Gradient Spin Echo Research Articles

Fast and robust measurement of microstructural dimensions using temporal diffusion spectroscopy

Mapping axon sizes non-invasively is of interest for neuroscientists and may have significant clinical potential because nerve conduction velocity is directly dependent on axon size. Current approaches to measuring axon sizes using diffusion-weighted MRI, e.g. q-space imaging with pulsed gradient spin echo (PGSE) sequences usually require long scan times and high q-values to detect small axons (diameter <2μm). The oscillating gradient spin echo (OGSE) method has been shown to be able to achieve very short diffusion times and hence may be able to detect smaller axons with high sensitivity. In the current study, OGSE experiments were performed to measure the inner diameters of hollow microcapillaries with a range of sizes (∼1.5–19.3μm) that mimic axons in the human central nervous system. The results suggest that OGSE measurements, even with only moderately high frequencies, are highly sensitive to compartment sizes, and a minimum of two ADC values with different frequencies may be sufficient to extract the microcapillary size accurately. This suggests that the OGSE method may serve as a fast and robust measurement method for mapping axon sizes non-invasively.

Probing membrane and interface properties in concentrated electrolyte solutions

This study deals with the membrane and interface electrical properties investigation by electrochemical impedance spectroscopy (EIS). The EIS is a powerful technique for characterizing electrical behavior of systems in which coupled electrical processes occur at different rates. A systematic study on the effect of solution concentration, temperature and velocity, on the electrical resistance of anion- and cation-exchange membranes (AEMs and CEMs) and their interfaces (electrical double layer and diffusion boundary layer), was carried out. At the best of our knowledge, for the first time electrolyte concentrations up to 4M were used for the study of membranes and interface by EIS.Moreover, Pulsed Gradient Spin Echo Nuclear Magnetic Resonance (PGSE-NMR) technique was used to measure the water self-diffusion coefficients in swelled membrane as a function of the solution concentration and temperature. These measurements gave additional important insights about the effect of the electrolyte solution and fixed charges concentration in membrane, on membrane microstructure and its transport and electrical properties.

MRI measurement of oxygen extraction fraction, mean vessel size and cerebral blood volume using serial hyperoxia and hypercapnia

Functional magnetic resonance imaging measures signal increases arising from a variety of interrelated effects and physiological sources. Recently there has been some success in disentangling this signal in order to quantify baseline physiological parameters, including the resting oxygen extraction fraction (OEF), cerebral blood volume (CBV) and mean vessel size. However, due to the complicated nature of the signal, each of these methods relies on certain physiological assumptions to derive a solution. In this work we present a framework for the simultaneous, voxelwise measurement of these three parameters. The proposed method removes the assumption of a fixed vessel size from the quantification of OEF and CBV, while simultaneously removing the need for an assumed OEF in the calculation of vessel size. The new framework is explored through simulations and validated with a pilot study in healthy volunteers. The MRI protocol uses a combined hyperoxia and hypercapnia paradigm with a modified spin labelling sequence collecting multi-slice gradient echo and spin echo data.

Simultaneous assessment of vessel size index, relative blood volume, and vessel permeability in a mouse brain tumor model using a combined spin echo gradient echo echo‐planar imaging sequence and viable tumor analysis

Combining multiple imaging biomarkers in one magnetic resonance imaging (MRI) session would be beneficial to gain more data pertaining to tumor vasculature under therapy. Therefore, simultaneous measurement of perfusion, permeability, and vessel size imaging (VSI) using a gradient echo spin echo (GE-SE) sequence with injection of a clinically approved gadolinium (Gd)-based contrast agent was assessed in an orthotopic glioma model. A combined spin echo gradient echo echo-planar imaging sequence was implemented using a single contrast agent Gd diethylenetriaminepentaacetic acid (Gd-DTPA). This sequence was tested in a mouse brain tumor model (U87_MG), also under treatment with an antiangiogenic agent (bevacizumab). T2 maps and the apparent diffusion coefficient (ADC) were used to differentiate regions of cell death and viable tumor tissue. In viable tumor tissue regional blood volume was 5.7 ± 0.6% in controls and 5.2 ± 0.3% in treated mice. Vessel size was 18.1 ± 2.4 μm in controls and 12.8 ± 2.0 μm in treated mice, which correlated with results from immunohistochemistry. Permeability (K(trans) ) was close to zero in treated viable tumor tissue and 0.062 ± 0.024 min(-1) in controls. Our MRI method allows simultaneous assessment of several physiological and morphological parameters and extraction of MRI biomarkers for vasculature. These could be used for treatment monitoring of novel therapeutic agents such as antiangiogenic drugs.

Assessing diffusion in enzyme loaded sol–gel matrices

Assessing the diffusion of solvent and reaction species within a sol–gel matrix using pulsed field gradient spin echo HR-MAS NMR.

Fast Proton Conduction Facilitated by Minimum Water in a Series of Divinylsilyl-11-silicotungstic Acid-co-Butyl Acrylate-co-Hexanediol Diacrylate Polymers

Studies of proton transport in novel materials are important to enable a large array of electrochemical devices. In this study, we show that heteropoly acids (HPAs) when immobilized in polymer matrixes have highly mobile protons. Divinyl-11-silicotungstic acid, an HPA, was copolymerized with butyl acrylate and hexanediol diacrylate at various weight percentage loadings from 25% to 85% using UV initiated polymerizations. The resultant films were tan colored flexible sheets of ca. 120 μm thickness. The morphology of these films varied with loading, showing phase separation into clustered HPA above a 50 wt % loading and lamella morphologies above an 80 wt % loading. Water uptake was strongly associated with the HPA clusters, which facilitated transport of protons. This was realized by proton conductivities as high as 0.4 S cm–1 at 95 °C and 95% RH and 0.1 S cm–1 at 85 °C and 50% RH. Pulse field gradient spin echo NMR measurements indicated that water self-diffusion was fast (1.4 × 10–5 and 4.4 × 10–5 cm2 s–1...

Assessing reproducibility of diffusion-weighted magnetic resonance imaging studies in a murine model of HER2 + breast cancer

Background and purposeThe use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a surrogate biomarker of response in preclinical studies is increasing. However, before a biomarker can be reliably employed to assess treatment response, the reproducibility of the technique must be established. There is a paucity of literature that quantifies the reproducibility of DW-MRI in preclinical studies; thus, the purpose of this study was to investigate DW-MRI reproducibility in a murine model of HER2+ breast cancer. Materials and methodsTest–Retest DW-MRI scans separated by approximately six hours were acquired from eleven athymic female mice with HER2+ xenografts using a pulsed gradient spin echo diffusion-weighted sequence with three b values [150, 500, and 800s/mm2]. Reproducibility was assessed for the mean apparent diffusion coefficient (ADC) from tumor and muscle tissue regions. ResultsThe threshold to reflect a change in tumor physiology in a cohort of mice is defined by the 95% confidence interval (CI), which was±0.0972×10-3mm2/s (±11.8%) for mean tumor ADC. The repeatability coefficient defines this threshold for an individual mouse, which was±0.273×10-3mm2/s. The 95% CI and repeatability coefficient for mean ADC of muscle tissue were±0.0949×10-3mm2/s (±8.30%) and±0.266×10-3mm2/s, respectively. ConclusionsMean ADC of tumors is reproducible and appropriate for detecting treatment-induced changes on both an individual and mouse cohort basis.

MRI of neonatal necrotizing enterocolitis in a rodent model

Neonatal necrotizing enterocolitis (NEC) is a poorly understood life-threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam-fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4-T scanner to obtain high-resolution anatomical MR images using both gradient echo and spin echo sequences, pixel-by-pixel T2 maps using a multi-slice–multi-echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T2 measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion-weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10–3 mm2/s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10–3 mm2/s] and nonstressed control pups [(1.10 ± 0.06) × 10–3 mm2/s]. Both T2 and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Brain's reward circuits mediate itch relief. a functional MRI study of active scratching.

Previous brain imaging studies investigating the brain processing of scratching used an exogenous intervention mimicking scratching, performed not by the subjects themselves, but delivered by an investigator. In real life, scratching is a conscious, voluntary, controlled motor response to itching, which is directed to the perceived site of distress. In this study we aimed to visualize in real-time by brain imaging the core mechanisms of the itch-scratch cycle when scratching was performed by subjects themselves. Secondly, we aimed to assess the correlations between brain patterns of activation and psychophysical ratings of itch relief or pleasurability of scratching. We also compared the patterns of brain activity evoked by self-scratching vs. passive scratching. We used a robust tridimensional Arterial Spin Labeling fMRI technique that is less sensitive to motion artifacts: 3D gradient echo and spin echo (GRASE) - Propeller. Active scratching was accompanied by a higher pleasurability and induced a more pronounced deactivation of the anterior cingulate cortex and insula, in comparison with passive scratching. A significant involvement of the reward system including the ventral tegmentum of the midbrain, coupled with a mechanism deactivating the periaqueductal gray matter (PAG), suggests that itch modulation operates in reverse to the mechanism known to suppress pain. Our findings not only confirm a role for the central networks processing reward in the pleasurable aspects of scratching, but also suggest they play a role in mediating itch relief.

Novel application of NMR relaxometry in studies of diffusion in virgin rape oil

Field cycling (FC) proton nuclear magnetic resonance (1H NMR) relaxometry was applied to study the dynamics of rape oil molecules. The spin–lattice relaxation data, measured in the frequency range from 0.01 to 30MHz, were analysed by applying relaxation theory combined with the force-free-hard-sphere (FFHS) diffusion model. In the low frequency range, the relaxation was dominated by the translational diffusion contribution. Therefore, the diffusion coefficient of rape oil was determined from a linear dependence of the 1H NMR relaxation dispersion drawn as a function of the square root of Larmor frequency. The results are consistent with those obtained from the pulse gradient spin echo (PGSE) NMR method. To estimate the density of oil protons, a parameter required to derive the diffusion coefficient from NMR relaxometry, a single point imaging (SPI) NMR experiment was proposed.

Influence of lithium salt addition on ionic conductivity and transporting properties of lithium bis(trifluoromethanesulfonyl)imide-doped glycine-based ionic liquid electrolyte

The effects of the incorporation of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) on the ionic transporting and physicochemical properties of a glycine-based ionic liquid (IL) are studied. The ionization conditions of each ionic species in LiTFSI-doped glycine-based ionic liquid electrolytes ([MGlyA][TFSI]), are characterized by diffusion coefficients of the species measured using the pulsed gradient spin-echo (PGSE) NMR technique. Temperature-dependent viscosity, ionic conductivity, molar conductivity, and self diffusion coefficient in neat [MGlyA][TFSI] and LiTFSI-doped [MGlyA][TFSI] followed the Vogel–Tamman–Fulcher equation at all concentrations. The experimental molar conductivity (Λ) of neat [MGlyA][TFSI] and LiTFSI-doped [MGlyA][TFSI] is lower than that of the calculated molar conductivity (ΛNMR) from PGSE NMR technique over the entire temperature range, demonstrating that not all the diffusive species contribute to the ionic conduction, that is, free-ions, ionic pairs, and/or clusters coexist in ILs.

Slice accelerated gradient‐echo spin‐echo dynamic susceptibility contrast imaging with blipped CAIPI for increased slice coverage

To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice (SMS) method. Data were acquired on 3 Tesla (T) MR scanners with a 32-channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two-fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2× in-plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor. Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images. Two-fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage.

Oscillating gradient spin‐echo (OGSE) diffusion tensor imaging of the human brain

The dependence of diffusion tensor imaging (DTI) eigenvalues and fractional anisotropy (FA) on short diffusion times was investigated using oscillating gradient spin echo (OGSE) and pulsed gradient spin echo (PGSE) DTI in the human brain in vivo. DTI was performed in seven healthy volunteers at 4.7 Tesla (T) with b = 300 s/mm(2) and diffusion times of 4.1 ms (OGSE 50 Hz), 7.4 ms (OGSE 25 Hz), 20 ms (PGSE), and 40 ms (PGSE). Eigenvalues and FA were compared in the corpus callosum body, splenium and genu, and the corticospinal, cingulum, inferior fronto-occipital, superior and inferior longitudinal fasciculi using tractography, and the thalamus and putamen using region-of-interest. Relative to 40 ms, the 4.1 ms diffusion time led to significant increases in DTI eigenvalues in seven white matter tracts (6% to 20% parallel, 13% to 40% perpendicular) and both deep gray matter regions (16% parallel, 18% to 26% perpendicular), and reductions of FA (-9% to -12%) in four tracts. DTI eigenvalues and FA depend on diffusion time in both white and gray matter in the human brain. The ability to target different length scales by means of the diffusion time may improve sensitivity to changes in tissue microstructure associated with pathology.

Relationship between the diffusion time and the diffusion MRI signal observed at 17.2 tesla in the healthy rat brain cortex

To investigate the diffusion time dependency of water diffusion in cortical brain tissue. We have combined an oscillating gradient spin-echo (OGSE) and a pulse gradient spin echo (PGSE) spin-echo sequence to acquire diffusion-weighted MRI images in vivo in healthy rat brains over a wide range of diffusion times (1.9-29.2 ms) and estimated the parameters of the biexponential and cumulant expansion diffusion MRI signal models. Diffusion images were obtained at 17.2 Tesla with maximum gradient strength of 1000 mT/m allowing 40 b values up to approximately 4000 s/mm(2). At all diffusion times the log plot of diffusion signal attenuation versus b value was curved, confirming that diffusion is not free, even at very short diffusion times. This suggests that the length scale of obstacles to diffusion must be smaller than the corresponding shortest observed diffusion distance (approximately 1.7 μm). The diffusion MRI signal was also not found in a steady-state, even at our longest diffusion time (29.2 ms), suggesting some degree of segregation of water in pools. Overall, the results showed that the parameters derived from the two diffusion models could not well be related to specific tissue features. More specific models must be developed taking into account diffusion signal behavior at high b values and short diffusion times.

Reduction in Cerebral Perfusion after Heroin Administration: A Resting State Arterial Spin Labeling Study

Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment.

Study of translational dynamics in molten polymer by variation of gradient pulse-width of PGSE

Pulsed gradient spin echo is a method of measuring molecular translation. Changing Δ makes it sensitive to diffusion spectrum. Spin translation effects the buildup of phase structure during the application of gradient pulses as well. The time scale of the self-diffusion measurement shortens if this is taken into account. The method of diffusion spectrometry with variable δ is also less sensitive to artifacts caused by spin relaxation and internal gradient fields. Here the method is demonstrated in the case of diffusion spectrometry of molten polyethylene. The results confirm a model of constraint release in a system of entangled polymer chains as a sort of tube Rouse motion.

X-ray Absorption Spectroscopy Proves the Trigonal-Planar Sulfur-Only Coordination of Copper(I) with High-Affinity Tripodal Pseudopeptides

A series of tripodal ligands L derived from nitrilotriacetic acid (NTA) and extended by three converging metal-binding cysteine chains were previously found to bind selectively copper(I) both in vitro and in vivo. The ligands L(1) (ester) and L(2) (amide) were demonstrated to form copper(I) species with very high affinities, close to that reported for the metal-sequestering metallothioneins (MTs; log K(Cu-MT) ≈ 19). Here, an in-depth study by Cu K-edge X-ray absorption spectroscopy (XAS) was performed to completely characterize the copper(I) coordination sphere in the complexes, previously evidenced by other physicochemical analyses. The X-ray absorption near-edge structure (XANES) spectra shed light on the equilibrium between a mononuclear complex and a cluster for both L(1) (ester) and L(2) (amide). The exclusive symmetric CuS3 geometry adopted in the mononuclear complexes (Cu-S ≈ 2.23 Å) was clearly demonstrated by extended X-ray absorption fine structure (EXAFS) analyses. The EXAFS analyses also proved that the clusters are organized on a symmetric CuS3 core (Cu-S ≈ 2.26 Å) and interact with three nearby copper atoms (Cu---Cu ≈ 2.7 Å), consistent with the Cu6S9-type clusters previously characterized by pulsed gradient spin echo NMR spectroscopy. XAS data obtained for other architectures based on the NTA template (L(3) acid, L(4) without a functionalized carbonyl group, etc.) demonstrated the formation of polymetallic species only, which evidence the necessity of the proximal ester or amide group to stabilize the CuS3 mononuclear species. Finally, XAS was demonstrated to be a powerful method to quantify the equilibrium between the two copper(I) environments evidenced with L(1) and L(2) at different copper concentrations and to determine the equilibrium constants between these two complexes.

Axon radius estimation with Oscillating Gradient Spin Echo (OGSE) diffusion MRI

The estimation of axon radius provides insights into brain function [1] and could provide progression and classification biomarkers for a number of white matter diseases [2-4]. A recent in silico study [5] has shown that optimised gradient waveforms (GEN) and oscillating gradient waveform spin echo (OGSE) have increased sensitivity to small axon radius compared to pulsed gradient spin echo (PGSE) diffusion MR sequences. In a follow-up study [6], experiments with glass capillaries show the practical feasibility of GEN sequences and verify improved pore-size estimates. Here, we compare PGSE with sine, sine with arbitrary phase, and square wave OGSE (SNOGSE, SPOGSE, SWOGSE, respectively) for axon radius mapping in the corpus callosum of a rat, ex-vivo. Our results suggest improvements in pore size estimates from OGSE over PGSE, with greatest improvement from SWOGSE, supporting theoretical results from [5] and other studies [7-9].

Numerical analysis of NMR diffusion measurements in the short gradient pulse limit

Pulsed gradient spin-echo (PGSE) NMR diffusion measurements provide a powerful technique for probing porous media. The derivation of analytical mathematical models for analysing such experiments is only straightforward for ideal restricting geometries and rapidly becomes intractable as the geometrical complexity increases. Consequently, in general, numerical methods must be employed. Here, a highly flexible method for calculating the results of PGSE NMR experiments in porous systems in the short gradient pulse limit based on the finite element method is presented. The efficiency and accuracy of the method is verified by comparison with the known solutions to simple pore geometries (parallel planes, a cylindrical pore, and a spherical pore) and also to Monte Carlo simulations. The approach is then applied to modelling the more complicated cases of parallel semipermeable planes and a pore hopping model. Finally, the results of a PGSE measurement on a toroidal pore, a geometry for which there is presently no current analytical solution, are presented. This study shows that this approach has great potential for modelling the results of PGSE experiments on real (3D) porous systems. Importantly, the FEM approach provides far greater accuracy in simulating PGSE diffraction data.

Two-electron-transfer redox systems. Part 8. Proving the electron stoichiometry for the electrochemical two-electron oxidation of N,N′-bis(ferrocenoyl)-1,2-diaminoethane

N,N′-Bis(ferrocenoyl)-1,2-diaminoethane is electrochemically oxidized at Pt electrodes in non-aqueous solvents with NBu4PF6 or NBu4[Al(pftb)4] (pftb=OC(CF3)3) as supporting electrolytes. Cyclic voltammetry (CV) at macro and ultramicro disk electrodes in propylene carbonate (PC) in the presence of the former electrolyte shows a single signal from which the number of transferred electrons n (equal to 2) and the diffusion coefficient D are estimated and confirmed by simulation. In a series of other solvents (DMF, DMSO, CH3CN, THF, CH2Cl2) with the same electrolyte, similar behavior is observed. The latter supporting electrolyte, however, induces signal broadening as compared to NBu4PF6 in PC for cyclic and differential pulse voltammetry as well as peak splitting in the case of THF and CH2Cl2. This is attributed to interaction between the two ferrocene moieties in the molecule, which is not relayed through a conjugated bridge. Diffusion coefficients in DMF and DMSO were determined by pulse gradient spin echo NMR experiments and compared to electrochemical values. The solvent dependence of D follows the Stokes–Einstein relation. Comproportionation equilibrium constants as calculated from the difference of the formal potentials E0 range from below 10 (PC, NBu4PF6) to approximately 150 (THF and CH2Cl2, NBu4[Al(pftb)4]).