Comparison of 3D UTE free-breathing lung MRI with hyperpolarized 129Xe MRI in pediatric cystic fibrosis.

PURPOSE: To compare phase-resolved functional lung (PREFUL) regional ventilation derived from a free breathing 3D UTE radial MRI acquisition to hyperpolarized 129Xe-MRI (Xe-MRI), conventional 2D multi-slice PREFUL MRI, and pulmonary function tests in pediatric cystic fibrosis (CF) lung disease. METHODS: Free-breathing 3D UTE and 2D multi-slice 1H MRI as well as Xe-MRI were acquired in 12 stable pediatric CF patients. Using PREFUL, regional ventilation (RVent) maps were calculated from the free-breathing data. Ventilation defect percentage (VDP) was determined from 3D and 2D RVent maps (2D VDPRVent and 3D VDPRVent, respectively) and Xe-MRI ventilation (VDPXe). VDP was calculated for the whole lung and for eight regions based on left/right, anterior/posterior, and superior/inferior divisions of the lung. Global and regional VDP was compared between the three methods using Bland-Altman analysis, linear mixed model-based correlation, and one-way analysis of variance and multiple comparisons tests. RESULTS: Global 3D VDPRVent, VDPXe, and 2D VDPRVent were all strongly correlated (all R2 > 0.62, p < 0.0001) and showed minimal, non-significant bias (all <2%, p > 0.05). Three dimensional and 2D VDPRVent significantly correlated to VDPXe in most of the separate lung regions (R2 = 0.18-0.74, p < 0.04), but showed lower inter-agreement. The superior/anterior lung regions showed the least agreement between all three methods (all p > 0.12). CONCLUSION: Absolute VDP assessed by 3D UTE PREFUL MRI showed good global agreement with Xe-MRI and 2D multi-slice PREFUL MRI in pediatric CF lung disease. Therefore, 3D UTE PREFUL MRI offers a sensitive and potentially more accessible alternative to Xe-MRI for regional volumetric evaluation of ventilation.

Temperature dependence of the protective effect of pressurized dissolution of xenon gas during cold storage of cells.

BACKGROUND: The preservation period afforded by cold storage of cells is short. However, the use of rare gases for cold storage as a means of extending the period of preservation would be highly beneficial. OBJECTIVE: To examine the effect of temperature on the protective effect of cold storage of cells using pressurized dissolution of xenon gas, with particular focus on the inhibition of substance transport by viscosity. METHODS: Human dermal fibroblast monolayers incubated in a culture dish for 48 h were used as a test sample, with culture medium used as a preservation solution. Samples were placed into a pressure-resistant vessel, which was pressurized with xenon gas at 0 or 0.5 MPa, and cells were stored at 0 to 5 °C for 18 h. Cell activity was evaluated by tetrazolium salt assay. The viscosity of the medium under pressurization at each storage temperature was estimated. RESULTS: The maximum protective effect against cell damage of cold storage with pressurized dissolution of xenon gas was observed at 4 °C. An increase in estimated viscosity by pressurization was correlated with increased cell activity at 4 °C. CONCLUSION: Analysis of the temperature dependence of the protective effect against cell damage of cold storage with pressurized dissolution of xenon gas revealed that the most effective temperature is 4 °C. The data also suggest that increased viscosity due to pressurization plays a role in the protective effect.

Short-term inhalation of xenon during anesthesia for prevention of postoperative delirium in elderly patients undergoing laparoscopic radical colectomy: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. METHODS/DESIGN: This is a prospective, randomized, controlled trial and 132 patients aged 65-80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. DISCUSSION: Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn .

Corrigendum: Xenon attenuated neonatal lipopolysaccharide exposure induced neuronal necroptosis and subsequently improved cognition in juvenile rats.

[This corrects the article DOI: 10.3389/fphar.2022.1002920.].

Improved Diffusion-Weighted Hyperpolarized 129Xe Lung MRI with Patch-Based Higher-Order, Singular Value Decomposition Denoising.

RATIONALE AND OBJECTIVES: Hyperpolarized xenon (129Xe) MRI is a noninvasive method to assess pulmonary structure and function. To measure lung microstructure, diffusion-weighted imaging-commonly the apparent diffusion coefficient (ADC)-can be employed to map changes in alveolar-airspace size resulting from normal aging and pulmonary disease. However, low signal-to-noise ratio (SNR) decreases ADC measurement certainty, and biases ADC to spuriously low values. Further, these challenges are most severe in regions of the lung where alveolar simplification or emphysematous remodeling generate abnormally high ADCs. Here, we apply Global Local Higher Order Singular Value Decomposition (GLHOSVD) denoising to enhance image SNR, thereby reducing uncertainty and bias in diffusion measurements. MATERIALS AND METHODS: GLHOSVD denoising was employed in simulated images and gas phantoms with known diffusion coefficients to validate its effectiveness and optimize parameters for analysis of diffusion-weighted 129Xe MRI. GLHOSVD was applied to data from 120 subjects (34 control, 39 cystic fibrosis (CF), 27 lymphangioleiomyomatosis (LAM), and 20 asthma). Image SNR, ADC, and distributed diffusivity coefficient (DDC) were compared before and after denoising using Wilcoxon signed-rank analysis for all images. RESULTS: Denoising significantly increased SNR in simulated, phantom, and in-vivo images, showing a greater than 2-fold increase (p < 0.001) across diffusion-weighted images. Although mean ADC and DDC remained unchanged (p > 0.05), ADC and DDC standard deviation decreased significantly in denoised images (p < 0.001). CONCLUSION: When applied to diffusion-weighted 129Xe images, GLHOSVD improved image quality and allowed airspace size to be quantified in high-diffusion regions of the lungs that were previously inaccessible to measurement due to prohibitively low SNR, thus providing insights into disease pathology.

Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial.

BACKGROUND: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA. METHODS: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA. RESULTS: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups. CONCLUSIONS: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00879892.

Testing the Conjecture That Quantum Processes Create Conscious Experience.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest-pain generates intense feelings and absorbs all our conscious awareness, yet nothing particularly intelligent is going on. In the hard sciences, this topic is frequently met with skepticism because, to date, no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here, we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human conscious experience through brain-quantum computer interfaces.

Xenon Antiaggregant Effects.

In in vitro model of short-term therapeutic inhalation of Xe/O2 mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.01). A slightly weaker but statistically significant reduction in aggregation appeared in response to ristocetin (by ≈12%, p≤0.01) and epinephrine (by ≈9%, p≤0.01). It should be noted that the spontaneous aggregation exceeded the reference values in the control group. Nevertheless, even at minimal absolute values, spontaneous platelet aggregation decreased by 2 times in response to xenon (p≤0.01). The reasons for the decrease of spontaneous and induced aggregation are xenon accumulation in the lipid bilayer of the membrane with subsequent nonspecific (mechanical) disassociation of membrane platelet structures and specific block of its distinct from neuronal NMDA receptor.

Effect of Xe/O2 Inhalation on Hemostasis in Experimental Thromboplastin Pneumonitis.

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.

Taming XeO3 with Aza-Crowns: Computational Studies into σ-Hole Mediated Host-Guest Interactions.

Various aza-crowns with different sizes and substituents have been explored computationally as potential hosts for stabilizing the explosive guest xenon trioxide (XeO3) through σ-hole-mediated aerogen bonding interactions. Interestingly, aza-crowns demonstrate superior binding towards XeO3 compared to their oxygen and thio counterparts. However, unlike the latter cases, where the binding was found to be increasingly favorable with the increase in the size of the crowns, aza-crowns exhibit a variable size preference for XeO3, peaking with aza-15-crown-5, and reducing thereafter with increase in crown size.

Synaptic effects of xenon on NMDA receptor-mediated response in rat spinal neuron.

To investigate the precise mechanism of xenon (Xe), pharmacologically isolated AMPA/KA and NMDA receptor-mediated spontaneous (s) and evoked (e) excitatory postsynaptic currents (s/eEPSCAMPA/KA and s/eEPSCNMDA) were recorded from mechanically isolated single spinal sacral dorsal commissural nucleus (SDCN) neurons attached with glutamatergic nerve endings (boutons) using conventional whole-cell patch-clamp technique. We analysed kinetic properties of both s/eEPSCAMPA/KA and s/eEPSCNMDA by focal single- and/or paired-pulse electrical stimulation to compare them. The s/eEPSCNMDA showed smaller amplitude, slower rise time, and slower 1/e decay time constant (τDecay) than those of s/eEPSCAMPA/KA. We previously examined how Xe modulates s/eEPSCAMPA/KA, therefore, examined the effects on s/eEPSCNMDA in the present study. Xe decreased the frequency and amplitude of sEPSCNMDA, and decreased the amplitude but increased the failure rate and paired-pulse ratio of eEPSCNMDA without affecting their τDecay. It was concluded that Xe might suppress NMDA receptor-mediated synaptic transmission via both presynaptic and postsynaptic mechanisms.

Gamma-spectrometry measurements of filtration media from an Advanced Gas-cooled Reactor.

Filtration media used to quantify particulate and gaseous releases have been collected from Hartlepool Power Station in the United Kingdom and measured using high-sensitivity gamma-spectrometry systems. Radionuclides that are relevant to the monitoring regime of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) have been detected. Results are reported and compared to detections recorded on the International Monitoring System (IMS). Time series activity plots have been produced and results interpreted with respect to known plant activities. The reported results improve the understanding of trace-level radionuclide emissions from Advanced Gas-cooled Reactors (AGRs) and aid interpretation of IMS measurements. This work is being performed as part of the Xenon Environmental Nuclide Analysis at Hartlepool (XENAH) collaboration between the Atomic Weapons Establishment (AWE, UK), EDF Energy (UK), Pacific Northwest National Laboratory (PNNL, US) and the Swedish Defence Agency (FOI, Sweden).

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

BACKGROUND: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. PURPOSE: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. METHODS: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. RESULTS: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. CONCLUSIONS: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

Red Blood Cell Storage with Xenon: Safe or Disruption?

Xenon, an inert gas commonly used in medicine, has been considered as a potential option for prolonged preservation of donor packed red blood cells (pRBCs) under hypoxic conditions. This study aimed to investigate how xenon affects erythrocyte parameters under prolonged storage. In vitro model experiments were performed using two methods to create hypoxic conditions. In the first method, xenon was introduced into bags of pRBCs which were then stored for 42 days, while in the second method, xenon was added to samples in glass tubes. The results of our experiment showed that the presence of xenon resulted in notable alterations in erythrocyte morphology, similar to those observed under standard storage conditions. For pRBC bags, hemolysis during storage with xenon exceeded the acceptable limit by a factor of six, whereas the closed-glass-tube experiment showed minimal hemolysis in samples exposed to xenon. Notably, the production of deoxyhemoglobin was specific to xenon exposure in both cell suspension and hemolysate. However, this study did not provide evidence for the purported protective properties of xenon.

Sampling pattern discrepancy in the application of compressed sensing hyperpolarized xenon-129 lung MRI.

Although hyperpolarized (HP) 129Xe ventilation MRI can be carried out within a breath hold, it is still challenging for many sick patients. Compressed sensing (CS) is a viable alternative to accelerate this approach. However, undersampled images with identical sampling ratios differ from one another. Twenty subjects (n = 10 healthy and n = 10 patients with asthma) were scanned using a GE MR750 3 T scanner, acquiring fully sampled 2D multi-slice HP 129Xe lung ventilation images (10 s breath hold, 128 × 80 (FE × PE-frequency encoding × phase encoding) and 16 slices). Using fully sampled data, 500 variable-density Cartesian random undersampling patterns were generated, each at eight different sampling ratios from 10% to 80%. The parallel imaging and compressed sensing (PICS) command from BART was employed to reconstruct undersampled data. The signal to noise ratio (SNR), structural similarity index measurement (SSIM) and sidelobe to peak ratio of each were subsequently compared. There was a high degree of variation in both SNR and SSIM results from each of the 500 masks of each sampling rate. As the undersampling increases, there is more variation in the quantifying metrics, for both healthy and asthmatic individuals. Our study shows that random undersampling poses a significant challenge when applied at sampling ratios less than 60%, despite fulfilling CS's incoherency criteria. Such low sampling ratios will result in a large variety of undersampling patterns. Therefore, skipped segments of k-space cannot be allowed to happen randomly at low sampling rates. By optimizing the sampling pattern, CS will reach its full potential and be able to be applied to a highly undersampled 129Xe lung dataset.

Batch Fabrication of Microelectrode Arrays with Glassy Carbon Microelectrodes and Interconnections for Neurochemical Sensing: Promises and Challenges.

Flexible multielectrode arrays with glassy carbon (GC) electrodes and metal interconnection (hybrid MEAs) have shown promising performance in multi-channel neurochemical sensing. A primary challenge faced by hybrid MEAs fabrication is the adhesion of the metal traces with the GC electrodes, as prolonged electrical and mechanical stimulation can lead to adhesion failure. Previous devices with GC electrodes and interconnects made of a homogeneous material (all GC) demonstrated exceptional electrochemical stability but required miniaturization for enhanced tissue integration and chronic electrochemical sensing. In this study, we used two different methods for the fabrication of all GC-MEAs on thin flexible substrates with miniaturized features. The first method, like that previously reported, involves a double pattern-transfer photolithographic process, including transfer-bonding on temporary polymeric support. The second method requires a double-etching process, which uses a 2 µm-thick low stress silicon nitride coating of the Si wafer as the bottom insulator layer for the MEAs, bypassing the pattern-transfer and demonstrating a novel technique with potential advantages. We confirmed the feasibility of the two fabrication processes by verifying the practical conductivity of 3 µm-wide 2 µm-thick GC traces, the GC microelectrode functionality, and their sensing capability for the detection of serotonin using fast scan cyclic voltammetry. Through the exchange and discussion of insights regarding the strengths and limitations of these microfabrication methods, our goal is to propel the advancement of GC-based MEAs for the next generation of neural interface devices.

Xenon ameliorates chronic post-surgical pain by regulating mitophagy in microglia and rats mediated by PINK1/Parkin pathway.

Background: Chronic post-surgical pain (CPSP) is one of the important causes of poor postoperative outcomes, the activation of microglia in the spinal cord is closely related to the generation, transmission and maintenance of CPSP. Xenon (Xe), an anesthetic gas, has been reported to be able to significantly reduce intraoperative analgesia and postoperative pain sensation at low doses. However, the mechanism of the regulatory effect of xenon on activated microglia after CPSP remains unclear. Methods: In this study, CPSP model rats were treated with 50% Xe inhalation for 1 h following skin/muscle incision and retraction (SMIR), once a day for 5 consecutive days, and then the painbehavioraltests (pain behavior indexes paw withdrawal mechanical threshold, PWMT and thermal withdrawal latency, TWL), microglial activation, oxidative stress-related indexes (malondialdehyde, MDA; superoxide dismutase, SOD; hydrogen peroxide, H2O2; and catalase, CAT), mitophagy and PINK1/Parkin pathway were examined. Results: The present results showed that a single dose of Xe treatment in SMIR rat model could significantly improve PWMT and TWL in the short-term at a single treatment and long-term at multiple treatments. Xe treatment inhibited microglia activation and oxidative stress in the spinal dorsal horn of SMIR rats, as indicated by the decrease of Iba1 and MDA/H2O2 levels and the increase of SOD/CAT levels. Compared with the control group, Xe further increased the CPSP promoted Mito-Tracker (a mitochondrial marker) and LC3 (an autophagy marker) co-localization positive spots and PINK1/Parkin/ATG5/BECN1 (autophagy-related proteins) protein expression levels, and inhibited the Mito-SOX (a mitochondrial reactive oxygen species marker) positive signal, indicating that Xe promoted microglia mitophagy and inhibited oxidative stress in CPSP. Mechanistically, we verified that Xe promoted PINK1/Parkin signaling pathway activation. Conclusion: Xe plays a role in ameliorating chronic post-surgical pain by regulating the PINK1/Parkin pathway mediated microglial mitophagy and provide new ideas and targets for the prevention and treatment of CPSP.

Environmentally sustainable ethyl levulinate synthesis from delignified sugarcane bagasse using ternary eutectic solvent under MW-xenon irradiation: engine performance and emission assessment.

For the first time, a synergistic energy-efficient combination of microwave-xenon (MW-XE) irradiations in presence of photoactive ternary acidic deep eutectic solvents (TADES) has been applied for intensification of ethyl levulinate synthesis from delignified sugarcane bagasse (DSB) under mild (90 min, 90 °C) and environmentally benign process conditions. The Taguchi orthogonal designed optimized conditions (20 W/cm3 of MW specific irradiation power input, 1 mol/mol of FeCl3 to citric acid ratio, 90 min of reaction time, 150 W of XE specific power input) rendered maximum 61.3 mol% of EL yield (selectivity: 87.70 [Formula: see text] 0.5%). Remarkably, synergistic effect of MW and XE irradiation significantly enhanced the EL yield (61.3 mol%) compared to the individual MW (34.52 mol%) and XE (22.67 mol%) irradiation at otherwise optimized reaction conditions. Moreover, the MWXE irradiated reactor (MWXER) exhibited a significant 79.10% increase in EL yield compared to the conventional thermal reactor (CTR), at the expense of 10% less energy consumption. The ethyl levulinate could be recovered efficiently through green protocol from reaction mix resulting in high purity (97 [Formula: see text] 0.5%) and TADES was sustainably reused in the process. The optimally generated product EL when blended (5 and 10 vol.%) with B10 and B20 (10% and 20% biodiesel-diesel blend) could provide 21-31% reduction in HC and 7.3-36% reduction in CO in comparison with petro-diesel. It was also explored that, at similar optimal parametric combinations, the TADES produced 29.5% greater EL yield in comparison with the standard ionic liquid BMIMCl. The life cycle environmental impact analysis (LCEIA) of the overall process revealed that the 5 vol.% EL blending with B10 contributed lowest environmental impacts mitigating marine ecotoxicity, human toxicity, fossil depletion, and climate change by 77.9%, 77.4%, 78.4% and 77.5%, respectively.

Hyperpolarized Xenon-129 Chemical Exchange Saturation Transfer (HyperCEST) Molecular Imaging: Achievements and Future Challenges.

Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) 129Xe biosensors have been recently developed, demonstrating their potential applications in molecular settings, and achieving notable success within in vitro studies. The favorable nuclear magnetic resonance properties of 129Xe, coupled with its non-toxic nature, high solubility in biological tissues, and capacity to dissolve in blood and diffuse across membranes, highlight its superior role for applications in molecular MRI settings. The incorporation of reporters that combine signal enhancement from both hyperpolarized 129Xe and chemical exchange saturation transfer holds the potential to address the primary limitation of low sensitivity observed in conventional MRI. This review provides a summary of the various applications of HP 129Xe biosensors developed over the last decade, specifically highlighting their use in MRI. Moreover, this paper addresses the evolution of in vivo applications of HP 129Xe, discussing its potential transition into clinical settings.

Combining a noble gas with radiotherapy: glutamate receptor antagonist xenon may act as a radiosensitizer in glioblastoma.

BACKGROUND: Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) modulate proliferation, invasion and radioresistance in glioblastoma (GB). Pharmacological targeting is difficult as many in vitro-effective agents are not suitable for in patient applications. We aimed to develop a method to test the well tolerated AMPAR- and NMDAR-antagonist xenon gas as a radiosensitizer in GB. METHODS: We designed a diffusion-based system to perform the colony formation assay (CFA), the radiobiological gold standard, under xenon exposure. Stable and reproducible gas atmosphere was validated with oxygen and carbon dioxide as tracer gases. After checking for AMPAR and NMDAR expression via immunofluorescence staining we performed the CFA with the glioblastoma cell lines U87 and U251 as well as the non-glioblastoma derived cell line HeLa. Xenon was applied after irradiation and additionally tested in combination with NMDAR antagonist memantine. RESULTS: The gas exposure system proved compatible with the CFA and resulted in a stable atmosphere of 50% xenon. Indications for the presence of glutamate receptor subunits were present in glioblastoma-derived and HeLa cells. Significantly reduced clonogenic survival by xenon was shown in U87 and U251 at irradiation doses of 4-8 Gy and 2, 6 and 8 Gy, respectively (p < 0.05). Clonogenic survival was further reduced by the addition of memantine, showing a significant effect at 2-8 Gy for both glioblastoma cell lines (p < 0.05). Xenon did not significantly reduce the surviving fraction of HeLa cells until a radiation dose of 8 Gy. CONCLUSION: The developed system allows for testing of gaseous agents with CFA. As a proof of concept, we have, for the first time, unveiled indications of radiosensitizing properties of xenon gas in glioblastoma.