Intratumoral genetic heterogeneity and the role of metabolic reprogramming in renal cell carcinoma 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 renal cell carcinoma using hyperpolarized carbon-13 (13C) MRI and describe the validation of in vivo lactate metabolic heterogeneity against multi regional ex vivo mass spectrometry. hyperpolarized carbon-13 (13C)-MRI provides an in vivo assessment of metabolism and provides a novel opportunity to safely and non-invasively assess cancer heterogeneity.

Hyperpolarised 13C 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.

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.

Cryotherapy is regularly used in our clinic for treating genital warts. Nitrous oxide was used as the cryogenic gas. Following a health and safety review it was decided to monitor the nitrous oxide levels in the treatment room under different conditions. The Occupational Exposure Standard for nitrous oxide is 100 parts per million (PPM) (8-h time weighted average) and an indicative short-term exposure limit of 300 PPM (15-min reference period). High levels of gas were detected, especially when the exhaust was not vented to the outside. Venting of the gas to the outside could also present a hazard to adjacent areas. The situation was considered to be unacceptable and carbon dioxide was proposed as an alternative. The Occupational Exposure Standard for carbon dioxide is 5000 PPM (8-h time weighted average) and a short-term limit of 15,000 PPM (15-min reference period). Carbon dioxide levels were found to be within the Occupational Exposure Standard. There is no noticeable difference in the cryogenic efficacy of the 2 gases. Carbon dioxide is, therefore, a safer alternative. It also offers significant savings when compared with nitrous oxide.

Cryotherapy is regularly used in our clinic for treating genital warts. Nitrous oxide was used as the cryogenic gas. Following a health and safety review it was decided to monitor the nitrous oxide levels in the treatment room under different conditions. The Occupational Exposure Standard for nitrous oxide is 100 parts per million (PPM) (8-h time weighted average) and an indicative short-term exposure limit of 300 PPM (15-min reference period). High levels of gas were detected, especially when the exhaust was not vented to the outside. Venting of the gas to the outside could also present a hazard to adjacent areas. The situation was considered to be unacceptable and carbon dioxide was proposed as an alternative. The Occupational Exposure Standard for carbon dioxide is 5000 PPM (8-h time weighted average) and a short-term limit of 15,000 PPM (15-min reference period). Carbon dioxide levels were found to be within the Occupational Exposure Standard. There is no noticeable difference in the cryogenic efficacy of the 2 gases. Carbon dioxide is, therefore, a safer alternative. It also offers significant savings when compared with nitrous oxide.