Paul Christian Lauterbur, Ph.D. - US grants

nonmammalian vertebrate embryology; cell motility; cell cycle;

The long-term objectives of this program are to study normal and pathological physiology and function, so as to provide a better basis for the diagnosis and treatment of disease. Its specific aims are to develop the necessary appartus and techniques, and carry out the investigations, needed to bring magnetic resonance techniques to bear on the problems of alcoholism, nutrition, neuronal development, reproduction, and the diagnosis of disease.

This application is for partial funding for the purchase of a 50OMHz NMR spectrometer. The instrument is to be used for biomedical research, including NMR spectroscopy of solutions, cells, tissues and organs, and for NMR microscopic imaging of cells, tissues, and small organisms. Emphasis will be on spectroscopy requiring high sensitivity, such as studies of biopsy specimens and single retinae, on those requiring high spectral dispersion, and on investigations involving advanced techniques, such as multiple quantum editing, not otherwise available. The microscopic studies will focus on those applications, to cell cultures, tissues specimens and developing organisms, requiring the highest sensitivity, speed and resolution.

The University of Illinois will establish a Science and Technology Center for Magnetic Resonance Technology for Basic Biological Research. The Director of the Center will be Professor Paul C. Lauterbur. The goal of the Center is to develop the world's most advanced magnetic resonance imaging instrumentation technically feasible for the study of living organisms, individual cells, live animals, and humans and apply it to the most challenging problems in the life sciences, with a specific focus on brain physiology, anatomy, and function. Five institutions will contribute to the program in a coordinated fashion. These comprise the University of Illinois, the Lawrence Berkeley Laboratory, the Texas Accelerator Center, the University of Chicago, and the IBM Watson Research Laboratory. The two principal elements of the Center's program are: 1. The development of magnetic resonance imaging instrumentation covering a wide range of methodologies and technical approaches, including the design and implementation of a four Tesla, one-meter bore magnetic resonance imaging and spectroscopy system, advanced NMR microscopy instrumentation for both imaging and spectroscopy, further development of targetable NMR reagents for the study of perfusion and cell labeling, and the development of tools for mathematical modeling of complex physiologic processes. 2. The application of this instrumentation and its associated methodologies for the study of a wide range of the most challenging life sciences problems. Specifically it will be devoted to the understanding of complex biological processes relating structure, dynamics, and chemistry of the living brain. Development of the magnetic resonance imaging instrumentation will allow metabolic processes in living animals and humans to be studied noninvasively in real time, and its application to brain physiology, metabolism and function would mark a major breakthrough in this field. The ability to construct images using nuclei other than protons (such as phosphorus) will add a new dimension to new ways of studying biological problems. This Center will stimulate enhanced activity in education and in the development of human resources.

The broad, long term objectives of this application are to establish a nuclear magnetic resonance resource that will advance important areas of technological research and development, provide opportunities for collaborative research, and offer service and training to the basic research and clinical communities. Health care will benefit from improvements in knowledge of the structure and function of the body and brain and in medical technology. The specific aims are (1) to establish a 4 tesla whole-body imaging and spectroscopy resource and to evaluate its capabilities, (2) to develop the technology and applications of NMR microscopy, (3) to further advance the technology of relaxation dispersion measurements and to make improved instrumentation available to all those who need it, (4) to provide proven quantitative methodology for basic and clinical in vitro and in vivo NMR spectroscopy, (5) to provide a firm theoretical basis for microscopic imaging and contrast agent development, and (6) to develop new and improved methods of imaging, image processing, and image analysis and visualization for multidimensional NMR and other modalities.

New dendrimer-based agents for blood pool contrast and targeting to cancer cells have been developed and tested in vitro and in vivo. Continuing studies of gel-based agents have revealed complex dynamic and morphological changes. A comprehensive theory of their effects on water relaxation has been developed and is under test.

New implementations of constrained spectroscopic imaging have been tested, including a selective method that suppresses all 1H spectroscopic signals except those of lactate. It has been successful in phantoms, isolated muscles, and the in vivo gerbil brain. An application to localized diffusion anisotropy measurements has also been demonstrated.

DESCRIPTION (Adapted from Applicant's Abstract): The broad, long-term objectives of this project are to extend and perfect a general solution to the problem of localizing nuclear magnetic resonance signals using a-priori information. This information may be combined mathematically with other signals to give the spectra, concentrations, and properties of metabolites and other substances in all anatomical regions simultaneously, but in a much shorter time than required by conventional imaging, and with fewer and less stringent demands on the imaging system than those made by less general methods. Only modest additions to signal processing software are required. The investigators have developed methodologies for these ideas, including a compartmental modeling approach (the SLIM model) and a generalized series approach (GSLIM) for compartmental imaging. In extending this concept to dynamic imaging, they have developed two novel model-based methods called RIGR (Reduced-Encoding Imaging by Generalized Series Reconstruction) and its variant TRIGR (Two-Referenced RIGR) and DIME (Dynamic Imaging by Motion Estimation). The goal of this proposal is refinement of these techniques to the point where wide-spread in-vivo applications are possible. During this continuation the applicants expect to achieve the following specific aims: (1) to improve the software tools developed during the first funding period so that they are convenient and user friendly; (2) to continue to test, by simulation and phantom experiments, theoretical predictions concerning corrections for B1 inhomogeneities, resonance offsets and other experimental nonidealities; (3) to develop criteria for prospective evaluation of the most effective data acquisition conditions for a specific study, and the probable reliability of the data which will be obtained, and criteria so that retrospective evaluation of data reliability (random and systematic errors) can be carried out; (4) to develop schemes using navigator signals and (k,t)-space sampling strategies to determine theoretically and practically the extent to which motion compensation can be accomplished in SLIM/GSLIM, RIGR/TRIGR and DIME; (5) to develop schemes using RIGR and related methods to further define possible boundaries within compartments so as to enhance the localization of SLIM and GSLIM analysis; and (6) to demonstrate the use of SLIM and GSLIM for quantitative analysis of 1H and 31P spectra of animal tissues, including muscle, brain and liver, and to compare the results with those of existing techniques.

technology /technique development; magnetic resonance imaging; statistics /biometry; human tissue; computers; nuclear magnetic resonance spectroscopy; biomedical resource; biomedical equipment development; bioengineering /biomedical engineering; biological products;

MRI allows the measurement of processing temperatures in multiphase (macroscopic solid and liquid components) foods. This information is essential in testing the efficacy of heating during aseptic processing.