The effects of iodinated CT contrast agent on phosphorus MRS

Synopsis Contrast-enhanced CT examination can influence H-MRI measurements performed within 24h after the CT scan, due to a reduction in water T and T caused by the iodinated contrast agents used in CT. We have investigated whether contrast from a previous CT examination would also influence metabolic measurements made using P-MRS, by measuring the T of H and P signals in human blood. We find that iodinated CT contrast agent has no effect on phosphorus T s. Therefore, P-MRS examinations will not be influenced by prior CT (unlike H-MRI scans).We acknowledge financial support from the British Heart Foundation (FS/10/002/28078; FS/14/17/30634; RG/11/9/28921), a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (098436/Z/12/Z), a Novo Nordisk Foundation Postdoctoral Research Fellowship and from the Slovak Grant Agencies VEGA (2/0001/17) and APVV (15-0029)

Microgravity, Mesh-Crawling Legged Robots

The design, fabrication, and microgravity flight-testing are part of a continuing development of palm-sized mobile robots that resemble spiders (except that they have six legs apiece, whereas a spider has eight legs). Denoted SpiderBots (see figure), they are prototypes of proposed product line of relatively inexpensive walking robots that could be deployed in large numbers to function cooperatively in construction, repair, exploration, search, and rescue activities in connection with exploration of outer space and remote planets

Compartment-based reconstruction of 3D acquisition-weighted 31P cardiac magnetic resonance spectroscopic imaging at 7 T: a reproducibility study

Even at 7 T, cardiac 31P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T. Twelve healthy volunteers were scanned twice. Each scan session consisted of a 6.5-min 3D acquisition-weighted (AW) cardiac 31P phase encode-based MRSI acquisition and two 6.5-min truncated k-space acquisitions with increased averaging (4 × 4 × 4 central k-space phase encodes and fractional SLAM [fSLAM] optimized k-space phase encodes). Spectra were reconstructed using (i) AW Fourier reconstruction; (ii) AW SLAM; (iii) AW SLIM; (iv) 4 × 4 × 4 SLAM; (v) 4 × 4 × 4 SLIM; and (vi) fSLAM acquisition–reconstruction combinations. The phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio, the PCr SNR, and spatial response functions were computed, in addition to coefficients of reproducibility and variability. Using the compartment-based reconstruction algorithms with the AW 31P acquisition resulted in a significant increase in SNR compared with previously published Fourier-based MRSI reconstruction methods while maintaining the measured PCr/ATP ratio and improving interscan reproducibility. The alternative acquisition strategies with truncated k-space performed no better than the common AW approach. Compartment-based spectroscopy approaches provide an attractive reconstruction method for cardiac 31P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k-space sampling strategy

Assessing metabolism and function of normothermically perfused ex vivo livers by multinuclear MR imaging and spectroscopy

Synopsis Liver transplantation is the only cure for end-stage liver disease. Unfortunately, 20% of patients die waiting for a donor. New techniques for preserving transplant livers, such as normothermic machine perfusion (NMP), provide an opportunity to utilise ‘marginal’ (currently discarded) donated livers if their viability can be assessed accurately. We present initial results from a CE-marked NMP system that we adapted for use in an MRI scanner. We demonstrate the power of NMP-MRI to assess structure and metabolism in a freshly donated pig liver, dynamically over a 10-hour period. Our protocol includes H imaging, P spectroscopy, and hyperpolarised C spectroscopy.This work was funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (Grant No. 098436/Z/12/Z) and by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)

Rapid, B1B_1-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux

Purpose: Phosphorus saturation-transfer experiments can quantify metabolic fluxes non-invasively. Typically, the forward flux through the creatine-kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of $\gamma$-ATP. The quantification of total ATP utilisation is currently under-explored, as it requires simultaneous saturation of inorganic phosphate (Pi) and PCr. This is challenging, as currently available saturation pulses reduce the already-low $\gamma$-ATP signal present. Methods: Using a hybrid optimal-control and Shinnar-Le-Roux method, a quasi-adiabatic RF pulse was designed for the dual-saturation of PCr and Pi to enable determination of total ATP utilisation. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before application to perfused rat hearts at 11.7 Tesla. Results: The quasi-adiabatic pulse was insensitive to a $>2.5$-fold variation in $B_1$, producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective $B_1$. This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux ($4.24\pm0.8$ mM/s, SEM) was not significantly different from degradation flux ($6.88\pm2$ mM/s, $p=0.06$) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi-to-ATP measurement that may explain a trend suggesting a possible imbalance. Conclusion: This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.Comment: 26 pages, Accepted at Magnetic Resonance in Medicine, 24/11/2020 [This version post reviews

Evaluation of Acute Supplementation With the Ketone Ester ( R )-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle 31 P Magnetic Resonance Spectroscopy

In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23–70 years for cardiac 31P-MRS, and 16 aged 60–75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (−28.8%, p ≪ 0.001; −28.2%, p = 0.02; and −49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in 31P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97\ub71 (95% UI 95\ub78-98\ub71) in Iceland, followed by 96\ub76 (94\ub79-97\ub79) in Norway and 96\ub71 (94\ub75-97\ub73) in the Netherlands, to values as low as 18\ub76 (13\ub71-24\ub74) in the Central African Republic, 19\ub70 (14\ub73-23\ub77) in Somalia, and 23\ub74 (20\ub72-26\ub78) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91\ub75 (89\ub71-93\ub76) in Beijing to 48\ub70 (43\ub74-53\ub72) in Tibet (a 43\ub75-point difference), while India saw a 30\ub78-point disparity, from 64\ub78 (59\ub76-68\ub78) in Goa to 34\ub70 (30\ub73-38\ub71) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4\ub78-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20\ub79-point to 17\ub70-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17\ub72-point to 20\ub74-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view-and subsequent provision-of quality health care for all populations