Relaxation of solvent protons by solute Gd3+-chelates,revisited

The magnetic field dependence (NMRD profile) of 1/T₁, of solvent protons in an aqueous solution of Gd(DTPA)^2? was remeasured at 5,15,25,30, and 35°C. The data were reanalyzed with the usual low-field theory, using recently published values for T_M, the residence lifetime of the single inner-coordinated waters of solute Gd(DTPA)^2?. (These T_M values are significantly longer than earlier estimates). Values were obtained for three dynamic parameters: T_R, the rotational relaxation time of solute ions, and T_SO and T_V, the low-field relaxation time of the Gd³⁺ magnetic moment and the related correlation time. These Gd(DTPA)²⁺ values, together with recent results for T_M for Gd(DTPA-BMA) — a nonionic structural analog of Gd(DTPA)^2? with an unusually long T_M — were used to calculate NMRD profiles at 5 and 35°C. These profiles agree very well with new data given here for a solution of Gd(DTPA-BMA). This reaffirms the importance of knowing the temperaturedependent values of T_M a priori in order to obtain unambiguous quantitative theoretical analyses of NMRD profiles of chelates of known structure. Additionally, the theory of inner sphere relaxation is extended to high fields, at which the magnetic energy of a solute moment is greater than its thermal energy.     

Magnetization transfer in cross-linked bovine serum albumin solutions at 200 MHz: A model for tissue

We report results for proton 1/T₁, 1/T₂, and K, the rate of magnetization transfer from solvent to solute, for 5 and 10 wt. % solutions of bovine serum albumin, both native and chemically cross-linked, in undeuterated and ～50% deuterated water, at 4.7 T (200.1 MHz) and 19°C. At this field, although K > 1/T₁ for the cross-linked samples, magnetization transfer contributes little to 1/T₁ directly. Therefore K was measured using off-resonance irradiation of the protein protons. The data for all the samples can be fit using a theoretical model for magnetization transfer, with three parameters: the intrinsic longitudinal relaxation rates of solute and solvent protons, and K. The magnitude of Kis so large that the newly-identified, long-lived (～1 μs) hydration sites (S. H. Koenig, R. D. Brown III, and R. Ugolini, Magn. Reson. Med., 29, 77 (1993)) must be invoked to account for K, as is necessary to explain the differential effects of cross linking on the magnetic field dependence of 1/T₁ of protons and deuterons and the large 1/T₁ and 1/T₂ values below ～20 MHz in immobilized systems. Although these sites are few in number, their long resident lifetime becomes the correlation time for magnetization transfer when protein is immobilized, accounting for the large value of K. Recent data from several laboratories have shown that cross-linked protein, as used here, is a good model for 1/T₁ and 1/T₂ of tissue, as a function of temperature and magnetic field.     

Inversion recovery at 7 T in the human myocardium: Measurement of T1, inversion efficiency and B1+

At clinical MRI field strengths (1.5 and 3 T), quantitative maps of the longitudinal relaxation time T₁ of the myocardium reveal diseased tissue without requiring contrast agents. Cardiac T₁ maps can be measured by Look‐Locker inversion recovery sequences such as ShMOLLI at 1.5 and 3 T. Cardiovascular MRI at a field strength of 7 T has recently become feasible, but doubts have remained as to whether magnetization inversion is possible in the heart due to subject heating and technical limitations. This work extends the repertoire of 7 T cardiovascular MRI by implementing an adiabatic inversion pulse optimized for use in the heart at 7 T. A “ShMOLLI+IE” adaptation of the ShMOLLI pulse sequence has been introduced together with new postprocessing that accounts for the possibility of incomplete magnetization inversion. These methods were validated in phantoms and then used in a study of six healthy volunteers to determine the degree of magnetization inversion and the T₁ of normal myocardium at 7 T within a 22‐heartbeat breathhold. Using a scanner with 16 × 1 kW radiofrequency outputs, inversion efficiencies ranging from ?0.79 to ?0.83 (intrasegment means; perfect 180° would give ?1) were attainable across the myocardium. The myocardial T₁ was 1925 ± 48 ms (mean ± standard deviation). Magn Reson Med, 70:1038–1046, 2013. © 2012 Wiley Periodicals, Inc.     

Magnetic resonance properties of ex vivo breast tissue at 1.5 T

The magnetic resonance absorption spectrum, T₁ and T₂ relaxation time distributions, and magnetization transfer properties of ex vivo breast tissue have been characterized at 1.5 T and 37°C. The fraction of fibroglandular tissue within individual tissue samples (n = 31) was inferred from the tissue volumetric water content obtained by integration of resolvable broad-line fat and water resonances. The spectroscopically estimated water content was strongly correlated with that extracted enzymatically (Pearson correlation coefficient 0.98, P « 0.01), which enabled the assignment of principal relaxation components for fibroglandular tissue (T₂ = 0.04 ± 0.01, T₁ = 1.33 ± 0.24 s), and for adipose tissue (T₂ = 0.13 ± 0.01, T₁ = 0.23 ± 0.01 s, and T₂ = 0.38 ± 0.03, T₁ = 0.62 ± 0.16 s). The relaxation components for fibroglandular tissue exhibited strong magnetization transfer, whereas those for adipose tissue showed little magnetization transfer effect. These results ultimately have applicability to the optimization of clinical magnetic resonance imaging and research investigations of the breast.     

T1 and T2 of ferritin solutions: Effect of loading factor

Proton magnetic relaxation times T₁ and T₂ were measured at field strengths from 0.05 T to 1.5 T in solutions of ferritin with loading factors from 90 to 3600 iron atoms per molecule. 1/T₂ increased linearly with field strength, as previously observed, and the slope per unit iron was approximately the same in all samples. This latter finding indicates that the field dependence of T₂ may be used as a measure of ferritin-bound iron, regardless of loading factor. A possible explanation is presented, based on the presumed antiferromagnetic structure of the ferritin core and the linear dependence of 1/T₂ on core magnetization. A nonzero contribution to 1/T₂ in the limit of low field and a contribution to 1/T₁ were also found, both of which increase linearly with loading factor for constant protein concentration; these effects represent quantum mechanical dipole-dipole relaxation of water protons either by iron atoms on the surface of the core or by the iron core itself. Finally, the extrapolated intercept at LF = 0 for both 1/T₁ and 1/T₂ indicates a contribution from a small number of iron ions bound to the protein shell. These results may help in the use of MRI to measure brain iron and possibly even ferritin loading factor.     

Intracellular and extracellular T1 and T2 relaxivities of magneto‐optical nanoparticles at experimental high fields

This study reports the T₁ and T₂ relaxation rates of rhodamine‐labeled anionic magnetic nanoparticles determined at 7, 11.7, and 17.6 T both in solution and after cellular internalization. Therefore cells were incubated with rhodamine‐labeled anionic magnetic nanoparticles and were prepared at decreasing concentrations. Additionally, rhodamine‐labeled anionic magnetic nanoparticles in solution were used for extracellular measurements. T₁ and T₂ were determined at 7, 11.7, and 17.6 T. T₁ times were determined with an inversion‐recovery snapshot‐flash sequence. T₂ times were obtained from a multispin‐echo sequence. Inductively coupled plasma‐mass spectrometry was used to determine the iron content in all samples, and r₁ and r₂ were subsequently calculated. The results were then compared with cells labeled with AMI‐25 and VSOP C‐200. In solution, the r₁ and r₂ of rhodamine‐labeled anionic magnetic nanoparticles were 4.78/379 (7 T), 3.28/389 (11.7 T), and 2.00/354 (17.6 T). In cells, the r₁ and r₂ were 0.21/56 (7 T), 0.19/37 (11.7 T), and 0.1/23 (17.6 T). This corresponded to an 11‐ to 23‐fold decrease in r₁ and an 8‐ to 15‐fold decrease in r₂. A decrease in r₁ was observed for AMI‐25 and VSOP C‐200. AMI‐25 and VSOP exhibited a 2‐ to 8‐fold decrease in r₂. In conclusion, cellular internalization of iron oxide nanoparticles strongly decreased their T₁ and T₂ potency. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

T1ρ of protein solutions at very low fields: Dependence on molecular weight,concentration, and structure

The effect of molecular weight, concentration, and structure on 1/T₁ρ, the rotating frame relaxation rate, was investigated for several proteins using the on-resonance spin-lock technique, for locking fields B₁ < 200 μT. The measured values of 1/T₁ρ, were fitted to a simple theoretical model to obtain the dispersion curves 1/T₁ρ(ω₁) and the relaxation rate at zero B₁ field, 1/T₁ρ,(O). 1/T₁ρ, was highly sensitive to the molecular weight, concentration, and structure of the protein. The amount of intra- and intermolecular hydrogen and disulfide bonds especially contributed to 1/T₁ρ. In all samples, 1/T₁ρ(O) was equal to 1/T₂ρ measured at the main magnetic field B_o = 0.1 T, but at higher locking fields the dispersion curves mono-tonically decreased. The results of this work indicate that a model considering the effective correlation time of molecular motions as the main determinant for 1/T₁ρ relaxation in protein solutions is not valid at very low B₁ fields. The underlying mechanism for the relaxation rate 1/T₁ρ at B₁ fields below 200 μT is discussed.     

T1 discrimination contributions to proton magnetization transfer in heterogeneous biological systems

Water proton spin-lattice relaxation times are commonly used as a guide in establishing the off-resonance irradiation time as well as the repetition time of the magnetization transfer experiment. T₁ discrimination effects occur if the motionally restricted spin bath longitudinal magnetization does not reach thermal equilibrium. In this study we developed the formalism necessary for the evaluation of T₁ discrimination contributions to proton magnetization transfer arising from the use of a short repetition time relative to the spin-lattice relaxation time of the motionally restricted spin bath. The results of computer simulation indicate that T₁, discrimination contributions occur when the repetition time is small relative to the spin-lattice relaxation time of the motionally restricted spin bath, and when the off-resonance irradiation is weak and far off-resonance. For somewhat longer repetition times, T₁ discrimination contributions become important only when the cross relaxation rate is small, and the fractional amount of motionally restricted component large. The occurrence of T₁ discrimination effects results in distortion of water proton intensity ratio dispersion curves thereby resulting in the estimation of erroneous magnetization transfer parameters, whereas in magnetization transfer contrast enhanced imaging, such contributions are manifested by a decrease in image contrast.     

Dependence of the solvent proton 1/T1 on the iron content in normal human serum

The iron content dependence of the spin-lattice relaxation rates (I / T₁) of solvent protons in healthy human serum has been studied by FT NMR at 60 MHz. A linear relationship has been established between 1/T₁ and the iron content (with a correlation of 0.89). Our data suggest that Fe(III)–transferrin can contribute to the relaxation rate in healthy human Serum. © 1988 Academic Press, Inc.     

T1ρ-relaxation in articular cartilage: Effects of enzymatic degradation

Spin-lattice relaxation in the rotating frame (T_1ρ) dispersion spectroscopy and imaging were used to study normal and enzymatically degraded bovine articular cartilage. Normal specimens demonstrate significant T_1ρ “dispersion” (～60 to ～130 ms) in the 100 Hz to 9 kHz frequency range. Proteoglycan-degraded specimens have 33% greater T_1ρ values than collagen-degraded or normal samples. T_1ρ-weighted images reveal structure not found in conventional T₁-or T₂-weighted images. Our results suggest that T_1ρ measurements are selectively sensitive to proteoglycan content. The potential of this method in distinguishing the early degenerative changes in cartilage associated with osteoarthritis is discussed.     

A molecular theory of relaxation and magnetization transfer: Application to cross-linked BSA,a model for tissue

Homogeneous soft tissue, as regards its magnetic relaxation properties, is well-modeled by solutions of cross-linked protein (see Koenig and Brown, Prog. NMR Specfr. 22,487 (1991)). Interactions at the solute-solvent interface alter the hydrodynamics of solvent water, and also couple the solute and solvent proton Zeeman energy reservoirs, giving hydrodynamic and cross-relaxation contributions to water proton relaxation that respond differently to deuteration of solvent. We report measurements of the magnetic field dependence of 1/T₁, of water protons in cross-linked bovine serum albumin (BSA), for partially deuterated solvent and, in order to separate these two contributions, of 1/T₁, of deuterons. The major experimental finding is that, in addition to recently identified water-binding sites on protein (covering ～0.2% of the surface) with water lifetimes of about 1 μs, there is another group of sites with lifetimes of about 23 ns, covering ～2% of the surface, which are evident in both proton and deuteron data. In addition, we have formulated a theory of interfacial proton-proton magnetic interactions which—with these four parameters, plus two that quantify the protein-water coupling at each site—can account for all the proton and deuteron data, in both native and cross-linked BSA.     

Magnetic microparticle aggregation for viscosity determination by MR

Micron‐sized magnetic particles were induced to aggregate when placed in homogeneous magnetic fields, like those of MR imagers and relaxometers, and then spontaneously returned to their dispersed state when removed from the field. Associated with the aggregation and dispersion of the magnetic particles were time‐dependent increases and decreases in the spin–spin relaxation time (T₂) of the water. Magnetic nanoparticles, with far smaller magnetic moments per particle, did not undergo magnetically induced aggregation and exhibited time‐independent values of T₂. The rate of T₂ change associated with magnetic microparticle aggregation was used to determine the viscosity of liquid samples, providing a method that can be of particular advantage for determining the viscosity of small volumes of potentially biohazardous samples of blood or blood plasma. Magn Reson Med 59:515–520, 2008. © 2008 Wiley‐Liss, Inc.     

New method for contrast manipulation in DNP-enhanced MRI

The magnetization subtraction technique (MS), which is equivalent to the inversion recovery technique in strong magnetic fields, has been implemented in dynamic nuclear polarization-enhanced magnetic resonance imaging (DNPI). The general theoretical basis of the MS method, which can be applied to DNPI or to prepolarized MRI in weak magnetic fields (such as Earth's magnetic field), is introduced. Details are provided about the signal amplitude, dynamic range of the method, and conditions required to observe signal void in samples with specific T₁ relaxation times. The experimental results obtained with MS DNPI are presented and discussed. In the experiments, electron spin resonance irradiation frequencies of 199 MHz and 16.2 MHz were employed. Also, T₁ contrast manipulation in the polarizing and in the detection magnetic field is discussed and demonstrated for MS DNPI.     

T1 corrected B1 mapping using multi‐TR gradient echo sequences

This work presents a new approach toward a fast, simultaneous amplitude of radiofrequency field (B₁) and T₁ mapping technique. The new method is based on the “actual flip angle imaging” (AFI) sequence. However, the single pulse repetition time (TR) pair used in the standard AFI sequence is replaced by multiple pulse repetition time sets. The resulting method was called “multiple TR B₁/T₁ mapping” (MTM). In this study, MTM was investigated and compared to standard AFI in simulations and experiments. Feasibility and reliability of MTM were proven in phantom and in vivo experiments. Error propagation theory was applied to identify optimal sequence parameters and to facilitate a systematic noise comparison to standard AFI. In terms of accuracy and signal‐to‐noise ratio, the presented method outperforms standard AFI B₁ mapping over a wide range of T₁. Finally, the capability of MTM to determine T₁ was analyzed qualitatively and quantitatively, yielding good agreement with reference measurements. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Effects of nitroxides on the magnetic field and temperature dependence of 1/T1 of solvent water protons

We report a study of the longitudinal NMRD profiles (proton longitudinal relaxation rates as a function of field strength) over a broad range of magnetic field (0.01 to 50 MHz proton Larmor frequency) and temperature (-9.6 to 37 degrees C) for aqueous solutions of (i) a fatty acid-nitroxide/albumin complex and (ii) 10 low molecular weight nitroxides. Analysis of the NMRD profile for the fatty acid-nitroxide/albumin complex provides a lower bound estimate for the rotational correlation time of the complex, which permits the calculation of an upper bound on the inner sphere contribution to relaxation of the uncomplexed nitroxides. Inner sphere processes, ostensibly due to water molecules hydrogen bonded to the nitroxide moiety, dominate the relaxation effects of the slowly rotating macromolecular nitroxide/albumin complex. By extrapolation, the contribution of these inner sphere processes are negligible for rapidly tumbling nitroxides free in solution, which affect solvent proton relaxation almost entirely through outer sphere processes (i.e., translational diffusion). A comparison of the relaxation data for aqueous solutions of the uncomplexed nitroxides with the theory of outer sphere relaxation of J.H. Freed (J. Chem. Phys. 68, 4034 (1978] yields values for the distance of closest approach of the water and nitroxide molecules, as well as for their relative diffusion constants, at five different temperatures. Our results indicate that the rather modest relaxivities of aqueous solutions of nitroxides increase substantially with increased solvent viscosity and with protein binding, supporting the potential utility of nitroxides for enhancement of contrast in nuclear magnetic resonance images.     

Compensation of Diffusion Effects in T2 Measurements

Measurements of the transverse relaxation time T₂ are usually conducted with the Carr Purcell Meiboom Gill (CPMG) pulse sequence, which causes T₂-weighted magnetization. Diffusion effects are a common source of error in measurements of this kind, because the incoherent motion of spins in external magnetic field gradients distorts T₂ weighting of the transverse magnetization. As a result, inaccurate T₂-values are obtained. In this work, we present a method which completely compensates for the effect of diffusion.     

Metabolite proton T2 mapping in the healthy rhesus macaque brain at 3 T

The structure and metabolism of the rhesus macaque brain, an advanced model for neurologic diseases and their treatment response, is often studied noninvasively with MRI and ¹H‐MR spectroscopy. Due to the shorter transverse relaxation time (T₂) at the higher magnetic fields these studies favor, the echo times used in ¹H‐MR spectroscopy subject the metabolites to unknown T₂ weighting, decreasing the accuracy of quantification which is key for inter‐ and intra‐animal comparisons. To establish the “baseline” (healthy animal) T₂ values, we mapped them for the three main metabolites' T₂s at 3 T in four healthy rhesus macaques and tested the hypotheses that their mean values are similar (i) among animals; and (ii) to analogs regions in the human brain. This was done with three‐dimensional multivoxel ¹H‐MR spectroscopy at (0.6 × 0.6 × 0.5 cm)³ = 180 μL spatial resolution over a 4.2 × 3.0 × 2.0 = 25 cm³ (～30%) of the macaque brain in a two‐point protocol that optimizes T₂ precision per unit time. The estimated T₂s in several gray and white matter regions are all within 10% of those reported in the human brain (mean ± standard error of the mean): N‐acetylaspartate = 316 ± 7, creatine = 177 ± 3, and choline = 264 ± 9 ms, with no statistically significant gray versus white matter differences. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Characterizing healthy and diseased white matter using quantitative magnetization transfer and multicomponent T2 relaxometry: A unified view via a four‐pool model

Nuclear magnetic resonance relaxation and magnetization transfer in cerebral white matter can be described using a four‐pool model: two for water protons (in separate myelin and intra/extracellular compartments) and two for protons associated with the lipids and proteins of biologic membranes (of myelin and nonmyelin semisolids). This model was used to gain insight into the observations from multicomponent quantitative T₂ relaxometry and quantitative magnetization transfer imaging, both based on simplified white matter models and experimentally feasible in vivo. Using a set of coupled Bloch equations describing the behavior of the magnetization in a four‐pool model of white matter, simulations of the quantitative T₂ relaxometry and quantitative magnetization transfer imaging techniques were performed. Pathology‐inspired modifications were made to the four‐pool model to gauge their impact on quantitative T₂ relaxometry and quantitative magnetization transfer imaging observations. Our results show that changes in the rate of water movement between microanatomic compartments may impact otherwise stable quantitative T₂ relaxometry observations; that the measure of the quantitative magnetization transfer imaging–based semisolid pool population is robust, despite the presence of two distinct semisolid components; and that quantitative magnetization transfer imaging compartment size estimates are not influenced by changes in the T₂ of the intra/extracellular water pool. The four‐pool model, while impractical for in vivo characterization, yields important insight into the interpretation of changes observed with these quantitative MRI methods based on simplified models of white matter. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: Comparison of T1, T2*, and synergistic T1 − T2* contrast mechanisms

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T₁ shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T₂*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T₁ and T₂* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T₁ contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T₂* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T₁ and T₂* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor‐targeted IONPs in vivo. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Pliosphocreatine T1 measurements with and without exchange in the heart

The intrinsic phosphocreatine (PCr) T₁ values measured by time-dependent magnetization transfer in isolated perfused rat, hamster, and turkey hearts were indistinguishable. The value of 3.5 ± 0.3 s for the rat heart is similar to values measured by other magnetization transfer methods. Irreversibly inhibiting the phosphoryl exchange between PCr and ATP in the rat heart using iodoacetamide changed the apparent T₁ values of the two exchanging species when measured by inversion recovery: The apparent T₁ of PCr increased from 1.92 ± 0.06 s to 3.55 ± 0.06 s, in excellent agreement with the intrinsic T₁, measured by magnetization transfer. The apparent T₁ of [γ-P]ATP decreased from 0.92 ± 0.07 s to 0.44 ± 0.03 s. The value for the T₁ of [γ-P]ATP in hearts with inhibited phosphoryl exchange was similar to T₁ values for [α-P]ATP and [β-P]ATP, which remained unchanged. This illustrates that apparent T₁ values for PCr and [γ-P]ATP measured by inversion recovery in the presence of exchange are average T₁ values in between the intrinsic values. The large differences between the intrinsic T₁ measured by magnetization transfer and the T₁ measured by inversion recovery makes the use of the appropriate value in different applications quantitatively important.