인공시각장치 개발을 위한 동물모델 평가와 수술기법 연구

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2019. 2. 서종모.본 연구진은 액정폴리머 기반의 일체형 인공망막장치를 개발하였는데, 이는 세라믹 또는 금속으로 만들어진 기존의 신경보철장치에 비해 얇고 가볍다는 장점이 있다. 그러나 인공망막장치 체내 삽입술은 고난위도의 수술기법을 요구하므로, 장기간 체내 안전성을 확보하기 위한 수술기법을 확립하기 위해서는 아직 많은 노력이 필요하다. 본 논문에서는 동물실험을 통해 액정폴리머 기반의 인공망막장치의 장기간 안전성을 최적화하기 위한 수술기법을 개발하고자 하였다. 예비연구에서 프로토타입 인공망막장치를 2마리의 토끼에 삽입하였다. 전극은 맥락막상강으로 삽입하고 시스템 패키지는 두개골 위에 장착하였다. 전극과 패키지 사이의 연결부는 안와 주변의 조직을 박리한 뒤 측두근 아래로 통과시켰다. 삽입술은 합병증 없이 성공적으로 시행되었다. 수술 후 시행한 안저검사, 빛간섭단층촬영과 X-선 촬영에서도 안내출혈, 망막박리, 절개부 벌어짐, 장치 이탈 등의 합병증은 관찰되지 않았다. 다음으로 액정폴리머 기반의 인공망막장치의 형태를 개선하여 안구에 완전히 이식할 수 있도록 수정하고, 11마리의 토끼에서 삽입술을 시행하였다. 전극은 맥락막상강으로 삽입하고, 패키지는 공막에 고정하였으며, 전극과 패키지 사이의 이행부는 공막에 고정하였다. 삽입술은 9마리(81.8%)에서 합병증 없이 성공적으로 이루어졌다. 그러나 2마리(18.2%)에서는 전극삽입 중 시신경 손상 및 망막 열공의 합병증이 발생하였다. 술 후 적어도 3개월동안은 10마리(90.9%)에서 인공망막장치가 체내에서 안정적으로 유지되었다. 그러나 3개월 후 9마리(81.8%)에서 패키지 또는 이행부를 덮은 결막의 미란 또는 벌어짐이 확인되었다. 그러나 이와 관계없이 맥락막상강에 삽입된 전극은 술 후에도 부작용 없이 안정적으로 유지되었다. 본 연구를 통해 수술기법 또는 장치의 형태와 관련된 몇몇 문제를 확인하였고, 추후 기술적인 개선책으로 인공망막장치 체내 삽입술의 장기간 안전성을 향상시킬 수 있을 것으로 기대한다. 또한 궁극적으로 사람에서 안전하게 인공망막장치를 삽입할 수 있는 수술기법 개발의 디딤돌이 될 것으로 기대한다. 사람과 동물모델을 기반으로 많은 연구들이 이루어져왔지만, 망막변성질환의 병태생리는 아직 명확히 밝혀지지 않았다. 생체내 망막의 구조적 변화에 대한 연구는 망막변성질환의 발병 및 진행을 이해하는데 중요하다. 근래에 빛간섭단층촬영은 망막 구조에 대한 생체연구에서 가장 유용한 검사법이지만, 아직 망막변성질환에서 비정상적인 빛간섭단층촬영 소견에 부합하는 해부학적 소견에 대해서는 명확히 알려지지 않았다. 본 논문에서는 유리체강내 요오드산나트륨을 주입한 토끼 망막변성모델에서 망막전위도 검사결과로 뒷받침되는 빛간섭단층촬영에서의 병적 변화에 부합하는 해부학적 소견을 분석하고자 하였다. 20마리의 토끼를 5마리씩 4군으로 나누어, 각 토끼의 단안에 요오드산나트륨을 군별로 0.1, 0.2, 0.4, 또는 0.8mg을 유리체강내 주입하였다. 투여 전 및 투여 후 28일 동안 각 토끼는 안저검사, 빛간섭단층촬영, 망막전위도 및 조직학적 검사를 시행하였다. 요오드산나트륨 0.2mg 군에서는 빛간섭단층촬영상 외경계막 소실 및 경도의 불분명한 타원체구역의 소견이 일시적으로 관찰되었으나, 조직학적 검사에서는 명확한 변화는 확인되지 않았다. 망막전위도 검사상 초기의 일시적인 a-파와 b-파의 감소는 투여 후 28일경에는 완전히 회복되었다. 0.4mg 군에서는 투여 후 1일째부터 빛간섭단층촬영상 외경계막 및 타원체구역이 소실되었지만, 초기 조직학적 검사에서는 빛수용세포의 핵, 내절 및 외절의 층판 구조는 비교적 유지되고 경도의 외절 및 내절의 구조적 손상만 관찰되었다. 이후에는 빛간섭단층촬영 및 조직학적 검사상 외망막층의 손상은 진행되어, 투여 후 28일경에는 빛수용세포는 완전히 소실되었다. 망막전위도 검사에서는 경과관찰 기간 동안 심한 a-파 및 b-파의 진폭의 감소가 지속되었다. 결론적으로 본 논문에서 빛간섭단층촬영은 조직학적 검사상 명확한 해부학적 변화가 나타나기 이전에 빛수용세포의 초미세구조의 변화를 초기에 확인할 수 있었다. 또한 빛간섭단층촬영상 외경계막 및 타원체구역의 손상 정도로 빛수용세포가 손상된 정도를 예측할 수 있었다.Our group has developed and manufactured a seamless liquid crystal polymer (LCP)-based monolithic retinal prosthesis. This device is thin and light which is superior to other prosthetic devices made of ceramic or metal. However, the establishment of reliable and reproducible surgical procedures ensuring the long-term safety of the prosthesis remains a challenge. In the first section of this dissertation, the reproducible surgical techniques were developed to optimize the long-term safety of implantation surgery of our LCP-based retinal prosthesis by in vivo experiments. In the pilot study, 2 eyes of 2 New Zealand white rabbits were operated to implant the prototype LCP-based prosthetic device. The electrode array was inserted into the suprachoroidal space and the system package was anchored on the skull. The interconnection cable was passed through the tunnel under the temporalis muscle. The implantation surgery was successfully performed without any complications. No postoperative complications were detected including intraocular hemorrhage, retinal detachment, wound dehiscence and displacement of the device under fundus examination, optical coherence tomography (OCT) images and x-ray. Next, our group has modified the device to implant the device in the eyeball as a whole. Eleven rabbits were operated for the implantation of totally implantable prosthetic device. The electrode array was inserted into the suprachoroid space and the package was fixed onto the sclera under the conjunctiva. The transition part between the electrode array and package were anchored onto the sclera. The surgical procedures for implantation of the entire system were easily performed in nine eyes (81.8%) without any intraoperative complications. In the other two eyes (18.2%), surgical complications related to electrode insertion, including optic nerve damage and retinal tear, arose. In 10 eyes (90.9%), the devices were well tolerated for at least 3 months. However, in most eyes (nine81.8%), two complications began to appear after 3 months, postoperatively, including conjunctival erosion or dehiscence over the package or transition part. The electrode arrays were maintained safely in the suprachoroidal space after surgery without any complications, regardless of the status of the extraocular components in all cases except two intraoperative complications. Although issues related to surgical technique or device configuration were identified, further technical solution would improve the long-term safety of device implantation. Finally, these experiments would provide a stepping stone to achieve the safe and reproducible surgical techniques for human in the future. Despite many studies in human and animal models, the pathophysiology of retinal degenerative diseases is not still clear. In vivo evaluation of the structural changes of retina is important for understanding the development and progression in retinal degenerative diseases. Currently, OCT is the most useful tool for in vivo evaluation of the retinal architecture. However, information is still lacking on the anatomic correspondences with abnormal OCT features in eyes with retinal degenerative diseases. In the second section of this dissertation, the anatomic correlates with pathologic OCT features were investigated supported by electroretinography (ERG) findings in experimental retinal degeneration model induced by intravitreal sodium iodate (NaIO3) administration. Twenty rabbits were underwent unilateral intravitreal injections of four different NaIO3 doses: 0.1, 0.2, 0.4 or 0.8mg (n=5 for each dose). Comprehensive ophthalmic examinations were performed including fundus examination, OCT, ERG and histologic analyses from baseline to 28 days after NaIO3 administration. In the 0.2-mg group, there were transient changes of outer retinal layers on OCT, including an indistinguishable external limiting membrane (ELM) and slightly obscure ellipsoid zone (EZ) without significant changes in the histologic sections. In addition, there was transient reduction of a- and b-wave amplitudes followed by complete restoration at day 28. In the 0.4-mg group, the EZ and ELM became completely indistinguishable as early as day 1, whereas the histologic analysis showed only slightly disorganized photoreceptor inner and outer segments (IS and OS) with relatively preserved overall laminations of photoreceptor cell nuclei, IS and OS. Damage to outer retinal layers progressed in both the OCT and histologic analyses, leading to complete loss of photoreceptors by day 28. Extreme reduction of the a- and b-wave amplitudes persisted throughout the study. In conclusion, OCT can reflect early ultrastructural changes of photoreceptors manifesting as disrupted EZ and ELM prior to overt morphologic changes in histologic sections. In addition, the degree of changes in the EZ and ELM on OCT might predict the severity of impairment of photoreceptors.Abstract……………………………………………………………………………. i Contents…………………………………………………………………………….v List of Tables………………………………………………………………………..x List of Figures………………………………………………………………………x 1. Chapter 1: Introduction………………………………………………………...1 1.1. Retinal prosthesis…………………………………………………………1 1.1.1. Concept of retinal prosthesis………………………………………….…..1 1.1.2. Basic components of retinal prosthesis…………………………………...2 1.1.3. Liquid crystal polymer-based retinal prosthesis…………………………..3 1.1.4. Current approaches for surgical implantation of electrode array…………3 1.1.5. Development of reproducible and safe surgical techniques for LCP-based retinal prosthesis…………………………………………………………...5 1.2. Experimental retinal degeneration……………………………………….8 1.2.1. Sodium iodate……………………………………………………………..8 1.2.2. Assessment tools for retinal structural changes in retinal degeneration….8 1.3. Dissertation outlines……………………………………………………11 1.3.1. Establishment of optimized surgical procedures for implantation of LCP-based retinal prosthesis…………………………………………………...11 1.3.2. Anatomic correspondence with pathologic OCT features in experimental retinal degeneration……………………………………………………….11 2. Chapter 2: Methods…………………………………………………………...12 2.1. LCP-based retinal prosthesis…………………………………………….12 2.1.1. Pilot study………………………………………………………………..12 2.1.1.1. Prototype LCP-based prosthetic device………………………..12 2.1.1.2. Surgical techniques for implantation of prototype prosthetic device……………………………………………………………………..13 2.1.1.3. Assessments of biocompatibility and safety after surgery……..15 2.1.2. Totally implantable LCP-based retinal prosthesis……………………….17 2.1.2.1. Totally implantable LCP-based retinal prosthesis……………..17 2.1.2.2. Surgical procedures for implantation of prosthetic device…….18 2.1.2.3. Assessment of safety during and after surgery………………...21 2.2. Experimental retinal degeneration……………………………………...21 2.2.1. Preparation of animals and NaIO3 solution……………………………...21 2.2.2. Assessments of structural and functional changes of retina……………..22 2.2.2.1. Fundus photography and optical coherence tomography……...22 2.2.2.2. Electroretinography……………………………………………23 2.2.2.3. Histology……………………………………………………….23 2.2.3. Statistical analysis……………………………………………………….24 3. Chapter 3: Results…………………………………………………………….25 3.1. LCP-based retinal prosthesis…………………………………………...25 3.1.1. Pilot study………………………………………………………………..25 3.1.2. Totally implantable LCP-based retinal prosthesis……………………….28 3.1.2.1. Implantation surgery…………………………………………...28 3.1.2.2. Postoperative assessments……………………………………..31 3.2. Experimental retinal degeneration……………………………………….36 3.2.1. Comparative analysis of morphological changes of retina……………...36 3.2.1.1. Low-dose NaIO3 group (0.1 and 0.2mg)………………………36 3.2.1.2. Intermediate-dose NaIO3 group (0.4mg)………………………39 3.2.1.3. High-dose NaIO3 group (0.8mg)………………………………42 3.2.2. Functional changes of retina……………………………………………..44 3.2.2.1. Low-dose NaIO3 group (0.1 and 0.2mg)………………………44 3.2.2.2. Intermediate-dose NaIO3 group (0.4mg)………………………44 3.2.2.3. High-dose NaIO3 group (0.8mg)………………………………45 4. Chapter 4: Discussion…………………………………………………………47 4.1. Surgical techniques to optimize the long-term outcomes of LCP-based retinal prosthesis………………………………………………………………47 4.1.1. Pilot study………………………………………………………………..47 4.1.2. Totally implantable LCP-based retinal prosthesis……………………….47 4.2. Anatomic correlations with retinal changes seen on OCT in NaIO3-induced retinal degeneration………………………………………………….52 5. Chapter 5: Conclusion………………………………………………………...57 References…………………………………………………………………………58 Abstract in Korean………………………………………………………………...62Docto

소형동물의 뇌신경 자극을 위한 완전 이식형 신경자극기

학위논문(박사)--서울대학교 대학원 :공과대학 전기·정보공학부,2020. 2. 김성준.In this study, a fully implantable neural stimulator that is designed to stimulate the brain in the small animal is described. Electrical stimulation of the small animal is applicable to pre-clinical study, and behavior study for neuroscience research, etc. Especially, behavior study of the freely moving animal is useful to observe the modulation of sensory and motor functions by the stimulation. It involves conditioning animal's movement response through directional neural stimulation on the region of interest. The main technique that enables such applications is the development of an implantable neural stimulator. Implantable neural stimulator is used to modulate the behavior of the animal, while it ensures the free movement of the animals. Therefore, stable operation in vivo and device size are important issues in the design of implantable neural stimulators. Conventional neural stimulators for brain stimulation of small animal are comprised of electrodes implanted in the brain and a pulse generation circuit mounted on the back of the animal. The electrical stimulation generated from the circuit is conveyed to the target region by the electrodes wire-connected with the circuit. The devices are powered by a large battery, and controlled by a microcontroller unit. While it represents a simple approach, it is subject to various potential risks including short operation time, infection at the wound, mechanical failure of the device, and animals being hindered to move naturally, etc. A neural stimulator that is miniaturized, fully implantable, low-powered, and capable of wireless communication is required. In this dissertation, a fully implantable stimulator with remote controllability, compact size, and minimal power consumption is suggested for freely moving animal application. The stimulator consists of modular units of surface-type and depth-type arrays for accessing target brain area, package for accommodating the stimulating electronics all of which are assembled after independent fabrication and implantation using customized flat cables and connectors. The electronics in the package contains ZigBee telemetry for low-power wireless communication, inductive link for recharging lithium battery, and an ASIC that generates biphasic pulse for neural stimulation. A dual-mode power-saving scheme with a duty cycling was applied to minimize the power consumption. All modules were packaged using liquid crystal polymer (LCP) to avoid any chemical reaction after implantation. To evaluate the fabricated stimulator, wireless operation test was conducted. Signal-to-Noise Ratio (SNR) of the ZigBee telemetry were measured, and its communication range and data streaming capacity were tested. The amount of power delivered during the charging session depending on the coil distance was measured. After the evaluation of the device functionality, the stimulator was implanted into rats to train the animals to turn to the left (or right) following a directional cue applied to the barrel cortex. Functionality of the device was also demonstrated in a three-dimensional maze structure, by guiding the rats to navigate better in the maze. Finally, several aspects of the fabricated device were discussed further.본 연구에서는 소형 동물의 두뇌를 자극하기 위한 완전 이식형 신경자극기가 개발되었다. 소형 동물의 전기자극은 전임상 연구, 신경과학 연구를 위한 행동연구 등에 활용된다. 특히, 자유롭게 움직이는 동물을 대상으로 한 행동 연구는 자극에 의한 감각 및 운동 기능의 조절을 관찰하는 데 유용하게 활용된다. 행동 연구는 두뇌의 특정 관심 영역을 직접적으로 자극하여 동물의 행동반응을 조건화하는 방식으로 수행된다. 이러한 적용을 가능케 하는 핵심기술은 이식형 신경자극기의 개발이다. 이식형 신경자극기는 동물의 움직임을 방해하지 않으면서도 그 행동을 조절하기 위해 사용된다. 따라서 동물 내에서의 안정적인 동작과 장치의 크기가 이식형 신경자극기를 설계함에 있어 중요한 문제이다. 기존의 신경자극기는 두뇌에 이식되는 전극 부분과, 동물의 등 부분에 위치한 회로부분으로 구성된다. 회로에서 생산된 전기자극은 회로와 전선으로 연결된 전극을 통해 목표 지점으로 전달된다. 장치는 배터리에 의해 구동되며, 내장된 마이크로 컨트롤러에 의해 제어된다. 이는 쉽고 간단한 접근방식이지만, 짧은 동작시간, 이식부위의 감염이나 장치의 기계적 결함, 그리고 동물의 자연스러운 움직임 방해 등 여러 문제점을 야기할 수 있다. 이러한 문제의 개선을 위해 무선통신이 가능하고, 저전력, 소형화된 완전 이식형 신경자극기의 설계가 필요하다. 본 연구에서는 자유롭게 움직이는 동물에 적용하기 위하여 원격 제어가 가능하며, 크기가 작고, 소모전력이 최소화된 완전이식형 자극기를 제시한다. 설계된 신경자극기는 목표로 하는 두뇌 영역에 접근할 수 있는 표면형 전극과 탐침형 전극, 그리고 자극 펄스 생성 회로를 포함하는 패키지 등의 모듈들로 구성되며, 각각의 모듈은 독립적으로 제작되어 동물에 이식된 뒤 케이블과 커넥터로 연결된다. 패키지 내부의 회로는 저전력 무선통신을 위한 지그비 트랜시버, 리튬 배터리의 재충전을 위한 인덕티브 링크, 그리고 신경자극을 위한 이상성 자극파형을 생성하는 ASIC으로 구성된다. 전력 절감을 위해 두 개의 모드를 통해 사용률을 조절하는 방식이 장치에 적용된다. 모든 모듈들은 이식 후의 생물학적, 화학적 안정성을 위해 액정 폴리머로 패키징되었다. 제작된 신경자극기를 평가하기 위해 무선 동작 테스트가 수행되었다. 지그비 통신의 신호 대 잡음비가 측정되었으며, 해당 통신의 동작거리 및 데이터 스트리밍 성능이 검사되었고, 장치의 충전이 수행될 때 코일간의 거리에 따라 전송되는 전력의 크기가 측정되었다. 장치의 평가 이후, 신경자극기는 쥐에 이식되었으며, 해당 동물은 이식된 장치를 이용해 방향 신호에 따라 좌우로 이동하도록 훈련되었다. 또한, 3차원 미로 구조에서 쥐의 이동방향을 유도하는 실험을 통하여 장치의 기능성을 추가적으로 검증하였다. 마지막으로, 제작된 장치의 특징이 여러 측면에서 심층적으로 논의되었다.Chapter 1 : Introduction 1 1.1. Neural Interface 2 1.1.1. Concept 2 1.1.2. Major Approaches 3 1.2. Neural Stimulator for Animal Brain Stimulation 5 1.2.1. Concept 5 1.2.2. Neural Stimulator for Freely Moving Small Animal 7 1.3. Suggested Approaches 8 1.3.1. Wireless Communication 8 1.3.2. Power Management 9 1.3.2.1. Wireless Power Transmission 10 1.3.2.2. Energy Harvesting 11 1.3.3. Full implantation 14 1.3.3.1. Polymer Packaging 14 1.3.3.2. Modular Configuration 16 1.4. Objectives of This Dissertation 16 Chapter 2 : Methods 18 2.1. Overview 19 2.1.1. Circuit Description 20 2.1.1.1. Pulse Generator ASIC 21 2.1.1.2. ZigBee Transceiver 23 2.1.1.3. Inductive Link 24 2.1.1.4. Energy Harvester 25 2.1.1.5. Surrounding Circuitries 26 2.1.2. Software Description 27 2.2. Antenna Design 29 2.2.1. RF Antenna 30 2.2.1.1. Design of Monopole Antenna 31 2.2.1.2. FEM Simulation 31 2.2.2. Inductive Link 36 2.2.2.1. Design of Coil Antenna 36 2.2.2.2. FEM Simulation 38 2.3. Device Fabrication 41 2.3.1. Circuit Assembly 41 2.3.2. Packaging 42 2.3.3. Electrode, Feedthrough, Cable, and Connector 43 2.4. Evaluations 45 2.4.1. Wireless Operation Test 46 2.4.1.1. Signal-to-Noise Ratio (SNR) Measurement 46 2.4.1.2. Communication Range Test 47 2.4.1.3. Device Operation Monitoring Test 48 2.4.2. Wireless Power Transmission 49 2.4.3. Electrochemical Measurements In Vitro 50 2.4.4. Animal Testing In Vivo 52 Chapter 3 : Results 57 3.1. Fabricated System 58 3.2. Wireless Operation Test 59 3.2.1. Signal-to-Noise Ratio Measurement 59 3.2.2. Communication Range Test 61 3.2.3. Device Operation Monitoring Test 62 3.3. Wireless Power Transmission 64 3.4. Electrochemical Measurements In Vitro 65 3.5. Animal Testing In Vivo 67 Chapter 4 : Discussion 73 4.1. Comparison with Conventional Devices 74 4.2. Safety of Device Operation 76 4.2.1. Safe Electrical Stimulation 76 4.2.2. Safe Wireless Power Transmission 80 4.3. Potential Applications 84 4.4. Opportunities for Further Improvements 86 4.4.1. Weight and Size 86 4.4.2. Long-Term Reliability 93 Chapter 5 : Conclusion 96 Reference 98 Appendix - Liquid Crystal Polymer (LCP) -Based Spinal Cord Stimulator 107 국문 초록 138 감사의 글 140Docto

Bio-Micro-Systems for Diagnostic Applications, Disease Prevention and Creating Tools for Biological Research

This thesis, divided into two parts, describes the development of 5 novel Bio-Micro-System devices. The term Bio-Micro-System has been used here to describe BioMEMS and 3D printed devices, with the dimensions of key components ranging from micrometers to a millimeter. Part A is focused on ‘Medical’ Micro-System devices that can potentially solve common medical problems. Part B is focused on ‘Biological’ Micro-System devices/tools for facilitating/enabling biological research. Specifically, Part A describes two implantable, electronics-free intraocular pressure (IOP) microsensors for the medical management of glaucoma: 1) Near Infrared Fluorescence-based Optomechanical (NiFO) technology - Consists of an implantable, pressure sensor that ‘optically encodes’ pressure in the near infrared (NIR) regime. A non-implantable, portable and compact optical head is used to excite the sensor and collect the emitted NIR light. The thesis discusses optimized device architecture and microfabrication approaches for best performance commercialization. 2) Displacement based Contrast Imaging (DCI) technology - A proof of concept, fluid pressure sensing scheme is shown to operate over a pressure range of 0–100 mbar (∼2 mbar resolution between 0–20 mbar,∼10 mbar resolution between 20–100 mbar), with a maximum error of <7% throughout its dynamic range. The thesis introduces the DCI technology and discusses its application as an IOP sensor. Moreover, Part A also describes a Touch-activated Sanitizer Dispensing (TSD) system for combating community acquired infections. The TSD can be mounted on any surface that is exposed to high human traffic and consists of an array of human-powered, miniaturized valves that deliver a small amount of disinfectant when touch actuated. The device disinfects the person’s hand that is touching it while being self-sterilized at the same time. The thesis describes the design and implementation of a proof of concept TSD that can disinfect an area equivalent to the size of a thumb. A significant (~ 10 fold) reduction in microbiological load is demonstrated on the fingertip and device surface within the first 24 hours. The size and footprint of the TSD can be scaled up as needed to improve hand hygiene compliance. In Part B, we developed a microfluidic chip for immobilizing Drosophila melanogaster larva by creating a cold micro-environment around the larva. After characterizing on chip temperature distribution and larval body movement, results indicate that the method is appropriate for repetitive and reversible, short-term (several minutes) immobilization. The method offers the added advantage of using the same chip to accommodate and immobilize larvae across all developmental stages (1st instar-late 3rd instar). Besides the demonstrated applications of the chip in high resolution observation of sub cellular events such as mitochondrial trafficking in neurons and neuro-synaptic growth, we envision the use of this method in a wide variety of biological imaging studies employing the Drosophila larval system, including cellular development and other studies. Finally, Part B also describes a 3D printed millifluidic device for CO2 immobilization of Caenorhabditis elegans populations. We developed a novel 3D printed device for immobilizing populations of Caenorhabditis elegans by creating a localized CO2 environment while the animals are maintained on the surface of agar. The results indicate that the method is easy to implement, is appropriate for short-term (20 minutes) immobilization and allows recovery within a few minutes. We envision its use in a wide variety of biological studies in Caenorhabditis elegan, including cellular development and neuronal regeneration studies.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144050/1/amritarc_1.pd

De animais a máquinas : humanos tecnicamente melhores nos imaginários de futuro da convergência tecnológica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Sociologia, 2020.O tema desta investigação é discutir os imaginários sociais de ciência e tecnologia que emergem a partir da área da neuroengenharia, em sua relação com a Convergência Tecnológica de quatro disciplinas: Nanotecnologia, Biotecnologia, tecnologias da Informação e tecnologias Cognitivas - neurociências- (CT-NBIC). Estas áreas desenvolvem-se e são articuladas por meio de discursos que ressaltam o aprimoramento das capacidades físicas e cognitivas dos seres humanos, com o intuito de construir uma sociedade melhor por meio do progresso científico e tecnológico, nos limites das agendas de pesquisa e desenvolvimento (P&D). Objetivos: Os objetivos nesse cenário, são discutir as implicações éticas, econômicas, políticas e sociais deste modelo de sistema sociotécnico. Nos referimos, tanto as aplicações tecnológicas, quanto as consequências das mesmas na formação dos imaginários sociais, que tipo de relações se estabelecem e como são criadas dentro desse contexto. Conclusão: Concluímos na busca por refletir criticamente sobre as propostas de aprimoramento humano mediado pela tecnologia, que surgem enquanto parte da agenda da Convergência Tecnológica NBIC. No entanto, as propostas de melhoramento humano vão muito além de uma agenda de investigação. Há todo um quadro de referências filosóficas e políticas que defendem o aprimoramento da espécie, vertentes estas que se aliam a movimentos trans-humanistas e pós- humanistas, posições que são ao mesmo tempo éticas, políticas e econômicas. A partir de nossa análise, entendemos que ciência, tecnologia e política estão articuladas, em coprodução, em relação às expectativas de futuros que são esperados ou desejados. Ainda assim, acreditamos que há um espaço de diálogo possível, a partir do qual buscamos abrir propostas para o debate público sobre questões de ciência e tecnologia relacionadas ao aprimoramento da espécie humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The subject of this research is to discuss the social imaginaries of science and technology that emerge from the area of neuroengineering in relation with the Technological Convergence of four disciplines: Nanotechnology, Biotechnology, Information technologies and Cognitive technologies -neurosciences- (CT-NBIC). These areas are developed and articulated through discourses that emphasize the enhancement of human physical and cognitive capacities, the intuition it is to build a better society, through the scientific and technological progress, at the limits of the research and development (R&D) agendas. Objectives: The objective in this scenery, is to discuss the ethic, economic, politic and social implications of this model of sociotechnical system. We refer about the technological applications and the consequences of them in the formation of social imaginaries as well as the kind of social relations that are created and established in this context. Conclusion: We conclude looking for critical reflections about the proposals of human enhancement mediated by the technology. That appear as a part of the NBIC technologies agenda. Even so, the proposals of human enhancement go beyond boundaries that an investigation agenda. There is a frame of philosophical and political references that defend the enhancement of the human beings. These currents that ally to the transhumanism and posthumanism movements, positions that are ethic, politic and economic at the same time. From our analysis, we understand that science, technology and politics are articulated, are in co-production, regarding the expected and desired futures. Even so, we believe that there is a space of possible dialog, from which we look to open proposals for the public discussion on questions of science and technology related to enhancement of human beings

The role of contrast enhanced ultrasonography in post-operative surveillance of endovascular aortic aneurysm stent graft repair

MD (Res)Abdominal aortic aneurysms are common and responsible for many deaths. They are treated increasingly by EndoVascular Aneurysm Repair (EVAR) rather than conventional surgery. Approximately 25% of EVAR patients require re-intervention to prevent aneurysm enlargement which can rupture despite previous repair. All EVAR patients undergo life-long surveillance for complications such as stent-graft migration or endoleak. Computed Tomography (CT) has been the ‘gold-standard’ for surveillance accounting for 65% of EVAR costs, and exposes patients to cumulative radiation and nephrotoxic contrast. Duplex Ultrasound Scanning (DUS) has been proposed as an alternative for surveillance with lesser cost and patient risk. However, clinical studies have reported varying results. The addition of microbubble contrast significantly improves endoleak detection rates, making it comparable with CT. The physical properties that affect endoleak detection with DUS have not been determined. It is also unknown specifically which endoleaks’ detection are improved by Contrast Enhanced Aortic Duplex UltraSound Scanning (CEADUSS). To investigate the physical properties of endoleaks, I constructed an EVAR phantom model with a simulated endoleak of variable velocity (fast/slow), position (near/far) and plane (anterior/lateral/posterior). Preliminary studies investigated the behavior of microbubble contrast in the phantom system, and then laboratory experiments tested subjects over 36 variable endoleaks using DUS and CEADUSS. These laboratory experiments were translated clinically with a pilot study of CEADUSS in 10 patients with endoleaks on CT not detected by DUS, undefined endoleak type or origin, or a sac enlargement with no endoleak present. My experiments reveal an insight into factors influencing ultrasound endoleak detection. With this knowledge, the use of these modalities for surveillance protocols can be increased, reducing current CT burden, radiation and nephrotoxic contrast exposure, and overall EVAR cost. Clinical assessment of an endoleak, specifically noting physical characteristics (plane, position and velocity) will improve detection and surveillance