PROGRAM

Opening Remarks 10:00-10:10

Minoru Seki, Vice-president of Chiba University Tatsuo Igarashi, Director of Center for Frontier Medical Engineering (CFME), Chiba University

Overview of the Multimodal Medical Engineering project 10:10-10:30

Hideaki Haneishi, Principal Investigator of MME, CFME, Chiba University

Recent Progress of the MME project (selected) 10:30-11:30

“Development of a multimodal drug delivery system” Hideki Hayashi, CFME, Chiba University “Progress in Tongue Image Analysis Project” Toshiya Nakaguchi, CFME, Chiba University “CNN, convolutional neural network, supports diagnosis of chronic gastritis induced by Helicobacter pylori” Hiroshi Kawahira, CFME, Chiba University “Improvement of Viscoelastic Imaging System using MRI” Mikio Suga, CFME, Chiba University “Progress in project for ultrasonic tissue characterization” Kenji Yoshida, CFME, Chiba University “Texture conversion of pathological image and registration into MR image” Takashi Ohnishi, CFME, Chiba University

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Poster Session 11:30-12:30

#1 Tissue characterization of micro tissues in liver with the multi-frequency ultrasound Kazuki Tamura, Kenji Yoshida, Hitoshi Maruyama, Hideyuki Hasegawa, Mamou Jonathan, Hiroyuki Hachiya, Tadashi Yamaguchi

#2 Analysis of speed of sound of organelles by acoustic microscopy Kazuyo Ito, Zhihao Deng, Hitoshi Maruyama, Kenji Yoshida, Tadashi Yamaguchi

#3 Development of echo signal analysis method for quantitative ultrasound diagnosis of skin ulcer tissue Masaaki Omura, Kenji Yoshida, Shinsuke Akita, Tadashi Yamaguchi

#4 Development of a Highly Viscous Tissue-Mimicking Phantom with Low Glycerin Content for Magnetic Resonance Elastography Kouki Ishii, Mikio Suga

#5 Rapid Imaging by Reducing Phase Numbers of Magnetic Resonance Elastography Pulse Sequence Koji Ohashi, Mikio Suga

#6 Development of intraoral imaging system for quantitative diagnosis of teeth-marked tongue Fumina Kobayashi, Toshiya Nakaguchi, Akira Morita, Takao Namiki

#7 Improvement of color estimation accuracy using tongue color chart and extraction of tongue coating using texture analysis Yudai Ota, Toshiya Nakaguchi, Vladimir Bochko

#8 Association analysis of tongue color distribution and physiological index based on tongue shape normalization Kazunari Murai, Toshiya Nakaguchi, Akira Morita, Takao Namiki

#9 Detection of tissue coagulation by radio frequency current Naoyuki Ogasawara and Kazuyuki Saito, Chiba University

#10 Estimation of electromagnetic energy absorption from wireless radio terminal for pregnant woman Ryota Takei, Kazuyuki Saito, Masaharu Takahashi, Tomoaki Nagaoka, Soichi Watanabe

#11 Visualization of oxygen transportation in microcirculation by sidestream dark-field oximetry Tomohiro Kurata, Minori Takahashi Takashi Ohnishi, Hideaki Haneishi

#12 Development of quantitative perfusion evaluation methods for obstruction of blood flow of microcirculation using a rat septic shock model Minori Takahashi, Tomohiro Kurata, Takashi Ohnishi, Hideaki Haneishi

#13 Fundamental analyses to develop an ultrasound activated drug delivery system Masahiko Ebata, Hideki Hayashi

#14 Development of a near infrared photoimmunotherapy for malignant diseases using ICG-C18 Yiting Zhang, Hideki Hayashi

Lunch 12:30-13:30

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Session 2 Keynote Lectures 13:30-15:00

“In vivo ultrasound imaging of developing mouse embryos” Jonathan Mamou F. L. Lizzi Center for Biomedical Engineering, Riverside Research “Multimodal Nonlinear Optical Microscopy Imaging and Raman Spectroscopy for Label-free Digital Pathology” Zhiwei Huang Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore “Approach to Multiscale Imaging using Micro-MRI and Functional Contrast Agents” Ichio Aoki Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), QST Coffee Break 15:00-15:30

Session 3 International Network of Multimodal Medical Engineering for Precision Medicine (Startup session of JSPS Core-to-Core Program) 15:30-17:30

“Spectral based eye fundus imaging” Roman Bednarik (in place of Markku Hauta-Kasari) Computational Spectral Imaging, School of Computing, University of Eastern Finland “Force field analysis for segmentation of ultrasound images of breast cancer” Stanislav S. Makhanov Biomedical Engineering Unit, School of Information and Computer Technology, Sirindhorn International Institute of Technology, Thammasat University “The application of special environmental physiology in the study of oceanauts selection, training and physiological functions of deep-sea manned submersible” Lu Shi Chinese Underwater Technology Institute, Shanghai Jiao Tong University & Chiba University International Cooperative Research Center, Shanghai Jiao Tong University “Time-resolved Imaging of Arterial Dynamics” Adrian J. Y. Chee Schlegel Research Institute for Aging, University of Waterloo

Closing Remarks 17:30-17:35

Hideki Hayashi, CFME, Chiba University

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Invited Lecturers: Biography and Lecture Abstract Jonathan Mamou, Research Manager Affiliation：F. L. Lizzi Center for Biomedical Engineering, Riverside Research, New York CV：In July 2000, Dr. Mamou graduated from the Ecole Nationale Supérieure des Télécommunications in Paris, France. In January 2001, he began his graduate studies in electrical and computer engineering at the University of Illinois at Urbana-Champaign, Urbana, IL. He received his M.S. and Ph.D. degrees in May 2002 and 2005, respectively. He is now a Research Manager at Riverside Research in New York, NY. His fields of interest include theoretical aspects of ultrasonic scattering, ultrasonic medical imaging, and biomedical image processing. Address：156 William St., 9th floor, New York, NY 10038, USA E-mail：jmamou@riversideresearch.org Lecture Title: In vivo ultrasound imaging of developing mouse embryos Abstract: High-frequency ultrasound (HFU, >20 MHz) offers a means of investigating biological tissue at the microscopic level with spatial resolutions better than 100 µm. After a brief review of conventional ultrasound imaging, this lecture will introduce HFU imaging and present a novel in vivo HFU imaging method used to form three-dimensional (3D) images of the brain of developing mouse embryos. Many genetically-engineered mice display abnormal development of the central nervous system (CNS) at early embryonic ages and HFU offers great potential for in vivo imaging and characterization. A 34-MHz, five-element annular array was excited using chirp-coded excitation to acquire In utero, in vivo 3D data sets from more than 150 embryos over five key developmental stages; i.e., from embryonic days E10.5 to E14.5 (Figure ). CNS volume renderings were obtained using automatic segmentation algorithms and provided an atlas of normal development. Data were also acquired from mutant embryos expressing CNS phenotypes. Mutants were automatically detected using novel image-processing methods and 3D renderings of their defective CNS were automatically obtained. These novel HFU imaging and processing methods pave the way for translational preclinical studies in animals for a wide range of applications and research studies. In particular, these approaches could streamline developmental biology studies routinely performed in normal and mutant mouse embryos.

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Zhiwei Huang, Associate Professor Department of Biomedical Engineering, Faculty of Engineering National University of Singapore Zhiwei Huang received the Ph.D. degree from Nanyang Technology University, Singapore in 1999. He did his postdoctoral work in Cancer Imaging Department, British Columbia Cancer Agency, and Faculty of Medicine at the University of British Columbia, Canada from 2000-2013. He is currently an Associate Professor with tenure in the Department of Biomedical Engineering at National University of Singapore. His major research areas are in the fields of biomedical optics, microscopy, spectroscopy and endoscopic imaging, particularly centering on the development of nonlinear optical microscopy imaging techniques (coherent Raman scattering microscopy and multiphoton microscopy) and their applications in label-free biomolecular imaging, as well as the development of novel endoscopic imaging and spectroscopy, enabling early diagnosis and detection of epithelial precancer and cancer. He has published over 100 peer-reviewed journal papers and delivered over 50 invited talks worldwide. He is the node leader in Singapore in Biophotonics4Life (BP4L) Worldwide Consortium. He is also a senior member of SPIE-the International Society for Optics and Photonics. Address: 9 Engineering Drive 1, Singapore 117576, Singapore. E-mail: biehzw@nus.edu.sg URL: http://www.bioeng.nus.edu.sg/people/PI/Huangzw/ Lecture Title: Multimodal Nonlinear Optical Microscopy Imaging and Raman Spectroscopy for Label-free Digital Pathology

Abstract: Nonlinear optical microscopy and Raman spectroscopy have been emerging as power tools for label-free tissue diagnosis and characterization in biomedical systems. In this talk, I will present our work on the development of a powerful multimodal nonlinear optical microscopy technique including coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), two-photon excitation fluorescence (TPEF), second harmonic generation (SHG) and third-harmonic generation (THG), serving as an imaging platform for biomedical applications. Some results using multimodal nonlinear microscopy technique developed for optical diagnosis and characterization of pathologic tissues and cells without labeling will be shown. I will also present our recent work on the development of a rapid fiber-optic Raman spectroscopy system, and its in vivo clinical applications for improving cancer detection and diagnosis in gastrointestinal tracts.

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Ichio Aoki, Ph.D. Team Leader Functional and Molecular Imaging Team, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS) National Institutes for Quantum and Radiological Science and Technology (QST) Biography: Ichio Aoki initially learned NMR science from Dr. Kohji Fukuda (physics/physiology) in 1993-1994, and received a MSc for quantitative brain perfusion MRI, working with Dr. Chuzo Tanaka (neurosurgery, 1996). He also received a Ph.D. for research and development of manganese-enhanced MRI (MEMRI) with Dr. Tanaka in 1999 (Kyoto/Japan). A visiting fellow position (2000-2002) in the National Institute of Neurological Disorders and Stroke (NINDS) at NIH (MD, USA) was focused on brain functional and contrast-agent research using high-field MRI with Dr. Alan P Koretsky. In the autumn of 2006, Dr. Aoki moved to the Molecular Imaging Center, National Institute of Radiological Sciences (NIRS, Chiba, Japan) as a senior researcher. He was leader of the Imaging Physics Team (2007-2011) and the Multimodal Molecular Imaging Team (2011-2016) in NIRS. At present, Dr. Aoki is the leader of the Functional and Molecular Imaging Team (fMIT) from April, 2016 at a newly organized research institute, the Japan Agency for Quantum and Radiological Science and Technology (QST). Executive boards: Japanese Society for Molecular Imaging (JSMI). Committees: International Society for Magnetic Resonance in Medicine (ISMRM, AMPC), the Japan Society of Drug Delivery System (councilor). Academic editor: Plos one (PLOS), Heliyon (Elsevier). Visiting lecturers: Kyoto University, Kyushu University, and Okayama University. Address: Molecular Imaging-build. 3F, Anagawa 4-9-1, Inage, Chiba, 263-8555 Japan Phone +81-43-206-3272; fax +81-43-206-3276 aoki.ichio@qst.go.jp iaoki.jp@gmail.com Lecture title: Approach to Multiscale Imaging using Micro-MRI and Functional Contrast Agents Abstract: MRI is a non-invasive 3D imaging technology. The spatial resolution of high-field MRI reaches 20-50 micron at 2D in vivo or 3D ex vivo. MRI can provide not only anatomical imaging but also functional (e.g. brain functional imaging; fMRI) and metabolic observation (e.g. magnetic resonance spectroscopic imaging; MRSI) without any contrast agents. Recently, the advent of functional contrast agents and nanoparticle drug delivery systems (nano-DDSs) is opening new pathways to understanding pathophysiology in vivo using MRI. I would like to introduce our progress of the functional contrast agents and nano-DDSs based on preclinical experimental micro-imaging studies. Divalent manganese ions (Mn2+) can be used as a positive intracellular MRI

contrast agent for small animal. Manganese-enhanced MRI (MEMRI) provides a unique opportunity to study neuronal activation and architecture1. The underlying principle of MEMRI relies in the fact that Mn2+ behaves in a manner similar to calcium ions (Ca2+) in many biological systems. Extracellular Mn2+ can enter cells through N-methyl-D-aspartate (NMDA) receptors for glutamate and/or voltage-

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gated calcium channels. Thus, Mn2+ can behave as a functional contrast agent depending on the cellular activity/viability. In this presentation, I would like to summarize the recent progress of MEMRI for neuroimaging2 and cancer research3. Nanoparticles have for many years also been investigated as possible MRI

functional contrast agents. Nano-carriers for DDSs can contain multiple functional elements, such as therapeutic drugs, MRI contrast agents, fluorescent or luminescent dyes, and radioisotopes, without serious changes to the particle kinetics/dynamics. The development of such multifunctional nano-DDSs and imaging has accordingly become a subject of widespread research. Various materials have also been reported as nano-DDS carriers, including micelles4, liposomes5, polymersomes6, emulsions, dendrimers, quantum dots7 and carbon materials such as fullerenes, with each material providing a different set of characteristics as a nano-DDS carrier. I will also summarize our recent researches into nano-DDS-based contrast agents for pathophysiological imaging8. [1] Y. J. Lin and A. P. Koretsky, Magn Reson Med 1997, 38, 378-388. [2] a) R. G. Pautler, et al., Magn Reson Med 2003, 50, 33-39; b) Y. Kawai, et al., Neuroimage

2010, 49, 3122-3131. [3] S. Saito, et al., Cancer Res 2013, 73, 3216-3224. [4] a) S. Kaida, et al., Cancer Res 2010, 70, 7031-7041; b) P. Mi, et al., Nat Nanotechnol 2016,

11, 724-730. [5] I. Aoki, et al., Transl Res 2015. [6] D. Kokuryo, et al., J Control Release 2013, 169, 220-227. [7] R. Bakalova, et al., Nat Photonics 2007, 1, 487-489. [8] K. M. Bennett, et al., Adv Drug Deliv Rev 2014, 74, 75-94.

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Roman Bednarik, Associate Researcher Computational Spectral Imaging, School of Computing, University of Eastern Finland CV: I am an adjunct professor (docent, 2012) with endless enthusiasm in interactive technologies. My research has been bridging eye-tracking in intelligent user interaction and cognitive science in HCI. I received my doctoral degree from the University of Joensuu, Finland, with honors in 2007 with an awarded PhD thesis: Methods to analyze visual attention strategies and a competitive Post-Doctoral Fellow position granted by the Academy of Finland. Since then, I have specialized in collaborative environments and medical interactive technologies, as influenced from wide international collaboration at Seikei University, Japan; SFU, Canada; and University of Pittsburgh, USA. My strongest inspiration emerged from observing the medical practice. In cooperation with the neurosurgeons from Kuopio University Hospital since 2011, I established an interdisciplinary research group to design and improve image-guided surgeries. Worldwide, our group is the first to develop an embeddable eye-tracking device for live surgery and to propose effective gaze-based interaction. My work was granted by Finnish Agency for Innovation (TEKES) and Academy of Finland. URL: http://cs.uef.fi/~rbednari Address：School of Computing, UEF, P.O.Box 111, FI-80101 Joensuu, Finland E-mail：roman.bednarik@uef.fi URL：http://cs.uef.fi/~rbednari） Lecture Title: Surgical Operating Room Eye Tracking and Spectral Imaging Abstract: In this talk I will introduce the needs for advanced interactive technologies in image-guided surgeries and present an overview of the recent research related to the understanding of human factors in image-guided surgical procedures. I will present the design and principles of eye-tracking for surgical microscopes and evaluation of its feasibility, along with new perspectives on applying spectral imaging for the future sensing and diagnostics medical devices. The research done in this topic has been supported financially by the Finnish Funding Agency for Innovation (Tekes) and by the Academy of Finland.

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Stanislav S. Makhanov, Professor Biomedical Engineering Unit, School of Information and Computer Technology, Sirindhorn International Institute of Technology, Thammasat University Stanislav S. Makhanov recieved MS in Applied Mathematics from Moscow State University in 1981 and PhD from Computing Center of the Russian Academy of Science in 1988, where he worked as an Associate Professor until 1993. From 1994 until 1999 he was a Visiting Professor with King Mongkut's Institute of Technology of Thailand. Dr. Makhanov joined Sirindhorn International Institute of Technology, Thammasat University of Thailand in 1999. He is currently a Full Professor and a Head of the Center of Excellency in Biomedical Engineering. He is teaching courses in Applied Mathematics and Computer Science. Dr. Makhanov has authored over 100 research papers and conference proceedings in medical image processing, CAD/CAM, robotics and reliability. He has been a consultant to UN (ESCAP) and other international organizations. His biography has been published by Who is Who in Asia(2007), Who is Who in Science and Engineering(2008) and Who is Who in the World (2005), (2009), (2012),(2015). Lecture title: Force field analysis for segmentation of ultrasound images of breast cancer Abstract: Breast cancer has become the leading cause of cancer deaths among women. Ultrasonography provides a criterion which helps the physicians to decide whether a certain solid tumor is benign, probably benign, or malignant. The computer aided diagnostics provides an additional tool to assists the radiologists in evaluating the tumors (second opinion, missed cases, data mining, etc.). However, assessing ultrasound images of breast tumors is still one of the most difficult problems in medical image processing. A number of popular codes for US segmentation are based on a generalized gradient vector flow method proposed by Prince and Xu[1]. A promising direction in the vector flow methods is the analysis of configurations of the underlying vector field. The presentation introduces methods based on the relative orientations the vectors and their application to segmentation of ultrasound images of breast cancer. This includes conventional methods such as discrete vector field analysis[2]-[3], continuous vector field analysis [4], phase portrait analysis [5] as well as recently proposed algorithms which include multi-feature gradient vector flow [6] and a combination of phase portrait analysis and trial snakes for initialization of active contours [7]. References [1] C. Xu and J.L.Prince (1998) Generalized gradient vector flow external forces for active

contours. Signal Process. 71 (2), pp. 131-139. [2] Z. Hou and C. Han (2005) Force field analysis snake: an improved parametric active

contour model, Pattern Recognition Letters 26: 513–526. [3] C.Li, J.Liu and M.D. Fox (2005) Segmentation of external force field for automatic

initialization and splitting of snakes, Pattern Recognition 38(11): 1947–1960. [4] A. Rodtook and S. S. Makhanov (2010) Continuous force field analysis for generalized

gradient vector flow field, Pattern Recognition 43(10): 3522 – 3538. [5] S. Chucherd, A. Rodtook and S.S. Makhanov (2010). Phase portrait analysis for

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multiresolution generalized gradient vector flow, IEICE Transactions on Information and Systems E93-D(10): 2822-2835

[6] A. Rodtook and S. S. Makhanov (2013). Multi-Feature Gradient Vector Flow Snakes for Adaptive Segmentation of the Ultrasound Images of Breast Cancer, Journal of Visual Communication and Image Representation 24(8): 1414-1430.

[7] K. Kirimasthong, A. Rodtook, U. Chaumrattanakul and S. S. Makhanov (2017) Phase portrait analysis for automatic initialization of multiple snakes for segmentation of the ultrasound images of breast cancer, Pattern Analysis and Applications 20(1): 239–251.

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Lu Shi, Associate Professor Chinese Underwater Technology Institute, Shanghai Jiao Tong University & Chiba University International Cooperative Research Center, Shanghai Jiao Tong University Lu Shi is the director of the Institute of Special Environmental Physiology and Medicine. In 2010, he was an assistant professor of Graduate School of Engineering at Chiba University, Japan. He received his Ph.D. degrees in environmental and physiological engineering, in 2009 from Chiba University. He is the author and a co-author of more than 80 papers in journals and international conferences. He is engaged in the research of environmental physiology, diving and hyperbaric physiology, ergonomics and physiological anthropology. He is the member of the standing committee of Youth Committee of Nautical medicine Branch of the Chinese Medical Association（CMA）, the deputy director of Specialized Committee on Diving medicine and the committeeman of Specialized Committee on Clinical Hyperbaric Medicine. He is also the council member of the Asian-Pacific Diving and Hyperbaric Medical Society (APUHMS), and the member of the second oceanauts’ selection and training expert group. Address: Room B511, 1500 Longwu Road, Shanghai 200231, P.R.China. E-mail: shilu@sjtu.edu.cn URL: http://icrc.sjtu.edu.cn/CN/Default.aspx; http://cuti.sjtu.edu.cn/n/26/default1 Lecture title: The application of special environmental physiology in the study of oceanauts selection, training and physiological functions of deep-sea manned submersible Abstract: JIAOLONG is China’s first deep manned submersible. Driving and operating submersible is a highly complex and stressful complicated system control engineering work. The complex underwater environment, limited activity space and high mental stress can lead to the human stress response， cause a series changes of psychological and physiological function. We discussed the change regulations of oceanauts physiological and psychological functions by monitoring brain function, cardiac function and circulatory system during daily training, virtual and practical diving operations. Keywords: JIAOLONG, deep sea, oceanauts, man-machine-environment system, physiological function

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Adrian J. Y. Chee, Associate Scientist University of Waterloo Schlegel Research Institute for Aging, University of Waterloo Adrian J. Y. Chee is currently an Associate Scientist in the Schlegel Research Institute for Aging at the University of Waterloo. Dedicated to ultrasound imaging innovations, Dr. Chee has formed a vibrant research partnership with Dr. Alfred Yu since 2012. He is now spearheading the design of novel vascular ultrasound techniques and the translation of these innovations towards clinical use. Dr. Chee obtained his B.Eng degree (with first class honors) in Electrical and Computer Systems Engineering from Monash University, Australia in 2011, and he received his PhD degree at the University of Hong Kong in 2016. In between, he completed a research internship at the Hitachi Central Research Laboratory, Tokyo, Japan. Dr. Chee is an active reviewer for ultrasound imaging related periodicals, including the IEEE Transactions on Medical Imaging and IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. Lecture title: Time-resolved Imaging of Arterial Dynamics Abstract: Capturing arterial wall mechanics and blood flow dynamics provides new information on the fluid-structure interaction inside the vasculature, and in turn offers new clinical insights for vascular diagnostics. Such a task is nevertheless technically challenging because of the highly dynamic events occurring within the short duration of a cardiac cycle – to resolve these dynamical changes, fine temporal resolution (sub-millisecond range) is crucial. In this seminar, a novel framework for achieving time-resolved imaging of arterial dynamics will be presented. Briefly, this framework involves simultaneous capture of arterial wall motion and hemodynamics using high frame rate ultrasound with an image acquisition rate of >1,000 frames per second. Complex flow dynamics are visualized through duplex rendering of flow trajectory (flow speckle motion) and flow velocity (Doppler color coding), while pulse wave propagation analysis is performed to track the transiting pulse wave (its speed is indicative of arterial stiffness). As an integrative imaging strategy, wall motion and flow dynamics are collectively rendered on the B-mode cine-loop to visualize the fluid-structure interaction within arteries. Corresponding results will be shown. Apparent differences in fluid-structure interaction can be found between thin-wall carotid bifurcation phantoms with healthy and diseased features.

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