Coherence Pathways Research Articles

High-resolution heteronuclear correlations between spin-1/2 and half-integer quadrupolar nuclei under fast MAS solid-state NMR

High isotropic resolution is essential for the structural elucidation of samples with multiple sites. In this study, utilizing the benefits of TRAPDOR-based heteronuclear multiple quantum coherence (T-HMQC) and a pair of one rotor period long cosine amplitude modulated low-power (cos-lp) pulse-based symmetric-split-t1 multiple-quantum magic angle spinning (MQMAS) methods, we have developed a proton-detected 2D 35Cl/1H T-HMQC-MQMAS pulse sequence under fast MAS (70 kHz) to achieve high-resolution in the indirect dimension of the spin-3/2 (35Cl) nuclei connected via protons. As T-HMQC polarizes not only single-quantum central transition (SQCT) but also triple-quantum (TQ) coherences, the proposed 2D pulse sequence is implemented via selection of two coherence pathways (SQCT→TQ →SQCT and TQ → SQCT→TQ) resulting in the 35Cl isotropic dimension and is superior to the existing double-quantum satellite-transition (DQST) T-HMQC in terms of resolution.

Magnetic resonance coherence pathway unraveling

Efficiently acquiring multi-contrast magnetic resonance imaging data is crucial for patient comfort and clinical throughput. Developing scan acceleration methods tailored for specific applications drastically improves the value of an MRI examination. Here, we propose a novel method to control the aliasing of simultaneously acquired images of multiple spin echo coherence pathways with the goal of producing high quality multi-contrast images from a single acquisition. Modulating the radiofrequency phase of several pulses applied in brief succession also uniquely modulates the phase of spin echo coherence pathways. A method, termed magnetic resonance coherence pathway unraveling (MR-CPU), to control the aliasing of simultaneously acquired coherence pathway images is developed here along with parallel imaging-based reconstruction methods to separate them. MR-CPU was validated in phantom experiments and tested in vivo. High levels of correlation between reference pathway images and MR-CPU-derived coherence pathway images were found from the phantom experiments. Minimal artifacts arising from the separation of the overlapped coherence pathway images were observed in vivo. MR-CPU provides a novel mechanism through which to acquire and separate multiple overlapped coherence pathway images, thus adding to the diagnostic potential of an MRI exam without the penalty of additional scan time.

Changes in the superior longitudinal fasciculus and anterior thalamic radiation in the left brain are associated with developmental dyscalculia.

Developmental dyscalculia is a neurodevelopmental disorder specific to arithmetic learning even with normal intelligence and age-appropriate education. Difficulties often persist from childhood through adulthood lowering the individual's quality of life. However, the neural correlates of developmental dyscalculia are poorly understood. This study aimed to identify brain structural connectivity alterations in developmental dyscalculia. All participants were recruited from a large scale, non-referred population sample in a longitudinal design. We studied 10 children with developmental dyscalculia (11.3 ± 0.7 years) and 16 typically developing peers (11.2 ± 0.6 years) using diffusion-weighted magnetic resonance imaging. We assessed white matter microstructure with tract-based spatial statistics in regions-of-interest tracts that had previously been related to math ability in children. Then we used global probabilistic tractography for the first time to measure and compare tract length between developmental dyscalculia and typically developing groups. The high angular resolution diffusion-weighted magnetic resonance imaging and crossing-fiber probabilistic tractography allowed us to evaluate the length of the pathways compared to previous studies. The major findings of our study were reduced white matter coherence and shorter tract length of the left superior longitudinal/arcuate fasciculus and left anterior thalamic radiation in the developmental dyscalculia group. Furthermore, the lower white matter coherence and shorter pathways tended to be associated with the lower math performance. These results from the regional analyses indicate that learning, memory and language-related pathways in the left hemisphere might be related to developmental dyscalculia in children.

Approximate analytical expressions for the Carr–Purcell–Meiboom–Gill sequences: Decay rates and modulation zeros of the echo train and the relation between the [formula omitted] and [formula omitted] relaxation times

Methods of multi-pulse sequences are widely used in magnetic resonance to study the local properties of magnetic particles and to increase the lifetime of spin coherence. Imperfect refocusing pulses lead to non-exponential signal decay due to the contribution of the coherence pathways in which T1 and T2 relaxation segments are mixed. Here, we present analytical approximations for echoes generated in the Carr-Purcell-Meiboom-Gill (CPMG) sequence. They provide simple expressions for the leading terms of the echo train decay and allow the relaxation times to be estimated for sequences with a relatively small number of pulses. For a given refocusing angle α, the decay times for the fixed phase and alternating phase CPMG sequences can be approximated as (T2-1+T1-1)/2 and T2O, respectively. The ability to estimate relaxation times from short pulse sequences can reduce the acquisition time, which is essential for the methods used in magnetic resonance imaging. In the case of a CPMG sequence with the fixed phase, the relaxation times can also be obtained from the points in the sequence at which the echo changes sign. Numerical comparison of the exact and approximate expressions shows the practical limits of the analytical formulas obtained. It is also shown that a double echo sequence in which the interval between the first two pulses is not equal to half the interval of the subsequent refocusing pulses provides the same information as two separate CPMG (or CP) sequences with fixed and alternating phases of the refocusing pulses. In addition, the two double-echo sequences differ in the parity of the number of intervals with longitudinal magnetization evolution (relaxation), i.e. the echo in one sequence is formed only from those coherence pathways that have an even number of intervals with longitudinal magnetization evolution, while the other sequence has an odd number of such intervals.

Filter exchange imaging with crusher gradient modelling detects increased blood–brain barrier water permeability in response to mild lung infection

Blood–brain barrier (BBB) dysfunction occurs in many brain diseases, and there is increasing evidence to suggest that it is an early process in dementia which may be exacerbated by peripheral infection. Filter-exchange imaging (FEXI) is an MRI technique for measuring trans-membrane water exchange. FEXI data is typically analysed using the apparent exchange rate (AXR) model, yielding estimates of the AXR. Crusher gradients are commonly used to remove unwanted coherence pathways arising from longitudinal storage pulses during the mixing period. We first demonstrate that when using thin slices, as is needed for imaging the rodent brain, crusher gradients result in underestimation of the AXR. To address this, we propose an extended crusher-compensated exchange rate (CCXR) model to account for diffusion-weighting introduced by the crusher gradients, which is able to recover ground truth values of BBB water exchange (kin) in simulated data. When applied to the rat brain, kin estimates obtained using the CCXR model were 3.10 s−1 and 3.49 s−1 compared to AXR estimates of 1.24 s−1 and 0.49 s−1 for slice thicknesses of 4.0 mm and 2.5 mm respectively. We then validated our approach using a clinically relevant Streptococcus pneumoniae lung infection. We observed a significant 70 ± 10% increase in BBB water exchange in rats during active infection (kin = 3.78 ± 0.42 s−1) compared to before infection (kin = 2.72 ± 0.30 s−1; p = 0.02). The BBB water exchange rate during infection was associated with higher levels of plasma von Willebrand factor (VWF), a marker of acute vascular inflammation. We also observed 42% higher expression of perivascular aquaporin-4 (AQP4) in infected animals compared to non-infected controls, while levels of tight junction proteins remain consistent between groups. In summary, we propose a modelling approach for FEXI data which removes the bias in estimated water-exchange rates associated with the use of crusher gradients. Using this approach, we demonstrate the impact of peripheral infection on BBB water exchange, which appears to be mediated by endothelial dysfunction and associated with an increase in perivascular AQP4.

A novel framework for in-vivo diffusion tensor distribution MRI of the human brain

Neural tissue microstructure plays an important role in developmental, physiological and pathophysiological processes. Diffusion tensor distribution (DTD) MRI helps probe subvoxel heterogeneity by describing water diffusion within a voxel using an ensemble of non-exchanging compartments characterized by a probability density function of diffusion tensors. In this study, we provide a new framework for acquiring multiple diffusion encoding (MDE) images and estimating DTD from them in the human brain in vivo. We interfused pulsed field gradients (iPFG) in a single spin echo to generate arbitrary b-tensors of rank one, two, or three without introducing concomitant gradient artifacts. Employing well-defined diffusion encoding parameters we show that iPFG retains salient features of a traditional multiple-PFG (mPFG/MDE) sequence while reducing the echo time and coherence pathway artifacts thereby extending its applications beyond DTD MRI. Our DTD is a maximum entropy tensor-variate normal distribution whose tensor random variables are constrained to be positive definite to ensure their physicality. In each voxel, the second-order mean and fourth-order covariance tensors of the DTD are estimated using a Monte Carlo method that synthesizes micro-diffusion tensors with corresponding size, shape, and orientation distributions to best fit the measured MDE images. From these tensors we obtain the spectrum of diffusion tensor ellipsoid sizes and shapes, and the microscopic orientation distribution function (μODF) and microscopic fractional anisotropy (μFA) that disentangle the underlying heterogeneity within a voxel. Using the DTD-derived μODF, we introduce a new method to perform fiber tractography capable of resolving complex fiber configurations. The results revealed microscopic anisotropy in various gray and white matter regions and skewed MD distributions in cerebellar gray matter not observed previously. DTD MRI tractography captured complex white matter fiber organization consistent with known anatomy. DTD MRI also resolved some degeneracies associated with diffusion tensor imaging (DTI) and elucidated the source of diffusion heterogeneity which may help improve the diagnosis of various neurological diseases and disorders.

Mapping LiNbO_{3} Phonon-Polariton Nonlinearities with 2D THz-THz-Raman Spectroscopy.

Two-dimensional terahertz-terahertz-Raman spectroscopy can provide insight into the anharmonicities of low-energy phonon modes-knowledge of which can help develop strategies for coherent control of material properties. Measurements on LiNbO_{3} reveal THz and Raman nonlinear transitions between the E(TO_{1}) and E(TO_{3}) phonon polaritons. Distinct coherence pathways are observed with different THz polarizations. The observed pathways suggest that the origin of the third-order nonlinear responses is due to mechanical anharmonicities, as opposed to electronic anharmonicities. Further, we confirm that the E(TO_{1}) and E(TO_{3}) phonon polaritons are excited through resonant one-photon THz excitation.

A modernized view of coherence pathways applied to magnetic resonance experiments in unstable, inhomogeneous fields.

This article presents a standardized alternative to the traditional phase cycling approach employed by the overwhelming majority of contemporary Nuclear Magnetic Resonance (NMR) research. On well-tested, stable NMR systems running well-tested pulse sequences in highly optimized, homogeneous magnetic fields, the hardware and/or software responsible for traditional phase cycling quickly isolate a meaningful subset of data by averaging and discarding between 3/4 and 127/128 of the digitized data. In contrast, the new domain colored coherence transfer (DCCT) approach enables the use of all the information acquired from all transients. This approach proves to be particularly useful where multiple coherence pathways are required, or for improving the signal when the magnetic fields are inhomogeneous and unstable. For example, the authors' interest in the nanoscale heterogeneities of hydration dynamics demands increasingly sophisticated and automated measurements deploying Overhauser Dynamic Nuclear Polarization (ODNP) in low-field electromagnets, where phase cycling and signal averaging perform suboptimally. This article demonstrates the capabilities of DCCT on ODNP data and with a collection of algorithms that provide robust phasing, avoidance of baseline distortion, and the ability to realize relatively weak signals amid background noise through signal-averaged correlation alignment. The DCCT schema works by combining a multidimensional organization of phase cycled data with a specific methodology for visualizing the resulting complex-valued data. It could be extended to other forms of coherent spectroscopy seeking to analyze multiple coherence transfer pathways.

MRSCloud: A cloud-based MRS tool for basis set simulation.

The purpose of this study is to present a cloud-based spectral simulation tool "MRSCloud," which allows MRS users to simulate a vendor-specific and sequence-specific basis set online in a convenient and time-efficient manner. This tool can simulate basis sets for GE, Philips, and Siemens MR scanners, including conventional acquisitions and spectral editing schemes with PRESS and semi-LASER localization at 3 T. The MRSCloud tool was built on the spectral simulation functionality in the FID-A software package. We added three extensions to accelerate computation (ie, one-dimensional projection method, coherence pathways filters, and precalculation of propagators). The RF waveforms were generated based on vendors' generic pulse shapes and timings. Simulations were compared within MRSCloud using different numbers of spatial resolution (21 × 21, 41 × 41, and 101 × 101). Simulated metabolite basis functions from MRSCloud were compared with those generated by the generic FID-A and MARSS, and a phantom-acquired basis set from LCModel. Intraclass correlation coefficients were calculated to measure the agreement between individual metabolite basis functions. Statistical analysis was performed using R in RStudio. Simulation time for a full PRESS basis set is approximately 11 min on the server. The interclass correlation coefficients ICCs were at least 0.98 between MRSCloud and FID-A and were at least 0.96 between MRSCloud and MARSS. The interclass correlation coefficients between simulated MRSCloud basis spectra and acquired LCModel basis spectra were lowest for glutamine at 0.68 and highest for N-acetylaspartate at 0.96. Substantial reductions in runtime have been achieved. High ICC values indicated that the accelerating features are running correctly and produce comparable and accurate basis sets.

Correcting for imaging gradients-related bias of T2 relaxation times at high-resolution MRI.

PurposeHigh‐resolution animal imaging is an integral part of preclinical drug development and the investigation of diseases' pathophysiology. Quantitative mapping of T2 relaxation times (qT2) is a valuable tool for both preclinical and research applications, providing high sensitivity to subtle tissue pathologies. High‐resolution T2 mapping, however, suffers from severe underestimation of T2 values due to molecular diffusion. This affects both single‐echo and multi‐echo spin echo (SSE and MESE), on top of the well‐known contamination of MESE signals by stimulated echoes, and especially on high‐field and preclinical scanners in which high imaging gradients are used in comparison to clinical scanners.MethodsDiffusion bias due to imaging gradients was analyzed by quantifying the effective b‐value for each coherence pathway in SSE and MESE protocols, and incorporating this information in a joint T2‐diffusion reconstruction algorithm. Validation was done on phantoms and in vivo mouse brain using a 9.4T and a 7T MRI scanner.ResultsUnderestimation of T2 values due to strong imaging gradients can reach up to 70%, depending on scan parameters and on the sample's diffusion coefficient. The algorithm presented here produced T2 values that agreed with reference spectroscopic measurements, were reproducible across scan settings, and reduced the average bias of T2 values from −33.5 ± 20.5% to −0.1 ± 3.6%.ConclusionsA new joint T2‐diffusion reconstruction algorithm is able to negate imaging gradient–related underestimation of T2 values, leading to reliable mapping of T2 values at high resolutions.

Identifying the source of spurious signals caused by B0 inhomogeneities in single-voxel 1 H MRS.

PurposeSingle‐voxel MRS (SV MRS) requires robust volume localization as well as optimized crusher and phase‐cycling schemes to reduce artifacts arising from signal outside the volume of interest. However, due to local magnetic field gradients (B0 inhomogeneities), signal that was dephased by the crusher gradients during acquisition might rephase, leading to artifacts in the spectrum. Here, we analyzed this mechanism, aiming to identify the source of signals arising from unwanted coherence pathways (spurious signals) in SV MRS from a B0 map.MethodsWe investigated all possible coherence pathways associated with imperfect localization in a semi‐localized by adiabatic selective refocusing (semi‐LASER) sequence for potential rephasing of signals arising from unwanted coherence pathways by a local magnetic field gradient. We searched for locations in the B0 map where the signal dephasing due to external (crusher) and internal (B0) field gradients canceled out. To confirm the mechanism, SV‐MR spectra (TE = 31 ms) and 3D‐CSI data with the same volume localization as the SV experiments were acquired from a phantom and 2 healthy volunteers.ResultsOur analysis revealed that potential sources of spurious signals were scattered over multiple locations throughout the brain. This was confirmed by 3D‐CSI data. Moreover, we showed that the number of potential locations where spurious signals could originate from monotonically decreases with crusher strength.ConclusionWe proposed a method to identify the source of spurious signals in SV 1H MRS using a B0 map. This can facilitate MRS sequence design to be less sensitive to experimental artifacts.

Coherence pathway analysis of J-coupled lipids and lactate and effective suppression of lipids upon the selective multiple quantum coherence lactate editing sequence

Objective. The selective multiple quantum coherence (Sel-MQC) sequence is a magnetic resonance spectroscopy (MRS) technique used to detect lactate and suppress co-resonant lipid signals in vivo. The coherence pathways of J-coupled lipids upon the sequence, however, have not been studied, hindering a logical design of the sequence to fully attenuate lipid signals. The objective of this study is to elucidate the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and find a strategy to effectively suppress lipid signals from these pathways while keeping the lactate signal. Approach. The product operator formalism was used to express the evolutions of the J-coupled spins of lipids and lactate. The transformations of the product operators by the spectrally selective pulses of the sequence were calculated by using the off-resonance rotation matrices. The coherence pathways and the conversion rates of the individual pathways were derived from them. Experiments were performed on phantoms and two human subjects at 3 T. Main results. The coherence pathways contributing to the various lipid resonance signals by the Sel-MQC sequence depending on the gradient ratios and RF pulse lengths were identified. Theoretical calculations of the signals from the determined coherence pathways and signal attenuations by gradients matched the experimental data very well. Lipid signals from fatty tissues of the subjects were successfully suppressed to the noise level by using the gradient ratio −0.8:−1:2 or 1:0.8:2. The new gradient ratios kept the lactate signal the same as with the previously used gradient ratio 0:−1:2. Significance. The study has elucidated the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and demonstrated how lipid signals can be effectively suppressed while keeping lactate signals by using information from the coherence pathway analysis. The findings enable applying the Sel-MQC sequence to lactate detection in an environment of high concentrations of lipids.

BOLD sensitivity and vessel size specificity along CPMG and GRASE echo trains.

To assess the vessel size specificity and sensitivity of rapid CPMG and GRASE for functional BOLD imaging for different echo train lengths, echo spacings, field strength, and refocusing flip angle schemes. In addition, the behavior of signals acquired before and after the refocusing time points is analyzed. Evolution of magnetization within a network of artificial cylinders is simulated with Monte Carlo methods for all relevant coherence pathways. In addition, measurements on microspheres were performed to confirm some of the theoretical results. For reduced refocusing flip angles, the peak of the vessel size sensitivity curve is shifting toward larger radii with increasing echo time. Furthermore, the BOLD-related signal change along the echo train depends on the chosen refocusing flip angle scheme and in general does not follow corresponding echo amplitudes. CPMG or GRASE can be used with low refocusing flip angles without significant loss of sensitivity to BOLD. The evolution of BOLD signal changes along the echo train can be used to design optimal k-space reordering schemes. Signals acquired before or after the spin echo time point show contributions from larger vessels similar to gradient echo sequences. Short echo spacing (time between refocusing pulses) suppresses gradient echo-related contributions from larger vessels, whereas the spin echo-related contribution from small vessels remains constant and is independent of the echo spacing.

The "Hole" Story in Ionized Water from the Perspective of Ehrenfest Dynamics.

The radiolysis of liquid water and the radiation-matter interactions that happen in aqueous environments are important to the fields of chemistry, materials, and environmental sciences, as well as the biological and physiological response to extreme conditions and medical treatments. The initial stage of radiolysis is the ultrafast response, or hole dynamics, that triggers chemical processes within complex energetic landscapes that may include reactivity. A fundamental understanding necessitates the use of theoretical methods that are capable of simulating both ultrafast coherence and non-adiabatic energy transfer pathways. In this work, we carry out an ab initio Ehrenfest dynamics study to provide a more complete description of the ultrafast dynamics and reactive events initiated by photoionization of water. After sudden ionization, a range of processes, including hole trapping and transfer, large OH oscillations, proton transfer and subsequent relay, formation of the metastable Zundel complex, and long-lived coherence, are identified and new insight into their driving forces is elucidated.

Modeling an equivalent b-value in diffusion-weighted steady-state free precession.

PurposeDiffusion‐weighted steady‐state free precession (DW‐SSFP) is shown to provide a means to probe non‐Gaussian diffusion through manipulation of the flip angle. A framework is presented to define an effective b‐value in DW‐SSFP.TheoryThe DW‐SSFP signal is a summation of coherence pathways with different b‐values. The relative contribution of each pathway is dictated by the flip angle. This leads to an apparent diffusion coefficient (ADC) estimate that depends on the flip angle in non‐Gaussian diffusion regimes. By acquiring DW‐SSFP data at multiple flip angles and modeling the variation in ADC for a given form of non‐Gaussianity, the ADC can be estimated at a well‐defined effective b‐value.MethodsA gamma distribution is used to model non‐Gaussian diffusion, embedded in the Buxton signal model for DW‐SSFP. Monte‐Carlo simulations of non‐Gaussian diffusion in DW‐SSFP and diffusion‐weighted spin‐echo sequences are used to verify the proposed framework. Dependence of ADC on flip angle in DW‐SSFP is verified with experimental measurements in a whole, human postmortem brain.ResultsMonte‐Carlo simulations reveal excellent agreement between ADCs estimated with diffusion‐weighted spin‐echo and the proposed framework. Experimental ADC estimates vary as a function of flip angle over the corpus callosum of the postmortem brain, estimating the mean and standard deviation of the gamma distribution as 1.50·10-4 mm2/s and 2.10·10-4 mm2/s.ConclusionDW‐SSFP can be used to investigate non‐Gaussian diffusion by varying the flip angle. By fitting a model of non‐Gaussian diffusion, the ADC in DW‐SSFP can be estimated at an effective b‐value, comparable to more conventional diffusion sequences.

Simultaneous optimization of crusher and phase cycling schemes for magnetic resonance spectroscopy: an extension of dephasing optimization through coherence order pathway selection.

To extend the dephasing optimization through coherence order pathway selection (DOTCOPS) algorithm, originally designed solely for gradient crusher schemes, to include tailored phase cycling schemes for arbitrary pulse sequences and arbitrary number of coupled spins. The effects all possible nested and cogwheel phase cycling schemes have on the coherence order pathways for an arbitrary experiment are considered. The DOTCOPS algorithm uses a cost function to maximally eliminate unwanted coherence pathways, with schemes preferentially eliminating unwanted coherence pathways that are less affected by the crusher scheme. Efficacy was demonstrated experimentally in 2 separate MR spectroscopy (MRS) sequences: semi-localized adiabatic selective refocusing (sLASER) and MEscher-GArwood sLASER both with phantom and in vivo experiments. For all sequences investigated, cogwheel was found to theoretically outperform typical nested phase cycling schemes. The chosen cogwheel phase cycling schemes through DOTCOPS were found to outperform a typical 2-step phase cycling scheme in both phantom and in vivo experiments. Both crusher schemes and phase cycling schemes with 8, 16, or 32 steps are presented for 6 of the most common advanced MRS sequences. The DOTCOPS algorithm has been extended to provide optimal crusher and phase cycling schemes considered in tandem. DOTCOPS can be applied to any pulse sequence of interest for any number of coupled spins. DOTCOPS is now able to alleviate the long-standing issue of designing effective crusher and phase cycling schemes for complex MRS modern sequences and, as a result, is expected to improve the data quality of virtually all applications.

Magnetic resonance Spectrum simulator (MARSS), a novel software package for fast and computationally efficient basis set simulation.

The aim of this study was to develop a novel software platform for the simulation of magnetic resonance spin systems, capable of simulating a large number of spatial points (1283 ) for large in vivo spin systems (up to seven coupled spins) in a time frame of the order of a few minutes. The quantum mechanical density-matrix formalism is applied, a coherence pathway filter is utilized for handling unwanted coherence pathways, and the 1D projection method, which provides a substantial reduction in computation time for a large number of spatial points, is extended to include sequences of an arbitrary number of RF pulses. The novel software package, written in MATLAB, computes a basis set of 23 different metabolites (including the two anomers of glucose, seven coupled spins) with 1283 spatial points in 26min for a three-pulse experiment on a personal desktop computer. The simulated spectra are experimentally verified with data from both phantom and in vivo MEGA-sLASER experiments. Recommendations are provided regarding the various assumptions made when computing a basis set for in vivo MRS with respect to the number of spatial points simulated and the consideration of relaxation.

RDEER: A Modified DEER Sequence for Distance Measurements Using Shaped Pulses

The DEER (double electron-electron resonance, also called PELDOR) experiment, which probes the dipolar interaction between two spins and thus reveals distance information, is an important tool for structural studies. In recent years, shaped pump pulses have become a valuable addition to the DEER experiment. Shaped pulses offer an increased excitation bandwidth and the possibility to precisely adjust pulse parameters, which is beneficial especially for demanding biological samples. We have noticed that on our home built W-band spectrometer, the dead-time free 4-pulse DEER sequence with chirped pump pulses suffers from distortions at the end of the DEER trace. Although minor, these are crucial for Gd(III)-Gd(III) DEER where the modulation depth is on the order of a few percent. Here we present a modified DEER sequence—referred to as reversed DEER (rDEER)—that circumvents the coherence pathway which gives rise to the distortion. We compare the rDEER (with two chirped pump pulses) performance values to regular 4-pulse DEER with one monochromatic as well as two chirped pulses and investigate the source of the distortion. We demonstrate the applicability and effectivity of rDEER on three systems, ubiquitin labeled with Gd(III)-DOTA-maleimide (DOTA, 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid) or with Gd(III)-DO3A (DO3A, 1,4,7,10-Tetraazacyclododecane-1,4,7-triyl) triacetic acid) and the multidrug transporter MdfA, labeled with a Gd(III)-C2 tag, and report an increase in the signal-to-noise ratio in the range of 3 to 7 when comparing the rDEER with two chirped pump pulses to standard 4-pulse DEER.

The BOLD sensitivity of rapid steady-state sequences.

Relaxation and dephasing of water protons embedded in a vascular network is driven by local magnetic field inhomogeneities around deoxygenated blood vessels. These effects strongly depend on the relation between mean diffusion length and diameter of blood vessels, as well as on the chosen imaging sequence. In this work, the BOLD sensitivity of steady-state sequences as a function of vessel size, field strength, and sequence parameters are analyzed. Steady-state magnetization within a network of artificial cylinders is simulated with Monte Carlo methods for different coherence pathways. In addition, measurements on microspheres were performed to confirm theoretical results. Simulations and phantom results demonstrate a vessel size-dependent signal attenuation effect of all coherence pathways. Both the FID and ECHO pathways show a signal profile similar to spin echo sequences where in the static dephasing regime the effect of larger vessels is suppressed. The BOLD effect measured in steady-state sequences is most sensitive to microvessels and might therefore be closer to the underlying neuronal event compared to gradient echo sequences.

Dephasing optimization through coherence order pathway selection (DOTCOPS) for improved crusher schemes in MR spectroscopy

To develop an algorithm which can robustly eliminate all unwanted coherence pathways for an arbitrary magnetic resonance spectroscopy experiment through the adjustment of the relative amplitudes of crusher gradients, thereby reducing the effects of spurious echoes and mislocalization. The effect of crushing gradients for all coherence pathways was modeled according to the associated physics, and a cost function was optimized which maximally crushes all unwanted coherence pathways, while unaffecting the desired coherence pathway(s). The efficacy of the method was tested versus literature schemes from 2 separate MR spectroscopy (MRS) sequences: sLASER and MEGA-sLASER with both phantom and in vivo experiments. Improved crushing power for 2 separate MRS sequences was demonstrated for 2 crushing schemes adopted from the literature in both phantom and in vivo data. A novel algorithm and associated software was developed based on rigorous treatment of all coherence pathways, which can be applied to any arbitrary magnetic resonance spectroscopic pulse sequence of interest and any arbitrary coupled spin system. This developed method solves a long-standing problem in in vivo MRS and is expected to critically improve the data quality of virtually all MRS applications.