David Mayerich, Ph.D. - US grants

DESCRIPTION (provided by applicant): A career development plan is proposed for Dr. David Mayerich, a computer scientist who is committed to developing an interdisciplinary career in biomedical engineering, with a focus on the collection and analysis of large-scale data sets at sub-micrometer resolution. His graduate research was in the areas of computer visualization and optical imaging, where his work lead to the development of the prototype Knife-Edge Scanning Microscope (KESM). This is the first instrument capable of imaging three-dimensional macro-scale tissue volumes at sub-micrometer resolution while providing a data rate approaching the transfer speed of most modern computer systems. Since receiving his Ph.D., Dr. Mayerich worked as a postdoctoral fellow at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign, where he has worked with biologists and biomedical engineers to develop tools for the segmentation and classification of large data sets. This provided experience in addressing the needs and limitations of the computational tools available to the interdisciplinary community. The goal of the mentored phase of this proposal is to provide Dr. Mayerich with the opportunity to work as a developer for the FARSIGHT Toolkit. The FARSIGHT Toolkit is an open-source segmentation toolkit that focuses on developing computer vision algorithms specifically tailored to deal with the unique structures found in microscopy data sets. This project is directed by Prof. Badrinath Roysam at the University of Houston, and was awarded first-place in the NIH-sponsored DIADEM Challenge in neuron segmentation. Dr. Mayerich will use his previous experience in biomedical segmentation, GPU-based computing, and efficient data structures to help make the FARSIGHT Toolkit scalable to the terabyte-scale data sets produced using next-generation high-throughput imaging techniques. Dr. Mayerich will receive mentoring in the algorithms and techniques used in the FARSIGHT Toolkit, as well as valuable experience working on a collaborative software development project. The goal of the independent phase is to use recently developed imaging techniques, along with scalable segmentation algorithms, to construct complete microvascular models of mouse organs. Recent advances in KESM demonstrate that sub-micrometer images of 1cm3 tissue samples can be collected in less than 50 hours. These images have the resolution and quality necessary for (a) complete reconstruction of microvascular networks in whole organs, and (b) the geometric distribution of cell soma in relation to this network. Models describing cellular and microvascular relationships have implications in several diseases, including neurodegenerative disease and tumor growth, as well as clinical applications in tissue engineering and the quantitative analysis of angiogenic drugs and therapies.

Age-related diseases are increasingly a leading cause of disability. Millions of younger adults live with neurological disorders, limb loss from amputation or paralysis from spinal cord injury. Traumatic brain injury can have lifelong effects on cognitive-motor function, significantly decreasing quality and length of life. There is a critical need for state-of-the art technology to effectively address the care and rehabilitation of these individuals. However, innovation in biomedical devices and other neurotechnologies faces several challenges: 1) The pace of innovation is moving more quickly than the rate of evaluation for acceptable performance; 2) Standards and regulatory science for the rigorous validation of safety, efficacy, and long-term reliability are missing; 3) Lack of open access to technologies that slows the transfer of novel technologies to the market; and 4) Current technologies are not affordable. To address these challenges, the University of Houston will partner with Arizona State University to establish and host a multi-institution Industry/University Cooperative Research Center (IUCRC) for Building Reliable Advances and Innovation in Neurotechnology (BRAIN).
The BRAIN Center's vision is a synergistic, interdisciplinary approach to develop and validate affordable patient-centered technologies. BRAIN will leverage expertise in neural systems, cognitive and rehabilitation engineering, robotics, device development, clinical testing and reverse-translational research at the University of Houston and Arizona State University to 1) enhance the rate of development and empirical validation of new technologies through partnerships with industry leaders and other strategic partners; 2) develop standards and technologies in human and non-human models, using a multi-scale approach ranging from single neurons to organismal systems; 3) characterize innovative technologies such as biosensors and quantitative analysis tools for systems and behaviors; 4) evaluate the impact of these technologies on quality of life; and 5) reduce the cost of neurotechnologies. The BRAIN Center's mission is multifold: to accelerate the progress of science and advance national health by transferring engineering innovations in neurotechnology to the end users, and to rectify underrepresentation in science, technology, engineering, and math (STEM) fields by broadening new participation and retaining current participants in STEM. It also will focus on problems in the neurological space that affect underrepresented groups disproportionately. BRAIN will become an innovative neurotechnology hub for the Southwest, creating a pipeline from discoveries to solutions while helping talented students, scientists, and engineers in the region take their innovations to the next level and solve one of the greatest unmet medical and health care needs of our time.

BRAIN will leverage a unique concentration of researchers and innovative research and development ecosystems with industrial partnerships to design, develop, test, and characterize neural technologies that can effectively transform the lives of disabled individuals. The Center will investigate all levels of neural function to enhance not only current technologies but also understanding of the mechanisms underlying neurological disease and injury. The University of Houston IUCRC Site - a Hispanic-Serving Institution - will focus on multi-scale, multi-modal, and multi-disciplinary and noninvasive approaches to understanding all aspects of human neural function "in action and in context" in complex natural settings, and to deploying noninvasive technologies treating human disability. The University of Houston IUCRC site will bring a broad range of expertise spanning the spectrum of cognitive, affective, neural, and rehabilitation engineering across the human lifespan, big data analytics, computational modeling, wearable electronics, mobile brain-body imaging devices, intervention techniques including peripheral, brain-machine interfaces, smart human-machine systems, wearable robots, virtual and augmented reality and other noninvasive solutions.

PROJECT SUMMARY The ability to correlate between large-scale developmental milestones and micro-scale cellular and protein- specific changes is a significant unmet need in the study of developmental biology. The overall objective of this work is to develop a multi-modality imaging platform that can provide time resolved three-dimensional images of tissue development, with high temporal and spatial resolutions at a molecular level. Current studies rely on multiple imaging modalities to collect information on critical stages of vertebrate embryogenesis, and most offer only static snapshots of a single developmental stage. Live imaging with optical coherence tomography (OCT) provides high temporal resolution with contrast between tissue structures, allowing researchers to identify and test the mechanisms underlying developmental processes. Three- dimensional fluorescence approaches such as confocal and light sheet microscopy (LSM) provide increased resolution and molecular specificity which can be used to observe cellular mechanisms, such as the presence of erythroblasts indicating active blood flow, that are inaccessible to lower-resolution techniques. This will be accomplished by designing and developing a novel microscopic imaging system that provides spatially and temporally aligned OCT and light sheet microscopy images. Simultaneous images will be collected through OCT scanning and fluorescent light sheet excitation of the same sample plane. Fluorescence emission will be imaged through a second objective, while the OCT signal will be collected through the same lens in reflection mode. Software will be designed to synchronize data collection with an integrated high-precision rotational stage. A novel software toolkit will be developed to analyze this rich multi-modal data. Novel reconstruction methods will be designed to fuse both modalities, while addressing the sparse and multiplex nature of the LSM images and high frame rate of OCT. Finally, we'll use this tool to test the central hypothesis that a combined LSM+OCT imaging system can reveal the precise structural and molecular events required to form a circulatory loop between the embryo and maternal chorio-allantoic placenta. Successful accomplishment of the proposed work will generate a novel, integrated imaging platform, including instrumentation and analytical software, which could be widely adopted by developmental biologists to bridge the gap between large-scale developing phenotypes and the underlying molecular and cellular processes. We will benchmark this accomplishment by identifying currently unknown critical milestones in murine embryonic development. Specifically, LSM+OCT will be used to define the precise series of events necessary to form the umbilical artery (UA) and umbilical vein (UV). This research will clarify the sequence of events, including cellular, molecular, and global phenotypic changes, that lead to the establishment of an embryonic circulatory system between the mother and developing fetus, a critical prerequisite for embryonic survival.