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Phaeochromocytomas (PCC) and paragangliomas (PGL), cumulatively referred to as PPGLs, are neuroendocrine tumours arising from neural crest-derived cells in the sympathetic and parasympathetic nervous systems. Predicting future tumour behaviour and the likelihood of metastatic disease remains problematic as genotype-phenotype correlations are limited, the disease has variable penetrance and, to date, no reliable molecular, cellular or histological markers have emerged. Tumour metabolism quantification can be considered as a method to delineating tumour aggressiveness by utilising hyperpolarised 13 C-MR (HP-MR). The technique may provide an opportunity to non-invasively characterise disease behaviour. Here, we present the first instance of the analysis of PPGL metabolism via HP-MR in a single case., (© 2023 The Authors. Published by the British Institute of Radiology.)

Hyperpolarised 13 C MRI (HP-MRI) is a novel imaging technique that allows real-time analysis of metabolic pathways in vivo . 1 The technology to conduct HP-MRI in humans has recently become available and is starting to be clinically applied. As knowledge of molecular biology advances, it is increasingly apparent that cancer cell metabolism is related to disease outcomes, with lactate attracting specific attention. 2 Recent reviews of breast cancer screening programs have raised concerns and increased public awareness of over treatment. The scientific community needs to shift focus from improving cancer detection alone to pursuing novel methods of distinguishing aggressive breast cancers from those which will remain indolent. HP-MRI offers the opportunity to identify aggressive tumour phenotypes and help monitor/predict therapeutic response. Here we report one of the first cases of breast cancer imaged using HP-MRI alongside correlative conventional imaging, including breast MRI.

Intratumoral genetic heterogeneity and the role of metabolic reprogramming in renal cell carcinoma (RCC) have been extensively documented. However, the distribution of these metabolic changes within the tissue has not been explored. We report on the first-in-human in vivo non-invasive metabolic interrogation of RCC using hyperpolarized carbon-13 ( 13 C) magnetic resonance imaging (HP-MRI) and describe the validation of in vivo lactate metabolic heterogeneity against multi-regional ex vivo mass spectrometry. HP-MRI provides an in vivo assessment of metabolism and provides a novel opportunity to safely and non-invasively assess cancer heterogeneity.

Background: Endotoxemia is commonly reported in patients receiving haemodialysis and implicated in the pathogenesis of systemic inflammation. The Limulus Amoebocyte Lysate (LAL) assay is the most commonly used blood endotoxin detection assay. Two kinetic variations of the assay are commercially available - the turbidimetric and chromogenic assay, it is unknown which assay is superior for endotoxin detection in uremic patients. Selection of the optimum LAL technique for endotoxin detection in haemodialysis patients is important to further understanding of the sequela of endotoxemia and development of endotoxin-lowering strategies in this population., Method: A turbidimetric and chromogenic LAL assay from the same manufacturer were directly compared. We investigated the ability of both LAL assays to detect endotoxin in uremic plasma. Plasma samples from haemodialysis patients and healthy controls were spiked with endotoxin and percentage spike recovery for the chromogenic and turbidimetric assay was determined. Assay accuracy and precision were compared between both LAL assays., Results: The turbidimetric assay had greater accuracy than the chromogenic assay. Spike recovery was 113.8 % vs. 53.8 % for the turbidimetric and chromogenic assay respectively. Assay bias was higher in the chromogenic assay (-0.384EU/mL vs. 0.011EU/mL). The turbidimetric assay demonstrated greater precision compared to the chromogenic assay. Coefficient of variation ranged from 4.5 to 24.1 % for the turbidimetric assay and 25.8-26.5 % for the chromogenic assay., Conclusion: The study findings suggest that the kinetic turbidimetric LAL assay has greater accuracy and precision than the chromogenic assay and is the optimum LAL technique for endotoxin detection in haemodialysis patients, though these findings should be verified using LAL reagents from other sources.

Aims: Endotoxin detection assays are not validated for use in end-stage kidney disease (ESKD). We investigated the accuracy and precision of the kinetic turbidimetric Limulus amoebocyte lysate (LAL) assay to detect endotoxin in plasma from patients with ESKD. Optimisation of endotoxin recovery from plasma using the detergent Tween 80 was also explored., Methods: Plasma samples from 7 patients with ESKD and 7 healthy subjects were spiked with different concentrations of endotoxin. Repeated measurements for endotoxin at each level of spike were performed to assess the accuracy and precision of spike recovery. Endotoxin recovery in plasma samples diluted in Tween 80 and water was compared., Results: Mean endotoxin spike recovery was 111.6% and 125.2% in ESKD and healthy subjects, respectively. There was no statistical difference in spike recovery between ESKD and healthy plasma. Precision of the LAL assay in plasma spiked with low (0.05 EU/mL) and high (0.5 EU/mL) concentration of endotoxin spikes was 24.1% and 8.9%, respectively. The use of Tween 80 as a diluent for plasma significantly improved spike recovery in ESKD plasma (100.1% vs 70.4%, p<0.001)., Conclusions: The kinetic LAL turbidimetric assay is a valid tool for the detection of blood endotoxin in patients with ESKD, although in blood specimens with low-level endotoxemia (≤0.05 EU/mL) the assay may be less accurate and precise. Tween 80 can be used as a diluent to optimise recovery of endotoxin in ESKD plasma., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)