Improving Detection of Multiple Sclerosis Lesions in the Posterior Fossa Using an Optimized 3D-FLAIR Sequence at 3T.

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.

Could we expect new praziquantel derivatives? A meta pharmacometrics/pharmacoinformatics analysis of all antischistosomal praziquantel derivatives found in the literature.

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.

A 3T Phase-Sensitive Inversion Recovery MRI Sequence Improves Detection of Cervical Spinal Cord Lesions and Shows Active Lesions in Patients with Multiple Sclerosis.

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.