The influence of chemical and diffusive exchange on water proton transverse relaxation in plant tissues

Transverse water proton relaxation in parenchyma tissue of courgette, onion and apple shows a dependence on CPMG pulse spacing characteristic of each tissue. An analysis of this dependence suggests that transverse relaxation in these tissues is caused by various combinations of fast proton exchange between water and cell biopolymers (or solutes) and diffusion through internally generated magnetic field gradients. Diffusion between intra- and extracellular water compartments also averages the water proton signal to an extent that depends on cell morphology and membrane permeability and this is calculated using a two-compartment model. No recourse need be made to popular concepts such as exchange between free and "bound" water. The implications of our results for NMR image contrast are discussed.     

Molecular masking and unmasking of the paramagnetic effect of iron on the proton spin-lattice (T1) relaxation time in blood and blood clots

The contribution of hemolysis, proteolysis and the paramagnetic effect of iron on the proton spin-lattice (T1) relaxation time in blood was examined. Hemolysis induced by sonication resulted in a significant (10%) increase in the T1 relaxation time of whole blood. Proteolysis in both sonicated and unsonicated whole blood samples eventually yielded T1 values which correlated well with the relaxation times of free iron in plasma or water at concentrations comparable to the concentration of iron in whole blood. It is concluded that proteolysis allows the iron atom to express its paramagnetic effect on water relaxation by gradually destroying the hydrophobic nature of the pocket in which iron resides on the hemoglobin molecule. The contribution of various blood components to the T1 relaxation of whole blood was also studied. The T1 values for packed erythrocytes, intact whole blood, sonicated whole blood, plasma and serum proved to be significantly different from each other. Serum was found to have a significantly (12%) longer T1 relaxation time than plasma. Packed clotted blood in vitro showed no change in the T1 time for at least 13 days while packed erythrocytes showed a shortening of T1 time after 6-8 days.     

Molecular oxygen spin-lattice relaxation in solutions measured by proton magnetic relaxation dispersion

Proton spin-lattice relaxation rate constants have been measured as a function of magnetic field strength for water, water-glycerol solution, cyclohexane, methanol, benzene, acetone, acetonitrile, and dimethyl sulfoxide. The magnetic relaxation dispersion is well approximated by a Lorentzian shape. The origin of the relaxation dispersion is identified with the paramagnetic contribution from molecular oxygen. In the small molecule cases studied here, the effective correlation time for the electron-nuclear coupling may include contributions from both translational diffusion and the electron T(1). The electron T(1) for molecular oxygen dissolved in several solvents was found to be approximately 7.5 ps and nearly independent of solvent or viscosity.     

On the strong field dependence and nonlinear response to gadolinium contrast agent of proton transverse relaxation rates in dairy cream

Dairy cream, as a suspension of lipid droplets in water, is a potentially useful magnetic resonance imaging (MRI) phantom material and an interesting material for studying fundamental relaxation mechanisms. Here we report a strong increase in the transverse relaxation rates with field strength for both the water and lipid protons in dairy cream. Also, studies at 4.7 T reveal a nonlinear response of transverse relaxation rates with increasing concentration of a common gadolinium (Gd)-based contrast agent, including an initial decrease of water relaxation rates as measured with Hahn spin echoes at the lower Gd concentrations. The results are treated within the framework of a model in which the magnetic susceptibility difference between the lipid droplets and the aqueous phase plays the prominent role for transverse relaxation. Second-order polynomial fits of the water proton transverse relaxation rate dependence on field strength and on Gd concentration at 4.7 T provided experimental parameters from which model parameters are extracted and compared with expectations available from the literature.     

Significance of proton relaxation time measurement in brain edema, cerebral infarction and brain tumors

We examined the proton relaxation times in vitro in various neurological diseases using experimental and clinical materials, and consequently obtained significant results for making a fundamental analysis of magnetic resonance imaging (MRI) as followings. 1) In the brain edema and cerebral infarction, T1 prolonged and T2 separated into two components, one fast and one slow. Prolongation of T1 referred to the volume of increased water in tissue. The slow component of T2 reflects both the volume and the content of increased edema fluid in tissue. 2) In the edematous brain tissue with the damaged Blood-Brain-Barrier (BBB), the slow component of T2 became shorter after the injection of Mn-EDTA. Paramagnetic ion could be used as an indicator to demonstrate the destruction of BBB in the brain. 3) After the i.v. injection of glycerol, the slow component of T2 became shorter in the edematous brain with the concomitant decrease of water content. The effects of therapeutic drug could be evaluated by the measurement of proton relaxation times. 4) Almost all tumor tissue showed a longer T1 and T2 values than the normal rat brain, and many of them showed two components in T2. It was difficult to determine the histology of tumor tissue by the relaxation time alone because of an overlap of T1 and T2 values occurred among various types of brain tumors. 5) In vivo T1 values of various brain tumor were calculated from the data of MRIs by zero-crossing method, and they were compared with the in vitro T1 values which were measured immediately after the surgical operation. Though the absolute value did not coincide with each other due to differences in magnetic field strength, the tendency of the changes was the same among all kinds of tumors. It is concluded that the fundamental analysis of proton relaxation times is essentially important not only for the study of pathophysiology in many diseases but also for the interpretation of clinical MRI.     

Transverse relaxation mechanisms in articular cartilage

Relaxation rates in the rotating frame (R1rho) and spin-spin relaxation rates (R2) were measured in articular cartilage at various orientations of cartilage layer to the static magnetic field (B0), at various spin locking field strengths and at two different static magnetic field strengths. It was found that R1rho in the deep radial zone depended on the orientation of specimens in the magnet and decreased with increasing the spin locking field strength. In contrast, R1rho values in the transitional zone were nearly independent of the specimen orientation and the spin locking field strength. Measurements of the same specimens at 2.95 and 7.05 T showed an increase of R1rho and most R2 values with increasing B0. The inverse B0 dependence of some R2 values was probably due to a multicomponent character of the transverse magnetization decay. The experiments revealed that the dominant T1rho and T2 relaxation mechanism at B0 < or = 3 T is a dipolar interaction due to slow anisotropic motion of water molecules in the collagen matrix. On average, the contribution of scalar relaxation due to rapid proton exchange in femoral head cartilage at 2.95 T is about 6% or less of the total R1rho at the spin locking field of 1000 Hz.     

Effects of intra- and extracellular space properties on diffusion and T(2) relaxation in a tissue model

The purpose of this study was to investigate the effects of biophysical factors on the diffusion and the relaxation time T(2) independently. Certain properties of the extracellular and the intracellular space may change radically in pathological conditions resulting in water diffusion changes. A tissue model consisting of red blood cells was studied. The extra- and intracellular spaces were modified osmotically and by suspending medium concentration. Diffusion measurements were evaluated with regard to the effective medium theory. Neither the nature of the protein in the extracellular space nor an increased level of intracellular hydration caused a significant net water diffusion change in the cell suspension. The relaxation time T(2) exhibited very little dependence on the extracellular volume fraction or the concentration or the nature of the protein in the extracellular space. An increased level of intracellular hydration resulted in systematically larger T(2) values. It seems probable that increases in extracellular protein concentrations or in the extent of intracellular hydration do not play a significant role in the diffusion changes detected in pathological conditions. T(2) appears to depend on the level of hydration or the total water content but is seemingly less dependent of the concentration and the nature of the extracellular protein in our model solutions.     

Restricted diffusion and exchange of water in porous media: average structure determination and size distribution resolved from the effect of local field gradients on the proton NMR spectrum

NMR Pulsed field gradient measurements of the restrained diffusion of confined fluids constitute an efficient method to probe the local geometry in porous media. In most practical cases, the diffusion decay, when limited to its principal part, can be considered as Gaussian leading to an apparent diffusion coefficient. The evolution of the latter as a function of the diffusion interval yields average information on the surface/volume ratio of porosities and on the tortuosity of the network. In this paper, we investigate porous model systems of packed spheres (polystyrene and glass) with known mean diameter and polydispersity, and, in addition, a real porous polystyrene material. Applying an Inverse Laplace Transformation in the second dimension reveals an evolution of the apparent diffusion coefficient as a function of the resonance frequency. This evolution is related to a similar evolution of the transverse relaxation time T2. These results clearly show that each resonance frequency in the water proton spectrum corresponds to a particular magnetic environment produced by a given pore geometry in the porous media. This is due to the presence of local field gradients induced by magnetic susceptibility differences at the liquid/solid interface and to slow exchange rates between different pores as compared to the frequency differences in the spectrum. This interpretation is nicely confirmed by a series of two-dimensional exchange experiments.     

Low-frequency proton NMR relaxometry of a polymer dispersed liquid crystal above TNI

Using proton NMR relaxometry in the kilohertz frequency range, we study dynamics of 5CB liquid crystal molecules dispersed in the form of spherical microdroplets in a PDLC material. The focus of the study is the spin-lattice relaxation in the rotating frame, T1rho(-1), measured above the nematic-isotropic transition TNI. We show that the relaxation rate T1rho(-1)--when induced by uniform molecular translational diffusion in a spherical cavity--depends on the strength of the rotating magnetic field as T1rho(-1) proportional to omega1(-alpha) where alpha varies between 0.7 and 1, depending on the thickness of the ordered surface layer. This relaxation mechanism governs mainly the transverse spin relaxation, whereas the measurements of the frequency and temperature dependence of T1rho(-1) indicate a strong effect of slowing-down of molecular translational diffusion in contact with the polymer surface and yield the average dwell-time of molecules at the surface of the order 10(-5) s.     

Application of high-resolution magic-angle spinning NMR spectroscopy to define the cell uptake of MRI contrast agents

A new method, based on proton high-resolution magic-angle spinning ((1)H HR-MAS) NMR spectroscopy, has been employed to study the cell uptake of magnetic resonance imaging contrast agents (MRI-CAs). The method was tested on human red blood cells (HRBC) and white blood cells (HWBC) by using three gadolinium complexes, widely used in diagnostics, Gd-BOPTA, Gd-DTPA, and Gd-DOTA, and the analogous complexes obtained by replacing Gd(III) with Dy(III), Nd(III), and Tb(III) (i.e., complexes isostructural to the ones of gadolinium but acting as shift agents). The method is based on the evaluation of the magnetic effects, line broadening, or induced lanthanide shift (LIS) caused by these complexes on NMR signals of intra- and extracellular water. Since magnetic effects are directly linked to permeability, this method is direct. In all the tests, these magnetic effects were detected for the extracellular water signal only, providing a direct proof that these complexes are not able to cross the cell membrane. Line broadening effects (i.e., the use of gadolinium complexes) only allow qualitative evaluations. On the contrary, LIS effects can be measured with high precision and they can be related to the concentration of the paramagnetic species in the cellular compartments. This is possible because the HR-MAS technique provides the complete elimination of bulk magnetic susceptibility (BMS) shift and the differentiation of extra- and intracellular water signals. Thus with this method, the rapid quantification of the MRI-CA amount inside and outside the cells is actually feasible.     

Relaxation of protons by radicals in rotationally immobilized proteins

Proton spin-lattice relaxation by paramagnetic centers may be dramatically enhanced if the paramagnetic center is rotationally immobilized in the magnetic field. The details of the relaxation mechanism are different from those appropriate to solutions of paramagnetic relaxation agents. We report here large enhancements in the proton spin-lattice relaxation rate constants associated with organic radicals when the radical system is rigidly connected with a rotationally immobilized macromolecular matrix such as a dry protein or a cross-linked protein gel. The paramagnetic contribution to the protein-proton population is direct and distributed internally among the protein protons by efficient spin diffusion. In the case of a cross-linked-protein gel, the paramagnetic effects are carried to the water spins indirectly by chemical exchange mechanisms involving water molecule exchange with rare long-lived water molecule binding sites on the immobilized protein and proton exchange. The dramatic increase in the efficiency of spin relaxation by organic radicals compared with metal systems at low magnetic field strengths results because the electron relaxation time of the radical is orders of magnitude larger than that for metal systems. This gain in relaxation efficiency provides completely new opportunities for the design of spin-lattice relaxation based contrast agents in magnetic imaging and also provides new ways to examine intramolecular protein dynamics.     

The first proton NMR imaging of ice: stray-field imaging and relaxation studies

A proton magnetic resonance image of ice was observed with the stray-field (STRAFI) technique. A preliminary study of proton relaxation times was performed in water and ice, at different temperatures. For example, a value of 3.5 micros for the spin-spin relaxation time, T(2), was found in ice at 258 K. Such a short T(2) value leads to significant signal loss, as compared to liquid water, and to a shortening of the STRAFI echo-trains. In particular, a STRAFI signal for protons in ice could be observed only at echo times as short as 15 and 25 micros, for RF pulse durations corresponding to 90 degrees and 50 degrees magnetisation tip angles, respectively. This behaviour is in contrast with that of deuteriated water. Imaging ice, as shown here, opens new prospects in studies involving environmental and materials science, for example.     

In vivo magnetic resonance diffusion measurement in the brain of patients with multiple sclerosis.

Measurement of water self-diffusion in the brain in 25 patients with multiple sclerosis was performed by magnetic resonance imaging. Quantitative diffusion measurements were obtained using single spin-echo pulse sequences with pulsed magnetic field gradients of different magnitude. Twenty-two of these patients also underwent measurement of the transverse relaxation time (T2). Only one plaque was evaluated in each patient. Based on prior knowledge, 12 plaques were classified as being 3 mo or less in age, and 7 plaques were classified as being more than 3 mo old. In all 25 plaques, water self-diffusion was found to be higher than in apparently normal white matter. Furthermore, water self-diffusion was found to be higher in acute plaques compared with chronic plaques. Finally, a slight tendency toward a relationship between the diffusion capability and T2 was found. We believe that an increased diffusion capability signifies an increase of the extracellular water space, which probably is related to the degree of demyelination. Thus, measurement of water self-diffusion in multiple sclerosis plaques may contribute to the study of pathogenesis of demyelination.     

Fast proton spin-lattice relaxation time in the rotating frame during the application of time averaged precession frequency

A relatively rapid phase alternation of the effective field in the time averaged precession frequency (TAPF) sequence results in averaging of the proton RF spin-lock field. The spin-locking of the proton magnetization becomes less efficient and thus shortens T(1rho)(H), the proton spin-lattice relaxation time in the rotating frame. The relaxation time also depends on the ratio of tau(1) and tau(2) intervals i.e. tau(1)/tau(2) and not only on the number of tau(c)=tau(1)+tau(2) blocks, i.e. the number of the phase transients. Experiments are performed on solid samples of ferrocene and glycine and for some time intervals, T(1rho)(H) is shortened by factors of 9-100 compared to the relaxation times obtained in the standard experiment.     

Temperature dependence of proton relaxation times in vitro

Accurate measurement of tissue relaxation characteristics is dependent on many factors, including field strength and temperature. The purpose of this study was to evaluate the relationship between sample temperature, viscosity and proton spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). A review of two basic models of relaxation the simple molecular motion model and the fast exchange two state model is given with reference to their thermal dependencies. The temperature dependence for both T1 and T2 was studied on a 0.15 Tesla whole body magnetic resonance imager. Thirteen samples comprising both simple and complex materials were investigated by using a standard spin-echo (SE) technique and a modified Carr-Purcell-Meiboom-Gill (CPMG) multi-echo sequence. A simple linear relationship between T1 and temperature was observed for all samples over the range of 20 degrees C to 50 degrees C. There is an inverse relationship between viscosity and T1 and T2. A quantity called the temperature dependence coefficient (TDC) is introduced and defined as the percent rate of change of the proton relaxation time referenced to a specific temperature. The large TDC found for T1 values, e.g. 2.37%/degrees C for CuSO4 solutions and 3.59%/degrees C for light vegetable oils at 22 degrees C, indicates that a temperature correction should be made when comparing in-vivo and in-vitro T1 times. The T2 temperature dependence is relatively small.     

An evaluation of the contributions of diffusion and exchange in relaxation enhancement by MRI contrast agents

Magnetic compounds are known to enhance water proton relaxation, either by diffusion or by proton exchange. An experimental procedure to distinguish both mechanisms is proposed and validated by relaxation measurements made in water-methanol solutions of Dy(3+), Ni(2+), Gd(3+), Tempo, and AMI-25. The test discriminates according to the character of the transverse relaxation in water-methanol solutions: a mono-exponential decay corresponds to diffusion, while a bi-exponential decay indicates the contribution of a proton exchange. The study of ferritin and akaganeite particle solutions confirms the occurrence of a proton exchange between protons belonging to hydroxyl groups of the particle surface and free water protons.     

Anomalous surface diffusion of water compared to aprotic liquids in nanopores

1H nuclear magnetic relaxation dispersion experiments show remarkable differences between water and acetone in contact with microporous glass surfaces containing trace paramagnetic impurities. Analyzed with surface relaxation theory on a model porous system, the data obtained for water show that proton surface diffusion limited by chemical exchange with the bulk phase permits long-range effectively one-dimensional exploration along the pores. This magnetic-field dependence coupled with the anomalous temperature dependence of the relaxation rates permits a direct interpretation in terms of the proton translational diffusion coefficient at the surface of the pores. A universal rescaling applied to these data collected for different pore sizes and on a large variety of frequencies and temperatures, supports this interpretation. The analysis demonstrates that acetone diffuses more slowly, which increases the apparent confinement and results in a two-dimensional model for the molecular dynamics close to surface relaxation sinks. Surface-enhanced water proton diffusion, however, permits the proton to explore a greater spatial extent of the pore, which results in an apparent one-dimensional model for the diffusive motions of the water that dominate nuclear spin relaxation.     

Proton N.M.R. studies of chemical and diffusive exchange in carbohydrate systems

A computer-simulated stochastic model is developed capable of predicting the combined effects of chemical and diffusive exchange on the transverse relaxation of spin-1/2 nuclei in a heterogeneous system. Comparison is first made with previous analytical theories for the special case of two site chemical exchange in a homogeneous system and the experimental data on several homogeneous aqueous carbohydrate systems are analysed. Results show that transverse water proton relaxation in these systems is dominated by proton exchange between water and carbohydrate hydroxyl groups. Analysis of model heterogeneous carbohydrate systems shows that in addition to chemical exchange, diffusion coefficients, particle morphology and local magnetic field gradients all have a role to play in determining the proton relaxation behaviour.     

Quantification of cerebral metabolites in glioma patients with proton MR spectroscopy using T2 relaxation time correction

This study was aimed to investigate the significance of absolute concentration of metabolites in glioma patients using proton MR spectroscopy (MRS) with T2 relaxation time correction using three different echo times. The absolute concentrations of metabolites in 7 normal subjects and in 23 gliomas (10 low-grade, 13 high-grade) were obtained by proton MRS using a tissue water signal as an internal standard. The signal intensities of metabolites and tissue water were corrected by T2 relaxation time. In low-grade glioma, the T2 relaxation time of NAA was shorter, and T2 relaxation time of water was prolonged as compared to normal subjects (p < 0.001). In high-grade glioma, the T2 relaxation time of NAA (p < 0.001) and T2 relaxation time of Cr (p < 0.01) were shorter, and T2 relaxation time of water (p < 0.001) was prolonged as compared to normal subjects. Moreover, high-grade gliomas revealed a shorter T2 relaxation time of Cr than low-grade gliomas (p < 0.05). In glioma, NAA and Cr concentration were decreased, and Cho were increased as compared to normal subjects. Moreover, high-grade glioma revealed a significant lower Cr (p < 0.001) and Cho (p < 0.01) concentration compared to low-grade gliomas. Low Cr concentration is the most reliable indicator of malignancy in glioma. Cho concentration did not correlate with malignancy in gliomas.     

MRI of thermally denatured blood: methemoglobin formation and relaxation effects

Focal regions of T₁-shortening have been observed in magnetic resonance imaging (MRI)-monitored thermal ablations of perfused tissues. The aims of this study were two-fold: to find evidence for heat-induced conversion of hemoglobin (Hb) to methemoglobin (mHb), and to investigate the effects of heat treatment of in-vitro blood components upon their MR relaxation times. Spectrophotometric studies were performed to confirm the heat-induced formation of methemoglobin. Preparations of whole and fractionated blood, previously submitted to elevated temperatures of 40°C to 80°C, were imaged and the relaxation times were calculated. Optical absorption spectra of samples containing free Hb, heated to 60°C, showed increased light absorption at 630 nm, evident of mHb presence. Short T₁ values in whole blood (1.13 s) and packed red blood cell (0.65 s) compartments, heated at 60°C, compared to their baseline values (1.62 s and 0.83 s, respectively), were attributed to mHb formation. In relation to MRI-guided thermal interventions, these results suggest a possible explanation for observation of hyperintense regions on T₁-weighted images.