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.

  • K Shung
    University of Southern California

    The focus of this resource is to develop very high frequency (above 20 MHz) ultrasonic transducers/arrays for applications in medicine and biology that include ophthalmology, dermatology, vascular surgery, and small animal imaging. The research is pursued simultaneously in three directions: novel piezoelectric materials, very high frequency single element transducers and linear arrays, and finite element modeling and material property measurements.

  • Mehmet Toner
    Massachusetts General Hospital

    The BioMEMS Resource Center's mission is to provide biomedical investigators with novel microsystems engineering tools for biological discovery, diagnostic, prognostic, and therapeutic applications. Thrust areas of interest for the BioMEMS Resource Center are the development of novel living cell-based, lab-on-a-chip type devices for sorting blood cells, for high-throughput biochemistry in small volumes, and for studying cellular behavior in controlled microenvironments.

  • 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.

  • Jonathan Wolpaw
    Nysdoh/Health Research, Inc.
  • Brett Bouma
    Massachusetts General Hospital

    The Center for Biomedical OCT Research and Translation (CBORT) pioneers and provides access to microscopic imaging instruments for biologic and clinical research. Optical coherence tomography (OCT) has evolved over the last two decades to become a standard of care for diagnostic ophthalmic imaging and is poised to make significant impact in the fields of cardiology and gastrointestinal endoscopy. Access to state-of-the-art instrumentation, however, has been limited to a relatively few research laboratories and the optimization of instruments for new biomedical applications has hindered the investigation of new opportunities. A major focus of CBORT will be to cultivate strategic research collaborations and respond to a pressing need for application-specific OCT instrumentation and hardware.

  • Bruce Rosen
    Massachusetts General Hospital

    The Center for Functional Neuroimaging Technologies is a Regional Resource located at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital. Working within the integrated multimodal imaging environment of the Martinos Center, the goal of the Resource is to develop and apply innovative neuroimaging technologies and techniques to enable closer examination of the human brain, and thereby contribute to better understanding of the brain in health and disease. To this end, we seek to develop new techniques and advance existing technologies for acquisition and analysis of functionally specific images of the working brain, with unprecedented physiological precision and spatiotemporal resolution. The research and development aims to improve and extend existing methods for non-invasive magnetic resonance image analysis and acquisition, electromagnetic source imaging, optical neuroimaging, and most recently, combined MR-PET neuroimaging. The Resource provides an essential interactive environment, within which an interdisciplinary team of highly skilled scientists, engineers, and clinicians with diverse expertise in multiple modalities and disciplines. The resource supports service use of the Center's facilities by neuroscientists throughout the country, provide extensive training opportunities for students, fellows, and staff scientists, and seek to advance the field of brain mapping through active dissemination of new knowledge and technology.

  • 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.

  • Daniel Vigneron
    University of California, San Francisco

    This Center will develop, investigate, and disseminate new hyperpolarized MR techniques, new 13C agents and specialized analysis open-source software for data reconstruction and interpretation. The Technology Research +amp; Development projects will leverage the extensive DNP facilities and experience of the project leaders to develop improved, robust hyperpolarized MRI methods. These technology developments will be driven by Collaborative Projects led by outstanding clinical and basic scientists who aim to use hyperpolarized 13C MRI to accomplish the scientific goals of their funded research. These technical developments will also be disseminated to the Service Project investigators for extramural feedback and then widely to the scientific community via a dedicated website and onsite training. This center will provide state-of-the-art training in this new metabolic imaging field and sponsor a yearly symposium focused on hyperpolarized MR technology development.

  • Ferenc Jolesz
    Brigham And Women'S Hospital

    The National Center for Image Guided Therapy (NCIGT), an NIH funded Biomedical Technology Resource Center, serves as a national resource for all aspects of research into medical procedures that are enhanced by imaging. Its common goal is to provide more effective patient care. The center is focused on the multidisciplinary development of innovative image-guided intervention technologies to enable effective, less invasive clinical treatments that are not only more economical, but also produce better results for patients. Through support from the National Center for Research Resources (NCRR), and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the NCIGT is helping to implement this vision by serving as a proving ground for some of the next generation of medical therapies.

  • 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.

  • Peter So
    Massachusetts Institute of Technology

    The MIT Laser Biomedical Research Center (LBRC) develops the basic scientific understanding and new techniques required for advancing the clinical applications of lasers and spectroscopy. To fulfill the significant and ever growing need for a more comprehensive and potentially non-invasive understanding of the human body, the LBRC merges optical spectroscopy, imaging, scattering, and interferometry techniques. Specifically, researchers at the LBRC study the biophysics and biochemistry of healthy and diseased biological structures from the subcellular to the entire-organ scale. For example, spectral diagnosis instruments based on near-infrared Raman scattering, intrinsic fluorescence, diffuse reflectance, and single light scattering provide complementary data on human disease. Combining these techniques into a single, multimodal instrument is applied for diagnostics in various organs, including cervix, oral cavity, Barrett's esophagus, artery, breast, skin, as well as for transcutaneous measurements of blood constituents. The LBRC has been and continues to be a pioneer in the field of developing novel optical probes for use under direct visualization or with endoscopes and biopsy devices.Similarly, new microscopy tools based on interferometry are designed and exploited for measuring cellular structures and their dynamics. In particular, these techniques provide the crucial and unique ability to non-invasively study cells in their native states at remarkably high spatial and temporal resolutions. Using these novel microscopy tools, the LBRC has conducted critical studies to elucidate the fundamental biology of diseases as diverse as malaria and multiple myeloma, and physiological processes such as cell growth and cell division. The interferometry concepts have also been vital in Center’s research efforts to develop optical tools for deep-tissue imaging while minimizing the adverse effects of light scattering or diffusion. Furthermore, the unique and powerful combination of the interferometric microscopy and vibrational spectroscopy tools adds a hitherto unexplored dimension to optical sensing by simultaneous probing of morphological and chemical information.A unique feature of the LBRC is its ability to form strong clinical collaborations with outside investigators in areas of common interest that further the Center's mandated research objectives. A major focus of these collaborations is to rapidly translate the novel photonic technologies introduced at the LBRC into the clinic and potentially into the field. Another focal point of the collaborations is to enable external researchers to exploit laser-based techniques for medical applications such as the spectral diagnosis of disease, investigation of biophysical and biochemical properties of cells and tissues, and development of novel imaging techniques.

  • Ron Kikinis
    Brigham And Women'S Hospital

    The Neuroimaging Analysis Center (NAC) develops image processing and analysis techniques for basic and clinical neurosciences. The NAC research approach emphasizes both specific core technologies and collaborative application projects.The core activity of the center is the development of algorithms and techniques for postprocessing of imaging data. New segmentation techniques aid identification of brain structures and disease. Registration methods are used for relating image data to specific patient anatomy or one set of images to another. Visualization tools allow the display of complex anatomical and quantitative information. High-performance computing hardware and associated software techniques further accelerate algorithms and methods. Digital anatomy atlases are developed for the support of both interactive and algorithmic computational tools. Although the emphasis of the NAC is on the dissemination of concepts and techniques, specific elements of the core software technologies have been made available to outside researchers or the community at large.The NAC's core technologies serve the following major collaborative projects: Alzheimer's disease and the aging brain, morphometric measures in schizophrenia and schizotypal disorder, quantitative analysis of multiple sclerosis, and interactive image-based planning and guidance in neurosurgery. One or more NAC researchers have been designated as responsible for each of the core technologies and the collaborative projects.

  • 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

  • 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.

  • Craig Malloy
    Ut Southwestern Medical Center

    The Southwestern NMR Center for In Vivo Metabolism exists to develop and apply new methods for analysis of metabolic networks in intact tissues, animals and human patients. The importance of understanding abnormal metabolism in common diseases such as cancer, diabetes and heart disease has long been appreciated. Because of constraints in technology, however, much of this research has been conducted in isolated systems where clinical relevance may be uncertain. Progress in magnetic resonance technology provides a foundation for major advances towards new ways of imaging metabolism in patients. These new techniques offer the advantage of imaging biochemical pathways without radiation. The focus of this Resource is to bring these technologies to a level where clinical research is feasible through the development of new MR contrast agents, NMR spectroscopy at high fields, and imaging of hyperpolarized 13C.

  • 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.

  • David Kaplan
    Tufts University Medford

    The Center is designed to advance the fundamental basis and clinical aspects of tissue engineering, to provide training for investigators and dissemination of scientific findings and new techniques. The expertise and facilities are focused on research, problem solving and training for the biomedical community through an integrated systems approach to the challenges in tissue engineering. A Service Core will enable and facilitate the implementation of solutions that would be impossible to attain from a single laboratory due to the diverse and complex skill sets.

  • 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.

  • 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.

  • Howard Halpern
    University of Chicago

    The major aim of this resource is the development of instrumentation, analysis techniques, spin probes and spin traps, and methodologies for imaging physiologically relevant aspects of tissue fluids, including high-resolution oxygen maps, with very low frequency electron paramagnetic resonance imaging (EPRI). Novel bridges and high-access, low-field magnet/gradient systems have produced physiologically relevant measurements and accommodate a number of resonant structures. The resource is a consortium among the University of Chicago, the University of Denver, and the University of Maryland.

  • 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 Hospital

    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.