Last update: 10. Apr 01 15:41
5th International Conference on Magnetic Resonance Microscopy
German Cancer Research Center, Heidelberg, Sept. 5 - 9, 1999
Abstracts for the Educational Session
Fourier Imaging: Spatial Resolution and Contrast
Bernhard Blümich
Magnetic Resonance Center MARC, RWTH Aachen, D-52056 Aachen
NMR is known to the public because of its significance as a diagnostic imaging method in medicine. In competition with X-ray tomography, NMR imaging provides unique features which are unsurpassed by other imaging methods. Although the spatial resolution often is less than microscopic, the possibilities to achieve contrast in soft matter and to map functional processes in a noninvasive fashion are most striking. These features are also of benefit in materials science and other non-medical fields of research, process and quality control.
Following a short introduction to NMR the concepts of space encoding and spatial resolution are introduced along with k space, the space which is obtained by inverse Fourier transformation of functions in real space. Most NMR imaging experiments are carried out in Cartesian k space. These imaging methods are referred to as Fourier imaging. Different basic methods of Fourier imaging are reviewed for imaging of liquids and soft matter as well as for solid-state imaging of rigid matter, where special techniques are required to cope with strong nuclear spin interactions, which are absent in most liquids. Particular attention is paid to different ways of introducing contrast. The various techniques addressed in the lecture are illustrated with examples from non-medical NMR. The presentation concludes with a short overview of single-sided NMR for process and quality control.
Literature
P. T. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy,
Clarendon Press, Oxford, 1991.
R. Kimmich, NMR Tomography, Diffusometry, Relaxometry, Springer, Berlin, 1997.
M. T. Vlaardingerbroek, J. A. den Boer, Magnetic Resonance Imaging, Springer,
Berlin, 1996.
B. Blümich, NMR Imaging of Materials, Clarendon Press, Oxford, in press.
B. Blümich, P. Blümler, R. Botto, E. Fukushima, Spatially Resolved Magnetic Resonance,
Wiley-VCH, Weinheim, 1998.
B. Blümich, W. Kuhn, Magnetic Resonance Microscopy, VCH, Weinheim, 1992.
J. B. Miller, Progr. Nucl. Magn. Reson. Spectrosc. 33, 273 (1998).
Biomedical NMR Imaging
Axel Haase
Physics Institute, University of Würzburg, 97074 Würzburg, Germany
NMR imaging has tremendous clinical importance, but it is now well-established that this technique has great potential in all areas of medicine and biology. Compared to other imaging modalities, NMR is non-invasive and has no harmful side-effects. NMR imaging is applicable to human studies, large but also very small animals, embryos, organs and cell cultures. In addition, plant physiology is a further area for biomedical NMR imaging. However, it must be noted that other imaging techniques exhibit a higher spatial resolution (e.g. X-ray), have shorter measuring times (e.g. ultrasound) and provide a deeper investigation of the biochemistry of tissues (e.g. positron emission tomography). The great advantage of NMR compared to other imaging techniques is that many aspects of the live tissue can be investigated using one experiment: characterization of the anatomy, function and biochemistry of the tissue. NMR imaging is a so-called "one-stop-shop".
The lecture will be limited to 1H-NMR imaging, other nuclei will be covered in another presentation. Furthermore, only some important applications of 1H-NMR spectroscopy in combination with imaging will be presented.
The spatial resolution in biomedical NMR-imaging is poor compared to other methods although some parameters (NMR relaxation times, chemical shift or J-coupling) in NMR provide very local information on a nanometer scale. The typical volume of an image element (voxel) in (human) medical NMR imaging is 1 mm3 while for small animals (and plants) it may reach 10-5 mm3. This later regime is the area of "NMR microscopy" which is one of the major topics of this conference. This wide range in spatial resolution is only possible with major hardware changes. Medical NMR imaging is entirely performed using static magnetic field strengths of below 2.0 T and magnetic field gradients of up to 40 mT/m. NMR microscopy on small animals, organs, etc. needs high magnetic field strengths up to 17.5 T and gradient strengths of more than 1000 mT/m. The main limitation in biomedical NMR imaging is the limited signal/noise ratio (note: the NMR signal is linearly dependent on the voxel volume!), technological limits (maximum magnetic field strength and gradient strength is dependent on the present state of magnet technology!) and safety concerns.
The most important topic for the biomedical application of NMR imaging is the image contrast. There exists an intrinsic image contrast due to the interaction of NMR properties of the tissue, image sequences and scan parameters. For the beginner in this field, NMR image contrast is the most confusing issue. The NMR signal intensity depends on intrinsic parameters (e.g., relaxation times T1, T2, spin density, magnetic susceptibility, bulk flow, perfusion, oxygenation, temperature, etc.), on the type of NMR experiment (spin-echo, gradient-echo, stimulated-echo, and their timing parameters), and on the NMR instrument (magnetic field strength, radiofrequency coil, stability, etc.).The dependencies are well understood and should be kept in mind in all biomedical applications. In addition, it is important that true biological information can be obtained, when these parameters are measured quantitatively (e.g. perfusion, oxygenation, temperature, blood flow, etc.). Furthermore extrinsic contrast can be obtained using contrast media. Here abnormal perfusion and tissue-specific information can be detected, like the detection of the breakdown of the blood-brain barrier.
A prerequisite for all biomedical NMR imaging applications is the use of a fast imaging technique. For example, it is needed to "freeze" cardiac motion which can be as fast as 600 beats/min in mice. In many applications, three-dimensional image acquisition, determination of quantitative parameters and functional information is needed. In order to keep the total experimental time as short as possible, some kind of fast acquisition is applied. During the last two decades, a large number of fast NMR imaging techniques was described. The lecture will summarize the important advantages and disadvantages of the different methods. The improvement of fast imaging methods is still going on. Recently, a dramatic decrease of the image acquisition time could be achieved using new hardware developments, e.g. phased-array coil technology.
Dramatic improvements were described in biomedical NMR imaging in the area of flow imaging and applications to angiography and the determination of perfusion. The method and applications to animal studies will be demonstrated in the lecture.
These methods were first described and applied in animal studies and clinical examinations. However, NMR imaging is not only limited to this area. Several groups have successfully applied NMR imaging to the study of plant physiology and function. Important studies, techniques and experimental difficulties for NMR of plants will be summarized in this lecture.
Q-space and beyond
Paul T. Callaghan
Institute of Fundamental Sciences, Physics, Massey University
Palmerston North, New Zealand
The use of pulsed magnetic field gradients in order to encode spin magnetization for position or positional displacement leads to a variety of spatial coherences in the spin phases, each coherence being manifest in a characteristic diffraction pattern, whether in k-space or q-space. These phenomena, which are sensitive to different temporal moments of the gradient waveform, range from the original Mansfield-Grannell position diffraction, through diffusive and flow diffraction, to diffraction patterns which arise due to dispersion in a heterogeneous velocity field. Each of these will be described and examples of their use given.
In fact the idea of applying single gradient pulses to phase encode for position, or double gradient pulses to phase encode for displacement, can be generalised to provide pulse sequences which are sensitive to other categories of motion. One approach is to use steady time-varying gradients which can then probe the frequency domain of motion. Another approach is to use the double PGSE sequence, which is especially effective in encoding for changes in motion. In particular the double Pulsed Gradient Spin Echo NMR experiment may be used to study stochastic processes in dispersive flow. We give a detailed analysis of this type of experiment, illustrated with the example of Poiseuille flow in a pipe.
1. Diffraction effects
1.1 Mansfield and k-space-position diffraction.
1.2 q-space and position correlation (diffusive) diffraction.
1.3 Interconnected porous media, diffusive and flow diffraction.
1.4 Finite pulse duration effects.
1.5 Dispersion and the gaussian limit.
2. PGSE NMR with generalised Gradient waveforms and restricted diffusion
2.1 Theoretical treatments - gaussian assumption.
2.2 Impulse-propagator formalism
2.3 Frequency Domain PGSE NMR
3. Dispersion and restricted diffusion
3.1 Stochastic fluctuations and dispersion
3.2 The double PGSE NMR experiment
3.3 Velocity correlation and stochastic displacement correlation
3.4 Taylor dispersion in pipe flow
Imaging of X-Nuclei
Gil Navon
School of Chemistry, Tel Aviv University, Tel Aviv 69978, Israel.
The talk will review various aspects of MR imaging of nuclei other than protons ("X-nuclei"). The review will start with direct imaging of high sensitivity X-nuclei, i.e. hyperpolarized noble gases and fluorine. Then methods of indirect detection of X-nuclei will be described. In these methods, proton images reflecting the distribution of the X-nuclei are obtained. Finally, MRI and multiple-quantum filtered (MQF) MRI of quadrupolar nuclei will be described.
The best known case of X-nuclei imaging with sensitivity comparable to that of protons is the case of the hyperpolarized noble gases – 129Xe and 3He. The basic principles and few examples will briefly be described.
The relative sensitivity of 19F is very close (83%) to that of protons. Fluorine is not a natural constituent of biological tissues. However it is present in many drugs. Consequently 19F NMR and MRI are useful for the study of the pharmacokinetics and the spatial distribution of fluorine-containing drugs.
Indirect detection of X-nuclei: spin polarization induced NOE (SPINOE) and proton imaging of oxygen-17 (PRIMO).
Quadrupolar nuclei. Examples will be given for 23Na and 2H imaging. The method of double-quantum filtered (DQF) MRI will be described. In this technique a new contrast mechanism is obtained, utilizing the residual quadrupolar interaction resulted from the anisotropic motion of molecules in ordered biological tissues.
EPR in Viable Systems
Harold M. Swartz
EPR Center for the Study of Viable Systems; Department of Radiology,
Dartmouth Medical School, Hanover, NH 03755
EPR (ESR) is a magnetic resonance technique that is similar in many ways to NMR, but is based on the magnetic properties of the electron rather than a nucleus. Because the magnetic moment of the electron is about 700 times larger than that of the proton, on a per spin basis EPR is considerably more sensitive. Because electrons usually are paired and therefore have no net magnetic moment, EPR features absolute specificity for species with unpaired electrons (paramagnetic species). The usual types of such molecules that are important in biomedical studies are free radicals (both naturally occurring and, especially, synthetic free radicals) and paramagnetic metals.
One of the most important and biologically useful aspects of EPR spectra is their sensitivity to the environment surrounding the unpaired electron. Like NMR this includes spectral splitting due to the presence of other magnetic species, especially nuclei with net magnetic moments. In addition, the EPR spectra, especially those spectra with hyperfine structure due to splittings from nuclei are changed significantly by many parameters of interest such as pH, molecular oxygen, charge, and motion of the molecule on which the unpaired electron is located. Many of these parameters are both important and difficult to measure by other means.
The three most important potential limiting factors for the use of EPR in biological systems are the typically short relaxation times of the unpaired electrons, the high frequency needed for high sensitivity, and the lack of naturally occurring high concentrations of paramagnetic species. When the biological sample is a living animal, additional problems may arise because of the presence of physiological motions.
Recently many of the potential technical limitations have been overcome and EPR studies of intact biological systems have become increasingly reported. The results indicate that this technique can provide very useful information that often is different or better than that obtainable by other techniques.
The presentation will review briefly the principles of EPR spectroscopy, consider in more detail the types of information and techniques that provide useful data, and then survey the areas in which EPR spectroscopy is being used successfully in experimental animals. The aim is to provide participants who have a background in NMR with sufficient information and orientation to obtain full benefit from the presentations in the regular sessions that use EPR techniques.