wave which expands clusters of cavitation bubbles when the tensile pressure is greater than a measured threshold of approximately 30 MPa. The interaction of this cavitation with tissue and cells was explored with a phantom containing agarose and red blood cells to measure cavitation-based mechanical damage. The observations indicated that cell lysis may be achieved by bubble-induced tensile strain upon expansion, causing membrane rupture. Based on these studies, focused histotripsy therapy transducers were designed to controllably generate cavitation clouds in the vasculature for performing thrombolysis. Transducers were integrated with ultrasound imagers to provide feedback for targeting and monitoring progress of treatment. Rapid thrombolysis was observed when histotripsy was applied to clots in-vitro, and the resulting debris was mainly subcellular and unlikely to cause embolism. Additionally, it was observed that histotripsy can attract, trap, and destroy free clot fragments in a vessel phantom. Based on these observations, a noninvasive embolus trap (NET) was developed, acting as a filter to prevent embolism during the thrombolysis procedure. An in-vivo porcine model of deep-vein thrombosis was used to evaluate the safety and efficacy of the histotripsy thrombolysis technique. These experiments demonstrated the feasibility of the treatment and suggest histotripsy can achieve rapid clot breakdown in a controlled manner.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91496/1/adamdm_1.pd

Treatment of brain cancer and ischaemic stroke utilising High Intensity Focus Ultrasound (HIFU) guide with MRI

In this thesis high intensity focused ultrasound (HIFU) is utilized for cancer treatment (thermal mode) and treatment of ischaemic stroke (mechanical mode). These two applications were investigated in vitro and in vivo models. MRI was utilized to monitor the lesions created by HIFU either in thermal or cavitation mode in freshly excised lamb brain tissue in vitro, and in rabbit brain in vivo. Additionally, MRI was used to monitor lesions deep in tissue for both in vitro and in vivo exposures. All three MRI sequences used (T1-W FSE, T2-W FSE and FLAIR) were able to detect lesions. Both thermal and bubbly lesions were best monitored using T1-W FSE with excellent contrast, proving the potential of HIFU to treat reliably tumours in the brain. A HIFU system was also used to assist thrombolysis in cooperation with a thrombolytic drug such as recombinant tissue plasminogen activator (rt-PA) in vitro and in vivo. It was shown that higher intensity results to higher volume of dissolved clot, but there is a limit of the intensity to be used in order to avoid heating of the clot and the surrounding tissue. The goal in this study was to achieve temperature elevation not exceeding 1ºC (called safe temperature). It was found that the larger the beam area the larger the dissolved clot volume. Also, the lower the frequency, the larger the volume of the dissolved clot. The results reported herein point to the use of frequency around 0.5 MHz and pulsing to optimize thrombolysis and skull penetration and at the same time avoiding unwanted heating. Finally, an Acrylonitrile Butadiene Styrene (ABS) phantom skull model was developed in order to evaluate the propagation of ultrasound using a single element transducer. The skull model was appropriately designed so that it has the same attenuation as a human skull. It was demonstrated that using a frequency of 0.5 MHz versus 1 MHz, ultrasound propagation through the phantom skull was higher. Therefore, higher frequency has poor skull penetration and a small beam size at the focus, while low frequencies have better skull penetration but with the risk of reaching the unpredictable effect of cavitation. The developed system has proven to successfully create large lesions in the brain and at the same time, these lesions are successfully monitored with excellent contrast using MRI (T1-W FSE) enabling the accurate determination of the margins of these lesions. The results reported in this study point to the use of frequency around 0.5 MHz and pulsing to optimize thrombolysis and skull penetration and at the same time avoiding unwanted heating. For treating tumours located deep in the brain and for dissolving thrombus causing an acute ischaemic stroke, further extensive clinical studies will be needed before this technology is applied to humans

How sonoporation disrupts cellular structural integrity: morphological and cytoskeletal observations

Posters: no. 1Control ID: 1672429OBJECTIVES: In considering sonoporation for drug delivery applications, it is essential to understand how living cells respond to this puncturing force. Here we seek to investigate the effects of sonoporation on cellular structural integrity. We hypothesize that the membrane morphology and cytoskeletal behavior of sonoporated cells under recovery would inherently differ from that of normal viable cells. METHODS: A customized and calibrated exposure platform was developed for this work, and the ZR-75-30 breast carcinoma cells were used as the cell model. The cells were exposed to either single or multiple pulses of 1 MHz ultrasound (pulse length: 30 or 100 cycles; PRF: 1kHz; duration: up to 60s) with 0.45 MPa spatial-averaged peak negative pressure and in the presence of lipid-shelled microbubbles. Confocal microscopy was used to examine insitu the structural integrity of sonoporated cells (identified as ones with exogenous fluorescent marker internalization). For investigations on membrane morphology, FM 4-64 was used as the membrane dye (red), and calcein was used as the sonoporation marker (green); for studies on cytoskeletal behavior, CellLight (green) and propidium iodide (red) were used to respectively label actin filaments and sonoporated cells. Observation started from before exposure to up to 2 h after exposure, and confocal images were acquired at real-time frame rates. Cellular structural features and their temporal kinetics were quantitatively analyzed to assess the consistency of trends amongst a group of cells. RESULTS: Sonoporated cells exhibited membrane shrinkage (decreased by 61% in a cell’s cross-sectional area) and intracellular lipid accumulation (381% increase compared to control) over a 2 h period. The morphological repression of sonoporated cells was also found to correspond with post-sonoporation cytoskeletal processes: actin depolymerization was observed as soon as pores were induced on the membrane. These results show that cellular structural integrity is indeed disrupted over the course of sonoporation. CONCLUSIONS: Our investigation shows that the biophysical impact of sonoporation is by no means limited to the induction of membrane pores: e.g. structural integrity is concomitantly affected in the process. This prompts the need for further fundamental studies to unravel the complex sequence of biological events involved in sonoporation.postprin