Multi-Parametric MRI for Evaluating Variations in Renal Structure, Function, and Endogenous Metabolites in an Animal Model With Acute Kidney Injury Induced by Ischemia Reperfusion.

BACKGROUND: Ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) may occur after renal ischemic injury. There is a lack of an accurate and comprehensive detection technique for IRI-AKI. PURPOSE: To longitudinally evaluate IRI-AKI in rats by renal structure, function, and metabolites using multi-parametric MRI (mpMRI). STUDY TYPE: Prospective. ANIMAL MODEL: Forty-eight rats undergoing IRI-AKI. FIELD STRENGTH/SEQUENCE: 7-T, T1 mapping, and arterial spin labeling (ASL): echo planar imaging (EPI) sequence; blood oxygen level-dependent (BOLD): gradient recalled echo (GRE) sequence; T2 mapping, quantitative magnetization transfer (qMT), and chemical exchange saturation transfer (CEST): rapid acquisition with relaxation enhancement (RARE) sequence. ASSESSMENT: The mpMRI for IRI-AKI was conducted at 0 (control), 1, 3, 7, 14, and 28 days, all included eight rats. The longitudinal mpMRI signal of manually outlined cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla, and medulla plus pelvis were calculated and compared, their diagnosis performance for IRI-AKI also been evaluated. STATISTICAL TESTS: Pearson correlations analysis for correlation between mpMRI signal and renal injury, unpaired t-tests for comparing the signal changes, and receiver operating characteristics (ROC) analysis was used to identify most sensitive indicator of mpMRI. A P-value <0.05 was considered statistically significant. RESULTS: Compared with control kidneys, the T1 and T2 values of the cortex and medulla in IRI kidneys increased and reached their highest values on day 14, and the kidneys also showed the most severe edema and segments blurred. The RBF in the cortex and OSOM showed a significant decline after day 3. The BOLD signal in the OSOM largest increased on day 28. The cortical PSR and the amine-CEST both decreased with IRI-AKI progression, and amine-CEST achieved the highest AUC for the diagnosis (0.899). DATA CONCLUSION: Multi-parametric MRI may show comprehensive variations in IRI-AKI, and amine-CEST may exhibit the highest accuracy for diagnosis of IRI-AKI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Deconvolved Fractional Fourier Domain Beamforming for Linear Frequency Modulation Signals.

To estimate the direction of arrival (DOA) of a linear frequency modulation (LFM) signal in a low signal-to-noise ratio (SNR) hydroacoustic environment by a small aperture array, a novel deconvolved beamforming method based on fractional Fourier domain delay-and-sum beamforming (FrFB) was proposed. Fractional Fourier transform (FrFT) was used to convert the received signal into the fractional Fourier domain, and delay-and-sum beamforming was subsequently performed. Noise resistance was acquired by focusing the energy of the LFM signal distributed in the time-frequency domain. Then, according to the convolution structure of the FrFB complex output, the influence of the fractional Fourier domain complex beam pattern was removed by deconvolution, and the target spatial distribution was restored. Therefore, an improved spatial resolution of DOA estimation was obtained without increasing the array aperture. The simulation and experimental results show that, with a small aperture array at low SNR, the proposed method possesses higher spatial resolution than FrFB and frequency-domain deconvolved conventional beamforming.

Early detection of increased marrow adiposity with age in rats using Z-spectral MRI at ultra-high field (7 T).

BACKGROUND: Nowadays, the drive towards high-field MRI is fueled by the pursuit of higher signal-to-noise ratio, spatial resolution, and imaging speed. However, high field strength is associated with field inhomogeneity, acceleration of T2 * decay, and increased chemical shift, which may pose challenges to conventional MRI for fat quantification in complex tissues such as bone marrow. With proton MRI spectroscopy (1 H-MRS), on the other hand, it is difficult to produce high resolution. As a novel alternative fat quantification method, high-resolution Z-spectral MRI (ZS-MRI) can achieve fat quantification by acquiring direct saturated images of both fat and water under the same TE , which may be less affected by T2 * decay and field inhomogeneity. PURPOSE: To demonstrate ZS-MRI for marrow adipose tissue (MAT) quantification in rat's lumbar spine and the early detection of MAT changes with age. METHODS: The accuracy of ZS-MRI for fat quantification at ultra-high-field MRI (7 T) was verified with MRS and conventional Dixon MRI in water-oil mixed phantoms with varying fat fraction (FF). Dixon MRI data were processed with iterative decomposition of water and fat with echo asymmetry and least-squares estimation. ZS-MRI was then used to longitudinally monitor the adiposity in the lumbar spine of young healthy rats at 13, 17, and 21 weeks to detect the early changes of FF with age in MAT. Hematoxylin-eosin staining of lumbar spines from separated rat groups was performed for verification. RESULTS: In ex vivo phantom experiments, both Dixon MRI and ZS-MRI were well correlated with 1 H-MRS for the quantification of FF at 7 T (R > 0.99). Compared with Dixon MRI, ZS-MRI showed reduced image artifacts due to field inhomogeneity and presented better agreement with 1 H-MRS for the early detection of increased MAT due to age at 7 T (ZS-MRI R = 0.78 versus Dixon MRI R = 0.34). The increased MAT FF due to age was confirmed by histology. CONCLUSION: ZS-MRI proves itself as an alternative fat quantification method for bone marrow in rats at 7 T.

Mn doped Prussian blue nanoparticles for T1/T2 MR imaging, PA imaging and Fenton reaction enhanced mild temperature photothermal therapy of tumor.

BACKGROUND: Combining the multimodal imaging and synergistic treatment in one platform can enhance the therapeutic efficacy and diagnosis accuracy. RESULTS: In this contribution, innovative Mn-doped Prussian blue nanoparticles (MnPB NPs) were prepared via microemulsion method. MnPB NPs demonstrated excellent T1 and T2 weighted magnetic resonance imaging (MRI) enhancement in vitro and in vivo. The robust absorbance in the near infrared range of MnPB NPs provides high antitumor efficacy for photothermal therapy (PTT) and photoacoustics imaging property. Moreover, with the doping of Mn, MnPB NPs exhibited excellent Fenton reaction activity for chemodynamic therapy (CDT). The favorable trimodal imaging and Fenton reaction enhanced mild temperature photothermal therapy in vitro and in vivo were further confirmed that MnPB NPs have significant positive effectiveness for integration of diagnosis and treatment tumor. CONCLUSIONS: Overall, this Mn doped Prussian blue nanoplatform with multimodal imaging and chemodynamic/mild temperature photothermal co-therapy provides a reliable tool for tumor treatment.

Magnetic graphene quantum dots facilitate closed-tube one-step detection of SARS-CoV-2 with ultra-low field NMR relaxometry.

The rapid and sensitive diagnosis of the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the crucial issues at the outbreak of the ongoing global pandemic that has no valid cure. Here, we propose a SARS-CoV-2 antibody conjugated magnetic graphene quantum dots (GQDs)-based magnetic relaxation switch (MRSw) that specifically recognizes the SARS-CoV-2. The probe of MRSw can be directly mixed with the test sample in a fully sealed vial without sample pretreatment, which largely reduces the testers' risk of infection during the operation. The closed-tube one-step strategy to detect SARS-CoV-2 is developed with home-made ultra-low field nuclear magnetic resonance (ULF NMR) relaxometry working at 118 µT. The magnetic GQDs-based probe shows ultra-high sensitivity in the detection of SARS-CoV-2 due to its high magnetic relaxivity, and the limit of detection is optimized to 248 Particles mL‒1. Meanwhile, the detection time in ULF NMR system is only 2 min, which can significantly improve the efficiency of detection. In short, the magnetic GQDs-based MRSw coupled with ULF NMR can realize a rapid, safe, and sensitive detection of SARS-CoV-2.

Fluorination Triggers Fluoroalkylation: Nucleophilic Perfluoro-tert-butylation with 1,1-Dibromo-2,2-bis(trifluoromethyl)ethylene (DBBF) and CsF.

Perfluoro-tert-butylation reaction has long remained a challenging task. We now report the use of 1,1-dibromo-2,2-bis(trifluoromethyl)ethylene (DBBF) as a practical reagent for perfluoro-tert-butylation reactions for the first time. Through a consecutive triple-fluorination process with DBBF and CsF, the (CF3 )3 C- species can be liberated and observed, which is able to serve as a robust nucleophilic perfluoro-tert-butylating agent for various electrophiles. The power of this synthetic protocol is evidenced by the efficient synthesis of structurally diverse perfluoro-tert-butylated molecules. Multiple applications demonstrate the practicability of this method, as well as the superiority of perfluoro-tert-butylated compounds as sensitive probes. The perfluoro-tert-butylated product was successfully applied in 1 H- and 19 F-magnetic resonance imaging (MRI) experiment with an ultra-low field (ULF) MRI system.

Sensor Configuration and Algorithms for Power-Line Interference Suppression in Low Field Nuclear Magnetic Resonance.

Low field (LF) nuclear magnetic resonance (NMR) shows potential advantages to study pure heteronuclear J-coupling and observe the fine structure of matter. Power-line harmonics interferences and fixed-frequency noise peaks might introduce discrete noise peaks into the LF-NMR spectrum in an open environment or in a conductively shielded room, which might disturb J-coupling spectra of matter recorded at LF. In this paper, we describe a multi-channel sensor configuration of superconducting quantum interference devices, and measure the multiple peaks of the 2,2,2-trifluoroethanol J-coupling spectrum. For the case of low signal to noise ratio (SNR) < 1, we suggest two noise suppression algorithms using discrete wavelet analysis (DWA), combined with either least squares method (LSM) or gradient descent (GD). The de-noising methods are based on spatial correlation of the interferences among the superconducting sensors, and are experimentally demonstrated. The DWA-LSM algorithm shows a significant effect in the noise reduction and recovers SNR > 1 for most of the signal peaks. The DWA-GD algorithm improves the SNR further, but takes more computational time. Depending on whether the accuracy or the speed of the de-noising process is more important in LF-NMR applications, the choice of algorithm should be made.

Simultaneous removal of ammonium and nitrate by HDTMA-modified zeolite.

In this study, surfactant (hexadecyltrimethylammonium, HDTMA) modified zeolite (clinoptilolite) (SMZ) was used for simultaneous removal of ammonium and nitrate in wastewater, and the sorption properties of SMZ were determined. Results showed that natural clinoptilolite had good affinity for ammonium, but low sorption ability for nitrate, and the ammonium sorption process was well described by the pseudo-second order kinetic model. The SMZ had a significant enhancement on nitrate sorption and could simultaneously remove ammonium and nitrate at specific conditions, with removal efficiency up to 93.6% and 81.8%, respectively. The sorption process fitted well with the Langmuir isotherm. Orthogonal experiments showed that ammonium concentration was the most important factor for ammonium sorption on SMZ. However, surfactant loading was the major factor for nitrate sorption. Meanwhile, phosphate did not interfere with nitrate removal. Semi-empirical quantum mechanics molecular simulation indicated that electrostatic attraction existed between HDTMA and nitrate. Results of this study demonstrated that SMZs may have great potential for removing cations and anions simultaneously in the aquatic environment.

[Effect of poly(ADP-ribose)polymerase inhibitor combined with carbo on apoptosis of human breast cancer cells].

OBJECTIVE: To investigate the effect of poly(ADP-ribose)polymerase(PARP)inhibitor ABT888 combined with carbo on apoptosis of human breast cancer cells. METHODS: MTT was used to detect the cell viability of MDA-MB-435s cells after treatment of carbo and ABT888 with different concentration. FACS and Western-blotting were used to detect the cell apoptosis rate and apoptosis-related protein expression, respectively. RESULTS: Combined application of carbo and ABT888 significantly inhibited the proliferation of MDA-MB-435s cells, and the inhibition rates were significantly higher than that of carbo or ABT888 alone. The combination of carbo and ABT888 markedly induced cell apoptosis(26.3%±1.5%) more than carbo(18.6%±1.6%, P<0.01) and ABT888(14.7%±2.3%, P<0.01) alone. Combination of carbo and ABT888 significantly down-regulated the expression of anti-apoptosis factors Bcl-2 and up-regulated the pro-apoptosis proteins Bax and cleaved caspase-3. CONCLUSION: The combination of carbo and ABT888 can suppress the proliferation and induce apoptosis of human breast cancer DA-MB-435s cells.

Low-frequency magnetic field therapy for glioblastoma: Current advances, mechanisms, challenges and future perspectives.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumour of the central nervous system. Despite recent advances in multimodal GBM therapy incorporating surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy), and supportive care, the overall survival (OS) remains poor, and long-term survival is rare. Currently, the primary obstacles hindering the effectiveness of GBM treatment are still the blood-brain barrier and tumor heterogeneity. In light of its substantial advantages over conventional therapies, such as strong penetrative ability and minimal side effects, low-frequency magnetic fields (LF-MFs) therapy has gradually caught the attention of scientists. AIM OF REVIEW: In this review, we shed the light on the current status of applying LF-MFs in the treatment of GBM. We specifically emphasize our current understanding of the mechanisms by which LF-MFs mediate anticancer effects and the challenges faced by LF-MFs in treating GBM cells. Furthermore, we discuss the prospective applications of magnetic field therapy in the future treatment of GBM. Key scientific concepts of review: The review explores the current progress on the use of LF-MFs in the treatment of GBM with a special focus on the potential underlying mechanisms of LF-MFs in anticancer effects. Additionally, we also discussed the complex magnetic field features and biological characteristics related to magnetic bioeffects. Finally, we proposed a promising magnetic field treatment strategy for future applications in GBM therapy.

Acquisition Acceleration of Ultra-low Field MRI with Parallel Imaging and Compressed Sensing in Microtesla Fields.

OBJECTIVE: In recent years, ultra-low field (ULF) magnetic resonance imaging (MRI) has gained widespread attention due to its advantages, such as low cost, light weight, and portability. However, the low signal-to-noise ratio (SNR) leads to a long scan time. Herein, we study the acceleration performance of parallel imaging (PI) and compressed sensing (CS) in different kspace sampling strategies at 0.12 mT. METHODS: This study employs phantoms to assess the efficiency of acceleration methods at ULF MRI, in which signals are detected by ultra-sensitive superconducting quantum interference devices (SQUIDs). We compare the performance of fast Fourier transform (FFT), generalized auto-calibrating partially parallel acquisitions (GRAPPA), and eigenvector-based SPIRiT (ESPIRiT) in Cartesian sampling, while also evaluating non-uniform FFT (NUFFT), GRAPPA operator gridding, and ESPIRiT in nonCartesian sampling. We design a resolution phantom to investigate the effectiveness of these methods in maintaining image resolution. RESULTS: In Cartesian sampling, GRAPPA and ESPIRiT jointly regularized by total variation and ℓ1-norm (TVJℓ1 -ESPIRiT) methods reconstructed good-quality phantom images with an acceleration factor of R = 2. In contrast, TVJℓ1-ESPIRiT exhibited improved image quality and much less signal loss even for R = 4. In radial sampling, TVJℓ1-ESPIRiT reduced the acquisition time to 1.69 minutes at R = 4, with a respective improvement of 12.26 dB in peak SNR compared to NUFFT. The resolution phantom imaging showed that the reconstructions by PI and CS maintained the original resolution of 2 mm. CONCLUSION AND SIGNIFICANCE: This study improves the practicality of ULF MRI at microtesla fields by implementing imaging acceleration with PI and CS in different k-space sampling.

Aberrant resting-state co-activation network dynamics in major depressive disorder.

Major depressive disorder (MDD) is a globally prevalent and highly disabling disease characterized by dysfunction of large-scale brain networks. Previous studies have found that static functional connectivity is not sufficient to reflect the complicated and time-varying properties of the brain. The underlying dynamic interactions between brain functional networks of MDD remain largely unknown, and it is also unclear whether neuroimaging-based dynamic properties are sufficiently robust to discriminate individuals with MDD from healthy controls since the diagnosis of MDD mainly depends on symptom-based criteria evaluated by clinical observation. Resting-state functional magnetic resonance imaging (fMRI) data of 221 MDD patients and 215 healthy controls were shared by REST-meta-MDD consortium. We investigated the spatial-temporal dynamics of MDD using co-activation pattern analysis and made individual diagnoses using support vector machine (SVM). We found that MDD patients exhibited aberrant dynamic properties (such as dwell time, occurrence rate, transition probability, and entropy of Markov trajectories) in some transient networks including subcortical network (SCN), activated default mode network (DMN), de-activated SCN-cerebellum network, a joint network, activated attention network (ATN), and de-activated DMN-ATN, where some dynamic properties were indicative of depressive symptoms. The trajectories of other networks to deactivated DMN-ATN were more accessible in MDD patients. Subgroup analyses also showed subtle dynamic changes in first-episode drug-naïve (FEDN) MDD patients. Finally, SVM achieved preferable accuracies of 84.69%, 76.77%, and 88.10% in discriminating patients with MDD, FEDN MDD, and recurrent MDD from healthy controls with their dynamic metrics. Our findings reveal that MDD is characterized by aberrant dynamic fluctuations of brain network and the feasibility of discriminating MDD patients using dynamic properties, which provide novel insights into the neural mechanism of MDD.

Accelerated proton dissociation in an excited state induces superacidic microenvironments around graphene quantum dots.

Investigating proton transport at the interface in an excited state facilitates the mechanistic investigation and utilization of nanomaterials. However, there is a lack of suitable tools for in-situ and interfacial analysis. Here we addresses this gap by in-situ observing the proton transport of graphene quantum dots (GQDs) in an excited state through reduction of magnetic resonance relaxation time. Experimental results, utilizing 0.1 mT ultra-low-field nuclear magnetic resonance relaxometry compatible with a light source, reveal the light-induced proton dissociation and acidity of GQDs' microenvironment in the excited state (Hammett acidity function: -13.40). Theoretical calculations demonstrate significant acidity enhancement in -OH functionalized GQDs with light induction ( p K a * = -4.62, stronger than that of H2SO4). Simulations highlight the contributions of edge and phenolic -OH groups to proton dissociation. The light-induced superacidic microenvironment of GQDs benefits functionalization and improves the catalytic performances of GQDs. Importantly, this work advances the understanding of interfacial properties of light-induced sp2-sp3 carbon nanostructure and provides a valuable tool for exploring catalyst interfaces in photocatalysis.

Deep learning for colorectal cancer detection in contrast-enhanced CT without bowel preparation: a retrospective, multicentre study.

BACKGROUND: Contrast-enhanced CT scans provide a means to detect unsuspected colorectal cancer. However, colorectal cancers in contrast-enhanced CT without bowel preparation may elude detection by radiologists. We aimed to develop a deep learning (DL) model for accurate detection of colorectal cancer, and evaluate whether it could improve the detection performance of radiologists. METHODS: We developed a DL model using a manually annotated dataset (1196 cancer vs 1034 normal). The DL model was tested using an internal test set (98 vs 115), two external test sets (202 vs 265 in 1, and 252 vs 481 in 2), and a real-world test set (53 vs 1524). We compared the detection performance of the DL model with radiologists, and evaluated its capacity to enhance radiologists' detection performance. FINDINGS: In the four test sets, the DL model had the area under the receiver operating characteristic curves (AUCs) ranging between 0.957 and 0.994. In both the internal test set and external test set 1, the DL model yielded higher accuracy than that of radiologists (97.2% vs 86.0%, p < 0.0001; 94.9% vs 85.3%, p < 0.0001), and significantly improved the accuracy of radiologists (93.4% vs 86.0%, p < 0.0001; 93.6% vs 85.3%, p < 0.0001). In the real-world test set, the DL model delivered sensitivity comparable to that of radiologists who had been informed about clinical indications for most cancer cases (94.3% vs 96.2%, p > 0.99), and it detected 2 cases that had been missed by radiologists. INTERPRETATION: The developed DL model can accurately detect colorectal cancer and improve radiologists' detection performance, showing its potential as an effective computer-aided detection tool. FUNDING: This study was supported by National Science Fund for Distinguished Young Scholars of China (No. 81925023); Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (No. U22A20345); National Natural Science Foundation of China (No. 82072090 and No. 82371954); Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No. 2022B1212010011); High-level Hospital Construction Project (No. DFJHBF202105).

A possible but unrecognized risk of acceptable daily intake dose triazole pesticides exposure-bile acid disturbance induced pharmacokinetic changes of oral medication.

Triazole antifungal pesticides work by inhibiting the activity of lanosterol-14-α-demethylase, a member of cytochrome P450 enzymes (CYPs), but this effect is non-specific. Bile acids (BAs) are important physical surfactants for lipids absorption in intestine, and synthesized by CYPs 7A1/27A1. Thus, we presume that triazole exposure might influence the therapeutic effect or safety of oral medication through disturbing the BAs pool, even though the exposure is under an acceptable daily intake (ADI) dose. Short- and long-term of ADI dose tebuconazole (TEB) exposure animal models were established through various routes, and statins with different hydrophilic and lipophilic properties were gavaged. It exhibited that the activity of CYP7A1/27A1 was indeed inhibited but the expression was up-regulated, the BAs pool was changed either the content and the composition, and the absorption behavior of statins with strong and medium degree of lipid-solubility were significantly changed. A series of experiments performed on models of intestinal mucus, Caco-2 cell monolayer and Caco-2/HT29 co-culture system revealed that the TEB-exposure induced BAs disturbance made impacts on drug absorption in many aspects, including drug solubility and the structure of intestinal barriers. This study suggests us to be more alert about the hazard of pesticides residues for elderly and chronically ill groups.

Assessment of rhabdomyolysis-induced acute kidney injury with chemical exchange saturation transfer magnetic resonance imaging.

Background: Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. Methods: AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Results: Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. Conclusions: The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

Ratiometric chemical exchange saturation transfer pH mapping using two iodinated agents with nonequivalent amide protons and a single low saturation power.

Background: As an essential physiological parameter, pH plays a critical role in maintaining cellular and tissue homeostasis. The ratiometric chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method using clinically approved iodinated agents has emerged as one of the most promising noninvasive techniques for pH assessment. Methods: In this study, we investigated the ability to use the combination of two different nonequivalent amide protons, chosen from five iodinated agents, namely iodixanol, iohexol, iobitridol, iopamidol, and iopromide, for pH measurement. The ratio of two nonequivalent amide CEST signals was calculated and compared for pH measurements in the range of 5.6 to 7.6. To quantify the CEST signals at 4.3 and 5.5 parts per million (ppm), we employed two analytic methods: magnetization transfer ratio asymmetry and Lorentzian fitting analysis. Lastly, the established protocol was used to measure the pH values in healthy rat kidneys (n=5). Results: The combination of iodixanol and iobitridol at a ratio of 1:1 was found to be suitable for pH mapping. The saturation power level (B1) was also investigated, and a low B1 of 1.5 µT was adopted for subsequent pH measurements. Improved precision and an extended pH detection range were achieved using iodixanol and iobitridol (1:1 ratio) and a single low B1 of 1.5 µT in vitro. In vivo renal pH values were measured as 7.23±0.09, 6.55±0.15, and 6.29±0.23 for the cortex, medulla, and calyx, respectively. Conclusions: These results show that the ratiometric CEST method using two iodinated agents with nonequivalent amide protons could be used for in vivo pH mapping of the kidney under a single low B1 saturation power.

Mitochondrial targeted ROS scavenger based on nitroxide for treatment and MRI imaging of acute kidney injury.

Overproduction of reactive oxygen species (ROS) during oxidative stress is hallmark of acute kidney injury (AKI), which induced the damage to the renal cells and mitochondrial injury. In this contribution, we prepared mitochondrial targeted nitroxide, which linked 3-carboxy-2,2,5,5-tetramethylpyrrolidine 1-oxyl (carboxy-PROXYL) with (2-aminoethyl)triphenylphosphonium bromide (TPP), named TPP-PROXYL to eliminate the ROS in situ and image the oxidative stress reaction by MRI. 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining, mitochondrial membrane potential assay (JC-1) staining and transmission electron microscope (TEM) experiments were processed to verify that TPP-PROXYL could target mitochondria, scavenge the ROS, and prevent damage to mitochondria in live cells. Contrast enhanced MRI also been used to monitor these redox reaction in AKI model. TPP-PROXYL demonstrated excellent ROS T1-weighted magnetic resonance imaging enhancement in vitro and in vivo, with r1 value about 0.190 mM-1 s-1. In vivo AKI treatment experiments proved that TPP-PROXYL could improve the survival rate of mice and inhibit kidney damage. Moreover, the great ROS scavenging capability and the renal damage reduction during AKI treatment of TPP-PROXYL was verified via MR imaging technology. Collectively, this research provides TPP-PROXYL would serve as a powerful platform to realize ROS scavenging, treatment, and MR imaging of AKI.

Synergistic Effect of Oxygen- and Nitrogen-Containing Groups in Graphene Quantum Dots: Red Emitted Dual-Mode Magnetic Resonance Imaging Contrast Agents with High Relaxivity.

Contrast agents (CAs) in magnetic resonance imaging generally involve the dissociative Gd3+. Because of the limited ligancy of Gd3+, the balance between Gd3+ coordination stability (reducing the concentration of dissociative Gd3+) and increases in the number of coordination water molecules (enhancing the relaxivity) becomes crucial. Herein, the key factor of the synergistic effect between the O- and N-containing groups of graphene quantum dots for the structural design of CAs with both high relaxivity and low toxicity was obtained. The nitrogen-doped graphene quantum dots (NGQDs) with an O/N ratio of 0.4 were selected to construct high-relaxivity magnetic resonance imaging (MRI)-fluorescence dual-mode CAs. The coordination stability of Gd3+ can be increased through the synergetic coordination of O- and N-containing groups. The synergetic coordination of O- and N-containing groups can result in the short residency time of the water ligand and achieve high relaxivity. The resulting CAs (called NGQDs-Gd) exhibit a high relaxivity of 32.04 mM-1 s-1 at 114 µT. Meanwhile, the NGQDs-Gd also emit red fluorescence (614 nm), which can enable the MRI-fluorescence dual-mode imaging as the CAs. Moreover, the bio-toxicity and tumor-targeting behavior of NGQDs-Gd were also evaluated, and NGQDs-Gd show potential in MRI-fluorescence imaging in vivo.

Liver Injury and Elevated Levels of Interleukins, Interleukin-2 Receptor, and Interleukin-6 Predict the Severity in Patients With COVID-19.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.