Our bodies maintain normal physiological functions by sensing and responding to various mechanical stresses not only from outside but also within the body. These mechanical stress sensing and response mechanisms contribute to the regulation of physiological functions on a broad space-time scale including cell division, developmental processes, and the emergence of organ-specific functions; evidence has accumulated which suggests that collapse of these mechanical stress sensing and response mechanisms is involved in various pathologies. Looking toward the goal of establishing mechanomedicine in order to devise novel therapeutic methods, we have developed a number of new research methods and systems as well as resolving issues based on the elucidation of pathology employing a vertical research approach covering mechanosensor molecules, cells, tissues, and organs, at individual levels, in combination with horizontal research on diseases affecting each organ, from the perspective of mechanobiology.

This lecture provides an overview of basic medical research on mechanobiology, specifically the mechanism of mechanical stress sensing, and introduces research derived from the aforementioned research processes, specifically as applied to regenerative medicine (three-dimensional culture using selfassembling peptide + mechanical stress loading system) and assisted reproduction technologies (microfluidic sperm sorting system/stretch-induced fertilized egg culture system).

Understanding, diagnosing and treating respiratory diseases is more important now than ever due to increasing pollution as well as the current and future pandemics. Inhaled air may contain dust, bacterial and viral particles that can irritate a person's nose, throat or airways. This irritation can easily turn into an allergic reaction. Furthermore, if particles reach deep alveolar regions of the lung, bacterial and viral particles can cause severe pneumonia leading to some form of acute respiratory distress syndrome (ARDS). For example, the SARS-Cov-2 virus can bind to cell surface receptors on type II alveolar epithelial cells and following internalization and replication, the virus may cause a lung disease, the Covid-19, which, in its severe form, invariably requires mechanical ventilation. The mortality rate of ARDS unrelated to SARSCov-2 is between 30% and 40%, whereas that of Covid-19 is higher than 50%. Thus, detection of particles, diagnosing the early symptoms and treating patients with the mild and severe form of lung diseases require tools that combine engineering and physics with biology, immunology and nanomedicine. In this presentation, I will discuss 4 areas of interdisciplinary research that are at the forefront of respiratory diagnostics and therapeutics. 1) Modeling the interaction of particle properties, airflow and complex airway geometry to better understand where inhaled particles are deposited. Our recent work suggests that particle transport in a complex branching structure can be modeled using a Markov chain approach which not only provides a deposition map, but can also be used to optimize inhalation strategies for targeted delivery of drug particles. 2) Mechanical ventilation methods to minimize the risk of full blown ARDS and maximize resources for optimal strategies ventilating patients. First, I will describe 2 types of mechanical ventilation, airway pressure release ventilation (APRV) and variable ventilation (VV), both of which have the potential to mitigate ARDS and accelerate recovery. Next, I will describe a new engineering method to safely individualize management of multiple patients using a single ventilator. 3) A novel method, called ZVV, which can be used both as a diagnostic and a therapeutic tool when ARDS patients require mechanical ventilation. The diagnostic aspect of ZVV is related to the specific mode of ventilation offered by VV, namely, that tidal volume and frequency is varied from cycle-to-cycle. Analyzing each breath separately, allows us to reconstruct the impedance spectrum Z of the respiratory system over a range of frequencies. Features of Z can in turn guide ventilation protocols, while VV itself helps recruiting the lung and hence minimizing ventilator-induced lung injury. 4) Mechanical vibrations utilized as therapeutic means to reduce irregular breathing in preterm infants. I will describe 2 methods of applying mild vibrations to infants that have the potential to reduce irregular breathing and hence the risk of sudden infants death syndrome. Before concluding, I will highlight possible areas where engineering and physics can be further utilized to solve outstanding biological and medical problems of our times. In summary, it may be expected that the presented engineering and physics methods together with other methods that already exist or are waiting to be developed, will help public health combat respiratory diseases in the future.

Cybernics is a new academic field that brings together differing realms of academia in brain/ neuroscience, behavioral science, robotic engineering, IT, artificial intelligence, system integration, biology, psychology, philosophy, ethics, law and business. "Cybernics", which fuses "Human" and "Cyber-Physical space", plays a central role in promoting innovation in the "Cybernics Industry" following the robotics industries and IT industries. And it can further contribute to the development of the Medical and Biological Engineering field. Now, the Cybernics Consortium is taking on the challenge of creating various innovative technologies, promoting social implementation, and pioneering the future in the medical, welfare, and living fields including the work environment.

HAL, which is a representative example of research and development of cybernics technologies, is called the world's first "Wearable Cyborg" that functionally fuses humans and robots, by connecting human and HAL using bioelectric signals derived from the brain-nerve system. It is very interesting from the viewpoint of Medical and Biological Engineering field. Wearing the HAL establishes the interactive Bio-Feedback (iBF) loop between the brain/body and HAL, strengthening and modulating synaptic connections between nerves and nerves, and between nerves and muscles. Functional improvement and functional regenerative therapy using medical HAL approved as a medical device as a new medical technology is called Cybernics treatment or HAL-Therapy/HALTreatment, and becomes being common as a cybernic/robotic medical device platform in Japan, the United States, Europe, ASIA etc. For HAL-treatment, public workers compensation insurance is applied in Germany, and in Japan, public medical insurance is applied for progressive neuromuscular diseases (8 diseases including SMA, ALS, muscular dystrophy, etc.), for which there was no treatment in the past.

In this talk, I will mention about the medical innovation and its global expansion through innovative Cybernic Systems, and the measures to prevent "Frail" in non-medical fields, the independent life support for people with reduced physical function and the labor support, in line with the major theme of this academic meeting "Global Development of Medical and Biological Engineering".The lecture will cover the latest information on various innovative cybernics technologies in the medical, welfare, and living fields including the work environment, such as the vital sensing of human and the labor support using AI-robots.

Minimally invasive procedure is commonly required for recent neurosurgical therapy. Neuroendoscopic procedure is becoming more and more popular for that purpose. Another recent topic is heads-up surgery by using exoscope, which locates between microscope and endoscope. Okayama University induced neuroendoscope and exoscope at an early stage of availability and a number of procedures has been accumulated. In this presentation, video will be used to demonstrate how we set up and how we use endoscope and exoscope.

1. ETV (endoscopic third ventriculostomy) for obstructive hydrocephalus : ETV is more commonly performed than VP (ventriculo-peritoneal) shunt these days. Flexible scope with CCD camera at the tip makes the vision very clearly.

2. Extirpation of intraventricular tumor : Accurate biopsy can be performed and sometimes total tumor resection is achieved by using endoscope only.

3. Endoscopic transsphenoidal surgery for pituitary adenoma and parasellar tumor : With the use of navigation and 4K monitor, fine visualization of anatomical structures is obtained.

4. Hybrid surgery using microscope and neuroendoscope simultaneously : Endoscope can make 30 and 70 degree view which conventional microscope cannot see. Hybrid surgery is a terminology for simultaneous usage of microscope and endoscope and I will show representative cases.

5. Introduction of 3D exoscope - a dawn of heads-up surgery : Exoscope became 3D with high vision or 4K, thus, heads-up surgery with 3D glasses is attracting attention. In this pattern of surgery, everyone in the operating theater watches the same display and there is a sense of unity. Education of surgery using exoscope is meaningful and effective for medical students and residents. Exoscope is much smaller than microscope and an operator's position is always the same, thus, the operator feels less fatigue.

In this presentation, I will show our neuroendoscopic and exoscopic surgery by using video.

Computed tomography (CT)-guided interventional procedures are performed by inserting a specific needle into a lesion under CT-guidance. Such procedures include cancer ablation, biopsy, and abscess drainage. The procedures are minimally invasive and thus their need is increasing in the super-aging society. However, major limitation is intraprocedural radiation exposure to the physicians, because they have to be close to CT gantry during CT scanning. In order to address this concern, I, together with robotic engineers, started to develop a robot (Zerobot®) at Okayama University in 2012. The robot for clinical study was completed at the end of 2015. The robot has six degrees of freedom to hold, position, orient, and insert a needle under CT-guidance. The robot may be remotely controlled by using an operation interface and thus, the physicians may be free from radiation exposure. In 2018, we have performed a first-in-human study for 10 cases of CT-guided biopsy using the robot in the kidney, lung, adrenal grand, mediastinum, and muscle, which resulted in success in all cases. We will start an investigator-initiated clinical study based on Good Clinical Practice in 2020, aiming at commercialization of the robot.

Recently, surgical robot (da Vinci surgical system) surgery, so-called robotic surgery, has been introduced and rapidly spread. In Japan, da Vinci was approved in November 2009, national health insurance was first applied to prostate cancer (robot-assisted radical prostatectomy (RALP)) in April 2012. In April 2016, renal cancer (robot-assisted partial nephrectomy (RAPN)) was also covered by insurance. Up to this point, robotic surgeries were approved only in urology in Japan. However, 12 new procedures were included in the insurance coverage, expanding to lung, rectal, and stomach cancers in April 2018. The number of robotic surgeries is on the rise. Japan is the world's second largest da Vinci holding country after the United States. As of March 2018, there are about 300 da Vinci in Japan, which are more than half of da Vinci in Asia.

da Vinci is revolutionizing minimally invasive surgery. Da Vinci has the following three features.

1. Minimally invasive: retains the advantages of traditional laparoscopic surgery with less wounds and less bleeding

2. Excellent visual field: enlarged and 3D visual field

3. Detailed surgery: The forceps with joints, enabling more detailed surgeries than human hands

Meta-analysis comparing robotic surgery to conventional laparoscopic surgery for prostate cancer demonstrated that

1. Less bleeding / Low transfusion rate

2. Excellent urinary incontinence

3. Less cancer positive margin rate

4. Better erectile nerve preservation

For renal cancer, robotic surgery compared with laparoscopic surgery in large-scale multicenter research demonstrated that higher achievement rate of Trifecta (negative surgical margin, no complications, warm ischemia time <25 minutes)In urology, although insurance is not yet covered in Japan, robotic pyeloplasty and renal autotransplantation are performed. Okayama University performed these operations for the first time in Japan.

The problem is the cost. It is expected to reduce the price of the main unit price of 270 million yen and the cost of the disposable port and forceps for each surgery.

Recently, new robots other than Da Vinci have been released. This area is expected to develop further.

Video photoplethysmography (VPG) is pulse wave extracted from skin color change and contains various vital information such as pulse rate. Since the pulse transit time (PTT) from proximal to distal region correlates with blood pressure, it is expected to estimate blood pressure from PTT. However, PTT is affected by not only blood pressure but vascular compliance. That is why, regular calibration is necessary for the estimation. Our group has proposed a VPG extraction algorithm based on repetitive periodic component analysis (rPiCA), which is more robust than conventional methods. It was also indicated the possibility to use VPG for evaluation of peripheral hemodynamics instead of PPG. In this study, the influence of the change in both blood pressure and peripheral vascular compliance to pulse wave propagation by using VPG.Consequently, the characteristic changes in not only PTT but the VPG waveform were observed according to the change in the peripheral hemodynamics.

The progress of the ultrasound diagnostic device enables to diagnose fetal diseases. It is reported that the postnatal disability can be prevented by treating these disease during fetal period. Though it is required to measure the fetus biological information after the treatment, the measurement is difficult because the fetus is inside the mother. In this study, we proposed a biological information measurement method based on pressure measurement by analyzing the ultrasound Doppler images of pressure sensing module containing microbubbles. Additionally, we evaluated the feasibility of the pressure measurement method by simulating a pressure sensing module being placed under pressure by changing the inner pressure of a tube enclosing microbubbles. The result shows that the number of pixels in the high brightness area increases linearly with the increase of the pressure in the range of 0 kPa to 20 kPa.

In Japan, reducing drug discovery costs is a major issue. Currently, preclinical studies are mainly conducted by animal experiments, but humans and animals do not always show the same drug effects. In order to solve this problem, research on establishing a drug evaluation system using an in vitro tissue constructed from human iPS cell-derived cardiomyocytes has attracted attention. In this study, we developed an ultra-thin 500 nm-thick sensor which can monitor field potential of cardiomyocytes while following beating. By using the ultra-thin film electronics, we succeeded in measuring field potential in multiple channels while following the beating of human iPS cell-derived cardiomyocytes. In addition, we succeeded in monitoring drug effect of adrenaline from the field potential waveform. Therefore the thin-film electronics is considered to be effective as a sensor for evaluating the drug response of human iPS cell-derived cardiomyocytes .

For titanium and its alloy removal implant devices, adhesion with bone might cause difficulty removing the implanted devices during removal operation. We thought that Diamond Like Carbon (DLC) coated on titanium could be a material to inhibit adhesion to bone. The purpose of this study was to evaluation of osteoinhibition response of pre-osteoblast cells on the DLC coated titanium scaffolds.Commercially pure titanium grade 2 plate was coated with DLC by ionization deposition method. The MC3T3-E1 pre-osteoblast seeded on DLC coated and uncoated titanium plates for 4 days cultivation. Then, the number of cells was counted and the ALP activity was measured.The ALP activity normalized by cell number of DLC coated titanium showed a significantly lower value than the titanium. It was suggested that the DLC coated titanium devices could inhibit adhesion to bone.

Bicuspid aortic valve disease is a common congenital valvular disease. There are several variations in valve morphology and its relationship with ascending aortic dilation is not clear. In this study, we newly developed a pulsatile circulatory system to investigate flow in ascending aorta using 4D-MRI. The simulator consists of the silicone-made left ventricle, aortic valve chamber, aortic arch, compliance tank, and reservoir. The aortic valve model was fabricated using bovine aorta and pericardium and installed in the valve chamber. Pulsatile pressure and flow were pneumatically generated and controlled by peripheral resistive unit. A tricuspid aortic valve model was investigated by 4D-MRI. In the ascending aorta, straight flow was observed in early-systole and physiological clockwise-twisted flow was observed in late-systole respectively. Therefore, the pulsatile circulatory system developed in this study can be useful for revealing the relationship between bicuspid valve morphology and flow pattern in ascending aorta.

In recent years, it is known that the pupillary light reflex occurs to the bilateral pupil when light stimulation is applied only to either pupil, but there remains the argument about the light reflex when distinct light stimulation presented to the left and right pupils. In this study, we observe the pupil responses when visual stimuli of 1.2 Hz are presented to the left eye and 1.5 Hz to the right eye for 10 participants. As a result of the frequency analysis of the pupil fluctuation, it is clarified that the peaks of the spectrum are detected in the same two frequency bands as the visual stimulation, and the time variations of the bilateral pupil are observed as the superposition. This result suggests the possibility that a pupillary light reflex treats the light stimulus to the left and right pupils as equals.

In Japanese Pharmaceutical and Medical Devices Act Law (PMDAL), medical software was incorporated into the framework for medical device regulation (MDR) as Medical Device (MD) Program. The MD Program utilizing the "Dynamic" characteristics of software can be achieved from the proto type stage to the productization while maintaining the design and development concept for the improvement more easily than traditional popular MDs.

On the other hands, at the current situation surrounding MDs, the development and improvement of new concept MDs that take advantage of the "Dynamic" characteristics of software are also remarkable both in Japan and overseas. Taking the latest diagnostic MDs utilizing AI technologies as an example, the characteristics is far more "Dynamic" than traditional popular MDs. The trial MD reviewing systems under the PMDAL were introduced into legislation, and the revised PMDAL was promulgated in December of 2019. In the MDR under the revised PMDAL, the consideration of the "Dynamic" characteristics was also applied to legalization. I consider that the direction of MD reviewing should also follow the spirit of "Dynamic" included with the purpose of the revised PMDAL.

On this session, I would like to describe about the direction of "Dynamic" MD reviewing under Newly additional MDR including utilization of "MD Registries".

In recent years, numerous medical databases have been constructed in a wide range of fields with the goal of applications aimed at improving the quality of medical care and welfare in each field. In the field of cardiovascular surgery, the Japan Cardiovascular Surgery Database (JCVSD) has been constructed, in which all cardiovascular surgery cases have been registered.

The number of input fields is about 500, with the information roughly divided into preoperative, surgical and postoperative groups. A risk model was constructed based on the JCVSD data, from which JapanSCORE, a risk analysis model, was developed.

The very high accuracy of the JCVSD data was confirmed by Site Visits. Furthermore, clinical research projects using this data were also carried out. In the future, in cooperation with external organizations, it is expected that the data will greatly benefit both medical device development and evaluation of medical technology.

Recently, high resolution medical images have become common tools for diagnosis and surgery because the use of the high resolution medical images enables medical doctors to get the information about human tissues which traditional images never obtain. On the contrary, Artificial Intelligence (AI) have achieved great successes in various applications in computer science. Owing to this, AI is introduced to diagnosis using medical images such as the human tissue segmentation and tumor detection from medical images. Recent researches have applied AI to the support system for surgery. In this talk, I present our research projects which have been developing AI-based support systems for diagnosis and surgery using 3D shapes of human tissues.

Measuring sizes of tumors is important in endoscopic diagnosis. Currently, size estimation is commonly performed by humans. However, more objective methods are desired. Furthermore, surgical robots began to be introduced to real clinical environments, where 3D measurement technologies have more importance. Our research group has been developing a 3D endoscopic system, using a micro pattern projector inserted into the instrument channel. In our system, by using an optical element called DOE, a clear pattern can be projected with wide varieties of distances to the target. The projected pattern is a grid-like pattern where codes are embedded into gaps between grid edges. The grid structure and the codes can be obtained from endoscope images using a CNN. As a result, three-dimensional measurement can be performed with high accuracy. In this talk, we will introduce the technical elements of our system and the 3D measurement results.

Personalized medicine is increasingly becoming a subject of intense interest, and studies on the utilization of data mining for implementing personalized medicine are on the rise. The increasing view that medical images are minable data on patients' personal traits have led to increased focus on quantitative analysis of these data, a field known as radiomics. Radiomics is a hybrid of the term "radiology" and the suffix "-omics", and aims to integrate and comprehensively analyze biological data. Researchers extract high-dimensional quantitative image information, known as the radiomic features, which are not detectable upon visual examination of regions of interest containing tumors. This information is subsequently linked to clinical, histopathological and molecular biological data and investigated regarding tumor phenotype, prognosis and treatment efficacy. The aim of this study is to predict prognosis for early-stage lung cancer patients after stereotactic body radiotherapy in multi-institution by CT-based radiomic features.

Fast and accurate visualization of body dynamics such as body composition, musculoskeletal state, body motion and interaction with environment is expected to evaluate and optimize the body function, thus giving contribution to the extension of healthy life expectancy and the enhancement of QoL. For developing a miniaturized measurement device that is in harmony with human body, combination of smart detection by electrical sensing and estimation by machine learning seems to be effective. The author has been studying about the active electrical sensing by using electrical excitation of the target to scan the internal and surface impedance distribution. The examples are body composition monitoring and muscle injury detection, hand motion capture from forearm deformation, and visualization of pressure distribution. In this presentation, the author introduces a part of these studies.

Most of the cognitive brain researches regarding human social cognition and interaction investigate how these social abilities represents in a brain. However, in real social environment, communication is dynamic and interactive, and this point seems to be essential. Some of the researchers focus on this live interaction between persons, and employ hyperscanning method which measures more than two brain activities simultaneously. It can be realized with several neuroimaging equipment such as MRI, NIRS, MEG, EEG. Recently, NIRS and EEG hyperscanning studies are increased, because it is relatively easy to set up live interactive situation in experimental room. However, these hyperscan studies using different equipment have several serious issues: difference of measurement parameters and none of integrative analytical method for such hyperscan records. Here, I introduce some hyperscan studies using several equipment, and discuss problem and future of this research field.

The social burden of depression is enormous . The development of its neuroscience-based therapy is an urgent issue. In our recent fMRI neuroimaging studies on depression, we found the function of dorsolateral prefrontal cortex (DLPFC) is decreased, while that of posterior cingulate (PCC) is increased. We also reported that this was improved with antidepressant and that the DLPFC-PCC functional connectivity is a potential biomarker of depression.DLPFC and PCC have an antagonistic effect, therefore we carried out clinical experiment of neurofeedback (NF) targeting DLPFC using fMRI, and found the antidepressive effect which suggested a potent non-pharmacological treatment for depression. In order to develop a more practical NF treatment for depression, fNIRS-NF targeting DLPFC was carried out on healthy subjects evaluating by depression questionnaires such as BDI and RRQ, and fMRI brain functional change. In this session, we will introduce our research and give a personal opinion on the future of fNIRS.

The first paper on Near-Infrared Spectroscopy (NIRS) was published in the Science journal in 1977. Single channel NIRS was commercialized in the early 1990s. The changes in haemoglobin parameters calculated by NIRS had the potential to explain brain and muscle activity. Then the NIRS used for brain imaging was called functional NIRS (fNIRS). The ISO/IEC international standard of fNIRS was published in 2015, led by Japan. However, when compared to X-ray CT and MRI developed at about the same time, fNIRS is not so popular. In this presentation, we will look back on the benefits of fNIRS in brain imaging and summarize future issues.

I report computational anatomy models along time or scale axes of embryos, children or cadavers of adults. First, novel technologies to solve problems in the spatio-temporal modelling of embryos or children caused by small sample for training, rapid growing or changes including topological changes of anatomical features, are given in the presentation. Subsequently, deep learning based super-resolution for lungs of adult cadaver is presented.

We report on the construction of a pancreatic tumor model that represents the relationship between the tumor growth and the micro anatomical structures. The former, the tumor growth, is described by referring to the temporal series of MRI images of the whole body and the latter, the micro structures of the tumor, is described by a spatial series of microscopic images of thin-sections sliced from the extracted pancreatic tumor. For the model construction, we developed new non-rigid registration methods for (1) accurate description of tumor growth, (2) reconstruction of 3D microscopic images, and (3) registration between an MRI image and corresponding microscopic images.

Musculoskeletal multidisciplinary computational anatomy (MCA) models are described,in which function, pathology, temporal and multi-scale anatomy are integrated.Specific topics include (1) deep-learning based musculoskeletal segmentation from medical images, (2) personalized functional anatomy modeling including muscle fiber arrangements and bone attachment areas required in musculoskeletal biomechanical analysis, and (3) Aging variation models of musculoskeletal anatomy. Finally, future perspectives of musculoskeletal MCA models are mentioned.

This presentation gives computer assisted diagnosis and intervention systems based on artificial intelligence and multi-disciplinary computational anatomy models. Multi-disciplinary computation anatomy is new academic area that tries to understand human anatomy from four different disciplinaries including space, time, function and pathology and assist diagnostic and therapeutic procedures based on multidisciplinary anatomical structure recognition. Multi-disciplinary computational anatomy is asking us to understand anatomical structures in the space spanned by these four disciplinaries and to provide clinicalassistance information. Artificial intelligence or machine learning techniques can be utilized for achievingaccurate analysis and information presentation.This talk convers the following topics: (a) anatomical structure analysis based on machine learning, (b) multi-scale registration covering 10 times scale gap, (c) laparoscopic surgery assistance based on anatomical structure analysis and (d) real-time endoscopic diagnosis assistance using artificial intelligence technique. In anatomical structure analysis, we present machine learning framework for whole-body anatomical structure recognition based on machine learning. This will cover macroscopic anatomical structure to microscopic structures. In multi-scale registration, we provide a method for registering macro and microscopic anatomical structures. We also show super-resolution technique that enables us to convert clinical CT images to very high-resolution images using micro CT image information. Surgical navigation system using analysis results of multi-disciplinary computational anatomical models will be demonstrated in this talk. Finally, we demonstrate real-time colonoscopic procedure assistance system.

To create safe and effective control systems for surgical robots, intraoperative biological information is required. However, this information is limited, making it difficult to predict accurate biological responses. If patient-specific models are constructed by combining multidisciplinary computational anatomy with intraoperative biological information, the robots can be controlled by accurately predicting biological responses to the surgery. This approach would imply the realization of safer and more sophisticated treatments. This formed the background for the proposed highly intelligent surgical robot that can approach a surgical area using multidisciplinary computational anatomy and limited intraoperative biological information.From these background, we conducted the following studies: (i) navigation and robotic system for colon surgery, (ii) study on stapler device control for pancreatic tissue damage suppression, and (iii) navigation and robotic system for oral and maxillofacial surgery. The robot will be controlled based on the prognostic prediction made by patient data.

We have been developing a wearable electroencephalograph (EEG) device. By using this device, EEG measurement outside hospitals and laboratories has become easier. Thus, the possibility of applications using EEG has been broadened. We are focusing on developing a system that can visualize a part of unconscious information in the brain. For example, neurofeedback training using a mismatch negative potential, which is an event-related potential (ERP) that responds to differences in sound, makes it possible that Japanese people can recognize the difference between "right" and "light" sounds. Moreover, it was clarified that we can estimate the English ability from an ERP equivalent to N400 extracted from EEG data during listening to English. Furthermore, it was suggested that the degree of immersion in the game can be estimated by error related potential, which was caused by an error recognition. These results suggested that the we can extract a part of information that is unconscious and difficult to verbalize from EEG data.

We investigated changes in cortical and autonomic nervous activity associated with discomfort feeling during experience in the virtual reality environment (VR sickness). Five young adults watched 3D-CG movies using a head-mounted display while their EEG and ECG responses were measured. Participants continuously reported their discomfort level by pinching a pressure sensor during their VR experience. The subjective discomfort level was negatively correlated with the delta wave activity of the parietal area and the beta wave activity of the central, parietal and occipital areas. No significant correlation was found with indices of cardiac autonomic nervous activity. Results suggest that the parietal cortical activity, which plays a crucial role in integrating the spatial and motor perception of the self, could be a potential biomarker for detecting VR sickness.

In the elderly brain, it is reported that the functions of the dorsal visual system weaken and that those of the ventral system become relatively superior (Moriguchi, 2009). Reinforcement of the dorsal system activities in the elderly may reduce the age-related decline in visuo-spatial/visuo-motor functions. For this purpose, mental rotation (MR) training is considered to be effective to reform neural networks connecting brain regions along the dorsal system (Berneiser, 2016). However, it is still not clear how the MR task difficulty (or rotation load) changes the brain activities, and consequently, the behavioral performance. Here we used fMRI to evaluate the effect of MR training on elderly people due to the difference in rotational load. MR tasks are divided into three categories depending on the rotation loads, namely, Easy, Medium and Difficult. The activities in the dorsal visual system significantly increased in Easy and Medium conditions after 2-week MR training sessions. The current preliminary results suggest that the effect of MR training depends on the difficulty setting of the MR trials. Results of the group statistics on elderly population will be also reported.

The purpose of the present study was to examine whether moderate and severe dementia patients living in a nursery home were able to perform the accessible electronic musical instrument Cymis with touch panel or switch, and to find cognitive functions necessary for performing Cymis. Subjects were thirty dementia patients of age 91.9 (SD 3.9), MMSE of 14.1(SD 5.0). Fifteen persons were able to perform Cymis, and while other fifteen were unable to do so, they seemed to have a good time in touching Cymis. Neuropsychological test including MMSE, Cube/Necker Cube Copying, FAB and NPI was applied. It was suggested that visuospatial ability should be preserved for the performance of Cymis. Additionally, a new type of user interface utilizing an air bag was investigated by applying to young healthy adults.

We carried out a robot-assisted activity (RAA) using a communication robot to examine the effect of alleviating behavioral and psychological symptoms of dementia (BPSD) in elderly individuals with dementia. We examined 10 elderly individuals with dementia. Following the usual 3-month care period, we established a 3-month RAA period. Measurements were taken before and after the usual care period and after the RAA period. We measured salivary cortisol and resting-state electroencephalography (EEG) before and after RAA, in addition to the Dementia Behavior Disturbance (DBD) score, which was considered an indicator of BPSD. Our results did not reveal any significant differences in DBD-scores and salivary cortisol during each of the three measurement points. The resting-state EEG of post-RAA showed a significantly higher alpha/beta Pz power-ratio on after the RAA period than before and after the normal care period. Three months of RAA may exert a relaxing effect on elderly individuals with dementia.

Recently, the population ratio of the elderly people is increasing rapidly in Japan. Therefore, to improve the QOL (quality of life) of the elderly people is a today's important social issue. Most urgent problem is how to prevent fall. In clinical gait analysis, a quantitative and effective evaluation of a human lower limb movement is very important to provide an appropriate training and rehabilitation program which matches the individual walking condition. In this presentation, we will show the results of the gait diagnosis based on gait classification map developed in our laboratory. And in addition to that, we will propose a training assist tool to improve the gait condition.

CKPT can detect minor hypofunction of the brain prior to MCI, and has attracted international attention today 1-3). Since 2018, a collaboration with Australia started to develop an English version,aiming a:Double the number of questions to expand the applied age younger, b:Inserting a narrator in the Powerpoint to deduce the error between the testers.1)Takaki Shimura etal: A neuropsychological test(CKPT: Color Word Pick-out Test) to be able to detect the slight disorder of prefrontal lobe: classify the level of the preclinical stage of Dementia, 24th International Conference on Neuroscience and Neurochemistry, July23-24,2018 in Birmingham, England.2)Takaki Shimura etal: A Neurophycological test for Mild Cognitive Impairment and Preclinical Stage of Dementia, Global Conference on Oral Health & Mental Disorders,July 01-02,2019 in Rome, Italy.3)Takaki Shimura etal: CWPT(Color Word Pick-out Test) Available for Classifying the Slight Disorder on the Preclinical Stage of Dementia, HSOA Journal of Alzheimers and Neurodegenerative Diseases, 2-5,Sep.23,2019.

Severely physically challenged children and their families have various needs including mobility, communication and so on, according to their individual accompanying disabilities and disorders.Even if they are only physically challenged, physical handicap may deprive them of oppotunities to participate in various social activities, resulting in various type of developmental delay. Recent innovation of assistive technologies in mobility, communication and dicision making will promote their development and abilities. Therefore, earlier application of such devices should be considered. The Basic Law for Child and Maternal Health and Child Development is expected to work as a platform to provide challenged children with an integrated social system including medical care, social welfare, education and vocational training.

It is increasing the children with severe disabilities living at home in Japan.They need a lot of body and mental care, assistive products, and barrier-free housing.However, most barrier-free housing is designed for elderly people. Barrier-free housing for children with severe disabilities should be designed to promote their growth.In particular, the environments for excretion care is most important for maintaining life and health.Therefore, in this session, we focus on assistive products and the housing environments that promote growth for children with severe disabilities from the architectural perspective.

Audition is one of the most important sensations as well as vision, and is playing a main role for the verbal communication. Especially, the auditory environment of infancy has significant effects on development of verbal ability. For instance, shortage of auditory inputs in infancy sometimes leads to an insufficient ability of speech production. On the other hand, hearing tests and auditory prostheses for infants, different from those for adults, need special technique. In this paper, we will introduce screening tests for hearing acuity of new-born babies and auditory prostheses (cochlear implant and hearing aids) for infants.

In order to promote welfare town development, it is necessary to promote not only hardware development but also software measures. I have been conducting concerts for parents of children with disabilities and infants at public planetarium facilities since 2017. The purpose of holding a concert at the planetarium is that even bedridden children like severely handicapped children can appreciate the planetarium slowly at the bar seat, According to the questionnaire after the concert, 93% of the parents answered that the children enjoyed the concert, and 97% said that the concert was easy for people with disabilities and infants to participate. For those who have limited opportunities to go out (social participation), such a barrier-free event provides a successful experience of being able to go out.

There exist several barriers in the process of medical device inovation. The Devil River means a wall between a basic research and development. The Valley of Death is a hurdle between the practical development and its market. Finally, the product needs to cross the Darwinian Sea for distribution. This session focuses on the basic of Darwinian Sea for conducting medical device development.

The goal of medtech company is neither premarket approval in regulatory process nor insurance coverage (reimbursement), but success in business. Premarket approval is necessary for business launch, but they are not enough for success. Insurance coverage is not unique method of monetization, but just ONE of various methods. A company must make enough profit to manage the company, to pay salaries to employees, to keep supplying products stably to hospitals, and to invest in development of new products.This presentation shares some basic knowledge of social insurance system in Japan (special treatment materials and doctors fee) to gain fundamental understandings of monetization of medtech business. In addition, some business models are introduced concerning self-pay care and health promotion including pre-symptomatic disease.

All HCPs are seeking breakthrough medical device to improve patients outcomes and enhancing QOL. However, there are several challenges to introduce new medical device. I would like to share medical device company perspective and priorities for successful launch of new devices.

Success in medical device development lies not in obtaining medical device approval, but in implementing devices in medical institutions.

Achieving this naturally requires compliance with the provisions of the Pharmaceuticals and Medical Devices Act, as well as wide-ranging processes that include sales channel development and post-market management. It is important that, from the start of development onward, business be undertaken with a clear understanding of the processes overall. A business perspective is also needed, in terms of understanding the needs of patients and healthcare practitioners and creating points of differentiation from competing products.

In recent years, particularly overseas, major companies from other industries have entered the medical business, while medical technology innovation accelerates. Looking at the reasons behind the US's 40% share of the global medical device market as an example, new perspectives required for medical device development are presented, based on over 10 years of experience with global companies and a current standpoint of supporting market entry of products from startup firms.

In the field of medical devices, new technologies are constantly being researched and developed across the globe. Corporate R & D focuses on how useful it is to the physicians and the patients who use the product and how it can contribute to the patient's quality of life, while the expectation cannot be met without constant product innovation. A completely new concept clear aligner-type orthodontic appliance (Invisalign) developed in the United States was specifically developed to maximize the benefits of patients. However, new innovations are associated with significant challenges to penetrate into the market. In this presentation, I will share how a new medical device developed overseas have been recognized by the industry and the market, and how they have spread in Japan.

Hiroshima University Biodesign (HUB) is a flagship Program of Medical-Technology Collaboration Project initiated by Hiroshima Prefectural Government in 2017. Under the supervision of School of International Biodesign (SIB), this biomedical technology innovation program is being implemented in collaboration with international partners, managed by Division of Biodesign in Hiroshima University.Our program aims to foster med-tech innovation in collaboration with multiple organizations: All India Institute of Medical Sciences; Indian Institute of Technology; and Harbor-UCLA Medical Center.From India, we learned "frugal innovation", and applied it into medical device development with industrial partners. Since its inception in 2019 by HUB, our program has been supported by Japan Agency for Medical Research and Development. We also have been successful in encouraging medical device innovation, promoting entrepreneurship in medical device sector by formation of startups, indigenous manufacturing of medical devices and dissemination of innovations at global level. The HUB Fellowship is an interdisciplinary, team-based, experiential hands-on training program spanning over one year wherein physicians, engineers, designers and researchers come together to identify needs of the healthcare system and develop affordable medical technology solutions with frugal approach.

The percentage of the population aged 65 and over in Japan reached 28.1% in 2018 and is expected 35.3% in 2040. Medical expenses have also increased sharply with this super-aging society, and in 2017, lifetime medical expenses reached 27 million yen per person, and over 75 years old spent 40 million yen, which is 40% of lifetime medical expenses. Therefore, especially for the elderly, it is required that vital signs such as pulse, respiration, body temperature, and blood pressure be continuously recorded in daily life and utilized for health management. At present, many wearable healthcare devices including a wristband type, are developed and sold, and the number of users is gradually increasing. Considering this situation, the leading experts will talk about the current situation of the sensor device and the market regarding "continuous vital sensing from body surface and fingertips," and we will discuss issues and solutions in this OS.

Flexible electronics are much attracted to next-generation electronics because of their features such as softness and flexibility. Recently, to utilize the softness of the electronics, the development of bio medical application is of particular interest.In this research, I will introduce various ultra-flexible electronics fabricated on an ultra-thin substrate with a thickness of about 1 micro-meter. The ultra-flexible electronics have extremely high flexibility, so that the device characteristics do not degrade even when the radius of curvature is reduced to 10 micro-meter. Furthermore, we can realize the stretchable electronics by integrating the device with stretchable substrate. By directly attaching the ultra-flexible devices to the skin, we succeeded in sensing biological information such as pulse, blood oxygen concentration, electrocardiogram, and electromyogram.

Recent wearable sensor devices such as smart watches and smart clothes use rigid electronic components for power sources such as batteries, analog front ends, microcontrollers, wireless communication modules, and housings. Here we show how to realize fully flexible wearable devices by developing organic film sensors, organic transistor circuits, organic passive wireless communication circuits, and biofuel cells.

Artificial nails can be worn for several weeks continuously. By embodying a measuring circuit, wireless transmission circuit and batteries in an artificial nail, this wearable sensor can monitor the vital signal for several weeks continuously. However usable battery is limited to a small battery due to small area of nails. Thus, power consumption must be reduced to realize the wearable sensor attaching to nail surface. In this research, pulse wave measurement using piezo film attaching to nail surface is presented. In the previous research, cyclic micro-strain of nails which have similar waveform with pulse wave was shown. In the experiment, piezo film on a nail surface converts micro-strain to electrical signal by piezoelectric effect. Piezo film is attached to left thumb nail by glue. As the results, cyclic signals were obtained and waveform was similar to typical pulse wave. Amplitude of output signal was around 70 mV.

Long-term measurement of vital conditions is essential for analysis of health conditions. For this purpose, it is required for high biocompatibility of sensing devices without having skin irritations. As ambient measurement is ideal, wearable approaches could be one of the solutions. Here we use conductive polymer based fiber electrode for analysis. The silk/washi fibers was treated with PEDOT-base conductive polymer. Treatment with conductive polymer does not alter the characteristic of the base material, such as flexibility and texture. We use this electrode for ECG, EMG and ECoG measurement. We have been developing the usage of this electrodes for various kind of fields including medical and others. Establishment of research community, flexible-silk-electrode research, was helpful for promoting the research and forming spin-out business. Interaction with various field researchers are extremely important for developing new technologies and materials. Recent activities will also be reported.