Hyperpolarized (HP) xenon-129 (129Xe) chemical exchange saturation transfer (HyperCEST) provides the opportunity to perform high-sensitivity molecular magnetic resonance imaging (MRI) due to superior signal enhancement. One of the most recently discovered candidates for future development of HyperCEST-active biosensors, resorcinarene trimer methanesulfonate (R3-Noria-MeSO3H), possesses unique complex molecular dynamics resulting in its aggregation around metal cations. To study and understand this behavior of R3-Noria-MeSO3H and its potential interaction with large biological molecules, we conducted time series of UV-vis spectroscopies of different R3-Noria-MeSO3H concentrations in deionized water, phosphate buffer saline, saline, solutions of potassium chloride, choline, and bovine serum albumin (BSA). For the first time, we have acquired R3-Noria-MeSO3H UV-vis spectra and identified the origin of all absorption bands. Our data suggested that Na+ promoted R3-Noria-MeSO3H aggregation the most, while choline hinders it, albeit did not stop it completely. The absorption bands around 353 and 497 nm are the most indicative of the aggregation process and, therefore, may be utilized in future studies of R3-Noria-MeSO3H molecular dynamics. Furthermore, using UV-vis spectroscopy and electrophoretic analysis, we discovered rapid aggregation of R3-Noria-MeSO3H around BSA, forming supramolecular assemblies that persist as dynamic but macroscopically stable populations.

Current-induced and photo-induced magnetoelectric (ME) coupling provides a powerful means of dynamically tuning magnetic resonance in microwave and spintronic devices. Although Yttrium iron garnet (YIG) is widely used for its exceptional magnetic performance, the inherently dielectric nature of YIG restricts the implementation of current-induced ME effects. Zn substitution substantially increases the electrical conductivity of YIG, but it also affects its magnetic properties, creating a critical trade-off that must be quantitatively understood. We investigated the ferromagnetic resonance behavior of Zn-substituted YIG nanocomposites synthesized using a sol-gel approach, $(\mathrm{Y}_{3} \text{Fe}_{5} \text{Zn}_{\mathrm{x}} \mathrm{O}_{12})$ with Zn concentrations of 0, 0.05, 0.1, 0.2, and 0.3, to quantitatively assess their influence on the gyromagnetic ratio, $\gamma$, and the effective saturation magnetization, ${4} {\pi} \mathrm{M}_{\mathrm{s}}{ }^{\text{eff}}$. For the undoped YIG sample $(\text{Zn}={0}), \gamma \approx {2.9} \text{MHz}/\text{Oe}$ and ${4} {\pi} \mathrm{M}_{\mathrm{s}}{ }^{\text{eff}} {\approx} {1352 \text{Gs}}$ are similar to the expected values for pure YIG. The effective saturation magnetization exhibits an increase from $1352 \text{Gs}(\text{Zn}=0)$ to approximately 1960 Gs at $\text{Zn}=0.2$ and $\text{Zn}=0.3$. The observed rise in $4 \pi \mathrm{M}_{\mathrm{s}}{ }^{\text{eff}}$ with increasing Zn content can be attributed to the combined effects of intrinsic anisotropy enhancement and the porosity of the synthesized nanocomposites.

Current-induced magnetoelectric (ME) effect offers the potential for broadband, low-power tunable microwave devices. While yttrium iron garnet (YIG) is the most used ferrite due to its superior magnetic properties, its high-quality dielectric properties hinder its potential tuning with an electric current. To increase YIG's conductivity, we investigated Zn2+-doped YIG nanoparticles and nanocomposites (Y3Fe5-2x 3+Fe x 4+Zn x O12) synthesized using the sol-gel method within a broad concentration range of dopants (0 < x < 1.0). Herein, for the first time, we report the effect of high-level Zn doping on the electrical conductivity and ferromagnetic resonance (FMR) of a YIG nanocomposite material. An increase in Zn concentration resulted in the formation of the yttrium iron perovskite (YIP) phase, and for concentrations above 0.6, the sol-gel synthesis yielded the predominant formation of YIP. Y3Fe4.7Zn0.3O12 had the highest Zn content when the garnet phase was predominantly formed during the synthesis. The increase in the Zn content in the lattice enhanced the conductivity of yttrium iron garnet doped with Zn (YIG:Zn) by up to 3 orders of magnitude compared to that of pure YIG. In addition, the increase in the Zn content yielded an increase in the domain and ferromagnetic resonance frequencies of the YIG:Zn material. Overall, highly doped YIG:Zn nanocomposites have the potential to enable current-induced ME due to their superior conductivity.

This report is on experiments and theory on the process of optically stimulated electron population density redistribution in Si-substituted yttrium-iron garnet single crystals at 77 K. It was determined that a photo-induced uniaxial anisotropy field arose in the YIG:Si sample in response to illumination by quasi-linearly polarized laser (λ = 808 nm) leading to redistribution of Fe2+ ions among the nonequivalent octahedral sites. The photo-induced field was measured by variation of ferromagnetic resonance (FMR) frequencies in the X-band. The measured FMR frequency shift demonstrated a pronounced dependence on the polarization vector orientation with respect to crystallographic axes, in accordance with the theory discussed here. The frequency shift dependence on light intensity (for optimal polarization orientation) was found to be nearly linear, at least within the output intensity range of the optical source. The maximum frequency shift was −130 MHz for 75 mW applied optical power. A similar phenomenon was also observed at room temperature but was attributed to the sample heating by the incident light. The results presented here demonstrate the potential of the phenomenon for application in the development of ferrite signal processing devices with dual tuning by both magnetic field and optical irradiation.

Objective. The need for increased sensitivity in magnetic resonance imaging (MRI) is crucial for its advancement as an imaging modality. The development of passive Lenz Resonators (LRs) for effective RF magnetic field (B1) focusing will improve MRI sensitivity via local amplification of MRI signal, thereby leading to more efficient diagnosis and patient treatment. Approach. While there are methods for amplifying the signal from specific nuclei in MRI, such as hyperpolarization, a general solution will be more advantageous and would work in combination with these preexisting methods. While the Lenz Lens proposed such a general solution based on Lenz's law and the reciprocity principle, it came at the cost of limited signal enhancement. In this work, the first-in-kind prototype LR was conceived and examined as a general frequency-selective passive flux-focusing element for significant MRI signal enhancement. A 3.0 T Philips Achieva MRI was used to compare the signal from a phantom in the presence of Lenz Lenses, LRs, and control trials with neither component. Main results. An MRI investigation demonstrated an experimental amplification of the signal-to-noise ratio up to 80% using an MRI insert of two coaxial LRs due to superior B1 focusing. The resonators displayed consistent amplification, nearly independent of their x-position within the MRI bore. Significance. This behavior demonstrates the feasibility of imaging large objects of varying shapes without penalties for signal amplification using LRs. The LRs versatility in geometrical design and consistent signal amplifying abilities between pulse sequences should allow for the development of LRs suitable for most commonly used MRI setups.

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.

Hyperpolarized (HP) noble gas magnetic resonance imaging (MRI) and inert fluorinated gas MRI are the main pulmonary functional imaging modalities capable of regional ventilation assessment. To quantify pulmonary ventilation, K-means-based segmentation of ventilation images is usually performed. K-means clustering, however, performs poorly on images with relatively low SNR and cannot effectively distinguish background noise from low-ventilated areas. Here, we demonstrate a novel ventilation segmentation approach based on the subsequent implementation of lung edge detection using the Kirsch Compass operator followed by K-means segmentation. Our segmentation algorithm resulted in significantly higher accuracy of ventilation defect volume (VDV) assessment compared to a conventional ventilation segmentation algorithm. There were no significant changes in ventilation volume (VV) between our segmentation approach and conventional K-means segmentation. These indicate that implementation of digital lung edge detection prior to K-means segmentation substantially decreases segmentation sensitivity to background noise and allows a much more accurate assessment of low-ventilated regions of the lungs.

Hyperpolarized (HP) xenon-129 (Xe-129) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSO3H). This molecule is capable of two different contrast mechanisms for xenon-MRI, resulting from an increase in the effective spin-spin relaxation and hyperpolarized chemical exchange saturation transfer (HyperCEST). We have demonstrated a superior negative contrast caused by R3-Noria-MeSO3H on HP Xe-129 MRI at 3.0 T as well as HyperCEST imaging of the studied macrocycle. Additionally, we have found that the complex aggregation behaviors of R3-Noria-methanesulfonate and its impact on xenon-129 relaxivity are an area for future study.

Cucurbit[6]uril (CB6) is a well-known hyperpolarized 129 Xe (HP 129 Xe) MRI contrast agent. Although in-vivo biodistribution detection of CB6 has already been achieved, no studies have been performed on optimization of the saturation pre-pulse train in order to maximize CB6 performance. In the present work, we demonstrate that utilization of sinusoidal saturation pulses for 129 Xe HyperCEST MRI, instead of using conventional three-lobe sinc pulses, yields substantial improvement of CB6 HyperCEST performance and a significant increase in HyperCEST MRI sensitivity. In addition, lower detectable CB6 concentrations are reported for both types of saturation pre-pulses at 3T using a whole-body scanner.

Hyperpolarized (HP) xenon-129 (129Xe), when dissolved in blood, has two NMR resonances: one in red blood cells (RBC) and one in plasma. The impact of numerous blood components on these resonances, however, has not yet been investigated. This study evaluates the effects of elevated glucose levels on the chemical shift (CS) and T2* relaxation times of HP 129Xe dissolved in sterile citrated sheep blood for the first time. HP 129Xe was mixed with sheep blood samples premixed with a stock glucose solution using a liquid–gas exchange module. Magnetic resonance spectroscopy was performed on a 3T clinical MRI scanner using a custom-built quadrature dual-tuned 129Xe/1H coil. We observed an additional resonance for the RBCs (129Xe-RBC1) for the increased glucose levels. The CS of 129Xe-RBC1 and 129Xe-plasma peaks did not change with glucose levels, while the CS of 129Xe-RBC2 (original RBC resonance) increased linearly at a rate of 0.015 ± 0.002 ppm/mM with glucose level. 129Xe-RBC1 T2* values increased nonlinearly from 1.58 ± 0.24 ms to 2.67 ± 0.40 ms. As a result of the increased glucose levels in blood samples, the novel additional HP 129Xe dissolved phase resonance was observed in blood and attributed to the 129Xe bound to glycated hemoglobin (HbA1c).

The front cover artwork is provided by Prof. Mitchell S. Albert's group at Lakehead University. The image shows the hyperpolarized chemical exchange saturation transfer (HyperCEST) effect in cucurbit[6]uril molecular biosensors within a blood vessel. Read the full text of the Research Article at 10.1002/cphc.202300346.

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (129Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18–80 years were enrolled between July 2020 and August 2021 from two quaternary care centers. 129Xe MRI VDP, diffusing capacity of lung for carbon monoxide (Dlco), spirometry, oscillometry, 6-minute walk distance (6MWD), and St George Respiratory Questionnaire (SGRQ) scores were evaluated 3 months and 15 months after COVID-19 infection. Differences between time points were evaluated using the paired t test. Multivariable models were generated to explain exercise capacity and quality-of-life improvement. Odds ratios (ORs) were used to evaluate potential treatment influences. Results Overall, 53 participants (mean age, 55 years ± 18 [SD]; 27 women) attended both 3- and 15-month visits and were included in the analysis. The mean values for 129Xe MRI VDP (5.8% and 4.2%; P = .003), forced expiratory volume in the 1st second of expiration percent predicted (84% and 90%; P = .001), Dlco percent predicted (86% and 99%; P = .002), and SGRQ score (35 and 25; P < .001) improved between the 3- and 15-month visit. VDP measured 3 months after COVID-19 infection predicted the change in 6MWD (β = −0.643, P = .006), while treatment with respiratory medication at 3 months predicted an improved quality-of-life score at 15 months (OR, 4.0; 95% CI: 1.2, 13.8; P = .03). Conclusion Pulmonary function, gas exchange, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) improved in participants with postacute COVID-19 syndrome at 15 months compared with 3 months after infection. VDP measured at 3 months after infection correlated with improved exercise capacity, while treatment with respiratory medication was associated with an improved quality-of-life score 15 months after infection. ClinicalTrials.gov registration no. NCT05014516 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Vogel-Claussen in this issue.

Supplementary Materials and Figure Legends 1-4 from Mutations in BRAF and KRAS Converge on Activation of the Mitogen-Activated Protein Kinase Pathway in Lung Cancer Mouse Models

Supplementary Figure 4 from Mutations in BRAF and KRAS Converge on Activation of the Mitogen-Activated Protein Kinase Pathway in Lung Cancer Mouse Models

Supplementary Figure 3 from Mutations in BRAF and KRAS Converge on Activation of the Mitogen-Activated Protein Kinase Pathway in Lung Cancer Mouse Models

Supplementary Figure 2 from Mutations in BRAF and KRAS Converge on Activation of the Mitogen-Activated Protein Kinase Pathway in Lung Cancer Mouse Models

The Front Cover illustrates the Hyperpolarized chemical exchange transfer (HyperCEST) of hyperpolarized 129Xe and cucurbit[6]uril molecules in a blood vessel. The polarized 129Xe gets depolarized inside the cucurbit[6]uril using a depolarization radio-frequency pulse. The performance of this process was optimized in the present work achieving the maximization of the HyperCEST effect. Dr. Yurii Shepelytskyi and Vira Grynko illustrated the cover design. More information can be found in the Research Article by Mitchell S. Albert and co-workers.

129Xe MRI red blood cell to alveolar tissue plasma ratio (RBC:TP) abnormalities have been observed in ever-hospitalised and never-hospitalised people with postacute COVID-19 syndrome (PACS). But, it is not known if such abnormalities resolve when symptoms and quality-of-life scores improve. We evaluated 21 participants with PACS, 7±4 months (baseline) and 14±4 months (follow-up) postinfection. Significantly improved diffusing capacity of the lung for carbon monoxide (DLCO, Δ=14%pred;95%CI 7 to 21, p<0.001), postexertional dyspnoea (Δ=−0.7; 95%CI=−0.2 to –1.2, p=0.019), St George’s Respiratory Questionnaire-score (SGRQ Δ=−6; 95% CI=−1 to –11, p=0.044) but not RBC:TP (Δ=0.03; 95% CI=0.01 to 0.05, p=0.051) were observed at 14 months. DLCOcorrelated with RBC:TP (r=0.60, 95% CI=0.22 to 0.82, p=0.004) at 7 months. While DLCOand SGRQ measurements improved, these values did not normalise 14 months post-infection. ClinicalTrials.govNCT04584671.

Background Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised 129Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of 129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured 129Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS). Methods Consenting participants with a confirmed diagnosis of PACS completed 129Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George’s Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed 129Xe MRI and pulmonary function tests only. Results Seventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. 129Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO2 (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO2 (p=0.03). Conclusion 129Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO2 but not SGRQ or mMRC scores. Trial registration number NCT05014516.