Quantification of superparamagnetic iron oxide using inversion recovery balanced steady-state free precession

Cellular and molecular MRI trafficking studies using superparamagnetic iron oxide (SPIO) have greatly improved non-invasive investigations of disease progression and drug efficacy, but thus far, these studies have largely been restricted to qualitative assessment of hypo- or hyperintense areas near SPIO. In this work, SPIO quantification using inversion recovery balanced steady-state free precession (IR-bSSFP) was demonstrated at 3 T by extracting R₂ values from a monoexponential model (P. Schmitt et al., 2004). A low flip angle was shown to reduce the apparent recovery rate of the IR-bSSFP time course, thus extending the dynamic range of quantification. However, low flip angle acquisitions preclude the use of traditional methods for combining RF phase-cycled images to reduce banding artifacts arising from off-resonance due to B₀ inhomogeneity. To achieve R₂ quantification of SPIO, we present a new algorithm applicable to low flip angle IR-bSSFP acquisitions that is specifically designed to identify on-resonance acquisitions. We demonstrate in this work, using both theoretical and empirical methods, that the smallest estimated R₂ from multiple RF phase-cycled acquisitions correspond well to the on-resonance time course. Using this novel minimum R₂ algorithm, homogeneous R₂ maps and linear R₂ calibration curves were created up to 100 μg(Fe)/mL with 20° flip angles, despite substantial B₀ inhomogeneity. In addition, we have shown this technique to be feasible for pre-clinical research: the minimum R₂ algorithm was resistant to off-resonance in a single slice mouse R₂ map, whereas maximum intensity projection resulted in banding artifacts and overestimated R₂ values. With the application of recent advances in accelerated acquisitions, IR-bSSFP has the potential to quantify SPIO in vivo, thus providing important information for oncology, immunology, and regenerative medicine MRI studies.     

Gyromagnetic ratios of 4+ and 6+ states in156Gd and158Gd

The followingg-factors have been derived from time integral measurements of γ-γ angular correlations in the static magnetic hyperfine field of magnetized gadolinium metal probes:¹⁵⁶Gd:g(4 ₁ ⁺ )=+0.310(19)g(6 ₁ ⁺ )=+0.25(21)g(4 ₃ ⁺ , 1511 keV)=+0.809(27)¹⁵⁸Gd:g(4 ₁ ⁺ )=+0.409(15). The 5.35d ¹⁵⁶Tb sources were produced by the reaction¹⁵⁶Gd(d, 2n)¹⁵⁶Tb in our cyclotron. A carrier-free 150y ¹⁵⁸Tb source was obtained from ISOLDE/CERN. In comparison with the precisely knowng-factors of the 2 ₁ ⁺ states,g(2 ₁ ^su+ ,¹⁵⁶Gd) =+0.386(4) andg(2 ₁ ⁺ ,¹⁵⁸Gd)=0.381(4), we observe a large reduction for the¹⁵⁶Gd 4 ₁ ⁺ state whereasg increases slightly for¹⁵⁸Gd. The half-life of the 4 ₁ ⁺ state of¹⁵⁸Gd was remeasured as¹⁵⁸Gd:T _1/2(4 ₁ ⁺ )=148(2) ps. A measurement of the rotation in the 4 ₃ ⁺ state of¹⁵⁶Gd in external magnetic fields of various strengths up toB _ext=9.5 T did not confirm the anomalous dependence of the magnetic hyperfine field in gadolinium metal on the external field, which has been reported by Persson et al. [29].     

Feasibility of MR fingerprinting using a high-performance 0.55 T MRI system

BackgroundMR fingerprinting (MRF) is a versatile method for rapid multi-parametric quantification. The application of MRF for lower MRI field could enable multi-contrast imaging and improve exam efficiency on these systems. The purpose of this work is to demonstrate the feasibility of 3D whole-brain T1 and T2 mapping using MR fingerprinting on a contemporary 0.55 T MRI system.Materials and methodsA 3D whole brain stack-of-spirals FISP MRF sequence was implemented for 0.55 T. Quantification was validated using the NIST/ISMRM Quantitative MRI phantom, and T1 and T2 values of white matter, gray matter, and cerebrospinal fluid were measured in 19 healthy subjects. To assess MRF performance in the lower SNR regime of 0.55 T, measurement precision was calculated from 100 simulated pseudo-replicas of in vivo data and within-session measurement repeatability was evaluated.ResultsT1 and T2 values calculated by MRF were strongly correlated to standard measurements in the ISMRM/NIST MRI system phantom (R² > 0.99), with a small constant bias of approximately 5 ms in T2 values. 3D stack-of-spirals MRF was successfully applied for whole brain quantitative T1 and T2 at 0.55 T, with spatial resolution of 1.2 mm × 1.2 mm × 5 mm, and acquisition time of 8.5 min. Moreover, the T1 and T2 quantifications had precision <5%, despite the lower SNR of 0.55 T.ConclusionA 3D whole-brain stack-of-spirals FISP MRF sequence is feasible for T1 and T2 mapping at 0.55 T.     

Development of fast deep learning quantification for magnetic resonance fingerprinting in vivo

PurposeA deep neural network was developed for magnetic resonance fingerprinting (MRF) quantification. This study aimed at extending previous studies of deep learning MRF to in vivo applications, allowing sub-second computation time for large-scale data.MethodsWe applied the deep learning methodology based on our previously published multi-layer perceptron. The number of layers was four, which was optimized to balance the model capacity and noise robustness. The training sets were obtained from MRF dictionaries with 9000 to 28,000 atoms, depending on the desired T1 and T2 ranges. The simulated MRF undersampling artifact based on the k-space acquisition scheme and noise were both added to the training data to reduce the error in estimates.ResultsThe neural network achieved high fidelity (R2 _ 0.98) as compared to the T1 and T2 values of the ISMRM standardized phantom. In brain MRF experiment, the model trained with simulated artifacts and noise showed less error compared to that without. The in vivo application of our neural network for liver and prostate were also demonstrated. For an MRF slice with 256 _ 256 image resolution, the computation time of our neural network was 0.12 s, compared with the _ 28 s-pre-slice for the conventional dictionary matching method.ConclusionOur neural network achieved fast computation speed for MRF quantification. The model trained with simulated artifacts and noise showed less error and achieved optimal performance for phantom experiment and in vivo normal brain and liver, and prostate cancer patient.     

A multi-scale residual network for accelerated radial MR parameter mapping

A deep learning MR parameter mapping framework which combines accelerated radial data acquisition with a multi-scale residual network (MS-ResNet) for image reconstruction is proposed. The proposed supervised learning strategy uses input image patches from multi-contrast images with radial undersampling artifacts and target image patches from artifact-free multi-contrast images. Subspace filtering is used during pre-processing to denoise input patches. For each anatomy and relaxation parameter, an individual network is trained. in vivo T₁ mapping results are obtained on brain and abdomen datasets and in vivo T₂ mapping results are obtained on brain and knee datasets. Quantitative results for the T₂ mapping of the knee show that MS-ResNet trained using either fully sampled or undersampled data outperforms conventional model-based compressed sensing methods. This is significant because obtaining fully sampled training data is not possible in many applications. in vivo brain and abdomen results for T₁ mapping and in vivo brain results for T₂ mapping demonstrate that MS-ResNet yields contrast-weighted images and parameter maps that are comparable to those achieved by model-based iterative methods while offering two orders of magnitude reduction in reconstruction times. The proposed approach enables recovery of high-quality contrast-weighted images and parameter maps from highly accelerated radial data acquisitions. The rapid image reconstructions enabled by the proposed approach makes it a good candidate for routine clinical use.     

Study of the electric field gradient at <Superscript>111</Superscript>Cd in the <Emphasis Type="Italic">R</Emphasis>Al<Subscript>3</Subscript> compounds synthesized under high pressure

The electric quadrupole interaction parameters for impurity ¹¹¹Cd nuclei in intermetallic RAl₃ compounds (R = La, Ce, Sm, Gd, Tb, Dy, Ho, Er, Yb, or Lu) synthesized under high (8 GPa) pressure at high (1800–1900°C) temperatures have been measured using the method of perturbed angular γγ correlations. It has been established by X-ray diffraction analysis that with an increase in the atomic number of the R element the obtained high-pressure phases are crystallized successively in the orthorhombic, hexagonal, and cubic structures. In the compounds with R = La, Ce, Sm, and Gd, deviation from the known structural types and formation of new ones due to the change in the stoichiometric composition have been observed. The data obtained by the method of perturbed angular γγ correlations have confirmed deviation from the specified stoichiometric composition 1R: 3Al for the LaAl₃, CeAl₃, SmAl₃, and GdAl₃ compounds and verified the correctness of the stoichiometric composition and the presence of the Cu₃Au structural type for the remaining RAl₃ high-pressure phases.     

Magnetism,spin relaxation and hyperfine interactions of rare earths in RM6Al6(M = Cr,Mn, Cu)

The systems RM₆Al₆ (R = rare earth or Y, M = Cr, Mn, Cu, Rh) were studied by magnetization measurements and by Mossbauer spectroscopy of ¹⁵⁵Gd, ¹⁶¹Dy, ¹⁶⁶Er and ¹⁷⁰Yb. The magnetization studies show weak R-R antiferromagnetic exchange interactions in RCu₆Al₆(T_n)Gd) = 21 K, less than 4 K for all other R and strong crystalline field effects. Similar phenomena are observed in RMn₆Al₆ and RCr₆Al₆, however, due to the presence of a Mn or Cr local moment the systems order ferrimagnetically. In RCr₆Al₆the order temperatures are low T_c ～ 25 K, yet T_c(GdCr₆Al₆) = 170 K. The Mossbauer studies observations are consistent with the magnetiza results. In the case where Er and Yb are not ordered at 4.1 K, the spectra still show magnetic hyperfine structure however of paramagnetic nature. The spectra yield the hyperfine interaction spin Hamiltonian parameters and the spin relaxation rates. These turn out to be extremely slow (1O⁸–1O⁹ sec^?1, a very uncommon phenomenon for a concentrated Er or Yb metallic system.     

Thermo and photoluminescence properties of Eu activated hexagonal, monoclinic and cubic gadolinium oxide nanorods

Different phases of Eu³⁺ activated gadolinium oxide (Gd (OH)₃, GdOOH and Gd₂O₃) nanorods have been prepared by the hydrothermal method with and without cityl trimethyl ammonium bromide (CTAB) surfactant. Cubic Gd₂O₃:Eu (8 mol%) red phosphor has been prepared by the dehydration of corresponding hydroxide Gd(OH)₃:Eu after calcinations at 350 and 600 °C for 3 h, respectively. When Eu³⁺ ions were introduced into Gd(OH)₃, lattice sites which replace the original Gd³⁺ ions, a strong red emission centered at 613 nm has been observed upon UV illumination, due to the intrinsic Eu³⁺ transition between ⁵D₀ and ⁷F configurations. Thermoluminescence glow curves of Gd (OH)₃: Eu and Gd₂O₃:Eu phosphors have been recorded by irradiating with gamma source (⁶⁰CO) in the dose range 10-60 Gy at a heating rate of 6.7 °C sec⁻¹. Well resolved glow peaks in the range 42-45, 67-76, 95-103 and 102-125 °C were observed. When γ-irradiation dose increased to 40 Gy, the glow peaks were reduced and with increase in γ-dose (50 and 60 Gy) results the shift in first two glow peak temperatures at about 20 °C and a new shouldered peak at 86 °C was observed. It is observed that there is a shift in glow peak temperatures and variation in intensity, which is mainly attributed to different phases of gadolinium oxide. The trapping parameters namely activation energy (E), order of kinetics (b) and frequency factor were calculated using peak shape and the results are discussed.     

155Gd and 161Dy Mössbauer study of R1+εFe4B4 alloys (R = Gd,Dy)

Tetragonal R_1+εFe₄B₄ alloys with R = Gd and Dy have been investigated by Mössbauer spectroscopy, using the ¹⁵⁵Gd and ¹⁶¹Dy resonances, respectively. The Gd quadrupolar interaction e²qQ = 12.65(5)mm/s is the largest observed to date in metallic compounds of Gd. For Dy this interaction is e²qQ = 74(2) mm/s, a value rather small for a Dy compound. Both results imply a strong lattice contribution to the electric field gradient. A crystal-field term A⁰₂ = -2450(50) K/a²_o is inferred. Our data are consistent with a point-charge calculation, provided charges of opposite signs are assumed for Fe and B atoms. Hyperfine parameters show some dispersion, reflecting the quasi incommensurate nature of the R and Fe+B sublattices in the R_1+εFe₄B₄ structure.     

High-pressure NMR study of water exchange on magnetic resonance imaging contrast agents

Abstract

The knowledge of water exchange reaction mechanism in aqueous solutions of Gd³⁺ polyaminocarboxylates is important for the understanding of the relatively slow water exchange rates measured for these complexes. Variable ressure measurements show a change of mechanism from associatively activated on [Gd(H₂O)₈]³⁺ and [Gd(PDTA)(H₂O₂)₂]^? to probably limiting dissociative on the MRI contrast agents [Gd(DOTA)(H₂O)]^?, [Gd(DTPA)(H₂O)]^2? and [Gd(DTPA-BMA)(H₂O)].     

g-Faktoren und Multipol-Mischungsverhältnisse in156Gd

By integral perturbedγ-γ-angular correlation the gyromagnetic ratios of a 2-quasi-particle state at 1,513 keV and the 4⁺ state of the ground state rotational band in¹⁵⁶Gd were measured, using sources prepared by¹⁵⁹Tb(γ, 3n) and¹⁵⁶Gd(d, 2n) reactions:g _{1;513 keV} ⁴⁺ =0.78±0.05;g _R ⁴⁺ =0.37±0.05. In addition we obtain the multipole mixing ratiosδ _{535 keV}(M2/E1)=?0.09±0.01;δ _{1,225 keV}(E2/M1)=+1.83±0.10 for the 535 keV and 1,225 keVγ-rays. The classification of the 1,513 keV state is discussed. The internal field of Gd in Tb metal at 77 °K was found to beH=(?192±16)kOe.     

Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent

This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n = 6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r₁), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r₁ of Gd-DTPA-CS₁₁ was up to 11.65 mM^− 1·s^− 1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS₁₁ showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA.     

Four-wave mixing and hyper-Raman scattering in CuCl

Non-degenerate four-wave mixing using two non-collinear laser beams with frequencies (wavevectors) ω_p, ω_t (k_p, k_t) respectively is studied in CuCl. Two emission lines at frequencies ω⁽¹⁾=2ω_t-ω_p, and ω⁽²⁾=2ω_p-ω_t are observed. Their excitation spectrum is sharply peaked if the phase-match condition k⁽¹⁾=2k_t-k_p is fulfilled. This is the case, if ω_p coincides with the hyper-Raman lines (R⁺_T, R^-_T) of the laser labelled (t) in a well-defined geometrical configuration.     

The relaxivity of Gd-EOB-DTPA and Gd-DTPA in liver and kidney of the Wistar rat

The NMR relaxivities of Gd-EOB-DTPA and Gd-DTPA were determined in the kidney and liver of intact male Wistar rats immediately following sacrifice and in vitro in solutions and gels, at 1.5 T using a clinical MR scanner. T₁ and T₂ values of tissue samples were derived from spin-echo image sequences. Tissue gadolinium concentrations were determined by radioassay of Gd¹⁵³. Gd-EOB-DTPA T₁ and T₂ relaxivities, R₁ and R₂ (s⁻¹ mmole⁻¹ kg), were found to be 10.7 ± 0.5 and 22.5 ± 3.2, respectively, for liver, 2.4 ± 0.2 and 12.1 ± 1.7 for kidney cortex, 2.7 ± 0.2 and 14.5 ± 1.9 for kidney outer medulla, 2.0 ± 0.2 and 11.4 ± 2.1 for kidney inner medulla. Gd-DTPA R₁ and R₂ were found to be 4.8 ± 0.4 and 14.5 ± 3.7 for liver, 1.2 ± 0.1 and 7.9 ± 0.8 for kidney cortex, 1.6 ± 0.1 and 10.2 ± 1.4 for kidney outer medulla, 1.3 ± 0.1 and 10.2 ± 1.2 for kidney inner medulla. Gd-EOB-DTPA and Gd-DTPA R₁ was increased in liver compared to agarose gels at 38°C (4.49 ± 0.03 and 3.47 ± 0.06), but reduced in kidney tissues. All R₂ were elevated compared to agarose gels at 38°C (5.72 ± 0.12 and 4.12 ± 0.03). Elevated R₂ and R₁ (expressed in terms of the concentration of gadolinium per kg of tissue) can be accounted for in part by the lower water content of tissues compared with gels or solutions, increased microviscosity and binding to macromolecules. In addition, susceptibility effects may give rise to further increases in R₂. By contract, the reduced R₁ observed in kidney may be the result of compartmentalization of the magnetopharmaceuticals. Statistically improved fits were obtained for T₁ recovery curves for liver in the presence of Gd-EOB-DTPA when a dual exponential model was used. Assuming in vitro values for the relaxivities of these artificial contrast agents will lead to inaccuracies when relating observed signal enhancement factors to tissue gadolinium concentration.     

Quantitative MR imaging of targeted SPIO particles on the cell surface and comparison to flow cytometry

Purpose

To detect anti-CEACAM5 targeted superparamagnetic iron oxide (SPIO) particles in vitro on the cell surface by quantitative magnetic resonance (MR) imaging and to compare with flow cytometry.

Materials and Methods

The monoclonal mouse antibody T84.1 and an appropriate IgG isotype antibody were conjugated to dextran-coated SPIO particles. HT29 cells expressing carcinoembryonic antigen (CEACAM5) were treated with antibody-conjugated SPIO particles. Purified cell samples were examined on a 3.0-T MR scanner using a multi-echo spin-echo sequence for MR relaxometry. Aliquots of the cell samples were further treated with a fluorescein isothiocyanate (FITC) anti-dextran antibody and an Alexa Fluor 488 anti-mouse antibody for the corresponding flow cytometry.

Results

MR relaxometry revealed a dose-dependent binding of T84.1-conjugated SPIO particles with a positive correlation between R₂ relaxation rate of cell samples and SPIO particle concentration during incubation (r=0.993, P<.01). Positive correlations were also observed between R₂ relaxation rate and flow cytometry (geometric mean) with both fluorescent antibodies (r=0.972 and r=0.953, both P<.01), respectively.

Conclusion

The study revealed the feasibility of quantitative MR imaging of targeted SPIO particles on the cell surface comparable to flow cytometry.     

Rapid high-resolution volumetric T1 mapping using a highly accelerated stack-of-stars Look Locker technique

PurposeTo develop a fast volumetric T₁ mapping technique.Materials and methodsA stack-of-stars (SOS) Look Locker technique based on the acquisition of undersampled radial data (>30× relative to Nyquist) and an efficient multi-slab excitation scheme is presented. A principal-component based reconstruction is used to reconstruct T₁ maps. Computer simulations were performed to determine the best choice of partitions per slab and degree of undersampling. The technique was validated in phantoms against reference T₁ values measured with a 2D Cartesian inversion-recovery spin-echo technique. The SOS Look Locker technique was tested in brain (n = 4) and prostate (n = 5). Brain T₁ mapping was carried out with and without k_z acceleration and results between the two approaches were compared. Prostate T₁ mapping was compared to standard techniques. A reproducibility study was conducted in brain and prostate. Statistical analyses were performed using linear regression and Bland Altman analysis.ResultsPhantom T₁ values showed excellent correlations between SOS Look Locker and the inversion-recovery spin-echo reference (r² = 0.9965; p < 0.0001) and between SOS Look Locker with slab-selective and non-slab selective inversion pulses (r² = 0.9999; p < 0.0001). In vivo results showed that full brain T₁ mapping (1 mm³) with k_z acceleration is achieved in 4 min 21 s. Full prostate T₁ mapping (0.9 × 0.9 × 4 mm³) is achieved in 2 min 43 s. T₁ values for brain and prostate were in agreement with literature values. A reproducibility study showed coefficients of variation in the range of 0.18–0.2% (brain) and 0.15–0.18% (prostate).ConclusionA rapid volumetric T₁ mapping technique was developed. The technique enables high-resolution T₁ mapping with adequate anatomical coverage in a clinically acceptable time.     

Lifetime of the second excited state in157Gd

The mean life of the 131.5 keV, 7/2^? state in¹⁵⁷Gd was measured using a modified version of the microwave method. The result obtained is \(\tau = 137 \pm 7ps.\) .The deduced magnetic parametersg _K, g_R are discussed and compared with theory.     

Trinuclear Gd(III) Metal Complex with Amide Core Display Remarkable Enhancement in Relaxivity

New trinuclear gadolinium(III) complex having 2-bromoisovaleric acid pendant arm is reported. The longitudinal relaxivity (r _1p) of the complex is 23.17 mM^?1 s^?1 which correspond to a “per Gd” relaxivity of 7.72 mM^?1 s^?1. The transverse relaxivity (r _2p) of the complex is 24.79 mM^?1 s^?1 which correspond to a “per Gd” value of 8.26. The complex exhibit r _1p and r _2p values of 29.19 and 35.20, respectively, in the presence of HSA. The complex also shows pH dependant relaxivity which is an added advantage of the complex for utilization in cancer cell magnetic resonance imaging. The higher relaxivity values in water and HSA indicates a compact solution structure for the complexes and a restricted internal motion about the amide spacer.     

An organic electroluminescent device made from a gadolinium complex

A gadolinium ternary complex, tris(1-phenyl-3-methyl-4-isobutyryl-5-pyrazolone) (phenanthroline) gadolinium [Gd(PMIP)₃(Phen)] was synthesized and used as a light emitting material in the organic electroluminescent (EL) devices. The triple layer device with a structure of indium tin oxide (ITO)/N,N′-diphenyl-N,N′-bis(3-methylphenyl)-1,1′-biphenyl-4,4′-diamine (TPD) (20 nm)/Gd(PMIP)₃(Phen) (80 nm)/2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (bathocuproine or BCP) (20 nm)/Mg: Ag(200 nm)/Ag(100 nm) exhibited green emission peaking at 535 nm. A maximum luminance of 230 cd/m² at 17 V and a peak power efficiency of 0.02 lm/w at 9 V were obtained.     

Hyperfine interactions in R x Gd1− x Fe3 intermetallics R = Tb,Y

The structural and magnetic properties of rare earth iron intermetallic compounds Tb _x Gd_1?x Fe₃ and Y _x Gd_1?x Fe₃ (x = 0. 0, 0. 1, 0. 2, 0. 4, 0. 5, 0. 6, 0. 8, 1. 0) was studied by X-ray diffraction, the ⁵⁷Fe Mössbauer effect and SQUID measurements. All investigated compounds crystallize in the rhombohedral PuNi3-type of crystal structure. The investigation of magnetic properties of R _x Gd_1?x Fe₃ proved their ferrimagnetic behavior. The Curie temperature of the investigated compounds decreases with the increase of R concentration from 721K (GdFe₃) to 655K (TbFe₃) and 533K (YFe₃). The saturation magnetic moment MS in the R _x Gd _1?x Fe₃ system increase with x parameter. The Mössbauer spectra are analyzed using four sextets, corresponding to three crystallographically (b, c, h) and four magnetically (b, c, h₁, h₂) inequivalent sites for iron. The mean hyperfine magnetic field increases with increase of the Gd concentration