A High-Precision US-Guided Robot-Assisted HIFU Treatment System for Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women. A strong treatment candidate is high-intensity focused ultrasound (HIFU), a non-invasive therapeutic method that has already demonstrated its promise. To improve the precision and lower the cost of HIFU treatment, our group has developed an ultrasound (US)-guided, five-degree-of-freedom (DOF), robot-assisted HIFU system. We constructed a fully functional prototype enabling easy three-dimensional (3D) US image reconstruction, target segmentation, treatment path generation, and automatic HIFU irradiation. The position was calibrated using a wire phantom and the coagulated area was assessed on heterogeneous tissue phantoms. Under the US guidance, the centroids of the HIFU-ablated area deviated by less than 2 mm from the planned treatment region. The overshoot around the planned region was well below the tolerance of clinical usage. Our system is considered to be sufficiently accurate for breast cancer treatment.     

In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI

In this paper, magnetic resonance imaging (MRI) is investigated for monitoring small and large lesions created by high-intensity focused ultrasound (HIFU) in freshly excised lamb brain and in rabbit brain in vivo. A single-element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at 1 MHz was used. A prototype MRI-compatible positioning device that is used to navigate the transducer is described. The effects of HIFU were investigated using T1-W and T2-W fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR). T2-W FSE and FLAIR show better anatomical details within the brain than T1-W FSE, but with T1-W FSE, the contrast between lesion and brain is higher for both thermal and bubbly lesions. The best contrast between lesion and brain with T1-W FSE is obtained with TR above 500 ms, whereas with T2-W FSE, the best contrast is observed between 40 and 60 ms. The maximum contrast to noise ratio (CNR) measured with T1-W FSE was approximately 20. With T2-W FSE, the corresponding CNR was approximately 12. With this system, we were able to create large lesions (by producing overlapping lesions), and it was possible to monitor these lesions with MRI with excellent contrast. The length of the lesions in vivo brain was much higher than the length in vitro, indicating that the penetration in the in vitro brain is limited, possibly by reflection due to trapped bubbles in the blood vessels. This paper demonstrates that HIFU has the potential to treat brain tumors in humans. This could be done either using a single-element transducer with a frequency around 1 MHZ or using a multi-element transducer.     

Monitoring of thermal therapy based on shear modulus changes: II. Shear wave imaging of thermal lesions

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is currently hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to a precise mapping of the lesion. HIFU treatment and monitoring were respectively performed using a confocal setup consisting of a 2.5-MHz single element transducer focused at 34 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Ultrasound-based strain imaging was combined with shear wave imaging on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created with pushing beams of 100 μs at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Thus, elasticity and strain mapping was achieved every 3 s, leading to real-time monitoring of the treatment. When thermal damage occurs, tissue stiffness was found to increase up to 4-fold and strain imaging showed strong shrinkages that blur the temperature information. We show that strain imaging elastograms are not easy to interpret for accurate lesion characterization, but SWI provides a quantitative mapping of the thermal lesion. Moreover, the concept of shear wave thermometry (SWT) developed in the companion paper allows mapping temperature with the same method. Combined SWT and shear wave imaging can map the lesion stiffening and temperature outside the lesion, which could be used to predict the eventual lesion growth by thermal dose calculation. Finally, SWI is shown to be robust to motion and reliable in vivo on sheep muscle.     

Axial control of thermal coagulation using a multi-element interstitial ultrasound applicator with internal cooling

A multi-element, direct-coupled ultrasound (US) applicator with internal water cooling was investigated for axial control of interstitial thermal coagulation. A prototype implantable applicator was constructed with a linear array of three tubular PZT ultrasound transducers (each 2.5 mm OD, 10 mm length, 360 degrees emittance). Acoustic beam distributions from each element were measured and found to be collimated within the transducer length. The internally cooled applicator could sustain high levels of applied power to each transducer (0 to 40 W) and maintain acceptable applicator surface temperatures (<100 degrees C). Thermal performance of the applicator was investigated through heating trials in vivo (porcine thigh muscle and liver) and in vitro (bovine liver). The radial depth of thermal lesions produced was dependent on the applied power and sonication time and was controlled independently with power levels to each transducer element. With 18 W per element (applied electrical power) for 3 min, cylindrical thermal lesions were produced with a diameter of ~3 cm and a length ranging from 1.2 cm (with one element) to 3.5 cm (three elements). Higher powers (24 to 30 W) for 3 to 5 min provided increased depths of coagulation (~4 cm diameter lesions). Analysis of axial lesion shapes demonstrated that individual variation of power to each transducer element provided control of axial heating and depth of coagulation (for custom lesion shapes); lesion lengths corresponded to the number of active transducers. This ability to control the heating distribution dynamically along the length of the applicator has potential for improved target localization of thermal coagulation and necrosis in high temperature thermal therapy.     

Feasibility of MR-temperature mapping of ultrasonic heating from a CMUT

In the last decade, high intensity focused ultrasound (HIFU) has gained popularity as a minimally invasive and noninvasive therapeutic tool for treatment of cancers, arrhythmias, and other medical conditions. HIFU therapy is often guided by magnetic resonance imaging (MRI), which provides anatomical images for therapeutic device placement, temperature maps for treatment guidance, and postoperative evaluation of the region of interest. While piezoelectric transducers are dominantly used for MR-guided HIFU, capacitive micromachined ultrasonic transducers (CMUTs) show competitive advantages, such as ease of fabrication, integration with electronics, improved efficiency, and reduction of self-heating. In this paper, we will show our first results of an unfocused CMUT transducer monitored by MR-temperature maps. This 2.51 mm by 2.32 mm, unfocused CMUT heated a HIFU phantom by 14 degrees C in 2.5 min. This temperature rise was successfully monitored by MR thermometry in a 3.0 T General Electric scanner.     

高强度聚焦超声热疗中组织损伤的一种监测方法

用特定频率和功率的高强度聚焦超声（HIFU）照射离体猪肉组织,研究了焦点区域的B超图像变化与HIFU导致的组织损伤之间的关系,并研究了M超信号变化和温度的相关性。结果表明：逐渐增加HIFU照射次数,焦点区域组织变性,B超图像发生明显改变。靶区内灰度超过设定的阈值的区域面积增大,区域内灰度升高,两者均与照射次数成近似线性关系;模拟加热实验中M超信号也随温度升高而变化,其变化较B超更显著。与以往的方法相比,实验系统可以实时地检测到组织损伤的程度和范围,提供了一种新的可视化的HIFU治疗实时监测方法。     

Effects of gas pockets on high-intensity focused ultrasound field

The paper describes experimental and numerical studies of the effects of gas pockets on a high-intensity focused ultrasound (HIFU) field. Air bubbles ranging from 0.8 to 2.4 mm in radius were produced in transparent polyacrylamide tissue-mimicking gels. A single-element 3.5-MHz HIFU transducer was used to sonicate the gel phantoms. The changes in the HIFU beam pattern for air bubbles at different positions were visualized by the Schlieren method. Quantitative measurements of pressure at the HIFU focus by a calibrated needle hydrophone showed considerable reduction in the focal pressure with the presence of an air pocket. The presence of a single 1.2-mm-radius air bubble, at a 5 mm axial pre-focal position, reduced the focal intensity by 50% and increased the lateral focal dimension by 50%. For air bubbles at pre-focal position close to the focus, lesion formation was observed not at the theoretical focus, but in front of the air bubble and the air bubble became a barrier for the post-focal ultrasound propagation. The effects of reflection were simulated numerically and were compared with the experiments. The results can be used as guidelines for evaluation of potential safety concerns produced by trapped gas-pockets in various HIFU therapies.     

准实时高强度聚焦超声背向散射积分监控成像

提出一种基于超声背向散射积分(IBS)参数估计的减影成像方法,用于检测高强度聚焦超声(HIFU)治疗过程中的组织损伤.在构建的HIFU/B超准实时治疗监控成像系统上,进行了离体猪肝组织实验.得到了不同组织深度下,IBS值随治疗时间的增加而变化的情况,以及不同治疗时间的IBS减影图像.比较了两种获得减影图像的方法,讨论了空化效应对IBS值的影响.此外还采用了一种双向彩色编码模式用以识别组织运动伪像.结果表明,IBS值能够较好地检测组织的损伤,还能一定程度地反映空化效应的情况,采用时间相邻的序列减影图像的叠加所获得的减影图像效果较好,双向彩色编码模式能够较有效地识别组织运动伪像.     

A new high intensity focused ultrasound applicator for surgical applications

Improved high-intensity focused ultrasound (HIFU) surgical applicators are required for use in a surgical environment. We report on the performance and characteristics of a new solid-cone HIFU applicator. Previous HIFU devices used a water-filled stand-off to couple the ultrasonic energy from the transducer to the treatment area. The new applicator uses a spherically-focused element and a solid aluminum cone to guide and couple the ultrasound to the tissue. Compared with the water-filled applicators, this new applicator is simpler to set up and manipulate, cannot leak, prevents the possibility of cavitation within the coupling device, and is much easier to sterilize and maintain during surgery. The design minimizes losses caused by shear wave conversion found in tapered solid acoustic velocity transformers operated at high frequencies. Computer simulations predicted good transfer of longitudinal waves. Impedance measurements, beam plots, Schlieren images, and force balance measurements verified strong focusing and suitable transfer of acoustic energy into water. At the focus, the -3 dB beam dimensions are 1.2 mm (axial)×0.3 mm (transverse). Radiation force balance measurements indicate a power transfer efficiency of 40%. In vitro and in vivo tissue experiments confirmed the applicator's ability to produce hemostasis     

1.5-D high intensity focused ultrasound array for non-invasive prostate cancer surgery

The aim of this study is to demonstrate the feasibility of a new spherically curved 1.5-D phased array for the treatment of localized prostatic cancer. The device is designed to conform to the Ablatherm(R) machine (EDAP-Technomed. France), a commercially available machine in which high intensity focused ultrasound (HIFU) treatment for prostate cancer is administered transrectally. It uses high intensity electronically focused ultrasound to steer a beam along two axes, allowing enough depth to be reached to treat large prostates and eliminating two degrees of mechanical movement. Through computer simulation, it was determined that a curved 1.5-D configuration offered the optimal design. Two configurations were then proposed, and their ability to steer a beam within a target volume centered on the geometric focus of the transducer was simulated. An eight-element prototype was constructed to test the piezo-composite material and its electro-acoustical efficiency. Then, an array was constructed, and a multichannel amplifier and control system were added, to permit remote operation. Acoustical and electrical measurements were made to verify performance. Finally, the 1.5-D array was tested in vitro on samples of pig liver to confirm the ability to induce lesions     

Integrated catheter for 3-D intracardiac echocardiography and ultrasound ablation

A catheter device with integrated ultrasound imaging array and ultrasound ablation transducer is introduced. This device has been designed for use in interventional cardiac procedures in which the cardiac anatomy is first imaged using real-time three-dimensional (3-D) ultrasound, then ablated to treat arrhythmias. The imaging array includes 112 elements operating at 5.4 MHz arranged in a 2-D matrix. Individual elements have a bandwidth of 21% and an insertion loss of 80 dB. The array has an azimuth resolution of 12 degrees and an elevation resolution of 8.7 degrees. The ablation transducer is a concentric piezoelectric transducer PZT-4 ring (outside diameter (O.D.), 4.5 mm, inside diameter (I.D.), 3.1 mm) operating at 10 MHz that surrounds the imaging array. It can produce a spatial-peak, temporal-average intensity up to 16 W/cm2. The entire device fits into a 9 Fr lumen with a 14 Fr tip to accommodate the ablation ring. With this device we have imaged, in realtime 3-D, a variety of targets including wire phantoms, fixed sheep hearts, and fresh bovine tissue. The ablation ring has been used to heat tissue-mimicking rubber 14 degrees C, as well as create lesions in fresh bovine tissue.     

Monitoring of thermal therapy based on shear modulus changes: I. shear wave thermometry

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is today hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to the 2-D mapping of temperature changes during HIFU treatments. This new concept of shear wave thermometry is experimentally implemented here using conventional ultrasonic imaging probes. HIFU treatment and monitoring were, respectively, performed using a confocal setup consisting of a 2.5-MHz single-element transducer focused at 30 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Thermocouple measurements and ultrasound-based thermometry were used as a gold standard technique and were combined with SWI on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created using 100-μs pushing beams at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Elasticity and temperature mapping was achieved every 3 s, leading to realtime monitoring of the treatment. Tissue stiffness was found to decrease in the focal zone for temperatures up to 43°C. Ultrasound-based temperature estimation was highly correlated to stiffness variation maps (r2 = 0.91 to 0.97). A reversible calibration phase of the changes of elasticity with temperature can be made locally using sighting shots. This calibration process allows for the derivation of temperature maps from shear wave imaging. Compared with conventional ultrasound-based approaches, shear wave thermometry is found to be much more robust to motion artifacts.     

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from Bmode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimetersized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.     

Interstitial instrumentation for therapeutic ultrasonic heating:modeling the discrete blood vessels

Instrumentation for interstitial ultrasound (US) heating is an important emerging technology in thermotherapy of deep seated tumors or those hard to reach by external devices. The instrumentation has special significance in case of radio-and/or chemotherapy resistant lesions. Its efficacy strongly depends on local tissue properties, especially local blood vessels. We evaluate effects of the vessels on temperature distribution elevated from basal by deposition of ultrasound energy. In the proposed model, we take into account several micron diameter vessels in proximity to the US four-applicator array. At large distances from the array, the volume is assigned a modified effective thermal conductivity. Our Finite Element Analysis of the so-defined problem shows that modelling under the assumption of constant, basal temperature across the vessels' lumen leads to erroneous results. The simulations agree best with experiments if fixed nodal temperature is applied at 60% of the lumen. We specify requirements on the array to avoid local underheating that could lead to performance failure of the instrumentation     

Noninvasive transesophageal cardiac thermal ablation using a 2-D focused, ultrasound phased array: a simulation study

This simulation study proposes a noninvasive, transesophageal cardiac-thermal ablation using a planar ultrasound phased array (1 MHz, 60 x 10 mm2, 0.525 mm interelement spacing, 114 x 20 elements). Thirty-nine foci in cardiac muscle were defined at 20, 40, and 60-mm distances and at various angles from the transducer surface to simulate the accessible posterior left atrial wall through the esophageal wall window. The ultrasound pressure distribution and the resulting thermal effect in a volume of 60 x 80 x 80 mm3, including esophagus and cardiac muscle, were simulated for each focus. For 1, 10, and 20-s sonications with 60 degrees C and 70 degrees C peak temperatures in cardiac muscle and without thermal damage in esophageal wall, the transducer acoustic powers were 105-727, 28-117, 21-79 W and 151-1044, 40-167, 30-114 W, respectively. The simulated lesions (thermal dose in equivalent minutes at 43 degrees C > or = 240 minutes) at these foci had lengths of 1-6, 3-11, 3-13 mm and 3-15, 5-19, 6-23 mm, respectively, and widths of 1-4, 2-7, 3-9 mm and 3-9, 4-13, 4-17 mm, respectively. As a first step toward feasibility, controllable tissue coagulation in cardiac tissue without damage to the esophagus was demonstrated numerically.     

高强度聚焦超声损伤兔肌肉组织的超声影像学变化的初步研究

探讨高强度聚焦超声损伤兔肌肉组织的超声图像变化。采用高强度聚焦超声经皮照射20只新西兰大白兔双侧后肢肌肉,其中18只于照射前1d、照射后10min、照射后1d,3d,7d,14d,21d,28d进行二维超声、彩色多普勒和能量多普勒超声检查,并于照射后28天处死后测量凝固灶大小。另2只分别于照射后1d及照射后50d解剖,行病理学检查。(1)HIFU照射后凝固灶外周可见强回声带至低回声带的演变过程。(2)HIFU照射后第1d,测量的凝固灶体积最大(1476.59±308.64mm3),第3d～第21d,凝固灶体积逐渐缩小(612.47±127.98mm3)。第28d凝固灶体积最小(343.29±54.79mm3)。超声检查在兔肌肉组织HIFU照射后的随访中发挥了重要的作用,为监测HIFU治疗人体软组织肿瘤超声图像的变化提供了实验依据。     

低场永磁MRI导引聚焦超声肿瘤消融系统的研究

研究了低场永磁磁共振(Magnetic Resonance Imaging,MRI)导引的高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)系统,使两者融合为一体。把磁共振的磁体设计为U字形,这样HIFU治疗头就可以放置于磁共振开口的上方;同时,在磁兼容、磁共振的快速成像、磁共振的测温、相控阵换能器、HIFU的治疗计划等方面做了一些研究。研究结果表明,在低场永磁的磁共振导引下,可以实现系统的所有设计功能,系统定位的图像比上一代B超导引的HIFU清晰,提高了实用性。     

Large improvement of the electrical impedance of imaging and high-intensity focused ultrasound (HIFU) phased arrays using multilayer piezoelectric ceramics coupled in lateral mode

With a change in phased-array configuration from one dimension to two, the electrical impedance of the array elements is substantially increased because of their decreased width (w)-to-thickness (t) ratio. The most common way to compensate for this impedance increase is to employ electrical matching circuits at a high cost of fabrication complexity and effort. In this paper, we introduce a multilayer lateral-mode coupling method for phased-array construction. The direct comparison showed that the electrical impedance of a single-layer transducer driven in thickness mode is 1/(n2(1/(w/t))2) times that of an n-layer lateral mode transducer. A large reduction of the electrical impedance showed the impact and benefit of the lateral-mode coupling method. A one-dimensional linear 32-element 770-kHz imaging array and a 42-element 1.45-MHz high-intensity focused ultrasound (HIFU) phased array were fabricated. The averaged electrical impedances of each element were measured to be 58 Ω at the maximum phase angle of -1.2° for the imaging array and 105 Ω at 0° for the HIFU array. The imaging array had a center frequency of 770 kHz with an averaged -6-dB bandwidth of approximately 52%. For the HIFU array, the averaged maximum surface acoustic intensity was measured to be 32.8 W/cm2 before failure.     

Noninvasive surgery of prostate tissue by high-intensity focusedultrasound

Modern ultrasound transducer material and matching layer technology has permitted us to combine the ultrasound visualization capability with production of high-intensity focused ultrasound (HIFU) on the same ceramic crystal. This development has lead to the design of a transrectal probe for noninvasive surgery of prostate tissue by HIFU. The combined capability using the same ceramic crystal simplifies treatment planning, targeting, and monitoring of tissue before and during the HIFU treatment. This mechanically scanning transrectal probe was introduced for clinical use in 1992 for noninvasive surgery of the prostate to treat benign prostatic hyperplasia (BPH) condition. This paper reviews major steps progressing from conception to the present clinical trial status of the HIFU device. During these clinical studies generation of microbubbles and cavitation were observed. Data from microbubble generation, temperature monitoring in tissue, and autopsy of HIFU-treated animal prostates are presented. Results of human clinical studies are briefly summarized to indicate performance of the device     

界面层对高强度聚焦超声所致焦斑的影响

用纳米铁磁性颗粒胶合体制作界面层,用同一剂量高强度聚焦超声(HIFU)在该界面层下方不同深度定点辐照.结果显示:焦点上缘与声学界面重合时,HIFU所致焦斑/损伤点(lesion)的体积增大,说明声学界面能够提高治疗效率；当焦点距离界面层10mm时,焦点处HIFU所致焦斑/损伤点的大小和形态与对照组相似,而界面处出现另一...