Single-scan longitudinal relaxation measurements in high-resolution NMR spectroscopy

Several single-scan experiments for the measurement of the longitudinal relaxation time (T1) are proposed. These experiments result in fast and accurate determinations of the relaxation rate, are relatively robust to pulse imperfections, and preserve information about the chemical shift. The method used in these experiments is to first encode the T1 values as a spatial variation of the magnetization and then to read out this variation either by applying a weak gradient during acquisition or by sequentially observing different slices of the sample. As a result, it is possible to reduce the time necessary to determine the T1 values by one or two orders of magnitude. This time saving comes at the expense of the signal-to-noise level of the resulting spectrum and some chemical shift resolution.     

TriTone: a radiofrequency field (B1)-insensitive T1 estimator for MRI at high magnetic fields

Fast, high-resolution, longitudinal relaxation time (T1) mapping is invaluable in clinical and research applications. It has been shown that two spoiled gradient recalled echo (SPGR) images acquired in steady state with variable flip angles is an attractive alternative to the multi-image sets previously acquired with inversion or saturation recovery. The known sensitivity of the two-point method to transmit radiofrequency field (B1) inhomogeneity exacerbated at 3 T and above, however, mandates its combination with an additional, time-consuming and possibly specific-absorption-rate-intensive B1 measurement, preventing direct migration of the method to these fields. To address this, we introduce a method designed to be free of systematic errors caused by B1 inhomogeneity in which the value of T1 is extracted from three SPGR images acquired with echo planar imaging (EPI) readout. The precision of the T1 maps produced is found to be comparable to the two-point method, while the accuracy is greatly improved in the same time and spatial resolution. A welcome byproduct of the method is a map of B1 that can be used to correct other acquisitions in the same session. Tables of the optimal acquisition protocols are provided for several total imaging times.     

In vivo multiecho T2 relaxation measurements using variable TR to decrease scan time

Multiecho T2 relaxation measurements to determine geometric mean T2 (GMT2) and myelin water fraction (MWF) are lengthy, resulting in increased motion artefacts from patient discomfort and reduced patient compliance. The goal of this study was to shorten the acquisition time for multiecho T2 measurements without affecting T1 weighting by varying TR across k-space. Six phantoms and 10 healthy volunteers were imaged with both a constant TR and a variable TR multiecho T2 sequence. T1 weighting was determined by TR at the center of k-space; for variable TR measurement, TR was shortened linearly from the center to the edges of k-space. Phantoms showed excellent agreement for proton density and GMT2 between constant and variable TR measurements. No significant differences were found in proton density or MWF for any of the brain structures between the two measurements. The average GMT2 over all structures between the two experiments was not significantly different. In summary, with the variable TR approach, scan time was reduced by >20%, with minimal loss of image resolution and no significant affect on proton density, MWF or GMT2.     

Oxygen-induced changes in longitudinal relaxation times in skeletal muscle

The objective was to measure the effect of 100% oxygen inhalation on T1 relaxation times in skeletal muscle. Healthy volunteers were scanned using three different MRI protocols while breathing medical air and 100% oxygen. Measurements of T1 were made from regions of interest (ROIs) within various skeletal muscle groups. Dynamic data of subjects breathing a sequence of air-oxygen-air allowed the calculation of characteristic wash-in and -out times for dissolved oxygen in muscle. Contrary to previous findings, a statistically significant decrease in T1 in skeletal muscle was observed due to oxygen inhalation. We report approximate baseline characteristic values for the response of skeletal muscle to oxygen inhalation. This measurement may provide new biomarkers for evaluation of oxygen delivery and consumption in normal and diseased skeletal muscle.     

The flipped longitudinal polarization sequence

By flipping the longitudinal magnetization with a chain of 180° pulses it is possible to effectively restore the effects of relaxation so that the same longitudinal magnetization is periodically recovered. The pulse sequence for achieving this, called Flipped LOngitudinal Polarization (FLOP), can be incorporated into any pulse sequence whenever it is desired to stop the attenuation in longitudinal magnetization caused by relaxation. We illustrate its use for fast, single-shot measurements of the longitudinal relaxation time and for three-dimensional T₁ mapping.     

Distributions of transverse relaxation times for soft-solids measured in strongly inhomogeneous magnetic fields

The single-sided NMR-MOUSE sensor that operates in highly inhomogeneous magnetic fields is used to record a CPMG ¹H transverse relaxation decay by CPMG echo trains for a series of cross-linked natural rubber samples. Effective transverse relaxation rates 1/T_2,short and 1/T_2,long were determined by a bi-exponential fit. A linear dependence of transverse relaxation rates on cross-link density is observed for medium to large values of cross-link density. As an alternative to multi-exponential fits the possibility to analyze the dynamics of soft polymer network in terms of multi-exponential decays via the inverse Laplace transformation was studied. The transient regime and the effect of the T₁/T₂ ratio in inhomogeneous static and radiofrequency magnetic fields on the CPMG decays were studied numerically using a dedicated C++ program to simulate the temporal and spatial dependence of the CPMG response. A correction factor T₂/T_2,eff is derived as a function of the T₁/T₂ ratio from numerical simulations and compared with earlier results from two different well logging devices. High-resolution T₁–T₂ correlations maps are obtained by two-dimensional Laplace inversion of CPMG detected saturation recovery curves. The T₁–T₂ experimental correlations maps were corrected for the T₁/T₂ effect using the derived T₂/T_2,eff correction factor.     

Assessment of interstitial water content of articular cartilage with T1 relaxation

The interstitial water content typically increases in the early degeneration of articular cartilage. Previously, T₂ relaxation has been related to water content, yet it is known to be strongly affected by the collagen orientation. Articular cartilage plugs from the bovine patella, femur and tibia (N=20) were mapped for T₁ and T₂ at 9.4 T to test the ability of T₁ relaxation to reflect cartilage water content. As a reference, water and proteoglycan (PG) contents were determined. Significant (P<.01) linear associations were demonstrated between the relaxation rates and tissue water content (R₁: r=−.81, R₂: r=−.60) and PG content (R₁: r=.75). After adjustment for the tissue water content, partial correlation analysis did not show significant associations between the relaxation rates and tissue PG content. After the effect of PGs was removed, significant (P<.05) linear correlation between the relaxation rates and tissue water content (R₁: r=−.48, R₂: r=−.50) was observed. Thus, the spin-lattice relaxation rate is proposed to provide a biomarker for water content in articular cartilage.     

Two-dimensional correlation relaxation studies of cement pastes

Two-dimensional nuclear magnetic resonance relaxation correlation studies of cement pastes have been performed on a unilateral magnet, the Surface GARField. Through these measurements, the hydration process can be observed by monitoring the evolution of porosity. Characteristic relaxation time distributions have been observed in different cement pastes: fresh white cement, prehydrated white cement and ordinary Portland cement. The observed T(1)/T(2) ratio in these cements has been shown to agree with expectations based on high field values.     

Sensitivity enhancement in (13)C solid-state NMR of protein microcrystals by use of paramagnetic metal ions for optimizing (1)H T(1) relaxation

We discuss a simple approach to enhance sensitivity for (13)C high-resolution solid-state NMR for proteins in microcrystals by reducing (1)H T(1) relaxation times with paramagnetic relaxation reagents. It was shown that (1)H T(1) values can be reduced from 0.4-0.8s to 60-70 ms for ubiquitin and lysozyme in D(2)O in the presence of 10 mM Cu(II)Na(2)EDTA without substantial degradation of the resolution in (13)C CPMAS spectra. Faster signal accumulation using the shorter (1)H T(1) attained by paramagnetic doping provided sensitivity enhancements of 1.4-2.9 for these proteins, reducing the experimental time for a given signal-to-noise ratio by a factor of 2.0-8.4. This approach presented here is likely to be applicable to various other proteins in order to enhance sensitivity in (13)C high-resolution solid-state NMR spectroscopy.     

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.     

Whole-body T2* mapping at 1.5 T

This study investigated the feasibility of an MRI protocol providing whole-body T2* maps at 1.5 T. Seven healthy volunteers (mean age=30.1+/-3.7, three women and four men) and two patients (both male, 53 and 46 years old) affected by transfusion-dependent anemias participated in the study. Coronally oriented images of five subsequent body levels were acquired using a fat-suppressed multiecho 2D gradient-echo sequence (12 echo times ranging from 4.8 to 76.3 ms were selected) and afterwards composed. Parametrical T2* maps of the whole body were reconstructed on a pixel-by-pixel basis. For both, healthy volunteers and patients, representative T2* values were computed from extended regions of interest (ROIs). Good-quality whole-body T2* maps were computed in all volunteers and patients. In healthy volunteers, T2* values were assessed in the cerebral white (58.5+/-4.2 ms) and gray (81.4+/-5.5 ms) matter, liver (34.3+/-7.0 ms), spleen (63.5+/-3.3 ms), kidneys (65.4+/-10.3 ms) and skeletal muscles (~30 ms). The liver presented faster relaxation rates in males as compared to females. One patient (serum ferritin concentration=927 microg/dl) showed shortened T2* values in liver (3.6+/-5.5 ms), spleen (3.1+/-4.8 ms), kidneys (11.1+/-7.1 ms) and muscles (25.1+/-3.4 ms). The second patient (serum ferritin concentration=346 microg/dl) presented reduced T2* values in liver (3.9+/-7.3 ms), spleen (20.1+/-9.8 ms) and kidneys (24.6+/-7.7 ms). The presented technique may find clinical application in the assessment of the iron burden in the entire body, and in monitoring of chelation therapies in patients treated with frequent blood transfusions.     

Formation of p-cresol:piperazine complex in solution monitored by spin-lattice relaxation times and pulsed field gradient NMR diffusion measurements

A study of the nature of the anthelmintic p-cresol:piperazine complex in chloroform solution has been conducted using different NMR techniques: self-diffusion coefficients using DOSY; NOE, NULL, and double-selective T1 measurements to determine inter-molecular distances; and selective and non-selective T1 measurements to determine correlation times. The experimental results in solution and CP-MAS were compared to literature X-ray diffraction data using molecular modeling. It was shown that the p-cresol:piperazine complex exists in solution in a very similar manner as it does in the solid state, with one p-cresol molecule hydrogen bonded through the hydroxyl hydrogen to each nitrogen atom of piperazine. The close correspondence between the X-ray diffraction data and the inter-proton distances obtained by NULL and double selective excitation techniques indicate that those methodologies can be used to determine inter-molecular distances in solution.     

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.     

1H relaxation study in (NH4)2SbF5

¹H spin-lattice relaxation rate (T ₁ ⁻¹ ) has been measured using inversion recovery technique in polycrystalline (NH₄)₂SbF₅ system in the temperature range 140–400 K. From the plot of log (M ₀−M) againstτ, we have estimated two differentT ₁ corresponding to two inequivalent ammonium ions in the unit cell. Temperature-dependence ofT ₁ in each case exhibits features of double minima indicating the influence of different correlation times corresponding to different types of motion. Activation energies at different temperature regions have been estimated. Some features of dynamics of motion of the different groups of ions across the phase transitions have been discussed.     

A simple way to acquire T(1)-weighted MR images of rat liver with respiratory triggering

To acquire high-resolution T(1)-weighted images of the liver in rats, for which breath-holding cannot be ensured, respiratory triggering is essential. At the respiratory rate of 30-60 times/min in rats, however, T(1)-weighted images cannot be obtained with simple triggering. As a simple solution to this, we applied multiple repeated acquisitions with one trigger signal. With this technique, sufficient T(1) contrast could be easily achieved in rat liver enhanced by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid infusion.     

A comparative study at 3 T of sequence dependence of T2 quantitation in the knee

Objective

T₂ mapping has been used widely in detecting cartilage degeneration in osteoarthritis. Several scanning sequences have been developed in the determination of T₂ relaxation times of tissues. However, the derivation of these times may vary from sequence to sequence. This study seeks to evaluate the sequence-dependent differences in T₂ quantitation of cartilage, muscle, fat and bone marrow in the knee joint at 3 T.

Methods

Three commercial phantoms and 10 healthy volunteers were studied using 3 T MR. T₂ relaxation times of the phantoms, cartilage, muscle, subcutaneous fat and marrow were derived using spin echo (SE), multiecho SE (MESE), fast SE (FSE) with varying echo train length (ETL), spiral and spoiler gradient (SPGR) sequences. The differences between these times were then evaluated using Student's t test. In addition, the signal-to-noise ratio (SNR) efficiency and coefficient of variation of T₂ from each sequence were calculated.

Results

The average T₂ relaxation time was 36.38±5.76 ms in cartilage and 34.08±6.55 ms in muscle, ranging from 27 to 45 ms in both tissues. The times for subcutaneous fat and marrow were longer and more varying, ranging from 41 to 143 ms and from 42 to 160 ms, respectively. In FSE acquisition, relaxation time significantly increases as ETL increases (P<.05). In cartilage, the SE acquisition yields the lowest T₂ values (27.52±3.10 ms), which is significantly lower than those obtained from other sequences (P<.002). T₂ values obtained from spiral acquisition (38.27±6.45 ms) were higher than those obtained from MESE (34.35±5.62 ms) and SPGR acquisition (31.64±4.53 ms). These differences, however, were not significant (P>.05).

Conclusion

T₂ quantification can be a valuable tool for the diagnosis of degenerative disease. Several different sequences exist to quantify the relaxation times of tissues. Sequences range in scan time, SNR efficiency, reproducibility and two- or three-dimensional mapping. However, when choosing a sequence for quantitation, it is important to realize that several factors affect the measured T₂ relaxation time.     

Improvement of duty-cycle heating compensation in NMR spin relaxation experiments

To reliably measure NMR relaxation properties of macromolecules is a prerequisite for precise experiments that identify subtle variations in relaxation rates, as required for the determination of rotational diffusion anisotropy, CSA tensor determination, advanced motional modeling or entropy difference estimations. An underlying problem with current NMR relaxation measurement protocols is maintaining constant sample temperature throughout the execution of the relaxation series especially when rapid data acquisition is required. Here, it is proposed to use a combination of a heating compensation and a proton saturation sequence at the beginning of the NMR relaxation pulse scheme. This simple extension allows reproducible, robust and rapid acquisition of NMR spin relaxation data sets. The method is verified with (15)N spin relaxation measurements for human ubiquitin.     

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.     

Lesion T(2) relaxation times and volumes predict the response of malignant breast lesions to neoadjuvant chemotherapy

The aim of this study was to investigate the utility of the water T(2) values of malignant breast lesions in predicting response after the first and second cycles of neoadjuvant chemotherapy (NAC), both alone and in combination with lesion volumes. Thirty-five patients were scanned before the commencement of chemotherapy and again after the first, second and final treatment cycles. Two methods of obtaining lesion T(2) were used: imaging, where a series of T(2)-weighted images was acquired (T(R)/T(E)=1000/30, 60, 90 and 120 ms), and spectroscopy, where the T(2) value of unsuppressed water signal was determined with a multiecho sequence (T(R)=1.5 s; initial T(E)=35 ms; 64 steps of 2.5 ms; 2 unsuppressed acquisitions per T(E)). Lesion volumes were computed from contrast-enhanced 3D fat-suppressed images. The study found that, using the imaging method of obtaining T(2), the ratio of the product of lesion T(2) and volume after the second cycle of NAC to pretreatment value is a good predictor of ultimate lesion response, defined as a > or =65% reduction in tumor volume after the final treatment cycle, with positive and negative predictive values of 95.5% and 84.6%, respectively.     

Gradient-induced longitudinal relaxation of hyperpolarized noble gases in the fringe fields of superconducting magnets used for magnetic resonance

When hyperpolarized noble gases are brought into the bore of a superconducting magnet for magnetic resonance imaging (MRI) or spectroscopy studies, the gases must pass through substantial field gradients, which can cause rapid longitudinal relaxation. In this communication, we present a means of calculating this spatially dependent relaxation rate in the fringe field of typical magnets. We then compare these predictions to experimental measurements of (3)He relaxation at various positions near a medium-bore 2-T small animal MRI system. The calculated and measured relaxation rates on the central axis of the magnet agree well and show a maximum (3)He relaxation rate of 3.83×10(-3) s(-1) (T(1)=4.4 min) at a distance of 47 cm from the magnet isocenter. We also show that if this magnet were self-shielded, its minimum T(1) would drop to 1.2 min. In contrast, a typical self-shielded 1.5-T clinical MRI scanner will induce a minimum on-axis T(1) of 12 min. Additionally, we show that the cylindrically symmetric fields of these magnets enable gradient-induced relaxation to be calculated using only knowledge of the on-axis longitudinal field, which can either be measured directly or calculated from a simple field model. Thus, while most MRI magnets employ complex and proprietary current configurations, we show that their fringe fields and the resulting gradient-induced relaxation are well approximated by simple solenoid models. Finally, our modeling also demonstrates that relaxation rates can increase by nearly an order of magnitude at radial distances equivalent to the solenoid radius.