Machine Learning in Cardiology

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Machine Learning in Cardiology

Technion scientists use machine learning for atrial fibrillation risk prediction

Shany Biton

Shany Biton and Sheina Gendelman, two M.Sc. students working under the supervision of Assistant Professor Joachim A. Behar, head of the Artificial Intelligence in Medicine laboratory (AIMLab.) in the Technion Faculty of Biomedical Engineering, wrote a machine learning algorithm capable of accurately predicting whether a patient will develop atrial fibrillation within 5 years. Conceptually, the researchers sought to find out whether a machine learning algorithm could capture patterns predictive of atrial fibrillation even though there was no atrial fibrillation diagnosed by a human cardiologist at the time.

Assistant Professor Joachim Behar

Atrial fibrillation is an abnormal heart rhythm that is not immediately life-threatening, but significantly increases patients’ risk of stroke and death. Warning patients that they are at risk of developing it can give them time to change their lifestyle and avoid or postpone the onset of the condition. It may also encourage regular follow-ups with the patient’s cardiologist, ensuring that if and when the condition develops, it will be identified quickly, and treatment will be started without delay. Known risk factors for atrial fibrillation include sedentary lifestyle, obesity, smoking, genetic predisposition and more.

Sheina Gendelman

Ms. Biton and Ms. Gendelman used more than one million 12-lead ECG recordings from more than 400,000 patients to train a deep neural network to recognize patients at risk of developing atrial fibrillation within 5 years. Then, they combined the deep neural network with clinical information about the patient, including some of the known risk factors. Both the ECG recordings and the patients’ electronic health record were provided by the Telehealth Network of Minas Gerais (TNMG), a public telehealth system assisting 811 of the 853 municipalities in the state of Minas Gerais, Brazil. The resulting machine learning model was able to correctly predict the development of atrial fibrillation risk in 60% of cases, while preserving a high specificity of 95%, meaning that only 5% of persons identified as being potentially at risk did not develop the condition.

“We do not seek to replace the human doctor – we don’t think that would be desirable,” said Prof. Behar of the results, “but we wish to put better decision support tools into the doctors’ hands. Computers are better equipped to process some forms of data. For example, examining an ECG recording today, a cardiologist would be looking for specific features which are known to be associated with a particular disease. Our model, on the other hand, can look for and identify patterns on its own, including patterns that might not be intelligible to the human eye.”

Overview of the experimental setting: digital biomarkers (HRV and MOR), deep learning features (DNN) and clinical data (EMR) are combined together in training a model to predict the future occurrence of atrial fibrillation

Doctors have progressed from taking a patient’s pulse manually, to using a statoscope, and then the ECG. Using machine learning to assist the analysis of ECG recordings could be the next step on that road.

Since ECG is a low-cost routine test, the machine learning model could easily be incorporated into clinical practice and improve healthcare management for many individuals. Access to more patients’ datasets would let the algorithm get progressively better as a risk prediction tool. The model could also be adapted to predict other cardiovascular conditions.

The study was conducted in collaboration with Antônio Ribeiro from the Uppsala University, Sweden and Gabriela Miana, Carla Moreira, Antonio Luiz Ribeiro from the Universidade Federal de Minas Gerais, Brazil.

The study was published in the European Heart Journal – Digital Health.

 

Tiny Lasers Acting Together as One: Topological Vertical Cavity Laser Arrays

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Tiny Lasers Acting Together as One: Topological Vertical Cavity Laser Arrays

International research team uses topological platform to demonstrate coherent array of vertical lasers

HAIFA, ISRAEL, AND WÜRZBURG, GERMANY, September 26, 2021 – Israeli and German researchers have developed a way to force an array of vertical cavity lasers to act together as a single laser – a highly effective laser network the size of a grain of sand. The findings are presented in a new joint research paper that was published online by Science on Friday, September 24.

Cell phones, car sensors, or data transmission in fiber optic networks all use so called Vertical-Cavity Surface-Emitting Lasers (VCSELs) – semiconductor lasers that are firmly anchored in our everyday technology. Though widely used, the VCSEL device has miniscule size of only a few microns, which sets a stringent limit on the output power it can generate. For years, scientists have sought to enhance the power emitted by such devices through combining many tiny VCSELs and forcing them to act as a single coherent laser, but with limited success. The current breakthrough uses a different scheme: it employs a unique geometrical arrangement of VCSELs on the chip that forces the flight to flow in a specific path – a photonic topological insulator platform.

From topological insulators to topological lasers
Topological insulators are revolutionary quantum materials that insulate on the inside but conduct electricity on their surface, without loss. Several years ago, the Technion group led by Distinguished Professor Mordechai (Moti) Segev introduced these innovative ideas into photonics, and demonstrated the first Photonic Topological Insulator, where light travels around the edges of a two-dimensional array of waveguides without being affected by defects or disorder. This opened a new field, now known as “Topological Photonics,” where hundreds of groups currently have active research. In 2018, the Technion group also found a way to use the properties of photonic topological insulators to force many micro-ring lasers to lock together and act as a single laser. But that system still had a major bottleneck: the light was circulating in the photonic chip confined to the same plane used for extracting the light. That meant that the whole system was again subject to a power limit, imposed by the device used to get the light out, similar to having a single socket for a whole power plant. The current breakthrough uses a different scheme: the lasers are forced to lock within the planar chip, but the light is now emitted through the surface of the chip from each tiny laser and can be easily collected.

Circumstances and participants
This German-Israeli research project originated primarily during the Corona pandemic. Without the enormous commitment of the researchers involved, this scientific milestone would not have been possible. The research was conducted by PhD student Alex Dikopoltsev from the team of Distinguished Professor Mordechai (Moti) Segev of Technion’s Physics and Electrical & Computer Engineering Faculties, the Solid State Institute and the Russell Berrie Nanotechnology Institute at the Technion – Israel Institute of Technology, and Ph.D. student Tristan H. Harder from the team of Professor Sebastian Klembt and Professor Sven Höfling at the Chair of Applied Physics at the University of Würzburg, and the Cluster of Excellence ct.qmat – Complexity and Topology in Quantum Materials, in collaboration with researchers from Jena and Oldenburg. The device fabrication took advantage of the excellent clean room facilities at the University of Würzburg.

A single coherent light beam (pink) is emitted by an array of 30 individual lasers. Credit: SimplySci Animations

The long road to new topological lasers
“It is fascinating to see how science evolves,” said Distinguished Prof. Moti Segev, the Dr. Robert J. Shillman Distinguished Professor of Physics and Electrical & Computer Engineering at the Technion. “We went from fundamental physics concepts to foundational changes therein, and now to real technology that is now being pursued by companies. Back in 2015, when we started to work on topological insulator lasers, nobody believed it was possible, because the topological concepts known at that time were limited to systems that do not, in fact, cannot, have gain. But all lasers require gain. So topological insulator lasers stood against everything known at that time. We were like a bunch of lunatics searching for something that was considered impossible. And now we have made a large step towards real technology that has many applications.”

The Israeli and German team utilized the concepts of topological photonics with VCSELs that emit the light vertically, while the topological process responsible for the mutual coherence and locking of the VCSELs occurs in the plane of the chip. The end result is a powerful but very compact and efficient laser, not limited by a number of VCSEL emitters, and undisturbed by defects or altering temperatures.

“The topological principle of this laser can generally work for all wavelengths and thus a range of materials,” explains German project leader Prof. Sebastian Klembt of the University of Würzburg, who is working on light-matter interaction and topological photonics within the ct.qmat cluster of excellence. “Exactly how many microlasers need to be arranged and connected would always depend entirely on the application. We can expand the size of the laser network to a very large size, and in principle it will remain coherent also for large numbers. It is great to see that topology, originally a branch of mathematics, has emerged as a revolutionary new toolbox for controlling, steering and improving laser properties.”

The groundbreaking research has demonstrated that it is in fact theoretically and experimentally possible to combine VCSELs to achieve a more robust and highly efficient laser. As such, the results of the study pave the way towards applications of numerous future technologies such as medical devices, communications, and a variety of real-world applications.

Click here for the paper in Science

Printing Blood Vessel Networks for Implantation

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Printing Blood Vessel Networks for Implantation

For the first time, Technion scientists succeeded in forming a network of big and small blood vessels, necessary for supplying blood to implanted tissue

Engineered constructs promote host functional vasculature ingrowth upon anastomosis with rats’ femoral artery. Transversal and side µCT images of perfused vascular networks in explanted engineered tissues. Vascular structures in the scaffold lumen (brown) communicate with vessels located in the surrounding hydrogel (green). The dashed line inserts show regions with vessel segments crossing the scaffold wall and communicating the luminal and external vasculatures.

 

Professor Shulamit Levenberg

Researchers led by Technion Professor Shulamit Levenberg, who specialises in tissue engineering, have succeeded in creating a hierarchical blood vessel network, necessary for supplying blood to implanted tissue. In the study, recently published in Advanced Materials, Dr. Ariel Alejandro Szklanny used 3D printing for creating big and small blood vessels to form for the first time a system that contained a functional combination of both. The breakthrough took place in Prof. Levenberg’s Stem Cell and Tissue Engineering Laboratory in the Technion’s Faculty of Biomedical Engineering.

In the human body, the heart pumps blood into the aorta, which then branches out into progressively smaller blood vessels, transporting oxygen and nutrients to all the tissues and organs. Transplanted tissues need similar support of blood vessels, and consequently so do tissues engineered for transplantation. Until now, experiments with engineered tissue containing hierarchical vessel networks have involved an intermediary step of transplanting first into a healthy limb, allowing the tissue to be permeated by the host’s blood vessels, and then transplanting the structure into the affected area. (e.g. this study by Idan Redenski about engineered bone grafts, published earlier this year.) With Dr. Szklanny’s new achievement, the intermediary step might become unnecessary.

Dr. Ariel Alejandro Szklanny

To create in the lab a tissue flap with all the vessels necessary for blood supply, Dr. Szklanny combined and expanded on two separate techniques. First, he created a fenestrated polymeric scaffold that mimics the large blood vessel, using 3D printing technologies. The fenestration served to create not just a hollow tube, but a tube with side openings that allowed the connection of smaller vessels to the engineered larger vessel. Using a collagen bio-ink, tissue was then printed and assembled around that scaffold, and a network of tiny blood vessels formed within. Finally, the large vessel scaffold was covered with endothelial cells, which are the type of cells that constitute the inner layer of all blood vessels in the body. After a week of incubation, the artificial endothelium created a functional connection with the smaller 3D bio-printed vessels, mimicking the hierarchical structure of the human blood vessel tree.

The resulting structure was then implanted in a rat, attached to its femoral artery. Blood flowing through it did what we would want blood to do: it spread through the vessel network, reaching to the ends of the structure, and supplied blood to the tissue without leaking from the blood vessels.

One interesting point to note is that while previous studies used collagen from animals to form the scaffolds, here, tobacco plants were engineered by the Israeli company CollPlant to produce human collagen, which was successfully used for 3D bioprinting the vascularized tissue constructs.

This study constitutes an important step towards personalized medicine. Large blood vessels of the exact shape necessary can be printed and implanted together with the tissue that needs to be implanted. This tissue can be formed using the patient’s own cells, eliminating rejection risk.

The study received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme.

For the full article in Advanced Materials click here

Click here for video demonstrating the research

 

Technion, Carasso Family & Carasso Motors to Establish the Carasso FoodTech Innovation Center

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Technion, Carasso Family & Carasso Motors to Establish the Carasso FoodTech Innovation Center

Yoel Carasso, Chairman of Carasso Motors (Left) and Technion President Prof. Uri Sivan

Haifa, Israel, September 14, 2021: Forty-five years after the family’s first contribution to the Technion – Israel Institute of Technology, and now as part of a multigenerational initiative, the Carasso Family and Carasso Motors are contributing toward a new initiative, promoting cutting-edge food technologies, teaching and R&D in the Faculty of Biotechnology and Food Engineering. The building that until now has housed the Food Industries Center will be renamed the Carasso FoodTech Innovation Center. The donation will be used to renovate the building, as well as expand and upgrade the Center’s research infrastructure. Alongside this activity, a scholarship fund will be established for advanced research.

The gift, which will enhance Israel’s research presence in the global food industry, is part of the family’s legacy – which emphasizes Zionism, excellence in science education, closing gaps in the Israeli society, and investment in infrastructure.

The expanded and upgraded building will be one of its kind in Israel and one of the most advanced in the world; it will feature an R&D center for industrial production, a packaging laboratory, an industrial kitchen, as well as tasting and evaluation units that will be used for teaching and research in the Faculty of Biotechnology and Food Engineering. The Carasso FoodTech Innovation Center will be housed in an existing, dedicated structure alongside the faculty, and will include a visitor area that will expose high-school students to the world of FoodTech, and serve as a hub for startups, where they can benefit from R&D services.

“Eradicating world hunger and improving food security are among the main challenges facing humanity in the 21st century, as defined by the UN’s Sustainable Development Goals,” said Technion President Prof. Uri Sivan. “The Technion has the only faculty in Israel for research in food engineering, a faculty that leads the Israeli FoodTech industry. We are grateful to the Carasso Family for their generous contribution, which will establish the Carasso FoodTech Innovation Center, and will help us promote groundbreaking scientific research in the field, train the next generation of the Israeli FoodTech industry, and maintain the faculty’s position at the global forefront of research and development.

Ioni Goldstein

Yoel Carasso, Chairman of Carasso Motors, said: “In 1924, our Grandfather Moshe immigrated with his family to Israel from Thessaloniki, where he was one of the leaders of the Jewish community. In Israel, he cofounded Discount Bank, Ophir Cinema (one of the first movie theaters in Tel Aviv), and of course Carasso Motors Company. For me and for my uncle Shlomo and my cousins – Ioni, Orli, Sarah, Tzipa and Arik – this is coming full circle from a century ago. We chose to support the Carasso FoodTech Innovation Center since the Technion is synonymous with excellence. The Technion is an engine for combining basic and applied science in the Galilee and in Israel as a whole. We believe the Carasso FoodTech Innovation Center will contribute to the industry, and to collaborative work in this field, and thus strengthen the Israeli economy and society. Our family has a history of supporting the Technion, and when the opportunity to establish this center sprang, we knew it was our calling to lead.”

Yoel Carasso, Chairman of Carasso Motors (Left) and Prof. Marcelle Machluf, Dean of the Faculty of Biotechnology and Food Engineering

Prof. Marcelle Machluf, Dean of the Faculty of Biotechnology and Food Engineering at the Technion, said “the faculty is one of the only ones in the world that combines the disciplines of bioengineering, technology, food sciences and life sciences. Coping with the COVID-19 pandemic has only emphasized the importance of food and biotechnology in maintaining our existence and meeting future existential challenges. To address the many challenges in this field, including access to healthy, affordable food and innovative medical treatments, we need advanced infrastructure that will enable the integration of new engineering and scientific tools; these will enable us to develop the necessary technologies, as well as the infrastructure and equipment that will support the development and assimilation of the knowledge required to tackle tomorrow’s food challenges. I would like to thank the Carasso Family for their generous contribution, which will allow the faculty to upgrade the infrastructure and equipment needed for the development and integration of the knowledge required to tackle future food challenges.” 

Izaac Weitz, CEO of Carasso Motors

Izaac Weitz, CEO of Carasso Motors: “Carasso Motors, with its various brands – Renault, Nissan, Infinity, and Dacia – is committed to innovation and connection with our diverse customer base in Israel. Food technology is an evolving field that brings value in many ways to our stakeholders. Food research tackles environmental and global warming challenges, providing food security and a balanced diet, accelerating paramedical developments that combine medicine and food, and of course contributing to the development of innovative solutions that will put Israel at the forefront of science globally. At Carasso Motors, we jumped at the opportunity to make such a significant contribution to the establishment of this advanced research center, which will also improve and advance Israel’s education and society.”

 

 

Hydrogen On the Way

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Hydrogen On the Way
Researchers in the Schulich Faculty of Chemistry at the Technion have developed a new system for producing hydrogen from water with a low energy investment and using available and inexpensive materials

Water electrolysis is an easy way to produce hydrogen gas. While hydrogen is considered a clean and renewable fuel, efficient electrolysis today requires high electric potential, high pH and in most cases, catalysts based on ruthenium and other expensive metals. Due to the inherent promise of hydrogen, many research groups are striving to develop electrolysis technologies that will make it possible to produce hydrogen fuel at a low electric potential, at a pH between 7-9 and with catalysts based on available and inexpensive metals such as copper, manganese, and cobalt.

Professor Galia Maayan

The Journal of the American Chemical Society  recently reported on a unique solution for this issue developed at the Technion – Israel Institute of Technology. It is the fastest system of its kind reported so far that operates with available metal (copper) catalysts. The research was led by Professor Galia Maayan, head of the Biomimetic Chemistry Laboratory in the Schulich Faculty of Chemistry, and doctoral student Guilin Ruan.

The Technion researchers designed and developed a homogeneous electrolysis system, or in other words, a system in which the catalyst is soluble in water, so that all components of the system are in the same medium. The innovative and original system is based on (1) copper ions; (2) a peptide-like oligomer (small molecule) that binds the copper and maintains its stability; and (3) a compound called borate whose function is to maintain the pH in a limited range. The main discovery in this study is the unique mechanism that the researchers discovered and demonstrated: the borate compound helps stabilize the metallic center and participates in the process so that it helps catalyze it.

Doctoral student Guilin Ruan

In previous studies, the research group demonstrated the efficacy of using peptide-like oligomers to stabilize metal ions exposed to oxygen – exposure that may oxidize them in the absence of the oligomer and break down the catalyst. Now, the researchers are reporting on the success in creating a very efficient and fast electrolysis system. The stable system oxidizes the water into hydrogen and oxygen under the same desired conditions: low electric potential, pH close to 9 and inexpensive catalysts. According to Prof. Maayan, the system was inspired by enzymes (biological catalysts) that use the protein’s peptide chain to stabilize the metallic center and by natural energetic processes such as photosynthesis, which are driven by units that use solar energy to transport electrons and protons.

Copper complex, consisting of two molecules of a peptide-like oligomer that binds two copper ions, reacts under electrolysis conditions with a molecule of the borate compound; the product of the reaction is the catalyst that allows the water to oxidize and create oxygen and hydrogen efficiently and quickly.

The research was supported by the Israel Science Foundation (ISF) and the Nancy and Stephen Grand Technion Energy Program.

Click here for the paper in The Journal of the American Chemical Society