This work has been supported in part by the National Natural Science Foundation of China (81402522), the Shanghai Key Technology R&#38;D Program (17441907400) from the Science and Technology Commission of Shanghai Municipality, and Shanghai Jiao Tong University Medical Engineering Research Fund (YG2017QN40, YG2015ZD10). Zhonghui Medical Technology (Shanghai) Co., Ltd. is also acknowledged for providing the USgHIFU system. The authors thank Wenzhen Zhu and Junhui Dong for the phantom preparation and their assistance in the experiments.

1. Marker design and fabrication
<ol>
	<li>Design a square model using computer-aided design software. Set each side as sticks with lengths of 40 mm and thicknesses of 2 mm. Place a solid ball with a 10 mm diameter at each corner of the square model.</li>
	<li>Use acrylonitrile butadiene styrene photosensitive resin as the material for printing.</li>
	<li>Send the 3D model file to a manufacturer for fabrication.</li>
</ol>
2. Phantom preparation
<ol>
	<li>Attach a plastic cylinder (with a diameter of 8 cm and a height of 3 cm) to an acrylic baseboard with silica gel to make a phantom holder at room temperature. Let it sit for 1 h.</li>
	<li>Slice fresh bovine muscle into a square shape (30 mm x 30 mm, with a thickness of 10 mm) and ventilate it for 2 h to evaporate moisture.</li>
	<li>Pour degassed and deionized water (115 mL) in a beaker, add in 13 g of acrylamide, and stir until dissolved. Add 0.24 g of bis-acrylamide and stir until dissolved. Then, add 0.2 mL of N,N,N&#39;,N&#39;-tetramethylethylenediamine and stir uniformly. 
	NOTE: Put on a mask and rubber gloves.</li>
	<li>Prepare 5 mL of degassed and deionized water in another beaker, add 0.3 g of ammonium persulfate, and stir to dissolve. 
	CAUTION: Acrylamide, bis-acrylamide, N,N,N&#39;,N&#39;-tetramethylethylenediamine, and ammonium persulfate are toxic. Pay close attention and avoid physical contact.</li>
	<li>Successively pour 40% of the solutions from steps 2.3 and 2.4 into the phantom holder, and stir for 5 s. Let the mixture sit for 20 min to solidify.</li>
	<li>Place the 3D-printed square model on the surface of the solidified phantom, and put the sliced bovine muscle in the middle of the model. Pour the rest of the solution from step 2.3 into the phantom holder. Move the bovine muscle back and forth to remove the air between the interface of the phantom and the slice.</li>
	<li>Pour the rest of the solution prepared in step 2.4 into the phantom holder, and stir for 5 s.</li>
	<li>Fine-tune the location of the sliced bovine muscle to the center of the phantom along the transverse direction. Let it sit for 20 min to solidify the phantom.</li>
	<li>Remove the silica gel between the cylindrical plastic and the acrylic baseboard, using a screwdriver.</li>
	<li>Slowly detach the acrylic baseboard from the cylindrical plastic.</li>
</ol>
3. Setup of the USgHIFU system
<ol>
	<li>Start the clinical USgHIFU system.</li>
	<li>Turn on the water-processing module, and set the speed of water circulation at 80 rounds/min.</li>
	<li>Fill an acrylic cylindrical water tank (with a diameter of 30 cm and a height of 13 cm) with degassed water at room temperature (22-25 &#176;C).</li>
	<li>Place the phantom holder into the degassed water and fix the holder tightly.</li>
	<li>Move the cylindrical water tank onto the treatment bed. Lift the treatment bed and move&#160;down the therapeutic unit into the degassed water.</li>
</ol>
4. US-guided targeting
<ol>
	<li>Move the therapeutic unit slowly up and down to make sure that the depth of the treatment plane is located at the upper interface of the sliced bovine muscle and transparent phantom in the US image.</li>
	<li>Rotate the US imaging probe to 0&#176; and move the cylindrical water tank to make the rotating axis (also referred to as imaging axis) pass through the middle point of the two parallel sticks in the US image.</li>
	<li>Rotate the imaging probe to 90&#176; and move the cylindrical water tank to make the rotating axis pass through the middle point of the two parallel sticks in the US image.</li>
	<li>Reconstruct the US image in the treatment plane at the depth of geometric focus.</li>
	<li>Check if the four balls are clearly shown in the reconstructed US image and whether the target is located at the center of the square model. 
	NOTE: The center of the target is predetermined at the center of the reconstructed image. The ball is determined by a circle with a 10 mm diameter, the average gray value of which is highest in a 15 mm x 15 mm square. The center of the square model is determined by the diagonal of the four balls in the reconstructed image.</li>
	<li>Move the water tank according to the relative positions between the target and the square model, and repeat steps 4.4 and 4.5.</li>
	<li>Lift the therapeutic unit and put the swine muscle with a thickness of around 30 mm above the phantom. Then, move down the therapeutic unit until the depth of geometric focus is 3 mm beneath the upper surface of the sliced bovine muscle. 
	NOTE: The 3 mm focal correction along the beam path is estimated according to the thickness of the swine muscle based on the empirical formula from a previous study19.</li>
</ol>
5. HIFU sonication
<ol>
	<li>Select the following sonication parameters: pulse duration (400 ms), duty cycle (80%), acoustic power (400 W), and cooling time between the sonication of successive focal spots (30 s).</li>
	<li>Set the exposure time for the focal spots in the target.
	<ol>
		<li>Repeat the procedure for three concentric regular hexagonal targets with respective diagonals of 5.4 mm, 9 mm, and 12.6 mm. Set exposure times of 2.0 s, 2.5 s, and 3.0 s for the focal spots located at the inner, middle, and outer hexagon, respectively, and 2.0 s for the focal spot at the geometric center of the phased array.</li>
	</ol>
	</li>
	<li>Start the sonication and put one foot on the foot pedal for HIFU sonication.</li>
	<li>Observe the change of echogenicity in the US image until the sonications are completed.</li>
</ol>
6. Evaluation of the targeting accuracy of the USgHIFU phased-array system
<ol>
	<li>Fetch the phantom holder, and smoothly press the phantom to take it out.</li>
	<li>Split the phantom along the treatment plane using a knife.</li>
	<li>Scan the treatment plane of the phantom that contains the sliced bovine muscle.</li>
	<li>Process the scanned image using mathematical software and extract the boundaries of the target and lesion.</li>
	<li>Calculate the intercenter distance dc and the maximal overshooting of the target boundary db. 
	NOTE: dc is the distance between the centers of the target and its respective lesion. db is the maximum overshooting distance between the boundary of the lesion and its respective target.</li>
	<li>Compute the ratio of the areas of lesion inside and outside the target to the target area as &#951;I = (SA&#160;&#8745;&#160;SP) / SP and &#951;O = (SA&#160;-&#160;SA&#160;&#8745;&#160;SP) / SP, respectively. 
	NOTE: SP indicates the target area, SA represents the lesion area.</li>
</ol>

<ol>
	<li>Wang, S. B., He, C. C., Li, K., Ji, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+a+112-channel+phased-array+ultrasonography-guided+focused+ultrasound+system+in+combination+with+switch+of+ultrasound+imaging+plane+for+tissue+ablation.">Design of a 112-channel phased-array ultrasonography-guided focused ultrasound system in combination with switch of ultrasound imaging plane for tissue ablation.</a> 2014 Symposium on Piezoelectricity, Acoustic Waves, and Device Applications (SPAWDA). , 134-137 (2014).</li><li>Choi, J. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Portable+high-intensity+focused+ultrasound+system+with+3D+electronic+steering,+real-time+cavitation+monitoring,+and+3D+image+reconstruction+algorithms:+a+preclinical+study+in+pigs.">Portable high-intensity focused ultrasound system with 3D electronic steering, real-time cavitation monitoring, and 3D image reconstruction algorithms: a preclinical study in pigs.</a> Ultrasonography. 33 (3), 191-199 (2014).</li><li>Hand, J. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+random+phased+array+device+for+delivery+of+high+intensity+focused+ultrasound.">A random phased array device for delivery of high intensity focused ultrasound.</a> Physics in Medicine and Biology. 54 (19), 5675-5693 (2009).</li><li>Khokhlova, V. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+HIFU+transducers+to+generate+specific+nonlinear+ultrasound+fields.">Design of HIFU transducers to generate specific nonlinear ultrasound fields.</a> Physics Procedia. 87, 132-138 (2016).</li><li>Melodelima, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermal+ablation+by+high-intensity-focused+ultrasound+using+a+toroid+transducer+increases+the+coagulated+volume+results+of+animal+experiments.">Thermal ablation by high-intensity-focused ultrasound using a toroid transducer increases the coagulated volume results of animal experiments.</a> Ultrasound in Medicine and Biology. 35 (3), 425-435 (2009).</li><li>McDannold, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uterine+leiomyomas:+MR+imaging-based+thermometry+and+thermal+dosimetry+during+focused+ultrasound+thermal+ablation.">Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during focused ultrasound thermal ablation.</a> Radiology. 240 (1), 263-272 (2006).</li><li>K&#246;hler, M. O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+HIFU+ablation+under+3D+guidance+of+rapid+MRI+thermometry.">Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry.</a> Medical Physics. 36 (8), 3521-3535 (2009).</li><li>Lu, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+256-element+phased-array+focused+ultrasound+surgery.">Image-guided 256-element phased-array focused ultrasound surgery.</a> IEEE Engineering in Medicine and Biology Magazine. 27 (5), 84-90 (2008).</li><li>Tong, S., Downey, D. B., Cardinal, H. N., Fenster, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+three-dimensional+ultrasound+prostate+imaging+system.">A three-dimensional ultrasound prostate imaging system.</a> Ultrasound in Medicine and Biology. 22 (6), 735-746 (1996).</li><li>Sakuma, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Navigation+of+high+intensity+focused+ultrasound+applicator+with+an+integrated+three-dimensional+ultrasound+imaging+system.">Navigation of high intensity focused ultrasound applicator with an integrated three-dimensional ultrasound imaging system.</a> Medical Image Computing and Computer-Assisted Intervention. , 133-139 (2002).</li><li>Masamune, K., Kurima, I., Kuwana, K., Yamashita, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HIFU+positioning+robot+for+less-invasive+fetal+treatment.">HIFU positioning robot for less-invasive fetal treatment.</a> Procedia CIRP. 5, 286-289 (2013).</li><li>Li, K., Bai, J. F., Chen, Y. Z., Ji, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+calibration+of+targeting+errors+for+an+ultrasound-guided+high-intensity+focused+ultrasound+system.">The calibration of targeting errors for an ultrasound-guided high-intensity focused ultrasound system.</a> 2017 IEEE International Symposium on Medical Measurements and Applications (MeMeA). , 10-14 (2017).</li><li>Ellens, N. P. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+targeting+accuracy+of+a+preclinical+MRI-guided+focused+ultrasound+system.">The targeting accuracy of a preclinical MRI-guided focused ultrasound system.</a> Medical Physics. 42 (1), 430-439 (2015).</li><li>McDannold, N., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quality+assurance+and+system+stability+of+a+clinical+MRI-guided+focused+ultrasound+system:+Four-year+experience.">Quality assurance and system stability of a clinical MRI-guided focused ultrasound system: Four-year experience.</a> Medical Physics. 33 (11), 4307-4313 (2006).</li><li>Gorny, K. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+guided+focused+ultrasound:+technical+acceptance+measures+for+a+clinical+system.">MR guided focused ultrasound: technical acceptance measures for a clinical system.</a> Physics in Medicine and Biology. 51 (12), 3155-3173 (2006).</li><li>Kim, Y. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+thermometry+analysis+of+sonication+accuracy+and+safety+margin+of+volumetric+MR+imaging-guided+high-intensity+focused+ultrasound+ablation+of+symptomatic+uterine+fibroids.">MR thermometry analysis of sonication accuracy and safety margin of volumetric MR imaging-guided high-intensity focused ultrasound ablation of symptomatic uterine fibroids.</a> Radiology. 265 (2), 627-637 (2012).</li><li>Chauhan, S., ter Haar, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=FUSBOTUS:+empirical+studies+using+a+surgical+robotic+system+for+urological+applications.">FUSBOTUS: empirical studies using a surgical robotic system for urological applications.</a> AIP Conference Proceedings. 911, 117-121 (2007).</li><li>An, C. Y., Syu, J. H., Tseng, C. S., Chang, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+ultrasound+imaging-guided+robotic+HIFU+ablation+experimental+system+and+accuracy+evaluations.">An ultrasound imaging-guided robotic HIFU ablation experimental system and accuracy evaluations.</a> Applied Bionics and Biomechanics. 2017, 5868695 (2017).</li><li>Li, D. H., Shen, G. F., Bai, J. F., Chen, Y. Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Focus+shift+and+phase+correction+in+soft+tissues+during+focused+ultrasound+surgery.">Focus shift and phase correction in soft tissues during focused ultrasound surgery.</a> IEEE Transactions on Biomedical Engineering. 58 (6), 1621-1628 (2011).</li><li>N'Djin, W. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Utility+of+a+tumor-mimic+model+for+the+evaluation+of+the+accuracy+of+HIFU+treatments.+results+of+in+vitro+experiments+in+the+liver.">Utility of a tumor-mimic model for the evaluation of the accuracy of HIFU treatments. results of in vitro experiments in the liver.</a> Ultrasound in Medicine and Biology. 34 (12), 1934-1943 (2008).</li><li>Tang, T. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+method+for+absolute+accuracy+evaluation+of+a+US-guided+HIFU+system+with+heterogeneous+phantom.">A new method for absolute accuracy evaluation of a US-guided HIFU system with heterogeneous phantom.</a> 2016 IEEE International Ultrasonics Symposium (IUS). , 1-4 (2016).</li><li>Li, K., Bai, J. F., Chen, Y. Z., Ji, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+evaluation+of+targeting+accuracy+of+an+ultrasound-guided+phased-array+high-intensity+focused+ultrasound+system.">Experimental evaluation of targeting accuracy of an ultrasound-guided phased-array high-intensity focused ultrasound system.</a> Applied Acoustics. 141, 19-25 (2018).</li></ol>

Xiang Ji is a paid consultant for Zhonghui Medical Technology (Shanghai) Co., Ltd. The other authors have nothing to disclose.

Robotic components have been used for extracorporeal USgHIFU systems. To evaluate the targeting accuracy of such systems, reference markers11,12,18, in vitro tissue17, tumor-mimic models, and temperature-sensitive phantoms have been used alone or in combination10,20. Compared with the protocols in those studies, this method is more clinically rele...

The phased array is increasingly designed and equipped in HIFU systems1,2,3,4,5,6,7. In USgHIFU phased-array systems, a US imaging probe is usually mounted in the central hole of the spherical HIFU transducer1,2,8. The probe is rotatable for targeting and image reconstruction in the three-dimensional space9. Precise targeting is required for the safety and efficacy of HIFU treatment. However, most of the studies for the evaluation of targeting accuracy have been performed for magnetic resonance-guided HIFU systems or USgHIFU systems configured with a self-focused HIFU transducer10,11,12,13,14,15,16. The purpose of the method described below is to evaluate the targeting accuracy in the focal plane for USgHIFU phased array systems.
A bovine muscle/marker-embedded phantom along the clinically relevant beam path is used in the evaluation of the targeting accuracy of a clinical USgHIFU phased-array system. A square model with four balls at the corners is fabricated and embedded, in combination with bovine muscle, into the transparent phantom. A regular hexagon is selected as the target based on the positions of the centers of four balls identified in the reconstructed US image on the treatment plane. After HIFU sonications, the treatment plane of the phantom is scanned, and the boundary of the lesion, as well as the positions of the four balls, can be determined in the scanned image. The targeting accuracy can be evaluated by measuring the distance between the centers of target and lesion, as well as three derivative parameters.
The method is simpler than the measurement of the targeting error using robotic movement with a specific reference object11,17,18 and more clinically relevant in comparison to the method based on single focal spot ablation in a homogeneous phantom10. This method can be used in the evaluation of the targeting accuracy of USgHIFU phased array systems. It can be also used for other USgHIFU systems equipped with self-focused HIFU transducers.

<table border="0" cellpadding="0" cellspacing="0" style="width:849px;" width="849">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:233px;">Acrylamide</td>
			<td style="width:276px;">Amresco</td>
			<td style="width:160px;">D403-2</td>
			<td style="width:180px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Acrylic baseboard</td>
			<td>LAO NIAO STORES</td>
			<td>customized</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Acrylic cylindrical water tank&#160;</td>
			<td>LAO NIAO STORES</td>
			<td>customized</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ammonium persulfate</td>
			<td>Yatai United Chemical Co., Ltd (Wuxi, China)</td>
			<td>2017-03-01</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Beaker</td>
			<td>East China Chemical Reagent Instrument Store</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Bis-acrylamide</td>
			<td>Amresco</td>
			<td>M0172</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Bovine muscle</td>
			<td>Market</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Chopping board</td>
			<td>JIACHI</td>
			<td dir="LTR">JC-ZB40</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Cylindrical plastic&#160;phantom holder</td>
			<td>QIYINPAI</td>
			<td>customized</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Degassed deionized water</td>
			<td style="width:276px;"></td>
			<td style="width:160px;"></td>
			<td>made by the USgHIFU system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Electric balance</td>
			<td>YINGHENG</td>
			<td>11119453359</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Glass rod</td>
			<td>East China Chemical Reagent Instrument Store</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Knife</td>
			<td>SHIBAZI</td>
			<td dir="LTR">SL1210-C</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Mask</td>
			<td>Medicom</td>
			<td>2498</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">N,N,N&#8217;,N&#8217;&#8211;Tetramethylethylenediamine</td>
			<td>Zhanyun Chemical Co., Ltd (Shanghai, China)</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Rubber glove</td>
			<td>AMMEX</td>
			<td>YZB/MAL 0587-2018</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Scanner</td>
			<td>Fuji Xerox</td>
			<td>DocuPrint M268dw</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Screwdriver</td>
			<td>Stanley</td>
			<td>T6</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Silica gel</td>
			<td>GE</td>
			<td>381</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Square model</td>
			<td>QIYINPAI</td>
			<td>customized</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stainless steel spoons</td>
			<td>East China Chemical Reagent Instrument Store</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sucker</td>
			<td>East China Chemical Reagent Instrument Store</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Swine muscle</td>
			<td>Market</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">USgHIFU system</td>
			<td>Zhonghui Medical Technology (Shanghai) Co., Ltd.</td>
			<td>SUA-I</td>
			<td></td>
		</tr>
	</tbody>
</table>

evaluating targeting accuracy in the focal plane for an ultrasound-guided high-intensity focused ultrasound phased-array system

Phased arrays are increasingly used as high-intensity focused ultrasound (HIFU) transducers in the existing extracorporeal ultrasound-guided HIFU (USgHIFU) systems. The HIFU transducers in such systems are usually spherical in shape with a central hole where a US imaging probe is mounted and can be rotated. The image on the plane of treatment can be reconstructed through the image sequence acquired during the rotation of the probe. Therefore, the treatment plan can be made on the reconstructed images. In order to evaluate the targeting accuracy in the focal plane of such systems, the protocol of a method using a bovine muscle and marker-embedded phantom is described. In the phantom, four solid balls at the corners of a square resin model serve as the reference markers in the reconstructed image. The target should be moved so that both its center and the center of the square model can coincide according to their relative positions in the reconstructed image. Swine muscle with a thickness of about 30 mm is placed above the phantom to mimic the beam path in clinical settings. After sonication, the treatment plane in the phantom is scanned and the boundary of the associated lesion is extracted from the scanned image. The targeting accuracy can be evaluated by measuring the distance between the centers of target and lesion, as well as three derivative parameters. This method cannot only evaluate the targeting accuracy of the target consisting of multiple focal spots rather than a single focal spot in a clinically relevant beam path of the USgHIFU phased-array system, but it can be also used in the preclinical evaluation or regular maintenance of USgHIFU systems configured with phased-array or self-focused HIFU transducer.

We made phantoms dedicated to evaluating the targeting accuracy of a clinical USgHIFU phased-array system with the targets of three different sizes. Figure 1 displays the US image at angles of 0&#176; and 90&#176;. The interfaces are clear, and the sticks of the square model are bright in the US images. Figure 2 demonstrates the reconstructed US image in the treatment plane and the focal spots of the largest target. The centers o...

Watch this Scientific Journal Video about Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System at JoVE.com

Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System

This study describes a protocol to evaluate the targeting accuracy in the focal plane of an ultrasound-guided high-intensity focused ultrasound phased-array system.

Phased arrays are increasingly used as high-intensity focused ultrasound (HIFU) transducers in the existing extracorporeal ultrasound-guided HIFU ...

evaluating-targeting-accuracy-focal-plane-for-an-ultrasound-guided

Research

JoVE Journal

Engineering

5.1K Views.  Shanghai Jiao Tong University. This study describes a protocol to evaluate the targeting accuracy in the focal plane of an ultrasound-guided high-intensity focused ultrasound phased-array system.

Video: Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System

Evaluating Plasmonic Transport in Current-carrying Silver Nanowires

Plasmonics is an emerging technology capable of simultaneously transporting a plasmonic signal and an electronic signal on the same information support1,2,3. In this context, metal nanowires are especially desirable for realizing dense routing networks4. A prerequisite to operate such shared nanowire-based platform relies on our ability to electrically contact individual metal nanowires and efficiently excite surface plasmon polaritons5 in this information support. In this article, we describe a protocol to bring electrical terminals to chemically-synthesized silver nanowires6 randomly distributed on a glass substrate7. The positions of the nanowire ends with respect to predefined landmarks are precisely located using standard optical transmission microscopy before encapsulation in an electron-sensitive resist. Trenches representing the electrode layout are subsequently designed by electron-beam lithography. Metal electrodes are then fabricated by thermally evaporating a Cr/Au layer followed by a chemical lift-off. The contacted silver nanowires are finally transferred to a leakage radiation microscope for surface plasmon excitation and characterization8,9. Surface plasmons are launched in the nanowires by focusing a near infrared laser beam on a diffraction-limited spot overlapping one nanowire extremity5,9. For sufficiently large nanowires, the surface plasmon mode leaks into the glass substrate9,10. This leakage radiation is readily detected, imaged, and analyzed in the different conjugate planes in leakage radiation microscopy9,11. The electrical terminals do not affect the plasmon propagation. However, a current-induced morphological deterioration of the nanowire drastically degrades the flow of surface plasmons. The combination of surface plasmon leakage radiation microscopy with a simultaneous analysis of the nanowire electrical transport characteristics reveals the intrinsic limitations of such plasmonic circuitry.

Silver nanowires can simultaneously transport electrons and optical information in the form of surface plasmons. A procedure is described here to realize such a shared circuitry and the limitations at propagating both information carriers are evaluated.

Plasmonics is an emerging technology capable of simultaneously transporting a plasmonic signal and an electronic signal on the same information ...

Measuring Material Microstructure Under Flow Using 1-2 Plane Flow-Small Angle Neutron Scattering

A new small-angle neutron scattering (SANS) sample environment optimized for studying the microstructure of complex fluids under simple shear flow is presented. The SANS shear cell consists of a concentric cylinder Couette geometry that is sealed and rotating about a horizontal axis so that the vorticity direction of the flow field is aligned with the neutron beam enabling scattering from the 1-2 plane of shear (velocity-velocity gradient, respectively). This approach is an advance over previous shear cell sample environments as there is a strong coupling between the bulk rheology and microstructural features in the 1-2 plane of shear. Flow-instabilities, such as shear banding, can also be studied by spatially resolved measurements. This is accomplished in this sample environment by using a narrow aperture for the neutron beam and scanning along the velocity gradient direction. Time resolved experiments, such as flow start-ups and large amplitude oscillatory shear flow are also possible by synchronization of the shear motion and time-resolved detection of scattered neutrons. Representative results using the methods outlined here demonstrate the useful nature of spatial resolution for measuring the microstructure of a wormlike micelle solution that exhibits shear banding, a phenomenon that can only be investigated by resolving the structure along the velocity gradient direction. Finally, potential improvements to the current design are discussed along with suggestions for supplementary experiments as motivation for future experiments on a broad range of complex fluids in a variety of shear motions.

A shear cell is developed for small-angle neutron scattering measurements in the velocity-velocity gradient plane of shear and is used to characterize complex fluids. Spatially resolved measurements in the velocity gradient direction are possible for studying shear-banding materials. Applications include investigations of colloidal dispersions, polymer solutions, and self-assembled structures.

A new small-angle neutron scattering (SANS) sample environment optimized for studying the microstructure of complex fluids under simple shear flow is ...

Laboratory Drop Towers for the Experimental Simulation of Dust-aggregate Collisions in the Early Solar System

For the purpose of investigating the evolution of dust aggregates in the early Solar System, we developed two vacuum drop towers in which fragile dust aggregates with sizes up to ~10 cm and porosities up to 70% can be collided. One of the drop towers is primarily used for very low impact speeds down to below 0.01 m/sec and makes use of a double release mechanism. Collisions are recorded in stereo-view by two high-speed cameras, which fall along the glass vacuum tube in the center-of-mass frame of the two dust aggregates. The other free-fall tower makes use of an electromagnetic accelerator that is capable of gently accelerating dust aggregates to up to 5 m/sec. In combination with the release of another dust aggregate to free fall, collision speeds up to ~10 m/sec can be achieved. Here, two fixed high-speed cameras record the collision events. In both drop towers, the dust aggregates are in free fall during the collision so that they are weightless and match the conditions in the early Solar System.

We present a technique to achieve low-velocity to intermediate-velocity collisions between fragile dust aggregates in the laboratory. For this purpose, two vacuum drop-tower setups have been developed that allow collision velocities between &#60;0.01 and ~10 m/sec. The collision events are recorded by high-speed imaging.

For the purpose of investigating the evolution of dust aggregates in the early Solar System, we developed two vacuum drop towers in which fragile dust ...

Single Plane Illumination Module and Micro-capillary Approach for a Wide-field Microscope

A module for light sheet or single plane illumination microscopy (SPIM) is described which is easily adapted to an inverted wide-field microscope and optimized for 3-dimensional cell cultures, e.g., multi-cellular tumor spheroids (MCTS). The SPIM excitation module shapes and deflects the light such that the sample is illuminated by a light sheet perpendicular to the detection path of the microscope. The system is characterized by use of a rectangular capillary for holding (and in an advanced version also by a micro-capillary approach for rotating) the samples, by synchronous adjustment of the illuminating light sheet and the objective lens used for fluorescence detection as well as by adaptation of a microfluidic system for application of fluorescent dyes, pharmaceutical agents or drugs in small quantities. A protocol for working with this system is given, and some technical details are reported. Representative results include (1) measurements of the uptake of a cytostatic drug (doxorubicin) and its partial conversion to a degradation product, (2) redox measurements by use of a genetically encoded glutathione sensor upon addition of an oxidizing agent, and (3) initiation and labeling of cell necrosis upon inhibition of the mitochondrial respiratory chain. Differences and advantages of the present SPIM module in comparison with existing systems are discussed.

A module for single plane illumination microscopy (SPIM) is described which is easily adapted to an inverted wide-field microscope and optimized for 3-dimensional cell cultures. The sample is located within a rectangular capillary, and via a microfluidic system fluorescent dyes, pharmaceutical agents or drugs can be applied in small quantities.

A module for light sheet or single plane illumination microscopy (SPIM) is described which is easily adapted to an inverted wide-field microscope and ...

Ambient Method for the Production of an Ionically Gated Carbon Nanotube Common Cathode in Tandem Organic Solar Cells

A method of fabricating organic photovoltaic (OPV) tandems that requires no vacuum processing is presented. These devices are comprised of two solution-processed polymeric cells connected in parallel by a transparent carbon nanotubes (CNT) interlayer. This structure includes improvements in fabrication techniques for tandem OPV devices. First the need for ambient-processed cathodes is considered. The CNT anode in the tandem device is tuned via ionic gating to become a common cathode. Ionic gating employs electric double layer charging to lower the work function of the CNT electrode. Secondly, the difficulty of sequentially stacking tandem layers by solution-processing is addressed. The devices are fabricated via solution and dry-lamination in ambient conditions with parallel processing steps. The method of fabricating the individual polymeric cells, the steps needed to laminate them together with a common CNT cathode, and then provide some representative results are described. These results demonstrate ionic gating of the CNT electrode to create a common cathode and addition of current and efficiency as a result of the lamination procedure.

A method of fabricating, in ambient conditions, organic photovoltaic tandem devices in a parallel configuration is presented. These devices feature an air-processed, semi-transparent, carbon nanotube common cathode.

A method of fabricating organic photovoltaic (OPV) tandems that requires no vacuum processing is presented. These devices are comprised of two ...

Characterization of Full Set Material Constants and Their Temperature Dependence for Piezoelectric Materials Using Resonant Ultrasound Spectroscopy

During the operation of high power electromechanical devices, a temperature rise is unavoidable due to mechanical and electrical losses, causing the degradation of device performance. In order to evaluate such degradations using computer simulations, full matrix material properties at elevated temperatures are needed as inputs. It is extremely difficult to measure such data for ferroelectric materials due to their strong anisotropic nature and property variation among samples of different geometries. Because the degree of depolarization is boundary condition dependent, data obtained by the IEEE (Institute of Electrical and Electronics Engineers) impedance resonance technique, which requires several samples with drastically different geometries, usually lack self-consistency. The resonant ultrasound spectroscopy (RUS) technique allows the full set material constants to be measured using only one sample, which can eliminate errors caused by sample to sample variation. A detailed RUS procedure is demonstrated here using a lead zirconate titanate (PZT-4) piezoceramic sample. In the example, the complete set of material constants was measured from room temperature to 120 &#176;C. Measured free dielectric constants <img alt="Equation 1" src="/files/ftp_upload/53461/image001.jpg" /> and&#160;<img alt="Equation 2" src="/files/ftp_upload/53461/image002.jpg" /> were compared with calculated ones based on the measured full set data, and piezoelectric constants d15 and d33 were also calculated using different formulas. Excellent agreement was found in the entire range of temperatures, which confirmed the self-consistency of the data set obtained by the RUS.

This protocol describes the procedure of measuring the temperature dependence of the full set material constants of piezoelectric materials using resonant ultrasound spectroscopy (RUS).

During the operation of high power electromechanical devices, a temperature rise is unavoidable due to mechanical and electrical losses, causing the ...

Focused Ion Beam Fabrication of LiPON-based Solid-state Lithium-ion Nanobatteries for In Situ Testing

Solid-state electrolytes are a promising replacement for current organic liquid electrolytes, enabling higher energy densities and improved safety of lithium-ion (Li-ion) batteries. However, a number of setbacks prevent their integration into commercial devices. The main limiting factor is due to nanoscale phenomena occurring at the electrode/electrolyte interfaces, ultimately leading to degradation of battery operation. These key problems are highly challenging to observe and characterize as these batteries contain multiple buried interfaces. One approach for direct observation of interfacial phenomena in thin film batteries is through the fabrication of electrochemically active nanobatteries by a focused ion beam (FIB). As such, a reliable technique to fabricate nanobatteries was developed and demonstrated in recent work. Herein, a detailed protocol with a step-by-step process is presented to enable the reproduction of this nanobattery fabrication process. In particular, this technique was applied to a thin film battery consisting of LiCoO2/LiPON/a-Si, and has further been previously demonstrated by in situ cycling within a transmission electron microscope.

Focused Ion Beam Fabrication of LiPON-based Solid-state Lithium-ion Nanobatteries for In Situ Testing

A protocol for the fabrication of electrochemically active LiPON-based solid-state lithium-ion nanobatteries using a focused ion beam is presented.

Solid-state electrolytes are a promising replacement for current organic liquid electrolytes, enabling higher energy densities and improved safety of ...

Controllable Nucleation of Cavitation from Plasmonic Gold Nanoparticles for Enhancing High Intensity Focused Ultrasound Applications

In this study, plasmonic gold nanoparticles were simultaneously exposed to pulsed near-infrared laser light and high intensity focused ultrasound (HIFU) for the controllable nucleation of cavitation in tissue-mimicking gel phantoms. This in vitro protocol was developed to demonstrate the feasibility of this approach, for both enhancement of imaging and therapeutic applications for cancer. The same apparatus can be used for both imaging and therapeutic applications by varying the exposure duration of the HIFU system. For short duration exposures (10 &#181;s), broadband acoustic emissions were generated through the controlled nucleation of inertial cavitation around the gold nanoparticles. These emissions provide direct localization of nanoparticles. For future applications, these particles may be functionalized with molecular-targeting antibodies (e.g. anti-HER2 for breast cancer) and can provide precise localization of cancerous regions, complementing routine diagnostic ultrasound imaging. For continuous wave (CW) exposures, the cavitation activity was used to increase the localized heating from the HIFU exposures resulting in larger thermal damage in the gel phantoms. The acoustic emissions generated from inertial cavitation activity during these CW exposures was monitored using a passive cavitation detection (PCD) system to provide feedback of cavitation activity. Increased localized heating was only achieved through the unique combination of nanoparticles, laser light and HIFU. Further validation of this technique in pre-clinical models of cancer is necessary.

This protocol demonstrates the controllable nucleation of cavitation in gel phantoms, through simultaneous exposure to both near-infrared pulsed laser light and high intensity focused ultrasound (HIFU). The cavitation activity can then be used for enhancing imaging and/or therapeutic uses of HIFU.

In this study, plasmonic gold nanoparticles were simultaneously exposed to pulsed near-infrared laser light and high intensity focused ultrasound (HIFU) ...

Multiplexing Focused Ultrasound Stimulation with Fluorescence Microscopy

By focusing low-intensity ultrasound pulses that penetrate soft tissues, LIPUS represents a promising biomedical technology to remotely and safely manipulate neural firing, hormonal secretion and genetically-reprogrammed cells. However, the translation of this technology for medical applications is currently hampered by a lack of biophysical mechanisms by which targeted tissues sense and respond to LIPUS. A suitable approach to identify these mechanisms would be to use optical biosensors in combination with LIPUS to determine underlying signaling pathways. However, implementing LIPUS to a fluorescence microscope may introduce undesired mechanical artefacts due to the presence of physical interfaces that reflect, absorb and refract acoustic waves. This article presents a step-by-step procedure to incorporate LIPUS to commercially-available upright epi-fluorescence microscopes while minimizing the influence of physical interfaces along the acoustic path. A simple procedure is described to operate a single-element ultrasound transducer and to bring the focal zone of the transducer into the objective focal point. The use of LIPUS is illustrated with an example of LIPUS-induced calcium transients in cultured human glioblastoma cells measured using calcium imaging.

Low-Intensity Pulsed Ultrasound Stimulation (LIPUS) is a modality for non-invasive mechanical stimulation of endogenous or engineered cells with high spatial and temporal resolution. This article describes how to implement LIPUS to an epi-fluorescence microscope and how to minimize acoustic impedance mismatch along the ultrasound path to prevent unwanted mechanical artefacts.

By focusing low-intensity ultrasound pulses that penetrate soft tissues, LIPUS represents a promising biomedical technology to remotely and safely ...

Evaluating Usability Aspects of a Mixed Reality Solution for Immersive Analytics in Industry 4.0 Scenarios

In medicine or industry, the analysis of high-dimensional data sets is increasingly required. However, available technical solutions are often complex to use. Therefore, new approaches like immersive analytics are welcome. Immersive analytics promise to experience high-dimensional data sets in a convenient manner for various user groups and data sets. Technically, virtual-reality devices are used to enable immersive analytics. In Industry 4.0, for example, scenarios like the identification of outliers or anomalies in high-dimensional data sets are pursued goals of immersive analytics. In this context, two important questions should be addressed for any developed technical solution on immersive analytics: First, is the technical solutions being helpful or not? Second, is the bodily experience of the technical solution positive or negative? The first question aims at the general feasibility of a technical solution, while the second one aims at the wearing comfort. Extant studies and protocols, which systematically address these questions are still rare. In this work, a study protocol is presented, which mainly investigates the usability for immersive analytics in Industry 4.0 scenarios. Specifically, the protocol is based on four pillars. First, it categorizes users based on previous experiences. Second, tasks are presented, which can be used to evaluate the feasibility of the technical solution. Third, measures are presented, which quantify the learning effect of a user. Fourth, a questionnaire&#160;evaluates the stress level when performing tasks. Based on these pillars, a technical setting was implemented that uses mixed reality smartglasses to apply the study protocol. The results of the conducted study show the applicability of the protocol on the one hand and the feasibility of immersive analytics in Industry 4.0 scenarios on the other. The presented protocol includes a discussion of discovered limitations.

This protocol delineates the technical setting of a developed mixed reality application that is used for immersive analytics. Based on this, measures are presented, which were used in a study to gain insights into usability aspects of the developed technical solution.

In medicine or industry, the analysis of high-dimensional data sets is increasingly required. However, available technical solutions are often complex to ...