Magnetic Resonance Imaging for the Exploitation of Bubble-Enhanced Heating by High-Intensity Focused Ultrasound: A Feasibility Study in ex Vivo Liver

Bubble-enhanced heating (BEH) may be exploited to improve the heating efficiency of high-intensity focused ultrasound in liver and to protect tissues located beyond the focal point. The objectives of this study, performed in ex vivo pig liver, were (i) to develop a method to determine the acoustic power threshold for induction of BEH from displacement images measured by magnetic resonance acoustic radiation force imaging (MR-ARFI), and (ii) to compare temperature distribution with MR thermometry for HIFU protocols with and without BEH. The acoustic threshold for generation of BEH was determined in ex vivo pig liver from MR-ARFI calibration curves of local tissue displacement resulting from sonication at different powers. Temperature distributions (MR thermometry) resulting from “conventional” sonications (20 W, 30 s) were compared with those from “composite” sonications performed at identical parameters, but after a HIFU burst pulse (0.5 s, acoustic power over the threshold for induction of BEH). Displacement images (MR-ARFI) were acquired between sonications to measure potential modifications of local tissue displacement associated with modifications of tissue acoustic characteristics induced by the burst HIFU pulse. The acoustic threshold for induction of BEH corresponded to a displacement amplitude of approximately 50 μm in ex vivo liver. The displacement and temperature images of the composite group exhibited a nearly spherical pattern, shifted approximately 4 mm toward the transducer, in contrast to elliptical shapes centered on the natural focal position for the conventional group. The gains in maximum temperature and displacement values were 1.5 and 2, and the full widths at half-maximum of the displacement data were 1.7 and 2.2 times larger than in the conventional group in directions perpendicular to ultrasound propagation axes. Combination of MR-ARFI and MR thermometry for calibration and exploitation of BEH appears to increase the efficiency and safety of HIFU treatment.     

Tissue Ablation Accelerated by Peripheral Scanning Mode with High-Intensity Focused Ultrasound: A Study on Isolated Porcine Liver Perfusion

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p < 0.01). This study revealed that the complete peripheral necrosis barrier within the target tissues can defined using linear-scanned HIFU in an isolated porcine liver perfusion model. Additionally, the flow rate in the major hepatic vessels may play an important role in the use of the peripheral ablation mode, and this novel mode of ablation may enhance the therapeutic efficacy and tolerability of the treatment of large tumors using HIFU ablation.     

The effect of the scanning pathway in high-intensity focused ultrasound therapy on lesion production

Because tumors are much larger in size compared with the beam width of high-intensity focused ultrasound (HIFU), raster scanning throughout the entire target is conventionally performed for HIFU thermal ablation. Thermal diffusion affects the temperature elevation and the consequent lesion formation. As a result, the lesion will grow continuously over the course of HIFU therapy. The purpose of this study was to investigate the influence of scanning pathways on the overall thermal lesion. Two new scanning pathways, spiral scanning from the center to the outside and spiral scanning from the outside to the center, were proposed with the same HIFU parameters (power and exposure time) for each treatment spot. The lesions produced in the gel phantom and bovine liver were compared with those using raster scanning. Although more uniform lesions can be achieved using the new scanning pathways, the produced lesion areas (27.5 ± 12.3 mm² and 65.2 ± 9.6 mm², respectively) in the gel phantom are significantly smaller (p < 0.05) than those using raster scanning (92.9 ± 11.8 mm²). Furthermore, the lesion patterns in the gel phantom and bovine liver were similar to the simulations using temperature and thermal dose-threshold models, respectively. Thermal diffusion, the scanning pathway and the biophysical aspects of the target all play important roles in HIFU lesion production. By selecting the appropriate scanning pathway and varying the parameters as ablation progresses, HIFU therapy can achieve uniform lesions while minimizing the total delivered energy and treatment time.     

Real-Time Monitoring of High-Intensity Focused Ultrasound Treatment Using Axial Strain and Axial-Shear Strain Elastograms

Axial strain elastograms (ASEs) have been found to help visualize sonographically invisible thermal lesions. However, in most studies involving high-intensity focused ultrasound (HIFU)-induced thermal lesions, elastography imaging was performed separately later, after the lesion was formed. In this article, the feasibility of monitoring, in real time, tissue elasticity variation during HIFU treatment and immediately thereafter is explored using quasi-static elastography. Further, in addition to ASEs, we also explore the use of simultaneously acquired axial-shear strain elastograms (ASSEs) for HIFU lesion visualization. Experiments were performed on commercial porcine liver samples in vitro. The HIFU experiments were conducted at two applied acoustic power settings, 35 and 20 W. The experimental setup allowed us to interrupt the HIFU pulse momentarily several different times during treatment to perform elastographic compression and data acquisition. At the end of the experiments, the samples were cut along the imaging plane and photographed to compare size and location of the formed lesion with those visualized on ASEs and ASSEs. Single-lesion and multiple-lesion experiments were performed to assess the contribution of ASEs and ASSEs to lesion visualization and treatment monitoring tasks. At both power settings, ASEs and ASSEs provided accurate location information during HIFU treatment. At the low-power setting case, ASEs and ASSEs provide accurate lesion size in real-time monitoring. Lesion appearance in ASEs and ASSEs was affected by the cavitation bubbles produced at the high-power setting. The results further indicate that the cavitation bubbles influence lesion appearance more in ASEs than in ASSEs. Both ASEs and ASSEs provided accurate size information after a waiting period that allowed the cavitation bubbles to disappear. The results indicate that ASSEs not only improve lesion visualization and size measurement of a single lesion, but, under certain conditions, also help to identify untreated gaps between adjacent lesions with high contrast.     

探讨高强度聚焦超声消融后残余子宫肌瘤组织转归的机制

目的分析超声消融对靶区外不同位点子宫肌瘤组织雌、孕激素受体以及芳香化酶的表达情况,探讨残余子宫肌瘤的转归的可能机制。方法采用MR引导下高强度聚焦超声(HIFU)肿瘤治疗系统消融8个子宫肌瘤,声功率400W,辐照时间60s,以MR检测靶区外子宫肌瘤组织的升温情况。治疗前取1cm×1cm子宫肌瘤组织为对照组。辐照完毕后取靶区外0.5cm、1.0cm、1.5cm处子宫肌瘤组织。以免疫组化法检测超声消融靶区边缘雌、孕激素受体及芳香化酶(P450酶)的表达,以Western-blot半定量检测P450酶蛋白表达水平。结果靶区周围肌瘤组织温度也有不同程度升高,并且靶区外位点的温度逐渐降低。与对照组比较,靶区外肌瘤组织雌、孕激素受体表达均无明显改变。免疫组化及Western-blot半定量结果显示P450酶蛋白在靶区外0.5cm、1.0cm的表达明显低于对照组(P<0.05)。结论超声消融部分子宫肌瘤后,在一定范围内的残余子宫肌瘤的生长会被抑制,其机制与温度影响P450酶的蛋白表达有关。     

肝癌高强度聚焦超声消融的增效方法

本文从肝癌高强度聚焦超声（HIFu）治疗的优势与不足出发,探讨肝癌HIFU增效剂的临床价值。通过改变肝癌组织声环境,增加靶区能量沉积,即肝癌组织内引入高声阻抗物质,改变肝癌组织声学特性及血供状态,引入微泡造影剂等,阐述HIFU增效剂的原理及应用。     

Pelvic applications of MR-guided high intensity focused ultrasound

MR-guided high intensity focused ultrasound (MRg HIFU) is a novel method of tissue ablation that incorporates high energy focused ultrasound for tissue heating and necrosis within an MR scanner that provides simultaneous stereotactic tissue targeting and thermometry. To date, MRg HIFU has been used primarily to treat uterine fibroids, but many additional applications in the pelvis are in development. This article reviews the basic technology of MRg HIFU, and the use of MRg HIFU to treat uterine fibroids, adenomyosis, and prostate cancer.     

高强度聚焦超声体外治疗肝肿瘤的剂量学研究

目的 探讨高强度聚焦超声（ＨＦＵ）破坏肝肿瘤剂量与效应的关系。为ＨＩＦＵ体外治疗肝肿瘤的临床剂量学提供参考数据,方法 在换能器聚焦参数和工作为的前提下,观察并测定不同的输出功率、单次脉冲时间和治疗总时间致离体牛肝组织和活体猪肝脏靶区内组织凝固性坏死灶的大小。结果 肝组织内凝固性坏死灶的大小是可变的,且可能与ＨＩＦＵ治疗剂量和活体组织的生物学特性有关系。结论 肝脏靶区出现凝固性坏死是聚焦超声束作用于     

Preclinical in vivo Evaluation of an Extracorporeal HIFU Device for Ablation of Pancreatic Tumors

Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas. The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned. (E-mail: jooha@u.washington.edu)     

An ex Vivo Human Lung Model for Ultrasound-Guided High-Intensity Focused Ultrasound Therapy Using Lung Flooding

The usability of an ex vivo human lung model for ablation of lung cancer tissue with high-intensity focused ultrasound (HIFU) is described. Lung lobes were flooded with saline, with no gas remaining after complete atelectasis. The tumor was delineated sono-morphologically. Speed of sound, tissue density and ultrasound attenuation were measured for flooded lung and different pulmonary cancer tissues. The acoustic impedance of lung cancer tissue (1.6–1.9 mega-Rayleighs) was higher than that of water, as was its attenuation coefficient (0.31–0.44 dB/cm/MHz) compared with that of the flooded lung (0.12 dB/cm/MHz). After application of HIFU, the temperature in centrally located lung cancer surrounded by the flooded lung increased as high as 80°C, which is sufficient for treatment. On the basis of these preliminary results, ultrasound-guided HIFU ablation of lung cancer, by lung flooding with saline, appears feasible and should be explored in future clinical studies.     

Synergistic Ablation of Liver Tissue and Liver Cancer Cells with High-Intensity Focused Ultrasound and Ethanol

We investigated the combined effect of ethanol and high-intensity focused ultrasound (HIFU), first, on heating and cavitation bubble activity in tissue-mimicking phantoms and porcine liver tissues and, second, on the viability of HepG2 liver cancer cells. Phantoms or porcine tissues were injected with ethanol and then subjected to HIFU at acoustic power ranging from 1.2 to 20.5 W (HIFU levels 1–7). Cavitation events and the temperature around the focal zone were measured with a passive cavitation detector and embedded type K thermocouples, respectively. HepG2 cells were subjected to 4% ethanol solution in growth medium (v/v) just before the cells were exposed to HIFU at 2.7, 8.7 or 12.0 W for 30 s. Cell viability was measured 2, 24 and 72 h post-treatment. The results indicate that ethanol and HIFU have a synergistic effect on liver cancer ablation as manifested by greater temperature rise and lesion volume in liver tissues and reduced viability of liver cancer cells. This effect is likely caused by reduction of the cavitation threshold in the presence of ethanol and the increased rate of ethanol diffusion through the cell membrane caused by HIFU-induced streaming, sonoporation and heating.     

Real-time passive acoustic monitoring of HIFU-induced tissue damage

Thermal ablation by high-intensity focused ultrasound (HIFU) shows great promise as a noninvasive cancer therapy. This work proposes a novel method of real-time HIFU treatment monitoring that uses the passively monitored acoustic signal emanating from the focus during HIFU exposure. We performed 212 exposures in seven freshly excised ox livers using 1.067-MHz HIFU at a 95% duty cycle for a range of insonation durations and acoustic intensities. Acoustic emissions were recorded using a 15-MHz passive detector aligned confocally and coaxially with the HIFU transducer. Lesion presence and size were ascertained by slicing the tissue in the transverse and axial focal planes post exposure. Our results demonstrate that successful formation of HIFU lesions in ex vivo ox liver is highly correlated with the presence of pronounced dips in the magnitude of the received signal at integer harmonics of the insonation frequency. A detector based on this observation predicted lesioning with >80% accuracy in regimes that were very likely to create lesions (≥60 J of energy) and had an error rate of <6% for exposures that were too short to cause lesioning (≤1 s long). The overall sensitivity and specificity of the detector were 75.6% and 74.2%, respectively. The proposed detector could therefore provide a low-cost means of effectively monitoring clinical HIFU treatments passively and in real time.     

Defining the Optimal Age for Focal Lesioning in a Rat Model of Transcranial HIFU

This study aimed at determining the optimal age group for high-intensity focused ultrasound (HIFU) experiments for producing lesions in rats. Younger rats have thinner skulls, allowing for the acoustic waves to propagate easily through the skull without causing burns of the skin and brain surface. Younger rats however, have a smaller brain that can make HIFU focusing in the brain parenchyma challenging because of the focus size. In this study, we conducted transcranial HIFU sonications in rat pups of different ages (from 9 to 43 d) with a 1.5MHz MR compatible transducer. The electric power was selected to always reach a target temperature of at least 50°C in the parenchyma. The thickness of the skull and of the brain parenchyma was measured using T2-weighted MR imaging. Results showed that the thickness of the brain parenchyma increased quickly from P9 to P12, reaching 8.5 mm at P16, and then increasing gradually along with age. The skull thickness increased gradually from P9 to P26, and then more quickly after P30. The ratio between brain parenchyma thickness and skull thickness decreased gradually with age. For the pups at 30 d, the temperature in the brain tissue adjacent to the skull increased to 48.9°C, and those from the rodents older than 33 d reached 60°C or higher, which can produce undesired irreversible damage in this location. We conclude that young rats aged 16–26 d are optimal for experiments producing transcranial HIFU lesions in rats with an intact skull.     

Fast and Selective Ablation of Liver Tumors by High-Intensity Focused Ultrasound Using a Toroidal Transducer Guided by Ultrasound Imaging: The Results of Animal Experiments

This study demonstrated that high-intensity focused ultrasound (HIFU) produced with an intra-operative toroidal-shaped transducer causes fast, selective liver tumor ablations in an animal model. The HIFU device is composed of 256 emitters working at 3 MHz. A 7.5 MHz ultrasound imaging probe centered on the HIFU transducer guided treatment. VX2 tumor segments (25 mg) were implanted into the right lateral liver lobes of 45 New Zealand rabbits. The animals were evenly divided into groups 1 (toroidal HIFU ablation), 2 (surgical resection) and 3 (untreated control). Therapeutic responses were evaluated with gross pathology and histology 11 d post-treatment. Toroidal transducer-produced HIFU ablation (average ablation rate 10.5 cc/min) allowed fast and homogeneous tumor treatment. Sonograms showed all ablations. VX2 tumors were completely coagulated and surrounded by safety margins without surrounding-organ secondary HIFU lesions. HIFU group tumor volumes at autopsy (39 mm³) were significantly lower than control group volumes (2610 mm³, p < 0.0001). HIFU group tumor metastasis (27%) was lower than resected (33%) and control (67%) group metastasis. Ultrasound imaging, gross pathology and histology results supported these outcomes. HIFU procedures had no complications. Rabbit liver tumor ablation using a toroidal HIFU transducer under ultrasound imaging guidance might therefore be an effective intra-operative treatment for localized liver metastases.     

常规MRI在子宫肌瘤超声消融疗效评价及随访中的价值

目的 探讨常规MRI在评价超声消融治疗子宫肌瘤疗效及随访中的价值。方法 回顾性分析158例经超声消融治疗后6个月内接受MR检查的子宫肌瘤患者。所有患者均接受FS TSE T2W序列及增强前后T1W VIBE FS序列成像。分析超声消融后肌瘤的MR平扫图像信号改变,并与增强图像进行比较,观察信号变化规律,计算信号变化区域的体积及其相关性。结果 超声消融治疗后, VIBE FS T1WI上子宫肌瘤高信号区域与增强后所测坏死区域一致,二者间体积差异无统计学意义。单变量分析发现平扫VIBE FS T1WI上高信号区域的体积与增强图像上坏死区域的体积呈高度相关(r=0.99,P<0.001)。FS TSE T2WI可以确定子宫肌瘤的边界、大小。结论 常规MR平扫可准确评价超声消融治疗子宫肌瘤的疗效,T2WI可确定子宫肌瘤的边界、大小,T1WI可准确测量肌瘤坏死区域的体积。     

Pre-Clinical Study of In Vivo Magnetic Resonance-Guided Bubble-Enhanced Heating in Pig Liver

Bubble-enhanced heating (BEH) can be exploited to increase heating efficiency in treatment of liver tumors with non-invasive high-intensity focused ultrasound (HIFU). The objectives of this study were: (i) to demonstrate the feasibility of increasing the heating efficiency of sonication exploiting BEH in pig liver in vivo using a clinical platform; (ii) to determine the acoustic threshold for such effects with real-time, motion-compensated magnetic resonance-guided thermometry; and (iii) to compare the heating patterns and thermal lesion characteristics resulting from continuous sonication and sonication including a burst pulse. The threshold acoustic power for generation of BEH in pig liver in vivo was determined using sonication of 0.5-s duration (“burst pulse”) under real-time magnetic resonance thermometry. In a second step, experimental sonication composed of a burst pulse followed by continuous sonication (14.5 s) was compared with conventional sonication (15 s) of identical energy (1.8 kJ). Modification of the heating pattern at the targeted region located at a liver depth between 20 and 25 mm required 600–800 acoustic watts. The experimental group exhibited near-spherical heating with 40% mean enhancement of the maximal temperature rise as compared with the conventional sonication group, a mean shift of 7 ± 3.3 mm toward the transducer and reduction of the post-focal temperature increase. Magnetic resonance thermometry can be exploited to control acoustic BEH in vivo in the liver. By use of experimental sonication, more efficient heating can be achieved while protecting tissues located beyond the focal point.     

An adaptive spectral estimation technique to detect cavitation in HIFU with high spatial resolution

In ultrasound-guided high-intensity focused ultrasound (HIFU) therapy, the changes observed on tissue are subtle during treatment; some ultrasound-guided HIFU protocols rely on the observation of significant brightness changes as the indicator of tissue lesions. The occurrence of a distinct hyperechogenic region (“bright-up”) around the focus is often associated with acoustic cavitation resulting in microbubble formation, but it may indicate different physical events such as larger bubbles from boiling (known to alter acoustic impedance) or sometimes lesion formation. A reliable method to distinguish and spatially localize these causes within the tissue would assist the control of HIFU delivery, which is the subject of this paper. Spectral analysis of the radio frequency (RF) signal underlying the B-mode image provides more information on the physical cause, but the usual techniques that are methods on the Fourier transform require a long series for good spectral resolution and so they give poor spatial resolution. This paper introduces an active spectral cavitation detection method to attain high spatial resolution (0.15 × 0.15 mm per pixel) through a parametric statistical method (ARMA modeling) used on finite-length data sets, which enables local changes to be identified more easily. This technique uses the characteristics of the signal itself to optimize the model parameters and structure. Its performance is assessed using synthesized cavitation RF data, and it is then demonstrated in ex vivo bovine liver during and after HIFU exposure. The results suggest that good spatial and spectral resolution can be obtained by the design of suitable algorithms. In ultrasound-guided HIFU, the technique provides a useful supplement to B-mode analysis, with no additional time penalty in data acquisition.     

Experimental Methods for Improved Spatial Control of Thermal Lesions in Magnetic Resonance-Guided Focused Ultrasound Ablation

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU, or MRgFUS) is a hybrid technology that was developed to provide efficient and tolerable thermal ablation of targeted tumors or other pathologic tissues, while preserving the normal surrounding structures. Fast 3-D ablation strategies are feasible with the newly available phased-array HIFU transducers. However, unlike fixed heating sources for interstitial ablation (radiofrequency electrode, microwave applicator, infra-red laser applicator), HIFU uses propagating waves. Therefore, the main challenge is to avoid thermo-acoustical adverse effects, such as energy deposition at reflecting interfaces and thermal drift of the focal lesion toward the near field. We report here our investigations on some novel experimental solutions to solve, or at least to alleviate, these generally known tolerability problems in HIFU-based therapy. Online multiplanar MR thermometry was the main investigational tool extensively used in this study to identify the problems and to assess the efficacy of the tested solutions. We present an improved method to cancel the beam reflection at the exit window (i.e., tissue-to-air interface) by creating a multilayer protection, to dissipate the residual HIFU beam by bulk scattering. This study evaluates selective de-activation of transducer elements to reduce the collateral heating at bone surfaces in the far field, mainly during automatically controlled volumetric ablation. We also explore, using hybrid US/MR simultaneous imaging, the feasibility of using disruptive boiling at the focus, both as a far-field self-shielding technique and as an enhanced ablation strategy (i.e., boiling core controlled HIFU ablation).     

Evaluation of Ultrasonic Attenuation in Primary and Secondary Human Liver Tumors and Its Potential Effect on High-Intensity Focused Ultrasound Treatment

Primary and secondary liver tumors are completely different diseases but are usually treated similarly using high-intensity focused ultrasound (HIFU). However, the acoustic parameters of these tissues are not well documented. In this study, attenuation coefficients were evaluated in fresh primary (N = 8) and secondary (N = 13) human liver tumor samples recovered by hepatectomy. The average attenuation coefficients of the primary and secondary liver tumors were 0.10 ± 0.03 and 0.20 ± 0.04 Np/cm/MHz, respectively. The average attenuation coefficients of the liver tissue surrounding the primary and secondary tumors were 0.16 ± 0.07 and 0.07 ± 0.02 Np/cm/MHz, respectively. Numerical simulations performed using these values revealed that completely different HIFU ablation patterns were created in primary and secondary liver tumors using the same exposure parameters. The dimensions of a typical HIFU lesion were two times larger in secondary liver tumors than in primary tumors. HIFU treatment parameters should be set properly according to the acoustic properties of the diseased liver tissue.     

Real-Time Monitoring of High-Intensity Focused Ultrasound Thermal Therapy Using the Manifold Learning Method

High-intensity focused ultrasound (HIFU) induces thermal lesions by increasing the tissue temperature in a tight focal region. The main ultrasound imaging techniques currently used to monitor HIFU treatment are standard pulse-echo B-mode ultrasound imaging, ultrasound temperature estimation and elastography-based methods. The present study was carried out on ex vivo animal tissue samples, in which backscattered radiofrequency (RF) signals were acquired in real time at time instances before, during and after HIFU treatment. The manifold learning algorithm, a non-linear dimensionality reduction method, was applied to RF signals which construct B-mode images to detect the HIFU-induced changes among the image frames obtained during HIFU treatment. In this approach, the embedded non-linear information in the region of interest of sequential images is represented in a 2-D manifold with the Isomap algorithm, and each image is depicted as a point on the reconstructed manifold. Four distinct regions are chosen in the manifold corresponding to the four phases of HIFU treatment (before HIFU treatment, during HIFU treatment, immediately after HIFU treatment and 10-min after HIFU treatment). It was found that disorganization of the points is achieved by increasing the acoustic power, and if the thermal lesion has been formed, the regions of points related to pre- and post-HIFU significantly differ. Moreover, the manifold embedding was repeated on 2-D moving windows in RF data envelopes related to pre- and post-HIFU exposure data frames. It was concluded that if mean values of the points related to pre- and post-exposure frames in the reconstructed manifold are estimated, and if the Euclidean distance between these two mean values is calculated and the sliding window is moved and this procedure is repeated for the whole image, a new image based on the Euclidean distance can be formed in which the HIFU thermal lesion is detectable.