BackgroundClinical treatment of cardiac arrhythmia by radiofrequency ablation (RFA) currently lacks quantitative and precise visualization of lesion formation in the myocardium during the procedure. This study aims at evaluating thermal dose (TD) imaging obtained from real-time magnetic resonance (MR) thermometry on the heart as a relevant indicator of the thermal lesion extent.MethodsMR temperature mapping based on the Proton Resonance Frequency Shift (PRFS) method was performed at 1.5 T on the heart, with 4 to 5 slices acquired per heartbeat. Respiratory motion was compensated using navigator-based slice tracking. Residual in-plane motion and related magnetic susceptibility artifacts were corrected online. The standard deviation of temperature was measured on healthy volunteers (N = 5) in both ventricles. On animals, the MR-compatible catheter was positioned and visualized in the left ventricle (LV) using a bSSFP pulse sequence with active catheter tracking. Twelve MR-guided RFA were performed on three sheep in vivo at various locations in left ventricle (LV). The dimensions of the thermal lesions measured on thermal dose images, on 3D T1-weighted (T1-w) images acquired immediately after the ablation and at gross pathology were correlated.ResultsMR thermometry uncertainty was 1.5 °C on average over more than 96% of the pixels covering the left and right ventricles, on each volunteer. On animals, catheter repositioning in the LV with active slice tracking was successfully performed and each ablation could be monitored in real-time by MR thermometry and thermal dosimetry. Thermal lesion dimensions on TD maps were found to be highly correlated with those observed on post-ablation T1-w images (R = 0.87) that also correlated (R = 0.89) with measurements at gross pathology.ConclusionsQuantitative TD mapping from real-time rapid CMR thermometry during catheter-based RFA is feasible. It provides a direct assessment of the lesion extent in the myocardium with precision in the range of one millimeter. Real-time MR thermometry and thermal dosimetry may improve safety and efficacy of the RFA procedure by offering a reliable indicator of therapy outcome during the procedure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-017-0323-0) contains supplementary material, which is available to authorized users.

This new fast imaging sequence provides real-time measurement of temperature distribution and displacement at the focus during HIFU ablation. Magn Reson Med 78:1911-1921, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

This fully automated MR thermometry pipeline (five images/heartbeat) provides direct assessment of lesion formation in the heart during catheter-based RFA, which may improve treatment of cardiac arrhythmia by ablation. Magn Reson Med 77:673-683, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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The growing need for the characterization of cytochrome P450 (P450) metabolites often necessitates their synthesis up to Gram-scale. This task may in principle be achieved by using various techniques including chemical synthesis, the use of laboratory animals, in vitro P450 systems or microbial biotransformation. However, these approaches are in many instances unfavorable due to low yields, laborious purification, costs of cofactors, or the formation of non-physiologic metabolites. The fission yeast Schizosaccharomyces pombe has previously been shown by others and us to be very well suited for the heterologous expression of human P450s. In this study, we demonstrate whole-cell biotransformation reactions carried out with fission yeast strains that coexpress human cytochrome P450 reductase (CPR) and one of the following P450 isoforms: CYP2B6, CYP2C9, CYP2C19, CYP2D6, or CYP3A4, respectively. These strains could successfully convert their respective standard substrates but showed different responses with respect to incubation pH, the presence of glucose, and temperature, respectively. In addition, the preparative of synthesis of 2.8 g of 4'-hydroxydiclofenac was achieved by whole-cell biotransformation of diclofenac using a CPR-CYP2C9 coexpressing fission yeast strain.

Monitoring thermal therapies through medical imaging is essential in order to ensure that they are safe, efficient and reliable. In this paper, we propose a new approach, halfway between MR acoustic radiation force imaging (MR-ARFI) and MR elastography (MRE), allowing for the quantitative measurement of the elastic modulus of tissue in a highly localized manner. It relies on the simulation of the MR-ARFI profile, which depends on tissue biomechanical properties, and on the identification of tissue elasticity through the fitting of experimental displacement images measured using rapid MR-ARFI. This method was specifically developed to monitor MR-guided high intensity focused ultrasound (MRgHIFU) therapy. Elasticity changes were followed during HIFU ablations (N  =  6) performed ex vivo in porcine muscle samples, and were compared to temperature changes measured by MR-thermometry. Shear modulus was found to increase consistently and steadily a few seconds after the heating started, and such changes were found to be irreversible. The shear modulus was found to increase from 1.49  ±  0.48 kPa (before ablation) to 3.69  ±  0.93 kPa (after ablation and cooling). Thanks to its ability to perform quantitative elasticity measurements in a highly localized manner around the focal spot, this method proved to be particularly attractive for monitoring HIFU ablations.

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This standalone 3D US-based motion correction technique is robust and allows maintaining the HIFU focal spot in the presence of motion without adding any burden or complexity to MR thermal imaging. In vitro and in vivo results showed about 35% improvement in heating efficiency when focus position was locked on the target using the proposed technique.