Creating Biomedical Technologies to Improve Health

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RESEARCH

NIBIB-Supported Biomedical Technology Resource Centers

  • Ravinder Reddy
    University of Pennsylvania

    The primary goal of the Center for Magnetic Resonance and Optical Imaging (CMROI) is to develop state-of-the-art core Magnetic Resonance and Optical biomedical imaging technologies for solving important problems in biomedical research with a special emphasis on the rapid clinical translation. These technological developments are driven by collaboration with scientists from within and outside University of Pennsylvania, the primary institution. Specifically, the Resource is focused on the development of quantitative, noninvasive MR and optical imaging based biomarkers for studying tissue metabolism and function, with an eye towards clinical translation through early diagnosis. The Center also provides support in the development and evaluation of new therapies in a variety of diseases.

  • Harrison Barrett
    University of Arizona

    The primary focus of the Center for Gamma-Ray Imaging (CGRI) is to develop new gamma-ray imaging instruments and techniques that yield substantially improved spatial and temporal resolutions. The Center makes its imagers and expertise available to a wide community of biomedical and clinical researchers through collaborative and service-oriented interactions. The collaborative research applies these new imaging tools to basic research in functional genomics, proteomics, cancer, cardiovascular disease and cognitive neuroscience, and to clinical research in tumor detection and other selected topics. There are five core research projects: Detector technology research and development; Reconstruction algorithms and system modeling; Data acquisition, signal processing, and system development; Image-quality assessment and system optimization; Techniques for molecular imaging.

  • George Johnson
    Duke University

    The Center for In Vivo Microscopy (CIVM) is dedicated to the development of novel imaging methods for the basic scientist and the application of the methods to important biomedical questions. The CIVM has played a major role in the development of magnetic resonance microscopy with specialized MR imaging systems capable of imaging at more than 500,000x higher resolution than is common in the clinical domain. The CIVM was the first to demonstrate MR images using hyperpolarized 3He which has been moved from mouse to man with recent clinical trials performed at Duke in collaboration with GE. More recently the CIVM has developed the molecular imaging workbench---a system dedicated to multimodality cardiopulmonary imaging in the rodent. Our collaborators are employing these unique imaging systems in an extraordinary range of mouse and rat models of neurologic disease, cardiopulmonary disease and cancer to illuminate the underlying biology and explore new therapies.

  • Joachim Kohn
    Rutgers, The State Univ of N.J.

    The Resource Integrated Technologies for Polymeric Biomaterials (RESBIO) works to develop integrated tools and technologies that advance the discovery of polymeric biomaterials for regenerative medicine, the delivery of biological agents, and the next generation of medical implants. To achieve its mission, RESBIO's research is focused on the development of combinatorial and computational approaches to biomaterials design and optimization. Within this framework, RESBIO employs and uses:Advanced multi-photon confocal laser microscopy to explore, understand, and control the response of cells in contact with artificial surfacesElectron microscopy techniques to study the effect of nano-scale surface morphological features on cell behaviorRESBIO research emphasizes the integration of a strong synthetic effort to create new biomaterial candidates with the development of rapid screening techniques for key material and biological properties relevant to the performance of a biomaterial in a given medical application.

  • Arthur Toga
    University of Southern California

    The Laboratory of Neuro Imaging Resource (LONIR) develops novel strategies to investigate brain structure and function in their full multidimensional complexity. There is a rapidly growing need for brain models comprehensive enough to represent brain structure and function as they change across time in large populations, in different disease states, across imaging modalities, across age and sex, and even across species. International networks of collaborators are provided with a diverse array of tools to create, analyze, visualize, and interact with models of the brain. A major focus of these collaborations is to develop four-dimensional brain models that track and analyze complex patterns of dynamically changing brain structure in development and disease, expanding investigations of brain structure-function relations to four dimensions.

  • Kamil Ugurbil
    University of Minnesota

    The Center for Magnetic Resonance Research (CMRR) focuses on development of unique magnetic resonance (MR) imaging and spectroscopy methodologies and instrumentation for the acquisition of structural, functional, and biochemical information non-invasively in humans, and utilizing this capability to investigate organ function in health and disease.The distinctive feature of this resource is the emphasis on ultrahigh magnetic fields (7 Tesla and above), which was pioneered by this BTRC. This emphasis is based on the premise that there exists significant advantages to extracting biomedical information using ultrahigh magnetic fields, provided difficulties encountered by working at high frequencies corresponding to such high field strengths can be overcome by methodological and engineering solutions.This BTRC is home to some of the most advanced MR instrumentation in the world, complemented by human resources that provide unique expertise in imaging physics, engineering, and signal processing. No single group of scientists can successfully carry out all aspects of this type of interdisciplinary biomedical research; by bringing together these multi-disciplinary capabilities in a synergistic fashion, facilitating these interdisciplinary interactions, and providing adequate and centralized support for them under a central umbrella, this BTRC amplifies the contributions of each of these groups of scientists to basic and clinical biomedical research.Collectively, the approaches and instrumentation developed in this BTRC constitute some of the most important tools used today to study system level organ function and physiology in humans for basic and translational research, and are increasingly applied world-wide.

  • Stanley Opella
    University of California San Diego

    The Resource is focused on the development of NMR spectroscopy for structure determination of proteins in biological supramolecular assemblies. The principal applications are to membrane-associated proteins; however, the approach is generally applicable to polypeptides that cannot be prepared in forms suitable for X-ray crystallography or multidimensional solution NMR spectroscopy. As a result, there are also applications to viruses and other biological systems.The principal instrumentation consists of high-field NMR spectrometers dedicated to high-resolution solid-state NMR spectroscopy. The spectrometers are capable of the full-range of multiple-resonance experiments on stationary and spinning samples; however, the major emphasis is on methods that utilize mechanically or magnetically oriented samples. Development encompasses preparation of samples, including:Expression and purification of membrane proteinsDesign and construction of instrumentation, especially probesImplementation of new pulse sequences and other experimental protocols for solid-state NMR spectroscopyCalculations for the processing of experimental data and protein structure determination from the orientational constraints derived from these data

  • David Castner
    University of Washington

    The National ESCA and Surface Analysis Center for Biomedical Problems (NESAC/BIO) provides state-of-the-art surface analysis expertise, instrumentation, experimental protocols, and data analysis methods to address surface-related biomedical problems. NESAC/BIO develops and applies surface science methodologies that produce a full understanding of the surface composition, structure, spatial distribution, and orientation of biomaterials and adsorbed biomolecules. The NESAC/BIO program identifies areas where surface science must evolve to keep pace with the growth in biochemical knowledge and biomaterial fabrication technology, and develops instrumentation, experimental protocols, and data analysis methods to achieve this evolution.

  • Richard Superfine
    Univ of North Carolina Chapel Hill

    The goal of CISMM is to develop force technologies applicable over a wide range of biological settings, from the single molecule to the tissue, with integrated systems that orchestrate facile instrument control, multimodal imaging, and analysis through visualization and modeling.Our Force Microscope Technologies Core designs instruments in an area of science where there are unusual opportunities: the measurement of forces and the integration with optical microscopy. Force technologies play the obvious role of both measuring events in the sample and modifying the sample during the experiment. It is through the microscope that the force data is correlated with simultaneous 3D optical images. The force technology development includes the magnetic bead technology in our 3D Force Microscope project, Atomic Force Microscopy in our nanoManipulator project, and Control Software to drive the instrumentation. This core is focused on providing the physical capability to perform the experiments and probe structure/property correlations.The Ideal User Interfaces core makes the connection between the user and the instrument, the model building, and the data. This includes control systems that allow the user to move the bead inside the cell culture with a handheld pen and the visualization techniques to view the optical microscope data as a rendered 3D image collocated with the force data.Using data to create, change, and understand a model is the focus of our Advanced Model Fitting and Analysis core. The quantitative reduction of images to structural, shape, and velocity parameters is the goal of Image Analysis. The immediate understanding of correlations across image fields and between data sets in the challenge of Visualization. The power of combining the strength of a computer science graphics group with a microscopy technology group is most evident in the Graphics Hardware Acceleration project, which seeks to harness the speed of graphics processors for microscope data analysis and simulation.Our Advanced Technology core pushes the boundaries of the Human Computer Interface through the investigation of improved techniques for the interaction of users with virtual environments, the real time lighting of virtual settings, and the enabling of multi-person collaboration. These techniques are validated and evaluated through physiological measures in virtual environments effectiveness evaluation studies.

  • Robert Griffin
    Massachusetts Institute of Technology

    The Harvard/MIT Center for Magnetic Resonance (CMR) is a joint effort between Harvard Medical School and the Massachussetts Institute of Technology. The CMR core research program is focused on the development and applicaton of new magnetic resonance technologies directed at structural biology using a cluster of high field solution and solid state NMR spectrometers. Investigations includes studies of membrane proteins, translation initiation, and amyloid fibrils associated with several diseases. Membrane proteins are examined in nanodiscs using solution NMR and in lipsomes and 2D crystals using magic angle spinning (MAS) dipolar recoupling techniques. Translation initiation is investigated with solution NMR. MAS is the method of choice for experiments on amyloid fibrils since they are both insoluble and do not diffract to high resolution. The CMR is also heavily involved in the development of new software and instrumentation for magnetic resonance. These include methods for non uniform sampling (NUS) to enable efficient acquisiton of higher dimensional NMR spectra and high frequency microwave technology (~150-600 GHz) is being developed for both DNP-NMR and EPR experiments at high magnetic fields. Recent DNP experiments have yielded significant signal enhancments from membrane and amyloid protein samples and enabled experiments that are otherwise not possible. The CMR has pioneered the development of low temperature MAS technology. In addition, there is an extensive effort focused on the creation of new pulse sequences for performing assignments and determining structures in both solution and MAS experiments. Finally, the staff at the CMR interact extensively with outside investigators.

  • David Brenner
    Columbia University

    The Columbia University Radiological Research Accelerator Facility (RARAF) is a dedicated facility for radiobiological research with available ionizing radiations such as protons, alpha particles, and neutrons. RARAF is well-established and highly user-friendly. The focus of RARAF is the development of high-throughput single-cell/single-particle microbeams, which can deliver defined amounts of ionizing radiation into individual cells with a spatial resolution of a few microns or better. The ability of a microbeam to put double strand break damage at any specific known location in a given cell has allowed new approaches to the study of damage signaling.

  • David D'Argenio
    University of Southern California

    The Biomedical Simulations Resource (BMSR) in the Department of Biomedical Engineering at the University of Southern California is dedicated to the advancement of the state-of-the-art in biomedical modeling and simulation through Core and Collaborative Research projects, as well as the dissemination of this knowledge and related software through Service, Training and Dissemination activities aimed at the biomedical community at large. The BMSR includes four core research projects:Pharmacokinetic/Pharmacodynamic Systems Analysis – David Z. D'Argenio, Ph.D., Co-DirectorNonlinear Modeling of Complex Biomedical Systems – Vasilis Z. Marmarelis, Ph.D., Co-DirectorModeling of Autonomic, Metabolic and Vascular Control Interactions – Michael C.K. Khoo, Ph.D., Co-InvestigatorNonlinear Modeling of the Hippocampus – Theodore W. Berger, Ph.D., Co-InvestigatorFifteen Collaborative Research Projects serve as challenging test grounds for the Resource's methodologies and expertise. The BMSR's service activities include the development and distribution of four software packages (ADAPT, LYSIS, PNEUMA +amp; EONS).The Resource's Training and Dissemination activities include short courses, advanced workshops and the publication of associated research volumes.

  • Bruce Tromberg
    University of California-Irvine

    The Laser Microbeam and Medical Program (LAMMP), is dedicated to the use of lasers and optics in biology and medicine. LAMMP is located within the Beckman Laser Institute, an interdisciplinary biomedical research, teaching, and clinical facility at the University of California, Irvine. The overall objective is to promote a well-balanced BTRC with activities in technological research and development, collaborative research, service, training, and dissemination. One of the primary goals of LAMMP is to facilitate ""translational"" research by rapidly moving basic science and technology discoveries from ""blackboard to benchtop to bedside"". This is accomplished by combining state of the art optical technologies with specialized resource facilities for cell and tissue engineering, histopathology, pre-clinical animal models, and clinical care. The resource center has been organized into 3 cores:Microscopy and Microbeam Technologies (MMT) for high-resolution functional imaging and manipulation of living cells and tissuesMedical Translational Technologies (MTT) for non- and minimally-invasive monitoring, treating, and imaging pre-clinical animal models and human subjects, andVirtual Photonics Technologies (VPT) for developing computational models and methods that advance the performance of biophotonic technologies, and enhance the information content derived from optical measurements.LAMMP cores contain complementary technologies that are capable of quantitatively characterizing, imaging, and perturbing structure and biochemical function in cells and tissues with scalable resolution and depth sensitivity ranging from micrometers to centimeters.

  • Gary Glover
    Stanford University

    The Center for Advanced Magnetic Resonance Technology develops innovative technologies in five core research areas of magnetic resonance imaging and spectroscopy (MRI/MRS):image reconstruction, fast imaging and radiofrequency (RF) pulse design methods,R hardware development,body imaging methods,neuroimaging methods.MR spectroscopy methods.In each of these areas, we capitalize on the long-standing, successful partnership and extensive experience in Stanford’s Radiology and Electrical Engineering departments to improve and expand imaging technology for use in basic research and clinical care, and to provide cutting edge opportunities to the extramural community for biomedical research with MRI.Over its more than 18 years of existence, CAMRT has been motivated by and has served a wide base of extramurally sponsored collaborators and service users from leading medical and research institutions. Examples of collaborative projects are the development of real-time functional MRI biofeedback methods for neuroscience and clinical applications such as pain remediation, development of methods to mitigate metal artifacts in musculoskeletal imaging, development of novel RF pulses for many applications, and studies of breast cancer with efficient MRS methods.

  • James Hyde
    Medical College of Wisconsin

    Development of multiquantum Q- and W-band spectrometers, including multiquantum ELDOR, development of time-locked sub-sampling (TLSS) for broadband detection of periodically modulated signalsDevelopment of loop-gap resonators using finite element modeling of Maxwell's equationsApplication of multifrequency (1 to 100 GHz) electron paramagnetic resonance (EPR) to characterize paramagnetic centersStudy of relaxation processes using multifrequency pulse saturation recoveryUse of nitroxide radical spin labels to measure translational and rotational diffusion in biological systems, site-directed spin labeling (SDSL), and use of EPR for the detection of nitric oxide and oxy radicals.

  • Claude Lechene
    Brigham And Women'S Hosp., Inc.

    The focus of this resource is the application to biomedical research of a new generation of secondary ion mass spectrometer (SIMS), the Multi-Isotope Imaging Mass Spectrometer (MIMS). MIMS is an ion microscope and an ion counter. MIMS provides high mass separation at high transmission (M/lambdaM +gt; 10,000), high spatial resolution (+lt; 40 nm) and has the unique capability of simultaneously recording several atomic mass images. Of the utmost importance, MIMS makes it possible for the first time (and at the intracellular level) to simultaneously image the distribution and measure the accumulation of molecules labeled with any isotopes, in particular with stable isotopes, for example with 15N. Thus, MIMS allows one to study localization, accumulation and turnover of proteins, fats, sugars and foreign molecules in cellular microdomains, donor-receiver cellular trafficking, stem cell nesting and localization of drugs.

  • Peter Van Zijl
    Hugo W. Moser Res Inst Kennedy Krieger

    This Resource is an interdepartmental and interdisciplinary laboratory combining facilities of the F.M. Kirby Research Center for Functional Brain Imaging at the Hugo Moser Research Institute at Kennedy Krieger (KKI) and the Center for Imaging Science (CIS) at Johns Hopkins University (JHU). It provides expertise for the design of quantitative magnetic resonance imaging (MRI) and spectroscopy (MRS) data acquisition and processing technologies that facilitate the biomedical research of a large community of clinicians and neuroscientists in Maryland and throughout the USA. These methods allow noninvasive assessment of changes in brain anatomy as well as in tissue metabolite levels, physiology, and brain functioning while the brain is changing size during early development and during neurodegeneration, i.e. the changing brain throughout our life span. The Kirby Center has 3 Tesla and 7 Tesla state of the art scanners equipped with parallel imaging (8, 16, and 32-channel receive coils) and multi-transmit capabilities. CIS has an IBM supercomputer that is part of a national supercomputing infrastructure.