Review of hyperpolarized pulmonary functional 129Xe MR for long-COVID

The respiratory consequences of acute COVID-19 infection and related symptoms tend to resolve 4 weeks post-infection. However, for some patients, new, recurrent, or persisting symptoms remain beyond the acute phase and persist for months, post-infection. The symptoms that remain have been referred to as long-COVID. A number of research sites employed 129Xe magnetic resonance imaging (MRI) during the pandemic and evaluated patients post-infection, months after hospitalization or home-based care as a way to better understand the consequences of infection on 129Xe MR gas-exchange and ventilation imaging. A systematic review and comprehensive search were employed using MEDLINE via PubMed (April 2023) using the National Library of Medicine's Medical Subject Headings and key words: post-COVID-19, MRI, 129Xe, long-COVID, COVID pneumonia, and post-acute COVID-19 syndrome. Fifteen peer-reviewed manuscripts were identified including four editorials, a single letter to the editor, one review article, and nine original research manuscripts (2020–2023). MRI and MR spectroscopy results are summarized from these prospective, controlled studies, which involved small sample sizes ranging from 9 to 76 participants. Key findings included: 1) 129Xe MRI gas-exchange and ventilation abnormalities, 3 months post-COVID-19 infection, and 2) a combination of MRI gas-exchange and ventilation abnormalities alongside persistent symptoms in patients hospitalized and not hospitalized for COVID-19, 1-year post-infection. The persistence of respiratory symptoms and 129Xe MRI abnormalities in the context of normal or nearly normal pulmonary function test results and chest computed tomography (CT) was consistent. Longitudinal improvements were observed in long-term follow-up of long-COVID patients but mean 129Xe gas-exchange, ventilation heterogeneity values and symptoms remained abnormal, 1-year post-infection. Pulmonary functional MRI using inhaled hyperpolarized 129Xe gas has played a role in detecting gas-exchange and ventilation abnormalities providing complementary information that may help develop our understanding of the root causes of long-COVID

The WOCE–era 3–D Pacific Ocean circulation and heat budget

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Progress In Oceanography 82 (2009): 281-325, doi:10.1016/j.pocean.2009.08.002.To address questions concerning the intensity and spatial structure of the 3–dimensional circulation within the Pacific Ocean and the associated advective and diffusive property flux divergences, data from approximately 3000 high–quality hydrographic stations collected on 40 zonal and meridional cruises have been merged into a physically consistent model. The majority of the stations were occupied as part of the World Ocean Circulation Experiment (WOCE), which took place in the 1990s. These data are supplemented by a few pre–WOCE surveys of similar quality, and time–averaged direct–velocity and historical hydrographic measurements about the equator. An inverse box model formalism is employed to estimate the absolute along–isopycnal velocity field, the magnitude and spatial distribution of the associated diapycnal flow and the corresponding diapycnal advective and diffusive property flux divergences. The resulting large–scale WOCE Pacific circulation can be described as two shallow overturning cells at mid– to low latitudes, one in each hemisphere, and a single deep cell which brings abyssal waters from the Southern Ocean into the Pacific where they upwell across isopycnals and are returned south as deep waters. Upwelling is seen to occur throughout most of the basin with generally larger dianeutral transport and greater mixing occurring at depth. The derived pattern of ocean heat transport divergence is compared to published results based on air–sea flux estimates. The synthesis suggests a strongly east/west oriented pattern of air–sea heat flux with heat loss to the atmosphere throughout most of the western basins, and a gain of heat throughout the tropics extending poleward through the eastern basins. The calculated meridional heat transport agrees well with previous hydrographic estimates. Consistent with many of the climatologies at a variety of latitudes as well, our meridional heat transport estimates tend toward lower values in both hemispheres.This work was funded by National Science Foundation grants OCE–9710102, OCE– 9712209 and OCE–0079383, and also benefited from work on closely related projects funded by NSF grants OCE–0223421 and OCE–0623261, and NOAA grant NA17RJ1223 funded through CICOR. For G.C.J. NASA funding came under Order W–19,314

Longitudinal lung function assessment of patients hospitalised 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 hospitalised due to COVID-19 without evidence of architectural distortion on structural imaging show longitudinal improvements in lung function measured using 1H and 129Xe magnetic resonance imaging between 6-52 weeks after hospitalisation? STUDY DESIGN AND METHODS: Patients who were hospitalised due to COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25 and 51 weeks after hospital admission in a prospective cohort study between 11/2020 and 02/2022. Imaging protocol: 1H ultra-short echo time, contrast enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion weighted and 129Xe spectroscopic imaging of gas exchange. RESULTS: 9 patients were recruited (57±14 [median±interquartile range] years, 6/9 male). Patients underwent MRI at 6 (N=9), 12 (N=9), 25 (N=6) and 51 (N=8) weeks after hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients demonstrated impaired 129Xe gas transfer (red blood cell 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 6-25 week period. At 12 weeks, all patients with lung perfusion data (N=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared to 6-week examinations, however 129Xe gas transfer remained abnormally low at weeks 12, 25 and 51. INTERPRETATION: 129Xe gas transfer was impaired up to one year after hospitalisation in patients who were hospitalised due to COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation wa normal at 52 weeks

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)