3D motion strategy for online volumetric thermometry using simultaneous multi-slice EPI at 1.5T: an evaluation study.

PURPOSE: In presence of respiratory motion, temperature mapping is altered by in-plane and through-plane displacements between successive acquisitions together with periodic phase variations. Fast 2D Echo Planar Imaging (EPI) sequence can accommodate intra-scan motion, but limited volume coverage and inter-scan motion remain a challenge during free-breathing acquisition since position offsets can arise between the different slices. METHOD: To address this limitation, we evaluated a 2D simultaneous multi-slice EPI sequence with multiband (MB) acceleration during radiofrequency ablation on a mobile gel and in the liver of a volunteer (no heating). The sequence was evaluated in terms of resulting inter-scan motion, temperature uncertainty and elevation, potential false-positive heating and repeatability. Lastly, to account for potential through-plane motion, a 3D motion compensation pipeline was implemented and evaluated. RESULTS: In-plane motion was compensated whatever the MB factor and temperature distribution was found in agreement during both the heating and cooling periods. No obvious false-positive temperature was observed under the conditions being investigated. Repeatability of measurements results in a 95% uncertainty below 2 °C for MB1 and MB2. Uncertainty up to 4.5 °C was reported with MB3 together with the presence of aliasing artifacts. Lastly, fast simultaneous multi-slice EPI combined with 3D motion compensation reduce residual out-of-plane motion. CONCLUSION: Volumetric temperature imaging (12 slices/700 ms) could be performed with 2 °C accuracy or less, and offer tradeoffs in acquisition time or volume coverage. Such a strategy is expected to increase procedure safety by monitoring large volumes more rapidly for MR-guided thermotherapy on mobile organs.

Real-time automatic temperature regulation during in vivo MRI-guided laser-induced thermotherapy (MR-LITT).

Precise control of tissue temperature during Laser-Induced Thermotherapy (LITT) procedures has the potential to improve the clinical efficiency and safety of such minimally invasive therapies. We present a method to automatically regulate in vivo the temperature increase during LITT using real-time rapid volumetric Magnetic Resonance thermometry (8 slices acquired every second, with an in-plane resolution of 1.4 mmx1.4 mm and a slice thickness of 3 mm) using the proton-resonance frequency (PRF) shift technique. The laser output power is adjusted every second using a feedback control algorithm (proportional-integral-derivative controller) to force maximal tissue temperature in the targeted region to follow a predefined temperature-time profile. The root-mean-square of the difference between the target temperature and the measured temperature ranged between 0.5 °C and 1.4 °C, for temperature increases between + 5 °C to + 30 °C above body temperature and a long heating duration (up to 15 min), showing excellent accuracy and stability of the method. These results were obtained on a 1.5 T clinical MRI scanner, showing a potential immediate clinical application of such a temperature controller during MR-guided LITT.

Endogenous assessment of myocardial injury with single-shot model-based non-rigid motion-corrected T1 rho mapping.

BACKGROUND: Cardiovascular magnetic resonance T1ρ mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1ρ mapping method that includes model-based non-rigid motion correction. METHODS: A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1ρ mapping sequence that collects five T1ρ-weighted (T1ρw) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1ρ fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~ 30 s) and direct visualization of T1ρ maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1ρ maps was scored. In patients, T1ρ mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1ρ values were assessed in remote and injured areas, using LGE as reference. RESULTS: Despite breath holds, respiratory motion throughout T1ρw images was much larger in patients than in healthy subjects (5.1 ± 2.7 mm vs. 0.5 ± 0.4 mm, P < 0.01). In patients, the model-based non-rigid motion correction improved the alignment of T1ρw images, with higher DSC (87.7 ± 5.3% vs. 82.2 ± 7.5%, P < 0.01), and lower MPD (3.5 ± 1.9 mm vs. 5.1 ± 2.7 mm, P < 0.01). This resulted in significantly improved quality of the T1ρ maps (3.6 ± 0.6 vs. 2.1 ± 0.9, P < 0.01). Using this approach, T1ρ mapping could be used to identify LGE in patients with 93% sensitivity and 89% specificity. T1ρ values in injured (LGE positive) areas were significantly higher than in the remote myocardium (68.4 ± 7.9 ms vs. 48.8 ± 6.5 ms, P < 0.01). CONCLUSIONS: The proposed motion-corrected T1ρ mapping framework enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new insight into myocardial structural disorders.

Fiber Bragg Grating Sensors for Performance Evaluation of Fast Magnetic Resonance Thermometry on Synthetic Phantom.

The increasing recognition of minimally invasive thermal treatment of tumors motivate the development of accurate thermometry approaches for guaranteeing the therapeutic efficacy and safety. Magnetic Resonance Thermometry Imaging (MRTI) is nowadays considered the gold-standard in thermometry for tumor thermal therapy, and assessment of its performances is required for clinical applications. This study evaluates the accuracy of fast MRTI on a synthetic phantom, using dense ultra-short Fiber Bragg Grating (FBG) array, as a reference. Fast MRTI is achieved with a multi-slice gradient-echo echo-planar imaging (GRE-EPI) sequence, allowing monitoring the temperature increase induced with a 980 nm laser source. The temperature distributions measured with 1 mm-spatial resolution with both FBGs and MRTI were compared. The root mean squared error (RMSE) value obtained by comparing temperature profiles showed a maximum error of 1.2 °C. The Bland-Altman analysis revealed a mean of difference of 0.1 °C and limits of agreement 1.5/-1.3 °C. FBG sensors allowed to extensively assess the performances of the GRE-EPI sequence, in addition to the information on the MRTI precision estimated by considering the signal-to-noise ratio of the images (0.4 °C). Overall, the results obtained for the GRE-EPI fully satisfy the accuracy (~2 °C) required for proper temperature monitoring during thermal therapies.

MRI monitoring of temperature and displacement for transcranial focus ultrasound applications.

BACKGROUND: Transcranial focus ultrasound applications applied under MRI-guidance benefit from unrivaled monitoring capabilities, allowing the recording of real-time anatomical information and biomarkers like the temperature rise and/or displacement induced by the acoustic radiation force. Having both of these measurements could allow for better targeting of brain structures, with improved therapy monitoring and safety. METHOD: We investigated the use of a novel MRI-pulse sequence described previously in Bour et al., (2017) to quantify both the displacement and temperature changes under various ultrasound sonication conditions and in different regions of the brain. The method was evaluated in vivo in a non-human primate under anesthesia using a single-element transducer (f = 850 kHz) in a setting that could mimic clinical applications. Acquisition was performed at 3 T on a clinical imaging system using a modified single-shot gradient echo EPI sequence integrating a bipolar motion-sensitive encoding gradient. Four slices were acquired sequentially perpendicularly or axially to the direction of the ultrasound beam with a 1-Hz update frequency and an isotropic spatial resolution of 2-mm. A total of twenty-four acquisitions were performed in three different sets of experiments. Measurement uncertainty of the sequence was investigated under different acoustic power deposition and in different regions of the brain. Acoustic simulation and thermal modeling were performed and compared to experimental data. RESULTS: The sequence simultaneously provides relevant information about the focal spot location and visualization of heating of brain structures: 1) The sequence localized the acoustic focus both along as well as perpendicular to the ultrasound direction. Tissue displacements ranged from 1 to 2 µm. 2) Thermal rise was only observed at the vicinity of the skull. Temperature increase ranged between 1 and 2 °C and was observed delayed relative the sonication due to thermal diffusion. 3) The fast frame rate imaging was able to highlight magnetic susceptibility artifacts related to breathing, for the most caudal slices. We demonstrated that respiratory triggering successfully restored the sensitivity of the method (from 0.7 µm to 0.2 µm). 4) These results were corroborated by acoustic simulations. CONCLUSIONS: The current rapid, multi-slice acquisition and real-time implementation of temperature and displacement visualization may be useful in clinical practices. It may help defining operational safety margins, improving therapy precision and efficacy. Simulations were in good agreement with experimental data and may thus be used prior treatment for procedure planning.

Assessment of the healing process after percutaneous implantation of a cardiovascular device: a systematic review.

The healing process, occurring after intra-cardiac and intra-vascular device implantation, starts with fibrin condensation and attraction of inflammatory cells, followed by the formation of fibrous tissue that slowly covers the device. The duration of this process is variable and may be incomplete, which can lead to thrombus formation, dislodgement of the device or stenosis. To better understand this process and the neotissue formation, animal models were developed: small (rats and rabbits) and large (sheep, pigs, dogs and baboons) animal models for intra-vascular device implantation; sheep and pigs for intra-cardiac device implantation. After intra-vascular and intra-cardiac device implantation in these animal models, in vitro techniques, i.e. histology, which is the gold standard and scanning electron microscopy, were used to assess the device coverage, characterize the cell constitution and detect complications such as thrombosis. In humans, optical coherence tomography and intra-vascular ultrasounds are both invasive modalities used after stent implantation to assess the structure of the vessels, atheroma plaque and complications. Non-invasive techniques (computed tomography and magnetic resonance imaging) are in development in humans and animal models for tissue characterization (fibrosis), device remodeling evaluation and device implantation complications (thrombosis and stenosis). This review aims to (1) present the experimental models used to study this process on cardiac devices; (2) focus on the in vitro techniques and invasive modalities used currently in humans for intra-vascular and intra-cardiac devices and (3) assess the future developments of non-invasive techniques in animal models and humans for intra-cardiac devices.

Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot.

BACKGROUND: Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae. METHODS: Piglets underwent a tetralogy of Fallot repair-like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot. RESULTS: Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols. CONCLUSIONS: We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.

MR-ARFI-based method for the quantitative measurement of tissue elasticity: application for monitoring HIFU therapy.

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.

Real-time 3D ultrasound based motion tracking for the treatment of mobile organs with MR-guided high-intensity focused ultrasound.

INTRODUCTION: Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatments of mobile organs require locking the HIFU beam on the targeted tissue to maximise heating efficiency. We propose to use a standalone 3 D ultrasound (US)-based motion correction technique using the HIFU transducer in pulse-echo mode. Validation of the method was performed in vitro and in vivo in the liver of pig under MR-thermometry. METHODS: 3 D-motion estimation was implemented using ultrasonic speckle-tracking between consecutive acquisitions. Displacement was estimated along four sub-apertures of the HIFU transducer by computing the normalised cross-correlation of backscattered signals followed by a triangulation algorithm. The HIFU beam was steered accordingly and energy was delivered under real-time MR-thermometry (using the proton resonance frequency shift method with online motion compensation and correction of associated susceptibility artefacts). An MR-navigator echo was used to assess the quality of the US-based motion correction. RESULTS: Displacement estimations from US measurements were in good agreement with 1 D MR-navigator echo readings. In vitro, the maximum temperature increase was improved by 37% as compared to experiments performed without motion correction and temperature distribution remained much more focussed. Similar results were reported in vivo, with an increase of 35% on the maximum temperature using this US-based HIFU target locking. CONCLUSION: 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.

Real-time monitoring of tissue displacement and temperature changes during MR-guided high intensity focused ultrasound.

PURPOSE: The therapy endpoint most commonly used in MR-guided high intensity focused ultrasound is the thermal dose. Although namely correlated with nonviable tissue, it does not account for changes in mechanical properties of tissue during ablation. This study presents a new acquisition sequence for multislice, subsecond and simultaneous imaging of tissue temperature and displacement during ablation. METHODS: A single-shot echo planar imaging sequence was implemented using a pair of motion-encoding gradients, with alternated polarities. A first ultrasound pulse was synchronized on the second lobe of the motion-encoding gradients and followed by continuous sonication to induce a local temperature increase in ex vivo muscle and in vivo on pig liver. Lastly, the method was evaluated in the brain of two volunteers to assess method's precision. RESULTS: For thermal doses higher than the lethal threshold, displacement amplitude was reduced by 21% and 28% at the focal point in muscle and liver, respectively. Displacement value remained nearly constant for nonlethal thermal doses values. The mean standard deviation of temperature and displacement in the brain of volunteers remained below 0.8 °C and 2.5 µm. CONCLUSION: 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.

Improved cardiac magnetic resonance thermometry and dosimetry for monitoring lesion formation during catheter ablation.

PURPOSE: A new real-time MR-thermometry pipeline was developed to measure multiple temperature images per heartbeat with 1.6×1.6×3 mm3 spatial resolution. The method was evaluated on 10 healthy volunteers and during radiofrequency ablation (RFA) in sheep. METHODS: Multislice, electrocardiogram-triggered, echo-planar imaging was combined with parallel imaging, under free breathing conditions. In-plane respiratory motion was corrected on magnitude images by an optical flow algorithm. Motion-related susceptibility artifacts were compensated on phase images by an algorithm based on Principal Component Analysis. Correction of phase drift and temporal filter were included in the pipeline implemented in the Gadgetron framework. Contact electrograms were recorded simultaneously with MR thermometry by an MR-compatible ablation catheter. RESULTS: The temporal standard deviation of temperature in the left ventricle remained below 2 °C on each volunteer. In sheep, focal heated regions near the catheter tip were observed on temperature images (maximal temperature increase of 38 °C) during RFA, with contact electrograms of acceptable quality. Thermal lesion dimensions at gross pathology were in agreement with those observed on thermal dose images. CONCLUSION: 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.

Energy Deregulation Precedes Alteration in Heart Energy Balance in Young Spontaneously Hypertensive Rats: A Non Invasive In Vivo31P-MR Spectroscopy Follow-Up Study.

INTRODUCTION: Gradual alterations in cardiac energy balance, as assessed by the myocardial PCr/ATP-ratio, are frequently associated with the development of cardiac disease. Despite great interest for the follow-up of myocardial PCr and ATP content, cardiac MR-spectroscopy in rat models in vivo is challenged by sensitivity issues and cross-contamination from other organs. METHODS: Here we combined MR-Imaging and MR-Spectroscopy (Bruker BioSpec 9.4T) to follow-up for the first time in vivo the cardiac energy balance in the SHR, a genetic rat model of cardiac hypertrophy known to develop early disturbances in cytosolic calcium dynamics. RESULTS: We obtained consistent 31P-spectra with high signal/noise ratio from the left ventricle in vivo by using a double-tuned (31P/1H) surface coil. Reasonable acquisition time (<3.2min) allowed assessing the PCr/ATP-ratio comparatively in SHR and age-matched control rats (WKY): i) weekly from 12 to 21 weeks of age; ii) in response to a bolus injection of the ß-adrenoreceptor agonist isoproterenol at age 21 weeks. DISCUSSION: Along weeks, the cardiac PCr/ATP-ratio was highly reproducible, steady and similar (2.35±0.06) in SHR and WKY, in spite of detectable ventricular hypertrophy in SHR. At the age 21 weeks, PCr/ATP dropped more markedly (-17.1%±0.8% vs. -3,5%±1.4%, P<0.001) after isoproterenol injection in SHR and recovered slowly thereafter (time constant 21.2min vs. 6.6min, P<0.05) despite similar profiles of tachycardia among rats. CONCLUSION: The exacerbated PCr/ATP drop under ß-adrenergic stimulation indicates a defect in cardiac energy regulation possibly due to calcium-mediated abnormalities in the SHR heart. Of note, defects in energy regulation were present before detectable abnormalities in cardiac energy balance at rest.

Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications.

Irrigated Needle Ablation Creates Larger and More Transmural Ventricular Lesions Compared With Standard Unipolar Ablation in an Ovine Model.

BACKGROUND: Ventricular tachycardia recurrence can occur after ventricular tachycardia ablation because of incomplete and nontransmural ventricular lesion formation. We sought to compare the lesions made by a novel irrigated needle catheter to conventional radiofrequency lesions. METHODS AND RESULTS: Thirteen female sheep (4.6±0.7 years, 54±8 kg) were studied. In 7 sheep, 60-s radiofrequency applications were performed using an irrigated needle catheter. In 6 sheep, conventional lesions were made using a 4-mm irrigated catheter. 1.5T in vivo and high-density magnetic resonance imaging (9.4T) were performed on explanted hearts from animals receiving needle radiofrequency. Conventional lesion volume was calculated as (1/6)×π×(A×B(2)+C×D(2)/2). Needle lesion volume was measured as Σ(π×r(2))/2 with a slice thickness of 1 mm. The dimensions of all lesions were also measured on gross pathology. Additional histological analysis of the needle lesions was performed. One hundred twenty endocardial left ventricular ablation lesions (conventional, n=60; needle, n=60) were created. At necropsy, more lesions were found using needle versus conventional radiofrequency (90% versus 75%; P<0.05). Comparing needle versus conventional radiofrequency: lesion volume was larger (1030±362 versus 488±384 mm(3); P<0.001), lesion depth was increased (9.9±2.7 versus 5±2.4 mm; P<0.001), and more transmural lesions were created (62.5% versus 17%; P<0.01). Pericardial contrast injection was observed in 4 apical attempts using needle radiofrequency, however, with no adverse effects. Steam pops occurred in 3 attempts using conventional radiofrequency. CONCLUSIONS: Irrigated needle ablation is associated with more frequent, larger, deeper, and more often transmural lesions compared with conventional irrigated ablation. This technology might be of value to treat intramural or epicardial ventricular tachycardia substrates resistant to conventional ablation.

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.

Identification of Region-Specific Myocardial Gene Expression Patterns in a Chronic Swine Model of Repaired Tetralogy of Fallot.

Surgical repair of Tetralogy of Fallot (TOF) is highly successful but may be complicated in adulthood by arrhythmias, sudden death, and right ventricular or biventricular dysfunction. To better understand the molecular and cellular mechanisms of these delayed cardiac events, a chronic animal model of postoperative TOF was studied using microarrays to perform cardiac transcriptomic studies. The experimental study included 12 piglets (7 rTOF and 5 controls) that underwent surgery at age 2 months and were further studied after 23 (+/- 1) weeks of postoperative recovery. Two distinct regions (endocardium and epicardium) from both ventricles were analyzed. Expression levels from each localization were compared in order to decipher mechanisms and signaling pathways leading to ventricular dysfunction and arrhythmias in surgically repaired TOF. Several genes were confirmed to participate in ventricular remodeling and cardiac failure and some new candidate genes were described. In particular, these data pointed out FRZB as a heart failure marker. Moreover, calcium handling and contractile function genes (SLN, ACTC1, PLCD4, PLCZ), potential arrhythmia-related genes (MYO5B, KCNA5), and cytoskeleton and cellular organization-related genes (XIRP2, COL8A1, KCNA6) were among the most deregulated genes in rTOF ventricles. To our knowledge, this is the first comprehensive report on global gene expression profiling in the heart of a long-term swine model of repaired TOF.

Pre-clinical study of in vivo magnetic resonance-guided bubble-enhanced heating in pig liver.

Bubble-enhanced heating (BEH) can be exploited to increase heating efficiency in treatment of liver tumors with non-invasive high-intensity focused ultrasound (HIFU). The objectives of this study were: (i) to demonstrate the feasibility of increasing the heating efficiency of sonication exploiting BEH in pig liver in vivo using a clinical platform; (ii) to determine the acoustic threshold for such effects with real-time, motion-compensated magnetic resonance-guided thermometry; and (iii) to compare the heating patterns and thermal lesion characteristics resulting from continuous sonication and sonication including a burst pulse. The threshold acoustic power for generation of BEH in pig liver in vivo was determined using sonication of 0.5-s duration ("burst pulse") under real-time magnetic resonance thermometry. In a second step, experimental sonication composed of a burst pulse followed by continuous sonication (14.5 s) was compared with conventional sonication (15 s) of identical energy (1.8 kJ). Modification of the heating pattern at the targeted region located at a liver depth between 20 and 25 mm required 600-800 acoustic watts. The experimental group exhibited near-spherical heating with 40% mean enhancement of the maximal temperature rise as compared with the conventional sonication group, a mean shift of 7 ± 3.3 mm toward the transducer and reduction of the post-focal temperature increase. Magnetic resonance thermometry can be exploited to control acoustic BEH in vivo in the liver. By use of experimental sonication, more efficient heating can be achieved while protecting tissues located beyond the focal point.

Feasibility of fast MR-thermometry during cardiac radiofrequency ablation.

Online MR temperature monitoring during radiofrequency (RF) ablation of cardiac arrhythmias may improve the efficacy and safety of the treatment. MR thermometry at 1.5 T using the proton resonance frequency (PRF) method was assessed in 10 healthy volunteers under normal breathing conditions, using a multi-slice, ECG-gated, echo planar imaging (EPI) sequence in combination with slice tracking. Temperature images were post-processed to remove residual motion-related artifacts. Using an MR-compatible steerable catheter and electromagnetic noise filter, RF ablation was performed in the ventricles of two sheep in vivo. The standard deviation of the temperature evolution in time (TSD) was computed. Temperature mapping of the left ventricle was achieved at an update rate of approximately 1 Hz with a mean TSD of 3.6 ± 0.9 °C. TSD measurements at the septum showed a higher precision (2.8 ± 0.9 °C) than at the myocardial regions at the heart-lung and heart-liver interfaces (4.1 ± 0.9 °C). Temperature rose maximally by 9 °C and 16 °C during 5 W and 10 W RF applications, respectively, for 60 s each. Tissue temperature can be monitored at an update rate of approximately 1 Hz in five slices. Typical temperature changes observed during clinical RF application can be monitored with an acceptable level of precision.

Real-time volumetric MRI thermometry of focused ultrasound ablation in vivo: a feasibility study in pig liver and kidney.

MR thermometry offers the possibility to precisely guide high-intensity focused ultrasound (HIFU) for the noninvasive treatment of kidney and liver tumours. The objectives of this study were to demonstrate therapy guidance by motion-compensated, rapid and volumetric MR temperature monitoring and to evaluate the feasibility of MR-guided HIFU ablation in these organs. Fourteen HIFU sonications were performed in the kidney and liver of five pigs under general anaesthesia using an MR-compatible Philips HIFU platform prototype. HIFU sonication power and duration were varied. Volumetric MR thermometry was performed continuously at 1.5 T using the proton resonance frequency shift method employing a multi-slice, single-shot, echo-planar imaging sequence with an update frequency of 2.5 Hz. Motion-related suceptibility artefacts were compensated for using multi-baseline reference images acquired prior to sonication. At the end of the experiment, the animals were sacrificed for macroscopic and microscopic examinations of the kidney, liver and skin. The standard deviation of the temperature measured prior to heating in the sonicated area was approximately 1 °C in kidney and liver, and 2.5 °C near the skin. The maximum temperature rise was 30 °C for a sonication of 1.2 MHz in the liver over 15 s at 300 W. The thermal dose reached the lethal threshold (240 CEM(43) ) in two of six cases in the kidney and four of eight cases in the liver, but remained below this value in skin regions in the beam path. These findings were in agreement with histological analysis. Volumetric thermometry allows real-time monitoring of the temperature at the target location in liver and kidney, as well as in surrounding tissues. Thermal ablation was more difficult to achieve in renal than in hepatic tissue even using higher acoustic energy, probably because of a more efficient heat evacuation in the kidney by perfusion.

A method for MRI guidance of intercostal high intensity focused ultrasound ablation in the liver.

PURPOSE: High intensity focused ultrasound (HIFU) is a promising method for the noninvasive treatment of liver tumors. However, the presence of ribs in the HIFU beam path remains problematic since it may lead to adverse effects (skin burns) by absorption and reflection of the incident beam at or near the bone surface. This article presents a method based on magnetic resonance (MR) imaging for identification of the ribs in the HIFU beam, and for selection of the transducer elements to deactivate. METHODS: The ribs are visualized on anatomical images acquired prior to heating and manually segmented. The resulting regions of interest surrounding the ribs are projected onto the transducer surface by ray tracing from the focal point. The transducer elements in the "shadow" of the ribs are then deactivated. The method was validated ex vivo and in vivo in pig liver during breathing under multislice real-time MR thermometry, using the proton resonance frequency shift method. RESULTS: Ex vivo and in vivo temperature data showed that the temperature increase near the ribs was substantial when HIFU sonications were performed with all elements active, whereas the temperature was reduced with deactivation of the transducer elements located in front of the ribs. The temperature at the focal point was similar with and without deactivation of the transducer elements, indicative of no loss of heat efficiency with the proposed technique. CONCLUSIONS: This method is simple, rapid, and reliable, and enables intercostal HIFU ablation while sparing ribs and their surrounding tissues.