High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades.

BACKGROUND: Clinical imaging tools to probe aggressiveness of renal masses are lacking, and T2-weighted imaging as an integral part of magnetic resonance imaging protocol only provides qualitative information. We developed high-resolution and accelerated T2 mapping methods based on echo merging and using k-t undersampling and reduced flip angles (TEMPURA) and tested their potential to quantify differences between renal tumour subtypes and grades. METHODS: Twenty-four patients with treatment-naïve renal tumours were imaged: seven renal oncocytomas (RO); one eosinophilic/oncocytic renal cell carcinoma; two chromophobe RCCs (chRCC); three papillary RCCs (pRCC); and twelve clear cell RCCs (ccRCC). Median, kurtosis, and skewness of T2 were quantified in tumours and in the normal-adjacent kidney cortex and were compared across renal tumour subtypes and between ccRCC grades. RESULTS: High-resolution TEMPURA depicted the tumour structure at improved resolution compared to conventional T2-weighted imaging. The lowest median T2 values were present in pRCC (high-resolution, 51 ms; accelerated, 45 ms), which was significantly lower than RO (high-resolution; accelerated, p = 0.012) and ccRCC (high-resolution, p = 0.019; accelerated, p = 0.008). ROs showed the lowest kurtosis (high-resolution, 3.4; accelerated, 4.0), suggestive of low intratumoural heterogeneity. Lower T2 values were observed in higher compared to lower grade ccRCCs (grades 2, 3 and 4 on high-resolution, 209 ms, 151 ms, and 106 ms; on accelerated, 172 ms, 160 ms, and 102 ms, respectively), with accelerated TEMPURA showing statistical significance in comparison (p = 0.037). CONCLUSIONS: Both high-resolution and accelerated TEMPURA showed marked potential to quantify differences across renal tumour subtypes and between ccRCC grades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741426 . Registered on 13 November 2018. RELEVANCE STATEMENT: The newly developed T2 mapping methods have improved resolution, shorter acquisition times, and promising quantifiable readouts to characterise incidental renal masses.

Detection of congenital heart disease by neonatologist performed cardiac ultrasound in preterm infants.

OBJECTIVE: We aimed to assess the frequency of de novo congenital heart disease (CHD) detection via neonatologist-performed cardiac ultrasounds (NPCU) in premature infants born at <30 weeks of gestation. STUDY DESIGN: In this cross-sectional study (2004-2023) clinicians completing NPCU flagged de novo suspected CHD. All flagged NPCUs were cross-checked with cardiologists to confirm CHD diagnosis. RESULTS: There were 2088 out of 3739 infants (56%) with at least one NPCU; 294 (14%) with cardiology referral. CHD diagnosis was confirmed in 109 of the 2088 (5.2%) infants. All major and critical CHD on NPCU imaging were suspected during NPCU and had prompt referral to the cardiology department. CONCLUSION: De novo presentation of significant CHD continues to occur in the preterm population, emphasizing the need for recognizing CHD during NPCU. Optimizing NPCU training may benefit patients with early cardiology referral and review.

23Na MRI: inter-reader reproducibility of normal fibroglandular sodium concentration measurements at 3 T.

BACKGROUND: To study the reproducibility of 23Na magnetic resonance imaging (MRI) measurements from breast tissue in healthy volunteers. METHODS: Using a dual-tuned bilateral 23Na/1H breast coil at 3-T MRI, high-resolution 23Na MRI three-dimensional cones sequences were used to quantify total sodium concentration (TSC) and fluid-attenuated sodium concentration (FASC). B1-corrected TSC and FASC maps were created. Two readers manually measured mean, minimum and maximum TSC and mean FASC values using two sampling methods: large regions of interest (LROIs) and small regions of interest (SROIs) encompassing fibroglandular tissue (FGT) and the highest signal area at the level of the nipple, respectively. The reproducibility of the measurements and correlations between density, age and FGT apparent diffusion coefficient (ADC) values were evaluatedss. RESULTS: Nine healthy volunteers were included. The inter-reader reproducibility of TSC and FASC using SROIs and LROIs was excellent (intraclass coefficient range 0.945-0.979, p < 0.001), except for the minimum TSC LROI measurements (p = 0.369). The mean/minimum LROI TSC and mean LROI FASC values were lower than the respective SROI values (p < 0.001); the maximum LROI TSC values were higher than the SROI TSC values (p = 0.009). TSC correlated inversely with age but not with FGT ADCs. The mean and maximum FGT TSC and FASC values were higher in dense breasts in comparison to non-dense breasts (p < 0.020). CONCLUSIONS: The chosen sampling method and the selected descriptive value affect the measured TSC and FASC values, although the inter-reader reproducibility of the measurements is in general excellent. RELEVANCE STATEMENT: 23Na MRI at 3 T allows the quantification of TSC and FASC sodium concentrations. The sodium measurements should be obtained consistently in a uniform manner. KEY POINTS: • 23Na MRI allows the quantification of total and fluid-attenuated sodium concentrations (TSC/FASC). • Sampling method (large/small region of interest) affects the TSC and FASC values. • Dense breasts have higher TSC and FASC values than non-dense breasts. • The inter-reader reproducibility of TSC and FASC measurements was, in general, excellent. • The results suggest the importance of stratifying the sodium measurements protocol.

Endotracheal epinephrine at standard versus high dose for resuscitation of asystolic newborn lambs.

INTRODUCTION: Endotracheal (ET) epinephrine administration is an option during neonatal resuscitation, if the preferred intravenous (IV) route is unavailable. OBJECTIVES: We assessed whether endotracheal epinephrine achieved return of spontaneous circulation (ROSC), and maintained physiological stability after ROSC, at standard and higher dose, in severely asphyxiated newborn lambs. METHODS: Near-term fetal lambs were asphyxiated until asystole. Resuscitation was commenced with ventilation and chest compressions. Lambs were randomly allocated to: IV Saline placebo (5 ml/kg), IV Epinephrine (20 micrograms/kg), Standard-dose ET Epinephrine (100 micrograms/kg), and High-dose ET Epinephrine (1 mg/kg). After three allocated treatment doses, rescue IV Epinephrine was administered if ROSC had not occurred. Lambs achieving ROSC were monitored for 60 minutes. Brain histology was assessed for microbleeds. RESULTS: ROSC in response to allocated treatment (without rescue IV Epinephrine) occurred in 1/6 Saline, 9/9 IV Epinephrine, 0/9 Standard-dose ET Epinephrine, and 7/9 High-dose ET Epinephrine lambs respectively. Blood pressure during CPR increased after treatment with IV Epinephrine and High-dose ET Epinephrine, but not Saline or Standard-dose ET Epinephrine. After ROSC, both ET Epinephrine groups had lower pH, higher lactate, and higher blood pressure than the IV Epinephrine group. Cortex microbleeds were more frequent in High-dose ET Epinephrine lambs (8/8 lambs examined, versus 3/8 in IV Epinephrine lambs). CONCLUSIONS: The currently recommended dose of ET Epinephrine was ineffective in achieving ROSC. Without convincing clinical or preclinical evidence of efficacy, use of ET Epinephrine at this dose may not be appropriate. High-dose ET Epinephrine requires further evaluation before clinical translation.

Do electromagnetic fields from subsea power cables effect benthic elasmobranch behaviour? A risk-based approach for the Dutch Continental Shelf.

Subsea power cables cause electromagnetic fields (EMFs) into the marine environment. Elasmobranchs (rays, skates, sharks) are particularly sensitive to EMFs as they use electromagnetic-receptive sensory systems for orientation, navigation, and locating conspecifics or buried prey. Cables may intersect with egg laying sites, mating, pupping, and nursery grounds, foraging habitat and migration routes of elasmobranchs and the effects of encountering EMFs on species of elasmobranchs are largely unknown. Demonstrated behavioural effects are attraction, disturbance and indifference, depending on EMF characteristics, exposed life stage, exposure level and duration. We estimated exposure levels of elasmobranchs to subsea power cable EMFs, based on modelled magnetic fields in the Dutch Continental Shelf and compared these to reported elasmobranch sensory sensitivity ranges and experimental effect levels. We conclude that the risk from subsea power cables has a large uncertainty and varies per life stage and species ecology. Based on estimated no-observed effect levels (from 10-3 to 10-1 µT) we discuss what will probably be the most affected species and life stage for six common benthic elasmobranchs in the Southern North Sea. We then identify critical knowledge gaps for reducing the uncertainty in the risk assessments for EMFs effects on benthic elasmobranchs.

Assessing the influence of abdominal compression on time to return of circulation during resuscitation of asphyxiated newborn lambs: a randomised preclinical study.

OBJECTIVE: During neonatal resuscitation, the return of spontaneous circulation (ROSC) can be achieved using epinephrine which optimises coronary perfusion by increasing diastolic pressure. Abdominal compression (AC) applied during resuscitation could potentially increase diastolic pressure and therefore help achieve ROSC. We assessed the use of AC during resuscitation of asystolic newborn lambs, with and without epinephrine. METHODS: Near-term fetal lambs were instrumented for physiological monitoring and after delivery, asphyxiated until asystole. Resuscitation was commenced with ventilation followed by chest compressions. Lambs were randomly allocated to: intravenous epinephrine (20 µg/kg, n=9), intravenous epinephrine+continuous AC (n=8), intravenous saline placebo (5 mL/kg, n=6) and intravenous saline+AC (n=9). After three allocated treatment doses, rescue intravenous epinephrine was administered if ROSC had not occurred. Time to achieve ROSC was the primary outcome. Lambs achieving ROSC were ventilated and monitored for 60 min before euthanasia. Brain histology was assessed for micro-haemorrhage. RESULTS: Use of AC did not influence mean time to achieve ROSC (epinephrine lambs 177 s vs epinephrine+AC lambs 179 s, saline lambs 602 s vs saline+AC lambs 585 s) or rate of ROSC (nine of nine lambs, eight of eight lambs, one of six lambs and two of eight lambs, respectively). Application of AC was associated with higher diastolic blood pressure (mean value >10 mm Hg), mean and systolic blood pressure and carotid blood flow during resuscitation. Cortex and deep grey matter micro-haemorrhage was more frequent in AC lambs. CONCLUSION: Use of AC during resuscitation increased diastolic blood pressure, but did not impact time to ROSC.

'Scaling up' our understanding of environmental effects of marine renewable energy development from single devices to large-scale commercial arrays.

Global expansion of marine renewable energy (MRE) technologies is needed to help address the impacts of climate change, to ensure a sustainable transition from carbon-based energy sources, and to meet national energy security needs using locally-generated electricity. However, the MRE sector has yet to realize its full potential due to the limited scale of device deployments (i.e., single devices or small demonstration-scale arrays), and is hampered by various factors including uncertainty about environmental effects and how the magnitude of these effects scale with an increasing number of devices. This paper seeks to expand our understanding of the environmental effects of MRE arrays using existing frameworks and through the adaptation and application of cumulative environmental effects terminology to key stressor-receptor interactions. This approach facilitates the development of generalized concepts for the scaling of environmental effects for key stressor-receptor interactions, identifying high priority risks and revealing knowledge gaps that require investigation to aid expansion of the MRE sector. Results suggest that effects of collision risk for an array may be additive, antagonistic, or synergistic, but are likely dependent on array location and configuration. Effects of underwater noise are likely additive as additional devices are deployed in an array, while the effects of electromagnetic fields may be dominant, additive, or antagonistic. Changes to benthic habitats are likely additive, but may be dependent on array configuration and could be antagonistic or synergistic at the ecosystem scale. Effects of displacement, entanglement, and changes to oceanographic systems for arrays are less certain because little information is available about effects at the current scale of MRE development.

Open source code for the generation of digital reference objects for dynamic contrast-enhanced MRI analysis software validation.

OBJECTIVES: Dynamic contrast-enhanced MR images can be analyzed through the application of a wide range of kinetic models. This process is prone to variability and a lack of standardization that can affect the measured metrics. There is a need for customized digital reference objects (DROs) for the validation of DCE-MRI software packages that undertake kinetic model analysis. DROs are currently available only for a small subset of the kinetic models commonly applied to DCE-MRI data. This work aimed to address this gap. METHODS: Code was written in the MATLAB programming environment to generate customizable DROs. This modular code allows the insertion of a plug-in to describe the kinetic model to be tested. We input our generated DROs into three commercial and open-source analysis packages and assessed the agreement of kinetic model parameter values output with the 'ground-truth' values used in the DRO generation. RESULTS: For the five kinetic models tested, the concordance correlation coefficient values were >98%, indicating excellent agreement of the results with 'ground-truth'. CONCLUSIONS: Testing our DROs on three independent software packages produced concordant results, strongly suggesting our DRO generation code is correct. This implies that our DROs can be used to validate other third party software for the kinetic model analysis of DCE-MRI data. ADVANCES IN KNOWLEDGE: This work extends published work of others to allow customized generation of test objects for any applied kinetic model and allows the incorporation of B1 mapping into the DRO for application at higher field strengths.

Lung aeration reduces blood pressure surges caused by umbilical cord milking in preterm lambs.

Background: Umbilical cord milking (UCM) at birth causes surges in arterial blood pressure and blood flow to the brain, which may explain the high risk of intraventricular haemorrhage (IVH) in extremely preterm infants receiving UCM. This high risk of IVH has not been reported in older infants. Objective: We hypothesized that lung aeration before UCM, reduces the surge in blood pressure and blood flow induced by UCM. Methods: At 126 days' gestation, fetal lambs (N = 8) were exteriorised, intubated and instrumented to measure umbilical, pulmonary, cerebral blood flows, and arterial pressures. Prior to ventilation onset, the umbilical cord was briefly (2-3 s) occluded (8 times), which was followed by 8 consecutive UCMs when all physiological parameters had returned to baseline. Lambs were then ventilated. After diastolic pulmonary blood flow markedly increased in response to ventilation, the lambs received a further 8 consecutive UCMs. Ovine umbilical cord is shorter than the human umbilical cord, with ∼10 cm available for UCMs. Therefore, 8 UCMs/occlusions were done to match the volume reported in the human studies. Umbilical cord clamping occurred after the final milk. Results: Both umbilical cord occlusions and UCM caused significant increases in carotid arterial blood flow and pressure. However, the increases in systolic and mean arterial blood pressure (10 ± 3 mmHg vs. 3 ± 2 mmHg, p = 0.01 and 10 ± 4 mmHg vs. 6 ± 2 mmHg, p = 0.048, respectively) and carotid artery blood flow (17 ± 6 ml/min vs. 10 ± 6 ml/min, p = 0.02) were significantly greater when UCM occurred before ventilation onset compared with UCM after ventilation. Conclusions: UCM after ventilation onset significantly reduces the increases in carotid blood flow and blood pressure caused by UCM.

Lesion-specific 3D-printed moulds for image-guided tissue multi-sampling of ovarian tumours: A prospective pilot study.

Background: High-Grade Serous Ovarian Carcinoma (HGSOC) is the most prevalent and lethal subtype of ovarian cancer, but has a paucity of clinically-actionable biomarkers due to high degrees of multi-level heterogeneity. Radiogenomics markers have the potential to improve prediction of patient outcome and treatment response, but require accurate multimodal spatial registration between radiological imaging and histopathological tissue samples. Previously published co-registration work has not taken into account the anatomical, biological and clinical diversity of ovarian tumours. Methods: In this work, we developed a research pathway and an automated computational pipeline to produce lesion-specific three-dimensional (3D) printed moulds based on preoperative cross-sectional CT or MRI of pelvic lesions. Moulds were designed to allow tumour slicing in the anatomical axial plane to facilitate detailed spatial correlation of imaging and tissue-derived data. Code and design adaptations were made following each pilot case through an iterative refinement process. Results: Five patients with confirmed or suspected HGSOC who underwent debulking surgery between April and December 2021 were included in this prospective study. Tumour moulds were designed and 3D-printed for seven pelvic lesions, covering a range of tumour volumes (7 to 133 cm3) and compositions (cystic and solid proportions). The pilot cases informed innovations to improve specimen and subsequent slice orientation, through the use of 3D-printed tumour replicas and incorporation of a slice orientation slit in the mould design, respectively. The overall research pathway was compatible with implementation within the clinically determined timeframe and treatment pathway for each case, involving multidisciplinary clinical professionals from Radiology, Surgery, Oncology and Histopathology Departments. Conclusions: We developed and refined a computational pipeline that can model lesion-specific 3D-printed moulds from preoperative imaging for a variety of pelvic tumours. This framework can be used to guide comprehensive multi-sampling of tumour resection specimens.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

Protocol for a Nested, Retrospective Study of the Australian Placental Transfusion Study Cohort.

Background Neonates, particularly if born preterm or with congenital anomalies, are among the pediatric patients most likely to need blood transfusion. However, they are also particularly vulnerable to adverse consequences of blood transfusion. Aiming to clamp the umbilical cord for at least a minute after birth is a simple safe procedure that is being increasingly adopted worldwide, although may be associated with increased rates of polycythemia and jaundice. It may also reduce the proportion of preterm babies who need a blood transfusion. The mechanisms for this are not fully understood. Potential mechanisms could include an increased volume of blood transfusion from the placenta to the baby after birth, and an overall reduction in the severity of illness in the first weeks after birth, which could lead to fewer blood tests and greater tolerance of anemia, or enhanced erythropoiesis. Objectives To investigate the mechanism behind the reduced need for blood transfusions after deferral of cord clamping. Methodology This protocol outlines the methods and data analysis plan for a study using nested retrospective data from a large randomized trial combined with additional data collected from patient medical and pathology records. The additional data items to be collected all relate to the receipt of transfusion and the factors that affect the risk for transfusion in preterm babies. The analysis will include all randomized babies from Australia and New Zealand for whom data are available. Causal mediation analysis is planned to estimate the effects of mediators on the relationship between the timing of cord clamping and the need for blood transfusion. The analysis is designed to discern whether initial severity of illness or the magnitude of placental transfusion mediates red blood cell transfusion dependence. Anticipated outcomes and dissemination We expect the study will identify potential strategies for reducing blood transfusions and associated negative outcomes in preterm infants. This will be relevant to researchers, clinicians, and parents. The results will be disseminated through publications, presentations, and inclusion in evidence-based guidelines.

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.

Particle motion observed during offshore wind turbine piling operation.

Measurement of particle motion from an offshore piling event in the North was conducted to determine noise levels. For this purpose, a bespoken sensor was developed that was both autonomous and sensitive up to 2 kHz. The measurement was undertaken both for unmitigated and mitigated piling. Three different types of mitigation techniques were employed. The acceleration zero-to-peak values and the acceleration exposure levels were determined. The results show that inferred mitigation techniques reduce the levels significantly as well as decreases the power content of higher frequencies. These results suggest that mitigation has an effect and will reduce the effect ranges of impact on marine species.

Demonstrating the Potential of Using Bio-Based Sustainable Polyester Blends for Bone Tissue Engineering Applications.

Healthcare applications are known to have a considerable environmental impact and the use of bio-based polymers has emerged as a powerful approach to reduce the carbon footprint in the sector. This research aims to explore the suitability of using a new sustainable polyester blend (Floreon™) as a scaffold directed to aid in musculoskeletal applications. Musculoskeletal problems arise from a wide range of diseases and injuries related to bones and joints. Specifically, bone injuries may result from trauma, cancer, or long-term infections and they are currently considered a major global problem in both developed and developing countries. In this work we have manufactured a series of 3D-printed constructs from a novel biopolymer blend using fused deposition modelling (FDM), and we have modified these materials using a bioceramic (wollastonite, 15% w/w). We have evaluated their performance in vitro using human dermal fibroblasts and rat mesenchymal stromal cells. The new sustainable blend is biocompatible, showing no differences in cell metabolic activity when compared to PLA controls for periods 1-18 days. FloreonTM blend has proven to be a promising material to be used in bone tissue regeneration as it shows an impact strength in the same range of that shown by native bone (just under 10 kJ/m2) and supports an improvement in osteogenic activity when modified with wollastonite.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

Standalone portable xenon-129 hyperpolariser for multicentre clinical magnetic resonance imaging of the lungs.

OBJECTIVES: Design and build a portable xenon-129 (129Xe) hyperpolariser for clinically accessible 129Xe lung MRI. METHODS: The polariser system consists of six main functional components: (i) a laser diode array and optics; (ii) a B0 coil assembly; (iii) an oven containing an optical cell; (iv) NMR and optical spectrometers; (v) a gas-handling manifold; and (vi) a cryostat within a permanent magnet. All components run without external utilities such as compressed air or three-phase electricity, and require just three mains sockets for operation. The system can be manually transported in a lightweight van and rapidly installed on a small estates footprint in a hospital setting. RESULTS: The polariser routinely provides polarised 129Xe for routine clinical lung MRI. To test the concept of portability and rapid deployment, it was transported 200 km, installed at a hospital with no previous experience with the technology and 129Xe MR images of a diagnostic quality were acquired the day after system transport and installation. CONCLUSION: This portable 129Xe hyperpolariser system could form the basis of a cost-effective platform for wider clinical dissemination and multicentre evaluation of 129Xe lung MR imaging. ADVANCES IN KNOWLEDGE: Our work successfully demonstrates the feasibility of multicentre clinical 129Xe MRI with a portable hyperpolariser system.

Single versus continuous sustained inflations during chest compressions and physiological-based cord clamping in asystolic lambs.

BACKGROUND: The feasibility and benefits of continuous sustained inflations (SIs) during chest compressions (CCs) during delayed cord clamping (physiological-based cord clamping; PBCC) are not known. We aimed to determine whether continuous SIs during CCs would reduce the time to return of spontaneous circulation (ROSC) and improve post-asphyxial blood pressures and flows in asystolic newborn lambs. METHODS: Fetal sheep were surgically instrumented immediately prior to delivery at ~139 days' gestation and asphyxia induced until lambs reached asystole. Lambs were randomised to either immediate cord clamping (ICC) or PBCC. Lambs then received a single SI (SIsing; 30 s at 30 cmH2O) followed by intermittent positive pressure ventilation, or continuous SIs (SIcont: 30 s duration with 1 s break). We thus examined 4 groups: ICC +SIsing, ICC +SIcont, PBCC +SIsing, and PBCC +SIcont. Chest compressions and epinephrine administration followed international guidelines. PBCC lambs underwent cord clamping 10 min after ROSC. Physiological and oxygenation variables were measured throughout. RESULTS: The time taken to achieve ROSC was not different between groups (mean (SD) 4.3±2.9 min). Mean and diastolic blood pressure was higher during chest compressions in PBCC lambs compared with ICC lambs, but no effect of SIs was observed. SIcont significantly reduced pulmonary blood flow, diastolic blood pressure and oxygenation after ROSC compared with SIsing. CONCLUSION: We found no significant benefit of SIcont over SIsing during CPR on the time to ROSC or on post-ROSC haemodynamics, but did demonstrate the feasibility of continuous SIs during advanced CPR on an intact umbilical cord. Longer-term studies are recommended before this technique is used routinely in clinical practice.