Digital reference object toolkit of breast DCE MRI for quantitative evaluation of image reconstruction and analysis methods.

PURPOSE: To develop a digital reference object (DRO) toolkit to generate realistic breast DCE-MRI data for quantitative assessment of image reconstruction and data analysis methods. METHODS: A simulation framework in a form of DRO toolkit has been developed using the ultrafast and conventional breast DCE-MRI data of 53 women with malignant (n = 25) or benign (n = 28) lesions. We segmented five anatomical regions and performed pharmacokinetic analysis to determine the ranges of pharmacokinetic parameters for each segmented region. A database of the segmentations and their pharmacokinetic parameters is included in the DRO toolkit that can generate a large number of realistic breast DCE-MRI data. We provide two potential examples for our DRO toolkit: assessing the accuracy of an image reconstruction method using undersampled simulated radial k-space data and assessing the impact of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity on estimated parameters. RESULTS: The estimated pharmacokinetic parameters for each region showed agreement with previously reported values. For the assessment of the reconstruction method, it was found that the temporal regularization resulted in significant underestimation of estimated parameters by up to 57% and 10% with the weighting factor λ = 0.1 and 0.01, respectively. We also demonstrated that spatial discrepancy of v p $$ {v}_p $$ and PS $$ \mathrm{PS} $$ increase to about 33% and 51% without correction for B 1 + $$ {\mathrm{B}}_1^{+} $$ field. CONCLUSION: We have developed a DRO toolkit that includes realistic morphology of tumor lesions along with the expected pharmacokinetic parameter ranges. This simulation framework can generate many images for quantitative assessment of DCE-MRI reconstruction and analysis methods.

Free-Breathing Liver Fat, R2* and B0 Field Mapping Using Multi-Echo Radial FLASH and Regularized Model-Based Reconstruction.

This work introduced a stack-of-radial multi-echo asymmetric-echo MRI sequence for free-breathing liver volumetric acquisition. Regularized model-based reconstruction was implemented in Berkeley Advanced Reconstruction Toolbox (BART) to jointly estimate all physical parameter maps (water, fat, R2∗ , and B0 field inhomogeneity maps) and coil sensitivity maps from self-gated k -space data. Specifically, locally low rank and temporal total variation regularization were employed directly on physical parameter maps. The proposed free-breathing radial technique was tested on a water/fat & iron phantom, a young volunteer, and obesity/diabetes/hepatic steatosis patients. Quantitative fat fraction and R2∗ accuracy were confirmed by comparing our technique with the reference breath-hold Cartesian scan. The multi-echo radial sampling sequence achieves fast k -space coverage and is robust to motion. Moreover, the proposed motion-resolved model-based reconstruction allows for free-breathing liver fat and R2∗ quantification in multiple motion states. Overall, our proposed technique offers a convenient tool for non-invasive liver assessment with no breath holding requirement.

Free-breathing myocardial T1 mapping using inversion-recovery radial FLASH and motion-resolved model-based reconstruction.

PURPOSE: To develop a free-breathing myocardial T 1 $$ {\mathrm{T}}_1 $$ mapping technique using inversion-recovery (IR) radial fast low-angle shot (FLASH) and calibrationless motion-resolved model-based reconstruction. METHODS: Free-running (free-breathing, retrospective cardiac gating) IR radial FLASH is used for data acquisition at 3T. First, to reduce the waiting time between inversions, an analytical formula is derived that takes the incomplete T 1 $$ {\mathrm{T}}_1 $$ recovery into account for an accurate T 1 $$ {\mathrm{T}}_1 $$ calculation. Second, the respiratory motion signal is estimated from the k-space center of the contrast varying acquisition using an adapted singular spectrum analysis (SSA-FARY) technique. Third, a motion-resolved model-based reconstruction is used to estimate both parameter and coil sensitivity maps directly from the sorted k-space data. Thus, spatiotemporal total variation, in addition to the spatial sparsity constraints, can be directly applied to the parameter maps. Validations are performed on an experimental phantom, 11 human subjects, and a young landrace pig with myocardial infarction. RESULTS: In comparison to an IR spin-echo reference, phantom results confirm good T 1 $$ {\mathrm{T}}_1 $$ accuracy, when reducing the waiting time from 5 s to 1 s using the new correction. The motion-resolved model-based reconstruction further improves T 1 $$ {\mathrm{T}}_1 $$ precision compared to the spatial regularization-only reconstruction. Aside from showing that a reliable respiratory motion signal can be estimated using modified SSA-FARY, in vivo studies demonstrate that dynamic myocardial T 1 $$ {\mathrm{T}}_1 $$ maps can be obtained within 2 min with good precision and repeatability. CONCLUSION: Motion-resolved myocardial T 1 $$ {\mathrm{T}}_1 $$ mapping during free-breathing with good accuracy, precision and repeatability can be achieved by combining inversion-recovery radial FLASH, self-gating and a calibrationless motion-resolved model-based reconstruction.

Physics-based reconstruction methods for magnetic resonance imaging.

Conventional magnetic resonance imaging (MRI) is hampered by long scan times and only qualitative image contrasts that prohibit a direct comparison between different systems. To address these limitations, model-based reconstructions explicitly model the physical laws that govern the MRI signal generation. By formulating image reconstruction as an inverse problem, quantitative maps of the underlying physical parameters can then be extracted directly from efficiently acquired k-space signals without intermediate image reconstruction-addressing both shortcomings of conventional MRI at the same time. This review will discuss basic concepts of model-based reconstructions and report on our experience in developing several model-based methods over the last decade using selected examples that are provided complete with data and code. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.

Illuminating solvent-free synthesis of zeolites.

With the merits of the accelerated crystallization process, high volume yields, and reduced waste production, solvent-free syntheses give new opportunities for the fabrication of zeolites. In this Frontier, a background overview is provided, consisting of a brief introduction of challenges in traditional zeolite syntheses and how solvent-free syntheses provide the right combination of properties for achieving a more sustainable route. Next, recent advancements in zeolites synthesized under solvent-free conditions are exemplified along with discussions about the strategies and principles involved. Finally, the remaining challenges and opportunities for this synthetic route are outlined.

Real-time multi-directional flow MRI using model-based reconstructions of undersampled radial FLASH - A feasibility study.

The purpose of this work was to develop an acquisition and reconstruction technique for two- and three-directional (2d and 3d) phase-contrast flow MRI in real time. A previous real-time MRI technique for one-directional (1d) through-plane flow was extended to 2d and 3d flow MRI by introducing in-plane flow sensitivity. The method employs highly undersampled radial FLASH sequences with sequential acquisitions of two or three flow-encoding datasets and one flow-compensated dataset. Echo times are minimized by merging the waveforms of flow-encoding and radial imaging gradients. For each velocity direction individually, model-based reconstructions by regularized nonlinear inversion jointly estimate an anatomical image, a set of coil sensitivities and a phase-contrast velocity map directly. The reconstructions take advantage of a dynamic phase reference obtained by interpolating consecutive flow-compensated acquisitions. Validations include pulsatile flow phantoms as well as in vivo studies of the human aorta at 3 T. The proposed method offers cross-sectional 2d and 3d flow MRI of the human aortic arch at 53 and 67 ms resolution, respectively, without ECG synchronization and during free breathing. The in-plane resolution was 1.5 × 1.5 mm2 and the slice thickness 6 mm. In conclusion, real-time multi-directional flow MRI offers new opportunities to study complex human blood flow without the risk of combining differential phase (i.e., velocity) information from multiple heartbeats as for ECG-gated data. The method would benefit from a further reduction of acquisition time and accelerated computing to allow for extended clinical trials.

Dynamic water/fat separation and B0 inhomogeneity mapping-joint estimation using undersampled triple-echo multi-spoke radial FLASH.

PURPOSE: To achieve dynamic water/fat separation and B0 field inhomogeneity mapping via model-based reconstructions of undersampled triple-echo multi-spoke radial FLASH acquisitions. METHODS: This work introduces an undersampled triple-echo multi-spoke radial FLASH sequence, which uses (i) complementary radial spokes per echo train for faster spatial encoding, (ii) asymmetric echoes for flexible and nonuniform echo spacing, and (iii) a golden angle increment across frames for optimal k-space coverage. Joint estimation of water, fat, B0 inhomogeneity, and coil sensitivity maps from undersampled triple-echo data poses a nonlinear and non-convex inverse problem which is solved by a model-based reconstruction with suitable regularization. The developed methods are validated using phantom experiments with different degrees of undersampling. Real-time MRI studies of the knee, liver, and heart are conducted without prospective gating or retrospective data sorting at temporal resolutions of 70, 158, and 40 ms, respectively. RESULTS: Up to 18-fold undersampling is achieved in this work. Even in the presence of rapid physiological motion, large B0 field inhomogeneities, and phase wrapping, the model-based reconstruction yields reliably separated water/fat maps in conjunction with spatially smooth inhomogeneity maps. CONCLUSIONS: The combination of a triple-echo acquisition and joint reconstruction technique provides a practical solution to time-resolved and motion robust water/fat separation at high spatial and temporal resolution.

Diffusion-weighted MRI of the prostate without susceptibility artifacts: Undersampled multi-shot turbo-STEAM with rotated radial trajectories.

The aim of this study was to develop and evaluate a clinically feasible approach to diffusion-weighted (DW) MRI of the prostate without susceptibility-induced artifacts. The proposed method relies on an undersampled multi-shot DW turbo-STEAM sequence with rotated radial trajectories and a multi-step inverse reconstruction with denoised multi-shot phase maps. The total acquisition time was below 6 min for a resolution of 1.4 × 1.4 × 3.5 mm3 and six directions at b = 600 s mm-2 . Studies of eight healthy subjects and two patients with prostate cancer were performed at 3 T employing an 18-channel body-array coil and elements of the spine coil. The method was compared with conventional DW echo-planar imaging (EPI) of the prostate. The results confirm that DW STEAM MRI avoids geometric distortions and false image intensities, which were present for both single-shot EPI (ssEPI) and readout-segmented EPI, particularly near the intestinal wall of the prostate. Quantitative accuracy of the apparent diffusion coefficient (ADC) was validated with use of a numerical phantom providing ground truth. ADC values in the central prostate gland of healthy subjects were consistent with those measured using ssEPI and with literature data. Preliminary results for patients with prostate cancer revealed a correct anatomical localization of lesions with respect to T2 -weighted MRI in both mean DW STEAM images and ADC maps. In summary, DW STEAM MRI of the prostate offers clinically relevant advantages for the diagnosis of prostate cancer compared with state-of-the-art EPI-based approaches. The method warrants extended clinical trials.

Magnetic resonance imaging of noradrenergic neurons.

Noradrenaline is a neurotransmitter involved in general arousal, selective attention, memory, inflammation, and neurodegeneration. The purpose of this work was to delineate noradrenergic neurons in vivo by T1-weighted MRI with magnetization transfer (MT). In the brainstem of human and mice, MRI identified the locus coeruleus, dorsal motor vagus nucleus, and nucleus tractus solitarius. Given (1) the long T1 and low magnetization transfer ratio for the noradrenergic cell groups compared to other gray matter, (2) significant correlation between MT MRI signal intensity and proton density, and (3) no correlation between magnetization transfer ratio (or R1) and iron, copper, or manganese in human brain, the high MRI signal of the noradrenergic neurons must be attributed to abundant water protons interacting with any T1-shortening paramagnetic ions in active cells rather than to specific T1-shortening molecules. The absence of a high MRI signal from the locus coeruleus of Ear2(-/-) mice lacking noradrenergic neurons confirms that cell bodies of noradrenergic neurons are the source of the bright MRI appearance. The observation of this high signal in DBH(-/-) mice, in 3-week-old mice, and in mice under hyperoxia/hypercapnia/hypoxia together with the general absence of neuromelanin (NM) in noradrenergic neurons of young rodents further excludes that it is due to NM, dopamine ß-hydroxylase, their binding to paramagnetic ions, blood inflow, or hemoglobin. Instead, these findings indicate a high density of water protons whose T1 is shortened by paramagnetic ions as the relevant source of the high MRI signal. In the brain of APP/PS1/Ear2(-/-) mice, a transgenic model of Alzheimer's disease, MRI detected noradrenergic neuron loss in the locus coeruleus. Proton magnetic resonance spectroscopy revealed that a 60-75% reduction of noradrenaline is responsible for a reduction of N-acetylaspartate and glutamate in the hippocampus as well as for a shortening of the water proton T2 in the frontal cortex. These results suggest that a concurrent shortage of noradrenaline in Alzheimer's disease accelerates pathologic processes such as inflammation and neuron loss.

Magnetic resonance imaging of brain cell water.

In the central nervous system of vertebrates, cell bodies of neurons are often assembled as nuclei or cellular layers that play specific roles as functional units. The purpose of this work was to selectively highlight such cell assemblies by magnetic resonance imaging using signals from water protons that are associated with intracellular paramagnetic ions, while saturating lipid-associated water protons as well as extracellular free water protons. Given the significant correlation between image signal intensity and water proton density, the high signal intensities observed for such cell assemblies must be attributed to their abundant paramagnetic-ion-associated water protons. In the hippocampal formation, the technique visualized cell assemblies that were so far not depicted in human in vivo. In the brainstem, the technique delineated noradrenergic neuron groups such as the locus coeruleus in human and mice in vivo. Their reduced magnetization-transfer ratios together with their prolonged relaxation times compared to other gray matter indicate that the source of their high signal intensity is not the presence of T1-shortening molecules, e.g., neuromelanin, but their high water content. Given the general absence of neuromelanin in noradrenergic neurons of rodents, their high signal intensity in mice in vivo further supports this view.

Carotid artery flow as determined by real-time phase-contrast flow MRI and neurovascular ultrasound: A comparative study of healthy subjects.

BACKGROUND: The assessment of carotid artery flow by neurovascular ultrasound (nvUS) can be complemented by real-time phase-contrast (RT-PC) flow MRI which apart from quantitative flow parameters offers velocity distributions across the entire vessel lumen. MATERIALS AND METHODS: The feasibility and diagnostic potential of RT-PC flow MRI was evaluated in 20 healthy volunteers in comparison to conventional nvUS. RT-PC flow MRI at 40 ms temporal resolution and 0.8 mm in-plane resolution resulted in velocity maps with low phase noise and high spatiotemporal accuracy by exploiting respective advances of a recent nonlinear inverse model-based reconstruction. Peak-systolic velocities (PSV), end-diastolic velocities (EDV), flow volumes and comprehensive velocity profiles were determined in the common, internal and external carotid artery on both sides. RESULTS: Flow characteristics such as pulsatility and individual abnormalities shown on nvUS could be reproduced and visualized in detail by RT-PC flow MRI. PSV to EDV differences revealed good agreement between both techniques, mean PSV and EDV were significantly lower and flow volumes were higher for MRI. CONCLUSION: Our findings suggest that RT-PC flow MRI adds to clinical diagnostics, e.g. by alterations of dynamic velocity distributions in patients with carotid stenosis. Lower PSV and EDV values than for nvUS mainly reflect the longer MRI acquisition time which attenuates short peak velocities, while higher flow volumes benefit from a proper assessment of the true vessel lumen.

Model-based T1 mapping with sparsity constraints using single-shot inversion-recovery radial FLASH.

PURPOSE: To develop a model-based reconstruction technique for single-shot T1 mapping with high spatial resolution, accuracy, and precision using an inversion-recovery (IR) fast low-angle shot (FLASH) acquisition with radial encoding. METHODS: The proposed model-based reconstruction jointly estimates all model parameters, that is, the equilibrium magnetization, steady-state magnetization, 1/ T1*, and all coil sensitivities from the data of a single-shot IR FLASH acquisition with a small golden-angle radial trajectory. Joint sparsity constraints on the parameter maps are exploited to improve the performance of the iteratively regularized Gauss-Newton method chosen for solving the nonlinear inverse problem. Validations include both a numerical and experimental T1 phantom, as well as in vivo studies of the human brain and liver at 3 T. RESULTS: In comparison to previous reconstruction methods for single-shot T1 mapping, which are based on real-time MRI with pixel-wise fitting and a model-based approach with a predetermination of coil sensitivities, the proposed method presents with improved robustness against phase errors and numerical precision in both phantom and in vivo studies. CONCLUSION: The comprehensive model-based reconstruction with L1 regularization offers rapid and robust T1 mapping with high accuracy and precision. The method warrants accelerated computing and online implementation for extended clinical trials. Magn Reson Med 79:730-740, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

An eigenvalue approach for the automatic scaling of unknowns in model-based reconstructions: Application to real-time phase-contrast flow MRI.

The purpose of this work is to develop an automatic method for the scaling of unknowns in model-based nonlinear inverse reconstructions and to evaluate its application to real-time phase-contrast (RT-PC) flow magnetic resonance imaging (MRI). Model-based MRI reconstructions of parametric maps which describe a physical or physiological function require the solution of a nonlinear inverse problem, because the list of unknowns in the extended MRI signal equation comprises multiple functional parameters and all coil sensitivity profiles. Iterative solutions therefore rely on an appropriate scaling of unknowns to numerically balance partial derivatives and regularization terms. The scaling of unknowns emerges as a self-adjoint and positive-definite matrix which is expressible by its maximal eigenvalue and solved by power iterations. The proposed method is applied to RT-PC flow MRI based on highly undersampled acquisitions. Experimental validations include numerical phantoms providing ground truth and a wide range of human studies in the ascending aorta, carotid arteries, deep veins during muscular exercise and cerebrospinal fluid during deep respiration. For RT-PC flow MRI, model-based reconstructions with automatic scaling not only offer velocity maps with high spatiotemporal acuity and much reduced phase noise, but also ensure fast convergence as well as accurate and precise velocities for all conditions tested, i.e. for different velocity ranges, vessel sizes and the simultaneous presence of signals with velocity aliasing. In summary, the proposed automatic scaling of unknowns in model-based MRI reconstructions yields quantitatively reliable velocities for RT-PC flow MRI in various experimental scenarios.

Model-based reconstruction for real-time phase-contrast flow MRI: Improved spatiotemporal accuracy.

PURPOSE: To develop a model-based reconstruction technique for real-time phase-contrast flow MRI with improved spatiotemporal accuracy in comparison to methods using phase differences of two separately reconstructed images with differential flow encodings. METHODS: The proposed method jointly computes a common image, a phase-contrast map, and a set of coil sensitivities from every pair of flow-compensated and flow-encoded datasets obtained by highly undersampled radial FLASH. Real-time acquisitions with five and seven radial spokes per image resulted in 25.6 and 35.7 ms measuring time per phase-contrast map, respectively. The signal model for phase-contrast flow MRI requires the solution of a nonlinear inverse problem, which is accomplished by an iteratively regularized Gauss-Newton method. Aspects of regularization and scaling are discussed. The model-based reconstruction was validated for a numerical and experimental flow phantom and applied to real-time phase-contrast MRI of the human aorta for 10 healthy subjects and 2 patients. RESULTS: Under all conditions, and compared with a previously developed real-time flow MRI method, the proposed method yields quantitatively accurate phase-contrast maps (i.e., flow velocities) with improved spatial acuity, reduced phase noise and reduced streaking artifacts. CONCLUSION: This novel model-based reconstruction technique may become a new tool for clinical flow MRI in real time. Magn Reson Med 77:1082-1093, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Advances in real-time phase-contrast flow MRI using asymmetric radial gradient echoes.

PURPOSE: To provide multidimensional velocity compensation for real-time phase-contrast flow MRI. METHODS: The proposed method introduces asymmetric gradient echoes for highly undersampled radial FLASH MRI with phase-sensitive image reconstruction by regularized nonlinear inversion (NLINV). Using an adapted gradient delay correction the resulting image quality was analyzed by simulations and experimentally validated at 3 Tesla. For real-time flow MRI the reduced gradient-echo timing allowed for the incorporation of velocity-compensating waveforms for all imaging gradients at even shorter repetition times. RESULTS: The results reveal a usable degree of 20% asymmetry. Real-time flow MRI with full velocity compensation eliminated signal void in a flow phantom, confirmed flow parameters in healthy subjects and demonstrated signal recovery and phase conservation in a patient with aortic valve insufficiency and stenosis. Exemplary protocols at 1.4-1.5 mm resolution and 6 mm slice thickness achieved total acquisition times of 33.3-35.7 ms for two images (7 spokes each) with and without flow-encoding gradient. CONCLUSION: Asymmetric gradient echoes were successfully implemented for highly undersampled radial trajectories. The resulting temporal gain offers full velocity compensation for real-time phase-contrast flow MRI which minimizes false-positive contributions from complex flow and further enhances the temporal resolution compared with acquisitions with symmetric echoes.

PVN c-fos expression, HPA axis response and immune cell distribution during restraint stress.

It is well known that stress affects the central nervous system (CNS), neuroendocrinoimmune system and other peripheral organs such as the gastrointestinal tract. However, the process of adaptation or recovery after acute stress reactions in these systems or organs during prolonged stress has not yet been adequately investigated. To clarify the process of adaptation or recovery in these systems and organs after acute stress reactions, the time course of these responses during a single long-duration restraint stress (RTS) was studied. The expression of c-fos in the hypothalamic paraventricular nucleus (PVN) region of the brain was induced and reached a peak at 0.5 hours for c-fos mRNA and 4 hours for c-fos protein (Fos), but disappeared at 2 hours for mRNA and 16 hours for Fos during continuous RTS. The activation of the hypothalamic-pituitary-adrenal (HPA) axis during stress resulted in rapid increases in the plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Whereas the increase in ACTH was transient, the rise in CORT was maintained throughout the duration of the stress. A rapid significant decrease after stress exposure and following a slow and complete or partial recovery were observed in a number of total white blood cells (WBC), lymphocytes (LYM), helper T cells (Th) and cytotoxic/suppressor T cells (CTL/Ts). A gastric ulcer was found in 1/6 and 6/6 rats at 8 hours and 16 hours RTS, respectively. These results suggest that adaptive changes may occur in c-fos expression in the PVN, ACTH release and immune response, but not for CORT release, following acute stress reaction during long-duration RTS. In addition, any associated organic damage, such as gastric ulceration, was also suggested to possibly be progressive according to the duration of RTS.

Superimposed cold stress-induced hypothalamic-pituitary-adrenal response during long-duration restraint stress.

It has been reported that animals exposed to prior stress exhibit enhanced, reduced or equivalent hypothalamic-pituitary-adrenal (HPA) response to a subsequent acute stressor. We demonstrated previously that a long-duration restraint stress (RTS) evoked adaptive change, characterized by transient increase and gradual recovery to basal level in c-fos mRNA/c-fos protein (Fos) expression in the hypothalamic paraventricular nucleus (PVN) and in plasma adrenocorticotropin (ACTH) levels, although circulating corticosterone (CORT) remained at a high level. In order to investigate the HPA response to another stressor during the adaptive phase of long-duration RTS, we superimposed acute cold stressor (CS) to 16 hours RTS rats. Superimposed CS-induced re-expression of c-fos mRNA/Fos in the parvocellular region of the PVN (PVNpv) was observed in 16 hours RTS rats. The degree of expression of c-fos gene in superimposed CS rats was the same as those observed in single CS rats. The plasma ACTH levels induced by superimposed CS in 16 hours RTS rats were significantly higher compared with those in single CS rats. On the other hand, there were no significant differences between plasma CORT levels induced by superimposed CS in 16 hours RTS rats and those in single CS rats, and between plasma CORT levels before and after additional CS exposure in 16 hours RTS rats. The present study indicated that c-fos gene expression in PVN induced by superimposed CS was normo-responsive, ACTH secretion was hyper-responsive (facilitation), CORT secretion was slightly increased, but not hyper-responsive in long-duration RTS rats. These findings suggest that stress response induced by superimposed CS during long-duration RTS may occur in a different way at each level of the HPA.