Invited review: biophysical properties and clinical applications of magnetic resonance imaging contrast agents.

Contrast enhanced magnetic resonance imaging (MRI) is a very versatile and effective technique for detecting and characterizing lesions, for identifying a variety of patho-physiological abnormalities, and for providing perfusion and functional information. The application of contrast enhanced MRI to many clinical and research indications has emerged because of the rapid evolution in imaging techniques, improved methodology, and the development of efficient and specific contrast agents. Problems related to optimizing parameters and dosage have been due to complex interplay of relaxation times, biophysical mechanisms and acquisition parameters. A knowledge of basic biophysical aspects is therefore essential for a full understanding of the results obtained for different organs under different conditions, and for optimizing the image parameters and dosage of contrast agents. This article underlines the biophysical basis of the effects of contrast agents in MRI, identifies the problems involved in optimizing the parameters for maximum efficiency, and presents a general overview of the clinical studies and research applications in the central nervous system, perfusion abnormalities, hepatobiliary system, musculoskeletal system and the gastrointestinal tract. The section on perfusion studies includes a discussion of quantitative analysis and kinetic models describing the effects of contrast agents. Finally, a critical evaluation of the scope and limitations of contrast enhanced MRI is presented.

Quality assessment in in vivo NMR spectroscopy: VI. Multicentre quantification of MRS test signals.

In this paper the results are presented of a joint European quantitative data-analysis study on a series of in vivo NMR time-domain test signals. The purpose of this study was to investigate, whether the quantitative MRS results from the various European biomedical research-centres can be made more comparable and reproducible. From the results of the study it can be concluded that in case of heavily overlapping NMR lines the quantifications should be done by some form of model function fitting and that, whenever possible, prior knowledge on the quantitative parameters should be incorporated into the quantification algorithms.

Spin-lattice relaxation times and nuclear Overhauser enhancement effect for 31P metabolites in model solutions at two frequencies: implications for in vivo spectroscopy.

The relaxation time T1 values and nuclear Overhauser enhancement factor for 31P signal were determined in model solutions of metabolites ATP, PCr and Pi, and AMP at two frequencies and in H2O and 2H2O solutions. The data were analyzed to resolve the contribution of different relaxation mechanisms. A knowledge of NOE is important in the light of recent applications of double resonance methods to enhance the sensitivity of in vivo 31P spectroscopy. The results show that chemical shift anisotropy is the dominant mechanism for 31P in ATP at the high field, whereas the dipolar interaction mechanism is the main feature for the 31P relaxation of PCr and Pi. The dipolar mechanism responsible for NOE originates from interactions of solvent water with 31P moiety. Implications for in vivo spectroscopy are indicated.

Multi-center trial with an in vitro NMR protocol. EEC Concerted Research Project.

The EEC Protocol for in vitro measurement of T1 and T2 presented in paper II of this series was tested in 15 centers on a variety of instruments. This article discusses the results of this protocol trial using biological samples (rat liver and thigh muscle) and two reference gel samples. Each reference gel was prepared as a single batch, dispensed into appropriate sample tubes and sent to all participants. Details of instrument types and operating conditions are given, along with measurement frequencies and temperatures and the results of precision testing. The relaxation time measurements from the gels for the trial are compared with temperature and frequency effects examined in independent centers under similar conditions. The relaxation time values for biological tissues are examined in the light of the scatter of such values in the general literature. To check the effects of data analysis methods on relaxation times, full relaxation data for one reference sample was provided by each group. This was re-analyzed in three centers using different methods; these results are compared with the values calculated by each group using its own method. In general, the results from different groups show good consistency with the reference values. The use of this Protocol has helped reduce scatter in results from biological samples and has provided information for improvement of individual operating conditions and improvement of the protocol to its final form.

Preparation of agarose gels as reference substances for NMR relaxation time measurement. EEC Concerted Action Program.

A standard method has been developed for the production of reference materials for NMR relaxation time measurement. These are based on agarose gels doped with gadolinium. The reproducibility and temporal stability of the gels have been found to be excellent. Electron microscope studies have shown good homogeneity. The relaxation behavior of such gels has been mathematically modeled with good agreement with experiment.

The use of agar gel as a basic reference material for calibrating relaxation times and imaging parameters.

The relaxation properties of agar gels render it a potentially useful basic reference material for calibrating the NMR equipment. The T1 and T2 values are close to the values observed for most biological tissues; they are stable and can be varied by controlling the concentration of MnCl2. The temperature, concentration, and volume dependence of T1 and T2 were studied.

Experimental protocol for tissue discrimination in vitro by N.M.R.

We have examined the n.m.r. relaxation times T1 and T2 of water protons for liver (mouse, human) and brain (mouse) at different temperatures and subjected to various conditions of conservation and degeneration. After tissue degeneration, T1 and T2 behave differently and their variations are characteristic of each tissue type. The results show that the initial values at +4 degrees C are consistent when the experimental protocol formulated in this study is followed.

The effects of gamma-irradiation on the hydration characteristics of DNA and polynucleotides. III. A comparative NMR study of frozen and liquid solutions.

The effects of gamma-irradiation and changes in the macromolecular structure on the water proton resonance spectra observed in frozen and liwuid solutions have been compared for the DNA and polynucleotide solutions, using H2O or mixed H2O/D2O solvents. The results indicate that in order to obtain information concerning the role of hydration water in mediating the overall radiation damage, the NMR studies must be performed in the frozen state.