Contrast methods based on dipolar coupling are of great interest for imaging tissues containing large macromolecules, such as myelin. Most of these conventional methods deal with various "relaxation" phenomena influenced by dipolar coupling such as inhomogeneous magnetization transfer. In this work we propose to investigate the benefit of using another method, called magic sandwich echo (MSE), which allows direct modulation of the dipolar coupling (Hd) as described by the work of Matsui and the Redfield theory. To verify the potential of this method in biological tissue, we first proposed an experimental model for dipolar coupling modulation in an ex vivo tendon (as a highly anisotropic tissue) and used it to prove Hd modulation by varying the amplitude of the spin-lock radiofrequency pulse of this sequence. We then proposed a potential in vivo usable metric, directly related to the residual amount of Hd, which we called MaSteR for Magic sandwich echo to Stimulated echo ratio, as it is based on the ratio of the signal acquired with the MSE sequence and a stimulated echo sequence. First, we show that the higher Hd, the more effective the spin-lock radiofrequency amplitude. We measured with MaSteR that the change in radiofrequency amplitude allowed us to distinguish between different Hd intensities, with a greater MaSteR when Hd is higher.

BACKGROUND:Non-human primate (NHP) could be an interesting model for osteoarthritis (OA) longitudinal studies but standard medical imaging protocols are not able to acquire sufficiently high-resolution images to depict the thinner cartilage (compared to human) in an in vivo context. The aim of this study was thus to develop and validate the acquisition protocols for knee joint examination of NHP using magnetic resonance imaging (MRI) at 1.5 T and X-ray micro-computed tomography arthrography (µCTA).METHODS:The first phase of the study focused on developing dedicated in vivo HR-MRI and µCTA protocols for simultaneous acquisitions of both knee joints on NHP. For MR, a dedicated two-channel receiver array coil and acquisition sequence were developed on a 1.5 T Siemens Sonata system and tuned to respect safety issues and reasonable examination time. For µCTA, an experimental setup was devised so as to fulfill similar requirements. The two imaging protocols were used during a longitudinal study so as to confirm that repeated injections of loxaglic acid (contrast agent used for µCTA) didn't induce any bias in cartilage assessment and to compare segmentation results from the two modalities. Lateral and medial cartilage tibial plateaus were assessed using a common image processing protocol leading to a 3D estimation of the cartilage thickness.RESULTS:From HR-MRI and µCTA images, thickness distributions were extracted allowing for proper evaluation of knee cartilage thickness of the primates. Results obtained in vivo indicated that the µCTA protocol did not induce any bias in the measured cartilage parameters and moreover, segmentation results obtained from the two imaging modalities were consistent.CONCLUSIONS:MR and µCTA are valuable imaging tools for the morphological evaluation of cartilage in NHP models which in turn can be used for OA studies.

Among the MR techniques playing on dipolar interaction (Hd), the magic sandwich echo sequence (MSE) is very seldom used in biological application. So far, the magic echo has been compared to the spin echo. However, MSE is closer to a stimulated echo thus a Magic Sandwich to Stimulated echo relative change (MaSteR) is of interest to study. The MaSteR evolution with spin-lock intensity increase was studied for thawed tendon for different orientations within B0 to modulate the dipolar interaction. We show that MaSteR is correlated to dipolar interaction, sample composition and its evolution with orientation is sensitive to Hd sign. Summary (250 characters): A marker of macromolecular dipolar interactions (Hd) is introduced as the Magic Sandwich to Stimulated Echo relative change (MaSteR). Different B1 spin lock intensities are used to modulate Hd. MaSteR is sensitive to Hd sign and fiber orientation.

This article presents a new motion encoding strategy to perform magnetic resonance elastography (MRE). Instead of using standard motion encoding gradients, a tailored RF pulse is designed to simultaneously perform selective excitation and motion encoding in presence of a constant gradient. The RF pulse is designed with a numerical optimal control algorithm, in order to obtain a magnetization phase distribution that depends on the displacement characteristics inside each voxel. As a consequence, no post-excitation encoding gradients are required. This offers numerous advantages, such as reducing eddy current artifacts, and relaxing the constraint on the gradients maximum switch rate. It also allows to perform MRE with ultra-short TE acquisition schemes, which limits T2 decay and optimizes signal-to-noise ratio. The pulse design strategy is developed and analytically analyzed to clarify the encoding mechanism. Finally, simulations, phantom and ex vivo experiments show that phase-to-noise ratios are improved when compared to standard MRE encoding strategies.

Purpose: This article proposes a rigorous optimal control framework for the design of preparation schemes that optimize MRI contrast based on relaxation time differences. Methods: Compared to previous optimal contrast preparation schemes, a drastic reduction of the optimization parameter number is performed. The preparation scheme is defined as a combination of several block pulses whose flip angles, phase terms and inter-pulse delays are optimized to control the magnetization evolution. Results: The proposed approach reduces the computation time of B-0-robust preparation schemes to around a minute (whereas several hours were required with previous schemes), with negligible performance loss. The chosen parameterization allows to formulate the total preparation duration as a constraint, which improves the overall compromise between contrast performance and preparation time. Simulation, in vitro and in vivo results validate this improvement, illustrate the straightforward applicability of the proposed approach, and point out its flexibility in terms of achievable contrasts. Major improvement is especially achieved for short-T-2 enhancement, as shown by the acquisition of a non-trivial contrast on a rat brain, where a short-T-2 white matter structure (corpus callosum) is enhanced compared to surrounding gray matter tissues (hippocampus and neocortex). Conclusions: This approach proposes key advances for the design of optimal contrast preparation sequences, that emphasize their ability to generate non-standard contrasts, their potential benefit in a clinical context, and their straightforward applicability on any MR system.

PurposeTo assess the T-1 and T-2 values in the hip cartilage of healthy volunteers and to evaluate the reproducibility of these measurements. Materials and MethodsThe right hip joint of 30 asymptomatic volunteers was explored with 3T magnetic resonance imaging (MRI). Quantitative 3D T-1- and T-2-maps sequences were repeated twice with a 30-minute delay (immediate reproducibility). The same protocol was repeated 14 days later (short-term reproducibility). Immediate and short-term reproducibility were estimated using coefficients of variation and correlation concordance coefficients (CCC). The precisions of the measurements were estimated by the ratio of the standard deviations. A mixed linear model was used to analyze the effect of patient's characteristics on T-1 and T-2 values. ResultsImmediate reproducibility was significantly better than short-term reproducibility for T-1 (CCC of 0.75 versus 0.55; P=0.007) and T-2 (CCC 0.65 versus 0.32; P < 0.001). The precisions of the measurements were estimated between 5.5% and 9.1%. Median T-1 values were 6.0 msec higher in women than in men (P=0.006), with no significant influence of age, body mass index (BMI), or sports activity. Median T-2 values were not significantly different between men and women (0.4 msec lower in women; P=0.76). There was no significant influence of age, BMI, or sports activity. T-1 and T-2 values were lower in lateral regions than in medial regions (4.9 msec and 2.5 msec lower respectively; P < 0.0001). ConclusionImmediate reproducibility of T-1 and T-2 values is better than short-term, with limited effect of 30 minutes decubitus. T-1 values are significantly higher in women. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1022-1033.

This work investigates the use of MRI radio-frequency (RF) pulses designed within the framework of optimal control theory for image contrast optimization. The magnetization evolution is modeled with Bloch equations, which defines a dynamic system that can be controlled via the application of the Pontryagin Maximum Principle (PMP). This framework allows the computation of optimal RF pulses that bring the magnetization to a given state to obtain the desired contrast after acquisition. Creating contrast through the optimal manipulation of Bloch equations is a new way of handling contrast in MRI, which can explore the theoretical limits of the system. Simulation experiments carried out on-resonance quantify the contrast improvement when compared to standard T1 or T2 weighting strategies. The use of optimal pulses is also validated for the first time in both in vitro and in vivo experiments on a small-animal 4.7 T MR system. Results demonstrate their robustness to static field inhomogeneities as well as the fact that they can be embedded in standard imaging sequences without affecting standard parameters such as slice selection or echo type. In vivo results on rat and mouse brains illustrate the ability of optimal contrast pulses to create non-trivial contrasts on well-studied structures (white matter versus gray matter).

This paper investigates the use of Optimal Control (OC) theory to design Radio-Frequency (RF) pulses that actively control the spatial distribution of the MRI magnetization phase. The RF pulses are generated through the application of the Pontryagin Maximum Principle and optimized so that the resulting transverse magnetization reproduces various non-trivial and spatial phase patterns. Two different phase patterns are defined and the resulting optimal pulses are tested both numerically with the ODIN MRI simulator and experimentally with an agar gel phantom on a 4.7 T small-animal MR scanner. Phase images obtained in simulations and experiments are both consistent with the defined phase patterns. A practical application of phase control with OC-designed pulses is also presented, with the generation of RF pulses adapted for a Magnetic Resonance Elastography experiment. This study demonstrates the possibility to use OC-designed RF pulses to encode information in the magnetization phase and could have applications in MRI sequences using phase images.

To study viscoelastic parameters of small ex vivo or engineered tissue samples, Magnetic Resonance Elastography (MRE) has been used during the last few years [1], [2]. It should enable a cautious sample-handling and be performed with a high spatial resolution. We describe here an elastography bench responding to those criteria. The setup is designed to image small samples (Fig.1). This requires an MRI coil with a high uniformity and filling factor to maximize the signal to noise ratio (SNR). Moreover the sample must be placed in the center of the coil and in contact with the mechanical transducer. Here, the sample holder is designed to slide into a 3D-printed support in which is included a Helmholtz coil tuned with two capacitor trimmers. Matching of the Helmholtz coil is done inductively using a circular coaxial coupling loop tuned at 200MHz. The sample holder is stopped at the center of the coil, guarantying the best RF uniformity and SNR. A cactus needle pierces the sample and is actuated by an MRI-compatible piezoelectric driver at 600Hz. Two samples were used to test the bench. The first one is made of polymerized fibrinogen (Sigma-F8630), which is used for engineered tissue. To limit motion of the sample, it was surrounded by a stiffer gel (DTM 133460). We also used a healthy rat brain embedded in agarose (Sigma A9414). The two embedding gels have well characterized mechanical properties and can serve as a reference.Acquisition of a FLASH and a MRE-compatible RARE sequence were made with a Bruker 4.7T scanner. Reconstruction of the viscoelastic parameters was done using an adapted method from Sinkus et al. [3].A voxel of 0.312x0.312x0.625mm3 with an SNR of 82.8 and 63.6 were obtained with the FLASH sequence, for the rat brain (Fig.2) and the phantom (Fig.3), respectively. Mean displacement amplitude for the RARE sequence was evaluated at 1.5µm and 5.6µm. Storage modulus representing elasticity was 1.8kPa and 1.4kPa. The gel surrounding the sample had an elasticity of 2.6kPa. Setup was easy to handle. It can be easily adapted to any MRI system. SNR is high and the induced mechanical displacement is enough to reconstruct viscoelastic parameters and highlight differences in elasticity between the commercial gel and the fibrinogen sample. Ex vivo results in brain are in agreement with literature [4].AcknowledgementThis work was supported by the LABEX PRIMES (ANR-XX-LABX-0063) of Universite de Lyon, within the program Investissements d'Avenir (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR).PEPS CNRS “Balanced”.References1-Boulet, J. Neurosci. Methods, 20112-Guertler, Proc. ISMRM, 20173-Sinkus, CR Mecanique, 20104-Millward, J. Neuroimmunol, 2014

L'etude presentee ici a pour objectif d'evaluer la pertinence des proprietes viscoelastiques estimees en elastographie par resonance magnetique (ERM), en les comparant aux resultats obtenus en rheologie a haute frequence (RHF), dans une gamme de frequence commune. Cette comparaison a deja fait l'objet d'un certain nombre etudes. Cependant, dans la plupart des travaux presentes, elle se trouvait limitee par des resultats experimentaux obtenus dans des gammes de frequences differentes, necessitant donc une extrapolation des resultats pour comparer les deux techniques.Trois fantomes de plastisol (dispersion de particules de chlorure de polyvinyle dans un plastifiant liquide) ont tout d'abord ete realises en variant la concentration en assouplissant (de 0 a 50%) afin d'obtenir trois fantomes ayant des proprietes viscoelastiques differentes.L'experience d'ERM a consiste a placer ces fantomes dans un IRM, et a faire propager une onde de cisaillement dans le fantome a l'aide d'un dispositif externe (Fig.1). Grâce a une sequence IRM specifique qui repose sur l'ajout de gradients de sensibilisation au mouvement, les deplacements induits dans le fantome par la propagation de l'onde ont ete codes dans la phase de l'image IRM. L'experience a ete repetee pour differentes frequences d'excitation mecanique, comprises entre 400 et 1200 Hz (Fig.2). Les modules de conservation G' (representant la partie elastique) et de perte G'' (partie visqueuse) ont ete reconstruits par traitement des images de phase en utilisant l'inversion de l'equation d'Helmholtz 2D.L'experience de RHF a ete faite dans des conditions similaires (temperature, âge du fantome) pour des frequences allant de 160 a 630 Hz et a partir de fines couches de fantomes issus des memes preparations que celles realisees pour l'ERM. Pour chaque fantome, quatre echantillons ont ete testes.Les resultats obtenus avec les deux techniques (Fig.3) sont concordants, mettant ainsi en avant l'interet de l'ERM pour l'examen des proprietes mecaniques des tissus biologiques in vivo. De plus, les resultats obtenus pour les modules de conservation et de perte pour les trois fantomes correspondent a ceux de differents tissus biologiques (foie, muscles ou encore cerveau), faisant ainsi de ces fantomes de bons candidats pour le developpement de fantomes permettant de tester de nouveaux algorithmes et methodes en ERM, avant experimentation sur le vivant.La prochaine etape de cette etude va consister a realiser la meme comparaison des proprietes visco-elastiques, mais sur foies de souris in vivo puis excises en ERM, et sur des echantillons de ces memes foies en RHF.

Membrane chromatography (MC) is increasingly used in downstream processes for biomolecule purification as a large range of axial or radial flow commercial membranes is available. The design of these devices plays a major role on flow distribution and biomolecule binding. To better understand the hydrodynamic in MC devices, the velocity field was measured for the first time using magnetic resonance imaging (MRI) and calculated by computational fluid dynamics (CFD) on reconstructed geometries obtained by MRI. The CFD model solved Navier⿿Stokes and Brinkman equations in the free and membrane regions, respectively. Both axial flow and radial flow devices were investigated. For the axial flow device, the velocities were found higher at the periphery for all membrane bed heights. This result suggests that the whole membrane housing has an effect on flow distribution, the inlet and outlet distributors as well as the peripheral walls of the module. In the radial flow device, a high decrease in velocity was observed along the membrane bed height, which could be due to the reduction of the diameter section at the module outlet. Overall, it was concluded that MRI and CFD are powerful methods to better understand the hydrodynamics within MC devices.

Magnetic Resonance Elastography (MRE): non-invasive MR method quantifying mechanical properties of tissues by imaging the propagation of a shear wave inside the investigated tissue, using a specific MRI sequence.Tissue motion is encoded in phase images thanks to a Motion- Encoding Gradient (MEG) synchronized to an external mechanical excitation.Context: some studies implemented innovative sequences for MRE, but, to our knowledge, none have so far simulated these sequences before experiments.Aim of the study: simulation of a MRE experiment, with a gradient-echo sequence and a dynamical phantom, using the software ODIN.