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Last modified: Wed May 29 10:33:19 PDT 1996
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The activities of the JMRM include:
- Scientific Meetings:
The annual scientific meeting of JMRM is held in fall. About 1200 scientists attend this meeting and about 400 papers are presented. JMRM95 is to be held in Tokyo and JMRM96 in Ooiso, Kanagawa Prefecture.
- Publication:
JMRM is publishing its official journal "Japanese Journal of Magnetic Resonance in Medicine" since 1981.
- Educational Activities:
MR Inroductory Course, MR Advanced Course, Workshops
(All pages are written in EUC code.)
Dr. Katsumi KoseMeasurement of unsteady flow using ultrafast NMR imaging, Spatiotemporal measurements of complex physical systems, Development of real-time NMR image reconstruction systems, and Processing methods for 3D NMR image data, NMR geometry
Dr. Sigeru Matsui
NMR Imaging of Solids
Our work aims to carry out and to support research on the structure and the dynamics of molecules, from small inorganic molecules to biological macromolecules, using nuclear magnetic resonance, circular dichroism, and other spectroscopic methods.Current NMR methods can determine 3-dimensional structures of biomolecules up to 20kD. We plan to develop new techniques to study the structures of larger molecules by designing new pulse sequences and by developing isotope labelling techniques. We will also cooperate with protein and nucleic acid biochemists to obtain three-dimensional structures of biomolecules.
You can ftp the NMR data files of Magnetic Resonance Research Group in KBSI.
Dr. Geoff P. Dobson(1) The application of classical thermodynamics to the study of metabolism and control of ion gradients and oxygen consumption in working skeletal muscle and isolated heart preparations with emphasis on work output, fuel utilization and intermediary metabolism.
(2) The role of the direct uptake and phosphorylation of plasma glucose to the replenishment of muscle glycogen following strenuous exercise compared to the C-3 compounds such as L-lactate and L-alanine.
(3) The biochemical nature of exercise-induced fatigued or traumatized skeletal muscle with particular emphasis on their relationship to plasma-tissue gradients of phosphate, free magnesium, pH and other ions.
(4) 31P NMR spectroscopy and its applicability to in vivo and whole animal comparative studies such as injury, exercise, hypoxia, anoxia or ischemia.
(5) D-lactate induced anaesthesia in the 48 hr starved rat and the role of free magnesium.
Dr Headrick is actively involved in the investigation of the intrinsic mechanisms orchestrating intracellular metabolism, cellular function, and tissue perfusion in the heart. Critical to normal function in the myocardium, the rates of energy production (ATP formation) and energy consumption (contraction/homeostasis) must be constantly balanced. Additionally, delivery of oxygen (and substrates) to this rapidly respiring tissue must also be tightly regulated. Unfortunately we understand very little regarding the mechanisms linking and regulating these processes. One possibility is that endogenous adenosine interacts with extracellular receptors to modulate coronary blood flow and intracellular substrate metabolism. Dr. Headrick’s recent research has focussed on the regulatory properties of this particular compound. In examining such regulatory mechanisms, in vitro and in vivo myocardium is studied using 31P-, 19F-, and 1H-NMR spectroscopy. The metabolic and functional effects of mooted regulatory compounds are probed with specific pharmacological interventions. Ultimately, these avenues of research will lead to a better understanding of the normal biochemistry and physiology of the heart, and will also provide us with a greater understanding of the processes involved in the pathogenesis of various disease states, including ischaemic heart disease, angina, and myocardial infarction.
Current research interests focus on the investigation of in vivo localised biochemical responses to oxidative stress processes, such as ischaemia-reperfusion injury (IRI) or exposure to xenobiotics, such as cyanobacteria toxins (microcystins), polyaromatic hydrocarbons (PAHs) and halogenated aliphatic hydrocarbons (halocarbons) in rat liver and/or kidneys utilising image-guided microvolume (20-200 l) 1H- and 31P-NMR spectroscopic techniques. The effect of free radical scavengers on the toxins that undergo free radical metabolism are also studied. Many of the xenobiotics studied are potent hepatotoxins and/or carcinogens.
These studies involve the use of a Varian 7 Tesla/ 18 cm horizontal bore spectrometer, with an imaging/spectroscopy bird-cage design (1H/31P) RF probe, and respiratory-gating. In addition, collaborative research with the Centre for Magnetic Resonance (Univ. of Queensland) involves the use of ESR spectroscopy in conjunction with spin trapping techniques, to study free radical intermediates from either halocarbon toxicity or ischaemia-reperfusion injury, both in vitro and in vivo.
Research interests centre around the characterisation of biochemical and physiological factors associated with development of irreversible tissue injury following traumatic brain and spinal cord injury. Magnetic resonance imaging and spectroscopy are used to monitor posttraumatic alterations in central nervous system metabolism particularly bioenergetic and ionic perturbations. Novel pharmacologic approaches to neurotrauma therapy are then developed to prevent or at least attenuate the development of neurological deficits.
Dr. Glenn KingProtein structure, protein-DNA interactions, protein engineering, Replication Termination Protein (RTP), blood proteins, muscle proteins, neuropeptides, leucine zippers, peptide toxins.
Cellular NMR, Rapid Membrane Transport measured by NMR, Magnetisation Transfer techniques, Complete modelling of metabolic pathways, Pulsed Field Gradient Diffusion measurments, Neural Networks applied to NMR diffusion data
Dr. Paul Callaghan
- Molecular dynamics and conformation under shear stress
(a) To study velocity profiles of flowing high polymer melts and solutions in both capillary and Couette geometry. To measure molecular dynamical properties in flow fields as a function of local strain rates with the purpose of elucidating the molecular origin of complex rheological behaviour in dense polymeric liquids.
(b) To study the internal translational dynamics of high-molar-mass random coil polymers in solution using pulsed gradient spin echo (PGSE) NMR. The time dependence and frequency dependence of both mean squared displacements and the velocity autocorrelation spectrum will be measured. To investigate local restrictions to polymer segmental motion. To test key signatures of the Doi-Edwards tube model of polymer reptation.
- Molecular translation in porous media
To investigate the influence of finite gradient pulse width and wall relaxation effects in the study of pore morphology using "q-space diffraction" PGSE-NMR. To develop an analytic theory of wall relaxation in rectangular barrier geometry. To investigate molecular self-diffusion in liquids absorbed in a range of porous solids, elucidating the relationship between morphology and motional restriction.
- Spectrometer Design/Construction
A new spectrometer is being developed for use in NMR imaging experiments involving a horizontal widebore superconducting magnet. This system will employ undersampling techniques and DSP technology. We are also developing new NMR probes, pulse sequences and analysis methods which enable the measurement of nuclear spin displacements and positions at the highest possible spatial resolution. In particular we are concerned to extend the resolution and range of contrasts available to NMR microscopy, applying these approaches to the study of biological tissue.
- NMR Processing and Analysis Software
New software is being developed for use in the analysis of multidimensional NMR spectroscopy. This software will be applied to NMR studies of protein conformation in the solution state. Special emphasis is being placed on the design of an appropriate user interface, and to this end, versions are being written for both Apple Macintosh as well as unix computers.
- Earth's Field NMR
An additional spectrometer has been designed and built for proton spin density measurements obtained using the Earth's magnetic field instead of the conventional high-field magnet. Two trips have been made to Scott Base in Antarctica, where this apparatus is used to study sea ice water and salt content, and obtain information on sea-ice structure using PGSE measurements. This work is done in collaboration with the New Zealand Antarctic Program.
Dr. F. Ebner
Corinne CerfWe work on the globular domain of histone H1 by 1H homonuclear and 1H-15N heteronuclear 2D NMR spectroscopy. The tertiary structure determination and comparison with the globular domain of histone H5 have been performed and will be soon published in Biochemistry (Cerf et al., 1994, in press). We are now interested in the study of the interaction of histone H1 with DNA.
Guy Lippens
Rene Wintjens
Dr. R. BlustDr. R. Dommisse
- High Resolution NMR Spectroscopy.
- In vivo NMR-Spectroscopy.
- In vivo NMR-Imaging.
Dr. E. Raman
- dynamical electron diffraction
- image interpretation
- image simulation
- image processing and reconstruction
- pattern recognition
- cognitive, auto adaptive processing, artificial intelligence
We are mostly involved with in vivo work and focus on the following application areas :
AGRICULTURE :
Non invasive localisation of sugar in sugar beet.
BIOLOGY :
Non invasive in vivo 31P NMR spectroscopy at the lateral muscle of fish (carp) in order to investigate the physiological condition of the animal under circumstances of stress and adaptation.MEDICAL AND PHARMACEUTICAL :
Non invasive in vivo imaging of the central nervous system of rats and mice in different animal disease models such as stroke and MS. As well morphometric as functional information is obtained on the progression of the disease and in some cases this can be used to evaluate therapeutic treatments.
VARIA : :
All sorts of NMR microscopical imaging for different purposes : in vivo mice brain, in vitro cochlea, in vivo invertebrates ...
Next to this we are engaged with the development of new techniques.
TECHNIQUES TO IMPROVE THE IMAGE QUALITY :
Improvement of the signal-to-noise ratio.
IMAGE PROCESSING TECHNIQUES :
Segmentation techniques applied on NMR images.
The NMR group at Roskilde University focus on several dynamic aspects of life :
- Dynamic NMR on hydrogen bonded and tautomeric systems
- Isotope effects on chemical shifts
- Dynamics and electrostatics in proteins and model peptides
- Metabolism in living cells
- Theoretical aspects of nuclear shielding
Les thèmes prioritaires concernent la détermination de la structure de protéines à l'état solide (rayons X) et en solution (RMN). Le centre s'attachera à développer de nouvelles méthodes d'analyse et s'efforcera de maîtriser toute la filière allant de la biochimie à la cristallisation passant par le marquage moléculaire, par les isotopes stables, par l'acquisition de données jusqu'aux simulations finales statiques et dynamiques des structures. Des collaborations sont initiées ou à développer dans le domaine des protéines constitutives ou régulatrices des systèmes contractiles, des protéines de la signalisation cellulaire et de leurs effecteurs, de peptides naturels, ou de systèmes isolés ou en interaction avec leurs récepteurs.
Michael NilgesThe primary aim of our group is to develop computational methods for solving protein structures from NMR data.
H.R. Kalbitzer
We work at the chemistry departement of the University of Ferrara. Although we are a part of the research group of organic chemistry directed by the Prof. Alessandro Dondoni, we perform nmr experiments for all the researhers of our University.Present research interests are in new synthetic methods, asymmetric and diastereoselective synthesis, and use of heterocycles as synthetic auxiliaries.
Silvio Aime
Mauro Botta
Mauro Fasano
Roberto Gobetto
Research activities include:
Cellular Pigments (Aime, Fasano)
Melanins from different sources and their metal ion adducts are investigated with solid-state NMR Spectroscopy. Particular emphasys is devoted to human midbrain neuromelanin, playing a fundamental role in the etiopathology of Parkinson's Disease.Coordination Compounds as MRI Contrast Agents (Aime, Botta, Fasano)
Design and characterization of lanthanide complexes as potential contrast agents for Magnetic Resonance Imaging; water proton relaxometry and high-resolution NMR Spectroscopy.Relaxometry of Hemoproteins (Aime, Fasano)
Water proton relaxometric investigation of the paramagnetic metal centre in wild-type and mutant hemoproteins from different sources. Ligand binding investigation via low-resolution (relaxometric) NMR techniques.
The NMR group activities concern both high resolution spectroscopy and microimaging. In the field of high resolution, the main research interests are focused on the structure characterisation of oligosaccharides and polysaccharides. Regarding microimaging the main research activities are related to the study of articular and growth plate cartilage.
Dr. A.F. Mehlkopf
- Overhauser Imaging
This project concerns a Dynamic Polarization Imager (DPI), based on the electron-nuclear Overhauser effect. Assuming that the correct free radicals are available, the Overhauser imager offers the opportunity of measuring Magnetic Resonance Images (MRI's) at very low magnetic fields. The complete open structure of the low-field magnets opens a whole new dimension towards interventional procedures.
In the first stage of the project the system requirements and architecture are formulated. In the second stage specific methods are developed, the effectiveness of Overhauser Imaging is evaluated and instrumentation is continued.
- Functional and Spectroscopic Imaging
In functional Imaging the functioning of tissues and organs is visualized. This can be done by following, with fast imaging techniques:
Spectroscopic Imaging concerns the visualization of biochemical compounds in humans and animals.
- Injected contrast reagents.
- Areas, prepared by RF irradiation.
- Effects of changing the metabolism or blood flow in the brain during enhanced activities.
- Signal Processing and Quantitative Data-analysis
Application areas are:
- Quantification of multi-dimensional in vivo NMR signals through model function fitting of time-domain data.
- MRI scan-time reduction through non-uniform sampling and edge-distribution modelling.
- Development of object-oriented in vivo NMR knowledge systems with domain knowledge of medical magnetic resonance applications and instruments.
- Development of MATLAB-based graphical user interfaces for integrating in vivo NMR quantification methods (The MRUI package).
Prof. R. Kaptein
- Introduction
The research of the Department of NMR Spectroscopy is focused on the elucidation of the molecular basis of protein-DNA recognition, using NMR spectroscopic techniques, which are in many cases specifically developed in the Department for answering specific questions on the nature and extent of the interacting groups and atoms. NMR spectra provide information on the geometry of direct neighbour groups in a molecule and on the spatial proximity of hydrogen atoms in the molecule. To obtain the necessary data, several kinds of mostly multi-dimensional NMR experiments have to be performed. These data can be transformed into realistic three dimensional molecular structures by extensive computer calculations, with methods adopted from computational chemistry techniques.
The NMR group under the direction of R. Kaptein has extensive experience in the area of structure determination of biomolecules using NMR spectroscopy. The group was involved in one of the first protein structure determinations by NMR (lac repressor headpiece, 1985) and determined the first structure of a protein-DNA complex (1987). Several contributions were made to the methodology of structural analysis by NMR (three-dimensional NMR, automated spectral analysis). The Restrained Molecular Dynamics method was worked out by the group in collaboration with W.F. van Gunsteren (then in Groningen).
- Protein-DNA Interactions
For many cellular processes the recognition of specific DNA sequences by proteins is a fundamental event, which lies at the root of e.g. the regulation of gene expression. The study of the interaction processes between proteins and DNA is therefore of crucial importance for the understanding of the fine-tuning found in nature for the cascade of processes in the cell leading to the predetermined effect. Interaction processes can only be understood on a fundamental and molecular level if the three-dimensional structures of the interacting biomolecules and the resulting molecular complexes are known under conditions which are close to their natural physiological environment. NMR spectroscopy is the method of choice for obtaining the experimental data that can be transformed into the desired three dimensional structures, because it is at present the only technique that in principle can give this information on biomolecules under natural physiological conditions.
At present the required detailed NMR spectroscopic information can only be obtained for relatively small biomolecules, up to a molecular mass of 20.000 Dalton, whereas protein-DNA complexes often are much larger. Therefore, usually the active domains of DNA-binding proteins are being studied. These domains are chosen in such a way that they retain the interaction mechanism of the complete molecules. The group has been highly succesful in this area in its study of the lac-repressor DNA binding domain or "headpiece" and its interaction with a DNA "operator" fragment. Similar studies are being done on lexA repressor, arc and mnt repressor and the receptors of the retinoic acid and glucocorticoid nuclear hormones, in order to establish the mechanism for the recognition of specific DNA sequences by proteins. At the moment it is already clear that several possible "structural motifs" are used in nature for specific recognition processes, but much has still to be learned about their detailed nature.
- Methodology
A major problem in the structure determination of proteins from NMR data is the unambiguous assignment of the spectra, which are very complex due to overlap of signals. One of the main research efforts of the group is therefore the development of new experimental techniques to alleviate this problem. The group has developed advanced (photo)chemically induced dynamic nuclear polarization techniques (photo-CIDNP) for the study of the surface structure of proteins and their interaction with ligands, thus providing information on the presence of certain amino acids in the active (binding) site of the protein.
Three- and four-dimensional NMR spectroscopy is another area that is being explored in order to alleviate the interpretation problem, and more specifically the ambiguity in the assignment of resonances. The succesful combination of various two-dimensional NMR techniques into non-selective three dimensional techniques has great promise for extending the molecular weight limits into the 30.000 Dalton area and furthermore, for the possible automation, at least partial, for the assignment procedures, one of the current bottlenecks in generating three-dimensional structures from NMR data.
Other important research topics involve the application of relaxation matrix methods in structure refinement, the use of NMR R-factors, the exploration and application (e.g. crambin) of direct NOE structure refinement methods, and automated secondary structure assignment.
Dr. R. Boelens
Dr. G. W. Vuitser
- Effects of environmental factors on chemical, physical and physiological processes in living systems studied by in vivo NMR spectroscopy and functional NMR imaging.
- The study of transport processes, osmoregulation, physiology and metabolism in healthy whole plants and plants stressed by infection, drought, temperature, xenobiotics and (heavy) metals.
- The study of bio-transformation and bio-activation of xenobiotics and agricultural chemicals in in vitro and in vivo systems.
- Study of metabolism and bio-energy conversion in micro-organisms, plant cells, plant embryos and plant organs.
- The study of mechanisms of plant virus infection.
- The study of mechanisms of plant fungus infection.
- Study of development and vitality of plant buds.
- Food chemistry, food physics, senescence, and internal quality of agricultural products and structure function relation of agricultural products studied by NMR.
- Multi-component analysis of biological systems in response of biochemical and environmental factors.
- Biophysical, biochemical and physiological characterisation of plant cells, plant embryos and micro-plants for in vitro multiplication.
- NMR studies of metabolic pathways and transport in biotechnological processes.
- MRI in studies on body development and composition of young layers.
Dagmar van Dusschoten (coordinator)
The Solid State Physics Department comprises:
- the laboratory of nuclear magnetic resonances,
- the laboratory of MR imaging in high and low magnetic fields,
- the laboratory of electron paramagnetic resonance and biophysics,
- the dielectric spectroscopy laboratory,
- the laboratory of quantum optics and laser physics,
- the laboratory of electron and tunneling microscopy,
- the liquid crystal laboratory.
The main subject of our research is the study of partially disordered condensed matter:
- liquid crystals (ferroelectric and antiferroelectric liquid crystals external fields and restricted geometries, volume stabilized ferroelectric liquid crystalline gels, polymer dispersed liquid crystals),
- incommensurate systems,
- proton and deuteron glasses and disordered ferroelectrics,
- fast protonic conductors,
- fullerene materials and glasses,
- thin films, surfaces, nanostructures and modulated phases,
- high temperature superconductors.
Dr. J. H. StrangeDr. M. E. Smith
Research has centred around application and development of solid state NMR techniques for the characterisation of structure and atmoic scale motion in materials of technological interest. Specific current projects include O17 characterisation of sol-gel formed materials including nanocrystalline oxides, catalyst supports and perovskites. There is interest in characterising highly disordered phases such as flash calcines and heat treated clay minerals. Ionic motion is also being studied by NMR relaxation with examples including the mixed alkali effect in glasses and transport in polymer electrolytes. Recently the interest has been extended to metallic alloys.
Dr. M. R. HalseNMR imaging and image reconstruction using computing techniques.
We are equipped with two Bruker spectrometers: DRX 400 and AMX 300 which can run a wide variety of 1D, 2D and multidimensional and multinuclear experiments.
" This chemistry group uses solution and solid-state NMR spectroscopy to probe molecular and electronic structure of materials, particularly those involving metal nuclei."
The QBI is part of the research center at the Saint Francois d'Assise Hospital and all of its members are also associated with various departments at Laval University. As the name suggests, the Quebec Biomaterials Institute is concerned with the development and characterization of biomaterials, and with assessing the effects of their implantation in the body. Magnetic resonance research at the QBI is focussed on detecting and characterizing the interactions between biomaterials and the body, by means of in-vivo MR imaging and spectroscopy in a 1.5 T GE Signa MR system. We are soon expecting an upgrade to enable us to do echo-planar imaging in the 1.5 T system and the Saint Francois d'Assise Hospital is to be one of the twelve sites world-wide to have one of the new GE MRT systems. This system has an open magnet design for MR guided surgery. If all goes as planned it will be operational in June 1996.Research Interests:
- The totally-implantable artificial heart project
- MR guided endovascular surgery
- The development and characterization of newer, safer, implantable biomaterials
Current Research Projects
- MR characterization of the interactions between implanted biodegradable biomaterials and the surrounding tissues. This is to determine whether or not the processes of encapsulation, healing, inflammation, etc. can influence the rate of drug delivery from biodegradable drug-delivery systems.
- Development of MR coils for monitoring biomaterials in the body
- Silicon-29 MR spectroscopy of silicone gel-filled implants
"The AMMRL is a group of individuals who are responsible for the operation of laboratories and instrumentation for magnetic resonance spectroscopy, including nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and magnetic resonance imaging (MRI). Our main goal is to assist one another in providing the best resources possible for research and applications using magnetic resonance spectroscopy, through exchange of information and experience."
The Department of Chemistry at Colorado State University, CSU, operates and maintains the Central Instrument Facility, CIF. The CIF has two basic instrument types, magnetic resonance spectrometers, MR, and mass spectrometers, MS. The instruments are available for use mainly by trained personnel at the University and by other academic collaborators or interested third parties after appropriate review.
"Our interests center around the use of animal models to study metabolic disorders, especially those disorders linked to oxygen utilization. We are concentrating on rodent models with a special interest in transgenic mice. These are some of the topics that interest us: "
- Brain Spectroscopy
- Tumor Spectroscopy
- High Resolution Imaging
- Echo Planar Imaging (EPI)
- Diffusion Imaging
The Center for In Vivo Microscopy, a NIH National Resource, is dedicated to the development and application of the technology of magnetic resonance microscopy to basic and applied science. The Center, located in the Bryan Research Building at Duke University Medical Center, is a collaborative effort between the Duke Department of Radiology, NIH, and the National Science Foundation. Additional funding for research comes from several pharmaceutical industries and the American Heart Foundation.Core research areas within the Center include:
- RF probe technology
- RF pulse and pulse sequences
- animal support and physiologic monitoring
- reconstruction/networking/visualization
Current collaborations with investigators throughout the life sciences include:
- theoretical and experimental verification of resolution limits
- hyperpolarized gas lung imaging
- molecular biology/embryology
- toxicology
- cerebrovascular research
- neurobiology
- 3D cardiac imaging
"MRI, EMR, and ICR spectroscopies. These fields share many conceptual (e.g., pulse sequences, heterodyning, quadrature excitation/detection, double resonance, two-dimensional FT methods, etc.) and technical (magnets, rf electronics, Fourier transform data reduction, etc.) aspects. For example, the Bloch equation formalism long established in NMR and EMR recently has been found to apply to the interconversion between cyclotron and magnetron motion in ICR, leading to methods for improving ICR signal-to-noise ratio and mass resolving power by factors of up to 100. Continued cross-fertilization between these fields is facilitated at NHMFL in the several ways through a broad-based external and internal user program."
"Our Department has one of the largest and best equipped MRI facilities in the country. Its clinical unit has two 1.5 Tesla superconducting Signa General Electric magnets, used for patient imaging and research, one 0.5 Tesla Signa used for outpatients, and the world's first open MRI for image-guided therapy. Two high-field imaging systems are dedicated to clinical research. A large number of inpatients and outpatients are seen seven days a week in the 12-room clinical area; the abnormalities range from the brain and spinal cord to the musculoskeletal and cardiovascular systems.Multifaceted clinical and basic research in the MRI division is supported by both federal and industrial funding. Projects are carried out in the Hospital and in nearby buildings, where additional high-field imaging and spectroscopic instruments are housed."
"The faculty and students associated with the lab are interested in the development of new imaging techniques and advanced applications of existing techniques to solve problems in medicine and biology."
- Functional Imaging of the Human Brain.
- In-vivo Spectroscopy.
- High Speed Imaging Techniques.
"During the past decade, tremendous advances in both NMR and computational methodologies have taken place. These advances now permit the determination of three-dimensional solution structures of proteins up to 20 to 30 kDa by NMR that are comparable to high-resolution crystal structures. Work is continuing to push this size limit up to 40 kDa, and it is clear that limited structural information, based on a specific site or structural feature, is available for proteins up to 50 kDa. These developments are extremely powerful and open up the possibility to investigate structural and dynamic properties of systems that may not be amenable to crystallography. The NMR approach is complementary to crystallography, and often one methodology can guide the other in structure refinement or in addressing some specific structural problem, such as the effects of site-specific mutagenesis. In addition to examination of systems that do not crystallize, NMR can reveal dynamic information about regions of macromolecular structure and conformation or structural changes that occur as a result of ligand binding. The investigation of solution properties and functions of native proteins or nucleic acids and the action of drugs developed against these systems may be examined in detail. Some excellent examples are referenced in the following profiles.The NIH is recognized world-wide as a leader in many of these developments and is enriched by a broad range of research groups participating in this field. The groups are complementary to one another and often share ideas and technology. There is also support and collaboration among other segments of the overall structural biology effort at NIH. Among these elements are the necessary molecular biology and protein expression required to pursue this type of research. This situation makes for a very vibrant and invigorating environment in which to pursue research interests that range from the development of new methodology to the structural elucidation of proteins, nucleic acids, and carbohydrates."
- Phase Encode Time Reduced Acquisition Sequence
- Echo Planar Imaging
"The Laboratory of Physical Biochemistry concentrates on using physical chemical methods,especially NMR, to elucidate structural and functional relations in biopolymers, principally proteins. The current major focus is on the structural biology of protein domains in intracellular signal transduction. Structures determined or in progress include SH2's, SH3's, SH(32), and PH domains. How natural ligands interact with these domains is also a major focus. A subsiduary focus is the development of NMR and related methods for structural biology. Synthetic chemical approaches are also used. The Laboratory strives to use chemical tools to answer biological questions.This site serves to provide access to public domain files of coordinates of measured structures, and related materials. The pointer may be to entries in the pdb or scop databases, when materials are deposited there, or may be to such data prior to database entry. "
"The purpose of this Page is increase the utility and capability of the of the SISCO family of Imaging NMR spectrometers."
"Our research goal is to develop a systematic understanding of chemical reactions in zeolites and on non-metal surfaces. Part of this effort is understanding the nature of acidity and basicity on surfaces as well as adsorbed reaction intermediates including carbenium ions and carbanions. Just as solutions chemists use NMR to follow reactions and characterize intermediates, we are using in situ solid state NMR to do the same in porous solid media. Our chemical experiments have frequently been outside the abilities of commercial instruments, so we develop our own instruments. Rapid temperature jumps and very high temperatures are achieved with our laser heater probe. MR imaging techniques in combination with spectroscopy will spatially profile chemistry in flow systems."
"The functional Magnetic Resonance Imaging (fMRI) laboratory, presently under construction with an estimated completion in November 1995, occupies approximately 1900 sq. ft. of the Ahmanson-Lovelace Brain Mapping Building. Like all other resources of the Brain Mapping Division, this instrument is dedicated to understanding the structure function relationships of the human brain.The facility houses a General Electric 3 Tesla magnetic imager, based upon a Signa 5.4 platform enhanced and optimized for neurological applications and activation studies. The very high field strength enhances both signal to noise ratio and contrast for fMRI applications and enables the collection of very high resolution structural images. The greater sensitivity of the high field unit to local changes in magnetic susceptibility makes practical the use of spin echo methods, whose sensitivity to macrovascular structures is less than that of the capillary system - thus biasing signal to the microvasculatur. The scanner is equipped for ultra-fast "echo-planar imaging" (EPI) through the inclusion of high performance gradient coils and amplifiers delivering over 3.6 gauss/cm in 125 microsec and 5 gauss/cm in 250 microsec, and rapid data processing that enables images to be acquired, processed and displayed at the rate of ten images per second. The hardware for the echo-planar component was developed in collaboration with Advanced NMR Systems of Wilmington, MA. With this unit we will be able to image complete cerebral volumes every 3 seconds. When not collecting echo-planar images, the device operates as a Signa unit (5.4 software level) including the standard suite of pulsing sequences, such as fast spin echo, SPGR, etc. In prototype performance, the system has a signal to noise ratio nearly double that of conventional 1.5 Tesla scanners, facilitating high resolution image data collection. The acquisition system is supported by a network of high performance DEC Alpha workstations equipped with data analysis and display software. It will shortly include a Macintosh 9500-based file server with 100baseT ether connections.
Cognitive science applications necessitate a variety of behavioral studies devices requiring special modification for use within the magnetic field. The fMRI unit is equipped with a stimulation and response recording environment consisting of a Macintosh computer system with its video output directed to an LCD projection system, devised by Resonance Technology Corporation, to be used within the instrument. Non-magnetic joystick and keypad devices will emulate keypresses through an electrically-isolated low voltage DC relay system connected to the Macintosh ADB port. An electrostatic pointing device (ALPS, inc.) allows mouse control from within the instrument. For experiments that require it, the lab is also developing the acquisition of cortical EEG's, electro-oculograms, electrocardiograms and pulse (using a photoplethysmograph), allowing synchronization of the imaging to these physiological signals and computer-based correction of the fMRI responses for physiological fluctuations."
"Our laboratory is involved in structure determination of biologically important molecules using NMR. The purpose of this work is to better understand the fundamental processes of biology and to design drugs. We determine molecular structures by analyzing NMR spectra. Using the experimental NMR information, we calculate structures with the aid of restrained molecular dynamics (simulated annealing), distance geometry or, less commonly, restrained Monte Carlo methods. The major goal of our research is to improve the capability for determining high-resolution structures in solution of proteins, DNA and RNA or complexes involving proteins and nucleic acids. One growing area of research is to elucidate the dynamic structure of biological molecules -- many biological processes entail conformational flexibility. We continue to improve methodology and apply it to larger molecules. Applications include DNA gene targets, anti-sense DNA, RNA, DNA-RNA hybrids, proteins which regulate gene transcription, toxins, and cellular receptors. The subjects for structure determination are often chosen as potential targets for subsequent drug design or as models for drug design."
Clinical ProjectsTechnique Development
- Alzheimer's Disease and Aging
The goal of this project is to accurately detect, diagnose, and measure the progression of Alzheimer's disease (AD) using MR spectroscopic imaging (MRSI) and quantitative MRI. Previous work from this lab showed that MRI together with MRSI discriminates AD patients from elderly controls better than either measure alone. Multiplane proton MRSI will be used to investigate metabolite changes in various brain regions which are known to be affected in AD.- Multiple Sclerosis
- Epilepsy
- Substance Abuse
Alcohol, nicotine, cocaine- HIV
Animal Studies
- Multiplane Proton MR Spectroscopic Imaging
Development of multiplane 1H spectroscopic imaging is being carried out in the Siemens Vision spectrometer. Current acquisition method obtains 3 slices, with circular k-space encoding (36 points diameter), in approximately 30 minutes.- Data Processing for 1H MRSI
If 1H MRSI data is acquired without some form of supression of subcutaneous lipids, the resultant MRSI data is severely contaminated by the intense lipid signal. By application of the Papoulis-Gerchberg algorithm an extrapolation of the k-space data for the lipid signal can be obtained.- Automated spectral analysis of 1H MRSI data is being developed using parametric modeling approach.
- Phosphorus Spectroscopic Imaging
- RF Coil Development
Double tuned, 31P, 1H, quadrature coil.- Optimized RF Pulses
- 1H Metabolite Changes with Brain Injury
The time couse and distribution of changes of NAA, Cre, Cho are being studied following focal administration of kainate in the rat. Results will provide information on the evolution of tissue damage in epilepsy, and demonstrate the role of 1H MRSI for detection of the epileptogenic focus, and secondary regions.- Cerebral Ischemia
- "Brownian Strings"
- Multimodaility Imaging
- Feature Recognizing MR
- Brain Pulsation
- Hemiparetic Brain
- Focused MRI
- FR vs. SVD MRI
"The goal of the Center for Structural Biology is to increase understanding of biological function by determining the structures of large biological molecules and supramolecular assemblies. This is accomplished using advanced spectroscopic, diffraction, and imaging techniques (nuclear magnetic resonance, optical microscopy, electron microscopy, and X-ray crystallography). This information is related to cellular structure and function; then to the morphology and physiology of the whole organism. The Center provides a framework for technological research, development, and collaboration to address structural studies of significant biological problems. "
"This World Wide Web server provides a focal point of scattered sources of information that are of interest to the NMR community."
"...the group is interested in the constraints imposed on brain architecture and function by the needs for metabolic support of neuronal activity."
"Work in the area of human-computer intelligent interaction is closely related to the efforts described above."
"The MRI Group's work with contrast agents for physiological monitoring has led to the development of magnetically-labeled particles of so-called "intelligent gels," similar in size to biological cells, that respond to electric fields and other environmental influences by changing their sizes, shapes, and NMR properties."
Despite the recent surge of ideas for processing magnetic resonance data, very little effort has been made to make them accessible to the general MR community. Very often, using an algorithm to process data requires developing programs from scratch based on the literature or, at best, tailoring programs in their original form obtained from the author to apply them to specific problems. This process is made especially difficult by the multitude of operating systems and hardware used by researchers and the relative complexity of the newer reconstruction techniques. All too frequently, it seems, good ideas are lost in the literature because they are not readily applied.V is our attempt to provide a general-purpose software system for magnetic resonance imaging and spectral reconstruction, processing, and analysis. It is intended not to be a comprehensive package including every known algorithm, but rather as a basic package including some of the popular reconstruction tools. Moreover, it is largely aimed at providing a means for distribution of functions among researchers in the MR community. V has been designed so that software development does not require an immense knowledge of the internal operation of the program. Rather, the programmer can develop individual functions indepently of V. After validation and testing, these functions can be incorporated into the V program with minimum modification.
"The Biomedical Magnetic Resonance Laboratory (BMRL) provides facilities, equipment and training for research on nuclear magnetic resonance imaging, spectroscopy, and relaxometry, and for their applications in biology, medicine, and other fields."
"The Nuclear Magnetic Resonance Laboratory is responsible for maintaining the high field NMR spectrometers, training users, providing spectra on a service basis, and assisting users with design, execution, and interpretation of NMR experiments."
" Professor Harbison's area of interest is Nuclear Magnetic Resonance (NMR) both of the conventional, high-field variety, and also zero-field NMR. The advantage of zero-field NMR is that allows research on a much larger set of nuclei with spin quantum numbers of 1 or greater, which are not accessible by ordinary NMR methods; zero-field NMR can be used to study most of the elements in the periodic table, including many which are of interest to biological chemists.Iodine, copper, and zinc are not normally thought of as 'NMR nuclei', but can be observed by NMR at zero-field. While the technical problems are greater than for high-field NMR, they can be solved, and Dr. Harbison's group recently obtained the first ever zero-field NMR spectrum of a single atomic species in the active site of an enzyme (63Cu in reduced superoxide dismutase, above).
Dr. Harbison's high field work includes solid-state NMR studies of biological and non-biological systems. He recently completed structure determinations of the intercalation site of several DNA binding drugs, and also of Kevlar, the ultra-strong polymer used in bullet-proof vests and Olympic bicycle wheels. He also has interests in experimentally measuring molecular dynamics in crystals and in biomolecules in the solution, in theoretical methods for treating NMR spin relaxation in complex molecules, and in developing inverse Laplace transform NMR methods, an alternative to Fourier transform methods which can be used, to observe chemical exchange between species with the same NMR frequency, for example, diffusion of water across cell membranes in living systems. "
"A new NIH sponsored Resource is being established at the University of Pennsylvania for the development and application of high-field solid-state NMR spectroscopy for the study of proteins. The instrumentation of the Resource includes two home-built NMR spectrometers capable of the full range of multiple-pulse, multiple-resonance, and sample spinning experiments that constitute high-resolution NMR spectroscopy. One spectrometer has a wide bore (89mm) 12.9T Magnex magnet with a 1H resonance frequency of 550 MHz. The second spectrometer currently under construction has a mid-bore (62 mm) 17.6T Magnex magnet with a 1H resonance frequency of 750 MHz. The main area of applications in our research laboratory is determining structure and dynamics of membrane proteins. Also available for collaborative studies are 360 (8.45T) and 400 MHz (9.38T) wide-bore magnets."
"The regional resources of the MMRRCC develop new methods for reliable quantitative assessment for physiological parameters from non-invasive magnetic resonance and optical measurements."
"NMR Concepts is a non-profit, tax-exempt school that was founded in direct response to requests from the NMR community. Since NMR Concepts held its first course in 1980, nearly 3800 people have attended NMR Concepts courses. Attendees at our courses have come from over 530 companies, government organizations, medical, and academic institutions throughout the world. Their NMR backgrounds vary from a few months to over thirty years experience. The contents of our courses are continually reviewed and updated to maintain the superior quality that NMR Concepts is known to deliver.Dr. Daniel Traficante, while serving as the director of the NMR Laboratory at Massachusetts Institute of Technology (MIT), developed a series of lectures concentrating on the fundamental concepts of NMR spectroscopy. From these lectures, he later developed a five-day course and offered it to the scientific and technical community in December 1980. There followed requests for courses in electronics, interpretation of 1D NMR spectra, 2D NMR, and other courses. All of these courses were developed by Dr. Traficante in direct response to the needs of the NMR community. NMR Concepts faculty are selected from industry and academia, and from foriegn countries when appropriate. Their scientific knowledge, coupled with their skills as educators, gives each course the necessary breadth and depth required to address the participants' needs.
The NMR Concepts administrative staff works as a unit to create an atmosphere conducive to learning. This includes attention to all details and peripherals that could detract from the learning experience. In addition to sending detailed correspondence to each attendee, administrative staff also telephone each attendee one week before the course to review travel plans and course schedule, and to answer any questions. Hence, attendees are free to focus on NMR and maximize their learning experience.
As an outgrowth of the courses, in 1989 NMR Concepts created Concepts in Magnetic Resonance, a unique educational journal, now published by John Wiley & Sons. Dr. Traficante remains Editor-in-Chief. The goal of this publication is to present both old and new topics in a form that is easily understandable to students and researchers. Many research supervisors have assigned every article as required reading for their students. "
"... our research is focused primarily on the engineering aspects of Magnetic Resonance Imaging. It includes the design and development of imaging instrumentation and improvements to image acqusition and signal processing techniques. In addition, we are actively pursuing the development of automated imaging processing techniques which implement functional MR imaging by allowing automated extraction and quantification of anatomical and physiological data from function-specific MR images."
"Our special interest is the determination of biomolecular structure using multidimensional NMR."
"Our goals are to elucidate the solution structure of cardiac troponin C using a combination of homonuclear and heteronuclear two and three-dimensional NMR. We intend to map the sites of protein-protein interaction between cTnC and cTnI using a combination of NMR, mutagenesis and selective use of paramagnetic probes."
Stuart S. BerrMy lab curently has several ongoing research projects. All of these projects involve either the development or utilization of magnetic resonance (MR) imaging and spectroscopy techniques.
The largest part of our effort is directed towards the quantification and identification of plaque constituents in atherosclerosis using magnetic resonance imaging techniques. We have examined the magnetic resonance properties of plaque constituents and of excised arterial specimens in order to elucidate the MR imaging conditions necessary to distinguish lipid rich tissue from hemorrhage, smooth muscle tissue, calcification, and lumen. We have used this information to modify MR pulse sequences that have allowed us to image the carotid arteries and aortas of a number of normal and diseased volunteers in vivo. Our hypothesis is that these images can be used to identify thrombolytic prone plaques, which are the cause of the majority of the most severe acute clinical events including heart attacks and strokes. We also hope to be able to follow the effectiveness of drug/diet regimes for individual patients.
Another area of research involves the use of novel chemical agents in the detection and treatment of tumors. An example of one such agent is Mn-BOPP, developed by Dr. Stephen Kahl (UCSF). Mn-BOPP contains manganese that serves as a T1 relaxation agent for MR imaging. It also contains 40 boron atoms per molecule that can be used as a neutron capture therapy agent to kill tumor cells. We are working in conjunction with investigators at UVa in Nuclear Engineering.
Funding for this research has been provided by grants from the Pratt Foundation.
Magnetic Resonance Imaging (MRI) is now a widely accepted clinical imaging modality for many radiologic procedures. However significant improvements continue to be introduced to enhance the nature of the image contrast, the speed of data acquisition and the range of clinical applications. These include new pulse sequences to encode tissue perfusion and diffusion to assess stroke and brain function, faster acquisitions to permit breathhold imaging of the abdomen and the heart and improved efficiency coils for musculoskelatel applications. There is also a need to reduce costs by simplifying the MRI procedures, and comprehensive 3-dimensional imaging provides the possibility to use one acquisition for subsequent multiplanar viewing.
The increased number of different image contrast types is driving the need for image analysis that is able to present to the physician the complex data in a simple visual format. Fortunately the costs of effective image workstations that can fuse and merge multiple images is now at a practical point that routine clinical use can be envisioned.
Our research is directed towards improved methods of both 2D and 3D MR image acquisition for both diagnosis and surgical planning and development of specialized coils for improved musculoskelatel imaging. We have patented a novel fast 3D MR imaging technique (3D-MP RAGE) that has been used for a wide range of applications.
Erik Fernandez, Ph.D
Denise Hinton, Ph.D
The research program in Magnetic Resonance Imaging (MRI) focuses on the development of MRI techniques to meet the research and clinical needs of the medical and biomedical community. Studies concentrate on both the theoretical analysis and optimization and the experimental implementation and testing of various methods. Recent research projects have included the development rapid imaging techniques, the optimization of image signal-to-noise and contrast-to-noise ratios, and the analysis of image artifacts. Equipment includes three 1.5 Tesla whole-body imagers, a 4.7 Tesla, 40cm bore imager/spectrometer, and several computer workstations.
The unifying theme of our projects is the application of magnetic resonance imaging and spectroscopy to dynamic questions. These include questions of metabolism, microcirculation and flow. In attempting to obtain high spatial and temporal resolution, we often find that our data sets are four-dimensional and that acquisition times are unacceptably long for routine use. Thus, we search for shortcuts which maintain resolution while shortening acquisition times. Recently, we developed a technique which allows three-dimensional data sets to be acquired in less than 30 seconds (a sixteen-fold improvement), and are applying this to the problem of breast-cancer diagnosis, where sub-minute resolution is adequate. Hardware improvements in the next year will allow imaging in several seconds; coupled with our technique, it will be possible to follow processes occurring on the sub-second time scale.
The number of images generated by these techniques can be overwhelming; we are exploring how best to gather information spread among many images to form a smaller set of images which better depict dynamic processes.
"Research in Dr. Klevit's laboratory is directed towards an understanding of molecular recognition, with an emphasis on protein-protein and protein-DNA interactions."
"This home page will attempt to include links to other well developed resources which are relevant to nuclear magnetic resonance spectroscopy and imaging."
"The current database contains NMR chemical shifts derived from proteins and peptides, reference data, amino acid sequence information, and data describing the source of the protein and the conditions used to study the protein. ... Our goal is to enlarge the content of the database to include a majority of the quantitative data produced in an NMR study of a protein and information describing the experiments and processes used to obtain these data."
The Center's Research focuses on:
- MR angiography
- MR mammography
- Image Segmentation
- Functional Brain Imaging
- Functional Renal Imaging
- Development and applications of NMR techniques for human imaging; the design and study of new NMR techniques and instrumentation for medical diagnostic applications. Two recent emphases has been the development of echo planar techniques for "snap shot" imaging on our 1.5T research scanner: and the development of MRI methods for functional brain imaging based on oxygenation susceptibility effects.
- Applications of functional MRI in neuroscience: language, reading, attention, memory, visual processing, sensorimotor systems.
- Methods of MRI data analysis.
- Development of NMR microscopy; studies of the performance limits of microscopic imaging; development of applications of MR microscopy. Development of q-space imaging of molecular displacements to assess microstructure and water transport. This work is being pursued on two 7.0T systems in our laboratories.
- Proton NMR relaxation mechanisms in heterogeneous media; cross-relaxation and magnetization transfer in biological tissues and tissue models.
- Studies of diffusion and restricted diffusion in tissues and other media. Development of applications of Diffusion weighted imaging (DWI). Causes of changes in DWI.
- Studies of the design factors and mechanisms of NMR contrast agents, including paramagnetic, superparamagnetic and susceptibility agents.
- Quantitation of flow and perfusion by NMR imaging; studies of turbulent and complex flow by NMR. Relationship of changes in MR measured flow and metabolic markers to muscle exercise in normals and patients with peripheral vascular disease.
- Improved methods of NMR spectral imaging and spectral quantitation; improvements in NMR signal processing; image restoration, segmentation and analysis.
- Development of spin tagging and phase contrast methods for cardiac imaging.
- High resolution multinuclear (31P , 1H and 13C ) spectroscopy in vivo for studies of metabolism; Development of 19F NMR imaging; assessment of regional oxygen tension.
- Applications of NMR imaging to non-medical problems: measurement of flow in porous media; relaxation and diffusion in compartmented systems; measurement of radiation dose distributions in irradiated gels by MRI.
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callahan@pmel.noaa.gov