Radiofrequency ablation of small liver malignancies under magnetic resonance guidance: progress in targeting and preliminary observations with temperature monitoring

Objectives: To evaluate the feasibility and effectiveness of magnetic resonance (MR)-guided radiofrequency (RF) ablation for small liver tumours with poor conspicuity on both contrast-enhanced ultrasonography (US) and computed tomography (CT), using fast navigation and temperature monitoring. Methods: Sixteen malignant liver nodules (long-axis diameter, 0.6-2.4cm) were treated with multipolar RF ablation on a 1.5-T wide-bore MR system in ten patients. Targeting was performed interactively, using a fast steady-state free precession sequence. Real-time MR-based temperature mapping was performed, using gradient echo-echo planar imaging (GRE-EPI) and hardware filtering. MR-specific treatment data were recorded. The mean follow-up time was 19 ± 7months. Results: Correct placement of RF electrodes was obtained in all procedures (image update, <500ms; mean targeting time, 21 ± 11min). MR thermometry was available for 14 of 16 nodules (88%) with an accuracy of 1.6°C in a non-heated region. No correlation was found between the size of the lethal thermal dose and the ablation zone at follow-up imaging. The primary and secondary effectiveness rates were 100% and 91%, respectively. Conclusions: RF ablation of small liver tumours can be planned, targeted, monitored and controlled with MR imaging within acceptable procedure times. Temperature mapping is technically feasible, but the clinical benefit remains to be prove

Cine and tagged cardiovascular magnetic resonance imaging in normal rat at 1.5 T: a rest and stress study

BACKGROUND: The purpose of this study was to measure regional contractile function in the normal rat using cardiac cine and tagged cardiovascular magnetic resonance (CMR) during incremental low doses of dobutamine and at rest. METHODS: Five rats were investigated for invasive left ventricle pressure measurements and five additional rats were imaged on a clinical 1.5 T MR system using a cine sequence (11-20 phases per cycle, 0.28/0.28/2 mm) and a C-SPAMM tag sequence (18-25 phases per cycle, 0.63/1.79/3 mm, tag spacing 1.25 mm). For each slice, wall thickening (WT) and circumferential strains (CS) were calculated at rest and at stress (2.5, 5 and 10 microg/min/kg of dobutamine). RESULTS: Good cine and tagged images were obtained in all the rats even at higher heart rate (300-440 bpm). Ejection fraction and left ventricular (LV) end-systolic volume showed significant changes after each dobutamine perfusion dose (p < 0.001). Tagged CMR had the capacity to resolve the CS transmural gradient and showed a significant increase of both WT and CS at stress compared to rest. Intra and interobserver study showed less variability for the tagged technique. In rats in which a LV catheter was placed, dobutamine produced a significant increase of heart rate, LV dP/dtmax and LV pressure significantly already at the lowest infusion dose. CONCLUSION: Robust cardiac cine and tagging CMR measurements can be obtained in the rat under incremental dobutamine stress using a clinical 1.5 T MR scanner

New horizons in MR-controlled and monitored radiofrequency ablation of liver tumours

There is a sustained interest in using magnetic resonance (MR) thermometry to monitor the radiofrequency ablation of liver tumours as a means of visualizing the progress of the thermal coagulation and deciding the optimal end-point. Despite numerous technical challenges, important progress has been made and demonstrated in animal studies. In addition to MR thermometry, MR can now be used for the guidance of the tumour targeting with ‘fluoroscopic’ rapid image acquisition, and it can provide several contrast mechanisms for post-procedural assessment of the extent of the thermal coagulation zone. Challenges of in vivo simultaneous MR thermometry implementation and the current limitations of the thermal dose model for the estimation of the extent of the thermal coagulation zone are discussed. MR imaging could enhance the success of RF ablation of liver tumours due to its potential to provide accurate targeting, monitoring, and post-procedural evaluation

Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy

Purpose: Transport across the plasma membrane is a critical step of drug delivery for weakly permeable compounds with intracellular mode of action. The purpose of this study is to demonstrate real-time monitoring of ultrasound (US)-mediated cell-impermeable model drug uptake with fibered confocal fluorescence microscopy (FCFM). Procedures: An in vitro setup was designed to combine a mono-element US transducer, a cell chamber with a monolayer of tumor cells together with SonoVue microbubbles, and a FCFM system. The cell-impermeable intercalating dye, SYTOX Green, was used to monitor US-mediated uptake. Results: The majority of the cell population showed fluorescence signal enhancement 10 s after US onset. The mean rate constant k of signal enhancement was calculated to be 0.23±0.04 min −1. Conclusions: Feasibility of real-time monitoring of US-mediated intracellular delivery by FCFM has been demonstrated. The method allowed quantitative assessment of model drug uptake, holding great promise for further local drug delivery studies

Real time monitoring of radiofrequency ablation based on MR thermometry and thermal dose in the pig liver in vivo

International audienceTo evaluate the feasibility and accuracy of MR thermometry based on the thermal dose (TD) concept for monitoring radiofrequency (RF) ablations, 13 RF ablations in pig livers were performed under continuous MR thermometry at 1.5 T with a filtered clinical RF device. Respiratory gated fast gradient echo images were acquired simultaneously to RF deposition for providing MR temperature maps with the proton resonant frequency technique. Residual motion , signal to noise ratio (SNR) and standard deviation (SD) of MR temperature images were quantitatively analyzed to detect and reject artifacted images in the time series. SD of temperature measurement remained under 2°C. Macroscopic analysis of liver ablations showed a white zone (Wz) surrounded by a red zone (Rz). A detailed histological analysis confirmed the ongoing nature of the coagulation necrosis in both Wz and Rz. Average differences (±SD) between macroscopic size measurements of Wz and Rz and TD predictions of ablation zones were 4.1 (±1.93) mm and −0.71 (±2.47) mm, respectively. Correlation values between TD and Wz and TD and Rz were 0.97 and 0.99, respectively. MR thermometry monitoring based on TD is an accurate method to delineate the size of the ablation zone during the RF procedure and provides a clinical endpoint

Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound

The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment

First clinical evaluation of real-time cardiac MR thermometry

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Assessment of left ventricle MR temperature stability in patients in the presence of arrhythmias

International audienceBACKGROUND:Magnetic resonance (MR) thermometry allows visualization of lesion formation in real-time during cardiac radiofrequency (RF) ablation. The present study was performed to evaluate the precision of MR thermometry without RF heating in patients exhibiting cardiac arrhythmia in a clinical setting. The evaluation relied on quantification of changes in temperature measurements caused by noise and physiological motion.METHODS:Fourteen patients referred for cardiovascular magnetic resonance imaging underwent an extra sequence to test the temperature mapping stability during free-breathing acquisition. Phase images were acquired using a multi-slice, cardiac-triggered, single-shot echo planar imaging sequence. Temperature maps were calculated and displayed in real-time while the electrocardiogram (ECG) was recorded. The precision of temperature measurement was assessed by measuring the temporal standard deviation and temporal mean of consecutive temperature maps over a period of three minutes. The cardiac cycle was analyzed from ECG recordings to quantify the impact of arrhythmia events on the precision of temperature measurement. Finally, two retrospective strategies were tested to remove acquisition dynamics related either to arrhythmia events or sudden breathing motion.RESULTS:ECG synchronization allowed categorization of inter-beat intervals (RR) into distinct beat morphologies. Five patients were in stable sinus rhythm, while nine patients showed irregular RR intervals due to ectopic beats. An average temporal standard deviation of temperature of 1.6°C was observed in patients under sinus rhythm with a frame rate corresponding to the heart rate of the patient. The temporal standard deviation rose to 2.5°C in patients with arrhythmia. The retrospective rejection strategies increased the temperature precision measurement while maintaining a sufficient frame rate.CONCLUSIONS:Our results indicated that real-time cardiac MR thermometry shows good precision in patients under clinical conditions, even in the presence of arrhythmia. By providing real-time visualization of temperature distribution within the myocardium during RF delivery, MR thermometry could prevent insufficient or excessive heating and thus improve safety and efficacy