Technical Note: Swing golden angle - A navigator-interleaved golden angle trajectory with eddy current suppression - Application in free-running cardiac MRI.

BACKGROUND: Golden angle (GA) radial trajectory is advantageous for dynamic magnetic resonance imaging (MRI). Recently, several advanced algorithms have been developed based on navigator-interleaved GA trajectory to realize free-running cardiac MRI. However, navigator-interleaved GA trajectory suffers from the eddy-current effect, which reduces the image quality. PURPOSE: This work aims to integrate the navigator-interleaved GA trajectory with clinical cardiac MRI acquisition, with the minimum eddy-current artifacts. The ultimate goal is to realize a high-quality free-running cardiac imaging technique. METHODS: In this paper, we propose a new "swing golden angle" (swingGA) radial profile order. SwingGA samples the k-space by rotating back and forth at the generalized golden ratio interval, with smoothly interleaved navigator readouts. The sampling efficiency and angle increment distributions were investigated by numerical simulations. Static phantom imaging experiments were conducted to evaluate the eddy current effect, compared with cartesian, golden angle radial (GA), and tiny golden angle (tGA) trajectories. Furthermore, 12 heart-healthy subjects (aged 21-25 years) were recruited for free-running cardiac imaging with different sampling trajectories. Dynamic images were reconstructed by a low-rank subspace-constrained algorithm. The image quality was evaluated by signal-to-noise-ratio and spectrum analysis in the heart region, and compared with traditional clinical cardiac MRI images. RESULTS: SwingGA pattern achieves the highest sampling efficiency (mSE > 0.925) and the minimum azimuthal angle increment (mAD < 1.05). SwingGA can effectively suppress eddy currents in static phantom images, with the lowest normalized root mean square error (nRMSE) values among radial trajectories. For the in-vivo cardiac images, swingGA enjoys the highest SNR both in the blood pool and myocardium, and contains the minimum level of high-frequency artifacts. The free-running cardiac images have good consistency with traditional clinical cardiac MRI, and the swingGA sampling pattern achieves the best image quality among all sampling patterns. CONCLUSIONS: The proposed swingGA sampling pattern can effectively improve the sampling efficiency and reduce the eddy currents for the navigator-interleaved GA sequence. SwingGA is a promising sampling pattern for free-running cardiac MRI.

The effect of acupuncture on gastrointestinal recovery after abdominal surgery: a narrative review from clinical trials.

Abdominal surgery is a critical surgery, with more and more attention being paid to postoperative life quality and associated complications in recent years. Among these complications, postoperative gastrointestinal dysfunction is the most common complication of abdominal surgery. Acupuncture therapy is a treatment approach based on the Traditional Chinese Medicine (TCM) theory, and its feasibility in aiding the gastrointestinal recovery after abdominal surgery is supported by both TCM theory and animal experiments. A lot of clinical research has been conducted to evaluate its efficacy, albeit with limitations and at preliminary stages. Moreover, intervention timing, acupoint selection, and patient benefits should also be considered in clinical practices. This article summarizes the progress of clinical research on acupuncture therapy in the gastrointestinal recovery after abdominal surgery, and discusses related issues and operations, with the aim to provide new insights and prospect for the incorporation of acupuncture into the Enhanced Recovery After Surgery (ERAS) protocol.

Highly-accelerated CEST MRI using frequency-offset-dependent k-space sampling and deep-learning reconstruction.

PURPOSE: To develop a highly accelerated CEST Z-spectral acquisition method using a specifically-designed k-space sampling pattern and corresponding deep-learning-based reconstruction. METHODS: For k-space down-sampling, a customized pattern was proposed for CEST, with the randomized probability following a frequency-offset-dependent (FOD) function in the direction of saturation offset. For reconstruction, the convolution network (CNN) was enhanced with a Partially Separable (PS) function to optimize the spatial domain and frequency domain separately. Retrospective experiments on a self-acquired human brain dataset (13 healthy adults and 15 brain tumor patients) were conducted using k-space resampling. The prospective performance was also assessed on six healthy subjects. RESULTS: In retrospective experiments, the combination of FOD sampling and PS network (FOD + PSN) showed the best quantitative metrics for reconstruction, outperforming three other combinations of conventional sampling with varying density and a regular CNN (nMSE and SSIM, p < 0.001 for healthy subjects). Across all acceleration factors from 4 to 14, the FOD + PSN approach consistently outperformed the comparative methods in four contrast maps including MTRasym, MTRrex, as well as the Lorentzian Difference maps of amide and nuclear Overhauser effect (NOE). In the subspace replacement experiment, the error distribution demonstrated the denoising benefits achieved in the spatial subspace. Finally, our prospective results obtained from healthy adults and brain tumor patients (14×) exhibited the initial feasibility of our method, albeit with less accurate reconstruction than retrospective ones. CONCLUSION: The combination of FOD sampling and PSN reconstruction enabled highly accelerated CEST MRI acquisition, which may facilitate CEST metabolic MRI for brain tumor patients.

The Differences in the Developmental Stages of the Cardiomyocytes and Endothelial Cells in Human and Mouse Embryos at the Single-Cell Level.

Our research focuses on expression patterns in human and mouse embryonic cardiomyocytes and endothelial cells at the single-cell level. We analyzed single-cell datasets containing different species, cardiac chambers, and cell types. We identified developmentally dynamic genes associated with different cellular lineages in the heart and explored their expression and possible roles during cardiac development. We used dynamic time warping, a method that aligns temporal sequences, to compare these developmental stages across two species. Our results indicated that atrial cardiomyocytes from E9.5 to E13.5 in mice corresponded to a human embryo age of approximately 5-6 weeks, whereas in ventricular cardiomyocytes, they corresponded to a human embryo age of 13-15 weeks. The endothelial cells in mouse hearts corresponded to 6-7-week-old human embryos. Next, we focused on expression changes in cardiac transcription factors over time in different species and chambers, and found that Prdm16 might be related to interspecies cardiomyocyte differences. Moreover, we compared the developmental trajectories of cardiomyocytes differentiated from human pluripotent stem cells and embryonic cells. This analysis explored the relationship between their respective developments and provided compelling evidence supporting the relevance of our dynamic time-warping results. These significant findings contribute to a deeper understanding of cardiac development across different species.

Free-breathing abdominal chemical exchange saturation transfer imaging using water presaturation and respiratory gating at 3.0 T.

Free-breathing abdominal chemical exchange saturation transfer (CEST) has great potential for clinical application, but its technical implementation remains challenging. This study aimed to propose and evaluate a free-breathing abdominal CEST sequence. The proposed sequence employed respiratory gating (ResGat) to synchronize the data acquisition with respiratory motion and performed a water presaturation module before the CEST saturation to abolish the influence of respiration-induced repetition time variation. In vivo experiments were performed to compare different respiratory motion-control strategies and B0 offset correction methods, and to evaluate the effectiveness and necessity of the quasi-steady-state (QUASS) approach for correcting the influence of the water presaturation module on CEST signal. ResGat with a target expiratory phase of 0.5 resulted in a higher structural similarity index and a lower coefficient of variation on consecutively acquired CEST S0 images than breath-holding (BH) and respiratory triggering (all p < 0.05). B0 maps derived from the abdominal CEST dataset itself were more stable for B0 correction, compared with the separately acquired B0 maps by a dual-echo time scan and B0 maps derived from the water saturation shift referencing approach. Compared with BH, ResGat yielded more homogeneous magnetization transfer ratio asymmetry maps at 3.5 ppm (standard deviation: 3.96% vs. 3.19%, p = 0.036) and a lower mean squared difference between scan and rescan (27.52‱ vs. 16.82‱, p = 0.004). The QUASS approach could correct the water presaturation-induced CEST signal change, but its necessity for in vivo scanning needs further verification. The proposed free-breathing abdominal CEST sequence using ResGat had an acquisition efficiency of approximately four times that using BH. In conclusion, the proposed free-breathing abdominal CEST sequence using ResGat and water presaturation has a higher acquisition efficiency and image quality than abdominal CEST using BH.

Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.

AIMS: Novel cancer therapies leading to increased survivorship of cancer patients have been negated by a concomitant rise in cancer therapies-related cardiovascular toxicities. Sunitinib, a first line multi-receptor tyrosine kinase inhibitor, has been reported to cause vascular dysfunction although the initiating mechanisms contributing to this side effect remain unknown. Long non-coding RNAs (lncRNAs) are emerging regulators of biological processes in endothelial cells (ECs); however, their roles in cancer therapies-related vascular toxicities remain underexplored. METHODS AND RESULTS: We performed lncRNA expression profiling to identify potential lncRNAs that are dysregulated in human-induced pluripotent stem cell-derived ECs (iPSC-ECs) treated with sunitinib. We show that the lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) is significantly diminished in sunitinib-treated iPSC-ECs. Sunitinib was found to down-regulate HAS2-AS1 by an epigenetic mechanism involving hypermethylation. Depletion of HAS2-AS1 recapitulated sunitinib-induced detrimental effects on iPSC-ECs, whereas CRISPR-mediated activation of HAS2-AS1 reversed sunitinib-induced dysfunction. We confirmed that HAS2-AS1 stabilizes the expression of its sense gene HAS2 via an RNA/mRNA heteroduplex formation. Knockdown of HAS2-AS1 led to reduced synthesis of hyaluronic acid (HA) and up-regulation of ADAMTS5, an enzyme involved in extracellular matrix degradation, resulting in disruption of the endothelial glycocalyx which is critical for ECs. In vivo, sunitinib-treated mice showed reduced coronary flow reserve, accompanied by a reduction in Has2os and degradation of the endothelial glycocalyx. Finally, we identified that treatment with high molecular-weight HA can prevent the deleterious effects of sunitinib both in vitro and in vivo by preserving the endothelial glycocalyx. CONCLUSIONS: Our findings highlight the importance of lncRNA-mediated regulation of the endothelial glycocalyx as an important determinant of sunitinib-induced vascular toxicity and reveal potential novel therapeutic avenues to attenuate sunitinib-induced vascular dysfunction.

Accelerated partial separable model using dimension-reduced optimization technique for ultra-fast cardiac MRI.

Objective.Imaging dynamic objects with high temporal resolution is challenging in magnetic resonance imaging (MRI). The partial separable (PS) model was proposed to improve imaging quality by reducing the degrees of freedom of the inverse problem. However, the PS model still suffers from a long acquisition time and an even longer reconstruction time. The main objective of this study is to accelerate the PS model, shorten the time required for acquisition and reconstruction, and maintain good image quality simultaneously.Approach.We proposed to fully exploit the dimension-reduction property of the PS model, which means implementing the optimization algorithm in subspace. We optimized the data consistency term and used a Tikhonov regularization term based on the Frobenius norm of temporal difference. The proposed dimension-reduced optimization technique was validated in free-running cardiac MRI. We have performed both retrospective experiments on a public dataset and prospective experiments onin vivodata. The proposed method was compared with four competing algorithms based on the PS model and two non-PS model methods.Main results.The proposed method has robust performance against a shortened acquisition time or suboptimal hyper-parameter settings, and achieves superior image quality over all other competing algorithms. The proposed method is 20-fold faster than the widely accepted PS+sparse method, enabling image reconstruction to be finished in just a few seconds.Significance.The accelerated PS model has the potential to save a great deal of time in clinical dynamic MRI examinations and is promising for real-time MRI applications.

Erratum: Negative regulation of cationic nanoparticle-induced inflammatory toxicity through the increased production of prostaglandin E2 via mitochondrial DNA-activated Ly6C+ monocytes: Erratum.

[This corrects the article DOI: 10.7150/thno.21693.].

NLRX1 Facilitates Histoplasma capsulatum-Induced LC3-Associated Phagocytosis for Cytokine Production in Macrophages.

LC3-associated phagocytosis (LAP) is an emerging non-canonical autophagy process that bridges signaling from pattern-recognition receptors (PRRs) to autophagic machinery. LAP formation results in incorporation of lipidated LC3 into phagosomal membrane (termed LAPosome). Increasing evidence reveals that LAP functions as an innate defense mechanism against fungal pathogens. However, the molecular mechanism involved and the consequence of LAP in regulating anti-fungal immune response remain largely unexplored. Here we show that Histoplasma capsulatum is taken into LAPosome upon phagocytosis by macrophages. Interaction of H. capsulatum with Dectin-1 activates Syk and triggers subsequent NADPH oxidase-mediated reactive oxygen species (ROS) response that is involved in LAP induction. Inhibiting LAP induction by silencing LC3α/ß or treatment with ROS inhibitor impairs the activation of MAPKs-AP-1 pathway, thereby reduces macrophage proinflammatory cytokine response to H. capsulatum. Additionally, we unravel the importance of NLRX1 in fungus-induced LAP. NLRX1 facilitates LAP by interacting with TUFM which associates with autophagic proteins ATG5-ATG12 for LAPosome formation. Macrophages from Nlrx1-/- mice or TUFM-silenced cells exhibit reduced LAP induction and LAP-mediated MAPKs-AP-1 activation for cytokine response to H. capsulatum. Furthermore, inhibiting ROS production in Nlrx1-/- macrophages almost completely abolishes H. capsulatum-induced LC3 conversion, indicating that both Dectin-1/Syk/ROS-dependent pathway and NLRX1-TUFM complex-dependent pathway collaboratively contribute to LAP induction. Our findings reveal new pathways underlying LAP induction by H. capsulatum for macrophage cytokine response.

Negative regulation of cationic nanoparticle-induced inflammatory toxicity through the increased production of prostaglandin E2 via mitochondrial DNA-activated Ly6C+ monocytes.

Rationale: Cationic nanocarriers present with well-known toxicities, including inflammatory toxicity, which limit their clinical application. How the cationic nanocarrier-induced inflammatory response is negatively regulated is unknown. Herein, we found that following a sublethal dose of cationic nanocarriers, the induced inflammatory response is characterized by early neutrophil infiltration and spontaneous resolution within 1 week. Methods: C57BL/6 mice were intravenously injected with a dosage of 1-100 mg/kg cationic DOTAP liposomes as well as other cationic materials. Cell necrosis was detected by flow cytometry. Release of mitochondrial DNA was quantified by qPCR via Taqman probes. Signal proteins were detected by Western blotting. PGE2 production in the supernatant was quantitated using an enzyme immunoassay (EIA). The infiltrated inflammatory cells were observed in WT mice, Ccr2-/- mice, Sting-/- mice and Tlr9-/- mice. Results: The early stage (24-48 h) inflammatory neutrophil infiltration was followed by an increasing percentage of monocytes; and, compared with WT mice, Ccr2-/- mice presented with more severe pulmonary inflammation. A previously uncharacterized population of regulatory monocytes expressing both inflammatory and immunosuppressive cytokines was identified in this model. The alteration in monocyte phenotype was directly induced by mtDNA release from cationic nanocarrier-induced necrotic cells via a STING- or TLR9-dependent pathway. Neutrophil activation was specifically inhibited by PGE2 from Ly6C+ inflammatory monocytes, and intravenous injections of dual-phenotype monocytes beneficially modified the immune response; this inhibitory effect was abolished after treatment with indomethacin. Moreover, we provide clear evidence that mitochondrial DNA activated Ly6C+ monocytes and increased PGE2 production through TLR9- or STING-mediated MAPK-NF-κB-COX2 pathways. Conclusion: Our findings suggest that Ly6C+ monocytes and mtDNA-induced Ly6C+ monocyte PGE2 production may be part of a feedback mechanism that contributes to the resolution of cationic nanocarrier-induced inflammatory toxicity and may have important implications for understanding nanoparticle biocompatibility and designing better, safer drug delivery systems.