京都大学 / 新制・課程博士 / 博士(医学) / 甲第24799号 / 医博第4991号 / 新制||医||1066(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 石見 拓, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Minimally invasive surgery (MIS) has several advantages over traditional methods. Scaling MIS instruments to smaller sizes and increasing their performance will enable surgeons to offer new procedures to a wider range of patients. In this work, two compliant mechanism-based minimally invasive surgical instrument wrist or gripper mechanisms are designed and analyzed.The cylindrical cross-axis flexural pivot (CCAFP) is a single-degree-of-freedom wrist mechanism that could be combined with existing gripper mechanisms to create a multi-degree-of freedom instrument. The simplicity of the CCAFP mechanism facilitates analysis and implementation. The flexures of the CCAFP are integral with the instrument shaft, enabling accessories to be passed through the lumen. The CCAFP is analyzed and determined to be a viable wrist mechanism for MIS instruments based on research results. A finite element (FE) model of the mechanism is created to analyze the force-deflection and strain-deflection relationships. Experimental results are used to verify the FE model. A 3 mm design is created that could undergo an angular deflection of +/- 90 degrees. The addition of cam surfaces to help guide the flexures and limit the maximum stress during deflection is explored. These cam surfaces can be integral to the instrument shaft along with the flexures. A 2 degree-of-freedom (DoF) CCAFP with intersecting axes of rotation is also introduced. The inverted L-Arm gripper compliant mechanism has 2 DoF, one wrist and one gripping. Three challenges associated with using compliant mechanisms in MIS instruments are considered: inadequate performance in compression, large flexure deformations, and a highly variable mechanical advantage. These challenges were resolved in the L-Arm design by inverting the flexures, tailoring flexure geometry and employing nitinol, and integrating pulleys into each jaw of the mechanism. The L-Arm was prototyped at several sizes to demonstrate functionality and scalability. A finite element model of the L-Arm flexure was created to determine the strain-deflection relationship. A fatigue test was completed to characterize nitinol for use in compliant mechanism MIS instruments.These concepts demonstrate the ability of compliant mechanisms to overcome the design and manufacturing challenges associated with MIS instruments at the 3 mm scale. The models and principles included in this work could be used in the application of compliant mechanisms to design new MIS instruments as well as in other areas that employ compliant mechanisms in a cylindrical form factor.

Background: Pediatric minimally invasive surgery (MIS) is a standard technique worldwide. We aimed to analyze the research activity in this field. Methods: Articles on pediatric MIS (1991–2020) were analyzed from the Web of Science™ for the total number of publications, citations, journals, and impact factors (IF). Of these, the 50 most cited publications were evaluated in detail and classified according to the level of evidence (i.e., study design) and topic (i.e., surgical procedure). Results: In total, 4464 publications and 53,111 citations from 684 journals on pediatric MIS were identified. The 50 most cited papers were published from 32 institutions in the USA/Canada (n = 28), Europe (n = 19), and Asia (n = 3) in 12 journals. Four authors (USA/Europe) contributed to 26% of the 50 most cited papers as first/senior author. Hot topics were laparoscopic pyeloplasty (n = 9), inguinal hernia repair (n = 7), appendectomy, and pyloromyotomy (n = 4 each). The majority of publications were retrospective studies (n = 33) and case reports (n = 6) (IF 5.2 ± 3.2; impact index 16.5 ± 6.4; citations 125 ± 39.4). They were cited as often as articles with high evidence levels (meta-analyses, n = 2; randomized controlled trials, n = 7; prospective studies, n = 2) (IF 12.9 ± 22.5; impact index 14.0 ± 6.5; citations 125 ± 34.7; p > 0.05). Conclusions: Publications on laparoscopic pyeloplasty, inguinal hernia repair, appendectomy, and pyloromyotomy are cited most often in pediatric MIS. However, the relevant number of studies with strong evidence for the advantages of MIS in pediatric surgery is missing.

Background: Majority of cancer interventions today are performed percutaneously using needle-based procedures, i.e. through the skin and soft tissue. Needle insertion is known as one of the recent needle-based techniques that is used in several diagnostic and therapeutic medical procedures such as brachytherapy, thermal ablations and breast biopsy. The difficulty in most of these procedures is to attain a precise navigation through tissue reaching target locations. Insufficient accuracy using conventional surgical needles motivated researchers to provide actuation forces to the needle’s body for compensating the possible errors of surgeons/physicians. Therefore, active needles were proposed recently where actuation forces provided by shape memory alloys (SMAs) are utilized to assist the maneuverability and accuracy of surgical needles. This work also aims to introduce a novel needle insertion simulation to predict the deflection of a bevel tip needle inside the tissue. Development of a model to predict the behavior of the needle steering in the soft tissue has been always a point of interest as it could improve the performance of many percutaneous needle-based procedures. Methods: In this work first, the actuation capability of a single SMA wire was studied. The complex response of SMAs was investigated via a MATLAB implementation of the Brinson model and verified via experimental tests. The material characteristics of SMAs were simulated by defining multilinear elastic isothermal stress-strain curves. Rigorous experiments with SMA wires were performed to determine the material properties as well as to show the capability of the code to predict a stabilized SMA transformation behavior with sufficient accuracy. The isothermal stress-strain curves of SMAs were simulated and defined as a material model for the Finite Element Analysis of the active needle. In the second part of this work, a three-dimensional finite element (FE) model of the active steerable needle was developed to demonstrate the feasibility of using SMA wires as actuators to bend the surgical needle. In the FE model, birth and death method of defining boundary conditions, available in ANSYS, was used to achieve the pre-strain condition on SMA wire prior to actuation. This numerical model was validated with needle deflection experiments with developed prototypes of the active needle. The third part of this work describes the design optimization of the active using genetic algorithm aiming for its maximum flexibility. Design parameters influencing the steerability include the needle’s diameter, wire diameter, pre-strain, and its offset from the needle. A simplified model was developed to decrease the computation time in iterative analyses of the optimization algorithm. In the fourth part of this work a design of an active needling system was proposed where actuation forces of SMAs as well as shape memory polymers (SMPs) were incorporated. SMP elements provide two major additional advantages to the design: (i) recovery of the SMP’s plastic deformation by heating the element above its glass transition temperature, and (ii) achieving a higher needle deflection by having a softer stage of SMP at higher temperatures with less amount of actuation force. Finally, in the fifth and last part of this study, an Arbitrary-Lagrangian-Eulerian formulation in LS-DYNA software was used to model the solid-fluid interactions between the needle and tissue. A 150mm long needle was considered to bend within the tissue due to the interacting forces on its asymmetric bevel tip. Some additional assumptions were made to maintain a reasonable computational time, with no need of parallel processing, while having practical accuracies. Three experimental tests of needle steering in a soft phantom were performed to validate the simulation. Results: The finite element model of the active needle was first validated experimentally with developed prototypes. Several design parameters affecting the needle’s deflection such as the needle’s Young’s modulus, the SMA’s pre-strain and its offset from the neutral axis of the cannula were studied using the FE model. Then by the integration of the SMA characteristics with the automated optimization schemes an improved design of the active needle was obtained. Real-time experiments with different prototypes showed that the quickest response and the maximum deflection were achieved by the needle with two sections of actuation compared to a single section of actuation. Also the feasibility of providing actuation forces using both SMAs and SMPs for the surgical needle was demonstrated in this study. The needle insertion simulation was validated while observing less than 10% deviation between the estimated amount of needle deflection by the simulation and by the experiments. Using this model the effect of needle diameter and its bevel tip angle on the final shape of the needle was investigated. Conclusion: The numerical and experimental studies of this work showed that a highly maneuverable active needle can be made using the actuation of multiple SMA wires in series. To maneuver around the anatomical obstacles of the human body and reach the target location, thin sharp needles are recommended as they would create a smaller radius of curvature. The insertion model presented in this work is intended to be used as a base structure for path planning and training purposes for future studies. / Mechanical Engineering

Malignant gliomas (MG), most notably glioblastoma multiforme (GBM), are among the most aggressive of all malignancies. High-grade variants of this type of brain cancer are generally considered incurable with singular or multimodal therapies. Many patients with GBM die within one year of diagnosis, and the 5-year survival rate in people is approximately 10%. Despite extensive research in diagnostic and therapeutic technologies, very few developments have emerged that significantly improve survival over the last seven decades. Irreversible electroporation (IRE) is a new non-thermal focal tissue ablation technique that uses low-energy electric pulses to destabilize cell membranes, thus achieving tissue death. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about one minute. The pulses create an electric field that induces an increase in the resting transmembrane potential (TMP) of the cells in the tissue. The induced increase in the TMP is dependent on the electric pulse parameters. Depending on the magnitude of the induced TMP the electric pulses can have no effect, transiently increase membrane permeability or cause spontaneous death. In this dissertation we hypothesize that irreversible electroporation is capable of ablating normal (gray and white matter) and pathological (MG and/or GBM) brain tissue in a highly focused non-thermal manner that is modulated through pulse parameters and electrode configuration. Through a comprehensive experimental and numerical investigation, we tested and attained results strongly supporting our hypothesis. Specifically, we developed numerical models that were capable of simulating an entire IRE treatment protocol and would take into account pulse parameters (e.g. duration, frequency, repetition rate and strength) in addition to the dynamic changes in tissue electrical conductivity due to electroporation and joule heating, as well as biologically relevant processes such as blood perfusion and metabolic heat. We also provided a method to isolate the IRE effects from undesired thermal damage in models that were validated with real-time temperature measurements during the delivery of the pulses. Finally we outlined a procedure to use 3D volumetric reconstructions of IRE lesions using patient specific MRI scans in conjunction with the models described for establishing field thresholds or performing treatment planning prior to the surgical procedure; thus supplying the readers with the tools and understanding necessary to design appropriate treatment protocols for their specific application. Experimentally we presented the first systematic in vivo study of IRE in normal canine brain and the multimodal treatment of a canine MG patient. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically. The lesions created with IRE were sub-millimeter in resolution and we achieved 75% tumor volume reduction within 3 days post-IRE in the patient. In addition to the sharp delineation between necrotic and normal brain, the treatments spared the major blood vessels, making it appropriate for treatment of tumors adjacent to, or enveloping critical vascular structures. We believe that irreversible electroporation will play a key role in the treatment of intracranial disorders including malignant brain cancer in which the intent is to focally kill undesired tissue while minimizing damage to surrounding healthy tissue. / Ph. D.

1. Bibliometric study in pediatric minimally invasive surgery (MIS) Pediatric MIS is a standard technique worldwide for many pediatric surgical diseases and we aimed to analyze the research activity in this field. Articles on pediatric MIS (1991–2020) were analyzed from the Web of ScienceTM for the total number of publications, citations, journals, and IFs. Of these, the 50 most cited publications were evaluated in detail and classified according to the level of evidence (i.e., study design) and topic (i.e., surgical procedure). In total, 4464 publications and 53,111 citations from 684 journals on pediatric MIS were identified. The 50 most cited papers were published from 32 institutions in the USA/Canada (n = 28), Europe (n = 19), and Asia (n = 3) in 12 journals. Four authors (USA/Europe) contributed to 26% of the 50 most cited papers as first/senior author. Hot topics were laparoscopic pyeloplasty (n = 9), inguinal hernia repair (n = 7), appendectomy, and pyloromyotomy (n = 4 each). The majority of publications were retrospective studies (n = 33) and case reports (n = 6) (IF 5.2 ± 3.2; impact index 16.5 ± 6.4; citations 125 ± 39.4). They were cited as often as articles with high evidence levels (meta-analyses, n = 2; randomized controlled trials, n = 7; prospective studies, n = 2) (IF 12.9 ± 22.5; impact index 14.0 ± 6.5; citations 125 ± 34.7; p > 0.05). 2. Altmetric study in pediatric surgery Altmetric analysis assessing online mentions of publications is a new method to evaluate awareness to research output. We aimed to identify and characterize the top 100 articles with the highest Altmetric Attention Score (AAS) in pediatric surgery. Publications from core pediatric surgical journals (J Pediatr Surg, J Pediatr Surg Case Rep, Eur J Pediatr Surg, European J Pediatr Surg Rep, Pediatr Surg Int, Semin Pediatr Surg) were retrieved from www.altmetric.com in January 2023 and the top 100 publications were identified. Characteristics of each publication were analyzed. Publications ranked 93 to 101 had an identical AAS of 21. Thus, 101 articles were included for further analysis. The top 101 AAS articles were published between 1974 and 2022, preferentially from the United States (64%) and mainly in J Pediatr Surg (73%), followed by J Pediatr Surg Case Rep, Pediatr Surg Int, Semin Pediatr Surg, and Eur J Pediatr Surg. Their AAS ranged between 21 and 389 (median 33) with X (formerly Twitter) being mostly responsible for online mentions (n=2189, 75%). The number of citations ranged from 0 to 358 (median 16) and did not correlate with the AAS. Retrospective study design (33%) with low evidence level IV (49%) was the dominant study type. 3. Conclusions According to our bibliometric study in pediatric MIS, research activity increased over the last 30 years, with a golden decade in the early 21st century. Laparoscopic pyeloplasty and inguinal hernia repair accounted for most of the top 50 citations. Retrospective studies and case reports were the most common type of publication. Studies with high level of evidence such as randomized controlled trials are missing, especially on advanced techniques in pediatric MIS. For our altmetric study of publications in core pediatric surgery journals, we analyzed the top 101 most mentioned pediatric surgery articles in six pediatric journals. Among the pediatric surgical journals, the Journal of Pediatric Surgery is the main source for high-profile publications in pediatric surgery. The altmetric score of articles is predominantly achieved by their propagation via X (formerly Twitter), irrespective of study design, level of evidence or recognition by the scientific community. Therefore, active “twitterism” may play the key role in reaching high AAS.

Thesis (MScEng)--Stellenbosch University, 2009. / ENGLISH ABSTRACT: Minimal invasive surgery (MIS) enables surgeons to operate through a few small incisions made in the patient’s body. Through these incisions, long rigid instruments are inserted into the body and manipulated to perform the necessary surgical tasks. Conventional instruments, however, are constrained by having only five degrees of freedom (DOF), as well as having scaled and mirrored movements, thereby limiting the surgeon’s dexterity. Surgeons are also deprived of depth perception and hand-eye coordination due to only having two-dimensional visual feedback. Surgical robotics attempt to alleviate these drawbacks by increasing dexterity, eliminating the fulcrum effect and providing the surgeon with three-dimensional visualisation. This reduces the risks to the patient as well as to the surgeon. However, existing MIS systems are extremely expensive and bulky in operating rooms, preventing their more widespread adoption. In this thesis, a new, inexpensive seven-DOF primary slave manipulator (PSM) is presented. The four-DOF wrist is actuated through a tendon mechanism driven by five 12 VDC motors. A repeatability study on the wrist’s joint position was done and showed a standard deviation of 0.38 degrees. A strength test was also done and demonstrated that the manipulator is able to resist a 10 N opposing tip force and is capable of a theoretical gripping force of 15 N. / AFRIKAANSE OPSOMMING: Minimale indringende chirurgie (MIC) maak dit vir chirurge moontlik om operasies uit te voer deur ’n paar klein insnydings wat op die pasiënt se liggaam gemaak word. Deur hierdie insnydings word lang onbuigsame instrumente in die liggaam ingesit en gemanipuleer om die nodige chirurgiese take uit te voer. Konvensionele instrumente is egter beperk vanweë die feit dat hulle net vyf vryheidsgrade het, asook afgeskaalde bewegings en spieëlbewegings, en gevolglik die chirurg se handvaardigheid beperk. Chirurge word ook ontneem van dieptewaarneming en hand-oog-koördinasie, want hulle is beperk tot tweedimensionele visuele terugvoer. Chirurgiese robotika poog om hierdie nadele aan te spreek deur handvaardigheid te vermeerder, die hefboomeffek uit te skakel en die chirurg driedimensionele visualisering te bied. Dit verminder die risiko’s vir die pasiënt én vir die chirurg. Bestaande MIC-stelsels is egter uiters duur en neem baie plek op in teaters, wat verhoed dat hulle op ’n groter skaal gebruik word. In hierdie tesis word ’n nuwe, goedkoop sewevryheidsgrade- primêre slaafmanipuleerder (PSM) voorgelê. Die viervryheidsgrade-pols word beweeg deur ’n tendonmeganisme wat aangedryf word deur vyf 12 VDC-motors. ’n Herhaalbaarheidstudie is op die pols se gewrigsposisie gedoen, wat ’n standaardafwyking van 0.38 grade aangetoon het. ’n Sterktetoets is ook gedoen en het gewys dat die manipuleerder in staat is om ’n 10 N-teenkantelkrag te weerstaan en dat dit oor ’n teoretiese greepsterkte van 15 N beskik.

Thesis (MScEng)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Minimally Invasive Surgery (MIS) in human beings is performed by making small incisions in the abdominal region of the patient and inflating the abdominal cavity with CO2. This procedure enables the surgeon to manipulate long rigid surgical instruments inside the patient in order to perform the surgery. Unfortunately the current methods of insertion and assembly of MIS instruments limit the surgeon to only five (of a possible seven) Degrees of Freedom (DOF). Along with this, the surgeon’s movements are mirrored (called the Fulcrum effect) and scaled around the point of incision. Minimally invasive surgical robots attempt to alleviate these drawbacks by eliminating the Fulcrum effect, as well as improving dexterity and accuracy. These robots’ abilities to improve the surgeon’s hand-eye coordination, enables the surgeon to perform surgeries using their natural movements with reduced fatigue. As a result of this, the risk to both patient and surgeon is reduced. Existing MIS robotic systems are extremely expensive and large, and as a result they are not widely used. In this thesis a new, lower cost, seven DOF robotic manipulator is further developed. The thesis focuses on the external three DOF Secondary Slave Manipulator (SSM) and combines it with the Primary Slave Manipulator (PSM) that was developed by a previous Masters student. Tests done on the SSM showed that the manipulator has a minimum resolution of 0.7 ± 0.2 mm (mean ± standard deviation) on the shoulder joint’s yaw rotation and 0.5 ± 0.2 mm in pitch rotation. The linear actuator used for insertion has a minimum resolution of 0.2 ± 0.2 mm. A strength test was also conducted and showed that the manipulator is easily capable of producing a 10 N actuation force as required during Minimally Invasive Robotic Surgery (MIRS) procedures. In conclusion the complete system has potential as a viable alternative to the existing systems due to its accuracy and lower cost. Future work will include the development of a user interface and control system for the complete robot. / AFRIKAANSE OPSOMMING: Minimaal Indringende Chirurgie (MIC) op mense word uitgevoer deur klein insnydings in die pasiënt se buik te maak en dan die abdominale holte met CO2 te vul. Dit stel die chirurg in staat om lang, onbuigbare instrumente binne die pasiënt te manipuleer om sodoende die operasie uit te voer. Die manier waarop die MIC instrument ontwerp is en die pasiënt binnegaan, laat egter slegs vyf vryheidsgrade toe, terwyl die chirurg self sewe vryheidsgrade in sy handbewegings het. Verder veroorsaak hierdie instrumente ook dat die chirurg se aksies in spieëlbeeld vertolk word (Fulcrum effek) en geskaleer is. Chirurgiese robotika poog om hierdie nadele teen te werk deur die Fulcrum effek te verwyder, en ook om handvaardigheid en akkuraatheid te bevorder. Die robot se potensiaal om die chirurg se hand-oog koӧrdinasie te verbeter, maak dit moontlik vir die chirurg om op ’n meer natuurlike en gemaklike manier te werk te gaan en bring minder vermoeienis mee. Dit verminder die risiko’s vir beide die pasiënt en die chirurg. Bestaande robotiese stelsels is egter baie duur en groot, en word dus nie meer algemeen gebruik nie. In hierdie tesis word ‘n nuwe sewe-vryheidsgraad robotiese manipuleerder ontwikkel. Die tesis fokus op die eksterne drie-vryheidsgraad Sekondêre Slaaf Manipuleerder (SSM) en kombineer dit met die Primêre Slaaf Manipuleerder (PSM) wat deur ʼn vorige Meestersstudent ontwikkel is. Toetse wat uitgevoer is op die SSM het getoon dat dit ’n minimum resolusie van 0.7 ± 0.2 mm (gemiddeld ± standaard afwyking) op die skouer se afwyking en 0.5 ± 0.2 mm om die onderskeie skouer aslyne toon. Die linieêre aktueerder wat vir inlassing gebruik word het ’n minimum resolusie van 0.2 ± 0.2 mm. ’n Sterktetoets is uitgevoer en het getoon dat die manipuleerder maklik die nodige 10 N krag soos benodig in Minimaal Indringende Robotiese Chirurgie (MIRC) prosedures kan lewer. Ter afsluiting, die volledige stelsel het die potensiaal as lewensvatbare alternatief tot die bestaande stelsels vanweë die akkuraatheid en laer koste verbonde. Toekomstige navorsing kan moontlik die ontwikkeling van ʼn gebruikerkoppelvlak en beheerstelsel vir die volledige robot insluit.

Minimally Invasive Surgery (MIS) differs from Open Surgery as surgeons view the surgical site indirectly on a monitor. The view shown is typically from an angled endoscope off to one side of the surgery (i.e., uncollocated with the view of the hands). This makes camera navigation a challenging ability to learn. MIS thus requires longer training periods, more practice and mental effort to achieve proficiency. Current training setups and Operating Room (OR) environments lack appropriate real-time visual cues for navigation and other perception related information that could help with learning and performance in the OR. The purpose of this research was to design and develop graphical aids for improving understanding of camera navigation and depth perception in a trainer box necessary for enhancing surgeon’s skills to perform endoscopic surgery. For the former, two alternate training methods: 1) using no graphics (control group) and 2) using three different types of graphics conveying different information, were considered for this study. The effectiveness of the training was evaluated by a comparative analysis of different performance measures across all the groups. It was observed that training using graphics did improve the performance of participants in performing a minimally invasive surgery training task. For the latter, the use of a proximity sensor was explored.

The purpose of this experiment was to determine if there existed techniques to more efficiently train prospective surgeons the skills necessary to capably perform minimally invasive surgical procedures. Also, we wanted to know if trainees could be pushed to cognitively define a laparoscopic environment with a novel hand-eye relationship. To explore these questions, a simulation was setup wherein subjects would perform a laparoscopic transfer task and receive active feedback during training. Different subjects would receive different metrics as feedback and a comparison would be made between subjects with respect to standard metrics. Results of this experiment show that all subjects adapt to a laparoscopic environment and that they do so at different rates and to different proficiencies. The difference was shown to be statistically significant. It was concluded that the techniques we utilized were effective enough to claim as useful techniques to utilize in current training systems.