Mri measurements of T1, T2 and D for gels undergoing volume phase transition

Gels consist of crosslinked polymer network swollen in solvent. The network of flexible long-chain molecules traps the liquid medium they are immersed in. Some gels undergo abrupt volume change, a phase transition process, by swelling-shrinking in response to external stimuli changes in solvent composition, temperature, pH, electric field, etc. We report that during volume phase transition changes of NMR longitudinal relaxation time T(1), NMR transverse relaxation time T(2), and diffusion coefficient D of the PMMA gel, and D of the NIPA gel. We describe how the gels were synthesized and the reason of using the snapshot FLASH imaging sequence to measure T(1), T(2), and D. Since T(1), T(2) and D maps have identical field of view and data are extracted from identical areas from their respective maps, these values can be correlated quantitatively on a pixel-by-pixel basis. Thus a complete set of NMR parameters is measured in-situ: the gels are in their natural state, immersed in the liquid, during the phase transition. The results of spectroscopic method agree with that of snapshot FLASH imaging method. For the PMMA gel T(1), T(2) and D decrease when gels undergo volume phase transition between deuterated acetone concentration of 30% and 40%. At its contracted state, T(1) is reduced to a little less than one order of magnitude, T(2) over two orders of magnitude, and D over one order of magnitude, smaller from values of PMMA gel at the swollen state. At an elevated temperature of 54 degrees C the thermosensitive NIPA gel is at a contracted state, with its D reduced to almost one order of magnitude smaller from that of the swollen NIPA at room temperature.     

Flow and oxygenation dependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T2*) and flow (via T1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T1-weighted images, with and without outer slice suppression, and calculated T2, T2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T1 and T2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T1 and 11% for T2 during carbogen breathing. The apparent T2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T2*. Carbogen breathing caused a threefold increase in arterial rat blood PaO2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T2* increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy.     

Analytical analysis of multi-pulse NMR

It is well known that in multi-pulse applications in high-resolution NMR and MRI a steady state is reached for the magnetisation vector by the effect of relaxation in combination with the pulse repetition time. In this paper, a mathematical model is developed to understand how the parameters of the pulse sequence and relaxation times T(1) and T(2) affect the behaviour of the magnetisation vector. It will be shown that even under strong simplifying conditions an analytical analysis becomes very complex and only an analytical solution can be found for 90 degrees pulses and T(1)=T(2). For other cases a numerical approach is needed. Nevertheless, the basic approach of the mathematical analysis provides a general tool for analytical multi-operator applications. Our results provide a quantitative insight in the process by which the magnetisation relaxes towards the steady-state situation in a multi-pulse sequence.     

Quantitative analysis of 17O exchange and T1 relaxation data: application to zirconium tungstate

The theoretical basis behind a recent quantitative analysis of 17O exchange in ZrW2O8 [M.R. Hampson, J.S.O. Evans, P. Hodgkinson, J. Am. Chem. Soc. 127 (2005) 15175-15181] is set out. Despite the complexities of combining the multi-exponential relaxation of half-integer quadrupolar nuclei with chemical exchange, it is shown how magnetisation transfer experiments can be analysed to obtain estimates of absolute exchange rates. The multi-exponential relaxation is best modelled using a magnetic mechanism, i.e. the rapid T1 relaxation observed, particularly at high temperatures, can be directly related to the relatively high degree of 17O labelling employed. The combination of the 1D EXSY results with T1 values as a function of temperature provides exchange rates and activation barriers over a wide temperature range (40-226 degrees C).     

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve

We report here a study of longitudinal relaxation (T₁) and magnetisation transfer (MT) in peripheral nerve. Amphibian sciatic nerve was maintained in vitro and studied at a magnetic field strength of 3 T. A CPMG pulse sequence was modified to include either a saturation pulse to measure T₁ relaxation or an off-resonance RF irradiation pulse to measure MT. The resulting transverse relaxation (T₂) spectra yielded four components corresponding to three nerve compartments, taken to result from myelinic, axonal, and inter-axonal water, and a fourth corresponding to the buffer solution water in which the nerve sample was bathed. Each nerve component was analysed for T₁ relaxation and MT. All three nerve T₂ components exhibited unique T₁ relaxation and MT characteristics, providing further support for the assignment of the components to unique physical compartments of water. Numerical investigation of T_1sat measurements of each of the three nerve T₂ components indicates that while the two shorter-lived exhibit similar steady-state magnetisation transfer ratios (MTRs), their respective MT properties are quite different. Simulations demonstrate that mobile water exchange between these two components is not necessary to explain their similar steady-state MTR. In the context of the assignment of these two components to signal from myelinic and axonal water, this is to say that these two microanatomical regions of nerve may exhibit similar steady-state MTR characteristics despite possessing widely different MT exchange rates. Therefore, interpreting changes in MTR solely to reflect a change in degree of myelination could lead to erroneous conclusions.     

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.     

Magnetization transfer of water T(2) relaxation components in human brain: implications for T(2)-based segmentation of spectroscopic volumes

Biexponential T(2) relaxation of the localized water signal can be used for segmentation of spectroscopic volumes. To assess the specificity of the components an iterative relaxation measurement of the localized water signal (STEAM, 12 echo times, geometric spacing from 30 ms to 2000 ms) was combined with magnetization transfer (MT) saturation (40 single lobe pulses, 12 ms duration, 1440 degrees nominal flip angle, 1 kHz offset, repeated every 30 ms). Voxels including CSF were examined in parietal cortex and periventricular parietal white matter (10 each), as well as 13 voxels in central white matter and 16 T(1)-hypointense non-enhancing multiple sclerosis lesions without CSF inclusion. Biexponential models (excluding myelin water) were fitted to the relaxation data. In periventricular VOIs the component of long T(2) (1736 +/- 168 ms) that is attributed to CSF was not affected by MT. In cortical VOIs this component had markedly shorter T(2)'s (961 +/- 239 ms) and showed both attenuation and prolongation with MT, indicating contributions from tissue. MS lesions and central WM showed a second tissue component of intermediate T(2) (160-410 ms). In white matter similar MT attenuation indicated strong exchange between the two tissue components, prohibiting segmentation. In MS lesions, however, markedly less MT of the intermediate component was found, which is consistent with decreased cellularity and exchange in a region that is large compared to diffusion motion.     

In vivo measurements of multi-component T2 relaxation behaviour in guinea pig brain

Multi-echo Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.5 T and 4.0 T imaging systems to test their ability to measure in vivo multi-component T2 relaxation behavior in normal guinea pig brain. The known dependence of accurate T2 measurements on the signal-to-noise ratio (SNR) was explored in vivo by comparing T2 decay data obtained using three methods to increase SNR (improved RF coil design, signal averaging and increased magnetic field strength). Good agreement between T2 values of nickel-doped agarose phantoms was found between imaging and spectroscopic methods. T2 values were determined for gray matter (GM) and white matter (WM) locations from images of guinea pig brain in vivo. T2 measurements of GM were found to be monoexponential at both field strengths. The mean T2 times for GM were 71 ms at 1.5 T, and 53 ms at 4.0T. The highest average SNR was achieved using an improved RF coil at 4.0T. In this case, two peaks were extracted in WM, a "short" T2 peak at approximately 6 ms, and a "medium" T2 peak at approximately 48 ms. T2 values in GM and the major component of WM were significantly decreased at 4.0T compared to 1.5 T. The improved SNR attained with this optimized imaging protocol at 4.0T has allowed for the first time extraction of the myelin-sensitive T2 component of WM in animal brain in vivo.     

Diffusion and relaxation effects in general stray field NMR experiments

We analyze the evolution of magnetization following any series of radiofrequency pulses in strongly inhomogeneous fields, with particular attention to diffusion and relaxation effects. When the inhomogeneity of the static magnetic field approaches or exceeds the strength of the RF field, the magnetization has contributions from different coherence pathways. The diffusion or relaxation induced decay of the signal amplitude is in general nonexponential, even if the sample has single relaxation times T(1), T(2) and a single diffusion coefficient D. In addition, the shape of the echo depends on diffusion and relaxation. It is possible to separate contributions from different coherence pathways by phase cycling of the RF pulses. The general analysis is tested on stray field measurements using two different pulse sequences. We find excellent agreement between measurements and calculations. The inversion recovery sequence is used to study the relaxation effects. We demonstrate two different approaches of data analysis to extract the relaxation time T(1). Finite pulse width effects on the timing of the echo formation are also studied. Diffusion effects are analyzed using the Carr--Purcell--Meiboom--Gill sequence. In a stray field of a constant gradient g, we find that unrestricted diffusion leads to nonexponential signal decay versus echo number N, but within experimental error the diffusion attenuation is still only a function of g(2)Dt(3)(E)N, where t(E) is the echo spacing.     

Cyclic variation of T1 in the myocardium at 3 T

Standard methods of longitudinal relaxation (T1) measurements in the heart produce only one T1 map of the myocardium, usually at the end diastole (ED). In this article, we investigated the feasibility of using a dual flip angle fast gradient echo technique in the steady state to generate a movie of T1 maps in the myocardium during the cardiac cycle. The effects of nonideal slice profile and transient steady state on the T1 measurements were evaluated by Bloch simulations. Based on these results, we introduce a linear correction to the measured T1 values, which was validated by phantom experiments. In vivo T1 cine maps in healthy volunteers show 70+/-7% drop in T1 from the ED to the end systole in the septum and a 43+/-13% drop in the left ventricular lateral wall. With further improvements, this technique could be used to assess the myocardial blood volume changes during the cardiac cycle.     

Simultaneous BOLD/perfusion measurement using dual-echo FAIR and UNFAIR: sequence comparison at 1.5T and 3.0T.

Functional MRI (fMRI) studies designed for simultaneously measuring Blood Oxygenation Level Dependent (BOLD) and Cerebral Blood Flow (CBF) signal often employ the standard Flow Alternating Inversion Recovery (FAIR) technique. However, some sensitivity is lost in the BOLD data due to inherent T1 relaxation. We sought to minimize the preceding problem by employing a modified UN-inverted FAIR (UNFAIR) technique, which (in theory) should provide identical CBF signal as FAIR with minimal degradation of the BOLD signal. UNFAIR BOLD maps acquired from human subjects (n = 8) showed significantly higher mean z-score of approximately 17% (p < 0.001), and number of activated voxels at 1.5T. On the other hand, the corresponding FAIR perfusion maps were superior to the UNFAIR perfusion maps as reflected in a higher mean z-score of approximately 8% (p = 0.013), and number of activated voxels. The reduction in UNFAIR sensitivity for perfusion is attributed to increased motion sensitivity related to its higher background signal, and, T2 related losses from the use of an extra inversion pulse. Data acquired at 3.0T demonstrating similar trends are also presented.     

Nuclear magnetic resonance for cultural heritage

Nuclear magnetic resonance (NMR) portable devices are now being used for nondestructive in situ analysis of water content, pore space structure and protective treatment performance in porous media in the field of cultural heritage. It is a standard procedure to invert T(1) and T(2) relaxation data of fully water-saturated samples to get "pore size" distributions, but the use of T(2) requires great caution. It is well known that dephasing effects due to water molecule diffusion in a magnetic field gradient can affect transverse relaxation data, even if the smallest experimentally available half echo time tau is used in Carr-Purcell-Meiboom-Gill experiments. When a portable single-sided NMR apparatus is used, large field gradients due to the instrument, at the scale of the sample, are thought to be the dominant dephasing cause. In this paper, T(1) and T(2) (at different tau values) distributions were measured in natural (Lecce stone) and artificial (brick samples coming from the Greek-Roman Theatre of Taormina) porous media of interest for cultural heritage by a standard laboratory instrument and a portable device. While T(1) distributions do not show any appreciable effect from inhomogeneous fields, T(2) distributions can show strong effects, and a procedure is presented based on the dependence of 1/T(2) on tau to separate pore-scale gradient effects from sample-scale gradient effects. Unexpectedly, the gradient at the pore scale can be, in some cases, strong enough to make negligible the effects of gradients at the sample scale of the single-sided device.     

Effects of thermal denaturation on the longitudinal relaxation time (T1) of water protons in protein solutions: study of the factors determining the T1 of water protons

The factors determining the longitudinal relaxation time (T1) of water protons in protein solutions were investigated by analyzing the effects of thermal denaturation on the T1 of the water protons. We treated the water protons and the protein protons "on a protein surface" as a dipole-dipole coupled two-spin system where relative translational diffusion is the dominant mechanism, and measured the change in the time development of the nuclear Overhauser effect (NOE) factors of the water protons. The T1 of the water protons was shortened markedly when the proteins were thermally denatured. Our analysis indicates that this relaxation enhancement is due to an increase in the value of the translational correlation time as well as the fraction of hydration water molecules, though the influence of "proton exchange" between the water protons and the labile protein protons cannot be completely neglected.     

Diffusion-relaxation correlation in simple pore structures

The effects of independent encoding for relaxation and for diffusion using separate time and gradient dimensions are calculated for spins diffusing in plane parallel and spherical pores with relaxing walls. Two-dimensional inverse Laplace transformation is used to obtain computed (D,T(2)) maps for both geometries, in the regime in which the dimensionless diffusion coefficient is less than unity and the dimensionless relaxation parameter of order unity or greater. It is shown that there exist two distinct branches on the (D,T(2)) maps, one with diffusion and relaxation strongly correlated and one in which the diffusion coefficients vary widely independently of relaxation.     

Theory of fast field-cycling NMR relaxometry of liquid systems undergoing chemical exchange

ABSTRACT

The time evolution of the nuclear magnetisation of chemically exchanging systems in liquids is calculated for the pre-polarised fast field-cycling sequence of nuclear magnetic resonance (NMR) relaxometry. The obtained parameter expressions of the magnetisation allow one to derive the longitudinal relaxation rates and the residence times of the exchanging sites from the experiment. In the particular cases of slow and fast exchange, approximations leading to simple analytic expressions are derived. The theory takes account of the delay time necessary to ensure that the field for acquiring the signal is stable enough after its rapid jump from its relaxation value. The domains of mono-exponential or bi-exponential relaxation of the magnetisation are displayed in a concise way through 3D and 2D logarithmic plots of the population ratio of the exchanging sites and of their intrinsic relaxation times. The influence of the acquisition delay on the fitted values of the populations, residence times, and intrinsic relaxation times of the sites is emphasised in the case of the bi-exponential water proton relaxation observed in a tumour tissue.     

Magnetic resonance imaging and relaxation analysis to predict noninvasively and nondestructively salt-to-moisture ratios in dry-cured meat

The current systems are unable to control and predict the cured meat composition nondestructively and in a reasonable time for production needs. In this work, T1 and T2 maps were obtained, with a monoexponential model, on internal sections of Longissimus dorsi muscle at increasing salting times. The maps allow one to visualize the salting process nondestructively and noninvasively. The method goes beyond the simple qualitative visualization, because, for each section of the sample and in any region of the section, it is possible to obtain quantitative information on the progress of salting and to predict salt-to-moisture ratios. In addition, detailed relaxation measurements were performed on samples cored after imaging in order to define better the relaxation properties of the dry-cured meat.     

Initially linear echo-spacing dependence of 1/T2 measurements in many porous media with pore-scale inhomogeneous fields

For a liquid sample with unrestricted diffusion in a constant magnetic field gradient g, the increase R in R2=1/T2 for CPMG measurements is 1/3(taugammag)2D, where gamma is magnetogyric ratio, tau is the half the echo spacing TE, and D is the diffusion constant. For measurements on samples of porous media with pore fluids and without externally applied gradients there may still be significant pore-scale local inhomogeneous fields due to susceptibility differences, whose contributions to R2 depend on tau. Here, diffusion is not unrestricted nor is the field gradient constant. One class of approaches to this problem is to use an "effective gradient" or some kind of average gradient. Then, R2 is often plotted against tau2, with the effective gradient determined from the slope of some of the early points. In many cases, a replot of R2 against tau instead of tau2 shows a substantial straight-line interval, often including the earliest available points. In earlier work [G.C. Borgia, R.J.S. Brown, P. Fantazzini, Phys. Rev. E 51 (1995) 2104; R.J.S. Brown, P. Fantazzini, Phys. Rev. B 47 (1993) 14823] these features were noted, and attention was called to the fact that very large changes in field and gradient are likely for a small part of the pore fluid over distances very much smaller than pore dimensions. A truncated Cauchy-Lorentz (C-L) distribution of local fields in the pore space was used to explain observations, giving reduced effects of diffusion because of the averaging properties of the C-L distribution, the truncation being at approximately +/-1/2chiB0, where chi is the susceptibility difference. It was also noted that, when there is a narrow range of pore size a, over a range of about 40 of the parameter xi=1/3chinua2/D, where nu is the frequency, R2 does not depend much on pore size a nor on diffusion constant D. Examples are shown where plots of R2 vs tau show better linear fits to the data for small tau values than do plots vs tau2. The present work shows that, if both grain-scale and sample-scale gradients are present for samples with narrow ranges of T2, it may be possible to identify the separate effects with the linear and quadratic coefficients in a second-order polynomial fit to the early data points. Of course, many porous media have wide pore size and T2 distributions and hence wide ranges of xi. For some of these wide distributions we have plotted R2 vs tau for signal percentiles, normalized to total signal for shortest tau, again showing initially linear tau-dependence even when available data do not cover the longest and/or shortest T2 values for alltau values. For the examples presented, both the intercepts and the initial slopes of the plots of R2 vs tau increase systematically with signal percentile, starting at smallest R2.     

Spin-lattice relaxation and a fast T1-map acquisition method in MRI with transient-state magnetization

The magnetization under the spin-lattice relaxation and the nuclear magnetic resonance radiofrequency (RF) pulses is calculated for a signal RF pulse train and for a sequence of multiple RF pulse-trains. It is assumed that the transverse magnetization is zero when each RF pulse is applied. The result expressions can be grouped into two terms: a decay term, which is proportional to the initial magnetization M0, and a recovery term, which has no M0 dependence but strongly depends on the spin-lattice relaxation and the equilibrium magnetization Meq. In magnetic resonance pulse sequences using magnetization in transient state, the recovery term produces artifacts and can seriously degrade the function of the preparation sequence for slice selection, contrast weighting, phase encoding, etc. This work shows that the detrimental effect can be removed by signal averaging in an eliminative fashion. A novel fast data acquisition method for constructing the spin-lattice relaxation (T1) map is introduced. The method has two features: (i) By using eliminative averaging, the curve to fit the T1 value is a decay exponential function rather than a recovery one as in conventional techniques; therefore, the measurement of Meq is not required and the result is less susceptible to the accuracy of the inversion RF pulse. (ii) The decay exponential curve is sampled by using a sequence of multiple pulse-trains. An image is reconstructed from each train and represents a sample point of the curve. Hence a single imaging sequence can yield multiple sample points needed for fitting the T1 value in contrast to conventional techniques that require repeating the imaging sequence for various delay values but obtain only one sample point from each repetition.     

Evidence for an oxygen diffusion model for the electric pulse induced resistance change effect in transition-metal oxides

Electric-pulse induced resistance hysteresis switching loops for Pr0.7Ca0.3MnO3 perovskite oxide films were found to exhibit an additional sharp "shuttle tail" peak around the negative pulse maximum for films deposited in an oxygen-deficient ambient. The resistance relaxation in time of this "shuttle tail" peak as well as resistance relaxation in the transition regions of the resistance hysteresis loop show evidence of oxygen diffusion under electric pulsing, and support a proposed oxygen diffusion model with oxygen vacancy pileup at the metal electrode interface region as the active process for the nonvolatile resistance switching effect in transition-metal oxides.