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Abstract As hyperpolarized (HP) carbon-13 (13C) metabolic imaging is clinically translated, there is a need for easy-to-implement, fast, and robust imaging techniques. However, achieving high temporal resolution without decreasing spatial and/or spectral resolution, whilst maintaining the usability of the imaging sequence is challenging. Therefore, this study looked to accelerate HP 13C MRI by combining a well-established and robust sequence called two-dimensional Chemical Shift Imaging (2D CSI) with prospective under sampling and SENSitivity Encoding (SENSE) reconstruction. Due to the low natural abundance of 13C, the sensitivity maps cannot be pre-acquired for the reconstruction. As such, the implementation of sodium (23Na) sensitivity maps for SENSE reconstructed 13C CSI was demonstrated in a phantom and in vivo in the pig kidney. Results showed that SENSE reconstruction using 23Na sensitivity maps corrected aliased images with a four-fold acceleration. With high temporal resolution, the kidney spectra produced a detailed metabolic arrival and decay curve, useful for further metabolite kinetic modelling or denoising. Metabolic ratio maps were produced in three pigs demonstrating the technique’s ability for repeat metabolic measurements. In cases with unknown metabolite spectra or limited HP MRI specialist knowledge, this robust acceleration method ensures comprehensive capture of metabolic signals, mitigating the risk of missing spectral data.

Abstract Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron‐10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron‐11 in an unstable form, which undergoes instantaneous nuclear fission to produce high‐energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high‐grade gliomas and their subsequent clinical use to treat patients with high‐grade gliomas. First, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

Abstract Background Magnetic resonance (MR) imaging of deuterated glucose, termed deuterium metabolic imaging (DMI), is emerging as a biomarker of pathway-specific glucose metabolism in tumors. DMI is being studied as a useful marker of treatment response in a scan-rescan scenario. This study aims to evaluate the repeatability of brain DMI. Methods A repeatability study was performed in healthy volunteers from December 2022 to March 2023. The participants consumed 75 g of [6,6′­2H2]glucose. The delivery of 2H-glucose to the brain and its conversion to 2H-glutamine + glutamate, 2H-lactate, and 2H-water DMI was imaged at baseline and at 30, 70, and 120 min. DMI was performed using MR spectroscopic imaging on a 3-T system equipped with a 1H/2H-tuned head coil. Coefficients of variation (CoV) were computed for estimation of repeatability and between-subject variability. In a set of exploratory analyses, the variability effects of region, processing, and normalization were estimated. Results Six male participants were recruited, aged 34 ± 6.5 years (mean ± standard deviation). There was 42 ± 2.7 days between sessions. Whole-brain levels of glutamine + glutamate, lactate, and glucose increased to 3.22 ± 0.4 mM, 1.55 ± 0.3 mM, and 3 ± 0.7 mM, respectively. The best signal-to-noise ratio and repeatability was obtained at the 120-min timepoint. Here, the within-subject whole-brain CoVs were -10% for all metabolites, while the between-subject CoVs were -20%. Conclusions DMI of glucose and its downstream metabolites is feasible and repeatable on a clinical 3 T system. Trial registration ClinicalTrials.gov, NCT05402566 , registered the 25th of May 2022. Relevance statement Brain deuterium metabolic imaging of healthy volunteers is repeatable and feasible at clinical field strengths, enabling the study of shifts in tumor metabolism associated with treatment response. Key points • Deuterium metabolic imaging is an emerging tumor biomarker with unknown repeatability. • The repeatability of deuterium metabolic imaging is on par with FDG-PET. • The study of deuterium metabolic imaging in clinical populations is feasible. Graphical Abstract

Background: The opportunities of perinatal medicine have improved, but this has also been accompanied by increasing ethical challenges. Clinical ethics consultation services (CEC) could support medical teams facing these. However, nothing is currently known about the availability, utilization and evaluation of CEC in German neonatology units. Methods: This study was designed as a national, descriptive, mixed quantitative–qualitative questionnaire study. The head physicians of the pediatric departments and the heads (medical and nursing) of the corresponding neonatal intensive care units of the 213 German perinatal centers were asked to participate. Results: Ninety percent of the respondents (responding rate 24.4–38.0%) stated that CEC are established and available. However, utilization is rather low [rarely N = 40 (54.1%), never N = 12, (16.2%), occasionally N = 19 (25.7%)], although it was rated as very helpful. There was a significant correlation between utilization and perceived general usefulness (r = 0.224, p = 0.033) and support (r = 0.41, p < 0.001); whereas evaluations differed significantly between professional groups (t = −2.298, p = 0.23, Cohen’s d = 0.42). Conclusions: The contradiction between the low utilization despite positive evaluations could be related to perceived hurdles. These and the different perceptions within the professional groups give rise to the consideration of whether alternative approaches, e.g., liaison services, would be preferable in neonatology.

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.

Abstract Background Postmenopausal women often have chronic cough. Hormonal changes might be affecting lung function and the mucous membrane of the airways, causing hypersensitivity of the cough reflex. Therefore, postmenopausal hormonal changes could play a key role in the association between increased cough and menopause. The aim of this study is to evaluate the relation of chronic cough and postmenopausal symptoms. Methods We performed a questionnaire-based cohort study in generally healthy postmenopausal women (age 45–65 years). Women with cough explained by a pre-existing diagnosis were excluded. Comorbidities, medication and baseline data were collected. The Menopause Rating Scale II (MRS II) was combined with the Leicester Cough Questionnaire. Groups were divided in chronic cough versus non-coughing participants, chronic cough was defined as symptoms over 8 weeks. We performed correlations and logistic regression for predicting cough based on postmenopausal symptoms. Results Sixty-six of 200 women (33%) reported symptoms of chronic cough over 8 weeks. No significant differences in baseline data (age, BMI, onset of menopause, years since menopause, concomitant diseases, and medication) were found between coughing and non-coughing women. The MRS II showed higher menopausal symptoms in patients with cough, with significant differences in 2 of the 3 MRS-domains (urogenital (p

Abstract Background Hyperpolarized (HP) [1-13C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-13C]pyruvate to either [1-13C]lactate or 13C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-13C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. Methods A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during adenosine stress. HP [1-13C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. Results Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (k PL) for lactate increased from 11 ± 9 *10–3 to 20 ± 10 * 10–3 s−1, p = 0.04. The pyruvate oxidation rate (k PB) increased from 4 ± 4 *10–3 to 12 ± 7 *10–3 s−1, p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R2 = 0.44, p = 0.02). Conclusions Adenosine stress testing combined with HP [1-13C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1-13C]pyruvate CMR into clinical cardiac imaging. Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15

Hyperpolarized carbon‐13 (13C) magnetic resonance imaging (MRI) has shown promise for non‐invasive assessment of the cerebral metabolism of [1‐13C]pyruvate in both healthy volunteers and patients. The exchange of pyruvate to lactate catalysed by lactate dehydrogenase (LDH) and that of pyruvate flux to bicarbonate through pyruvate dehydrogenase (PDH) are the most widely studied reactions in vivo. Here we show the potential of the technique to probe additional enzymatic activity within the brain. Approximately 50 s after intravenous injection of hyperpolarized pyruvate, high‐flip‐angle pulses were used to detect cerebral 13C‐labelled carbon dioxide (13CO2), in addition to the 13C‐bicarbonate (H13CO3−) subsequently formed by carbonic anhydrase (CA). Brain pH measurements, which were weighted towards the extracellular compartment, were calculated from the ratio of H13CO3− to 13CO2 in seven volunteers using the Henderson–Hasselbalch equation, demonstrating an average pH ± SD of 7.40 ± 0.02, with inter‐observer reproducibility of 0.04. In addition, hyperpolarized [1‐13C]aspartate was also detected, demonstrating irreversible pyruvate carboxylation to oxaloacetate by pyruvate carboxylase (PC) and subsequent transamination by aspartate aminotransferase (AST), with the average flux being on average 11% ± 3% of that through PDH. A hyperpolarized [1‐13C]alanine signal was also detected, but this was localized to extracranial muscle tissue in keeping with skeletal alanine aminotransferase (ALT) activity. The results demonstrate the potential of hyperpolarized 13C‐MRI to assess cerebral and extracerebral [1‐13C]pyruvate metabolism in addition to LDH and PDH activity. Non‐invasive measurements of brain pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid–base balance. [ABSTRACT FROM AUTHOR]

Background: The opportunities of perinatal medicine have improved, but this has also been accompanied by increasing ethical challenges. Clinical ethics consultation services (CEC) could support medical teams facing these. However, nothing is currently known about the availability, utilization and evaluation of CEC in German neonatology units. Methods: This study was designed as a national, descriptive, mixed quantitative–qualitative questionnaire study. The head physicians of the pediatric departments and the heads (medical and nursing) of the corresponding neonatal intensive care units of the 213 German perinatal centers were asked to participate. Results: Ninety percent of the respondents (responding rate 24.4–38.0%) stated that CEC are established and available. However, utilization is rather low [rarely N = 40 (54.1%), never N = 12, (16.2%), occasionally N = 19 (25.7%)], although it was rated as very helpful. There was a significant correlation between utilization and perceived general usefulness (r = 0.224, p = 0.033) and support (r = 0.41, p < 0.001); whereas evaluations differed significantly between professional groups (t = −2.298, p = 0.23, Cohen's d = 0.42). Conclusions: The contradiction between the low utilization despite positive evaluations could be related to perceived hurdles. These and the different perceptions within the professional groups give rise to the consideration of whether alternative approaches, e.g., liaison services, would be preferable in neonatology. [ABSTRACT FROM AUTHOR]

(1) Background: Mothers of very preterm (VPT) infants may experience psychological symptoms compromising long-term emotional wellbeing. This study describes the emotional wellbeing of mothers of five-year-old children born VPT. We assess the association between sociodemographic, perinatal and neonatal characteristics, and the child’s health and development at five years old and maternal emotional wellbeing. (2) Methods: Data are from the prospective European “Effective Perinatal Intensive Care in Europe” (EPICE) and subsequent “Screening for Health In very Preterm infantS in Europe” (SHIPS) projects including births

* Context.--The purpose of this review was to compare 3 coronavirus diseases, including severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses, respectively. Objective.--To cover the following topics: clinical considerations, viral characteristics, pathology, immune response, pathogenesis, and the prognosis associated with each coronavirus disease in humans. Data Sources.--Clinically, flu-like symptoms are usual at the time of presentation for all 3 diseases, but these vary from asymptomatic to severe multisystem involvement. The pathology associated with symptomatic severe acute respiratory syndrome and COVID-19 has been well described, the most prominent of which is diffuse alveolar damage. The immune response to each of these viruses is highly complex and includes both humoral and cellular components that can have a significant impact on prognosis. In severe cases of COVID-19, a dysregulated innate host immune system can initiate a hyperinflammatory syndrome dominated by endothelial dysfunction that can lead to a hypercoagulable state with microthrombi, resulting in a systemic microvascular and macrovascular disease. Conclusions.--The severe acute respiratory syndrome and Middle East respiratory syndrome epidemics have been limited, involving approximately 8000 and 2500 individuals, respectively. In contrast, COVID-19 has resulted in a worldwide pandemic with more than 177 million cases and 3.9 million deaths as of June 15, 2021, and fatality rates ranging from less than 0.1% to approximately 10% depending upon the country. Ending on a positive note, the development of a number of vaccines, at least 6 of which now are in clinical use, should mitigate and eventually control the devastating COVID-19 pandemic. doi: 10.5858/arpa.2020-0820-SA, The purpose of this review was to compare the following 3 coronavirus diseases: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) with an [...]

ObjectiveBreaking bad news in neonatology is a frequent and difficult challenge. Although there are guidelines for communicating with parents in pediatrics and neonatology, the specific framework for breaking bad news in neonatology has not been studied in more detail. Therefore, we aimed to identify determinants that are important for successful managing breaking bad news in neonatology from professionals' perspective and to develop a conceptual framework that underpins this challenging task.MethodsWe conducted seventeen semi-structured interviews with senior neonatologists of six perinatal centers of the highest level of care in Germany. The transcripts were analyzed according to Mayring's method of qualitative content analysis using inductive and deductive coding.ResultsEight determinants of breaking bad news in neonatology could be identified from the interviews. From these, we developed the conceptual framework NEO-SPEAK. The first three determinants, Neonatal prognostic uncertainty, Encounter in (triangular-)partnerships, Organization and teamwork (NEO) are directly related to the specific care situation in neonatology, whereas the others, Situational stress, Processuality, Emotional burden, Attention to individuality, Knowledge and experience, play a role for difficult conversations in general, but are subject to special modifications in neonatology (SPEAK). In addition, the results show that the context in neonatology as well as reciprocal effects on the team and the individual level of the physicians are important influencing factors in breaking bad news.ConclusionOn the one hand, the constitutional framework NEO-SPEAK shows which special aspects play a role in neonatology for the delivery of bad news, and on the other hand, it can help to identify and consider these aspects in clinical routine and training. Considering or reinforcing each NEO-SPEAK element when planning or delivering bad news may guide healthcare professionals through communication with parents of critically ill or premature newborns and support the resilience of the caring team.