This work was supported by the National Institutes of Health (R01-EB014496). The authors would like to thank Iason Apostolakis for his contribution to the experiments.

This protocol was approved by the Institutional Animal Care and Use Committee of Columbia University. All the data acquisition and processing were performed using the Matlab environment.
1. Experimental Set-up
<ol>
	<li>Degas an ex vivo canine liver sample during 90 min. Put the liver sample in a tank filled with degassed Phosphate Buffered Solution (Figure 1). Fix the liver sample on an acoustic absorber with needles at the extremities of the liver.</li>
	<li>Inser...

<ol>
	<li>Al-Bataineh, O., Jenne, J., Huber, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+and+future+applications+of+high+intensity+focused+ultrasound+in+cancer.">Clinical and future applications of high intensity focused ultrasound in cancer.</a> Cancer Treat Rev. 38, 346-353 (2012).</li><li>Dewhirst, M. W., Viglianti, B. L., Lora-Michiels, M., Hanson, M., Hoopes, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Basic+principles+of+thermal+dosimetry+and+thermal+thresholds+for+tissue+damage+from+hyperthermia.">Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia.</a> Int J Hyperthermia. 19, 267-294 (2003).</li><li>Napoli, 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=MR-guided+high-intensity+focused+ultrasound:+current+status+of+an+emerging+technology.">MR-guided high-intensity focused ultrasound: current status of an emerging technology.</a> Cardiovasc Intervent Radiol. 36, 1190-1203 (2013).</li><li>Gudur, M. S., Kumon, R. E., Zhou, Y., Deng, C. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-frequency+rapid+B-mode+ultrasound+imaging+for+real-time+monitoring+of+lesion+formation+and+gas+body+activity+during+high-intensity+focused+ultrasound+ablation.">High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation.</a> IEEE Trans Ultrason Ferroelectr Freq Control. 59, 1687-1699 (2012).</li><li>Jensen, C. R., Cleveland, R. O., Coussios, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-time+temperature+estimation+and+monitoring+of+HIFU+ablation+through+a+combined+modeling+and+passive+acoustic+mapping+approach.">Real-time temperature estimation and monitoring of HIFU ablation through a combined modeling and passive acoustic mapping approach.</a> Phys Med Biol. 58, 5833-5850 (2013).</li><li>Mariani, 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=Real+time+shear+waves+elastography+monitoring+of+thermal+ablation:+in+vivo+evaluation+in+pig+livers.">Real time shear waves elastography monitoring of thermal ablation: in vivo evaluation in pig livers.</a> J Surg Res. 188, 37-43 (2014).</li><li>Bing, K. F., Rouze, N. C., Palmeri, M. L., Rotemberg, V. M., Nightingale, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+ultrasonic+thermal+ablation+with+interleaved+ARFI+image+monitoring+using+a+single+diagnostic+curvilinear+array:+a+feasibility+study.">Combined ultrasonic thermal ablation with interleaved ARFI image monitoring using a single diagnostic curvilinear array: a feasibility study.</a> Ultrason Imaging. 33, 217-232 (2011).</li><li>Athanasiou, 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=Breast+lesions:+quantitative+elastography+with+supersonic+shear+imaging--preliminary+results.,+Radiology.">Breast lesions: quantitative elastography with supersonic shear imaging--preliminary results., Radiology.</a> 256, 297-303 (2010).</li><li>Maleke, C., Konofagou, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Harmonic+motion+imaging+for+focused+ultrasound+(HMIFU):+a+fully+integrated+technique+for+sonication+and+monitoring+of+thermal+ablation+in+tissues.">Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues.</a> Phys Med Biol. 53, 1773-1793 (2008).</li><li>Maleke, C., Konofagou, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+feasibility+of+real-time+monitoring+of+focused+ultrasound+surgery+(FUS)+using+harmonic+motion+imaging+(HMI).">In vivo feasibility of real-time monitoring of focused ultrasound surgery (FUS) using harmonic motion imaging (HMI).</a> IEEE Trans Biomed Eng. 57, 7-11 (2010).</li><li>Hou, G. Y., 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=Sparse+matrix+beamforming+and+image+reconstruction+for+2-D+HIFU+monitoring+using+harmonic+motion+imaging+for+focused+ultrasound+(HMIFU)+with+in+vitro+validation.">Sparse matrix beamforming and image reconstruction for 2-D HIFU monitoring using harmonic motion imaging for focused ultrasound (HMIFU) with in vitro validation.</a> IEEE Trans Med Imaging. 33, 2107-2117 (2014).</li></ol>

The authors declare that they have no competing financial interests.

Real-time monitoring of HIFU lesions is important to ensure proper and efficient lesion delivery. As the lesion forms, the tissue stiffens and its motion amplitude under excitation decreases. Applying HIFU in a region of the tissue results in an acoustic radiation force that induces tissue displacement. The relative change in displacement is a surrogate of relative change in tissue stiffness. This technique offers the advantage of monitoring HIFU lesion without stopping the treatment in contrast to other ultrasound based...

High Intensity Focused Ultrasound (HIFU) is a technique that generates temperature elevation at the focal region and can be used to ablate cancerous tissue 1. Temperature elevation at the focus causes thermal lesions in the tissue 2. In order to avoid overtreating a region and to reduce treatment duration, it is imperative to reliably monitor the ablation. Magnetic resonance-guided focused ultrasound (MRgFUS) is the main technique used in clinic to guide and monitor HIFU treatment 3. MRI provides high spatial resolution images of the treated region with tissue displacement or thermal dose but has a frame rate of 0.1-1 Hz and is costly. Several ultrasound-based techniques such as B-mode imaging 4, passive acoustic mapping 5, shear wave imaging 6 and acoustic radiation force impulse 7 have been developed to guide and monitor thermal ablation. However, B-mode imaging and passive acoustic mapping do not provide imaging of mechanical properties of the ablated region which is useful to the operator to improve lesion delivery. 
Shear wave imaging and acoustic radiation force impulse can both characterize the elasticity of the tissue by measuring acoustic radiation force-induced displacements 7,8. However, in both methods, the HIFU treatment is typically interrupted to monitor the ablation. Our group has developed a technique called Harmonic Motion Imaging for Focus Ultrasound (HMIFU) which can monitor the HIFU treatment with ultrasound without stopping the ablation9,10. Briefly, a HIFU transducer sends an amplitude-modulated wave to the region to ablate while simultaneously generating an oscillatory motion in the focal region. A co-axially aligned ultrasound transducer is used to image this oscillation. The magnitude of the induced motion is related to the stiffness of the tissue.
To ensure proper lesion delivery, the temporal resolution of real-time monitoring is of key interest in ablation guidance. Recently, our group has shown real-time streaming of displacement at a frame rate up to 15 Hz, imaged with diverging waves in a narrow field of view and using a fast image reconstruction method 11. Several beamforming techniques can be used to image the displacements. A large field of view can be obtained with diverging wave imaging by changing the delay profile but the axial direction is not aligned with the HIFU beam on the lateral regions and the wave is attenuated due to geometric spreading in the lateral direction, which can affect the quality of the displacement estimation. In contrast, the lateral field of view for plane wave is upper bounded by the active aperture but the axial direction is aligned with the HIFU beam at the focus and there is no geometric spreading in the lateral direction. Depending on the type of application, one or the other imaging method can be selected. The objectives of this protocol are to show how plane wave imaging can provide real-time streaming of displacements images using HMIFU during ablation and to compare the quality of the motion estimation between diverging and plane wave imaging.

<table border="0" cellpadding="0" cellspacing="0">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr>
			<td>P4-2 Phased array</td>
			<td>ATL</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>H-178 HIFU transducer</td>
			<td>Sonic Concepts</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>3-D positioner</td>
			<td>Velmex Inc.</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>AT33522A function generator</td>
			<td>Agilent Technologies</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>V-1 ultrasound system</td>
			<td>Verasonics</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>3100L RF amplifier</td>
			<td>ENI</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Matching network</td>
			<td>Sonic Concepts</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Degasing system</td>
			<td>Sonic Concepts</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Programming software</td>
			<td>Matlab</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Jacket software package</td>
			<td>Accelereyes</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

real-time monitoring of high intensity focused ultrasound (hifu) ablation of in vitro canine livers using harmonic motion imaging for focused ultrasound (hmifu)

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An oscillatory motion is generated at the focus of a 93-element and 4.5 MHz center frequency HIFU transducer by applying a 25 Hz amplitude-modulated signal using a function generator. A 64-element and 2.5 MHz imaging transducer with 68kPa peak pressure is confocally placed at the center of the HIFU transducer to acquire the radio-frequency (RF) channel data. In this protocol, real-time monitoring of thermal ablation using HIFU with an acoustic power of 7 W on canine livers in vitro is described. HIFU treatment is applied on the tissue during 2 min and the ablated region is imaged in real-time using diverging or plane wave imaging up to 1,000 frames/second. The matrix of RF channel data is multiplied by a sparse matrix for image reconstruction. The reconstructed field of view is of 90&#176; for diverging wave and 20 mm for plane wave imaging and the data are sampled at 80 MHz. The reconstruction is performed on a Graphical Processing Unit (GPU) in order to image in real-time at a 4.5 display frame rate. 1-D normalized cross-correlation of the reconstructed RF data is used to estimate axial displacements in the focal region. The magnitude of the peak-to-peak displacement at the focal depth decreases during the thermal ablation which denotes stiffening of the tissue due to the formation of a lesion. The displacement signal-to-noise ratio (SNRd) at the focal area for plane wave was 1.4 times higher than for diverging wave showing that plane wave imaging appears to produce better displacement maps quality for HMIFU than diverging wave imaging.

Real-time streaming of HMI displacement during HIFU ablation can be obtained using diverging and plane wave imaging. Figure 2 is a video screen capture showing real-time display of acoustic radiation force induced displacement using plane wave imaging in in vitro canine livers during HIFU ablation. The displacements are streamed in real-time on the computer screen at a display frame rate of 4.5 Hz. Positive displacements are shown in red and negative displacements in blue. Lesions were successfu...

Watch this Scientific Journal Video about Real-time Monitoring of High Intensity Focused Ultrasound HIFU Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound HMIFU a

Real-time Monitoring of High Intensity Focused Ultrasound HIFU Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound HMIFU

This article describes real-time monitoring of HIFU ablation in canine liver with high frame rate ultrasound imaging using diverging and plane wave imaging. Harmonic Motion Imaging for Focused Ultrasound is used to image the decrease of acoustic radiation force induced displacement in the ablated region.

Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU)

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An ...

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9.9K ビュー.  Columbia University. This article describes real-time monitoring of HIFU ablation in canine liver with high frame rate ultrasound imaging using diverging and plane wave imaging. Harmonic Motion Imaging for Focused Ultrasound is used to image the decrease of acoustic radiation force induced displacement in the ablated region.

ビデオ: Real-time Monitoring of High Intensity Focused Ultrasound HIFU Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound HMIFU