Fat-free noncontrast whole-heart CMR with fast and power-optimized off-resonant water excitation pulses

Background: Cardiovascular MRI (CMR) faces challenges due to the interference of bright fat signals in visualizing anatomical structures. Effective fat suppression is crucial when using whole-heart CMR. Conventional methods often fall short due to rapid fat signal recovery and water-selective off-resonant pulses come with tradeoffs between scan time and RF energy deposit. A lipid-insensitive binomial off-resonant (LIBOR) RF pulse is introduced, addressing concerns about RF energy and scan time for CMR at 3T. Methods: A short LIBOR pulse was developed and implemented in a free-breathing respiratory self-navigated whole-heart sequence at 3T. A BORR pulse with matched duration, as well as previously used LIBRE pulses, were implemented and optimized for fat suppression in numerical simulations and validated in healthy subjects (n=3). Whole-heart CMR was performed in healthy subjects (n=5) with all four pulses. The SNR of ventricular blood, skeletal muscle, myocardium, and subcutaneous fat, and the coronary vessel sharpness and length were compared. Results: Experiments validated numerical findings and near homogeneous fat suppression was achieved with all pulses. Comparing the short pulses (1ms), LIBOR reduced the RF power two-fold compared with LIBRE, and three-fold compared with BORR, and LIBOR significantly decreased overall fat SNR. The reduction in RF duration shortened the whole-heart acquisition from 8.5min to 7min. No significant differences in coronary arteries detection and sharpness were found when comparing all four pulses. Conclusion: LIBOR enabled whole-heart CMR under 7 minutes at 3T, with large volume fat signal suppression, while reducing RF power compared with LIBRE and BORR. LIBOR is an excellent candidate to address SAR problems encountered in CMR where fat suppression remains challenging and short RF pulses are required.Comment: 25 pages, 7 figures, 2 table

Advances in machine learning applications for cardiovascular 4D flow MRI

Four-dimensional flow magnetic resonance imaging (MRI) has evolved as a non-invasive imaging technique to visualize and quantify blood flow in the heart and vessels. Hemodynamic parameters derived from 4D flow MRI, such as net flow and peak velocities, but also kinetic energy, turbulent kinetic energy, viscous energy loss, and wall shear stress have shown to be of diagnostic relevance for cardiovascular diseases. 4D flow MRI, however, has several limitations. Its long acquisition times and its limited spatio-temporal resolutions lead to inaccuracies in velocity measurements in small and low-flow vessels and near the vessel wall. Additionally, 4D flow MRI requires long post-processing times, since inaccuracies due to the measurement process need to be corrected for and parameter quantification requires 2D and 3D contour drawing. Several machine learning (ML) techniques have been proposed to overcome these limitations. Existing scan acceleration methods have been extended using ML for image reconstruction and ML based super-resolution methods have been used to assimilate high-resolution computational fluid dynamic simulations and 4D flow MRI, which leads to more realistic velocity results. ML efforts have also focused on the automation of other post-processing steps, by learning phase corrections and anti-aliasing. To automate contour drawing and 3D segmentation, networks such as the U-Net have been widely applied. This review summarizes the latest ML advances in 4D flow MRI with a focus on technical aspects and applications. It is divided into the current status of fast and accurate 4D flow MRI data generation, ML based post-processing tools for phase correction and vessel delineation and the statistical evaluation of blood flow

Mitral valve regurgitation assessed by intraventricular CMR 4D-flow: a systematic review on the technological aspects and potential clinical applications.

Cardiac magnetic resonance (CMR) four-dimensional (4D) flow is a novel method for flow quantification potentially helpful in management of mitral valve regurgitation (MVR). In this systematic review, we aimed to depict the clinical role of intraventricular 4D-flow in MVR. The reproducibility, technical aspects, and comparison against conventional techniques were evaluated. Published studies on SCOPUS, MEDLINE, and EMBASE were included using search terms on 4D-flow CMR in MVR. Out of 420 screened articles, 18 studies fulfilled our inclusion criteria. All studies (n = 18, 100%) assessed MVR using 4D-flow intraventricular annular inflow (4D-flowAIM) method, which calculates the regurgitation by subtracting the aortic forward flow from the mitral forward flow. Thereof, 4D-flow jet quantification (4D-flowjet) was assessed in 5 (28%), standard 2D phase-contrast (2D-PC) flow imaging in 8 (44%) and the volumetric method (the deviation of left ventricle stroke volume and right ventricular stroke volume) in 2 (11%) studies. Inter-method correlations among the 4 MVR quantification methods were heterogeneous across studies, ranging from moderate to excellent correlations. Two studies compared 4D-flowAIM to echocardiography with moderate correlation. In 12 (63%) studies the reproducibility of 4D-flow techniques in quantifying MVR was studied. Thereof, 9 (75%) studies investigated the reproducibility of the 4D-flowAIM method and the majority (n = 7, 78%) reported good to excellent intra- and inter-reader reproducibility. Intraventricular 4D-flowAIM provides high reproducibility with heterogeneous correlations to conventional quantification methods. Due to the absence of a gold standard and unknown accuracies, future longitudinal outcome studies are needed to assess the clinical value of 4D-flow in the clinical setting of MVR

Getting the phase consistent: The importance of phase description in balanced steady-state free precession MRI of multicompartment systems

Purpose: Determine the correct mathematical phase description for balanced steady-state free precession (bSSFP) signals in multicompartment systems. Theory and Methods: Based on published bSSFP signal models, two distinct phase descriptions can be formulated: one predicting the presence and the other predicting the absence of destructive interference effects in multicompartment systems. Numerical simulations of bSSFP signals of water and acetone were performed to evaluate the predictions of these two distinct phase descriptions. For experimental validation, bSSFP profiles were measured at 3T using phase-cycled bSSFP acquisitions performed in a phantom containing mixtures of water and acetone, which replicates a system with two signal components. Localized single voxel MRS was performed at 7T to determine the relative chemical-shift of the acetone-water mixtures. Results: Based on the choice of phase description, the simulated bSSFP profiles of water-acetone mixtures varied significantly, either displaying or lacking destructive interference effects, as predicted theoretically. In phantom experiments, destructive interference was consistently observed in the measured bSSFP profiles of water-acetone mixtures, an observation which excludes the phase description that predicts an absence of destructive interference. The connection between the choice of phase description and predicted observation enables an unambiguous experimental identification of the correct phase description for multicompartment bSSFP profiles, which is consistent with Bloch equations. Conclusion: The study emphasizes that consistent phase descriptions are crucial for accurately describing multi-compartment bSSFP signals, as incorrect phase descriptions result in erroneous predictions.Comment: Submitted to Magn. Reson. Me

Hyperpolarized ¹³C Magnetic Resonance Spectroscopy Reveals the Rate-Limiting Role of the Blood-Brain Barrier in the Cerebral Uptake and Metabolism of l-Lactate in Vivo.

The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized <sup>13</sup> C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1- <sup>13</sup> C]lactate, we observed that the distribution of the <sup>13</sup> C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1- <sup>13</sup> C]lactate to [1- <sup>13</sup> C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized <sup>13</sup> C MRS can be used to detect a variation in cerebral lactate uptake of <40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in brain metabolism

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals

Purpose To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Methods Droplets of mixed [1-13C]pyruvic and [1-13C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Results Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Conclusion Copolarization of two different 13C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection

Optimal Protocol for Contrast-enhanced Free-running 5D Whole-heart Coronary MR Angiography at 3T.

Free-running 5D whole-heart coronary MR angiography (MRA) is gaining in popularity because it reduces scanning complexity by removing the need for specific slice orientations, respiratory gating, or cardiac triggering. At 3T, a gradient echo (GRE) sequence is preferred in combination with contrast injection. However, neither the injection scheme of the gadolinium (Gd) contrast medium, the choice of the RF excitation angle, nor the dedicated image reconstruction parameters have been established for 3T GRE free-running 5D whole-heart coronary MRA. In this study, a Gd injection scheme, RF excitation angles of lipid-insensitive binominal off-resonance RF excitation (LIBRE) pulse for valid fat suppression and continuous data acquisition, and compressed-sensing reconstruction regularization parameters were optimized for contrast-enhanced free-running 5D whole-heart coronary MRA using a GRE sequence at 3T. Using this optimized protocol, contrast-enhanced free-running 5D whole-heart coronary MRA using a GRE sequence is feasible with good image quality at 3T

Combined Free-running 4D anatomical and flow MRI with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS).

BACKGROUND 4D flow MRI often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses Pilot Tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running 3D radial acquisitions, to create co-registered anatomy and flow images. METHODS Thirteen volunteers and two Marfan Syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional 2D flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation. RESULTS Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5±0.3) was significantly higher than for Native 4D flow (0.7±0.1, p<0.01), and was comparable to 2D flow (2.3±0.9, p=0.02). Image quality scores of SyNAPS 4D flow from the experts (MP: 1.9±0.3, ET: 2.5±0.5) were overall significantly higher than the scores from Native 4D flow (MP: 1.6±0.6, p=0.03, ET: 0.8±0.4, p<0.01) but still significantly lower than the scores from the reference 2D flow datasets (MP: 2.8±0.4, p<0.01, ET: 3.5±0.7, p<0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69±0.24 for the AAo and 0.83±0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12±0.48 for the AAo and 0.08±0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r2=0.83) and peak flow (r2=0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r2=0.79) and peak flow (r2=0.76). DISCUSSION AND CONCLUSION The feasibility and utility of SyNAPS was demonstrated for joint whole-heart anatomical and flow MRI without requiring ECG gating, respiratory navigators, or contrast agents. Using SyNAPS a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents