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Journal of Therapeutic Ultrasound20186 (Suppl 1) :2

Published: 15 May 2018

Oral Presentations

O1 Neuroinflammation after disrupting the blood brain barrier with pulsed focused ultrasound and microbubbles imaged by 18F-DPA-714 PET and MRI

Zsofia I. Kovacs, Georgios Z. Papadakis, Tsang-Wei Tu, Sanhita Sinharay, William C. Reid, Bobbi Lewis, Dima A. Hammoud, Joseph A. Frank

National Institutes of Health, Bethesda, Maryland, United States

Correspondence: Zsofia I. Kovacs

via 1.5f₀ ultra harmonic acoustic emission detection for every single pulse (9 focal points, 120 sec/9 focal points – striatum, 120 sec/4 focal points – hippocampus) using an 825 kHz hydrophone with a single-element spherical FUS transducer (center frequency: 589.636 kHz; focal number: 0.8; aperture: 7.5 cm; RK-100, FUS Instruments, Toronto, Ontario, Canada). T2* map were created from multiecho gradient echo sequence at 3T (Achieva, Philips Healthcare, Andover, MA) through the rat brain with TE=7 msec, echo train length 5 and echo spacing 7 and Tr=1500 msec. T2* maps were created by fitting signal intensity at each voxel to a single exponential fit with in-house software and histogram analysis was performed on volume of interests (VOI). Static microPET/CT scans emission data was acquired 30-60 min after injection of 18F-DPA-714. VOIs were drawn in the targeted areas and uptake was compared to the contralateral unaffected side. Uptake values were normalized to cerebellum.

increase in uptake for both regions compared to normal brain. The neuroinflammatory changes persisted for at least 14 days after 2 weekly sonications. The coefficient of variation for PET scans was <10%. This corresponded to Iba1 activation visible on histology. Figure 2 contains normalized histograms from VOI for Group 2 and Group 3 rats derived from pFUS+MB treated (ipsilateral) and contralateral brain that shows a shift to lower T2* values for sonicated regions.

Kovacs, Z. I., et al. (2017). 'Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation.' Proc Natl Acad Sci U S A 114(1): E75-E84.

O'Reilly, M. A. and K. Hynynen (2012). 'Blood-brain barrier: real-time feedback-controlled focused ultrasound disruption by using an acoustic emissions-based controller.' Radiology 263(1): 96-106.

O2 Long term effects of pulsed focused ultrasound and microbubbles detected by multivariate imaging modalities

Zsofia I. Kovacs, Tsang-Wei Tu, Georgios Z. Papadakis, William C. Reid, Dima A. Hammoud, Joseph A. Frank

National Institutes of Health, Bethesda, Maryland, United States

Correspondence: Zsofia I. Kovacs

et al. 2016; Downs, in vivo. T2, T2* and Gd-enhanced T1-weighted images were obtained by 3.0T MRI (Achieva, Philips Healthcare, Andover, MA), T2, T2* and diffusion tensor imaging (DTI) were performed by 9.4T MRI (Bruker, Billerica, MA). Parameters for DTI: 3D spin echo EPI; TR/TE 700 ms/37 msec; b-value 800 sec/mm² with 17 encoding directions; voxel size 200 μm (isotropic). Fractional anisotropy (FA) and the asymmetry of magnetization transfer ratio (MTRasym) were derived for mapping structural injury and glucose levels. Rats received ~1.1 mCi of 18F-FDG Arvanitis, C. D., et al. (2016). 'Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model.' J Neurosurg 124(5): 1450-1459.

Downs, M. E., et al. (2015). 'Long-Term Safety of Repeated Blood-Brain Barrier Opening

O3 Characterization of different microbubbles in assisting focused ultrasound-induced blood-brain barrier opening

Sheng-Kai Wu¹, Po-Chun Chu^{2, 3}, Wen Yen Chai^{3, 4}, Shih-Tsung Kang⁵, Chih-Hung Tsai³, Ching-Hsiang Fan⁵, Chih-Kuang Yeh⁵, Hao-Li Liu³

¹Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; ²Department of Research and Development, NaviFUS corp, Taipei, Taiwan; ³Department of Electrical Engineering, Chang-Gung University, Taoyuan City, Taiwan; ⁴Department of Diagnostic Radiology and Intervention, Chang-Gung Memorial Hospital, Taoyuan City, Taiwan; ⁵Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

Correspondence: Sheng-Kai Wu

Wu S-K, Chu P-C, Chai WY, Kang S-T, Tsai C-H, Fan C-H, Yeh C-K, Liu H-L. Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening. Sci Rep. 2017; 7. Available from: http://www.nature.com/articles/srep46689 doi:10.1038/srep46689

O4 Development of an A-Synuclein (SNCA)-based mouse model for Parkinson's disease by ultrasound-guided CNS delivery

Chung-Yin Lin¹, Yu-Chien Lin², Hao-Li Liu²

¹Institute for Radiological Research, Chang Gung University, Taoyuan City, Taiwan; ²Department of Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan

Correspondence: Chung-Yin Lin

via ultrasound-guided CNS delivery of SNCA gene.

via an via immunoblotting, and histological staining will be used to identify transfected cells via HPLC.

via Western blotting. Immunoblotting and histological staining confirmed the expression of reporter genes in neuronal cells.

1,4, Vasileios Askoxylakis², Yutong Guo¹, Jonas Kloepper², Meenal Datta², Miguel Bernabeu³, Dai Fukumura², Nathan McDannold⁵, Rakesh Jain²

¹Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA; ²Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; ³Centre for Medical Informatics, University of Edinburgh, Edinburgh, UK; ⁴Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA; ⁵Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Costas Arvanitis

in vivo and in silico data demonstrate significant changes in the tumor microenvironment after FUS-BBB/BTB disruption. The most notable changes included: i) increase in BBB/BTB permeability, ii) transition to convection dominated drug transport, and iii) increased cellular transmembrane transport in endothelial cells and stroma cells. Sensitivity analysis showed that the system has become more amenable to interventions, suggesting that FUS can lead to the development of new therapeutic strategies to treat brain tumors.

O6 Acoustic emissions during blood-brain barrier disruption with focused ultrasound and real-time feedback control under infusion administration of microbubbles – feasibility study in rodent model

Chenchen Bing¹, Debra Szczepanski¹, Imalka Munaweera¹, Yu Hong¹, Ian Corbin², Rajiv Chopra^1,2

¹Radiology, UT Southwestern Medical Center, Dallas, Texas, USA; ²Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, USA

Correspondence: Chenchen Bing

f₀ = 0.5MHz was attached to a stereotactic system and used to deliver ultrasoundenergy into the target brain region. One piezocomposite hydrophone with resonant frequency at 0.75MHz was built to acquire the signals emitted from stimulatedmicrobubbles. A feedback control algorithm was implemented in LabVIEW to quantify the area under curve (AUC) within sub-/ultra-harmonic bands during theultrasound exposure and to adjust the focal pressure accordingly based on the difference between current AUC and a desired threshold. Initial f₀, 1.5f₀ as a function offocal pressure and microbubble concentration. Due to the significant response detected at 1.5in vitro. Next an in-vivo study was performed in a rat model toevaluate the acoustic emissions and the feasibility of real-time control of the AUC at a target level. Acoustic emissions from a bolus injection and continuous infusionwere evaluated. For bolus injection, a fixed pressure level of 0.54 MPa was applied, while for infusion experiment, the feedback control was used to control the AUC atvarious levels. Evans blue dye was used as an indicator of BBB opening.

in vitro, with the greatestchanges occurring at 0.75 MHz (1.5f₀ and tested with a continuous infusion of microbubbles. Successful maintenance of the AUC at different target value was achieved invivo at multiple locations in the brain, and BBB opening was confirmed as leakage of Evans Blue at the target locations (Fig. 1D).

Maria Eleni Karakatsani¹, Tara Kugelman¹, Shutao Wang¹, Karen Duff³, Elisa E. Konofagou^1,2

¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Radiology, Columbia University, New York, New York, USA; ³Pathology and Cell Biology, Columbia University, New York, New York, USA

Correspondence: Maria Eleni Karakatsani

1, Cyril Lafon², Jean-Louis Mestas², Shin-ichiro Umemura¹

¹Graduate School of Biomedical Engineering - Umemura-Yoshizawa Laboratory, Tohoku University, Sendai, Miyagi, Japan; ²LabTAU, INSERM U1032, Université deLyon, Lyon, France

Correspondence: Maxime Lafond

A classic method for source localization is triangulation. The localization of the cavitation cloud is deduced from the delays obtained between threereceptors with known positions. In our case, the receptors are PVDF hydrophones. Two confocal transducers are emitting a pulse at 1.1 MHz in order to generate cavitation in the optical field of a high-speed camera. The signals from the three hydrophones were recorded during the US pulse on a digital oscilloscope and the delays between the hydrophones were calculated by finding the delay maximizing the inter-correlation between the recorded signals. The source position calculated from thedelays was finally superimposed over the images from the camera (Fig. 1). The positions calculated with this method were compared to the positions of the clouds visually estimated. The mean discrepancy was calculated. The method was firstly applied using the signals with full frequency bandwidth. Then, the post-processing operation was repeated after keeping only the bandwidth of 200 kHz around the sub-harmonic frequency (550 kHz). Also, simulations are performed to evaluate the versatility of the method in various test cases. Notably, spatial spreading of the source, source separation and the influence of the hydrophones repartition are evaluated.

1, Martijn de Greef¹, Rémi Berriet², Chrit Moonen¹, Mario Ries¹

¹UMC Utrecht, Utrecht, Netherlands; ²Imasonic SAS, Voray-sur-l'Ognon, France

Correspondence: Pascal Ramaekers

1, Matthieu Guedra¹, Jean-Christophe Bera¹, Wen-Shiang Chen², Hao-Li Liu³, Claude Inserra¹

¹Univ Lyon, Université Lyon 1, INSERM, LabTAU, F-69003, LYON, France, Lyon, France; ²Department of Physical Medicine & Rehabilitation, National TaiwanUniversity Hospital, Taipei, Taiwan; ³Department of Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan

Correspondence: Corentin Cornu

1, Eilon Hazan^1,3, Omer Naor¹, Michael Plaksin¹, Inbar Brosh¹, Noam Maimon², Yoav Levy², Eitan Kimmel¹, Itamar Kahn³, Shy Shoham¹

¹Department of Biomedical Engineering, Technion I.I.T, Haifa, Israel; ²Insightec LTD, Tirat HaCarmel, Israel; ³Department of Medicine, Technion I.I.T., Haifa, Israel

Correspondence: Steve Krupa

Shoham S, Krupa S, Hazan E, Naor O, Levy Y, Maimon N, Brosh I, Kimmel E, Kahn I. A126 Research platform for rodent studies of wavefront engineered ultrasonic neuromodulation. J Ther Ultrasound. 2016; 4(Suppl 1):31. Available from: https://jtultrasound.biomedcentral.com/articles/10.1186/s40349-016-0076-5

O12 Image-guided dual-target brain stimulation on mouse by array ultrasound

Guofeng Li, Jiehan Hong, Qiuju Jiang, Peitian Mu, Ge Yang, Congzhi Wang, Weibao Qiu, Hairong Zheng

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Correspondence: Guofeng Li

2,1, David Moore³, Matthew Eames³, John Snell^3,4, James Larner², Neal Kassell^3,4

¹LabTAU, INSERM, Lyon, France; ²Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA; ³FUS Foundation, Charlottesville, Virginia, USA; ⁴Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA

Correspondence: Cyril Lafon

1, Ben Lucht, Rohan Ramdoyal¹, Samuel Gunaseelan¹, Tyler Portelli¹, Ping Wu¹, Kullervo Hynynen^1,2

¹Sunnybrook Research Institute, Toronto, Ontario, Canada; ²Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Correspondence: Ben Lucht

1, Wayne Brisbane¹, Stella Whang², Yak-Nam Wang³, Kayla Gravelle², Venu Pillarisetty⁴, W. Conrad Liles⁵, Vera Khokhlova³, Michael Bailey³, Tatiana D. Khokhlova², Joo Ha Hwang²

¹Department of Urology, University of Washington, Seattle, Washington, USA; ²Department of Gastroenterology, University of Washington, Seattle, Washington, USA; ³Center for Industrial and Medical Ultrasound, University of Washington, Seattle, Washington, USA; ⁴Department of Surgery, University of Washington, Seattle, Washington, USA; ⁵Department of Medicine, University of Washington, Seattle, Washington, USA

Correspondence: George R. Schade

in vivo. We characterized the long-term immune response to BH RCC tumor ablation in a ratmodel.

2, Aaron Prodeus^{1, 2}, Jean Gariepy^{1, 2}, Kullervo Hynynen^{1, 2}, David Goertz^{1, 2}

¹University of Toronto, Toronto, Ontario, Canada; ²Sunny brook Research Institute, Toronto, Ontario, Canada

Correspondence: Sharshi Bulner

1, Tsang-Wei Tu¹, Scott R. Burks¹, Bobbie K. Lewis¹, Joseph A. Frank^1,2

¹Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, USA; ²National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: Kee W. Jang

^1,2, Jeremy Vion^1,2_, Loïc DAUNIZEAU^1,2, Christopher Bawiec², Guillaume BOUCHOUX^{1, 3}, Nicolas Sénégond⁴, Jean-Yves Chapelon^1,2, Alexandre CARPENTIER^3,5

¹LabTAU, INSERM, U1032, Lyon, Rhone-Alpes, France; ²Univ Lyon, Université Lyon 1, Lyon, F-69003, France; ³CarThera Research Team, Brain and Spine Institute, Paris, France; ⁴Vermon SA, Tours, France; ⁵Department of Neurosurgery, Assistance Publique, Hopitaux de Paris, Pitie Salpetriere, Paris, France

Correspondence: William Apoutou N'Djin

in vivo on 10 pigs and monitored under real-time multi-planar magnetic resonance thermometry (MRT) (Fig. 1).

in vivo. Further investigations are ongoing to improve the robustness of the CMUTdevices and increase the treatment volumes. This project was supported by CarThera, the French National Research Agency (ANR, 2010) and Single InterministerialFund (FUI, 2013).

O20 Real-time HIFU beam imaging using beamforming in an ultrasound scanner

Kazuhiro Matsui¹, Françoise CHAVRIER^{2, 4}, Takashi Azuma³, Ichiro Sakuma^{1, 5}, William Apoutou N'Djin^{2, 4}, Rémi Souchon^2,4

¹Engineering, The University of Tokyo, Tokyo, Japan; ²LabTAU, INSERM unité 1032, Lyon, France; ³Medicine, The University of Tokyo, Tokyo, Japan; ⁴Univ Lyon, Université Lyon 1, Lyon, France; ⁵Medical Device Development and Regulation Research Center, Tokyo, Japan

Correspondence: Kazuhiro Matsui

The object of this study is to provide a method for imaging, in real time, the HIFU beam inside an acoustically propagative medium using beamforming in an ultrasound scanner.Novelty and advantagesThe novelty of the method can be found in its implementation of beamforming in an ultrasound scanner, which is analogous to the backward reconstruction using time reversal. The advantage of this method is its real-time imaging capability owing to digital parallel processing of the scanner. Further advantage is simplicity of the imaging system without requiring additional equipment aside from an ultrasound scanner and an ultrasound array serving as a time-reversal mirror.

via plane-wave beamforming. Evaluations: The feasibility of the method was evaluated using either the time-reversal reconstruction or the beamforming reconstruction, with and without HIFU beam aberrations. First, in the experiment in water without HIFU beam aberrations, performance of the method was demonstrated in comparison with the reference field obtained by numerical calculation of the forward propagation using the Rayleigh integral and hydrophone scanning. Then, in the experiment with HIFU beam aberrations induced by heterogeneous hydrogel, HIFU beam visibility was evaluated with referred to the HIFU pressure field measured by hydrophone scanning.

Burks S, Nagle M, Kim S, Milo B, Frank J. A90 Low-intensity ultrasound prolongs lifetimes of transplanted mesenchymal stem cells. J Ther Ultrasound. 2016; 4(Suppl 1):31. Available from: https://jtultrasound.biomedcentral.com/articles/10.1186/s40349-016-0076-5

O22 Impact of microbubble-enhanced radiofrequency ablation of rabbit liver

Zhong Chen, Xueyan Qiao

Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China

Correspondence: Zhong Chen

Dai H, Chen F, Yan S, Ding X, Ma D, Wen J, Xu D, Zou X. In Vitro and In Vivo Investigation of High-Intensity Focused Ultrasound (HIFU) Hat-Type Ablation Mode. Med Sci Monit. 2017; 23:3373-3382. Available from: https://www.medscimonit.com/abstract/index/idArt/902528 DOI: 10.12659/MSM.902528

**O24 Image-based predicition of focusing gain in situ using dual-mode ultrasound arrays**

Brogan T. McWilliams, Dalong Liu, Emad S. Ebbini

Electrical Engineering, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence: Brogan T. McWilliams

in situ utilizing simplified propagation models and calibration power measurements.

in vitro setup used to provide a validation for the image-based approach. In particular, an acoustic power meter (Omega, Ohmic instruments Easton, MD) was modified to allow the measurement of the insertion loss due to a slab of tissue-mimicking phantom between the DMUA and the tip of the cone (treated as the target). The TM phantom was fabricated from animal skin bovine gelatine, graphite,1-propanol, glutaraldehyde, and deionized water. Absorption of the phantom is predominately due to the presence of graphite and was determined to be 0.6 and 1.0dB/cm/MHz for two 4-mm disk-shaped slaps. Two modes of the imaging were used to characterize the FUS beam propagation through the tissue: 1) Synthetic-aperture(SA) imaging, which provides larger field of view (FoV) to characterize the propagation medium, and 2) Single-transmit focus (STF), which provides specific feedback about the interactions between the FUS beam and the tissue in its path to the target. The STF imaging is performed using the same beamforming parameters of the intended therapeutic HIFU beam, but at diagnostic levels and with sub-microsecond pulse duration. HIFU was applied at 4 different frequencies (2.4 to 4.2 MHz in stepsof 0.6 MHz). HIFU shots of 1-sec durations were used and repeated 4 times. SA and STF images were collected before, during and after the application of therapeutic HIFU. The STF frame rate was 400 fps, which was helpful to fully characterize the incidence of cavitation and/or instability in the power measurement.

in vitro at multiple frequencies. The method has been applied for the estimation of the focusing gain in vivo. As described, STF imaging of the phantom slab allowed for measuring the beam dimensions and the FUS interaction with the tissue and could be used in future studies to extract details of an inhomogeneous medium to provide accurate estimates of the focusing gain (or heating rate). Further validation of the calculated heating rate will be performed in vivo by measuringtemperature with thermocouples in the vicinity of the focus.

O25 An automatic approach to lesion planning for robotic HIFU

Tom Williamson, Scott Everitt, Ranjaka De Mel, Sunita Chauhan

Mechanical and Aerospace Engineering, Monash University, Melbourne, Victoria, Australia

Correspondence: Tom Williamson

in situ’ in variousorgans. At this stage, the neoplasm is generally spherical in shape while, conventionally, focused ultrasound (FUS) treatment involves ‘raster’ scanning the formation ofthe HIFU lesions in the ROI, an approach that will generally not conform to the spherical tumor geometry. This may lead to two major undesirable effects: large gaps or overlaps at the tumor margins (physical spacing isn’t optimized) and between individual lesions, or significant ‘lesion-to-lesion’ interaction creating uncertainty in the shape, size and extent of the subsequent lesions due to the remnant effect of previously laid lesions. Furthermore, the gaps between adjacent lesions may have a seeding effect, leading to further growth of malignancies due to the untreated sections. To avoid lesion interactions, several authors suggested a pre-defined time delay betweenlesions or change in exposure parameters. The former results in unnecessary treatment delays while the latter involves capacious real-time computations for optimizing the treatment (dynamically computing thermal dose) as well as remotely and frequently switching on/off high power equipment. In order to overcome these deficiencies, we propose a method for determining the optimal lesion arrangement within any arbitrary tumor size and shape, based on an extension of the bubble packing algorithm first described by Shimada in 1995 [1]. The original algorithm was extended to allow lesions to take any arbitrary position andorientation within the specified tumor volume, and evaluated on spherical and ellipsoidal tumor models.

1, Jonathan Caloone¹, Anthony Kocot¹, Cyril Huissoud²

¹LabTAU - U1032, INSERM, Lyon, Rhône Alpes, France; ²CHU Croix Rousse, LYON, France

Correspondence: David Melodelima

ex vivo model. The effectiveness of this HIFU device applied to the perfused placental unit must be studied in a preclinical animal study under conditions similar to those in humans before starting a clinical trial. Here, we report a feasibility study using a monkey model of pregnancy. The 3 objectives of this work were (i) to evaluate the feasibility and reproducibility of HIFU lesions in the placenta of pregnant monkeys 2,1, Raj Aravalli¹, Emad S. Ebbini¹

¹Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota, USA; ²Siemens, Seattle, Washington, USA

Correspondence: Dalong Liu

1, Christian Aurup¹, Carlos J. Sierra Sánchez¹, Julien Grondin¹, Wenlan Zheng¹, Vincent Ferrera², Elisa E. Konofagou^1,3

¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Neuroscience, Columbia University, New York, New York, USA, ³Radiology, Columbia University, New York, New York, USA

Correspondence: Shih-Ying Wu

in vivo in preparation for clinical trials.

in vivo experiments, for the first time the noninvasive FUS treatment was achieved within 30 min outside the MRI system for primates, and targeting flexibility allowed BBB opening in both the peripheral cerebral cortex and deeply-seated subcortical structures with the use of a free-guide arm and the inflatable bladder system of the FUS transducer to couple with the scalp. Moreover, the achieved targeting accuracy were proximal to the predicted 2-mm limit in simulation. The accuracy in the awake animal setting (3.0 mm) was found to be comparable to the sedate animal setting (3.2 mm), which was higher compared to the frame-based stereotaxis due to the improvement of lateral positioning of the animal, and the focal shift in the acoustic beam path was due to the skull distortion. On the other hand, real-time cavitation mapping was performed with neuronavigation guidance during the entire sonication, with the frequency spectra data showed a dramatic increase of the cavitation signal (harmonics and ultraharmonics) after injecting microbubbles. The acoustic mapping provided real-time spatial monitoring during the sonication and successfully confirmed the location of BBB opening. Finally, in all the experiments performed, no acute damage such as hemorrhage (SWI) or edema (T2-weighted imaging) was detected upon radiologic examination 2 h after sonication.

in vitro that these limitations may be due to the conventional ultrasound sequences used to disrupt the BBB. These sequences consist of long-pulses emitted at a slow rate and generate a mixture of both desired and undesired cavitation activities. We have recently developed and tested a new low pressure rapid short-pulse (RaSP) sequence in vivo efficiency and safety of ultrasound-mediated drug delivery to the brain.

in vivo in C57BL/6 mice would improve the efficiency and safety of brain drug delivery. We compared our RaSP sequence (peak-negative pressure: 400 kPa; pulse length (PL): 5 cycles; pulse repetition frequency (PRF): 1.25 kHz; burst length: 10 ms) to the current gold standard, conventional sequence at the same acoustic pressure (PL: 10,000 cycles; PRF: 0.5 Hz; burst length: 10 ms). Fluorescently-tagged (Texas Red) 3 kDa dextran and microbubbles were intravenously injected in mice while sonicating the left hippocampus with a 1 MHz focused ultrasound transducer. A 7.5 MHz passive cavitation detector captured the microbubble acoustic emissions. The relative dose and distribution of the drug were quantified by calculating the normalised optical density (NOD, average increase in fluorescence in the targeted area normalised by the control) and the coefficient of variation (COV, standard deviation over the average fluorescence intensity in the targeted region). Safety was assessed by haematoxylin and eosin (H&E) histological staining.

Nappoli A, Zaccagna F, Catocci G, Giulia B, Caliolo G, Andrani F, Catalano C. Magnetic resonance guided focused ultrasound surgery (MRgFUS) treatment of osteoid osteoma: a prospective development study. J Ther Ultrasound. 2015; 3(Suppl 1): O44. Available from: https://jtultrasound.biomedcentral.com/articles/10.1186/2050-5736-3-S1-O44

O32 Transoesophageal HIFU for cardiac ablation: experiments on beating hearts

Paul Greillier¹, Bénédicte Ankou², Ali Zorgani¹, Francis Bessière², Fabrice Marquet³, Julie Magat³, Sandrine Melot-Dusseau⁴, Romain Lacoste⁴, Bruno Quesson³, Mathieu Pernot⁵, Philippe Chevalier², Cyril Lafon^{1, 6}

¹LabTau - U1032, INSERM, LYON, Rhône, France; ²Hôpital Louis-Pradel, Lyon, France; ³IHU-LIRYC - CHU Bordeaux, Pessac, France; ⁴Station de primatologie -CNRS- UPS846, Rousset, France; ⁵Institut Langevin - Ondes et Images - ESPCI ParisTech, CNRS UMR 7587, Paris, France; ⁶University of Virginia, Charlottesville, Virginia, USA

Correspondence: Paul Greillier

Greillier P, Ankou B, Bessière, Zorgani A, Pioche M, Kwiecinski W, Magat J, Melot-Dusseau S, Lacoste R, Quesson B, Pernot M, Catheline S, Chevalier P, Lafon C. A75 Trans esophageal HIFU for cardiac ablation: first experiment in non-human primate. J Ther Ultrasound. 2016; 4(Suppl 1):31. Available from: https://jtultrasound.biomedcentral.com/articles/10.1186/s40349-016-0076-5

O33 In-vivo investigation of the combination of focused ultrasound and radiotherapy, using photoacoustic imaging as aplanning and monitoring tool

Marcia M. Costa, Anant Shah, Ian Rivens, Tuathan O'Shea, Carol Box, Jeff Bamber, Gail ter Haar

Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, UK

Correspondence: Marcia M. Costa

1, Takashi Azuma¹, Kosuke Minamihata², Satoshi Yamaguchi¹, Shinya Yamahira¹, Etsuko Kobayashi¹, Mariko Iijima¹, Yoshikazu Shibasaki¹, TeruyukiNagamune¹, Ichiro Sakuma¹

¹The University of Tokyo, Tokyo, Japan; ²Kyushu University, Fukuoka, Japan

Correspondence: Ayumu Ishijima

1. Kawabata K et al. Jpn J Appl Phys 2005; 44: 4548.

2. Ishijima A et al. Ultrasonics 2016; 69: 97–105.

3. Lee YH et al. Biochem Biophys Res Commun 2013; 441: 1011–1017.

4. Wang CH et al. Biomaterials 2012; 33: 1939–1947.

O35 Dual mode time reversal cavity for US shockwave therapy and 3D imaging

J. Robin^1,2, B. Arnal¹, M. Tanter¹, M. Pernot¹

¹Institut Langevin, Paris, France; ²Université Paris 7, Paris, France

Correspondence: J. Robin

[1] Arnal et al, Appl Phys Lett, 101 1-5, 2012

[2] Robin et al, IEEE IUS, 2015

[3] Sarvazyan et al, Acoust Phys 55 630–7, 2009

[4] Luong et al, Sci Rep 6 36096, 2016

[5] Montaldo et al, Appl Phys Lett 2004 (No Image Selected)

O36 The effects of steroids on the myocardial reduction induced by myocardial cavitation-enabled therapy (MCET)

Y. I. Zhu¹, X. Lu², C. Dou², D. L. Miller², O. D. Kripfgans^{2, 1}

¹O.D. Kripfgans, Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; ²Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA

Correspondence: Y. I. Zhu

in vivo model for HCM. Under ketamin/zylazine IP anesthesia, contrast agent was infused at a rate of 5μL/min/kg (tail vein catheter). The shaved and depilated left thorax was aimed at with a cardiac phased array (10S, Vivid 7, GE Healthcare) to center on the left ventricular myocardium. In this arrangement a 19 mm diameter single element therapy transducer was co-aligned to aim at a registered region of interest in the field of view of the 10S array. For therapy 10-cycle tone bursts at 1.5 MHz, 4 repetitions at 0.25 ms pulse interval, i.e. 4.0 kHz PRF, were sent every 8 heartbeats, aligned with trigger end systole (RR/3, using ECG gating). Peak negative free field pressures of 4 MPa were used to induce cavitation for 10 min. Therapy and sham therapy groups were followed up with MP administered at 0, 3, 6 and 24 hours after ultrasound exposure. Specifically, 30 mg/kg was chosen as high dose while 1 mg/kg was used as low dose alternative. Myocardial wall thickness 24 hours after therapy, measured from echocardiography was used to gauge the effect of initial myocardial swelling. White blood cell count was carried out 24 hours after therapy. Hearts were removed after 4 weeks and examined for evidence of the MP treatment effect. Histological sections with Masson’s trichrome staining were quantitatively analyzed for extent of fibrosis, i.e. tissue scarring.

Imaging protocol was: TR=600ms, TE=36ms, slice thickness=5mm, resolution=1.6*1.6mm2, matrix=54*128, EPI factor=9. Acquisition time=8.4s. Two sets of images with opposite polarity of DEG were used to quantify the displacement in each measurement. Ten measurements of ARFI were scanned before and immediately after HIFU sonication. T-test was used to determine whether tissue displacements have significantly changed. Temperature rise was monitored by GREduring HIFU sonication. The protocol was: TR=29ms, TE=10ms with the same FOV and resolution. The ambient temperature was 19°C. T2w image was acquired after HIFU sonication with TR=5000ms, TE=89ms, resolution=0.8*0.8 mm2, matrix=108*256.

p = 0.18 from 1, Xue Feng¹, Helen L. Sporkin¹, Jeff Elias², Kim Butts-Pauly³, Craig H. Meyer¹

¹Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA; ²Neurological Surgery, University of Virginia Hospital, Charlottesville, Virginia, USA; ³Radiology, Stanford University, Palo Alto, Virginia, USA

Correspondence: Steven P. Allen

[1] Plata et al. “A feasibility study on monitoring the evolution of apparent diffusion coefficient decrease during thermal ablation,” Med. Phys., 42(8), 5130–5137, 2015

[2] Smith et al. “Reduced field of view MRI with rapid, B1-robust outer volume suppression,” Magn. Reson. Med., 67(5), 1316–1323, 2012.

O41 Selection of MR-HIFU hyperthermia treatment sites based on MR thermometry evaluation in healthy volunteers

Satya V.V.N. Kothapalli¹, Michael Altman², Ari Partanen³, Lifei Zhu¹, Galen Cheng¹, H. Michael Gach², William Straube², Dennis Hallahan², Hong Chen^1,2

¹Biomedical Engieering, Washington University in Saint Louis, Saint Louis, Missouri, USA; ²Department of Radiation Oncology, Washington University in St. Louis, Saint Louis, Missouri, USA; ³Clinical Science MR Therapy, Philips, Andover, Massachusetts, USA

Correspondence: Satya V.V.N. Kothapalli

in vitro and intravascular bioeffects. Therefore, our study investigated the behaviors of ADV-Bs in vessels and tissue triggered by ultrasound (US), and then evaluated the feasibility of using intertissue ADV-Bs to treat resistant tumor cells by physical damage.

in vitro to deliver drugs into cells. Through these studies, it was discovered that several mechanisms of trans-membrane drug delivery exist and that they are highly dependent on the acoustic parameters, microbubble conditions, and the cell-type used. Despite promising results from these study, the advancement from single cell-bubble interactions to clinical use has not been made. This gap in development is largely because the underlying mechanism of trans-membrane drug delivery under high flow condition and for a large population of cells, remains poorly understood and poorly controlled. Our study explores the ultrasound and microbubble-mediated trans-membrane drug delivery efficiency and safety to a monolayer of endothelial cells using a state-of-theart physiologically-relevant cultivation system under different ultrasound exposure conditions. In the end, we will evaluate the critical question on whether safe transmembrane drug delivery can be achieved in such a complex, physiologically relevant environment.

1,2, Melissa Lin², Eric O'Neill², Oliver D. Kripfgans^{2, 1}, Renny T. Franceschi^{3, 4}, Andrew J. Putnam⁴, Mario L. Fabiilli^{1, 2}

¹Applied Physics Program, University of Michigan, Ann Arbor, Michigan, USA; ²Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA; ³School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA; ⁴Department of Biomedical Engineering, University of Michigan, AnnArbor, Michigan, USA

Correspondence: Alexander Moncion

in vivo model via CD31 immunohistochemical staining on days 7 and 14.

ex vivo. The ability to non-invasively stimulate and inhibit the PNS with FUS would allow clinicians an alternative therapeutic modality to treat peripheral neuropathy, as current treatment procedures can generate systemic side effects or require invasive procedures. In this study, we aim to show that FUS can elicit excitatory effects targeting the PNS and generate downstream physiological responses.

ex vivo mouse limbs alongside the sciatic nerve and exposed to FUS stimulation. A force balance was used to determine the acoustic radiation force generated by the transducer to estimate the tissue deformation in the focal region. To confirm neural activity at the single-unit level, a via FUS was shown capable of eliciting both observable leg twitching and measurable EMG responses when using the following FUS parameters: 0.2-5.7 MPa, 35-100% DC (continuous wave), 0.1-1kHz PRF, 0.8-10.5 ms stimulation duration. Increasing the pressure and DC raised the average peak-to-peak EMG response along with the success rate (Fig. 1). Varying the PRF or stimulation duration did not have a significant effect on response. Both delay and peak-to-peak EMG responses for FUS stimulation were found to be comparable to direct electrical stimulation of the sciatic nerve. Mice stimulated with efficacious parameters did not display any significant deviation in behavior compared to the control group or baseline values. The blinded histology study did not detect any damage for the stimulated group, only for the positive control. In in vivo. This demonstrates that FUS can be a non-invasive alternative to conventional therapeutic methods. Specific FUS parameters has been identified for successful and safe stimulation. Future work to explore the potential mechanisms of generation of the action potential will dictate the FUS parameters to translate this technique to clinical applications.

O46 The safety and feasibility of high intensity focused ultrasound in treatment of resistant hypertension

P. You

State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology,Chongqing Key Laboratory of Ultrasound in Medicine and Engineering,College of Biomedical Engineering,Chongqing Medical University, Chongqing, China

1,2

¹The College of Biomedical Engineering, Chongqing Medical University, Chongqing, Chongqing, China; ²Haifu Hospital of the First Hospital Affiliated Hospital, Chongqing Medical University, Chongqing, China

1,2, A. Dupre^{1, 2}, Y. Chen², D. Perol², J. Vincenot^1, M. Rivoire^{1, 2}

¹LabTAU - U1032, INSERM, Lyon, Rhône Alpes, France; ²Centre Leon Berard, Lyon, France

Correspondence: D. Melodelima

Melodelima D, Dupre A, Vincenot J, Chen Y, Perol D, Rivoire M. A49 Clinical experience of intra-operative High Intensity Focused Ultrasound in patients with colorectal liver metastases. Results of a Phase II study. J Ther Ultrasound. 2016; 4(Suppl 1):31. Available from: https://jtultrasound.biomedcentral.com/articles/10.1186/s40349-016-0076-5.

Modena Cam

O49 Catheter-directed thrombolysis of deep vein thrombosis enhanced by intraclot microbubbles and ultrasound: A clinical study

Q. Zhu¹, S. GAO¹, G. Dong², M. Guo¹, F. XIE³

¹Department of Ultasound, XinQiao Hospital,Third Military Medical University, Chongqing, China; ²Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; ³Internal Medicine Cardiology, University of Nebraska Medical Center, Omaha, NE, China

Correspondence: Q. Zhu

S. Yeo¹, Y. Kim^{2, 3}, H. Lim^{3, 4}, H. Rhim³, S. Jung^{4, 5}, N. Hwang⁵

¹Radiology, University Hospital of Cologne, Cologne, Germany; ²Radiology, Mint Hospital, Seoul, Korea; ³Radiology and Center for Imaging Science, Samsung Medical Center, Seoul, Korea; ⁴Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea; ⁵Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea

Correspondence: S. Yeo

1, G. G. Powathil², P. Ziegenhein¹, J. Ijaz³, I. Rivens¹, M. Chaplain⁴, U. Oelfke¹, G. ter Haar¹

¹Joint Department of Physics, The Institute of Cancer Research, Sutton, UK; ²Swansea University, Swansea, UK; ³Bristol University, Bristol, UK; ⁴St. Andrew's University, St. Andrews, UK

Correspondence: S. C. Brueningk

in vitro FUS experiments, (2) to verify FUS simulation using measured temperature distributions, (3) to predict the cellular effects of combination treatments.

via mitotic catastrophe. The CAM was compared to results from experiments designed to characterise the response of HCT116 cells [1] G. Powathil et al., Semin Cancer Biol, (30, p.13–20), 2015 [2] B. Clarke, Ultrasound Med Biol, (21, p. 353–363), 1995

O53 Lithotripter shock wave interaction with a bubble near various bio-material

S. Ohl¹, E. Klaseboer¹, A. Szeri², B. Khoo³

¹Institute of High Performance Computing, Singapore, Singapore; ²University of California, Berkeley, Berkeley, California, USA; ³National University of Singapore, Singapore, Singapore

Correspondence: S. Ohl

Sankin, G. N. & Zhong, P. (2006), ‘Interaction between shock wave and single inertial bubbles near an elastic boundary’, Phys. Rev. E 74, 046304.

O54 Three-dimensional passive acoustic localization and mapping for cavitation: a preliminary study

S. Lu, X. Du, M. Wan

Biomedical Engineering, Xi’an Jiaotong University, Xi’an, China

Correspondence: S. Lu

M can only provide a plane distribution of cavitation, which is not conducive to clinical diagnosis. PAM based on a hemispherical array has been used for three-dimensional (3D) vascular imaging with high resolution in the brain, but it is not suitable for treatment monitoring of other biological tissues, such as liver and kidney. This means that 3D PAM based on an area array for omnibearing monitoring of ultrasound therapy is required. The objective of this work is to develop a three-dimensional super-resolution passive imaging technique for microvessel and an omnibearing monitoring of ultrasound therapy in real time.

1, L. Sebeke², M. Baragona³, A. Elevelt⁴, R. Maessen³, D. Bošnački¹, H. Ten Eikelder¹

¹Eindhoven University of Technology, Eindhoven, Netherlands; ²University Hospital Cologne, Cologne, Germany; ³Department of Multiphysics & Optics, Philips Research Eindhoven, Eindhoven, Netherlands; ⁴Department of Oncology Solutions, Philips Research Eindhoven, Eindhoven, Netherlands

Correspondence: D. Modena

1,2, A. Wright², D. Goertz^1,2

¹University of Toronto, Toronto, Ontario, Canada; ²Sunnybrook Research Institute, Toronto, Ontario, Canada

Correspondence: C. Acconcia

Correspondence: S. Zhang

in vivo and in vivo and ex vivo tissue optical properties during high-intensity focused ultrasound (HIFU) exposures. Baseline changes in optical properties have been previously measured as a function of thermal dose for chicken breast exposed to a temperature- controlled water bath (doi:10.1088/0031-9155/59/13/3249). In this work, the wavelength-dependent optical scattering and absorption coefficients of ². In Fig. 2, the reduced scattering coefficient (μ_s') at 975 nm is plotted as a function of the measured thermal dose for all sonications. Results show that HIFU-induced thermal damage results in changes in scattering at all optical wavelengths from 400-1300 nm (Fig. 1). Furthermore, the reduced optical scattering coefficient increases dramatically for exposures exceeding approximately 10^3 cumulative equivalent minutes at 43°C (CEM₄₃) (Fig. 2).

2, 1, S. Sethuraman², B. Cheng¹, J. Kruecker², R. Chopra¹

¹Department of Radiology, UT Southwestern Medical Center, Dallas, Texas, USA; ²Ultrasound Imaging & Interventions, Philips Research North America, Cambridge, Massachusetts, USA

in vivo feasibility of using strain-based ultrasound (US) thermometry to monitor mild HIFU heating in muscle tissue, by direct comparison of temperature measurements made simultaneously using US strain estimation, magnetic resonance (MR) thermometry, and implanted optical sensors.

in vivo rabbit muscle under normal respiration and perfusion, strain-based ultrasound thermometry is feasible in the mild hyperthermia range.

O62 Changes in backscatter of liver tissue due to thermal heating can be used for guiding focused ultrasound ablations

V. Barrere^1,2, D. Melodelima^1,2

¹LabTAU, INSERM, Lyon, France; ²Université Claude Bernard, Lyon 1, Lyon, France

Correspondence: V. Barrere

1, S. Wang¹, T. Payen¹, E. Konofagou^1,2

¹BME, Columbia University, New York, New York, USA; ²Radiology, Columbia University, New York, New York, USA

Correspondence: Y. Han

in vivo environment and characterize tumor at different depth for better tumor localization and identification before and after HIFU treatment.

Figure 2 shows the HIFU sequence consisting of high-intensity short pulses to generate bubble clouds, named “trigger pulses”, and following moderate-intensity long bursts for the enhancement of the ultrasonic heating, named “heating bursts”. The focal point of the trigger pulse was electronically scanned at each corner of a regular hexagon 3 mm each side and a ring focal region was generated employing a sector vortex method in the heating burst exposure to cover the six foci of the trigger pulse for the volumetric cavitation-enhanced heating. The total acoustic power for the trigger pulse and heating burst were 1800 and 90 W, respectively. The duration and interval time for trigger pulses at each focal point were 25 and 3 μs, respectively. The trigger pulses were laterally scanned for four times. For heating bursts, the duration and interval time for trigger pulses at each focal point were 5 ms and 4 μs, respectively. The focal spot was scanned 5 times. The subtotal durations of trigger pulses and heating bursts were 0.67 and 50 ms, respectively. Immediately after the end of the heating bursts, a 2-ms interval time was reserved for ultrasonic imaging with plane wave transmissions at a frequency of 1.88 MHz. Ultrasonic RF data were also acquired during the HIFU exposure for the passive coagulation detection.

1,2, B. He^1,2, N. Deng^1,2, X. Chen^1,2, S. Chen^1,2, C. Chin^1,2

¹Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, China; ²National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Shenzhen, China

Correspondence: Y. Peng

in situ focal point of FUS, and therefore, it is possible to compensate for navigational error due to beam distortion by the heterogeneous human body. However, ultrasound still cannot assist in determining correct ultrasound dosage in a realistic clinical setting. Microbubbles has been investigated as a biocompatible, internal “probe” to convert a local parameter to an echo characteristic that can be measured externally. We accessed the main challenge is that the multiple acoustic parameters are not easily isolated from the multiple measureable characteristics of the echo signals (such as frequency shifts and harmonic component). In order to isolate the multiple factors (such as attenuation and perfusion rate) contributing to measurable echo characteristics, we sought to exploit the highly specific behaviors of microbubble destruction when exposed to intense ultrasound. This paper reports a feasibility study of a pre-treatment scheme to determine effective attenuation and other relevant parameters and subsequently compensate for them during the actual therapeutic procedure.

in situ beam intensity without controlling the microbubble concentration. The data sets of destruction curves obtained with attenuating layers were matched to the un-attenuated reference data set using a multi-parameter fitting algorithm (Fig. 3). The resulting fitted beam intensity was found to match closely the actual values, verified by independent measurement of attenuation. The errors of in-situ intensity, and compensation to the therapy planning applied, before the actual course of treatment is applied. This study also demonstrated some capabilities of the in-house designed 2D array therapy system. Particularly interesting is that an arbitrary treatment ROI can be exposed in less than 32 ms. In this study the scanning speed of the treatment focus was exploited to ensure that the entire ROI is exposed evenly in between excessive imaging events.

O66 Enhanced sonodynamic therapy using oxygen-rich nano gas vesicle

Y. Yang, X. Hou, L. Sun

Interdisciplinary Division of Biomedical Engineering, Hong Kong Polytechnic University, Hong Kong, China

Correspondence: Y. Yang

in vitro cytotoxicity by ultrasound treatment for 5 mins with the intensity of 5W/cm ² after MCF-7 and HeLa tumor cells were incubated with sonosensitizer Protoporphyrin IX (PpIX) and Oxy-NGV. Then the singlet oxygen level, as the major cytotoxic agent, was imaged using Singlet Oxygen Sensor Green (SOSG) in both cell-free model and intracellular scenario. Meanwhile the oxygen level was also tested by dissolved oxygen meter compared with conventional SDT method. These studies were repeated in both normal oxygen level and hypoxia condition.

in vivo.

in vivo study was performed using the xenograft mouse models of human liver and prostate cancers. Hep3B human cancer cells and DU145 human prostate cancer cells (2.0×106) were injected on flanks of athymic nude mice. Tumors were allowed to grow to 8-10 mm size and then separated into the following treatment groups: HIFU alone, PEI (50%Etoh, 50 μl) alone, PEI+HIFU (50%Etoh, 50 μl), and sham. Tumor sizes were measured by caliper every day and a veterinary diagnostic ultrasound system was used pre-treatment, 5 days, and 12 days’ post- treatment. Tumor volumes were calculated from the ellipsoid formula V=πabc/6, where a, b, c are tumor sizes in three orthogonal directions. Tumors were surgically removed and fixed using 10% formaldehyde solution. Samples were sent for H&E staining with a single blinded pathologist, and live/dead percentages of tumor cross sections were determined at 5 and 12 days post treatment. Cryogenic-Scanning Electron Microscopy (Cryo-SEM) was also used to capture membrane disruption post HIFU+PEI exposure on DU145 prostate cancer cells.

1, S. Song¹, M. Kajimoto¹, J. Chen¹, R. Fu1, K. Morrison², G. W. Keilman², C. H. Miao^1,3

¹Center for Immunity and Immunotherapies, Seattle Children's Research, Seattle, Washington, USA; ²Sonic Concepts Inc., Bothell, Washington, USA; ³Pediatrics, University of Washington, Seattle, Washington, USA

Correspondence: J. Harrang

via a midline incision. Next, using contrast US to confirm placement and perfusion, we catheterized a specific branch of the portal vein. Just prior to therapeutic US exposure, the inferior vena cava was temporarily occluded. Then US exposure and infusion of a solution containing pGL4 plasmid and phospholipid microbubbles (MBs) were initiated simultaneously. Therapeutic US was delivered 1, Q. Zhu¹, X. Dong¹, Z. Chen¹, Z. Liu¹, F. Xie²

¹Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China; ²Internal Medicine Cardiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

Correspondence: S. Gao

in situ cellular responses (e.g., cytoskeleton arrangement and intracellular delivery) to microbubble-mediated sonoporation process generated withdifferent microbubble-cell distances were systemically assessed based on an integrated system combining ultrasound exposure apparatus with real-time fluorescencemicroscope imaging. The microstreaming and shear stress generated by an oscillating microbubble was simulated based on an encapsulated microbubble dynamic modelwith considering nonlinear rheological effects of both shell elasticity and viscosity.

ex vivo. The simplified two-stage hundred-microsecond pulsing scheme was used. The lesion formation process in the BSA phantom was monitored by high-speed photography and passive cavitation detection.

ex vivo porcine kidney was shown in Fig. 2, and the voids appeared with no marked thermally coagulated component remaining after the homogenate had been removed. The root mean square (RMS) amplitude of the broadband noise from filtered passive cavitation detection (PCD) data revealed the strong inertial-cavitation activities, and the increase of RMS demonstrated that the boiling bubbles arose (Fig. 3a). Meanwhile, the inertial cavitation effect transferred to a higher band increment, which was beneficial to the frequency absorption efficiency (Fig. 3b).

Feng Y, Hu L, Chen W, Zhang R, Wang X, Chen J. Safety of ultrasound-guided high-intensity focused ultrasound ablation for diffuse adenomyosis: A retrospective cohort study. Ultrason Sonochem. 2017; 36: 139-145. Available from: http://www.sciencedirect.com/science/article/pii/S1350417716304096.

O76 Preliminary results of synthetic aperture imaging using random phased array

M. Zubair, R. J. Dickinson

Bioengineering, Imperial College London, London, United Kingdom

Correspondence: M. Zubair

1, I. Apostolakis¹, E. Konofagou^1,2

¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Radiology, Columbia University, New York, New York, USA

Correspondence: M. T. Burgess

in vivo.

in vivo imaging performance of synthesized microbubbles, which could provide guidance to the design and safe application of ultrasound contrast agents.

in-vivo and tumor imaging performance of synthesized bubbles was well explained by acoustic property measurements and shell elastic and viscous parameters. Possible correlation between physical/acoustical properties and

Correspondence: H. Zhong

in-vivo experimental conditions, when considering the areal strains expected to form in brain tissue during normal sonication.

2,1, A. Houdouin², T. Deffieux², M. Tanter², J. Aubry²

¹Université Paris Diderot, Paris, France; ²Institut Langevin, ESPCI Paris, CNRS UMR7587, INSERM U 979, Paris, France

Correspondence: G. Maimbourg

This work was supported by the Bettencourt Schueller Foundation and the 'Agence Nationale de la Recherche' under the program “Future Investments” with the reference ANR-10-EQPX-15.

[1] Clement G et al, A hemisphere array for non-invasive ultrasound brain therapy and surgery. Phys Med Biol, 2000 [2] Pernot M et al., High power transcranial beam steering for ultrasonic brain therapy. Phys Med Biol, 2003

[3] Jeanmonod D et al, Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus, 2012

[4] Fjield T et al, Low-profile lenses for ultrasound surgery. Phys Med Biol, 1999

[5] Melde K et al, Holograms for acoustics. Nature, 2016

[6] Patent: FR 1556217, July 2015

O82 Correlation of the lesion size in histology and mr images of the pig brain tissue by transcranial MR-guided focused ultrasound

D. Paeng^1,2, Z. Xu³, J. Snell⁴, A. H. Quigg⁵, M. Eames⁴, C. Jin^1,4, A. C. Everstine³, J. P. Sheehan³, B. S. Lopes⁶, N. Kassell⁴

¹Ocean System Engineering, Jeju National University, Jeju, Jeju, Korea; ²Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA; ³Neurosurgery, University of Virginia, Charlottesville, Virginia, USA; ⁴Focused Ultrasound Foundation, Charlottesville, Virginia, USA; ⁵Medical School, Virginia Common University, Richmond, Virginia, USA; ⁶Pathology, University of Virginia, Charlottesville, Virginia, USA

Correspondence: D. Paeng

Electrical Engineering, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence: H. Aldiabat

ex vivo results demonstrating the feasibility of image-based refocusing to regain the focusing gain.

ex vivo. In some experiments, the target was the nose of a cone positioned near the geometric focus of the DMUA behind the skull sample (Fig. 1). In other experiments, skull samples were embedded in a tissue- mimicking phantom and positioned at a distance of approximately 32-mm from the apex of the DMUA (corresponding to the skull position during ex-vivo human skullcaps mounted centrally within a 500 kHz, 256-element histotripsy transducer with transmit-receive capable elements. Aberration correction was applied in two ways, 1) based on hydrophone measurements and 2) based on histotripsy pulse-backscatter measurements (from bubbles generated transcranially without aberration correction) acquired using the array elements as receivers. Following aberration correction, hydrophone measurements of the focal pressure amplitudes and focal beam profiles were acquired, as were measurements of the focal pressure amplitudes as a function of the electronic steering distance through the skull. Lesioning experiments were carried out in red blood cell tissue phantoms to compare how the different aberration correction modalities affected lesioning. Finally, volumetric treatments of large clots through the skull were conducted and treatment efficacy for each aberration correction case was evaluated as a function of clot volumes liquefied.

1, R. M. Jones^1,2, N. Lipsman³, M. L. Schwartz³, K. Hynynen^1,2

¹Sunnybrook Research Institute, Toronto, Ontario, Canada; ²Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; ³Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Correspondence: J. R. Sukovich

In vivo studies were performed in two steps. For the first step, multiple BBB-openings were performed at four different FUS condition along with microbubbles (SonoVue) to find safe and effective treatment condition. The treatment was performed once a week for six weeks. In the second step, breast cancer cells (BT-474) were pre-treated with chemo-agent prior to the inoculation in the rat brain for the brain metastasis model. Animals were treated in three groups: control, chemo-agent treatment only, and chemo-agent treatment with BBB-opening. FUS condition and injection volume of microbubbles for BBB-opening were obtained from the first step experiment. Animals were treated on a weekly basis for six weeks and post-treatment tumor growth monitoring was followed for 12 weeks.

1,2, Calum Crake¹, Brian Tracey², Costas Arvanitis¹, Eric Miller², Nathan McDannold¹

¹Radiology, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA; ²Electrical and Computer Engineering, Tufts University, Medford, Massachusetts, USA

Correspondence: Tao Sun

in vivo for monitoring FUS-induced blood-brain barrier disruption in a clinical MRIguided FUS system (ExAblate 4000, InSightec, Haifa, Israel), which was integrated with a clinical 3T MRI unit (GE Healthcare). A 1024-element phased array was driven to transmit 10-ms pulsed FUS at 220 kHz. RF data for PAM were acquired using a research ultrasound imaging system (Verasonics, Redmond, WA) passively. The imaging probe (L382, Acuson, WA) was a 128-element linear array (fc = 3.21 MHz; bandwidth: ~ 75%). Transition and receiving systems were synchronized and the first180 μs of RF-data were recorded for each burst.

1, Sultan Deborah⁴, Hannah Luehmann⁴, Yuanchun Tai⁴, Josh Rubin², Yongjian Liu⁴, Hong Chen^{3, 5}

¹Mechanical Engineering and Material Science, Washington University in St. Louis, Saint Louis, Missouri, USA; ²Pediatrics Hematology/Oncology, WashingtonUniversity in St. Louis, Saint Louis, Missouri, USA; ³Biomedical Engineering, Washington University in St. Louis, Saint Louis, Missouri, USA; ⁴Radiology - Rad Sciences, Washington University in St. Louis, Saint Louis, Missouri, USA; ⁵Radiation Oncology, Washington University in St. Louis, SaintLouis, Missouri, USA

Correspondence: Dezhuang Ye

ex vivo brain slices and safety was assessed using histological staining. Second, another group of six mice was used for demonstrating the feasibility of FUS-enabled 64CuAuNCs delivery to the pons. FUS sonicated the left pons in the presence of systemically administrated microbubbles. After FUS sonication, mice were transferred to microPET/CT facility. 64CuAuNCs in 100 μL saline was injected into the mice ex vivo brain slices was performed, followed by inductively coupled plasma mass spectrometry (ICP-MS) quantification of the gold concentration in the brain. At last, the biodistribution of 64CuAuNCs was evaluated using gamma counting and ICP-MS.

1, Yu-Chien Lin¹, Chih-Hung Tsai¹, Wen-Shiang Chen², Claude Inserra³, Hao-Li Liu^1,4

¹Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan; ²Physical Medicine & Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan; ³Université de Lyon, Lyon, France; ⁴Neurosurgery, Chang Gung Memorial, Taoyuan City, Taiwan

Correspondence: Yu-Xian Lin

via this technique, large molecular delivery (MW > 500 kDa) is still challenging and the delivered effeminacy is still unknown. In this study, we aim to test the CNS delivered efficacy of a novel large molecule, virus-like particles (VLPs;MW = 2000 kDa), into the brain 1,2, Yi-Hsiu Chung², KunJu Lin³, LiangYo Yang^4,5, Tzu-Chen Yen², Hao-Li Liu^1,6

¹Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan; ²Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan City, Taiwan; ³Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan; ⁴Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; ⁵Department of Biotechnology, Asia University, Taichung, Taiwan; ⁶Medical Imaging Research Center, Institute forRadiological Research, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan City, Taiwan

Correspondence: PoHung Hsu

in vivo, and autoradiography (ARG) was conducted in vivo, and in vivo quantitation of plaque clearance, while in vivo in the near future.

P9 A low-cost phased array system for ultrasound neuromodulation

Wu Sun, Juan Zhou, WenBin Yan, JiaXing Yang, Weibao Qiu, Hairong Zheng

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Correspondence: Wu Sun

in vivo will be carried out.

P10 Test study for the electro-acoustic conversion efficiency of focused ultrasonic transducer based on virtual instrument

Yang Liu¹, Jianwen Tan^{2, 1}, Deping Zeng^{1, 3}, Zhiming Zhong¹

¹Biomedical Engineering, Chingqing Medical University, Chongqing, China; ²Chongqing Communication Institute., Chongqing, China; ³National Engineering ResearchCenter of Ultrasound Medicine, Chongqing, China
Correspondence: Yang Liu
2,1, Shin Yoshizawa², Shin-ichiro Umemura²
¹Hitachi, Ltd., Kokubunji, Japan; ²Tohoku Univ., Sendai, Japan
Correspondence: Satoshi Tamano
1, Gepu Guo¹, Qingyu Ma¹, Juan Tu², Dong Zhang²
¹Nanjing Normal University, Nanjing, China; ²Nanjing University, Nanjing, China
Correspondence: Yuzhi Li
1, Qingyu Ma¹, Juan Tu², Dong Zhang²
¹Nanjing Normal University, School of Physics and Technology, Nanjing, Jiangsu, China; ²Nanjing University, Nanjing, China
Correspondence: Gepu Guo
1, Yutong Lin¹, Alfred C. Yu², Peng Qin¹
¹Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, China; ²Department of Electrical and Computer Engineering, TheUniversity of waterloo, Waterloo, Alberta, Canada
Correspondence: Mouwen Cheng
1, Min He¹, Zhou Lin², man luo¹, Guangrong Lei³, Xiaobo Gong³, Jun Dang⁴, Deping Zeng¹, Faqi Li¹, Junru Wu⁵, Dong Zhang², Zhibiao Wang¹
¹Chongqing medical university, Chongqing, China; ²Institute of Acoustics, Key Laboratory of Modern Acoustics, MOE, Nanjing University, Nanjing, China; ³National Engineering Research Center of Ultrasound Medicine, Chongqing, China; ⁴Department of Oncology, 1st Affiliated Hospital of Chongqing Medical University, Chongqing, China; ⁵Physics, School of Engineering, the University of Vermont, Burlington, Vermont, United States
Correspondence: Hua Cao
1, Takashi Azuma^{2, 1}, Tatsuya Umeda³, Tomomichi Oya³, Masashi Koizumi³, Ryo Suzuki⁴, Naoto Yamamura¹, Kazuo Maruyama⁴, Kazuhiko Seki³, Shu Takagi¹
¹Bioengineering Dept., The University of Tokyo, Tokyo, Japan; ²Faculty of Medicine, The University of Tokyo, Tokyo, Japan; ³National Center of Neurology andPsychiatry, Kodiara-shi, Tokyo, Japan; ⁴Teikyo University, Tokyo, Japan
Correspondence: Yohei Kobayashi
2, Li-Chen Chiu¹, Win-Li Lin², Gin-Shin Chen¹
¹Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes; ²Institute of Biomedical Engineering, NationalTaiwan University
Correspondence: Meng-Hung Tsai
in vivo rat model.
in vivo studies showed that the transducer could produce a hot spot to noninvasively cause superficial skin necrosis as the electrical power and time of ultrasonic sonication were in a range of 6-9 W and 2 s.
1, Luis Hernandez-Garcia²
¹Access Business Group, Grand Rapids, Michigan, USA; ²Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
via TTL pulses, such that the EPI images were collected between ultrasound bursts. Spatiotemporal temperature changes were computed using proton resonant frequency shift relationship from the MR phase images. Finally, skin samples were stored in 10% formalin, fixed in paraffin, sliced, and stained with H&E and masson’s trichrome to investigate thermal damage on skin cells.
Transdermal drug delivery (TDD) can effectively bypass the first-pass effect, which can be valuable in cosmetic industry. In our work, ultrasound-facilitated TDD on fresh porcine skin was studied in various conditions of acoustic parameters. The delivery of fluorescent nanoparticles and high molecular weight hyaluronic acid (HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers (e.g., their penetration depth and concentration) could be obviously raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents (UCAs). When the ultrasound was applied without UCAs, low ultrasound frequency will give better drug delivery effect than high frequency, but the penetration depth was in a less level around 200 μm. However, with the help of ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications (e.g., nanoparticle drug carriers, transdermal patches and cosmetics) in cosmetic industry, protocols and methods presented had shown us the potentially attractive application for moisture and treatment of Skin Deapth.
P24 Comparative study on ultrasonic monitoring of pHIFU and cHIFU peripheral ablation mode
Wen Jing
Chongqing Medical University, Chongqing, China
in vitro bovine liver.
ex vivo bovine liver.
ex vivo bovine livers were exposing 2 seconds per time under two ambient pressure of atmospheric pressure and subatmospheric pressure. B mode US monitoring the strong echo signal before and after HIFU exposing. A passive cavitation test system (PCD) test the acousticcavitation signal in the process of exposing.
ex vivo bovine liversby HIFU. The followings were clarified in the experiment.1. The reduce of dissolved oxygen concentration could decrease the volume of lesions generated by HIFU.2. Subatmospheric pressure could restrain the cavitation, thus reshape the lesions to elliptical and smaller the size of lesion in focus.
P28 The effect of phased-hifu with discontinuous operating mode on coagulative necrosis region
Xiongfei Qu, Guofeng Shen, Nan Wu, Yazhu Chen
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
Correspondence: Xiongfei Qu
ex vivo porcine muscle, compared with slender spindle like region in continuous operating mode. The aim of this study was to demonstrate the mechanism and influence of this method on tissue ablation.
ex vivo porcine muscle and tissue-mimicking phantom (NIPAMbased hydrogel phantom with cloud point temperatures at 52°C) heating experiments were performed in procedures (1) and (3), to investigate the shape of coagulative necrosis region and temperature above 52°C, respectively.
ex vivo porcine muscle and tissue-mimicking phantom experiments.
This work was supported by the Bettencourt Schueller Foundation and the 'Agence Nationale de la Recherche' under the program “Future Investments” with the reference ANR-10-EQPX-15.
[1] Fry et al. 'Production of reversible changes in the central nervous system by ultrasound.' Science (1958)
[2] Lele et al. 'Effects of focused ultrasonic radiation on peripheral nerve, with observations on local heating.' Experimental Neurology (1963)
[3] Younan et al. 'Influence of the pressure field distribution in transcranial ultrasonic neurostimulation.' Medical physics (2013)
[4] Ye et al. 'Frequency Dependence of Ultrasound Neurostimulation in the Mouse Brain.' Ultrasound in medicine & biology (2016)
[5] Li et al. 'Improved Anatomical Specificity of Non-invasive Neuro-stimulation by High Frequency (5 MHz) Ultrasound.' Scientific reports (2016).
[6] Yoo et al. 'Transcranial focused ultrasound to the thalamus alters anesthesia time in rats.' Neuroreport (2011)
[7] Kamimura et al. 'Focused ultrasound neuromodulation of cortical and subcortical brain structures using 1.9 MHz.' Medical Physics (2016)
[8] B. Cox et al, k-space propagation models for acoustically heterogeneous media: Application to biomedical photoacoustics, J. Acoust. Soc. Am., 2007.
[9] Burgoon et al. 'Temperature-sensitive properties of rat suprachiasmatic nucleus neurons.' American Journal of Physiology-Regulatory, Integrative and ComparativePhysiology (2001)
P32 Numerical simulation of the effect of phase transformation on standing waves and transcranial focusing in HIFU
Miaomiao Zeng¹, Shihui Chang¹, Rui Cao², Xiqi Jian¹
¹Biomedical engineering, Tianjin Medical University, Tianjin, China; ²Tianjin University of Science and Technology, Tianjin, China
Correspondence: Miaomiao Zeng
COACHING WUSHU VOLUME TWO: ASSESSMENT OF WUSHU TAOLU EVENTS, ATHLETES, AND JUDGING.
via cresyl violet staining. Edema regions were monitored by magnetic resonance imaging.
Electrical and Computer Engineering, University of Minnesota--Twin Cities, Richfield, Minnesota, USA
Correspondence: Parker D. O'Brien
ex vivo through various regions of the skulls to understand how different frequencies can be used to refocus distorted or recover lost transmission through the use of multiple frequencies.
2,1, Emad S. Ebbini¹
¹Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota, USA; ²Siemens, Seattle, Washington, USA
Correspondence: Dalong Liu
in vivo.
in situ, designed to reach the temperature set point in ~0.5 sec. Ultrasound thermography basedon DMUA beamformed echo data from the target region was used for feedback. A PID controller was employed to adjust the tFUS intensity to maintain the temperature at the set point. All animals were survived for 3 - 5 days after tFUS application and observed for any abnormal behavior or adverse reaction. Histological evaluation was performed to determine whether the delivered tFUS dose produced a BBB opening. For some animals, we extracted the skull and performed 1, Oluyemi Olumolade¹, Tara Kugelman¹, Vernice Jackson-Lewis², Maria Eleni Karakatsani¹, Serge Przedborski², and Elisa E. Konofagou^1,3
¹Department of Biomedical Engineering, Columbia University, New York, NY, USA; ²Department of Neurology, Columbia University, New York, NY, USA; ³Department of Radiology, Columbia University, New York, NY, USA
Correspondence: Shutao Wang
via intraperitoneal injections of MPTP toxin at 30 μg/kg over five consecutive days. Animals were then divided into four groups (n = 7-10 per group): control, FUS only, AAV injection only, and FUS+/AAV+. For the FUS only and FUS+/AAV+ groups, both striatum and substantia nigra were sonicated unilaterally using a single element FUS transducer. For the AAV+/FUS+ group, a 100 μl mixture of AAV-GDNF vectors and polydispersed microbubbles were administered intravenously before sonication. Mice were allowed to survive up to three months’ post sonication, which was followed by transcardial perfusion and tissue analysis.
via passive imaging reconstruction.
1,2, Mehmet S. Özdas², Esra Neufeld¹, Théo Lemaire³, Silvestro Micera³, Mehmet F. Yanik², Niels Kuster^{1, 2}
¹Computational Life Sciences, IT'IS Foundation for Research on Information Technologies in Society, Zurich, Zurich, Switzerland; ²Swiss Federal Institute ofTechnology (ETHZ), Zurich, Switzerland; ³Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
Correspondence: Hazael Montanaro
via systematic transvascularroute is an attractive alternative since it is non-invasive. However, a high-yield and targeted gene delivery platform is still lacking. In order to improve the efficiency of gene delivery, this study proposed an ultrasonic sensing vector for gene delivery into brain through polyethylenimine (PEI)-superparamagnetic iron oxide (SPIO)-pDNAloaded microbubbles (PSp-MBs). Cooperating with ultrasound exposure, PSp-MBs could transport the PSp nanoparticles into the desired brain region by acoustic MBs cavitation activity. The rate of gene transfection would be enhanced by the modification of PEI onto PSp nanoparticles. In addition, by an externally applied magnetic field, magnetic targeting (MT) can further increase the deposition of PSp at the targeted location, enhancing the gene delivery.
via ligand exchange. The PSPIO were then conjugated with pDNA and loaded onto the lipid surface of MBs by electrostatic force. PSPIO-pDNA (luciferase plasmid) modulated onto the MBs was confirmed by Prussian blue staining and propidium iodide staining. The size, concentration and PSPIO payload were measured by multisizer and plate reader, respectively. C6 glioma cell and Sprague-Dawleyrats (N = 4) were used in this study. The gene transfection efficiency and BBB opening region resulted from PSp-MBs with ultrasound (frequency = 1 MHz, energy = 0.1-0.5MPa, cycle = 5000, PRF = 1 Hz, sonication time = 60 s) were evaluated by bioluminescence imaging and Evans blue staining, individually. The MT process was performed by a 0.48 Tesla external magnet.
via magnetic resonance imaging.
P41 Numerical study of bubble area evolution during acoustic droplet vaporization enhanced HIFU treatment
Ying Xin¹, Aili Zhang¹, Lisa X. Xu¹, Jeffrey B. Fowlkes²
¹School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; ²Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA
Correspondence: Ying Xin
1, Florentina de Comtes¹, Hasan Koruk², Ali Mohammed³, James J. Choi¹
¹Department of Bioengineering, Imperial College London, London, UK; ²Mechanical Engineering, MEF University, Istanbul, Turkey; ³Materials, Imperial College London, London, UK
Correspondence: Ahmed Elghamrawy
1, Dehong Hu¹, Mengjie Chen², Zonghai Sheng¹, Jun Zhou², Xin Liu¹, Hairong Zheng¹
¹Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China; ²Medical College of Chinese Three Gorges University, Yichang, China
Correspondence: Qian Wan
in vivo and thus, suitable for theranostic applications in cancer.
in vivo MRI imaging experiments were acquired using a 3.0 T clinical MR scanner (TIM TRIO, Siemens, Germany) with a small animal coil. T1-weighted MR images were acquired using the following parameters: TSE sequence, TR= 700 ms, TE =13 ms, FOV =32 × 45 mm, slice thickness= 1 mm and flip angle=180°.
in vitro of HSA-Ce6 NAs could be further improved. It was found that single HSA-Ce6 NAs or ultrasound treatment could only induce partial cell death at the current conditions. In marked contrast, the combination treatments (SDT) were found to be highly effective in destructing cancer cells. Indicating that ultrasound has a good penetrability and SDT effect (Fig. 3). In addition, the HSA-Ce6 NAs can serve as chelating agents to capture Mn2+ for MRI imaging by forming stable chelates. The in vivo and that they can be targeted by FUS to deliver and release reactive oxygen species (ROS) to kill cancer cells, paving the way for their theranostic applications under MRI-guided sonodynamic therapy.
P44 Towards rapid MR thermometry in cortical bone
Phoebe Miller¹, Sina Tafti¹, David Keder², Quinton Miller³, Darius Hossainian³, Wilson Miller¹
¹Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, USA; ²Physics, University of Virginia, Charlottesvle, Virginia, USA; ³Biomedical Engineering, University of Virginia, Charlottesvle, Virginia, USA
Correspondence: Phoebe Miller
in vivo.
P45 Multi-disciplinary integration of ultrasound molecular imaging
Zhigang Wang
Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing, China
in vivo drug deliveryand controlled release and evaluation of treatment efficacy. It provides an innovative research platform for ultrasound molecular imaging and therapy.
P46 MR and fluorescence dual-modal imaging-guided sonodynamic therapy of gliomas through a multifunctional theranostic nanoplatform
Fei Yan¹, Meijun Zhou², Hairong Zheng¹
¹Shenzhen Institutes of Advanced Technology, Shenzhen, China; ²Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
Correspondence: Fei Yan
in vitro and in vivo studies. Animals were treated in five groups: control, Doxorubicin-only (Dox), Doxorubicin combined with FUS treatment (Dox-FUS), Doxorubicin loaded microbubble complex (MB-NP-Dox) only, and MB-NPDox combined with FUS treatment (MB-NP-Dox-FUS). Animals were treated on a weekly basis for three weeks and post-treatment monitoring was followed for five weeks.
1, Faqi Li²
¹University of Vermont, Burlington, Vermont, USA; ²Chongqing Medical University, Chongqing, China
Correspondence: Junru Wu
via continuous vortex-mixing overnight. Biofilms were generated using 1x106 Ralstonia insidiosa in 1.5% alginate solution and allowed to stand for 5 minutes to assure that the surface of the solution flat. 600 ml of 2% CaCl2 was added to the alginate from the top for two hours. After polymerization, the film was washed with sterile water and incubated with R2B overnight at room temperature. A two-step treatment was applied. The first step is the penetration of the liposomes into the biofilm. The front part of the transducer was immersed in the liposome suspension. The distance between the transducer surface and the top of the alginate-flm was 1cm.Tone-bursts ultrasound (2.25MHz with duty cycle 10%) were emitted downward into the liposome solution. Experiments were conducted with ultrasound spatially and temporally averaged intensity, ISATA = 0.14 W/cm2.The ultrasound transducer used is a single-element non-focusing piezo-ceramic transducer operated at 2.25 MHz, with active radius a =10 mm. An arbitrary waveform function generator was programmed to produce a tone-burst sinusoidal signal of duty cycle of 10% for 1 min insonation duration, and the output of the waveform generator was used as the input of a 55 dB RF power amplifier whose output was used to drive the transducer. The experiment step two uses a focused ultrasound to burst the liposomes inside the biofilm and release the drug from the liposomes in vitro were observed. The tumor homing and cell-penetrating properties of the nanoparticles were examined by confocal laser scanning microscopy and flow cytometry. The cytotoxicity of the nanoparticles was evaluated by CCK8 assay.
in vitro(P<0.05). The confocal laser scanning microscopy showed that nanoparticles can targetedly aggregate to cell membrane of MDA-MB-231 and penetrate into the cell, but not to HUVEC. The flow cytometry showed that intracellular fluorescence intensity of MDA-MB-231 was higher than that of HUVEC(P<0.05). The CCK8 assay indicated that different concentrations of nanoparticles had no significant effects on cell activity (P>0.05).
in vitro, and enhance ultrasound imaging in vivo applications, when intravenous injection of AMLs, the targeting of AMLs to tumor was enhanced under exposure to an external magnetic field. Time-dependent in vitro of the prepared lipids-shelled nanobubbles were investigated. The mechanism of the incubation was also discussed.
in vitro indicated that ultrasound imaging enhancement could be acquired by both perfusion imaging and accumulation imaging. The dispersed phospholipid molecular in the prefabricated free nanobubbles water was expected to be assembled to form controllable stable lipid encapsulation gas containing ultrasound-sensitive liposome (GU-Liposome). Compared with conventional mechanical agitation methods, pre-prepared free gas bubble-based nanobubbleshave exhibited the controllable nano-size, lower polydispersity index.
Correspondence: Siyuan Zhang
Zhang S, Cui Z, Xu T, Liu P, Li D, Shang S, Xu R, Zong Y, Niu G, Wang S, He X, Wan M. Inverse effects of flowing phase-shift nanodroplets and lipid-shelled microbubbles on subsequent cavitation during focused ultrasound exposures. Ultrason Sonochem. 2017; 34: 400-409. Available from: http://www.sciencedirect.com/science/article/pii/S1350417716302139.
P55 Sonodynamic Therapy (SDT) polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic High Intensity Focused Ultrasound (HIFU) therapy
Lan Hao
Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital University, Chongqing, China
in vitro and in vivo target ovarian cancer and enhance ultrasound imaging after acoustic droplet vaporization (ADV) induced by low-intensity focused ultrasound (LIFU).
in vitro targeted efficiency were tested with SKOV3 cells and in vivo targeted efficiency and acoustic droplet vaporization were evaluated with SKOV3 tumor-bearing nude mice.
ex vivo fluorescence imaging displayed that FA-NDs possessed outstanding specificity to targeted solid tumor. Both the qualitative and quantitative results of via ADV using LIFU.
P57 Targeted Pegylated PLGA coated prussian blue nanocomposite for dual-modality PA/MR imaging and synergistic chemo-thermal tumour therapy
Tingting Shang
Institute of Ultrasound Imaging Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China.
in vitro cell targeting and in vitro and in vitro or in vitro with laser irradiation indicated the great potential as a controlled-release system for the anticancer drug. In vitro cell targeting and in vivo of PLGA-PB-PTX-PEG-FA nanocomposite. After the tail intravenous injection of thePLGA-PB-PTX-PEG-FA nanocomposite, the PA images and MR images of tumor of nude mice were significantly enhanced, while there were almost no distinct enhancement in non-targeted group and blank control group. The result of the photothermal cytotoxicity of PLGA-PB-PTX-PEG-FA nanocomposite showed that the viability of the cells of PLGA-PB-PTX-PEG-FA nanocomposite+Laser group was lowest. The results of photothermal conversion property of PLGA-PB-PTX-PEG-FA suggested the character of photothermal effect was positively correlated with the heating power and the nanoparticles concentration and exhibited good photostability. Upon near-infrared laser irradiation, the PLGA-PB-PTX-PEG-FA nanocomposite showed an enhanced synergistic photothermal and chemical therapeutic efficacy forbreast cancer than solo photothermal therapy or chemotherapy.
in vitro and 1,2, Xiufang Liu^{1, 2}, Fei Yan¹, Hairong Zheng¹
¹Shenzhen Institutes of Advanced Technology, Chinese academy of Sciences, Shenzhen, China; ²Shaanxi Normal University, Xi'an, China
Correspondence: Xiaobing Wang
in vitro and even on normal tissues 1,2
¹Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China; ²State Key Laboratory of Ultrasound Engineering in MedicineCo-Founded by Chongqing and the Ministry of Science and Technology, State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing andthe Ministry of Science and Technology, Chongqing, Chongqing, China
Escherichia coli (E. coli biofilms. This part of the study was conducted according to the method described by Singh in vitro.
P61 mechanisms of intracellular gene delivery via ultrasound and DNA-loaded microbubbles
Ching-Hsiang Fan¹, Yu-Chun Lin², Chih-Kuang Yeh¹
¹Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; ²Institute of Molecular Medicine, National TsingHua University, Hsinchu, Taiwan
Correspondence: Ching-Hsiang Fan
1,2, C. Olivier4, J.L. Thomas⁴, M. Guedra3, F. Coulouvrat³, T. Lacour³, Wladimir URBACH^{1, 2}, N. Taulier²
¹ENS Paris, Lab. Phys. Stat., Paris, France; ²LIB, Sorbonne Universités UPMC and CNRSLIB, 75005-Paris, France; ³Sorbonne Universites, UPMC Univ Paris 06and CNRS UMR 7190F-75005 Paris, Institut Jean Le Rond d’Alembert, Paris, France; ⁴INSP, Sorbonne Universités UPMC 75005 Paris, France
Correspondence: A. Podkovskiy
in vitro the relationship between ADV and Inertial Cavitation.
via sonoporation, are determined by investigating parameters that could influence both thresholds; bulk fluid properties such as gas saturation, temperature, viscosity, and surface tension; droplet parameters such assurfactant type; and acoustic properties such as pulse repetition frequency and pulse width.
in vivo, will be the next step.
P63 Ultrasound theranostics for tumor
Kazuo Maruyama
Faculty of Pharma-Sciences, Teikyo University, Tokyo, Japan
in vitro and via tail vein and 9 MHzlinear ultrasound was exposed to solid tumor site transdermally. Following the recognition of neovasculature in tumor tissue, 1 MHz therapeutic ultrasound was exposed transdermally over the site of solid tumor tissue.
via tail vein and 9 MHz linear ultrasound was exposed to solid tumor site transdermally. The flow of bubbles in blood was observed and neovasculature of tumor tissue was imaged clearly. Following the recognition of neovasculature in tumor tissue, 1 MHz therapeutic ultrasound was exposed transdermally over the site of solid tumor tissue. This process induced cavitation of bubbles in the tumor tissue, resulted in rising the temperature of tumor tissue to 45-55C, and also significant reduction of tumor growth. Cavitation leads to localized heating and cloud be use for ablative cancer therapy. Transfection of pCMV-IL-12 with LBs and US suppressed tumor growth significantly. To investigate the mechanism behind the anti-tumor effects of pCMV-IL-12 transfected using bubbles and US, we assessed the involvement of CD4+ and CD8+ T cells and NK cells. The depletion of CD8+ T cells effectively blocked the antitumor effect of pCMV-IL-12 transfected using bubbles and US. These results suggest that the combination of bubbles and US can effectively induce sufficient IL-12 expression to cause anti-tumor immune responses.
1, Xiaoxia Liu², Hairui Xiong¹, Zhenwei Yao¹, Qian Zhou¹, Haoxiong Li¹, Ying Tang¹
¹Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China; ²Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, China
Correspondence: Junhai Zhang
1, Jiri Jaros^{2, 1}, Heather Payne^{3, 1}, Clare Allen³, Taimur T. Shah⁴, Hashim Ahmed⁴, Eli Gibson¹, Dean Barratt¹, Bradley Treeby¹
¹Medical Physics and Biomedical Engineering, University College London, London, UK; ²Computer Systems, Brno University of Technology, Brno, CzechRepublic; ³Oncology, University College London Hospitals, London, UK; ⁴Surgery and Interventional Science, University College London, London, UK
Correspondence: Panayiotis S. Georgiou
1, Qian Zhou¹, Junhai Zhang¹, Haoxiong Li¹, Ye Chen¹, Qiong Li², Ying Tang¹, Zhenwei Yao¹, Xiaoyuan Feng¹
¹Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China; ²Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China
Correspondence: Hairui Xiong
1, 2, William Apoutou N'Djin^{1, 2}, Guillaume Bouchoux¹, Nicolas Sénégond³, Nicolas Guillen⁴, Jean-Yves Chapelon^{1, 2}
¹Inserm, U1032, LabTau, Lyon, France; ²Université Lyon 1, Lyon, Rhone-Alpes, France; ³Vermon, Tours, France; ⁴Edap TMS, Vaulx-en-Velin, France
in vitro lesion formation). Numerical models of the therapeutic acoustic field were performed using the Rayleigh integral to determine the feasibility of electronic focusing and inducing thermal lesions. For comparison, simulations of a geometrically focused existing piezo-based technology (16-element annular array) was also performed. Experimentally, key static parameters (collapse-, snapback-, andbreakdown voltages) for use in the different modes of operation (conventional, collapse, and collapse-snapback) were identified. The HIFU capabilities of the device were also investigated experimentally (pressure field and radiation force measurements) with the creation of in vitro tissue confirmed that the probe was capable of creating lesions in tissue.
1,2, Z. Hu^2,3, J. Li^2,3, Q. Liu³, S. Yuan³, Y. Paulus⁴, X. Yang⁵, and X. Wang^1,2
¹Institute of Acoustics, Tongji University, Shanghai, P.R. China; ²Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; ³Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China; ⁴Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA; ⁵Department of Mechanical Engineering, University of Kansas, Lawrence, KS, USA
Correspondence: H. Zhang
Angiogenesis and neovascularization are hallmarks for a variety of pathological conditions, including cancer and many eye diseases, and play a crucial role in disease onset and progression. Antivascular therapies that aim at either removing microvessels or slowing down their growth represent a proven new strategy to intervene the progress of these conditions and improve the prognosis. Here we report the development of a photo-mediated ultrasound therapy (PUT) technique as a new concept of localized antivascular therapy. Unlike any of the previous optical- or ultrasonic-alone techniques, laser pulses and ultrasound bursts are synergistically applied in PUT, which facilitate noninvasive treatment of subsurface microvessels with unprecedented high precision. PUT takes advantages from the high native optical contrast among biological tissues, and has the unique capability to self-target on blood vessels without causing unwanted damage to surrounding tissue. As demonstrated through the experiments on animal models, PUT can treat microvessels in target tissue 1,2, Huan Liu^{1, 2}, Xiaobo Gong¹, Faqi Li^{1, 2}
¹State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing, China; ²College ofBiomedical Engineering Chongqing Medical University, Chongqing, China
Correspondence: Zonggui Chen
in vivo dermatological conditions. Current temperature measurement methods are expensive, time consuming, application specific/organ dependent and provide unsatisfactory spatiotemporal resolution. We propose a method including a multiphysics model to quickly estimate skin temperature distribution in 2D, which was validated using multiple approaches and lends itself to an iterative development process.
Correspondence: Chen Bai
via a 128-element linear array transducer with 2 MHz frequency will be performed.
P74 Enhanced ultrasonic focusing and temperature rise by using sub-wavelength periodic structure
Chenghai Li, Xiasheng Guo, Juan Tu, Dong Zhang, Zhou Lin
Key Laboratory of Modern Acoustics (Nanjing University), Ministry of Education, Nanjing University, Nanjing, Jiangsu, China
Correspondence: Chenchen Bing
1, RUI CAO², Yabin Zhang¹, Shijing Wu1, Xiqi Jian¹
¹Tianjin Medical Univercity, Tianjin, China; ²Tianjin University of Science & Technology, Tianjin, China
Correspondence: Shihui Chang
1,2, Tony W.H Sheu², Manuel Diaz¹, Peter Deng¹
¹Institutes of Biomedical Engineering and Nanomedicine, National Health Research Institutes; ²Engineering Science and Ocean Engineering Department, National Taiwan University
Correspondence: Maxim Solovchuk
[1] Herbert et al., IEEE Trans. Ultrason. Ferroelectr. Freq. Control 56(11) 2388 – 99, 2009
[2] Larrat et al., IEEE Trans. Ultrason. Ferroelectr. Freq. Control 57(8) 1734 – 7, 2010
[3] Kaye et al., Medical Physics 39 6254 (2012)
[4] Koskela et al., J.Acoust.Soc.Am. 136(3), 2014
P78 A fast 3-D transcranial focused ultrasound simulation based on ray tracing
Changzhu Jin^{1, 2}, John Snell², Dong-Guk Paeng^1,2
¹Ocean System Engineering, Jeju National University, Jeju, Korea; ²Focused Ultrasound Foundation, Charlottesville, Virginia, USA
[1] Clement, G.T. and K. Hynynen, Phys Med Biol, 2002. 47(8): p. 1219-36.
P79 Efficacy of ultrasound mediated microbubbles in diclofenac gel to enhance transdermal permeation in rheumatoid arthritis induced rat
Ai-Ho Liao¹, Ho-Chiao Chuang²
¹National Taiwan University of Science and Technology, Taipei, Taiwan; ²National Taipei University of Technology, Taipei, Taiwan
Correspondence: Ai-Ho Liao
Liao A.H, Chuang H.C, Chung H.Y. Efficacy of ultrasound mediated microbubbles in diclofenac gel to enhance transdermal permeation in rheumatoid arthritis induced rat. IEEE. 2015. Available from: http://ieeexplore.ieee.org/document/7319152/.
P80 Vascular effect of rabbit VX2 tumour induced by diagnostic ultrasound with microbubbles
Xueyan Qiao, Zhong Chen, Cuo Yi, Wenhong Gao, Shunji Gao, Zheng Liu
Ultrasound Department, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Correspondence: Xueyan Qiao
2,1, Mouwen Cheng¹, Fan Li², Lianfang Du², Alfred C. Yu³, Peng Qin¹
¹Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, China; ²Department of Ultrasound, Shanghai First People’sHospital, Shanghai Jiao Tong University, Shanghai, China, 3Department of Electrical and Computer Engineering, The University of waterloo, Waterloo, Alberta, Canada
Correspondence: Lizhou Lin
1, S. Buravkov², V. Chernikov³, T. D. Khokhlova¹, G. R. Schade¹, W. Kreider¹, A. Maxwell1, M. Bailey¹, V. Khokhlova^{1, 2}
¹University of Washington, Seattle, Washington, USA; ²M.V. Lomonosov Moscow State University, Moscow, Russian Federation; ³Research Institute of Human Morphology, Moscow, Russian Federation
Correspondence: Y. Wang
in vivo porcine model.
in vivo animal model. TEM evaluation revealed that aside from the presence of intact erythrocytes, the lesion contents were similar in characteristic to that observed in ex vivo and via overproduction of heat-shock protein 70 (HSP70), death receptor Fas, its ligand FasL and TNF-α receptor.
via an increase in expression of Fas, FasL and TNF-α receptor. All these factors lead to phenotypic changes in surviving cancer cells that reduce their aggressiveness.
P86 Therapeutic effect of focused ultrasound combined with dendritic cell treatment for melanoma: preliminary study
Eun-Joo Park, Yun Deok Ahn, Yuri Cheon, Jae Young Lee
Radiology, Seoul National University Hospital, Seoul, Korea
Correspondence: Eun-Joo Park
2,1, Caixia Jia¹, Alfred C. Yu³, Lianfang Du², Peng Qin¹
¹Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, China; ²Department of Ultrasound, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai, China; ³Department of Electrical and Computer Engineering, The University of waterloo, Waterloo, Alberta, Canada
Correspondence: Lizhou Lin
in vivo porcine model have shown the feasibility of using histotripsy to noninvasively create well-confined lesions in the liver through the intact chest, with sharp boundaries between treated and untreated tissue. In this study, the feasibility of using histotripsy for non-invasive liver cancer ablation was tested in an in situ peak negative pressure >30 MPa.The targeted tumor volume was mechanically scanned using a robotic micro-positioner controlled by a PC console. After treatment, lesion characteristics were assessed using ultrasound imaging and MRI (7T small animal scanner), and the treated tissues were then harvested for gross analysis and histological evaluation. All procedures were approved by the ICUCA at the University of Michigan.
in vivo liver cancer models.
P90 Comparison of ultrasound-guided high intensity focused ultrasound and surgery for abdominal wall endometriosis: a retrospective cohort study
Ling Zhao², Jinyun Chen¹, Chunquan Zhao²
¹College of Biomedical Engineering, Chongqing Medical University, Chongqing, China; ²Department of Obstetrics and Gynecology, The 1st Affiliated Hospital of Chongqing Medical University, Chongqing, China
Correspondence: Ling Zhao
1, Ryo Takagi², Shin Yoshizawa², Shin-ichiro Umemura¹
¹Biomedical Engineering, Tohoku University, Sendai, Miyagi, Japan; ²Communications Engineering, Tohoku University, Sendai, Miyagi, Japan
Correspondence: Ryosuke Iwasaki
via high-speed ultrasound imaging. The distribution of axial displacements between before and after push pulse exposure was calculated from the phase shift in 1D cross-correlation. After that, tissue was coagulated by the repetition of the trigger pulse followed by a HIFU burst with a duration of 44.9 ms, which was continued for 6 s with a duty cycle of 90%. The resulting tissue coagulation was compared with the distribution of the HIFU induced displacement and the B-mode image.
1,2, Faqi Li^1,2, Xiaobo Gong², Qi Wang², Guangrong Lei², Zhibiao Wang^1,2
¹State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, College of BiomedicalEngineering, Chongqing Medical University, Chongqing, China; ²National Engineering Research Center of Ultrasound Medicine, Chongqing, China
Correspondence: Yurong Zhang
1, Hiroki Hanayama², Ryo Takagi², Shin Yoshizawa², Shin-ichiro Umemura¹
¹Biomedical Engineering, Tohoku University, Miyagi, Japan; ²Communication Engineering, Tohoku University, Miyagi, Japan
Correspondence: Takuya Nakamura
1, Guofeng Shen², Chunlei Lei¹, Helin Zhang¹
¹School of Computer, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China; ²School of Biomedical Engineering, Shanghai Jiao TongUniversity, Shanghai, Shanghai, China
Correspondence: Ying Yu
2, Ying Yu¹, Chunlei Lei¹, Helin Zhang¹
¹School of computer, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China; ²School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China
Correspondence: Guofeng Shen
2,1, Faqi Li^2,1, Zonggui Chen^2,1, Yurong Zhang^2,1
¹National Engineering Research Center of Ultrasound Medicine, Chongqing, China; ²State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China
Correspondence: Man Luo
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P102 Feasibility of using nakagami distribution in structure characterization of the different lesions treated by HIFU
Meng Han, Na Wang, Mingxi Wan
Biomedical Engineering, Xi' an="" jiaotong="" university,="" xi'an,="" shaanxi,="">
Correspondence: Meng Han
1,2, Fang Yang^1,2, Ning Gu^1,2
¹School of Biological Science & Medical Engineering, Southeast University, Nanjing, China; ²State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory forBiomaterials and Devices, Nanjing, China
Correspondence: Dong Liu
in vitro indicated that ultrasound imaging enhancement could be acquired by both perfusion imaging and accumulation imaging (Fig. 1).
1, William Apoutou N'Djin¹, Jean-Yves Chapelon¹, Jahan Tavakkoli^2,3
¹U1032, Inserm, Lyon, France; ²Physics, Ryerson University, Toronto, Ontario, Canada; ³Institute for Biomedical Engineering, Science and Technology, Toronto, Ontario, Canada
Correspondence: Jeremy Vion
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1, Kenneth Olive², Elisa E. Konofagou^1,3
¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Medicine and Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA; ³Radiology, Columbia University Medical Center, New York, New York, USA
Correspondence: Thomas Payen
2, Hang Su³, Yonghong Du², Dairong Li¹
¹Department of Respiratory disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; ²Chongqing medical university, Chongqing, China; ³Food and Drug Administration of Huiji, Zhengzhou, China
Correspondence: Yu Dong
1, Chen Yang¹, Fang Yuan², Defei Liao¹, Guilak Farshid³, Pei Zhong¹
¹Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina, USA; ²HuaCells Corporation, Natick, Massachusetts, USA; ³Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, USA
Correspondence: Fenfang Li
1, H. Zhou², R. Liu², Z. FAN¹
¹Biomedical Engineering, Tianjin University, Tianjin, Tianjin, China; ²College of Life Sciences, Nankai University, Tianjin, Tianjin, China
Correspondence: N. Rong
1, Lisa Landgraf¹, Xinrui Zhang¹, Michael Unger¹, Ina Patties², Johann Berger¹, Shaonan Hu¹, Lydia Koi^3,4, Antje Dietrich^3,5, Aswin Hoffmann^3,4, Mechthild Krause^3,4, Thomas Neumuth¹, Andreas Melzer¹
¹Innovation Center Computer Assisted Surgery, Universität Leipzig, Leipzig, Germany; ²Department of Radiation Therapy, Universität Leipzig, Leipzig, Germany; ³OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany; ⁴Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; ⁵German Cancer Consortium (DKTK), partner site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
Correspondence: Doudou Xu
The two ZIK-Centers for Innovation Competence, ICCAS in Leipzig and OncoRay in Dresden, have joined forces to start a new multidisciplinary 6.3 million Euro research project: SONO-RAY - Tumor therapy combining image-guided (PET-MR and MR) focused ultrasound and radiation therapy. The goal of SONO-RAY is to combine noninvasive image-guided therapy approaches of magnetic resonance guided focused ultrasound and radiation therapy to improve the efficacy of cancer treatment.
SONO-RAY project aims to combine therapeutic focused ultrasound (FUS) and radiation therapy (RT) to treat malignant solid tumors and tumor metastases. The hypothesis underlying this approach is that the combination of two tissue-destroying energies (the energy of high-intensity acoustic waves and ionizing radiation) is more effective in cancer treatment than the effect of employing one of the above two energy forms alone [1-3]. The central scope of the project is to develop tumor cell biology fundamentals, the computer-aided model formation and to evaluate the success potential of a future clinical use of a FUS-RT combination therapy. Within the framework of this project, the basic principle of the combined FUS and RT effect on tumor cells (in vivo) is going to be investigated preclinically. Clinical applications could be the treatment of various tumors of the head and neck, prostate carcinoma and glioblastoma.
In order to provide the basis for the combined FUS-RT method, in vivo experiments are being be carried out to elaborate the thermal and mechanical effect on the tumor tissue [4]. After identification of the thermal and mechanical individual parameters for FUS, these are transferred into simulation models in order to predict the behavior of the fabric on FUS[5]. The simulation models are validated using the parameters. Based on the data obtained above, FUS and RT will be generated spatially dispersed biologically active doses. Algorithms will be used for the anatomical co-registration and accumulation of the biologically active dose distributions generated by FUS and RT on MR images. Furthermore, software modules will be developed and validated, which support the clinical user in therapy planning. Optimization of application sequences of the FUS-RT technology and the incorporation in therapy into the treatment process (clinical workflow) of the patient will also be investigated and developed.
in vitro 96-well sonicator was designed and allows individual sonication for each of the wells in a 96-well plate. It consists of 96 single transducers at an operating frequency of 1 MHz and a maximum energy of 0.05 W/cm². A 150 kV X-ray machine (DARPAC 150-MC) was employed for irradiation at doses of 0 – 20 Gy. The analysis was conducted by using three different cell lines for prostate cancer (PC-3, Vcap, LNcap), glioblastoma (LN405, U87, T98G) and head/neck tumor (FaDu, UT-SCC 5, UT-SCC 8). Effects at the cellular level on metabolism (WST-1), proliferation (BrdU), membrane integrity (LDH release) and apoptosis (Annexin V) were detected after treatment.
[1] R. Cirincione, F.M. Di Maggio, G.I. Forte, L. Minafra, V. Bravata, L. Castiglia, V. Cavalieri, G. Borasi, G. Russo, D. Lio, C. Messa, M.C. Gilardi, F.P. Cammarata, High-Intensity Focused Ultrasound- and Radiation Therapy-Induced Immuno-Modulation: Comparison and Potential Opportunities, Ultrasound in medicine & biology, 43 (2017) 398-411.
[2] T. Refaat, S. Sachdev, V. Sathiaseelan, I. Helenowski, S. Abdelmoneim, M.C. Pierce, G. Woloschak, W. Small, Jr., B. Mittal, K.D. Kiel, Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer, Breast, 24 (2015) 418-425.
[3] S.K. Wu, C.F. Chiang, Y.H. Hsu, H.C. Liou, W.M. Fu, W.L. Lin, Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer, Ultrasonics sonochemistry, 36 (2017) 198-205.
[4] J. Beik, Z. Abed, F.S. Ghoreishi, S. Hosseini-Nami, S. Mehrzadi, A. Shakeri-Zadeh, S.K. Kamrava, Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications, Journal of controlled release : official journal of the Controlled Release Society, 235 (2016) 205-221.
[5] J. Hu, Y. Ding, S. Qian, X. Tang, Simulations of adaptive temperature control with self-focused hyperthermia system for tumor treatment, Ultrasonics, 53 (2013) 171-177.
[6] A.J. Loeve, J. Al-Issawi, F. Fernandez-Gutierrez, T. Lango, J. Strehlow, S. Haase, M. Matzko, A. Napoli, A. Melzer, J. Dankelman, Workflow and intervention times of MR-guided focused ultrasound - Predicting the impact of new techniques, Journal of biomedical informatics, 60 (2016) 38-48.
[7] A. Yaromina, T. Kroeber, A. Meinzer, S. Boeke, H. Thames, M. Baumann, D. Zips, Exploratory study of the prognostic value of microenvironmental parameters during fractionated irradiation in human squamous cell carcinoma xenografts, International journal of radiation oncology, biology, physics, 80 (2011) 1205-1213.
[8] A.J. Krafft, J.W. Jenne, F. Maier, R.J. Stafford, P.E. Huber, W. Semmler, M. Bock, A long arm for ultrasound: a combined robotic focused ultrasound setup for magnetic resonance-guided focused ultrasound surgery, Medical physics, 37 (2010) 2380-2393.
[9] N.V. Tsekos, A. Khanicheh, E. Christoforou, C. Mavroidis, Magnetic resonance-compatible robotic and mechatronics systems for image-guided interventions and rehabilitation: a review study, Annual review of biomedical engineering, 9 (2007) 351-387.
[10] Y.S. Kim, B. Keserci, A. Partanen, H. Rhim, H.K. Lim, M.J. Park, M.O. Kohler, Volumetric MR-HIFU ablation of uterine fibroids: role of treatment cell size in the improvement of energy efficiency, European journal of radiology, 81 (2012) 3652-3659.
[11] M.J. Voogt, H. Trillaud, Y.S. Kim, W.P. Mali, J. Barkhausen, L.W. Bartels, R. Deckers, N. Frulio, H. Rhim, H.K. Lim, T. Eckey, H.J. Nieminen, C. Mougenot, B. Keserci, J. Soini, T. Vaara, M.O. Kohler, S. Sokka, M.A. van den Bosch, Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy, European radiology, 22 (2012) 411-417.
[12] M. Huisman, M.K. Lam, L.W. Bartels, R.J. Nijenhuis, C.T. Moonen, F.M. Knuttel, H.M. Verkooijen, M. van Vulpen, M.A. van den Bosch, Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases, Journal of therapeutic ultrasound, 2 (2014) 16.
[13] M.K. Lam, M. Huisman, R.J. Nijenhuis, M.A. van den Bosch, M.A. Viergever, C.T. Moonen, L.W. Bartels, Quality of MR thermometry during palliative MR-guided high-intensity focused ultrasound (MR-HIFU) treatment of bone metastases, Journal of therapeutic ultrasound, 3 (2015) 5.
[14] E.J. Dorenberg, F. Courivaud, E. Ring, K. Hald, J.A. Jakobsen, E. Fosse, P.K. Hol, Volumetric ablation of uterine fibroids using Sonalleve high-intensity focused ultrasound in a 3 Tesla scanner--first clinical assessment, Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy, 22 (2013) 73-79.
[15] N.M. Hijnen, E. Heijman, M.O. Kohler, M. Ylihautala, G.J. Ehnholm, A.W. Simonetti, H. Grull, Tumour hyperthermia and ablation in rats using a clinical MR-HIFU system equipped with a dedicated small animal set-up, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 28 (2012) 141-155.
[16] M. Burtnyk, T. Hill, H. Cadieux-Pitre, I. Welch, Magnetic resonance image guided transurethral ultrasound prostate ablation: a preclinical safety and feasibility study with 28-day followup, The Journal of urology, 193 (2015) 1669-1675.
P116 Combination therapy for cancer by PET-MR and MR image guided focused ultrasound and radiation
Doudou Xu¹, Lisa Landgraf¹, Xinrui Zhang¹, Michael Unger¹, Ina Patties², Johann Berger¹, Shaonan Hu¹, Lydia Koi^3,4, Marc Fournelle⁵, Steffen Tretbar⁵, Thomas Neumuth¹, Andreas Melzer¹
¹Innovation Center Computer Assisted Surgery, Universität Leipzig, Leipzig, Germany; ² Department of Radiation Therapy, Universität Leipzig, Leipzig, Germany; ³ OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany; ⁴Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; ⁵Fraunhofer IBMT, St. Ingbert, Germany
Correspondence: Doudou Xu
in vitro sonicator with 1.14 MHz single transducer made by piezoelectric ceramic material was employed and allows individual sonication for wells in a 96-well plate. T98G glioma cells were exposure to acoustic intensity of 71 W/cm² with hyperthermia (40-45°C) duration of 134 sec, and 109 W/cm² with hyperthermia (40-45°C) duration of 65 sec, respectively. A 150 kV X-ray machine (DARPAC 150-MC) was employed for irradiation at doses of 0-20 Gy to investigate the radiation curve of T98G cells. For FUS and RT combinations, 5 and 10 Gy were used to treat T98G cells 24hrs post sonication. Effects at the cellular level on metabolism (WST-1), proliferation (BrdU) and membrane integrity (LDH release) were detected after treatment.
in vitro investigations of effects of FUS hyperthermia as well as of a combined therapy on other tumor cells need to be conducted.
Declarations
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Oral Presentations

O1 Neuroinflammation after disrupting the blood brain barrier with pulsed focused ultrasound and microbubbles imaged by 18F-DPA-714 PET and MRI

Zsofia I. Kovacs, Georgios Z. Papadakis, Tsang-Wei Tu, Sanhita Sinharay, William C. Reid, Bobbi Lewis, Dima A. Hammoud, Joseph A. Frank

National Institutes of Health, Bethesda, Maryland, United States

Correspondence: Zsofia I. Kovacs

O2 Long term effects of pulsed focused ultrasound and microbubbles detected by multivariate imaging modalities

Zsofia I. Kovacs, Tsang-Wei Tu, Georgios Z. Papadakis, William C. Reid, Dima A. Hammoud, Joseph A. Frank

National Institutes of Health, Bethesda, Maryland, United States

Correspondence: Zsofia I. Kovacs

O3 Characterization of different microbubbles in assisting focused ultrasound-induced blood-brain barrier opening

Sheng-Kai Wu1, Po-Chun Chu2, 3, Wen Yen Chai3, 4, Shih-Tsung Kang5, Chih-Hung Tsai3, Ching-Hsiang Fan5, Chih-Kuang Yeh5, Hao-Li Liu3

Correspondence: Sheng-Kai Wu

O4 Development of an A-Synuclein (SNCA)-based mouse model for Parkinson's disease by ultrasound-guided CNS delivery

Chung-Yin Lin1, Yu-Chien Lin2, Hao-Li Liu2

1Institute for Radiological Research, Chang Gung University, Taoyuan City, Taiwan; 2Department of Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan

Correspondence: Chung-Yin Lin

Correspondence: Costas Arvanitis

O6 Acoustic emissions during blood-brain barrier disruption with focused ultrasound and real-time feedback control under infusion administration of microbubbles – feasibility study in rodent model

Chenchen Bing1, Debra Szczepanski1, Imalka Munaweera1, Yu Hong1, Ian Corbin2, Rajiv Chopra1,2

1Radiology, UT Southwestern Medical Center, Dallas, Texas, USA; 2Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, USA

Correspondence: Chenchen Bing

Maria Eleni Karakatsani1, Tara Kugelman1, Shutao Wang1, Karen Duff3, Elisa E. Konofagou1,2

1Biomedical Engineering, Columbia University, New York, New York, USA; 2Radiology, Columbia University, New York, New York, USA; 3Pathology and Cell Biology, Columbia University, New York, New York, USA

Correspondence: Maria Eleni Karakatsani

1Graduate School of Biomedical Engineering - Umemura-Yoshizawa Laboratory, Tohoku University, Sendai, Miyagi, Japan; 2LabTAU, INSERM U1032, Université deLyon, Lyon, France

Correspondence: Maxime Lafond

1UMC Utrecht, Utrecht, Netherlands; 2Imasonic SAS, Voray-sur-l'Ognon, France

Correspondence: Pascal Ramaekers

1Univ Lyon, Université Lyon 1, INSERM, LabTAU, F-69003, LYON, France, Lyon, France; 2Department of Physical Medicine & Rehabilitation, National TaiwanUniversity Hospital, Taipei, Taiwan; 3Department of Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan

Correspondence: Corentin Cornu

1Department of Biomedical Engineering, Technion I.I.T, Haifa, Israel; 2Insightec LTD, Tirat HaCarmel, Israel; 3Department of Medicine, Technion I.I.T., Haifa, Israel

Correspondence: Steve Krupa

O12 Image-guided dual-target brain stimulation on mouse by array ultrasound

Guofeng Li, Jiehan Hong, Qiuju Jiang, Peitian Mu, Ge Yang, Congzhi Wang, Weibao Qiu, Hairong Zheng

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Correspondence: Guofeng Li

1LabTAU, INSERM, Lyon, France; 2Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA; 3FUS Foundation, Charlottesville, Virginia, USA; 4Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA

Correspondence: Cyril Lafon

1Sunnybrook Research Institute, Toronto, Ontario, Canada; 2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Correspondence: Ben Lucht

Correspondence: George R. Schade

1University of Toronto, Toronto, Ontario, Canada; 2Sunny brook Research Institute, Toronto, Ontario, Canada

Correspondence: Sharshi Bulner

1Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, USA; 2National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: Kee W. Jang

Correspondence: William Apoutou N'Djin

O20 Real-time HIFU beam imaging using beamforming in an ultrasound scanner

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1Engineering, The University of Tokyo, Tokyo, Japan; 2LabTAU, INSERM unité 1032, Lyon, France; 3Medicine, The University of Tokyo, Tokyo, Japan; 4Univ Lyon, Université Lyon 1, Lyon, France; 5Medical Device Development and Regulation Research Center, Tokyo, Japan

Correspondence: Kazuhiro Matsui

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Zhong Chen, Xueyan Qiao

Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China

Correspondence: Zhong Chen

O24 Image-based predicition of focusing gain in situ using dual-mode ultrasound arrays

Brogan T. McWilliams, Dalong Liu, Emad S. Ebbini

Electrical Engineering, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence: Brogan T. McWilliams

O25 An automatic approach to lesion planning for robotic HIFU

Tom Williamson, Scott Everitt, Ranjaka De Mel, Sunita Chauhan

Mechanical and Aerospace Engineering, Monash University, Melbourne, Victoria, Australia

Correspondence: Tom Williamson

1LabTAU - U1032, INSERM, Lyon, Rhône Alpes, France; 2CHU Croix Rousse, LYON, France

Correspondence: David Melodelima

1Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota, USA; 2Siemens, Seattle, Washington, USA

Correspondence: Dalong Liu

1Biomedical Engineering, Columbia University, New York, New York, USA; 2Neuroscience, Columbia University, New York, New York, USA, 3Radiology, Columbia University, New York, New York, USA

Correspondence: Shih-Ying Wu

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O33 In-vivo investigation of the combination of focused ultrasound and radiotherapy, using photoacoustic imaging as aplanning and monitoring tool

Marcia M. Costa, Anant Shah, Ian Rivens, Tuathan O'Shea, Carol Box, Jeff Bamber, Gail ter Haar

Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, UK

Correspondence: Marcia M. Costa

1The University of Tokyo, Tokyo, Japan; 2Kyushu University, Fukuoka, Japan

Correspondence: Ayumu Ishijima

O35 Dual mode time reversal cavity for US shockwave therapy and 3D imaging

J. Robin1,2, B. Arnal1, M. Tanter1, M. Pernot1

1Institut Langevin, Paris, France; 2Université Paris 7, Paris, France

Sheng-Kai Wu¹, Po-Chun Chu^{2, 3}, Wen Yen Chai^{3, 4}, Shih-Tsung Kang⁵, Chih-Hung Tsai³, Ching-Hsiang Fan⁵, Chih-Kuang Yeh⁵, Hao-Li Liu³

Chung-Yin Lin¹, Yu-Chien Lin², Hao-Li Liu²

¹Institute for Radiological Research, Chang Gung University, Taoyuan City, Taiwan; ²Department of Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan

Chenchen Bing¹, Debra Szczepanski¹, Imalka Munaweera¹, Yu Hong¹, Ian Corbin², Rajiv Chopra^1,2

¹Radiology, UT Southwestern Medical Center, Dallas, Texas, USA; ²Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, USA

Maria Eleni Karakatsani¹, Tara Kugelman¹, Shutao Wang¹, Karen Duff³, Elisa E. Konofagou^1,2

¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Radiology, Columbia University, New York, New York, USA; ³Pathology and Cell Biology, Columbia University, New York, New York, USA

¹Graduate School of Biomedical Engineering - Umemura-Yoshizawa Laboratory, Tohoku University, Sendai, Miyagi, Japan; ²LabTAU, INSERM U1032, Université deLyon, Lyon, France

¹UMC Utrecht, Utrecht, Netherlands; ²Imasonic SAS, Voray-sur-l'Ognon, France

¹Univ Lyon, Université Lyon 1, INSERM, LabTAU, F-69003, LYON, France, Lyon, France; ²Department of Physical Medicine & Rehabilitation, National TaiwanUniversity Hospital, Taipei, Taiwan; ³Department of Electrical Engineering, Chang Gung University, Taoyuan City, Taiwan

¹Department of Biomedical Engineering, Technion I.I.T, Haifa, Israel; ²Insightec LTD, Tirat HaCarmel, Israel; ³Department of Medicine, Technion I.I.T., Haifa, Israel

¹LabTAU, INSERM, Lyon, France; ²Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA; ³FUS Foundation, Charlottesville, Virginia, USA; ⁴Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA

¹Sunnybrook Research Institute, Toronto, Ontario, Canada; ²Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

¹University of Toronto, Toronto, Ontario, Canada; ²Sunny brook Research Institute, Toronto, Ontario, Canada

¹Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, USA; ²National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA

Kazuhiro Matsui¹, Françoise CHAVRIER^{2, 4}, Takashi Azuma³, Ichiro Sakuma^{1, 5}, William Apoutou N'Djin^{2, 4}, Rémi Souchon^2,4

¹Engineering, The University of Tokyo, Tokyo, Japan; ²LabTAU, INSERM unité 1032, Lyon, France; ³Medicine, The University of Tokyo, Tokyo, Japan; ⁴Univ Lyon, Université Lyon 1, Lyon, France; ⁵Medical Device Development and Regulation Research Center, Tokyo, Japan

**O24 Image-based predicition of focusing gain in situ using dual-mode ultrasound arrays**

¹LabTAU - U1032, INSERM, Lyon, Rhône Alpes, France; ²CHU Croix Rousse, LYON, France

¹Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota, USA; ²Siemens, Seattle, Washington, USA

¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Neuroscience, Columbia University, New York, New York, USA, ³Radiology, Columbia University, New York, New York, USA

Paul Greillier¹, Bénédicte Ankou², Ali Zorgani¹, Francis Bessière², Fabrice Marquet³, Julie Magat³, Sandrine Melot-Dusseau⁴, Romain Lacoste⁴, Bruno Quesson³, Mathieu Pernot⁵, Philippe Chevalier², Cyril Lafon^{1, 6}

¹The University of Tokyo, Tokyo, Japan; ²Kyushu University, Fukuoka, Japan

J. Robin^1,2, B. Arnal¹, M. Tanter¹, M. Pernot¹

¹Institut Langevin, Paris, France; ²Université Paris 7, Paris, France

Y. I. Zhu¹, X. Lu², C. Dou², D. L. Miller², O. D. Kripfgans^{2, 1}

¹O.D. Kripfgans, Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; ²Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA

¹Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA; ²Neurological Surgery, University of Virginia Hospital, Charlottesville, Virginia, USA; ³Radiology, Stanford University, Palo Alto, Virginia, USA

Satya V.V.N. Kothapalli¹, Michael Altman², Ari Partanen³, Lifei Zhu¹, Galen Cheng¹, H. Michael Gach², William Straube², Dennis Hallahan², Hong Chen^1,2

¹Biomedical Engieering, Washington University in Saint Louis, Saint Louis, Missouri, USA; ²Department of Radiation Oncology, Washington University in St. Louis, Saint Louis, Missouri, USA; ³Clinical Science MR Therapy, Philips, Andover, Massachusetts, USA

¹The College of Biomedical Engineering, Chongqing Medical University, Chongqing, Chongqing, China; ²Haifu Hospital of the First Hospital Affiliated Hospital, Chongqing Medical University, Chongqing, China

¹LabTAU - U1032, INSERM, Lyon, Rhône Alpes, France; ²Centre Leon Berard, Lyon, France

Q. Zhu¹, S. GAO¹, G. Dong², M. Guo¹, F. XIE³

¹Department of Ultasound, XinQiao Hospital,Third Military Medical University, Chongqing, China; ²Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; ³Internal Medicine Cardiology, University of Nebraska Medical Center, Omaha, NE, China

S. Yeo¹, Y. Kim^{2, 3}, H. Lim^{3, 4}, H. Rhim³, S. Jung^{4, 5}, N. Hwang⁵

¹Joint Department of Physics, The Institute of Cancer Research, Sutton, UK; ²Swansea University, Swansea, UK; ³Bristol University, Bristol, UK; ⁴St. Andrew's University, St. Andrews, UK

S. Ohl¹, E. Klaseboer¹, A. Szeri², B. Khoo³

¹Institute of High Performance Computing, Singapore, Singapore; ²University of California, Berkeley, Berkeley, California, USA; ³National University of Singapore, Singapore, Singapore

¹Eindhoven University of Technology, Eindhoven, Netherlands; ²University Hospital Cologne, Cologne, Germany; ³Department of Multiphysics & Optics, Philips Research Eindhoven, Eindhoven, Netherlands; ⁴Department of Oncology Solutions, Philips Research Eindhoven, Eindhoven, Netherlands

¹University of Toronto, Toronto, Ontario, Canada; ²Sunnybrook Research Institute, Toronto, Ontario, Canada

¹Department of Radiology, UT Southwestern Medical Center, Dallas, Texas, USA; ²Ultrasound Imaging & Interventions, Philips Research North America, Cambridge, Massachusetts, USA

V. Barrere^1,2, D. Melodelima^1,2

¹LabTAU, INSERM, Lyon, France; ²Université Claude Bernard, Lyon 1, Lyon, France

¹BME, Columbia University, New York, New York, USA; ²Radiology, Columbia University, New York, New York, USA

¹Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, China; ²National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Shenzhen, China

¹Center for Immunity and Immunotherapies, Seattle Children's Research, Seattle, Washington, USA; ²Sonic Concepts Inc., Bothell, Washington, USA; ³Pediatrics, University of Washington, Seattle, Washington, USA

¹Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China; ²Internal Medicine Cardiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

¹Biomedical Engineering, Columbia University, New York, New York, USA; ²Radiology, Columbia University, New York, New York, USA