Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

<p>Abstract</p> <p>Background</p> <p>Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap.</p> <p>Methods</p> <p>Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm²for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to <it>in vivo </it>studies on pig esophagi.</p> <p>Results</p> <p>Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases.</p> <p>Conclusion</p> <p>This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.</p

Transcriptome response to pollutants and insecticides in the dengue vector Aedes aegypti using next-generation sequencing technology

<p>Abstract</p> <p>Background</p> <p>The control of mosquitoes transmitting infectious diseases relies mainly on the use of chemical insecticides. However, mosquito control programs are now threatened by the emergence of insecticide resistance. Hitherto, most research efforts have been focused on elucidating the molecular basis of inherited resistance. Less attention has been paid to the short-term response of mosquitoes to insecticides and pollutants which could have a significant impact on insecticide efficacy. Here, a combination of LongSAGE and Solexa sequencing was used to perform a deep transcriptome analysis of larvae of the dengue vector <it>Aedes aegypti </it>exposed for 48 h to sub-lethal doses of three chemical insecticides and three anthropogenic pollutants.</p> <p>Results</p> <p>Thirty millions 20 bp cDNA tags were sequenced, mapped to the mosquito genome and clustered, representing 6850 known genes and 4868 additional clusters not located within predicted genes. Mosquitoes exposed to insecticides or anthropogenic pollutants showed considerable modifications of their transcriptome. Genes encoding cuticular proteins, transporters, and enzymes involved in the mitochondrial respiratory chain and detoxification processes were particularly affected. Genes and molecular mechanisms potentially involved in xenobiotic response and insecticide tolerance were identified.</p> <p>Conclusions</p> <p>The method used in the present study appears as a powerful approach for investigating fine transcriptome variations in genome-sequenced organisms and can provide useful informations for the detection of novel transcripts. At the biological level, despite low concentrations and no apparent phenotypic effects, the significant impact of these xenobiotics on mosquito transcriptomes raise important questions about the 'hidden impact' of anthropogenic pollutants on ecosystems and consequences on vector control.</p

Characterization of High Intensity Ultrasound Exposures by Quantitative Ultrasound

International audienceHigh Intensity Ultrasound (HIU) is of proven value in the treatment of many medical disorders by using US energy without incisions or radiation. The development of an effective method for guiding HIU therapies remains necessary. Changes in spectral-based Quantitative UltraSound (QUS) parameters have been correlated with the temperature changes during HIU exposure (Ghoshal et al. IEEE UFFC 2016). The aim of this study is to quantify the changes in QUS parameters due to temperature elevation after HIU exposure of ex vivo bovine livers. The QUS experiments are conducted in high frequencies (12-38 MHz) to provide insight into the specific changes in liver tissues that cause the changes of backscatter properties for fixed temperature ranging from 37°C up to 80°C after HIU exposure. Samples of porcine livers are exposed to HIU using a plane 3 MHz transducer with aperture diameter of 4 cm. Samples were heated up to 37, 50, 60, 65, 70, 75, 80°C. After reaching the desired temperature, the sample is cut in half at the center of the lesion. US backscatter signals were recorded from the cut samples by using the Visualsonics Vevo 770 imaging system with the RMV710 probe of center frequency 25 MHz. The backscatter coefficients (BSCs) were estimated using the reference phantom technique and the attenuation coefficients were determined using a standard substitution method. Structural scatterer properties were estimated by fitting the measured BSCs with the spherical Gaussian model (SGM) or with the Structure Factor Model (SFM) to estimate the effective scatterer diameter (ESD) and acoustic concentration (EAC). The QUS parameters estimated by the sparse SGM and the concentrated SFM differ strongly from each other for HIU treated samples and suggests that the treated livers can be considered as concentrated media. Results showed that both integrated BSC and ESD estimated by the SFM increased as a function of temperature. Keywords-high intensity ultrasound, backscatter coefficient, quantitative ultrasound

Data from: An ultrasound image-based dynamic fusion modeling method for predicting the quantitative impact of in vivo liver motion on intraoperative HIFU therapies: investigations in a porcine model

Organ motion is a key component in the treatment of abdominal tumors by High Intensity Focused Ultrasound (HIFU), since it may influence the safety, efficacy and treatment time. Here we report the development in a porcine model of an Ultrasound (US) image-based dynamic fusion modeling method for predicting the effect of in vivo motion on intraoperative HIFU treatments performed in the liver in conjunction with surgery. A speckle tracking method was used on US images to quantify in vivo liver motions occurring intraoperatively during breathing and apnea. A fusion modeling of HIFU treatments was implemented by merging dynamic in vivo motion data in a numerical modeling of HIFU treatments. Two HIFU strategies were studied: a spherical focusing delivering 49 juxtapositions of 5-second HIFU exposures and a toroidal focusing using 1 single 40-second HIFU exposure. Liver motions during breathing were spatially homogenous and could be approximated to a rigid motion mainly encountered in the cranial-caudal direction (f = 0.20Hz, magnitude >13mm). Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96Hz, magnitude 75%). Fusion modeling predictions were preliminarily validated in vivo and showed the potential of using a long-duration toroidal HIFU exposure to accelerate the ablation process during breathing (from 0.5 to 6 cm3·min-1). To improve HIFU treatment control, dynamic fusion modeling may be interesting for assessing numerically focusing strategies and motion compensation techniques in more realistic conditions

Caractérisation ex vivo du changement de la rétrodiffusion ultrasonore lors d'un traitement par ultrasons focalisés

Les ultrasons focalisés de haute intensité (\textit{High Intensity Focused Ultrasound}, HIFU)) permettent le traitement de nombreuses pathologies, de manière non-invasive et sans radiation. Le guidage de l'effet thermique induit par HIFU nécessite un suivi temps réel quantitatif. Le développement d'une telle technique reste un enjeu majeur à l'heure actuelle. Dans ce contexte, la technique quantitative ultrasonore (QUS) basée sur la mesure du coefficient de rétrodiffusion (\textit{Back-Scattering Coefficient} , BSC) semble prometteuse pour faire le suivi des changements de microstructure lors de l'ablation thermique HIFU. Le travail présenté ici a pour objectif de quantifier l'évolution des paramètres d'atténuation, de BSC et de microstructure avant et après le traitement thermique d'échantillons hépatiques par HIFU ou bain marie. \\ Des lésions thermiques sur des foies de porc ex vivo ont été réalisées par HIFU avec un transducteur monoélément fonctionnant à 3 MHz, ou par bain marie en immergeant les tissus durant 10 min dans une solution saline chauffée. Une trentaine d'échantillons ont été traités à des températures comprises entre 37 et 80°C. L'élévation en température a été mesurée grâce à un thermocouple, et le BSC calculé par la technique de fantôme de référence, puis comparé aux prédictions de modèles analytiques basés sur un modèle gaussien ou un modèle de facteur de structure. \\ Dans le cas de lésions créées par HIFU, une relation quasi linéaire de +8 dB entre la température et le BSC jusqu'à environ 75°C est mise en évidence. Pour les échantillons chauffés au bain marie, les mesures ultrasonores jusqu'à 80 MHz permettent d'estimer les caractéristiques (taille et concentration) des sources acoustiques à l'origine des changements de rétrodiffusion observés, et sont corrélés aux microstructures observées sur les coupes histologiques. L'ensemble des résultats présentés permet une meilleure compréhension de l'évolution de la rétrodiffusion ultrasonore des tissus hépatiques lors des traitements HIFU, ouvrant la voie au guidage par imagerie QUS

Development of a hifu treatment using a toroidal transducer for pancreatic adenocarcinoma: Preliminary in vivo study

International audiencePancreatic adenocarcinoma is one of the most aggressive cancer. Regardless of the treatment used, the survival rate after 5 years is lower than 6%. Toroidal transducers can treat up to 60 cm3 of tissues in 370 seconds without the need to displace the HIFU probe. In this study, which included fourteen pigs, we evaluated in vivo the use of this device for treating the pancreas and peripancreatic vessels. The device was used intra-operatively. The transducer, working at 2.5MHz, has a toroidal shape with a radius of curvature of 70 mm focusing on a circle of 30 mm. An ultrasound-imaging probe working at 7.5 MHz was placed in the center of the HIFU transducer. Ablations were created in 440 seconds using an acoustic power of 85 or 100 watts. In total eight pigs were included in this study. Eight lesions were created in the pancreas and around peri-pancreatic vessels and observed immediately after treatment. Homogenous ablations were obtained in all cases and were confirmed histologically. The average diameter of the pancreatic ablations was 33.1 � 5.0 mm. These ablations were also homogeneous all around the peripancreatic artery and without occlusion as confirmed by Doppler examination. Using this toroidal HIFU transducer it is possible to treat the most challenging region of the pancreas and its surrounding vessels without any occlusion. This may allow to treat locally advanced pancreatic tumors which are the main contra-indication to curative resection

Towards 4DCT-US image fusion for liver motion monitoring

International audienceHigh-intensity focused-ultrasound (HIFU) is a promising technique for treating liver tumors. However, liver motion due to breathing imposes a real-time monitoring of the treatment. To reach this goal and following on previous work, we propose to encase an ultrasound (US) imaging probe into an extracorporeal HIFU device, such that the imaging plane is aligned with the HIFU acoustic axis. Because the tumor itself may not always be visible on US images, we plan to rely on a pre-operative 4D-Computed Tomography (CT) model to infer the tumor location during treatment, using intensity- or feature-based registration techniques. In order to study the feasibility of US guidance according to a pre-operative planning image, we decided to perform US acquisitions on patients after informed consent. These patients undergo radiotherapy treatment and have a 4D-CT image for planning (Philips Brillance), with injected contrast-agent. A hand-held US imaging probe was used to provide 2D images sequences in the coordinate system of the CT scanner thanks to an optical tracking system. No device was available to record a breathing signal during US acquisitions. A breathing signal was estimated for each US sequences using Principal Component Analysis. Inhalation versus exhalation was identified by the user, and the respiratory phase was estimated from the breathing signal using the Hilbert transform. Using this signal and the information from the tracking device, it was possible to approximately register both modalities spatially, and throughout the respiration cycle

An Ultrasound Image-Based Dynamic Fusion Modeling Method for Predicting the Quantitative Impact of In Vivo Liver Motion on Intraoperative HIFU Therapies: Investigations in a Porcine Model.

Organ motion is a key component in the treatment of abdominal tumors by High Intensity Focused Ultrasound (HIFU), since it may influence the safety, efficacy and treatment time. Here we report the development in a porcine model of an Ultrasound (US) image-based dynamic fusion modeling method for predicting the effect of in vivo motion on intraoperative HIFU treatments performed in the liver in conjunction with surgery. A speckle tracking method was used on US images to quantify in vivo liver motions occurring intraoperatively during breathing and apnea. A fusion modeling of HIFU treatments was implemented by merging dynamic in vivo motion data in a numerical modeling of HIFU treatments. Two HIFU strategies were studied: a spherical focusing delivering 49 juxtapositions of 5-second HIFU exposures and a toroidal focusing using 1 single 40-second HIFU exposure. Liver motions during breathing were spatially homogenous and could be approximated to a rigid motion mainly encountered in the cranial-caudal direction (f = 0.20 Hz, magnitude > 13 mm). Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96 Hz, magnitude 75%). Fusion modeling predictions were preliminarily validated in vivo and showed the potential of using a long-duration toroidal HIFU exposure to accelerate the ablation process during breathing (from 0.5 to 6 cm3 · min(-1)). To improve HIFU treatment control, dynamic fusion modeling may be interesting for assessing numerically focusing strategies and motion compensation techniques in more realistic conditions

Combination of thermal and cavitation effects to generate deep lesions with an endocavitary applicator using a plane transducer: ex vivo studies.: Combination of thermal and cavitation effects

International audienceIn the high-intensity focused ultrasound (US), or HIFU, field, it is well-known that the cavitation effect can be used to induce lesions of larger volume. The principle is based on the increase in the equivalent attenuation coefficient of the tissue in the presence of the bubbles created by cavitation. The elementary lesions produced by combination of cavitation and thermal effects, using focused transducers, were spherical and developed upstream of the focal point. This paper presents a method that combines cavitation with a thermal effect to obtain deeper lesions using a plane transducer, rather than a focused one. The cavitation effect was produced by delivering intensities of 60 W/cm2 at the face of the transducer for 0.5 s. The applicator was then rotated through 90 degrees at a constant speed of between 0.5 and 1.5 degrees /s. During this rotation, ex vivo tissues were exposed continuously to an acoustic intensity of 14 W/cm2 to combine the cavitation effect with a thermal effect. The necroses were, on average, twice as deep when the cavitation effect was used as those obtained with a thermal effect alone. Observed macroscopically, the lesions have a very well-delimited geometry. Temperature measurements made at different angles of treatment have shown that they were coagulation necroses