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Background: Magnetic resonance imaging (MRI) quantification of intramuscular fat accumulation is a responsive biomarker in neuromuscular diseases. Despite emergence of automated methods, manual muscle segmentation remains an essential foundation. We aimed to develop a training programme for new observers to demonstrate competence in lower limb muscle segmentation and establish reliability benchmarks for future human observers and machine learning segmentation packages. Methods: The learning phase of the training programme comprised a training manual, direct instruction, and eight lower limb MRI scans with reference standard large and small regions of interest (ROIs). The assessment phase used test–retest scans from two patients and two healthy controls. Interscan and interobserver reliability metrics were calculated to identify underperforming outliers and to determine competency benchmarks. Results: Three experienced observers undertook the assessment phase, whilst eight new observers completed the full training programme. Two of the new observers were identified as underperforming outliers, relating to variation in size or consistency of segmentations; six had interscan and interobserver reliability equivalent to those of experienced observers. The calculated benchmark for the Sørensen-Dice similarity coefficient between observers was greater than 0.87 and 0.92 for individual thigh and calf muscles, respectively. Interscan and interobserver reliability were significantly higher for large than small ROIs (all p < 0.001). Conclusions: We developed, implemented, and analysed the first formal training programme for manual lower limb muscle segmentation. Large ROI showed superior reliability to small ROI for fat fraction assessment. Relevance statement: Observers competent in lower limb muscle segmentation are critical to application of quantitative muscle MRI biomarkers in neuromuscular diseases. This study has established competency benchmarks for future human observers or automated segmentation methods. Key points: • Observers competent in muscle segmentation are critical for quantitative muscle MRI biomarkers. • A training programme for muscle segmentation was undertaken by eight new observers. • We established competency benchmarks for future human observers or automated segmentation methods. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patent foramen ovale (PFO)is associated with cryptogenic stroke, especially in young adults. Transcranial Doppler (TCD) ultrasound is used as a screening tool before transesophageal echocardiography (TEE). However, the use of Valsalva maneuver (VM) to identify a right‐to‐left‐shunt underlies interindividual variability. Here, we aimed to assess whether a pressure‐controlled standardization of VM is useful to estimate PFO size. Methods: We included patients aged 18–80 years with a PFO according to TEE. Subjects underwent TCD with microembolic signals (MES) counted under four pressure conditions (i.e., at rest, 15 mbar, 40 mbar, and maximum expiratory pressure). Findings were correlated with TEE‐based PFO size. The predictive value of TCD at rest and VM‐based TCD for PFO size estimation was assessed by stepwise multivariate linear regression models and multiple cross‐tab‐analyses. Results: We screened 203 subjects after a cerebrovascular event, of which 78 (48 males [61.5%], median age 55 years [22–80]) with PFO were included. We found an association between MES count and expiratory pressure (p <.001). Predefined MES count categories at TCD pressure conditions correlated significantly with PFO size measured by TEE. We propose a PFO size estimation model based on TCD at rest and under VM, which classified PFO size correctly in 64.1% with the highest accuracy for small PFOs. Conclusion: Our data provide evidence that TCD with step‐wise barometric standardization allows an estimation of PFO size with good accuracy. Though TCD will not replace TEE in future, this might be of clinical value in circumstances where TEE cannot be easily performed. [ABSTRACT FROM AUTHOR]

Background: The anti-inflammatory and antiproliferative agent curcumin has poor oral bioavailability and solubility in plasma. Liposomal formulations have therefore been developed, but the toxicity of these preparations is not yet established. We investigated the influence of free and liposomally formulated curcumin on human red blood cell (RBC) morphology in vitro., Materials and Methods: EDTA-buffered whole blood from two healthy individuals was incubated with different concentrations (1, 10, 100 μg/ml) of free or liposomal curcumin. RBC morphology and mean cellular volume (MCV) were examined at up to 4 hours of incubation., Results: Dose-dependent echinocyte formation was observed after incubation with free, and liposomal curcumin, with a threshold concentration of 10 μg/ml and peak effect after 30 minutes. A concomitant increase in mean cellular volume was detectable., Conclusion: Curcumin and liposomal curcumin cause dose-dependent changes in the shape of RBCs. This effect may represent an early sign of dose-limiting toxicity following intravenous administration.