Name: Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System (Video) | JoVE Journal
Uploaded: 2019-03-06T14:45:00.000+00:00
Duration: 8 min 8 s
Description: Learn to evaluate targeting accuracy in ultrasound-guided high-intensity focused ultrasound systems using a self-focused transducer and image reconstruction methods. This protocol ensures safety and efficacy in clinical applications.

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5 minutes

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>

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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><tbody><tr><td>Acrylamide</td><td>Amresco</td><td>D403-2</td><td></td></tr><tr><td>Acrylic baseboard</td><td>LAO NIAO STORES</td><td>customized</td><td></td></tr><tr><td>Acrylic cylindrical water tank&amp;nbsp;</td><td>LAO NIAO STORES</td><td>customized</td><td></td></tr><tr><td>Ammonium persulfate</td><td>Yatai United Chemical Co., Ltd (Wuxi, China)</td><td>2017-03-01</td><td></td></tr><tr><td>Beaker</td><td>East China Chemical Reagent Instrument Store</td><td></td><td></td></tr><tr><td>Bis-acrylamide</td><td>Amresco</td><td>M0172</td><td></td></tr><tr><td>Bovine muscle</td><td>Market</td><td></td><td></td></tr><tr><td>Chopping board</td><td>JIACHI</td><td>JC-ZB40</td><td></td></tr><tr><td>Cylindrical plastic&amp;nbsp;phantom holder</td><td>QIYINPAI</td><td>customized</td><td></td></tr><tr><td>Degassed deionized water</td><td></td><td></td><td>made by the USgHIFU system</td></tr><tr><td>Electric balance</td><td>YINGHENG</td><td>11119453359</td><td></td></tr><tr><td>Glass rod</td><td>East China Chemical Reagent Instrument Store</td><td></td><td></td></tr><tr><td>Knife</td><td>SHIBAZI</td><td>SL1210-C</td><td></td></tr><tr><td>Mask</td><td>Medicom</td><td>2498</td><td></td></tr><tr><td>N,N,N&amp;rsquo;,N&amp;rsquo;&amp;ndash;Tetramethylethylenediamine</td><td>Zhanyun Chemical Co., Ltd (Shanghai, China)</td><td></td><td></td></tr><tr><td>Rubber glove</td><td>AMMEX</td><td>YZB/MAL 0587-2018</td><td></td></tr><tr><td>Scanner</td><td>Fuji Xerox</td><td>DocuPrint M268dw</td><td></td></tr><tr><td>Screwdriver</td><td>Stanley</td><td>T6</td><td></td></tr><tr><td>Silica gel</td><td>GE</td><td>381</td><td></td></tr><tr><td>Square model</td><td>QIYINPAI</td><td>customized</td><td></td></tr><tr><td>Stainless steel spoons</td><td>East China Chemical Reagent Instrument Store</td><td></td><td></td></tr><tr><td>Sucker</td><td>East China Chemical Reagent Instrument Store</td><td></td><td></td></tr><tr><td>Swine muscle</td><td>Market</td><td></td><td></td></tr><tr><td>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

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° and 90°. 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 of the four...

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

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A High-Throughput Image-Guided Stereotactic Neuronavigation and Focused Ultrasound System for Blood-Brain Barrier Opening in Rodents

This protocol delineates steps necessary for the gene delivery through focused ultrasound blood brain barrier (BBB) opening, evaluation of the resulting gene expression, and measurement of neuromodulation activity of chemogenetic receptors through histological tests.

Focused Ultrasound Induced Blood-Brain Barrier Opening for Targeting Brain Structures and Evaluating Chemogenetic Neuromodulation

Presented here is a protocol to use controlled hyperthermia, generated by magnetic resonance-guided high intensity focused ultrasound, to trigger drug release from temperature-sensitive liposomes in a rhabdomyosarcoma mouse model.

Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model

Here, we present a protocol to allow providers to perform focused cardiac ultrasound (FoCUS) in the clinical environment. We describe methods of transducer manipulation, review common pitfalls of transducer movements, and suggest tips to optimize phased array transducer use.

Troubleshooting FoCUS Image Acquisition: Patient Positioning, Transducer Manipulation, and Image Optimization

Transcranial ultrasonic stimulation (TUS) is a promising non-invasive technique capable of stimulating the human brain at any depth, offering new therapeutic possibilities to treat various neurological conditions. This protocol provides a standardized yet adaptable empirical framework for applying TUS in neurotypical adults and patients with neurological diseases such as stroke.

A Methodological Protocol and Considerations for Transcranial Ultrasonic Stimulation in Exploratory Clinical Human Studies

Learn to evaluate targeting accuracy in ultrasound-guided high-intensity focused ultrasound systems using a self-focused transducer and image reconstruction methods. This protocol ensures safety and efficacy in clinical applications.

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

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