There is a crucial need for noninvasive assessment tools after cell transplantation. This study investigates whether a magnetic resonance imaging (MRI) strategy could be clinically applied to islet transplantation. The purest fractions of seven human islet preparations were labeled with superparamagnetic iron oxide particles (SPIO, 280 lg/mL) and transplanted into four patients with type 1 diabetes. MRI studies (T2 * ) were performed prior to and at various time points after transplantation. Viability and in vitro and in vivo functions of labeled islets were similar to those of control islets. All patients could stop insulin after transplantation. The first patient had diffuse hypointense images on her baseline liver MRI, typical for spontaneous high iron content, and transplant-related modifications could not be observed. The other three patients had normal intensity on pretransplant images, and iron-loaded islets could be identified after transplantation as hypointense spots within the liver. In one of them, i.v. iron therapy prevented subsequent visualization of the spots because of diffuse hypointense liver background. Altogether, this study demonstrates the feasibility and safety of MRI-based islet graft monitoring in clinical practice. Iron overload (spontaneous or induced) represents the major obstacle to the technique.

Purpose:To evaluate the feasibility and precision of magnetic resonance imaging (MRI) thermometry for monitoring radiofrequency (RF) liver ablation in vivo and predicting the size of the ablation zone.Materials and Methods: At 1.5T, respiratory-triggered real-time MR temperature mapping (the proton resonance frequency (PRF) method) was used to monitor RF ablation in rabbit liver (N ϭ 6) under free breathing. The size of the ablation zones, as assessed by histological analyses, was compared with that predicted from MR thermal dose (TD) maps or derived from conventional T1-weighted (T1w), T2-weighted (T2w), and T1w gadolinium (Gd)-enhanced (T1w-Gd) images acquired immediately after the ablation, and on days 4 and 8 postprocedure.Results: MR temperature uncertainty remained under 1-2°C even during RF deposition. The TD maps were shown to be more predictive and precise than the other MR images, with an average predictive precision for the final ablation zone size of about 1 mm as compared to the histologically proven lesion on day 8. Conclusion:Quantitative temperature MRI during RF ablation is feasible and offered a precise indication of the ablation zone size in this preclinical study based on the lethal dose threshold.

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.

The temporal window of increased membrane permeability is much longer in these studies than previously suggested. This may have important repercussions for in vivo studies in which membrane permeability may be temporally separated from drug delivery.

Ex vivo labeling of islets with superparamagnetic iron oxide (SPIO) nanoparticles allows posttransplant MRI imaging of the graft. In the present study, we compare two clinical grade SPIOs (ferucarbotran and ferumoxide) in terms of toxicity, islet cellular uptake, and MRI imaging. Human islets (80-90% purity) were incubated for 24 h with various concentrations of SPIOs (14-280 µg/ml of iron). Static incubations were performed, comparing insulin response to basal (2.8 mM) or high glucose stimulation (16.7 mM), with or without cAMP stimulation. Insulin and Perl's (assessment of iron content) staining were performed. Electronic microscopy analysis was performed. Labeled islets were used for in vitro or in vivo imaging in MRI 1.5T. Liver section after organ removal was performed in the same plane as MRI imaging to get a correlation between histology and radiology. Postlabeling islet viability (80 ± 10%) and function (in vitro static incubation and in vivo engraftment of human islets in nude mice) were similar in both groups. Iron uptake assessed by electron microscopy showed iron inclusions within the islets with ferucarbotran, but not with ferumoxide. MRI imaging (1.5T) of phantoms and of human islets transplanted in rats, demonstrated a strong signal with ferucarbotran, but only a weak signal with ferumoxide. Signal persisted for >8 weeks in the absence of rejection. An excellent correlation was observed between radiologic images and histology. The hepatic clearance of intraportally injected ferucarbotran was faster than that of ferumoxide, generating less background. A rapid signal decrease was observed in rejecting xenogeneic islets. According to the present data, ferucarbotran is the most appropriate of available clinical grade SPIOs for human islet imaging.Key words: Islet imaging; Islet transplantation; Iron nanoparticles; Magnetic resonance; Imaging INTRODUCTIONone of the most promising strategies (11,12,23,(29)(30)(31).The aim of the present study is to compare the use of the two commercially available, clinical grade iron oxUnlike for other types of organ transplantation, tests allowing the detection of early rejection after islet transide nanoparticles, ferucarbotran (Resovist) and ferumoxide (Feridex), in terms of iron uptake, toxicity, inplantation are lacking (9,19). Alteration of glycemic control occurs too late in the graft destruction process to sulin response, and MRI imaging ability, both in vitro and in vivo. enable graft salvage and islet graft biopsy (i.e., liver biopsy) is not sensitive enough, due to sampling issues MATERIALS AND METHODS (3,28). New strategies are currently under development, Animal Selection including immune monitoring, molecular monitoring (2), and islet graft imaging. Magnetic resonance imaging Male Lewis rats (Janvier, Le Genest, France; 300-500 g) and athymic nu/nu (nude) mice (Janvier, Le Gen-(MRI) after ex vivo islet labeling currently appears to be est, France) were used. All experiments were performed CMRL 1066-based medium, as described above, with SPIOs at iron co...

The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient-echo echo planar imaging (GRE-EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE-EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR-compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland- Altman analysis. In a preliminary clinical feasibility study, the rapid GRE-EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland-Altman mean of differences between MR and optical probe temperature measurements was <0.4 degrees C, and the 95% limits of agreement value was <1.4 degrees C. For the in vivo studies, respiratory-triggered GRE-EPI acquisitions yielded a temperature accuracy of 1.3 +/- 0.4 degrees C (acquisition time = 0.6 s/image, spatial coverage of three slices/respiratory cycle). MR proton resonance frequency thermometry at 1.5 T yields precise and accurate measurements of temperature increment with both classical GRE and rapid GRE-EPI sequences. Rapid GRE-EPI sequences minimize intra-scan motion effects and can be used for MR thermometry during RF ablation in moving organs.