Deep-mantle krypton reveals Earth's early accretion of carbonaceous matter.

Establishing when, and from where, carbon, nitrogen and water were delivered to Earth is a fundamental objective in understanding the origin of habitable planets such as Earth. Yet, volatile delivery to Earth remains controversial1-5. Krypton isotopes provide insights on volatile delivery owing to their substantial isotopic variations among sources6-10, although pervasive atmospheric contamination has hampered analytical efforts. Here we present the full suite of krypton isotopes from the deep mantle of the Galápagos and Iceland plumes, which have the most primitive helium, neon and tungsten isotopic compositions11-16. Except for 86Kr, the krypton isotopic compositions are similar to a mixture of chondritic and atmospheric krypton. These results suggest early accretion of carbonaceous material by proto-Earth and rule out any combination of hydrodynamic loss with outgassing of the deep or shallow mantle to explain atmospheric noble gases. Unexpectedly, the deep-mantle sources have a deficit in the neutron-rich 86Kr relative to the average composition of carbonaceous meteorites, which suggests a nucleosynthetic anomaly. Although the relative depletion of neutron-rich isotopes on Earth compared with carbonaceous meteorites has been documented for a range of refractory elements1,17,18, our observations suggest such a depletion for a volatile element. This finding indicates that accretion of volatile and refractory elements occurred simultaneously, with krypton recording concomitant accretion of non-solar volatiles from more than one type of material, possibly including outer Solar System planetesimals.

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.

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.

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.

Local Xenon-Protein Interaction Produces Global Conformational Change and Allosteric Inhibition in Lysozyme.

Noble gases have well-established biological effects, yet their molecular mechanisms remain poorly understood. Here, we investigated, both experimentally and computationally, the molecular modes of xenon (Xe) action in bacteriophage T4 lysozyme (T4L). By combining indirect gassing methods with a colorimetric lysozyme activity assay, a reversible, Xe-specific (20 ± 3)% inhibition effect was observed. Accelerated molecular dynamic simulations revealed that Xe exerts allosteric inhibition on the protein by expanding a C-terminal hydrophobic cavity. Xe-induced cavity expansion results in global conformational changes, with long-range transduction distorting the active site where peptidoglycan binds. Interestingly, the peptide substrate binding site that enables lysozyme specificity does not change conformation. Two T4L mutants designed to reshape the C-terminal Xe cavity established a correlation between cavity expansion and enzyme inhibition. This work also highlights the use of Xe flooding simulations to identify new cryptic binding pockets. These results enrich our understanding of Xe-protein interactions at the molecular level and inspire further biochemical investigations with noble gases.

Protein Kinase A Is Responsible for the Presynaptic Inhibition of Glycinergic and Glutamatergic Transmissions by Xenon in Rat Spinal Cord and Hippocampal CA3 Neurons.

The effects of a general anesthetic xenon (Xe) on spontaneous, miniature, electrically evoked synaptic transmissions were examined using the "synapse bouton preparation," with which we can clearly evaluate pure synaptic responses and accurately quantify pre- and postsynaptic transmissions. Glycinergic and glutamatergic transmissions were investigated in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xe presynaptically inhibited spontaneous glycinergic transmission, the effect of which was resistant to tetrodotoxin, Cd2+, extracellular Ca2+, thapsigargin (a selective sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor), SQ22536 (an adenylate cyclase inhibitor), 8-Br-cAMP (membrane-permeable cAMP analog), ZD7288 (an hyperpolarization-activated cyclic nucleotide-gated channel blocker), chelerythrine (a PKC inhibitor), and KN-93 (a CaMKII inhibitor) while being sensitive to PKA inhibitors (H-89, KT5720, and Rp-cAMPS). Moreover, Xe inhibited evoked glycinergic transmission, which was canceled by KT5720. Like glycinergic transmission, spontaneous and evoked glutamatergic transmissions were also inhibited by Xe in a KT5720-sensitive manner. Our results suggest that Xe decreases glycinergic and glutamatergic spontaneous and evoked transmissions at the presynaptic level in a PKA-dependent manner. These presynaptic responses are independent of Ca2+ dynamics. We conclude that PKA can be the main molecular target of Xe in the inhibitory effects on both inhibitory and excitatory neurotransmitter release. SIGNIFICANCE STATEMENT: Spontaneous and evoked glycinergic and glutamatergic transmissions were investigated using the whole-cell patch clamp technique in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xenon (Xe) significantly inhibited glycinergic and glutamatergic transmission presynaptically. As a signaling mechanism, protein kinase A was responsible for the inhibitory effects of Xe on both glycine and glutamate release. These results may help understand how Xe modulates neurotransmitter release and exerts its excellent anesthetic properties.

Depression of Synaptic N-methyl-D-Aspartate Responses by Xenon and Nitrous Oxide.

In "synapse bouton preparation" of rat hippocampal CA3 neurons, we examined how Xe and N2O modulate N-methyl-D-aspartate (NMDA) receptor-mediated spontaneous and evoked excitatory post-synaptic currents (sEPSCNMDA and eEPSCNMDA). This preparation is a mechanically isolated single neuron attached with nerve endings (boutons) preserving normal physiologic function and promoting the exact evaluation of sEPSCNMDA and eEPSCNMDA responses without influence of extrasynaptic, glial, and other neuronal tonic currents. These sEPSCs and eEPSCs are elicited by spontaneous glutamate release from many homologous glutamatergic boutons and by focal paired-pulse electric stimulation of a single bouton, respectively. The s/eEPSCAMPA/KA and s/eEPSCNMDA were isolated pharmacologically by their specific antagonists. Thus, independent contributions of pre- and postsynaptic responses could also be quantified. All kinetic properties of s/eEPSCAMPA/KA and s/eEPSCNMDA were detected clearly. The s/eEPSCNMDA showed smaller amplitude and slower rise and 1/e decay time constant (τ Decay) than s/eEPSCAMPA/KA Xe (70%) and N2O (70%) significantly decreased the frequency and amplitude without altering the τ Decay of sEPSCNMDA They also decreased the amplitude but increased the Rf and PPR without altering the τ Decay of the eEPSCNMDA These data show clearly that "synapse bouton preparation" can be an accurate model for evaluating s/eEPSCNMDA Such inhibitory effects of gas anesthetics are primarily due to presynaptic mechanisms. Present results may explain partially the powerful analgesic effects of Xe and N2O. SIGNIFICANCE STATEMENT: We could record pharmacologically isolated NMDA receptor-mediated spontaneous and (action potential-evoked) excitatory postsynaptic currents (sEPSCNMDA and eEPSCNMDA) and clearly detect all kinetic parameters of sEPSCNMDA and eEPSCNMDA at synaptic levels by using "synapse bouton preparation" of rat hippocampal CA3 neurons. We found that Xe and N2O clearly suppressed both sEPSCNMDA and eEPSCNMDA. Different from previous studies, present results suggest that Xe and N2O predominantly inhibit the NMDA responses by presynaptic mechanisms.

Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.

PURPOSE: To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. METHODS: 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. RESULTS: The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5 s in blood dilutions as low as 0.4% volume. CONCLUSION: SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.

Establishing a hemoglobin adjustment for 129 Xe gas exchange MRI and MRS.

PURPOSE: 129 Xe MRI and MRS signals from airspaces, membrane tissues (M), and red blood cells (RBCs) provide measurements of pulmonary gas exchange. However, 129 Xe MRI/MRS studies have yet to account for hemoglobin concentration (Hb), which is expected to affect the uptake of 129 Xe in the membrane and RBC compartments. We propose a framework to adjust the membrane and RBC signals for Hb and use this to assess sex-specific differences in RBC/M and establish a Hb-adjusted healthy reference range for the RBC/M ratio. METHODS: We combined the 1D model of xenon gas exchange (MOXE) with the principle of TR-flip angle equivalence to establish scaling factors that normalize the dissolved-phase signals with respect to a standard H b 0 $$ H{b}^0 $$ (14 g/dL). 129 Xe MRI/MRS data from a healthy, young cohort (n = 18, age = 25.0 ± $$ \pm $$ 3.4 years) were used to validate this model and assess the impact of Hb adjustment on M/gas and RBC/gas images and RBC/M. RESULTS: Adjusting for Hb caused RBC/M to change by up to 20% in healthy individuals with normal Hb and had marked impacts on M/gas and RBC/gas distributions in 3D gas-exchange maps. RBC/M was higher in males than females both before and after Hb adjustment (p < 0.001). After Hb adjustment, the healthy reference value for RBC/M for a consortium-recommended acquisition of TR = 15 ms and flip = 20° was 0.589 ± $$ \pm $$ 0.083 (mean ± $$ \pm $$ SD). CONCLUSION: MOXE provides a useful framework for evaluating the Hb dependence of the membrane and RBC signals. This work indicates that adjusting for Hb is essential for accurately assessing 129 Xe gas-exchange MRI/MRS metrics.

A 3D stack-of-spirals approach for rapid hyperpolarized 129 Xe ventilation mapping in pediatric cystic fibrosis lung disease.

PURPOSE: To demonstrate the feasibility of a rapid 3D stack-of-spirals (3D-SoS) imaging acquisition for hyperpolarized 129 Xe ventilation mapping in healthy pediatric participants and pediatric cystic fibrosis (CF) participants, in comparison to conventional Cartesian multislice (2D) gradient-recalled echo (GRE) imaging. METHODS: The 2D-GRE and 3D-SoS acquisitions were performed in 13 pediatric participants (5 healthy, 8 CF) during separate breath-holds. Images from both sequences were compared on the basis of ventilation defect percent (VDP) and other measures of image similarity. The nadir of transient oxygen saturation (SpO2 ) decline due to xenon breath-holding was measured with pulse oximetry, and expressed as a percent change relative to baseline. RESULTS: 129 Xe ventilation images were acquired in a breath-hold of 1.2-1.8 s with the 3D-SoS sequence, compared to 6.2-8.8 s for 2D-GRE. Mean ± SD VDP measures for 2D-GRE and 3D-SoS sequences were 5.02 ± 1.06% and 5.28 ± 1.08% in healthy participants, and 18.05 ± 8.26% and 18.75 ± 6.74% in CF participants, respectively. Across all participants, the intraclass correlation coefficient of VDP measures for both sequences was 0.98 (95% confidence interval: 0.94-0.99). The percent change in SpO2 was reduced to -2.1 ± 2.7% from -5.2 ± 3.5% with the shorter 3D-SoS breath-hold. CONCLUSION: Hyperpolarized 129 Xe ventilation imaging with 3D-SoS yielded images approximately five times faster than conventional 2D-GRE, reducing SpO2 desaturation and improving tolerability of the xenon administration. Analysis of VDP and other measures of image similarity demonstrate excellent agreement between images obtained with both sequences. 3D-SoS holds significant potential for reducing the acquisition time of hyperpolarized 129 Xe MRI, and/or increasing spatial resolution while adhering to clinical breath-hold constraints.

Imaging gas-exchange lung function and brain tissue uptake of hyperpolarized 129 Xe using sampling density-weighted MRSI.

PURPOSE: Imaging of the different resonances of hyperpolarized 129 Xe in the brain and lungs was performed using a 3D sampling density-weighted MRSI technique in healthy volunteers. METHODS: Four volunteers underwent dissolved-phase hyperpolarized 129 Xe imaging in the lung with the MRSI technique, which was designed to improve the point-spread function while preserving SNR (1799 phase-encoding steps, 14-s breath hold, 2.1-cm isotropic resolution). A frequency-tailored RF excitation pulse was implemented to reliably excite both the 129 Xe gas and dissolved phase (tissue/blood signal) with 0.1° and 10° flip angles, respectively. Images of xenon gas in the lung airspaces and xenon dissolved in lung tissue/blood were used to generate quantitative signal ratio maps. The method was also optimized and used for imaging dissolved resonances of 129 Xe in the brain in 2 additional volunteers. RESULTS: High-quality regional spectra of hyperpolarized 129 Xe were achieved in both the lung and the brain. Ratio maps of the different xenon resonances were obtained in the lung with sufficient SNR (> 10) at both 1.5 T and 3 T, making a triple Lorentzian fit possible and enabling the measurement of relaxation times and xenon frequency shifts on a voxel-wise basis. The imaging technique was successfully adapted for brain imaging, resulting in the first demonstration of 3D xenon brain images with a 2-cm isotropic resolution. CONCLUSION: Density-weighted MRSI is an SNR and encoding-efficient way to image 129 Xe resonances in the lung and the brain, providing a valuable tool to quantify regional spectroscopic information.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

PURPOSE: The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests. METHODS: Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross-correlation maps were determined from the free-breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent ), regional flow volume loop cross-correlation maps (VDPCC ), VDPRVent ∪ VDPCC , and multi-slice Xe-MRI. Repeatability was evaluated using Bland-Altman analysis, coefficient of repeatability (CR), and intraclass correlation. RESULTS: Minimal bias and no significant differences were reported for all PREFUL MRI and Xe-MRI VDP parameters between intra- and intervisits (all P > 0.05). Repeatability of VDPRVent , VDPCC , VDPRVent ∪ VDPCC , and multi-slice Xe-MRI were lower between the two-visit scans (CR = 14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same-day scans (CR = 3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe-MRI. CONCLUSION: PREFUL MRI, similar to Xe-MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.

Simultaneous quantification of hyperpolarized xenon-129 ventilation and gas exchange with multi-breath xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of a multi-breath xenon-polarization transfer contrast (XTC) MR imaging approach for simultaneously evaluating regional ventilation and gas exchange parameters. METHODS: Imaging was performed in five healthy volunteers and six chronic obstructive pulmonary disease (COPD) patients. The multi-breath XTC protocol consisted of three repeated schemes of six wash-in breaths of a xenon mixture and four normoxic wash-out breaths, with and without selective saturation of either the tissue membrane or red blood cell (RBC) resonances. Acquisitions were performed at end-exhalation while subjects maintained tidal breathing throughout the session. The no-saturation, membrane-saturation, and RBC-saturation images were fit to a per-breath gas replacement model for extracting voxelwise tidal volume (TV), functional residual capacity (FRC), and fractional ventilation (FV), as well as tissue- and RBC-gas exchange (fMem and fRBC , respectively). The sensitivity of the derived model was also evaluated via simulations. RESULTS: With the exception of FRC, whole-lung averages for all metrics were decreased in the COPD subjects compared to the healthy cohort, significantly so for FV, fRBC , and fMem . Heterogeneity was higher overall in the COPD subjects, particularly for fRBC , fMem , and fRBC:Mem . The anterior-to-posterior gradient associated with the gravity-dependence of lung function in supine imaging was also evident for FV, fRBC , and fMem values in the healthy subjects, but noticeably absent in the COPD cohort. CONCLUSION: Multi-breath XTC imaging generated high-resolution, co-registered maps of ventilation and gas exchange parameters acquired during tidal breathing and with low per-breath xenon doses. Clear differences between healthy and COPD subjects were apparent and consistent with spirometry.

Improving HyperCEST performance by favorable xenon exchange conditions in liposomal nanocarriers.

MRI reporters that combine signal enhancement from saturation transfer with hyperpolarized 129 Xe show nanomolar detection sensitivity for in vitro studies. However, they need further improvement for accelerated CEST build-up that sufficiently dominates the intrinsic loss of hyperpolarization under in vivo conditions. This study introduces liposomes with a HyperCEST-active lipopeptide to enhance the efficiency of a well known Xe host, CrA-ma, with medium Xe exchange kinetics in aqueous environment, by two orders of magnitude. The depolarization time for constant saturation power but increasing saturation time is used as a comparative measure to rank different nanocarrier formulations. A variable cage load illustrates that the available CEST sites should be well distributed throughout the nanocarriers to avoid inefficiency from back exchange. For a liposome loading with only 2 mol% CrA-lipopeptide, the higher exchange kinetics allowed us to work even with 17-fold lower saturation power than for CrA-ma itself to achieve significant image contrast with 129 Xe. Overall, this study illustrates the wide parameter space that is now available when incorporating CrA-labelled lipopeptides into liposomal carriers.

Intra- and Inter-visit Repeatability of 129 Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease.

BACKGROUND: Multiple-breath washout (MBW) 129 Xe MRI (MBW Xe-MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies. PURPOSE: To assess intravisit and intervisit repeatability of MBW Xe-MRI in healthy and CF children. STUDY TYPE: Prospective, longitudinal cohort study. SUBJECTS: A total of 18 pediatric subjects (7 healthy, 11 CF). FIELD STRENGTH/SEQUENCE: A 3 T/2D coronal hyperpolarized (HP) 129 Xe images using GRE sequence. ASSESSMENT: All subjects completed MBW Xe-MRI, pulmonary function tests (PFTs) (spirometry, nitrogen [N2 ] MBW for lung clearance index [LCI]) and ventilation defect percent (VDP) at baseline (visit 1) and 1-month after. Fractional ventilation (FV), coefficient of variation (CoVFV ) maps were calculated from MBW Xe-MRI data acquired between intervening air washout breaths performed after an initial xenon breath-hold. Skewness of FV and CoVFV map distributions was also assessed. STATISTICAL TESTS: Repeatability: intraclass correlation coefficients (ICC), within-subject coefficient of variation (CV%), repeatability coefficient (CR). Agreement: Bland-Altman. For correlations between MBW Xe-MRI, VDP and PFTs: Spearman's correlation. Significance threshold: P < 0.05. RESULTS: For FV, intravisit median [IQR] ICC was high in both healthy (0.94 [0.48, 0.99]) and CF (0.83 [0.04, 0.97]) subjects. CoVFV also had good intravisit ICC in healthy (0.92 [0.42, 0.99]) and CF (0.79 [0.02, 0.96]) subjects. Similarly, for FV, intervisit ICC was high in health (0.94 [0.68, 0.99]) and CF (0.89 [0.61, 0.97]). CoVFV also had good intervisit ICC in health (0.92 [0.42, 0.99]) and CF (0.78 [0.26, 0.94]). FV had better intervisit repeatability than VDP. CoVFV correlated significantly with LCI (R = 0.56). Skewness of FV distributions significantly distinguished between cohorts at baseline. DATA CONCLUSION: MBW Xe-MRI had high intravisit and intervisit repeatability in healthy and stable CF subjects. CoVFV correlated with LCI, suggesting the importance of ventilation heterogeneity to early CF. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Gas exchange and ventilation imaging of healthy and COPD subjects using hyperpolarized xenon-129 MRI and a 3D alveolar gas-exchange model.

OBJECTIVES: To investigate the utility of hyperpolarized xenon-129 (HPX) gas-exchange magnetic resonance imaging (MRI) and modeling in a chronic obstructive pulmonary disease (COPD) cohort in comparison to a minimal CT-diagnosed emphysema (MCTE) cohort and a healthy cohort. METHODS: A total of 25 subjects were involved in this study including COPD (n = 8), MCTE (n = 3), and healthy (n = 14) subjects. The COPD subjects were scanned using HPX ventilation, gas-exchange MRI, and volumetric CT. The healthy subjects were scanned using the same HPX gas-exchange MRI protocol with 9 of them scanned twice, 3 weeks apart. The coefficient of variation (CV) was used to quantify image heterogeneities. A three-dimensional computational fluid dynamic (CFD) model of gas exchange was used to derive functional volumes of pulmonary tissue, capillaries, and veins. RESULTS: The CVs of gas distributions in the images showed that there was a statistically significant difference between the COPD and healthy subjects (p < 0.0001). The functional volumes of pulmonary tissue, capillaries, and veins were significantly lower in the subjects with COPD than in the healthy subjects (p < 0.001). The functional volume of pulmonary tissue was found to be (i) statistically different between the healthy and MCTE groups (p = 0.02) and (ii) dependent on the age of the subjects in the healthy group (p = 0.0008) while their CVs (p = 0.13) were not. CONCLUSION: The novel HPX gas-exchange MRI and CFD model distinguished the healthy cohort from the MCTE and COPD cohorts. The proposed technique also showed that the functional volume of pulmonary tissue decreases with aging in the healthy group. KEY POINTS: • The ventilation and gas-exchange imaging with hyperpolarized xenon-129 MRI has enabled the identification of gas-exchange variation between COPD and healthy groups. • This novel technique was promising to be sensitive to minimal CT-diagnosed emphysema and age-related changes in gas-exchange parameter in a small pilot cohort.

Interaction at a distance: Xenon migration in Mb.

The transport of ligands, such as NO or O2, through internal cavities is essential for the function of globular proteins, including hemoglobin, myoglobin (Mb), neuroglobin, truncated hemoglobins, or cytoglobin. For Mb, several internal cavities (Xe1 through Xe4) were observed experimentally and they were linked to ligand storage. The present work determines barriers for xenon diffusion and relative stabilization energies for the ligand in the initial and final pocket, linking a transition depending on the occupancy state of the remaining pockets from both biased and unbiased molecular dynamics simulations. It is found that the energetics of a particular ligand migration pathway may depend on the direction in which the transition is followed and the occupancy state of the other cavities. Furthermore, the barrier height for a particular transition can depend in a non-additive fashion on the occupancy of either cavity A or B or simultaneous population of both cavities, A and B. Multiple repeats for the Xe1 → Xe2 transition reveal that the activation barrier is a distribution of barrier heights rather than one single value, which is confirmed by a distribution of transition times for the same transition from unbiased simulations. Dynamic cross correlation maps demonstrate that correlated motions occur between adjacent residues or through space, residue Phe138 is found to be a gate for the Xe1 → Xe2 transition, and the volumes of the internal cavities vary along the diffusion pathway, indicating that there is dynamic communication between the ligand and the protein. These findings suggest that Mb is an allosteric protein.

Long-term effects of combined brilliant blue G and xenon light induced retinal toxicity following macular hole repair surgery.

BACKGROUND: The purpose of this study was to look at the long-term effects of retinal phototoxicity after macular hole repair surgery using xenon endolight illumination and Brilliant blue G (BBG) dye. CASE PRESENTATION: An elderly man in his late seventies underwent para plana vitrectomy with BBG dye to repair an idiopathic full-thickness macular hole (MH) in his right eye. Prior to macular hole surgery, his visual acuity in the right eye was 6/60, N24 at the time of presentation. The MH closed with type 1 closure immediately after surgery, but there was extensive damage to the outer retinal layers and retinal pigment epithelium (RPE) at the macula, resulting in a reduction in visual acuity to 2/60. We presumed that the combination of BBG and xenon light, is the probable reason of retinotoxicity in the current patient. There was a progressive increase in the area of retinal and RPE layer damage and choroidal thinning over a 4-year period. CONCLUSION: Due to combined BBG-induced dye and endoilluminator toxicity, a rare case of continuously progressing RPE layer damage with choroidal thinning over a long follow-up interval was described. Such long-term effects of BBG and endolight induced retinotoxicity have not been reported in the literature, to the best of our knowledge.

Effects of xenon anesthesia on postoperative neurocognitive disorders: a systematic review and meta-analysis.

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.

Performance of the bispectral index and electroencephalograph derived parameters of anesthetic depth during emergence from xenon and sevoflurane anesthesia.

Many processed EEG monitors (pEEG) are unreliable when non-GABAergic anesthetic agents are used. The primary aim of the study was to compare the response of the Bispectral Index (BIS) during emergence from anesthesia maintained by xenon and sevoflurane. To better understand the variation in response of pEEG to these agents, we also compared several EEG derived parameters relevant to pEEG monitoring during emergence. Twenty-four participants scheduled for lithotripsy were randomized to receive xenon or sevoflurane anesthesia. Participants were monitored with the BIS and had simultaneous raw EEG collected. BIS index values were compared at three key emergence timepoints: first response, eyes open and removal of airway. Two sets of EEG derived parameters, three related to the BIS: relative beta ratio, SynchFastSlow and SynchFastSlow biocoherence, and two unrelated to the BIS: spectral edge frequency and the composite cortical state, were calculated for comparison. BIS index values were significantly lower in the xenon group than the sevoflurane group at each emergence timepoint. The relative beta ratio parameter increased significantly during emergence in the sevoflurane group but not in the xenon group. The spectral edge frequency and composite cortical state parameters increased significantly in both groups during emergence. The BIS index is lower at equivalent stages of behavioural response during emergence from xenon anesthesia when compared to sevoflurane anesthesia, most likely due to differences in how these two agents influence the relative beta ratio. The spectral edge frequency and composite cortical state might better reflect emergence from xenon anaesthesia.Clinical trial number and registry Australia New Zealand Clinical Trials Registry Number: ACTRN12618000916246.