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BACKGROUND: 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.
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Arritmias Cardíacas/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Imagen por Resonancia Magnética , Temperatura , Adolescente , Adulto , Anciano , Automatización , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento (Física) , Respiración , Nodo Sinoatrial/diagnóstico por imagen , Adulto JovenRESUMEN
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.
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Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Imagen por Resonancia Magnética/métodos , Cirugía Asistida por Computador/métodos , Termografía/métodos , Animales , Temperatura Corporal , Encéfalo/diagnóstico por imagen , Humanos , Hígado/diagnóstico por imagen , PorcinosRESUMEN
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.
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Ablación por Catéter/métodos , Corazón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Cirugía Asistida por Computador/métodos , Termometría/métodos , Adulto , Algoritmos , Animales , Arritmias Cardíacas/cirugía , Artefactos , Humanos , Procesamiento de Imagen Asistido por Computador , Planificación de la Radioterapia Asistida por Computador , Ovinos , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Clinical 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. METHODS: MR 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. RESULTS: MR 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. CONCLUSIONS: Quantitative 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.
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Ablación por Catéter , Imagen por Resonancia Cinemagnética , Miocardio/patología , Termometría/métodos , Animales , Artefactos , Temperatura Corporal , Catéteres Cardíacos , Ablación por Catéter/instrumentación , Estudios de Factibilidad , Frecuencia Cardíaca , Humanos , Modelos Animales , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Mecánica Respiratoria , Oveja Doméstica , Termometría/instrumentación , Factores de TiempoRESUMEN
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, 0.6-2.4 cm) 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 +/- 7 months. RESULTS: Correct placement of RF electrodes was obtained in all procedures (image update, <500 ms; mean targeting time, 21 +/- 11 min). MR thermometry was available for 14 of 16 nodules (88%) with an accuracy of 1.6 degrees 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 proven.
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Hepatectomía/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Cirugía Asistida por Computador/métodos , Termografía/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
To assess the practical feasibility and effectiveness of real-time magnetic resonance (MR) temperature monitoring for the radiofrequency (RF) ablation of liver tumours in a clinical setting, nine patients (aged 49-87 years, five men and four women) with one malignant tumour (14-50 mm, eight hepatocellular carcinomas and one colorectal metastasis), were treated by 12-min RF ablation using a 1.5-T closed magnet for real-time temperature monitoring. The clinical monopolar RF device was filtered at 64 MHz to avoid electromagnetic interference. Real-time computation of thermal-dose (TD) maps, based on Sapareto and Dewey's equation, was studied to determine its ability to provide a clear end-point of the RF procedure. Absence of local recurrence on follow-up MR images obtained 45 days after the RF ablation was used to assess the apoptotic and necrotic prediction obtained by real-time TD maps. Seven out of nine tumours were completely ablated according to the real-time TD maps. Compared with 45-day follow-up MR images, TD maps accurately predicted two primary treatment failures, but were not relevant in the later progression of one case of secondary local tumour. The real-time TD concept is a feasible and promising monitoring method for the RF ablation of liver tumours.
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Ablación por Catéter/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Cirugía Asistida por Computador/métodos , Termografía/métodos , Anciano , Anciano de 80 o más Años , Sistemas de Computación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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.
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Cardiotónicos/administración & dosificación , Dobutamina/administración & dosificación , Prueba de Esfuerzo , Imagen por Resonancia Cinemagnética , Contracción Miocárdica/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Variaciones Dependientes del Observador , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Volumen Sistólico/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
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.
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Células de la Médula Ósea/diagnóstico por imagen , Células de la Médula Ósea/patología , Regulación Neoplásica de la Expresión Génica , Imagen por Resonancia Magnética/métodos , Microambiente Tumoral , Animales , Células de la Médula Ósea/citología , Carcinoma/metabolismo , Línea Celular Tumoral , Citometría de Flujo , Genes Reporteros , Genotipo , Calor , Hipertermia Inducida , Inmunohistoquímica , Luz , Macrófagos/citología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Fluorescente , Trasplante de Neoplasias , Fenotipo , Regiones Promotoras Genéticas , Ultrasonografía/métodosRESUMEN
There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.2 T using nitroxide-labeled elastin orally administered in mice. In vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser enhancements (19-fold at 18 mm nitroxide) upon proteolysis by pancreatic porcine elastase. In vivo three-dimensional OMRI detection of proteolysis was carried out. A keyhole fully balanced steady-state free precession sequence was used, which allowed 3D OMRI acquisition within 20 s at 0.125 mm(3) resolution. About 30 min after mouse gavage, proteolysis was detected in the duodenum, where Overhauser enhancements were 7.2 ± 2.4 (n = 7) and was not observed in the stomach. Conversely, orally administered free nitroxides or pre-digested nitroxide-labeled elastin were detected in the mouse's stomach by OMRI. Combined with specific molecular probes, this Overhauser-enhanced MRI technique can be used to evaluate unregulated proteolytic activities in various models of experimental diseases and for drug testing.
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Medios de Contraste/química , Elastina/química , Imagen por Resonancia Magnética/métodos , Óxidos de Nitrógeno/química , Animales , Espectroscopía de Resonancia por Spin del Electrón , Ratones , Proteolisis , Marcadores de SpinRESUMEN
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.
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Sistemas de Liberación de Medicamentos/métodos , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Imagen Molecular/métodos , Ultrasonografía/métodos , Animales , Línea Celular Tumoral , Permeabilidad de la Membrana Celular/efectos de la radiación , Humanos , Cinética , Microburbujas , Modelos Biológicos , Compuestos Orgánicos/química , Compuestos Orgánicos/farmacocinética , RatasRESUMEN
PURPOSE: This study aims to quantitatively analyze cellular uptake following local ultrasound (US)-mediated cell permeabilization. PROCEDURES: A 2 µM cell-impermeable dye Sytox Green was co-injected with 3 × 10(7) microbubbles in the presence of C6 rat glioblastoma cell monolayer in total volume of 10 ml. A 5.8-mm diameter mono-element US transducer was positioned at a distance of 8 mm to the Opticell® membrane. Acoustical pressure of pulsed US was varied from 0.62 MPa peak-to-peak (p-p) to 1.25 MPa p-p. Large field of view (FOV = 15 × 15 mm) 22 × 22 mosaic acquisitions were done under epifluorescence Leica DMR microscope and analyzed in Metamorph software to evaluate cell density as well as model drug uptake percentage. RESULTS: The size of acoustical field of the transducer closely matches the spatial pattern of the model drug internalized into the cells by US. Maximum of uptake percentage (42 ± 15 %) was found at 0.88 MPa p-p. CONCLUSIONS: Spatial aspect of US-mediated model drug uptake has been quantitatively evaluated on adherent cells using robust 2D-mapping approach.
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Endocitosis , Glioblastoma/metabolismo , Preparaciones Farmacéuticas/metabolismo , Animales , Línea Celular Tumoral , Procesamiento de Imagen Asistido por Computador , Microscopía Fluorescente , Imagen Molecular , Compuestos Orgánicos/metabolismo , Ratas , UltrasonidoRESUMEN
Many chemotherapeutic drugs are characterized by high systemic toxicity and/or suffer from limited bioavailability. Thermosensitive liposomes (TSLs) encapsulating drugs in their aqueous lumen are promising activatable nanocarriers for ultrasound (US)-mediated drug delivery in response to mild hyperthermia. On the other hand, US is known to locally break biological barriers and as a consequence enable internalization of molecules. In this work, a two-step protocol for intracellular delivery of cell-impermeable molecules comprising of US-induced permeabilization followed by temperature-controlled release of the model drug from thermosensitive liposomes has been developed. TSLs containing TO-PRO-3, a cell-impermeable molecule that displays a significant increase in fluorescence upon binding to nucleic acids thus serving as a 'sensor' for internalization have been prepared and characterized in detail. US-mediated permeabilization followed by temperature-controlled release was applied to tumor bearing mice following i.v. injection of TSLs and microbubbles. The efficacy of this approach was evaluated by in vivo fluorescence imaging followed by histological analysis. A 2.4-fold increase of fluorescence signal was observed and intracellular delivery of TO-PRO-3 was confirmed by a characteristic nuclear staining. These results demonstrate the feasibility of novel drug delivery system to tumors comprising of local cell permeabilization by US followed by in situ release of the payload from thermosensitive liposomes. Possible applications include local and controlled intracellular delivery of molecules with otherwise limited bioavailability.
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Carbocianinas/administración & dosificación , Colorantes Fluorescentes/administración & dosificación , Hipertermia Inducida , Liposomas/química , Neoplasias/diagnóstico , Ultrasonido , Animales , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Femenino , Fluorescencia , Humanos , Ratones , Microscopía Fluorescente , TemperaturaRESUMEN
Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.
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Diferenciación Celular , Células Madre Embrionarias/citología , Corazón/fisiología , Infarto del Miocardio/terapia , Trasplante de Células Madre , Animales , Células Madre Embrionarias/fisiología , Técnicas para Inmunoenzimas , Imagen por Resonancia Magnética , Masculino , Ratones , RatasRESUMEN
PURPOSE: Ultrasound-induced cavitation facilitates cellular uptake of drugs via increased membrane permeability. Here, the purpose was to evaluate the duration of enhanced membrane permeability following ultrasound treatment in cell culture. PROCEDURES: Optical chromophores with fluorescence intensity increasing 100-1,000-fold upon intercalation with nucleic acids served as smart agents for reporting cellular uptake. Opticell chambers with a monolayer of C6 cells were subjected to ultrasound in the presence of microbubbles followed by varying delays between 0 and 24 h before addition of Sytox Green optical contrast agent. Micro- and macroscopic fluorescence were used for qualitative and quantitative analysis. RESULTS: Up to 25% of viable cells showed uptake of contrast agent with a half time of 8 h, with cellular uptake persisting even at 24 h. Only cells exposed to ultrasound showed the effect. CONCLUSION: 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.
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Permeabilidad de la Membrana Celular , Sistemas de Liberación de Medicamentos/métodos , Ultrasonido/métodos , Animales , Línea Celular Tumoral , Supervivencia Celular , Endocitosis , Fluorescencia , Colorantes Fluorescentes/metabolismo , Imagenología Tridimensional , Espacio Intracelular/metabolismo , Compuestos Orgánicos/metabolismo , Ratas , Factores de TiempoRESUMEN
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.
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Medios de Contraste/metabolismo , Dextranos/metabolismo , Hierro/metabolismo , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/metabolismo , Imagen por Resonancia Magnética/métodos , Animales , Células Cultivadas , AMP Cíclico/farmacología , Glucosa/farmacología , Humanos , Insulina/farmacología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/ultraestructura , Hígado/citología , Hígado/metabolismo , Nanopartículas de Magnetita , Masculino , Ratas , Ratas Endogámicas LewRESUMEN
To 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 degrees 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.
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Ablación por Catéter/métodos , Imagen Eco-Planar/métodos , Hígado/patología , Temperatura , Animales , Estudios de Factibilidad , Calor , Procesamiento de Imagen Asistido por Computador , Masculino , Modelos Animales , Reproducibilidad de los Resultados , Respiración , Porcinos , Factores de TiempoRESUMEN
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.
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Temperatura Corporal/fisiología , Imagen Eco-Planar/métodos , Interpretación de Imagen Asistida por Computador/métodos , Termografía/métodos , Imagen Eco-Planar/instrumentación , Estudios de Factibilidad , Humanos , Fantasmas de Imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Termografía/instrumentaciónRESUMEN
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.
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Ablación por Catéter/tendencias , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética Intervencional/tendencias , Animales , Ablación por Catéter/instrumentación , Ablación por Catéter/métodos , Electrodos , Humanos , Imagen por Resonancia Magnética Intervencional/instrumentación , Imagen por Resonancia Magnética Intervencional/métodos , Termografía/instrumentación , Termografía/métodosRESUMEN
We evaluated the feasibility and accuracy of real-time magnetic resonance (MR) thermometry for monitoring radiofrequency (RF) ablation in the liver. Continuous MR temperature mapping was used to monitor bipolar RF ablations performed in ex vivo livers with and without flow using two parallel electrodes. Macroscopic inspection of ablation zones was compared with thermal dose maps (TDm) and T1-weighted inversion recovery turbo spin echo (IR-TSE) images for their size and shape and the influence of flow. Pearson's correlation (r), Bland and Altman tests and kappa (chiK) tests were performed. The mean differences in ablation zone size between macroscopic and TDm and IR-TSE measurements were +4 mm and -2 mm, respectively. TDm was well correlated with macroscopy (r=0.77 versus r=0.44 for IR-TSE). TDm was found to be more precise for shape recognition (chiK=0.73 versus chiK=0.55 for IR-TSE) and for detection of an intact ring of liver due to the cooling effect of flow which was impossible with IR-TSE. Simultaneous monitoring of RF ablation by MR thermometry is feasible and reliable for predicting the shape of ablation zones and the impact of the heat-sink effect of flow. Further studies are needed to confirm these results in vivo.
Asunto(s)
Ablación por Catéter , Hígado/patología , Imagen por Resonancia Magnética Intervencional/métodos , Animales , Bovinos , Estudios de Factibilidad , Calor , Sensibilidad y Especificidad , TemperaturaRESUMEN
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 = 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 degrees 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.