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Background: Although several studies have evaluated dynamic contrast-enhanced (DCE) MRI in the orbit, showing its utility when detecting and diagnosing orbital lesions, none have evaluated the pharmacokinetic models., Purpose: To provide a quality-based pharmacokinetic model selection for characterizing orbital lesions using DCE-MRI at 3.0T., Study Type: Prospective., Population: From December 2015 to April 2017, 151 patients with an orbital lesion underwent MRI prior to surgery, including a high temporal resolution DCE sequence, divided into one training and one test dataset with 100 and 51 patients, respectively., Field Strength/sequence: 3T/DCE., Assessment: Six different pharmacokinetic models were tested., Statistical Tests: Univariate and multivariate analyses were performed using Wilcoxon-2-sample tests and a logistic regression to compare parameters between malignant and benign tumors for each pharmacokinetic model for the whole cohort. Receiver operating characteristic (ROC) curve analyses were performed on the training dataset to determine area under curve (AUC) and optimal cutoff values for each pharmacokinetic model, then validated on the test dataset to calculate sensitivity, specificity, and accuracy., Results: Regardless of the model, tissue blood flow and tissue blood volume values were significantly higher in malignant vs. benign lesions: 103.8-195.1 vs. 65-113.8, P [<10 -4 -2.10 -4 ] and 21.3-36.9 vs. 15.6-33.6, P [<10 -4 -0.03] respectively. Extracellular volume fraction and permeability-surface area product or transfer constant appeared to be less relevant: 17.3-27.5 vs. 22.8-28.2, P [0.01-0.7], 1.7-4.9, P [0.2-0.9] and 9.5-38.8 vs. 8.1-22.8, P [<10 -4 -0.6], respectively. ROC curves showed no significant differences in AUC between the different models. The two-compartment exchange (2CX) model ranked first for quality., Data Conclusion: DCE MRI pharmacokinetic model-derived parameters appeared to be useful for discriminating benign from malignant orbital lesions. The 2CX model provided the best quality of modeling and should be recommended. Perfusion-related DCE parameters appeared to be significantly more relevant to the diagnostic process. Level of Evidence 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1514-1525., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: There is no consensus regarding the best MR imaging sequence for detecting MS lesions. The aim of our study was to assess the diagnostic value of optimized 3D-FLAIR in the detection of infratentorial MS lesions compared with an axial T2-weighted imaging, a 3D-FLAIR with factory settings, and a 3D double inversion recovery sequence., Materials and Methods: In this prospective study, 27 patients with confirmed MS were included. Two radiologists blinded to clinical data independently read the following sequences: axial T2WI, 3D double inversion recovery, standard 3D-FLAIR with factory settings, and optimized 3D-FLAIR. The main judgment criterion was the overall number of high-signal-intensity lesions in the posterior fossa; secondary objectives were the assessment of the reading confidence and the measurement of the contrast. A nonparametric Wilcoxon test was used to compare the MR images., Results: Twenty-two patients had at least 1 lesion in the posterior fossa. The optimized FLAIR sequence detected significantly more posterior fossa lesions than any other sequence: 7.5 versus 5.8, 4.8, and 4.1 ( P values of .04, .03, and .03) with the T2WI, the double inversion recovery, and the standard FLAIR, respectively. The reading confidence index was significantly higher with the optimized FLAIR, and the contrast was significantly higher with the optimized FLAIR than with the standard FLAIR and the double inversion recovery., Conclusions: An optimized 3D-FLAIR sequence improved posterior fossa lesion detection in patients with MS., (© 2019 by American Journal of Neuroradiology.)

Praziquantel (PZQ) is the first line drug for the treatment of human Schistosoma spp. worm infections. However, it suffers from low activity towards immature stages of the worm, and its prolonged use induces resistance/tolerance. During the last 40 years, 263 PZQ analogues have been synthesized and tested against Schistosoma spp. worms, but less than 10% of them showed significant activity. Here, we propose a rationalization of the chemical space of the PZQ derivatives by a ligand-based approach. First, we constructed an in-house database with all PZQ derivatives available in the literature. This analysis shows a high heterogeneity in the data. Fortunately, all studies include PZQ as a reference, permitting the classification of compounds into three classes according to their activities. Models involving ligand-based pharmacophore and logistic regression were performed. Five physicochemical parameters were identified as the best to explain the biological activity. In the end, we proposed new PZQ derivatives with modifications at positions 1 and 7, we analysed them with our models, and we observed that they can be more active than the previously synthesized derivatives. The main goal of this work was to conduct the most valuable meta-pharmacometrics/pharmacoinformatics analysis with all Praziquantel medicinal chemistry data available in the literature.

Background and Purpose: Magnetic Resonance Imaging is the modality of choice to detect spinal cord lesions in patients with Multiple Sclerosis (MS). However, this imaging is challenging. New sequences such as phase-sensitive inversion recovery have been developed to improve detection. Our aim was to compare a 3D phase-sensitive inversion recovery and a conventional imaging dataset including postcontrast T2WI and T1WI to detect MS spinal cord lesions., Materials and Methods: This retrospective single-center study included 100 consecutive patients with MS (mean age, 41 years) from January 2015 to June 2016. One senior neuroradiologist and 1 junior radiologist blinded to clinical data checked for new spinal cord lesions, individually analyzing conventional and 3D phase-sensitive inversion recovery datasets separately, placing a 3-week delay between the 2 readings. A consensus reading was done with a third senior neuroradiologist. A Wilcoxon test was used to compare the 2 imaging datasets. Intra- and interobserver agreement was assessed by the κ coefficient., Results: 3D phase-sensitive inversion recovery detected significantly more lesions than conventional imaging (480 versus 168, P < .001). Eleven patients had no detected lesions on T2WI, whereas 3D phase-sensitive inversion recovery detected at least 1 lesion. All postcontrast T1WI enhancing lesions were also visible on 3D phase-sensitive inversion recovery. The signal-to-noise ratio was significantly higher using 3D phase-sensitive inversion recovery (0.63 versus 0.46, P = .03). Mean reading confidence was significantly higher using 3D phase-sensitive inversion recovery. Inter- and intraobserver agreement was good for both datasets., Conclusions: Our study showed that 3D phase-sensitive inversion recovery significantly improved detection of cervical spinal cord lesions, including both enhancing and nonenhancing lesions in patients with MS., (© 2019 by American Journal of Neuroradiology.)

Objective: Given the impact of individuals' habits on health, it is important to study how behaviors can become habitual. Cortisol has been well documented to have a role in habit formation. This study aimed to elucidate the influence of the circadian rhythm of cortisol on habit formation in a real-life setting., Method: Forty-eight students were followed for 90 days during which they attempted to adopt a health behavior (psoas iliac stretch). They were randomly assigned to perform the stretch either upon waking in the morning, when cortisol concentrations are high, or before evening bedtime, when cortisol levels approach the nadir. A smartphone application was used to assess the Self-Report Behavioural Automaticity Index every day and to provide reminders for salivary measurements every 30 days. The speed of the health habit formation process was calculated by modeling the learning curves., Results: Extrapolation of the curves indicated that the morning group achieved automaticity at an earlier time point (105.95 days) than did the evening group (154.01 days). In addition, the cortisol level during the performance of the health behavior was identified as a significant mediator of the time point when the health behavior became habitual., Conclusion: The present findings suggest that the time course of the development of healthy habits depends on the time of the day and that the effect is mediated through diurnal variation in cortisol levels. Future studies are now needed to determine to what extent cortisol rhythmicity can help individuals to adopt new health behaviors. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)