Parahydrogen-induced 13C hyperpolarizer using a flow guide for magnetic field cycling to evoke 1H-13C spin order transfer toward metabolic MRI.

OBJECTIVE: The pair-wise addition of parahydrogen, the singlet form of molecular hydrogen, to unsaturated precursors evokes the hyperpolarization of two parahydrogen-derived 1H nuclear spins through a process known as parahydrogen-induced polarization (PHIP). Subsequent spin order transfer (SOT) from the 1H to the surrounding 13C nuclear spins via magnetic field cycling (MFC) results in substantial signal enhancement in 13C magnetic resonance imaging (MRI). Here, we report the development of a unique PHIP 13C hyperpolarizer system using a flow guide for MFC. METHODS: The optimal MFC scheme for 1H to 13C spin order transfer was quantum-chemically simulated using the J-coupling values of 13C-labeled metabolic tracers. The flow guide system was three-dimensionally designed based on the simulated MFC scheme and pre-measured magnetic field distribution in a zero-field chamber. RESULTS: The system efficiently transfers the spin order of hyperpolarized 1H to a particular 13C spin when the parahydrogenated tracer passes through the flow guide at a designated flow rate. The 13C MRI signal is enhanced more than 40,000 times in 13C-labeled pyruvate and fumarate, compared to the thermal equilibrium level at 1.5 T, was achieved for conducting in vivo metabolic MRI of mice. CONCLUSION: A fully automated PHIP-based 13C polarizer was developed using a unique flow guide to conduct the MFC for 1H to 13C SOT. SIGNIFICANCE: The PHIP hyperpolarizer with a flow guide can conduct efficient 1H-13C SOT without a MFC magnetic field sweep system and offers a cost-effective alternative to conventional dynamic nuclear polarization.

A Framework for Predicting X-Nuclei Transmitter Gain Using 1H Signal.

Commercial human MR scanners are optimised for proton imaging, containing sophisticated prescan algorithms with setting parameters such as RF transmit gain and power. These are not optimal for X-nuclear application and are challenging to apply to hyperpolarised experiments, where the non-renewable magnetisation signal changes during the experiment. We hypothesised that, despite the complex and inherently nonlinear electrodynamic physics underlying coil loading and spatial variation, simple linear regression would be sufficient to accurately predict X-nuclear transmit gain based on concomitantly acquired data from the proton body coil. We collected data across 156 scan visits at two sites as part of ongoing studies investigating sodium, hyperpolarised carbon, and hyperpolarised xenon. We demonstrate that simple linear regression is able to accurately predict sodium, carbon, or xenon transmit gain as a function of position and proton gain, with variation that is less than the intrasubject variability. In conclusion, sites running multinuclear studies may be able to remove the time-consuming need to separately acquire X-nuclear reference power calibration, inferring it from the proton instead.

Initial feasibility and challenges of hyperpolarized 129 Xe MRI in neonates with bronchopulmonary dysplasia.

PURPOSE: The underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized 129 Xe MRI in neonates with BPD. METHODS: Neonatal intensive care patients with established BPD were recruited (N = 9) and imaged at a corrected gestational age of median:40.7 (range:37.1, 44.4) wk using a 1.5T neonatal scanner. 2D 129 Xe ventilation and diffusion-weighted images and dissolved phase spectroscopy were acquired, alongside 1 H 3D radial UTE. 129 Xe images were acquired during a series of short apneic breath-holds (˜3 s). 1 H UTE images were acquired during tidal breathing. Ventilation defects were manually identified and qualitatively compared to lung structures on UTE. ADCs were calculated on a voxel-wise basis. The signal ratio of the 129 Xe red blood cell (RBC) and tissue membrane (M) resonances from spectroscopy was determined. RESULTS: Spiral-based 129 Xe ventilation imaging showed good image quality and sufficient sensitivity to detect mild ventilation abnormalities in patients with BPD. 129 Xe ADC values were elevated above that expected given healthy data in older children and adults (median:0.046 [range:0.041, 0.064] cm2 s-1 ); the highest value obtained from an extremely pre-term patient. 129 Xe spectroscopy revealed a low RBC/M ratio (0.14 [0.06, 0.21]). CONCLUSION: We have demonstrated initial feasibility of 129 Xe lung MRI in neonates. With further data, the technique may help guide management of infant lung diseases in the neonatal period and beyond.

Use of protracted CPAP as supportive treatment for COVID-19 pneumonitis and associated outcomes: a national cohort study.

BACKGROUND: Continuous positive airway pressure (CPAP) has been increasingly deployed to manage patients with COVID-19 and acute respiratory failure, often for protracted periods. However, concerns about protracted CPAP have been raised. This study aimed to examine the use of CPAP for patients with COVID-19 and the outcomes after protracted use. METHODS: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to December 25, 2021 who received CPAP. Protracted CPAP was defined as ≥ 5 continuous days of CPAP. Outcomes included CPAP failure rate (institution of invasive mechanical ventilation [IMV] or death), mortality, and outcomes after institution of IMV. Multivariable logistic regression was performed to assess the impact of protracted CPAP on mortality after IMV. RESULTS: A total of 1961 patients with COVID-19 received CPAP for COVID-19 pneumonitis, with 733 patients (37.4%) receiving protracted CPAP. CPAP failure occurred in 891 (45.4%): 544 patients (27.7%) received IMV and 347 patients (17.7%) died in critical care without IMV. Hospital mortality rate was 41.3% for the population. For patients who subsequently commenced IMV, hospital mortality was 58.7% for the standard duration CPAP group and 73.9% for the protracted duration CPAP group (P=0.003); however, there was no statistical difference in hospital mortality after adjustment for confounders (odds ratio 1.4, 95% confidence interval 0.84-2.33, P=0.195). CONCLUSIONS: Protracted CPAP was used frequently for managing patients with COVID-19. Whilst it was not associated with worse outcomes for those patients who subsequently required IMV, this might be due to residual confounding and differences in processes of care.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using 1H and 129Xe Lung MRI.

BACKGROUND: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. RESEARCH QUESTION: Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization? STUDY DESIGN AND METHODS: Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. RESULTS: Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51. INTERPRETATION: 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.

Targeted Imaging of Lung Cancer with Hyperpolarized 129Xe MRI Using Surface-Modified Iron Oxide Nanoparticles as Molecular Contrast Agents.

Hyperpolarized 129Xe (HP 129Xe) MRI enables functional imaging of various lung diseases but has been scarcely applied to lung cancer imaging. The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (IONPs) as molecular targeting contrast agents. A mouse model of lung cancer (LC) was induced in nine mice by intra-peritoneal injection of urethane. Three months after the urethane administration, the mice underwent lung imaging with HP 129Xe MRI at baseline (0 h). Subsequently, the LC group was divided into two sub-groups: mice administered with polyethylene glycol-coated IONPs (PEG-IONPs, n = 4) and folate-conjugated dextran-coated IONPs (FA@Dex-IONPs, n = 5). The mice were imaged at 3, 6, and 24 h after the intravenous injection of IONPs. FA@Dex-IONPs mice showed a 25% reduction in average signal intensity at cancer sites at 3 h post injection, and a 24% reduction at 24 h post injection. On the other hand, in PEG-IONPs mice, while a signal reduction of approximately 28% was observed at cancer sites at 3 to 6 h post injection, the signal intensity was unchanged from that of the baseline at 24 h. Proton MRI of LC mice (n = 3) was able to detect cancer five months after urethane administration, i.e., later than HP 129Xe MRI (3 months). Furthermore, a significant decrease in averaged 1H T2 values at cancer sites was observed at only 6 h post injection of FA@Dex-IONPs (p < 0.05). As such, the targeted delivery of IONPs to cancer tissue was successfully imaged with HP 129Xe MRI, and their surface modification with folate likely has a high affinity with LC, which causes overexpression of folate receptors.

Prevention of posttraumatic stress during inpatient rehabilitation post spinal cord injury: Study protocol for a randomized controlled trial of Brief Prolonged Exposure Therapy (Brief PE).

Background: Scant research has focused on posttraumatic stress disorder (PTSD) in the SCI population, despite high prevalence estimates. Fortunately, prolonged exposure therapy (PE) is a well-researched and highly effective treatment for PTSD. Our recent clinical trial showed that standard 12-session PE was effective for PTSD treatment among inpatients with SCI. Early intervention with brief PE (3-sessions) delivered in the emergency department has also been effective for PTSD prevention, but has not been tested among people post-SCI. Thus, we aim to conduct the first test of the Brief PE intervention to prevent PTSD among patients with SCI. Methods: Adults who have experienced a SCI (N = 200) will be randomly assigned during inpatient rehabilitation to either: (a) 3 60-min sessions of Brief PE (intervention group) or (b) treatment as usual (control group). Results: The primary outcome measure (PTSD symptoms measured by the PSSI-5) and secondary outcome measures (depression, anxiety, pain, quality of life, sleep disturbance, and resilience) will be assessed at baseline, 1-month, 3-months, and 6-months. Hierarchical linear modeling (HLM) will be used to evaluate the effectiveness of the PE intervention on PTSD and secondary outcomes. Descriptive statistics will examine feasibility and will include the number of participants enrolled, the number of sessions completed, fidelity of Brief PE delivery, and average scores for difficulty and helpfulness of the intervention scales for those randomized to intervention. Conclusions: Successful completion of this study will provide an evidence-based program to alleviate posttraumatic distress post spinal cord injury and prevent long-term development of PTSD.

Prevalence, characteristics, and longer-term outcomes of patients with persistent critical illness attributable to COVID-19 in Scotland: a national cohort study.

BACKGROUND: Patients with COVID-19 can require critical care for prolonged periods. Patients with persistent critical Illness can have complex recovery trajectories, but this has not been studied for patients with COVID-19. We examined the prevalence, risk factors, and long-term outcomes of critically ill patients with COVID-19 and persistent critical illness. METHODS: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to September 4, 20. Persistent critical illness was defined as a critical care length of stay (LOS) of ≥10 days. Outcomes included 1-yr mortality and hospital readmission after critical care discharge. Fine and Gray competing risk analysis was used to identify factors associated with persistent critical Illness with death as a competing risk. RESULTS: A total of 2236 patients with COVID-19 were admitted to critical care; 1045 patients were identified as developing persistent critical Illness, comprising 46.7% of the cohort but using 80.6% of bed-days. Patients with persistent critical illness used more organ support, had longer post-critical care LOS, and longer total hospital LOS. Persistent critical illness was not significantly associated with long-term mortality or hospital readmission. Risk factors associated with increased hazard of persistent critical illness included age, illness severity, organ support on admission, and fewer comorbidities. CONCLUSIONS: Almost half of all patients with COVID-19 admitted to critical care developed persistent critical illness, with high resource use in critical care and beyond. However, persistent critical illness was not associated with significantly worse long-term outcomes compared with patients who were critically ill for shorter periods.

Workplace inequality is associated with status-signaling expenditure.

Regional inequality is known to magnify sensitivity to social rank. This, in turn, is shown to increase people's propensity to acquire luxury goods as a means to elevate their perceived social status. Yet existing research has focused on broad, aggregated datasets, and little is known about how individual-level measures of income interact with inequality within peer groups to affect status signaling. Using detailed financial transaction data, we construct 32,008 workplace peer groups and explore the longitudinal spending and salary data associated with 683,677 individuals. These data reveal links between people's status spending, their absolute salary, salary rank within their workplace peer group, and the inequality of their workplace salary distribution. Status-signaling luxury spending is found to be greatest among those who have higher salaries, whose workplaces exhibit higher inequality, and who occupy a lower rank position within the workplace. We propose that low-rank individuals in unequal workplaces suffer status anxiety and, if they can afford it, spend to signal higher status.

Hyperpolarized 13C Magnetic Resonance Imaging as a Tool for Imaging Tissue Redox State, Oxidative Stress, Inflammation, and Cellular Metabolism.

Significance: Magnetic resonance imaging (MRI) with hyperpolarized (HP) 13C-labeled redox-sensitive metabolic tracers can provide noninvasive functional imaging biomarkers, reflecting tissue redox state, oxidative stress, and inflammation, among others. The capability to use endogenous metabolites as 13C-enriched imaging tracers without structural modification makes HP 13C MRI a promising tool to evaluate redox state in patients with various diseases. Recent Advances: Recent studies have demonstrated the feasibility of in vivo metabolic imaging of 13C-labeled tracers polarized by parahydrogen-induced polarization techniques, which offer a cost-effective alternative to the more widely used dissolution dynamic nuclear polarization-based hyperpolarizers. Critical Issues: Although the fluxes of many metabolic pathways reflect the change in tissue redox state, they are not functionally specific. In the present review, we summarize recent challenges in the development of specific 13C metabolic tracers for biomarkers of redox state, including that for detecting reactive oxygen species. Future Directions: Applications of HP 13C metabolic MRI to evaluate redox state have only just begun to be investigated. The possibility to gain a comprehensive understanding of the correlations between tissue redox potential and metabolism under different pathological conditions by using HP 13C MRI is promoting its interest in the clinical arena, along with its noninvasive biomarkers to evaluate the extent of disease and treatment response.

Lung MRI with hyperpolarised gases: current & future clinical perspectives.

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique - hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe - a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease: Results from the MOPEAD project.

INTRODUCTION: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. METHODS: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC). RESULTS: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). CONCLUSION: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD.

Protocols for multi-site trials using hyperpolarized 129 Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129 Xe MRI clinical trials consortium.

Hyperpolarized (HP) 129 Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129 Xe MRI for multi-site pulmonary research.

Human upper-airway respiratory airflow: In vivo comparison of computational fluid dynamics simulations and hyperpolarized 129Xe phase contrast MRI velocimetry.

Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject's natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD.

Inflammation during Lung Cancer Progression and Ethyl Pyruvate Treatment Observed by Pulmonary Functional Hyperpolarized 129Xe MRI in Mice.

This study aimed to assess the suitability of hyperpolarized 129Xe (HPXe) MRI for noninvasive longitudinal evaluation of pulmonary function in preclinical lung cancer models. A mouse model of lung cancer (LC) was induced in 5 mice by intraperitoneal injection of urethane, while a negative-control (NC) mice (N = 5) was prepared by injection of saline solution. Longitudinal HPXe MRI was performed over a 5-month period to monitor lung ventilation and gas exchange. The treatment efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, to the mouse LC model was monitored using HPXe MRI by commencing administration of EP pre (early-phase) and 1-month post (late-phase) injection of urethane (N = 5 mice for each group). Gas-exchange function in LC mice was significantly reduced at 1-month after urethane injection compared with NC mice administered with saline (P < 0.01). Thereafter, it remained consistently lower than that of the NC group for the full 5-month measurement period. In contrast, the ventilation function of the LC model mice was not significantly different to that of the NC mice. Histological analysis revealed alveolar epithelial hyperplasia in LC mice alveoli at 1 month after urethane injection, and adenoma was confirmed 3 months after the injection. The early- and late-phase EP interventions were found to improve HPXe MRI metrics (reduced at 1 month postinjection of urethane) and significantly inhibit tumor growth. These results suggest that HPXe MRI gas-exchange metrics can be used to quantitatively assess changes in the precancerous lesion microenvironment and to evaluate therapeutic efficacy in cancer. Thus, HPXe MRI can be utilized to noninvasively monitor pulmonary pathology during LC progression and can visualize functional changes during therapy.

Influence of socioeconomic deprivation on interventions and outcomes for patients admitted with COVID-19 to critical care units in Scotland: A national cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to significant respiratory failure with between 14% and 18% of hospitalised patients requiring critical care admission. This study describes the impact of socioeconomic deprivation on 30-day survival following critical care admission for COVID-19, and the impact of the COVID-19 pandemic on critical care capacity in Scotland. METHODS: This cohort study used linked national hospital records including ICU, virology testing and national death records to identify and describe patients with COVID-19 admitted to critical care units in Scotland. Multivariable logistic regression was used to assess the impact of deprivation on 30-day mortality. Critical care capacity was described by reporting the percentage of baseline ICU bed utilisation required. FINDINGS: There were 735 patients with COVID-19 admitted to critical care units across Scotland from 1/3/2020 to 20/6/2020. There was a higher proportion of patients from more deprived areas, with 183 admissions (24.9%) from the most deprived quintile and 100 (13.6%) from the least deprived quintile. Overall, 30-day mortality was 34.8%. After adjusting for age, sex and ethnicity, mortality was significantly higher in patients from the most deprived quintile (OR 1.97, 95%CI 1.13, 3.41, p=0.016). ICUs serving populations with higher levels of deprivation spent a greater amount of time over their baseline ICU bed capacity. INTERPRETATION: Patients with COVID-19 living in areas with greatest socioeconomic deprivation had a higher frequency of critical care admission and a higher adjusted 30-day mortality. ICUs in health boards with higher levels of socioeconomic deprivation had both higher peak occupancy and longer duration of occupancy over normal maximum capacity. FUNDING: None.

Hyperpolarized 13 C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen-induced Polarization: A Proof-of-Concept in†vivo Study.

The front cover artwork is provided by the group of Dr. Neil J. Stewart, Prof. Hiroshi Hirata, and Dr. Shingo Matsumoto (Hokkaido University, Japan) as well as Dr. Takuya Hashimoto (Chiba University, Japan). The image shows hyperpolarized 13 C fumarate metabolism to hyperpolarized 13 C malate, which is released into the extracellular space in regions of necrotic cell death, where the cell membrane is disrupted. Read the full text of the Article at 10.1002/cphc.202001038.

In vivo methods and applications of xenon-129 magnetic resonance.

Hyperpolarised gas lung MRI using xenon-129 can provide detailed 3D images of the ventilated lung airspaces, and can be applied to quantify lung microstructure and detailed aspects of lung function such as gas exchange. It is sensitive to functional and structural changes in early lung disease and can be used in longitudinal studies of disease progression and therapy response. The ability of 129Xe to dissolve into the blood stream and its chemical shift sensitivity to its local environment allow monitoring of gas exchange in the lungs, perfusion of the brain and kidneys, and blood oxygenation. This article reviews the methods and applications of in vivo129Xe MR in humans, with a focus on the physics of polarisation by optical pumping, radiofrequency coil and pulse sequence design, and the in vivo applications of 129Xe MRI and MRS to examine lung ventilation, microstructure and gas exchange, blood oxygenation, and perfusion of the brain and kidneys.

Hyperpolarized 13 C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen-induced Polarization: A Proof-of-Concept in†vivo Study.

Hyperpolarized [1-13 C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1-13 C]fumarate metabolism using parahydrogen-induced polarization (PHIP), a low-cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost-effective and high-yield synthetic pathway of hydrogenation precursor [1-13 C]acetylenedicarboxylate (ADC) was developed. The trans-selectivity of the hydrogenation reaction of ADC using a ruthenium-based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set-up was used to generate hyperpolarized [1-13 C]fumarate at sufficient 13 C polarization for ex vivo detection of hyperpolarized 13 C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo 13 C MR spectroscopy and imaging in a murine model of acetaminophen-induced hepatitis.