GE Global Research. The Future of Brain Health

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1 GE Global Research The Future of Brain Health

2 mission statement We will know the brain as well as we know the body. Future generations won t have to face Alzheimer s, TBI and other neurological diseases.

3 It is an ambitious vision, but one that GE believes is achievable through an unwavering commitment to technology and the growth of a collaborative research ecosystem that brings top researchers together to rally behind this cause. Worldwide more than 450M people live with neuropsychiatric and neurodegenerative diseases and yet our understanding of the brain is well behind that of nearly every other organ in the body. At GE Global Research, we have launched a global innovation effort aimed at closing this gap and accelerating the advancement of brain health technologies. Across our research labs, GE brings a diverse set of skillsets from across the science and engineering spectrum to solve tough problems and move the needle of what s possible in the industries we play in. Now, we are collaborating with top researchers and institutions to find new insights about brain health previously not possible. These efforts include: Seeing the brain more clearly in more places GE was the first to introduce a MRI scanner in hospitals in the early 1980s. Today, we are pushing new frontiers in the development of a dedicated MRI brain scanner in collaboration with the NIH and Mayo Clinic. The goal is to design a dedicated brain scanner with high quality imaging power that could be mobile and portable. If we can see the brain more clearly and easily, we can better understand its functions. Seeing the brain in new ways We re developing a new platform to help neuroscientists increase their understanding of neurons, immune cells and other types of brain cells. GE scientists have developed such a platform to see and study cancer in new ways. We believe it could similarly help researchers study the brain at a much deeper level that could yield insights previously not possible. Understanding how brain cells react to injury or illness, for example, could promote earlier diagnosis and provide more targeted treatments. Knowing the brain s circuitry like we know the electric grid We re developing new medical devices to enhance our understanding of the circuitry of the brain. This could lead to a more fundamental understanding of the brain s function and in turn, lead to new discoveries about treating brain-related disorders such as autism, TBI and even finding ways to enable paralyzed individuals to walk again. The brains behind GE s imaging and diagnostics GE has long had a world-class computer vision team that has been the brains behind the image analysis tools that accompany GE s world-class imaging systems. To support new advancements in brain health, this team is developing new ways to pull data together from our imaging systems and perform analytics to help researchers make new discoveries about brain health. With each research initiative, GE scientists and engineers hope to build important connections with top neuroscience researchers and deliver innovative tools to accelerate new discoveries. For an organ as complex as the brain, it will take nothing less than collective minds of this growing and engaged research community to solve the mysteries of brain health that still elude us today.

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5 Seeing the Brain More Clearly in More Places Background In November 2010, GE Global Research, together with the Mayo Clinic, received a five-year, $5.7 million grant from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and the National Institute of Neurological Disorders and Stroke (NINDS) components of the National Institutes of Health (NIH) to develop a dedicated Magnetic Resonance Imaging (MRI) brain scanner to conduct research on a range of neurological and psychiatric disorders such as: stroke; Alzheimer s Disease; Parkinson s Disease; Traumatic Brain Injury (TBI); depression; and autism. GE researchers are among the earliest pioneers in MRI development, introducing the first high field MRI system to market in MRI is a sophisticated technology that helps physicians see detailed anatomy and physiology inside the human body without the use of ionizing radiation. A key strength of MRI scanners is the ability to differentiate various soft tissues inside the body. Clinicians typically use MRI scanners for neurological, orthopedic and body examinations. Today, 25 30% of all MRI scans are brain scans. As disease modifying drugs for neurodegenerative diseases become available, use of these drugs is likely to require more frequent monitoring through repeated scans. Another factor driving more scans is the trend toward more quantitative imaging, as clinicians look to refine diagnosis of neuropsychiatric disorders that today are entirely diagnosed based on a clinical examination (depression, bipolar disorder, schizophrenia). Finally, as the demand for scans increases, GE is pushing to expand the access of MRI systems to more locations as part of its healthymagination campaign, so that millions of more patients can benefit from this technology. GE Technology Focus GE researchers are developing a dedicated brain MRI scanner that could potentially lead to new specialized imaging approaches, improve imaging capabilities and expansions in the range of functionality for imaging the brain. The goal of reducing system size and weight is aimed at allowing easier installation and increased access to MRI technology for both research and clinical purposes, especially when space and infrastructure are considerations. In parallel, GE researchers also are working on improving image acquisition technologies to enhance our understanding of brain connectivity and wiring, as well as of the functional centers. This is essential to uncovering the basis of how the brain works (including memory and recall), how we process information (cognition), and make decisions (executive processes). What are brain researchers hoping to learn and do? A dedicated brain scanner will provide researchers with a more robust platform for studying a wide range of neurological disorders. Furthermore, new methods may be developed that could better probe the microstructure of the brain to deepen our understanding of the fundamentals of brain function. This may possibly lead to improved treatment options to work toward addressing neurological disorders from dementia to neuropsychiatric disease.

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7 Seeing the Brain in New Ways Background No one knows the exact count, but most estimates peg the number of neurons in a human brain at around 100 billion. Each of these cells produces thousands of proteins that enable cells to function and communicate with one another. It is these cells and proteins that neuroscientists believe hold the key to understanding many fundamental questions about normal brain function as well as the underpinning of brain disorders. Chief among them are what causes cells to change into diseased cells, which can then cause the onset of brain-related illnesses such as Alzheimer s disease, autism, Parkinson s disease, or Amyothrophic Lateral Sclerosis (ALS). GE Technology Focus GE researchers are developing new tools for studying the brain at the molecular and cellular levels. We re collaborating with Dr. Sam Gandy and Dr. Patrick Hof from the Icahn School of Medicine at Mount Sinai and others, with the aim of enabling researchers to see and study cellular behavior in the brain in ways it could never be studied before. Last year, GE introduced a ground-breaking new pathology platform in cancer diagnostics called MultiOmyx, which allows pathologists to see cancer in ways previously not possible. The platform enables pathologists to view multiple stains on a single tumor slice rather than requiring them to use separate slices from tumor samples for each stain. The results can be analyzed at the single cell level and the platform allows for more than 60 proteins to be examined on a single tissue sample. This is providing pathologists with a much more complete picture of cancer, which has the potential to greatly improve the efficiency and effectiveness of clinical research and could yield new insights into tumor behavior. Much in the same way MultiOmyx is enabling new insights about cancer; GE researchers believe it could help brain researchers learn more about neurodegenerative diseases. It could take the observation of brain activity to subcellular level. The idea is to use MultiOmyx to study new and existing molecular markers on post-mortem brain tissue to gain new insights into neurodegenerative disease processes. But that s not all. In related work, we also want to use these new insights to develop new functional imaging agents that can visualize diseased tissue in living people. What are brain researchers hoping to learn and do? Currently, GE has an ongoing study with Dr. Patrick Hof, Professor of Neuroscience and Vice-Chair of the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. Dr. Hof is using GE s molecular and cellular tools to study a subclass of neurons related to neurodegenerative illnesses like Alzheimer s disease that are most vulnerable in the initial stages of the these diseases. A molecular marker has been uncovered by Dr. Hof that can identify these particular neurons. Using GE s molecular and imaging analysis tools, he is hoping to learn about why some cells are more vulnerable than others. It not only could lead to an earlier marker of these diseases, but a better understanding of why certain cells change could pave the way to new treatments to stop or prevent them from progressing. Similarly Dr. Gandy is leading a study with GE to study a class of brain-specific immune cells called microglia. These cells can be activated in states that can be either neuroprotective or cause excessive neuroinflammation leading to the death of neurons. These cells are relevant across many neurological disorders including Alzheimer s disease, Chronic Traumatic Encephalopathy (CTE) and ALS, among others. Better understanding of these cells could lead to better treatment strategies.

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9 Knowing the Brain s Circuitry Like We Know the Electric Grid Background Since Thomas Edison s light bulb and demonstration of the first power station in New York City in the late 1800s, the General Electric Company pioneered many of the technologies that built today s modern electric grid from generators to transmission and distribution lines to home appliances and lighting products. More recently, GE researchers have been driving advancements in the so-called smart grid that is taking our understanding of and control of electricity to whole new levels. Today, we re trying to do the same for mapping the circuitry of the human brain. GE has been in healthcare almost as long as the power business. It was GE physicist William Coolidge who developed the first practical use of X-ray technology for medical diagnosis in We have been innovating and pioneering new advancements in medical imaging and diagnostics ever since. Among the key areas where we have made key technology contributions is in the field of microelectronics and sensing for medical devices. Through the years, our efforts in electronics miniaturization have helped take the size of imaging and monitoring systems like ultrasound from as big as a refrigerator to one you can hold in the palm of your hand. We re also developing new wireless sensing applications in smaller packages to monitor vital signs that will have their own dedicated radio frequencies to deliver critical medical information to doctors instantaneously. GE Technology Focus GE researchers are working with John Donoghue, one of the world s foremost experts in neural recording, and his team at Brown University to develop wireless implantable devices as tiny as the lead point on the end of a pencil that can record signals from individual neurons in the brain and communicate the information outside the body. This technology is being designed to receive commands and apply stimuli to help correct neuron function. Present day neural recording systems connect implantable probes to electronic modules using cables and connectors, often making it hard to reach many areas of the brain. Leveraging GE s experience in materials, miniaturization and fabrication, the goal of these new implantable devices is to integrate the probes and electronics so they can be placed throughout different regions of the brain and can scale using networks that will interface with thousands of neurons (as opposed to hundredss today). This capability could one day advance the understanding to decode how the brain works and improve our ability to treat disease with devices and systems that can work continuously for long periods of time. The ultraminiature integrated devices are also being designed to reduce physical stresses, resulting in less irritation and inflammation for longer, more accurate and robust interfacing to neurons. What are brain researchers hoping to learn and do? Already, Donoghue has been using present-day neural recording systems that have enabled paralyzed individuals to control external prosthetic devices or to interact with computer interfaces. Working with GE researchers, the goal is to enable a new fundamental understanding of how large collections of neurons interact, while providing real-time, continuous control for disease treatment and control of assistive devices. GE s expertise in electronic circuits, micromachining and electronic packaging all will come to play to build highly reliable yet tiny circuits and structures for effective implants. In addition, our experience in wearable non-invasive patient monitoring systems will enable the design and development of robust wireless communication systems and analytics that will be critical to the device s functionality as well.

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11 The Brains Behind GE s Imaging and Diagnostics Background Complementing every great X-ray, MRI or CT scan are worldclass image analysis tools that give these pictures interpretation and meaning. GE, which develops and manufactures virtually every medical imaging modality from X-ray and Computed Tomography (CT) to Ultrasound, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) imaging has a world class computer vision team at GE Global Research developing image analysis tools to support these systems. The team spans multiple labs around the world. As more advances are being made in the capabilities of the various medical imaging systems, especially MRI, the amount of neuroimaging data acquired alone is expected to double every two years. To appreciate how much data, just consider that each new study accumulates 20 GB of raw data on average. This number, while huge, is dwarfed by the terabytes (one terabyte is the typical memory capacity of a computer hard drive) of data generated by genomic data from Next Generation Sequencing (NGS) and proteomic data from high content, high-resolution in-vitro microscopy of tissue samples. Organizing, storing, sharing, and analyzing the combination of all these datatypes poses significant challenges with potential for unraveling the mysteries of the brain; the most complex organ in the human body. GE Technology Focus GE Image Analysis and Computer Vision teams at Global Research are developing new methods and tools for integrating large amounts of data from multiple modalities and at different scales to better characterize and understand the human brain and its function. GE is utilizing advanced computing platforms and big data technologies to develop a modular, scalable platform for integrative data analytics and visualization. GE s research initiatives involve the development of novel, high resolution in-vivo imaging techniques, mapping of the brain s connectivity and networks, understanding neuronal cell types and function, and characterizing gene expression. As vast amounts and different forms of medical data are getting generated, informatics techniques that can integrate and extract useful and actionable knowledge from these datasets, and also visualize and analyze it in novel and scalable ways, are critical. This could permit fundamental breakthroughs and new insights into brain structure and function and guide the development of new diagnostic and therapeutic approaches. What are brain researchers hoping to learn and do? The aim is to create the same types of integrated data analytics platform for brain researchers that exist today for oncology research. Such integrative approaches have not been extensively developed for neuroscience research, and there is a large unmet need for software solutions that can integrate in-vivo anatomic and functional brain imaging data with genotypic information and other clinical and cognitive measures, and with tissue and cell-based data and atlases where available. The technology GE is developing will provide a common platform for being able to analyze data across multiple spatial and temporal scales, providing clues for treating brain disorders, many of which are currently managed rather than treated.

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