Nuclear magnetic resonance technology for medical studies.

Nuclear magnetic resonance proton imaging provides anatomical definition of normal and abnormal tissues with a contrast and detection sensitivity superior to those of x-ray computed tomography in the human head and pelvis and parts of the cardiovascular and musculoskeletal systems. Recent improvements in technology should lead to advances in diagnostic imaging of the breast and regions of the abdomen. Selected-region nuclear magnetic resonance spectroscopy of protons, carbon-13, and phosphorus-31 has developed into a basic science tool for in vivo studies on man and a unique tool for clinical diagnoses of metabolic disorders. At present, nuclear magnetic resonance is considered safe if access to the magnet environment is controlled. Technological advances employing field strengths over 2 teslas will require biophysical studies of heating and static field effects.

Positron tomography and nuclear magnetic resonance imaging.

Noninvasive imaging methods for medical diagnosis and biological investigations, have evolved from qualitative radiological techniques to quantitative methods of measuring biochemical and physiological processes in human body. In particular, new developments in emission tomography, nuclear magnetic resonance imaging, and in vivo spectroscopy offer new horizons for medical research and clinical activities. These methods and their potentials are reviewed and contrasted.

Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat.

Plastic changes in motor cortex capillary structure and function were examined in three separate experiments in adult rats following prolonged exercise. The first two experiments employed T-two-star (T(2)*)-weighted and flow-alternating inversion recovery (FAIR) functional magnetic resonance imaging to assess chronic changes in blood volume and flow as a result of exercise. The third experiment used an antibody against the CD61 integrin expressed on developing capillaries to determine if motor cortex capillaries undergo structural modifications. In experiment 1, T(2)*-weighted images of forelimb regions of motor cortex were obtained following 30 days of either repetitive activity on a running wheel or relative inactivity. The proton signal intensity was markedly reduced in the motor cortex of exercised animals compared with that of controls. This reduction was not attributable to alterations of vascular iron levels. These results are therefore most consistent with increased capillary perfusion or blood volume of forelimb regions of motor cortex. FAIR images acquired during experiment 2 under normocapnic and hypercapnic conditions indicated that resting cerebral blood flow was not altered under normal conditions but was elevated in response to high levels of CO(2), suggesting that prolonged exercise increases the size of a capillary reserve. Finally, the immunohistological data indicated that exercise induces robust growth of capillaries (angiogenesis) within 30 days from the onset of the exercise regimen. Analysis of other regions failed to find any changes in perfusion or capillary structure suggesting that this motor activity-induced plasticity may be specific to motor cortex.These data indicate that capillary growth occurs in motor areas of the cerebral cortex as a robust adaptation to prolonged motor activity. In addition to capillary growth, the vascular system also experiences heightened flow under conditions of activation. These changes are chronic and observable even in the anesthetized animal and are measurable using noninvasive techniques.

Paramagnetic contrast agents in nuclear magnetic resonance medical imaging.

Relaxation time differences are the sources of most of the contrast observed in proton NMR images, not only among normal organs and tissues but between lesions and the adjacent tissue. Although these differences are often large, there are low-contrast situations in which it would be desirable to increase the visibility of an organ or region. The study of time-dependent phenomena would also be aided by the ability to change selected relaxation times deliberately. One way to achieve these goals is to administer substances that change proton relaxation times in tissues without causing significant toxic effects or other physiologic changes. Paramagnetic ions and molecules, those with unpaired electrons, may be useful for this purpose because the very large magnetic effects associated with such electrons can drastically decrease water proton relaxation times at concentrations of the order of 100 to 1000 microM, which may be reached in certain organs after doses of 10 to 100 microM/kg. The general characteristics of such paramagnetic substances are described, and specific animal experiments with manganous ion and its complexes, and with stable nitroxide free radicals and molecular oxygen, are reviewed. The paramagnetic contrast agents already studied are effective, and many more are potentially possible, but the most important questions to be answered are whether acute and chronic toxicity are low enough to permit research and diagnosis on humans.

Diffusion measurement in phantoms and tissues using SLIM localization.

A new approach to efficient localized diffusion measurements has been developed and evaluated on phantoms and isolated tissues. The combination of a diffusion-sensitive pulse sequence with SLIM (spectral localization by imaging) makes efficient and accurate localized water and metabolite diffusion measurements possible with a substantial improvement in spatial or time resolution compared to standard methods. Phantom experiments showed that diffusion of substances present in relatively low concentration within small compartments can be measured accurately by this method, suggesting potential applications for diffusion measurements of metabolites in vivo. Experiments on excised rat uterine horns demonstrated the ability of this method to measure localized diffusion of water within irregularly shaped regions of biological samples. Accurate diffusion measurements were achieved in the localized regions with acquisition times less than would have been required by standard diffusion imaging methods.

An efficient method for dynamic magnetic resonance imaging.

Many magnetic resonance imaging applications require the acquisition of a time series of images. In conventional Fourier transform based imaging methods, each of these images is acquired independently so that the temporal resolution possible is limited by the number of spatial encodings (or data points in the Fourier space) collected, or one has to sacrifice spatial resolution for temporal resolution. Here, a generalized series based imaging technique is proposed to address this problem. This technique makes use of the fact that, in most time-sequential imaging problems, the high-resolution image morphology does not change from one image to another, and it improves imaging efficiency (and temporal resolution) over the conventional Fourier imaging methods by eliminating the repeated encodings of this stationary information. Additional advantages of the proposed imaging technique include a reduced number of radio frequency (RF) pulses for data collection, and thus lower RF power deposition. This method should prove useful for a variety of dynamic imaging applications, including dynamic studies of contrast agents and functional brain imaging.

A generalized series approach to MR spectroscopic imaging.

The problem of precise spatial localization of spectral information in magnetic resonance (MR) spectroscopic imaging is addressed. A novel method, called GSLIM (generalized spectral location by imaging), is proposed to make possible the marriage of high-resolution proton imaging with spectroscopic imaging and localization. This method improves on the conventional Fourier series inversion method used in chemical shift imaging (CSI) and the compartmental modeling method used in SLIM by using a generalized series framework for optimal representation of the spectral function. In this way, a priori information extracted from proton imaging can be used, as in SLIM, and the robustness and data consistency of CSI are also retained. Simulation results show that GSLIM can significantly reduce spectral leakage in CSI and inhomogeneity errors in SLIM. It can also reveal compartmental inhomogeneities, and can easily be extended to handle other a priori constraints when necessary. This approach, with some further development, may achieve an optimal combination of sensitivity, quantitative accuracy, speed, and flexibility for in vivo spectroscopy.

Reconstruction from NMR data acquired with imaging gradients having arbitrary time dependence.

An algebraic reconstruction method for NMR imaging from data acquired with imaging gradients having essentially arbitrary time dependence is presented. With reasonable discretization, an overdetermined linear system is obtained for which there exist simple factorized 1-inverses of the coefficient matrices; a computationally efficient reconstruction scheme then follows. Some numerical simulations are also described.

Four-dimensional spectral-spatial imaging using projection reconstruction.

An n-dimensional (n-D) filtered backprojection image reconstruction algorithm has been developed and used in the reconstruction of 4-D spectral-spatial magnetic resonance imaging (MRI) data. The algorithm uses n-1 successive stages of 2-D filtered backprojection to reconstruct an n-D image. This approach results in a reduction in computational time on the order of N(n-2) relative to the single-stage technique, where N(n) is the number of elements in an n-D image. The authors describe implementation of the algorithm, including digital filtering and sampling requirements. Images obtained from simulated data are presented to illustrate the accuracy and potential utility of the technique.

True three-dimensional image reconstruction by nuclear magnetic resonance zeugmatography.

Nuclear magnetic resonance (NMR) zeugmatographic imaging may become a safe and versatile alternative to medical imaging techniques that employ ionising and ultrasonic radiation. Most of the techniques that have been described for obtaining NMR images use single point, line, or plane scans to give a single slice, or reconstruct only a two-dimensional projection, and are relatively inefficient, complex, or difficult to scale up for use on the human body. There are a number of advantage to scanning simultaneously an approximately spherical volume to obtain a true three-dimensional image. A simple two-stage reconstruction method is described for obtaining such images efficiently with isotropic resolution, and examples are presented to demonstrate the validity and usefulness of this mode. The feasibility of high-resolution imaging on large objects is also discussed.

Three-dimensional nuclear-magnetic-resonance zeugmatographic imaging of surgical specimens.

Three-dimensional NMR zeugmatographic images of surgical specimens have been obtained with spin-lattice relaxation time (T1) discrimination. The extent of a primary malignant tumor and its metastasis to lymph nodes can be clearly seen and correlated with microscopic histological studies. 24CA15300

Rapid medium- resolution 3-D NMR zeugmatographic imaging of the head.

A true three-dimensional NMR zeugmatographic image of the human head, with an isotropic spatial resolution of 3.8 mm has been obtained in a total imaging time of 10 min. using a saturation-recovery (SR) pulse sequence. The 65 X 65 X 65 point 3-D image array has been displayed as three orthogonal sets of computer generated slices: transverse, coronal and sagittal. Intensities in such an image depend not only on the concentrations of protons but also on the spin-lattice relaxation time, T1 and the spin-spin relaxation time, T2.

Aspects of cardiac diagnosis using synchronized NMR imaging.

In vivo synchronized 3D Proton NMR zeugmatographic images of the beating heart have been obtained. The images clearly show the cardiac anatomy and changes in the anatomy accompanying the cardiac cycle. Transverse, coronal and sagittal slices are presented.

[NMR imaging of fluorine-containing substances. 19-Fluorine ventilation and perfusion studies]. / NMR-Imaging von fluorhaltigen Substanzen. 19Fluor-Ventilations- und -Perfusionsdarstellungen.

Physiologically inert perfluorinated gases may be used for lung ventilation imaging by Nuclear Magnetic Resonance (NMR). Because the nuclear concentration in the gas is lower than in tissue, signals from large gas volumes must be integrated to produce an acceptable image quality. After a series of phantom studies, preliminary dog studies have been carried out, using breathable mixtures of CF4 and O2. The resulting images have been compared with Xe ventilation scans. Furthermore, perfluorinated solutions were imaged using phantoms. The results are described and the future potential of the technique discussed.

Contrast agents for nuclear magnetic resonance imaging.

Nuclear magnetic resonance imaging relies upon differences in relaxation times for much of its ability to resolve anatomical structures and to detect changes in tissue. The natural differences can be changed by the administration of paramagnetic substances, such as metal complexes and stable organic free radicals, and ferromagnetic materials, such as small particles of magnetite. Detailed studies of the chemistry and biophysics of such substances in the body are required if they are to become safe and effective contrast agents for use in medical NMR imaging.