Finite element modeling of temperature elevation due to NIR exposure in neural tissue

Near infrared (NIR) lasers have been used in various types of medical applications. Heating is one of the most important concerns in the neural tissue when illuminated with NIR light. Rodent models are frequently used to study laser-tissue interactions. As a part of ongoing research project in the neural interface laboratory, direct measurements of temperature in the rat brain cortex as a response to a pulsed sequence of NIR laser beam are available. In this thesis, finite element modeling approach is used to model and simulate the temperature elevation in neural tissue under the effect of NIR laser pulsing. Steady state and transient analyses are conducted, and spatio-temporal temperature maps are generated. The effect of pulse frequency is investigated. The results are compared with experimental data and found to be in good agreement. The finite element modeling allows studying various variables on the heating effect of NIR in neural tissue that would otherwise be very difficult to investigate experimentally

Temperature elevations due to NIR exposure in the brain tissue

Near infrared (NIR) lasers have been used in medical applications both for diagnostic and therapeutic purposes. Temperature elevation profile inside the tissue is a critical factor that needs to be better understood in these applications. The purpose of this study is to determine the temperature distribution due to a low power N I R laser irradiation in living neural tissue. Temperature measurements were made directly using a thermocouple probe inside the rat brain cortex within the sagittal plane. The spatial map indicates that N I R light penetrates more readily in the vertical directions than the spreading in the horizontal axis. The decrease in the vertical direction can be approximated with a single order exponentially decaying function. The results also suggest that the temperature elevation can be kept below 0.5 °C anywhere in the tissue if the incident laser beam power density is less than 27 mW/cm2. These experiments should be repeated in other types of neural tissue such as the white matter of the brain and the spinal cord to obtain more complete results

Experimental evaluation of near infrared light penetration into neural tissue

Near infrared (NIR) lasers find applications in medicine both for diagnostic and treatment purposes. Penetration depth into the tissue is a critical parameter to be considered in these NIR laser applications. Published data on the optical properties of rodent neural tissue are rare, despite the frequent use of rats as animal models. The aim of this study was to directly measure the light intensity profile inside the rat brain gray matter that is illuminated by an NIR laser beam. The local light intensities were sampled using an optical fiber inserted into the brain. The intensity profile in the axial direction to the laser beam had an initial fast decreasing phase followed by a less steeper slope by distance. In general, the light penetrated several times farther in the direction of the beam than its spread in the radial direction

금나노입자의 국소표면플라즈몬공명을 이용한 향상된 신경자극 시스템

학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2016. 8. 김성준.Modulating neural activity is essential to clinical treatment of neurological disorder and to the study of neural function. In particular, there has been growing interest in the development of a contact-free and high spatial selective infrared neural stimulation (INS) technique for use in clinics as well as research area. Despite a potential of INS for modulating neural activities, INS suffers from limited light confinement and tissue damage due to bulk heating. This dissertation provides fundamental information on the development of enhanced INS that could circumvent the limitations of conventional INS. The first part of this dissertation demonstrates for the first time that localized surface plasmon resonance of gold nanorods (GNRs) could induce neural depolarization with safe manner by lowering the stimulation threshold. To perform optical stimulation of neural tissue with GNRs, controllable fiber-coupled laser diode system, GNRs complex and neural cells are prepared. Pulsed near-infrared (NIR) light to efficiently absorbed to GNRs rather than bulk tissue and converted into localized heat which finally triggers neural activation. In the second part of this dissertation, surface-modified GNRs are used to bind to neuronal membrane to achieve washout resistance and to locally heat the neuronal membrane for which neural activation is responsible. INS using cell-targeted GNRs are employed in other types of cells, which is discussed in third part of this dissertation. Transient intracellular calcium waves are evoked in the astrocyte cells revealing GNRs-mediated INS stimulation can be applied in variety of cells. In the last part of this dissertation, the mechanism underlying GNRs-mediated INS is discussed. Illumination of NIR light to the GNRs at their resonant wavelength leads to local electromagnetic field enhancement and the generation localized heat. Local heat diffuses to the nearby plasma membrane which result transient temperature elevation. Transient temperature increase lead to capacitance change and/or opening of the temperature sensitive ion-channel (e.g. transient receptor potential vanilloid 1 (TRPV1) channel) which both trigger the neural depolarization. A neuron model is developed to theoretically and mathematically demonstrate on the mechanism underlying GNRs-mediated INS. These experimental and theoretical findings are expected to open up new possibilities for applications to non-invasive investigations of diverse excitable tissues and treatments of neurological disorders.Chapter 1: Introduction 1 1.1. Background 1 1.1.1. Neuroprosthetic devices 1 1.1.2. Neural stimulation techniques 2 1.1.3. Infrared neural stimulation (INS) 3 1.1.4. Localized surface plasmon resonance (LSPR) 6 1.2. Objectives 8 1.2.1. GNRs-mediated NIR neural stimulation system 8 1.2.2. Theoretical elucidation on the origin of GNRs-mediated INS 9 Chapter 2: Materials and Methods 11 2.1. Experimental overview 11 2.2. Laser system 13 2.2.1. Design 13 2.2.2. Hardware 14 2.2.3. Software 17 2.2.4. Calibration 18 2.3. GNRs complex 20 2.3.1. Characteristics of GNRs 20 2.3.2. Photothermal effect of GNRs 21 2.3.3. Orientation of GNRs 24 2.4. Neural cells 29 2.5. Experimental protocols 30 2.5.1. Safe INS 30 2.5.2. Effective INS 32 2.5.3. Wide applicable INS 41 2.6. Numerical modeling 45 2.6.1. Overview 46 2.6.2. Background theory 47 2.6.3. Laser induced heat modeling 56 2.6.4. Neuronal membrane modeling 60 2.6.5. Capacitance change and conductance change induced action potential 69 Chapter 3: Results 73 3.1. GNRs-mediated safe INS 73 3.1.1. In vivo rat sciatic nerve 73 3.2. Cell-targeted GNRs-mediated effective INS 78 3.2.1. In vitro cultured rat hippocampal neuron 78 3.2.2. In vivo rat motor cortex 84 3.3. Cell-targeted GNRs-mediated wide applicable INS 90 3.3.1. In vitro cultured astrocyte 90 3.4. Numerical analysis 97 3.4.1. Numerical analysis using capacitance change considered H-H model 97 3.4.2. Numerical analysis using TRPV1 channel considered H-H model 98 3.4.3. Numerical analysis using capacitance change and TRPV1 channel considered H-H model 102 Chapter 4: Discussion 104 4.1. Comparison with previous results 104 4.2. Safety of gold nanoparticle mediated infrared neural stimulation 107 4.3. Link between experimental and simulation results 109 4.4. TRPV1 channel and membrane capacitance 112 4.5. Possible mechanisms of GNRs-mediated INS 113 4.6. Potential applications 114 4.7. Opportunities for further improvements 115 Chapter 5: Conclusion 118 Reference 120 국문 초록 129Docto

A simulation study of the combined thermoelectric extracellular stimulation of the sciatic nerve of the Xenopus laevis: the localized transient heat block

The electrical behavior of the Xenopus laevis nerve fibers was studied when combined electrical (cuff electrodes) and optical (infrared laser, low power sub-5 mW) stimulations are applied. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP). The calculations involve a finite-element model (COMSOL) to represent the electrical properties of the nerve and cuff. Electric-field distribution along the nerve was computed for the given stimulation current profile and imported into a NEURON model, which was built to simulate the electrical behavior of myelinated nerve fiber under extracellular stimulation. The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. Some preliminary experimental data in support of this conclusion are also shown

Hyperspectral imaging for the remote sensing of blood oxygenation and emotions

This PhD project is a basic research and it concerns with how human’s physiological features, such as tissue oxygen saturation (StO2), can be captured from a stand-off distance and then to understand how this remotely acquired physiological feature can be deployed for biomedical and other applications. This work utilises Hyperspectral Imaging (HSI) within the diffuse optical scattering framework, to assess the StO2 in a contactless remote sensing manner. The assessment involves a detailed investigation about the wavelength dependence of diffuse optical scattering from the skin as well as body tissues, under various forms of optical absorption models. It is concluded that the threechromophore extended Beer Lambert Law model is better suited for assessing the palm and facial tissue oxygenations, especially when spectral data in the wavelengths region of [516-580]nm is used for the analysis. A first attempt of using the facial StO2 to detect and to classify people’s emotional state is initiated in this project. The objective of this work is to understand how strong emotions, such as distress that caused by mental or physical stimulations, can be detected using physiological feature such as StO2. Based on data collected from ~20 participants, it is found that the forehead StO2 is elevated upon the onset of strong emotions that triggered by mental stimulation. The StO2 pattern in the facial region upon strong emotions that are initiated by physical stimulations is quite complicated, and further work is needed for a better understanding of the interplays between bodily physique, individual’s health condition and blood transfusion control mechanism. Most of this work has already been published and future research to follow up when the author returns back to China is highlighted

Infrared light activated floating micro stimulators for neuro-prosthetic applications

The most common failures in neural stimulation implants are due to interconnect complications such as tissue response, lead migration, and lead breakages. The challenge in eliminating interconnects lies in minimizing device size to maintain spatial selectivity required in the CNS. One approach to this problem is a current generating device that can be stimulated by an external signal, such as light or sound. Here, we report the design, construction and testing of rnicrophotodiode devices that can be stimulated remotely with near-infrared (NIR) light to generate current that can be injected locally into the peripheral nervous system. The use of near-infrared (NIR) light to activate microphotodiodes was investigated. The chip size of the prototype device is 300μm by 500μm, and the small stimulation area necessitates a contact material capable of delivering a minimum charge injection rate of 0.5 mC/cm2. The charge transfer properties of iridium oxide, platinum, and titanium nitride were analyzed, and titanium nitride was found to have a stable charge injection rate above 0.5 mC/cm2. The volume conductor response of the diode showed a primarily capacitive transfer of energy into the tissue. Three diode geometries were implanted in a peripheral nerve, and an EMG signal was recorded in response to laser stimulation of two diode types. The diodes with the largest active area achieved successful stimulation despite size differences in contact area; this suggests the importance of active area size for stimulation. Further characterization of diode performance in vivoestablished an optimum pulse width for minimum light energy needed for diode activation. This optimum pulse width increased as implantation depth increased. For an implantation depth of 3.5 mm, the energy threshold was 0.53 mJ/cm2 which is 30 times below the maximum permissible exposure for λ = 830 nm. The total energy required for stimulation at a given pulse width increased as tissue depth increased

Biomedical Photoacoustic Imaging and Sensing Using Affordable Resources

The overarching goal of this book is to provide a current picture of the latest developments in the capabilities of biomedical photoacoustic imaging and sensing in an affordable setting, such as advances in the technology involving light sources, and delivery, acoustic detection, and image reconstruction and processing algorithms. This book includes 14 chapters from globally prominent researchers , covering a comprehensive spectrum of photoacoustic imaging topics from technology developments and novel imaging methods to preclinical and clinical studies, predominantly in a cost-effective setting. Affordability is undoubtedly an important factor to be considered in the following years to help translate photoacoustic imaging to clinics around the globe. This first-ever book focused on biomedical photoacoustic imaging and sensing using affordable resources is thus timely, especially considering the fact that this technique is facing an exciting transition from benchtop to bedside. Given its scope, the book will appeal to scientists and engineers in academia and industry, as well as medical experts interested in the clinical applications of photoacoustic imaging

Application of nanoparticles and nanomaterials in thermal ablation therapy of cancer

Cancer is one of the major health issues with increasing incidence worldwide. In spite of the existing conventional cancer treatment techniques, the cases of cancer diagnosis and death rates are rising year by year. Thus, new approaches are required to advance the traditional ways of cancer therapy. Currently, nanomedicine, employing nanoparticles and nanocomposites, offers great promise and new opportunities to increase the efficacy of cancer treatment in combination with thermal therapy. Nanomaterials can generate and specifically enhance the heating capacity at the tumor region due to optical and magnetic properties. The mentioned unique properties of nanomaterials allow inducing the heat and destroying the cancerous cells. This paper provides an overview of the utilization of nanoparticles and nanomaterials such as magnetic iron oxide nanoparticles, nanorods, nanoshells, nanocomposites, carbon nanotubes, and other nanoparticles in the thermal ablation of tumors, demonstrating their advantages over the conventional heating methods