Magnetic resonance elastography with guided pressure waves.

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.

Glycemic response, satiety, gastric secretions and emptying after bread consumption with water, tea or lemon juice: a randomized crossover intervention using MRI.

PURPOSE: Numerous studies, including our previous work with lemon juice, have reported that low-pH meals reduce the glycemic response to starchy foods. However, the underlying mechanism is not yet understood. Tea, for its polyphenol content, has also been investigated. The main objective of this research was to concurrently study gastric emptying, appetite perceptions and glycemic responses to bread consumed with water, tea, or lemon juice. METHODS: In this randomized, crossover intervention, ten participants consumed equal portions of bread (100 g) with 250 mL of water, water-diluted lemon juice, or black tea at breakfast. Gastric volumes, blood glucose concentrations and appetite perceptions were alternately assessed over 180 min using magnetic resonance imaging, the finger-prick method and visual analogue scales, respectively. RESULTS: Compared to water, lemon juice led to a 1.5 fold increase of the volume of gastric contents, 30 min after the meal (454.0 ± 18.6 vs. 298.4 ± 19.5 mL, [Formula: see text] ± SEM P < 0.00001). Gastric emptying was also 1.5 times faster (P < 0.01). Conversely, lemon juice elicited a lower glycemic response than water (blood glucose concentrations at t = 55 min were 35% lower, P = 0.039). Tea had no effect. Changes in appetite perceptions and gastric volumes correlated well, but with no significant differences between the meals. CONCLUSIONS: Lemon juice lowered the glycemic response and increased both gastric secretions and emptying rate. The results are compatible with the hypothesis that the reduction of the glycemic response is mainly due to the interruption of starch hydrolysis via the acid-inhibition of salivary α-amylase. TRIAL REGISTRATION NUMBER: NCT03265392, August 29, 2017.

AZTEK: Adaptive zero TE k-space trajectories.

PURPOSE: Because of short signal lifetimes and respiratory motion, 3D lung MRI is still challenging today. Zero-TE (ZTE) pulse sequences offer promising solutions as they overcome the issue of short T2∗ . Nevertheless, as they rely on continuous readout gradients, the trajectories they follow in k-space are not adapted to retrospective gating and inferred motion correction. THEORY AND METHODS: We propose AZTEK (adaptive ZTE k-space trajectories), a set of 3D radial trajectories featuring three tuning parameters, to adapt the acquisition to any moving organ while keeping seamless transitions between consecutive spokes. Standard ZTE and AZTEK trajectories were compared for static and moving phantom acquisitions as well as for human thoracic imaging performed on 3 volunteers (1 healthy and 2 patients with lung cancer). RESULTS: For the static phantom, we observe comparable image qualities with standard and AZTEK trajectories. For the moving phantom, spatially coherent undersampling artifacts observed on gated images with the standard trajectory are alleviated with AZTEK. The same improvement in image quality is obtained in human, so details are more delineated in the lung with the use of the adaptive trajectory. CONCLUSION: The AZTEK technique opens the possibility for 3D dynamic ZTE lung imaging with retrospective gating. It enables us to uniformly sample the k-space for any arbitrary respiratory motion gate, while preserving static image quality, improving dynamic image quality and guaranteeing continuous readout gradient transitions between spokes, which makes it appropriate to ZTE.

Quantitative Gd-DOTA-based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE-MRI.

Asthma is a chronic respiratory disease, commonly treated with inhaled therapy. Better understanding of the mechanisms of aerosol deposition is required to improve inhaled drug delivery. Three-dimensional ultrashort echo time (UTE) MRI acquisitions at 1.5 T were combined with spontaneous nose-only inhalation of aerosolized gadolinium (Gd) to map the aerosol deposition and to characterize signal enhancement in asthmatic rat lungs. The rats were sensitized to ovalbumin (OVA) to develop asthmatic models and challenged before imaging by nebulization of OVA to trigger asthmatic symptoms. The negative controls were not sensitized or challenged by nebulization of saline. The animal lungs were imaged before and after administration of Gd-based aerosol in freely breathing rats, by using a T1 -weighted 3D UTE sequence. A contrast-enhanced quantitative analysis was performed to assess regional concentration. OVA-sensitized rats had lower signal enhancement and lower deposited aerosol concentration. Their enhancement dynamics showed large inter-subject variability. The signal intensity was homogeneously enhanced for controls while OVA-sensitized rats showed heterogeneous enhancement. Contrast-enhanced 3D UTE was applied with aerosolized Gd to efficiently measure spatially resolved deposition in asthmatic lungs. The small administered dose (around 1 µmol/kg body weight) and the use of standard clinical MRI suggest a potential application for the exploration of asthma.

Aerosol deposition in the lungs of spontaneously breathing rats using Gd-DOTA-based contrast agents and ultra-short echo time MRI at 1.5 Tesla.

PURPOSE: Aerosol toxicology and drug delivery through the lungs, which depend on various parameters, require methods to quantify particle deposition. Intrapulmonary-administered MRI contrast agent combined with lung-specific imaging sequences has been proposed as a high performance technique for aerosol research. Here, aerosol deposition is assessed using ultra-short echo (UTE) sequences. METHODS: Before and after administration of Gd-DOTA-based aerosol delivered nose-only in free-breathing healthy rats, a T1 -weighted 3D UTE sequence was applied in a clinical 1.5 Tesla scanner. Administration lasted 14 min, and the experiment was performed on six rats. A contrast-enhanced quantitative analysis was done. RESULTS: Fifty percent signal enhancement was obtained in the lung parenchyma. Lung clearance of the contrast agent was evaluated to be 14% per h (corresponding to a characteristic clearance time of 3.6 h) and aerosol deposition was shown to be homogeneous throughout the lung in healthy rats. The total deposited dose was estimated to be 1.05 µmol/kg body weight, and the concentration precision was 0.02 mM. CONCLUSION: The UTE protocol with nebulized Gd-DOTA is replicable to significantly enhance the lung parenchyma and to map aerosol deposition. This functional strategy, applied in a clinical system with a clinical nebulization setup and a low inhaled dose, suggests a feasible translation to human.

Novel inductive decoupling technique for flexible transceiver arrays of monolithic transmission line resonators.

PURPOSE: This article presents a novel inductive decoupling technique for form-fitting coil arrays of monolithic transmission line resonators, which target biomedical applications requiring high signal-to-noise ratio over a large field of view to image anatomical structures varying in size and shape from patient to patient. METHODS: Individual transmission line resonator elements are mutually decoupled using magnetic flux sharing by overlapping annexes. This decoupling technique was evaluated by electromagnetic simulations and bench measurements for two- and four-element arrays, comparing single- and double-gap transmission line resonator designs, combined either with a basic capacitive matching scheme or inductive pickup loop matching. The best performing array was used in 7T MRI experiments demonstrating its form-fitting ability and parallel imaging potential. RESULTS: The inductively matched double-gap transmission line resonator array provided the best decoupling efficiency in simulations and bench measurements (<-15 dB). The decoupling and parallel imaging performance proved robust against mechanical deformation of the array. CONCLUSION: The presented decoupling technique combines the robustness of conventional overlap decoupling regarding coil loading and operating frequency with the extended field of view of nonoverlapped coils. While demonstrated on four-element arrays, it can be easily expanded to fabricate readily decoupled form-fitting 2D arrays with an arbitrary number of elements in a single etching process.

Phase-contrast helium-3 MRI of aerosol deposition in human airways.

One of the key challenges in the study of health-related aerosols is predicting and monitoring sites of particle deposition in the respiratory tract. The potential health risks of ambient exposure to environmental or workplace aerosols and the beneficial effects of medical aerosols are strongly influenced by the site of aerosol deposition along the respiratory tract. Nuclear medicine is the only current modality that combines quantification and regional localization of aerosol deposition, and this technique remains limited by its spatial and temporal resolutions and by patient exposure to radiation. Recent work in MRI has shed light on techniques to quantify micro-sized magnetic particles in living bodies by the measurement of associated static magnetic field variations. With regard to lung MRI, hyperpolarized helium-3 may be used as a tracer gas to compensate for the lack of MR signal in the airways, so as to allow assessment of pulmonary function and morphology. The extrathoracic region of the human respiratory system plays a critical role in determining aerosol deposition patterns, as it acts as a filter upstream from the lungs. In the present work, aerosol deposition in a mouth-throat phantom was measured using helium-3 MRI and compared with single-photon emission computed tomography. By providing high sensitivity with high spatial and temporal resolutions, phase-contrast helium-3 MRI offers new insights for the study of particle transport and deposition.

Experimental system to detect a labeled cell monolayer in a microfluidic environment.

PURPOSE: To investigate the feasibility of detecting a living cell monolayer labeled with gadoterate (Gd-DOTA) in a microfluidic environment, by micromagnetic resonance imaging (MRI) in a 2.35T small-animal system. The development of new targeted contrast agents (CAs) requires proof-of-concept studies in order to establish the detectability of the CA and to predict the role of biodistribution in its uptake mechanisms. A promising approach is to carefully mimic the in vivo pharmacokinetic context with reduced experimental complexity compared to in vivo situations. MATERIALS AND METHODS: A dedicated experimental system was built by combining a microfluidic slide and a radiofrequency probe based on a 6 mm diameter multiturn transmission-line resonator. Adherent KB cells were incubated with different concentrations of Gd. MRI data were acquired at 2.35T with a 3D gradient echo and a resolution of 12.4 µm perpendicular to the cell layer. The longitudinal relaxation rate, R1 , was measured as a function of the amount of Gd internalized by the cells. RESULTS: R1 measurements for different Gd concentrations per cell were performed using data with an signal-to-noise ratio (SNR) of 100. Relaxation-rate variations ΔR1 of 0.035 s(-1) were measured. A quenching effect was observed at Gd concentrations above 20 fmol/cell. CONCLUSION: Our results suggest that this dedicated experimental system is suitable for specifically assessing new high-relaxivity targeted CAs under real-time uptake conditions.

In vivo MR imaging of the human skin at subnanoliter resolution using a superconducting surface coil at 1.5 Tesla.

PURPOSE: To demonstrate the feasibility of a highly sensitive superconducting surface coil for microscopic MRI of the human skin in vivo in a clinical 1.5 Tesla (T) scanner. MATERIALS AND METHODS: A 12.4-mm high-temperature superconducting coil was used at 1.5T for phantom and in vivo skin imaging. Images were inspected to identify fine anatomical skin structures. Signal-to-noise ratio (SNR) improvement by the high-temperature superconducting (HTS) coil, as compared to a commercial MR microscopy coil was quantified from phantom imaging; the gain over a geometrically identical coil made from copper (cooled or not) was theoretically deduced. Noise sources were identified to evaluate the potential of HTS coils for future studies. RESULTS: In vivo skin images with isotropic 80 µm resolution were demonstrated revealing fine anatomical structures. The HTS coil improved SNR by a factor 32 over the reference coil in a nonloading phantom. For calf imaging, SNR gains of 380% and 30% can be expected over an identical copper coil at room temperature and 77 K, respectively. CONCLUSION: The high sensitivity of HTS coils allows for microscopic imaging of the skin at 1.5T and could serve as a tool for dermatology in a clinical setting.

Generalized double-acquisition imaging for radiofrequency inhomogeneity mitigation in high-field MRI: experimental proof and performance analysis.

Transmit arrays have been developed to compensate for radiofrequency inhomogeneities in high-field MRI using different excitation schemes. They can be classified into static or dynamic shimmings depending on the target: homogenizing the radiofrequency field directly or homogenizing the flip angle distribution using the Bloch equation. We have developed an intermediate solution to compare shimming performances between different transmit arrays. This solution, called generalized double-acquisition imaging, is easier to implement than most dynamic shimming methods and offers more degrees of freedom than static shimmings. It uses two acquisitions so that the second acquisition complements the excitation of the first one to obtain by superposition an image that minimizes radiofrequency artefacts. For validation, the method is demonstrated experimentally for a gradient echo sequence on a spherical homogeneous phantom and by simulation on a human head model.

Publisher Correction: 3D Magnetic Resonance Spirometry.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3D Magnetic Resonance Spirometry.

Spirometry is today the gold standard technique for assessing pulmonary ventilatory function in humans. From the shape of a flow-volume loop measured while the patient is performing forced respiratory cycles, the Forced Vital Capacity (FVC) and the Forced Expiratory Volume in one second (FEV1) can be inferred, and the pulmonologist is able to detect and characterize common respiratory afflictions. This technique is non-invasive, simple, widely available, robust, repeatable and reproducible. Yet, its outcomes rely on the patient's cooperation and provide only global information over the lung. With 3D Magnetic Resonance (MR) Spirometry, local ventilation can be assessed by MRI anywhere in the lung while the patient is freely breathing. The larger dimensionality of 3D MR Spirometry advantageously allows the extraction of original metrics that characterize the anisotropic and hysteretic regional mechanical behavior of the lung. Here, we demonstrated the potential of this technique on a healthy human volunteer breathing along different respiratory patterns during the MR acquisition. These new results are discussed with lung physiology and recent pulmonary CT data. As respiratory mechanics inherently support lung ventilation, 3D MR Spirometry may open a new way to non-invasively explore lung function while providing improved diagnosis of localized pulmonary diseases.

A temperature-controlled cryogen free cryostat integrated with transceiver-mode superconducting coil for high-resolution magnetic resonance imaging.

Small-sized High Temperature Superconducting (HTS) radiofrequency coils are used in a number of micro-magnetic resonance imaging applications and demonstrate a high detection sensitivity that improves the signal-to-noise ratio. However, the use of HTS coils could be limited by the rarity of cryostats that are suitable for the MR environment. This study presents a magnetic resonance (MR)-compatible and easily operated cryogen-free cryostat based on the pulse tube cryocooler technology for the cooling and monitoring of HTS coils below the temperature of liquid nitrogen. This cryostat features a real-time temperature control function that allows the precise frequency adjustment of the HTS coil. The influence of the temperature on the electrical properties, resonance frequency (f0), and quality factor (Q) of the HTS coil was investigated. Temperature control is obtained with an accuracy of over 0.55 K from 60 K to 86 K, and the sensitivity of the system, extracted from the frequency measurement from 60 K to 75 K, is of about 2 kHz/K, allowing a fine retuning (within few Hz, compared to 10 kHz bandwidth) in good agreement with experimental requirements. We demonstrated that the cryostat, which is mainly composed of non-magnetic materials, does not perturb the electromagnetic field in any way. MR images of a 10 × 10 × 15 mm3 liquid phantom were acquired using the HTS coil as a transceiver with a spatial resolution of 100 × 100 × 300 µm3 in less than 20 min under experimental conditions at 1.5 T.

Performance of a miniature high-temperature superconducting (HTS) surface coil for in vivo microimaging of the mouse in a standard 1.5T clinical whole-body scanner.

The performance of a 12-mm high-temperature superconducting (HTS) surface coil for in vivo microimaging of mice in a standard 1.5T clinical whole-body scanner was investigated. Systematic evaluation of MR image quality was conducted on saline phantoms with various conductivities to derive the sensitivity improvement brought by the HTS coil compared with a similar room-temperature copper coil. The observed signal-to-noise ratio (SNR) was correlated to the loaded quality factor of the radio frequency (RF) coils and is theoretically validated with respect to the noise contribution of the MR acquisition channel. The expected in vivo SNR gain was then extrapolated for different anatomical sites by monitoring the quality factor in situ during animal imaging experiments. Typical SNR gains of 9.8, 9.8, 5.4, and 11.6 were found for brain, knee, back, and subcutaneous implanted tumors, respectively, over a series of mice. Excellent in vivo image quality was demonstrated in 16 min with native voxels down to (59 microm)(3) with an SNR of 20. The HTS coil technology opens the way, for the first time at the current field strength of clinical MR scanners, to spatial resolutions below 10(-3) mm(3) in living mice, which until now were only accessible to specialized high-field MR microscopes.

In vivo single cell detection of tumor-infiltrating lymphocytes with a clinical 1.5 Tesla MRI system.

We demonstrate the feasibility of detecting individual tumor-infiltrating cells in vivo, by means of cellular magnetic labeling and a 1.5 Tesla clinical MRI device equipped with a high-resolution surface coil. Using a recently developed high-temperature superconducting (HTS) surface coil, single cells were detected in vitro in voxels of (60 microm)(3) at magnetic loads as low as 0.2 pg of iron per cell. The same imaging protocol was used in vivo to monitor infiltration of ovalbumin-expressing tumors by transferred OVA antigen-specific cytotoxic lymphocytes with low iron load.

A flexible 12-channel transceiver array of transmission line resonators for 7 T MRI.

A flexible transceiver array based on transmission line resonators (TLRs) combining the advantages of coil arrays with the possibility of form-fitting targeting cardiac MRI at 7 T is presented. The design contains 12 elements which are fabricated on a flexible substrate with rigid PCBs attached on the center of each element to place the interface components, i.e. transmit/receive (T/R) switch, power splitter, pre-amplifier and capacitive tuning/matching circuitry. The mutual coupling between elements is cancelled using a decoupling ring-based technique. The performance of the developed array is evaluated by 3D electromagnetic simulations, bench tests, and MR measurements using phantoms. Efficient inter-element decoupling is demonstrated in flat configuration on a box-shaped phantom (Sij < -19 dB), and bent on a human torso phantom (Sij < -16 dB). Acceleration factors up to 3 can be employed in bent configuration with reasonable g-factors (<1.7) in an ROI at the position of the heart. The array enables geometrical conformity to bodies within a large range of size and shape and is compatible with parallel imaging and parallel transmission techniques.

Method for nonlinear characterization of radio frequency coils made of high temperature superconducting material in view of magnetic resonance imaging applications.

A contactless method based on reflectometry to accurately characterize an inductive radio frequency (rf) resonator even in the occurrence of a strong electrical nonlinearity is presented. Nonlinear extraction of the unloaded quality factor and resonance frequency is possible by combining an initial low-level swept-frequency calibration with high-level single-frequency measurements. The extraction protocol relies on a simple intrinsic R, L, C model and does not involve a fitting procedure according to a particular nonlinearity model. It includes a correction for strong coupling conditions between the probe and the rf coil, which allows extending the analysis over a wide range of transmitted power. Electrical modeling based on the extracted intrinsic data allows predicting the coil behavior when loaded by any kind of matching network. The method will have implications in different domains such as Magnetic Resonance (MR) applications with superconducting probe heads or analysis of rf properties in nonlinear materials. The method is demonstrated here by characterizing a high temperature superconducting (HTS) coil dedicated to MR imaging at 64 MHz. The coil consists in a multiturn spiral design that is self-resonant close to the MR frequency of interest. The Q factor and the resonance frequency are determined as a function of the actual power dissipated in the HTS coil accounting for losses occurring in the measurement system. Further characteristics of the HTS coil are considered in the present paper. The relation between the transmitted power and the magnetic field generated by the coil, which is the most relevant characteristics for MR applications, is directly accessible. The equivalent impedance of the coil under test is also expressed as a function of the total current flowing in the windings. The method could be extended to assess the fundamental properties of the nonlinear material (e.g., the London penetration depth or the critical current density) by including any pertinent model.

Multi-turn multi-gap transmission line resonators - Concept, design and first implementation at 4.7T and 7T.

A novel design scheme for monolithic transmission line resonators (TLRs) is presented - the multi-turn multi-gap TLR (MTMG-TLR) design. The MTMG-TLR design enables the construction of TLRs with multiple turns and multiple gaps. This presents an additional degree of freedom in tuning self-resonant TLRs, as their resonance frequency is fully determined by the coil geometry (e.g. diameter, number of turns, conductor width, etc.). The novel design is evaluated at 4.7T and 7T by simulations and experiments, where it is demonstrated that MTMG-TLRs can be used for MRI, and that the B1 distribution of MTMG-TLRs strongly depends on the number and distribution of turns. A comparison to conventional loop coils revealed that the B1 performance of MTMG-TLRs is comparable to a loop coil with the same mean diameter; however, lower 10g SAR values were found for MTMG-TLRs. The MTMG-TLR design is expected to bring most benefits at high static field, where it allows for independent size and frequency selection, which cannot be achieved with standard TLR design. However, it also enables more accurate geometric optimization at low static field. Thereby, the MTMG-TLR design preserves the intrinsic advantages of TLRs, i.e. mechanical flexibility, high SAR efficiency, mass production, and coil miniaturization.

Contrast-enhanced dynamic MRI protocol with improved spatial and time resolution for in vivo microimaging of the mouse with a 1.5-T body scanner and a superconducting surface coil.

Magnetic resonance imaging (MRI) is well suited for small animal model investigations to study various human pathologies. However, the assessment of microscopic information requires a high-spatial resolution (HSR) leading to a critical problem of signal-to-noise ratio limitations in standard whole-body imager. As contrast mechanisms are field dependent, working at high field do not allow to derive MRI criteria that may apply to clinical settings done in standard whole-body systems. In this work, a contrast-enhanced dynamic MRI protocol with improved spatial and time resolution was used to perform in vivo tumor model imaging on the mouse at 1.5 T. The needed sensitivity is provided by the use of a 12-mm superconducting surface coil operating at 77 K. High quality in vivo images were obtained and revealed well-defined internal structures of the tumor. A 3-D HSR sequence with voxels of 59x59x300 microm3 encoded within 6.9 min and a 2-D sequence with subsecond acquisition time and isotropic in-plane resolution of 234 microm were used to analyze the contrast enhancement kinetics in tumoral structures at long and short time scales. This work is a first step to better characterize and differentiate the dynamic behavior of tumoral heterogeneities.

Evaluation of lung recovery after static administration of three different perfluorocarbons in pigs.

BACKGROUND: The respiratory properties of perfluorocarbons (PFC) have been widely studied for liquid ventilation in humans and animals. Several PFC were tested but their tolerance may depend on the species. Here, the effects of a single administration of liquid PFC into pig lungs were assessed and compared. Three different PFC having distinct evaporative and spreading coefficient properties were evaluated (Perfluorooctyl bromide [PFOB], perfluorodecalin [PFD] and perfluoro-N-octane [PFOC]). METHODS: Pigs were anesthetized and submitted to mechanical ventilation. They randomly received an intra-tracheal administration of 15 ml/kg of either PFOB, PFD or PFOC with 12 h of mechanical ventilation before awakening and weaning from ventilation. A Control group was submitted to mechanical ventilation with no PFC administration. All animals were followed during 4 days after the initial PFC administration to investigate gas exchanges and clinical recovery. They were ultimately euthanized for histological analyses and assessment of PFC residual concentrations within the lungs using dual nuclei fluorine and hydrogen Magnetic Resonance Imaging (MRI). Sixteen animals were included (4/group). RESULTS: In the PFD group, animals tended to be hypoxemic after awakening. In PFOB and PFOC groups, blood gases were not significantly different from the Control group after awakening. The poor tolerance of PFD was likely related to a large amount of residual PFC, as observed using MRI in all lung samples (≈10% of lung volume). This percentage was lower in the PFOB group (≈1%) but remained significantly greater than in the Control group. In the PFOC group, the percentage of residual PFC was not significantly different from that of the Control group (≈0.1%). Histologically, the most striking feature was an alveolar infiltration with foam macrophages, especially in the groups treated by PFD or PFOB. CONCLUSIONS: Of the three tested perfluorocarbons, PFOC offered the best tolerance in terms of lung function, gas exchanges and residuum in the lung. PFOC was rapidly cleared from the lungs and virtually disappeared after 4 days whereas PFOB persisted at significant levels and led to foam macrophage infiltration. PFOC could be relevant for short term total liquid ventilation with a rapid weaning.