Calibration of Ultrasound Backscatter Temperature Imaging for High-Intensity Focused Ultrasound Treatment Planning

High-intensity focused ultrasound (HIFU) is rapidly gaining acceptance as a non-invasive method for soft tissue tumor ablation, but improvements in the methods of treatment delivery, planning and monitoring are still required. Backscatter temperature imaging (BTI) uses ultrasound to visualize heating-induced echo strain and may be used to indicate the position of the HIFU focal region using low-power “sub-lesioning” exposure. The technique may also provide a quantitative tool for assessing the efficacy of treatment delivery if apparent strain measurements can be related to the underlying temperature rise. To obtain temperature estimates from strain measurements, the relationship between these variables has to be either measured or otherwise assumed from previous calibrations in similar tissues. This article describes experimental measurements aimed at deriving the relationship between temperature rise and apparent strain in the laboratory environment using both ex vivo bovine liver tissue samples and normothermically perfused porcine livers. A BTI algorithm was applied to radiofrequency ultrasound echo data acquired from a clinical ultrasound scanner (Z.One, Zonare Medical Systems, Mountain View, CA, USA) where the imaging probe was aligned with the focal region of a HIFU transducer. Temperature measurements were obtained using needle thermocouples implanted in the liver tissue. A series of “non-ablative” HIFU exposures giving peak temperatures below 10°C were made in three separate ex vivo bovine livers, yielding an average strain/temperature coefficient of 0.126 ± 0.088 percentage strain per degree Celsius. In the perfused porcine livers at a starting temperature of 38°C (normal body temperature) the strain/temperature coefficients were found to be 0.040 ± 0.029 percentage strain per degree Celsius. The uncertainty in these results is directly linked to the precision of the strain measurement, as well as the naturally occurring variance between different tissue samples, indicating that BTI may lack the accuracy required to be implemented successfully in practice as a quantitative treatment planning technique at a sub-lesioning exposure level. This is because, to be of use in treatment planning, temperature-rise estimates may require an accuracy greater (<10%) than that offered by BTI measurement. BTI may, however, still play a role in ensuring the correct positioning of the focal region and as a treatment monitoring modality capable of detecting an increased rate of heating in tissue after HIFU ablation.     

Simultaneous Evaluation of Thermal and Non-Thermal Effects of High-Intensity Focused Ultrasound on a Tissue-Mimicking Phantom

Physiologically relevant phantoms with high reliability are essential for extending the therapeutic applications of high-intensity therapeutic ultrasound. Here we describe a tissue-mimicking phantom capable of quantifying temperature changes and observing non-thermal phenomena by high-intensity therapeutic ultrasound. Using polydiacetylene liposomes, we fabricated agar-based polydiacetylene hydrogel phantoms (PHPs) that not only respond to temperature, but also have acoustic properties similar to those of human liver tissue. The color of PHPs changed from blue to red depending on the temperature in the range 40°C–70°C, where the red/blue ratio of PHP had a good linearity of 99.06% for the temperature changes. Furthermore, repeated high-intensity focused ultrasound led to histotripsy on the PHP with liquefied and damaged areas measuring 0.7 and 4.0 cm², respectively, at the signal generator amplitude setting voltage of 80 mV. Our results indicate not only the usability of the thermochromic phantom, but also its potential for evaluating non-thermal phenomena in various high-intensity focused ultrasound therapies.     

Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis of Pancreatic Cancer Xenograft with Gemcitabine

We sought to investigate whether concurrent exposure to pulsed high-intensity focused ultrasound (HIFU) and the chemotherapeutic drug gemcitabine would enhance apoptosis in pancreatic cancer. A pancreatic cancer xenograft model was established using BALB/c nude mice and human pancreatic cancer cells (PANC-1). In the first study, mice were randomly allocated into one of four groups: control (n = 4), HIFU alone (n = 4), gemcitabine (GEM) alone (n = 28) and concurrent treatment with HIFU and gemcitabine (HIGEM) (n = 28). The GEM and HIGEM groups were subdivided into four subgroups (16 mice) according to the drug dose injected (50–200 mg/kg) and another four subgroups (16 mice) according to the time interval between drug injection and HIFU treatment (each subgroup, n = 4). Apoptosis rates were evaluated using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and percentage of necrosis, as evaluated with Harris' hematoxylin solution and eosin Y stain, 3 d after treatment. The second study was performed to evaluate tumor growth rates of the four groups. Each group was treated weekly for 3 wk, and tumor size was periodically measured for up to 4 wk from the beginning of treatment. In the first study, overall rates of apoptosis were significantly higher in the HIGEM group than in the GEM group (p = 0.02). In a subgroup analysis, HIGEM was superior to GEM in enhancing apoptosis at gemcitabine dosages of 150–200 mg/kg gemcitabine and intervals between gemcitabine and HIFU less than 2 h (p = 0.01). In the second study, HIGEM treatment resulted in the slowest tumor growth. However, despite a visible distinction, none of the differences found between the HIGEM and GEM groups were statistically significant (p > 0.05). Treatment with both HIFU and gemcitabine might enhance cell apoptosis and reduce tumor growth in pancreatic carcinoma. For this concurrent treatment, a high dosage of gemcitabine and a short-term delay before HIFU are recommended to maximize the therapeutic effect.     

Tomographic Reconstruction of Tissue Properties and Temperature Increase for High-Intensity Focused Ultrasound Applications

The acoustic and thermal properties as well as the temperature change within a tissue volume during high-intensity focused ultrasound ablation are critically important for treatment planning and monitoring. Described in this article is a tomographic reconstruction method used to determine the tissue properties and increase in temperature in a 3-D volume. On the basis of the iterative finite-element solution to the bioheat equation coupled with Tikhonov regularization techniques, our reconstruction algorithm solves the inverse problem of bioheat transfer and uses the time-dependent temperature measured on a tissue surface to obtain the acoustic absorption coefficient, thermal diffusivity and temperature increase within the subsurface volume. Numerical simulations were performed to validate the reconstruction algorithm. The method was initially conducted in ex vivo experiments in which time-dependent temperature on a tissue surface was measured using high-resolution, non-invasive infrared thermography.     

Experimental Studies and Clinical Experiences on Treatment of Secondary Hypersplenism with Extracorporeal High-Intensity Focused Ultrasound

The aim of this study is to investigate the efficacy and safety of extracorporeal high-intensity focused ultrasound (HIFU) in treatment of hypersplenism. Fifteen adult dogs, weighing 13–18 kg were divided into three groups: sham group, SVL group undergoing splenic vein ligation (SVL) after laparotomy, and SVL + HIFU group receiving SVL followed by extracorporeal HIFU. Pathologic and hematologic analyses were performed. We also reviewed the clinical data of 19 patients with secondary hypersplenism caused by liver cirrhosis or hepatocellular carcinoma who underwent extracorporeal HIFU. Extracorporeal HIFU significantly diminished the volume of the spleen of animals, coupled with occurrence of coagulation necrosis and fibrosis in the target area. Both platelet and red blood cell counts were significantly restored by HIFU intervention. Similarly, HIFU treatment improved the hematologic parameters in patients with hypersplenism, and no major complications were encountered. Extracorporeal HIFU intervention is effective and safe in managing secondary hypersplenism.     

High-Intensity Focused Ultrasound Leads to Histopathologic Changes of the Inferior Turbinate Mucosa with Allergic Inflammation

This study was aimed at understanding the histopathologic changes that occur in the nasal mucosa of patients with perennial allergic rhinitis after high-intensity focused ultrasound (HIFU) treatment. Biopsy specimens of the inferior turbinate mucosa were taken from 11 PAR patients before, immediately after and 1 y after HIFU treatment. Morphometric analysis revealed that the density of eosinophils and other inflammatory cells increased immediately after treatment and then were decreased significantly 1 y post-treatment. Submucosal glands were swollen and venous sinusoids were dilated, but there was no statistically significant change in their density, immediately after treatment. However, both glands and venous sinusoids significantly decreased in number 1 y after HIFU treatment. The ciliated epithelium or basement membrane of the nasal mucosa was well preserved at all stages. In conclusion, HIFU is a tolerable and effective treatment to reduce inflammation of the inferior turbinate mucosa in patients with perennial allergic rhinitis.     

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.     

Pulsed High-Intensity Focused Ultrasound Therapy Enhances Targeted Delivery of Cetuximab to Colon Cancer Xenograft Model in Mice

Our aim was to evaluate whether pulsed high-intensity focused ultrasound (HIFU) therapy enhances the effect of an epidermal growth factor receptor–targeted chemotherapeutic drug, cetuximab, in treating human colon cancer xenografts in a mouse model. Balb/c nude mice with subcutaneous xenografts of HT-29 cells were randomly categorized into control (n = 9), pulsed HIFU alone (n = 10), cetuximab monotherapy (n = 8) or combined pulsed HIFU and cetuximab therapy (n = 9) group. Cetuximab, pulsed HIFU therapy, or both were administered three times per week starting from day 8 after tumor cell injection. Based on tumor growth curves up to 34 days, the combination therapy group showed more suppressed tumor growth than all other groups (p < 0.05). The final relative tumor volumes were 5.4 ± 2.1, 5.2 ± 1.3, 4.8 ± 1.8, and 3.1 ± 0.9 for control, pulsed HIFU alone, cetuximab monotherapy, and combination therapy groups, respectively. In conclusion, pulsed HIFU therapy appears to enhance the anti-tumor effect of epidermal growth factor receptor–targeted cetuximab on human colon cancer xenograft models in mice.     

Inactivation of Planktonic Escherichia coli by Focused 2-MHz Ultrasound

This study was motivated by the desire to develop a non-invasive means to treat abscesses, and represents the first steps toward that goal. Non-thermal, high-intensity focused ultrasound (HIFU) was used to inactivate Escherichia coli (～1 × 10⁹ cells/mL) in suspension. Cells were treated in 96-well culture plate wells using 1.95-MHz ultrasound and incident focal acoustic pressures as high as 16 MPa peak positive and 9.9 MPa peak negative (free field measurements). The surviving fraction was assessed by coliform culture and the alamarBlue assay. No biologically significant heating was associated with ultrasound exposure. Bacterial inactivation kinetics were well described by a half-life model, with a half-time of 1.2 min. At the highest exposure levels, a 2log inactivation was typically achieved within 10 min. The free field-equivalent peak negative acoustic pressure threshold for inactivation was ～7 MPa. At the highest acoustic pressures used, inactivation efficacy was insensitive to reciprocal changes in pulse length and pulse repetition frequency at constant duty factor. Although treated volumes were very small, proof of principle was provided by these experiments.     

Non-invasive Magnetic Resonance Imaging Follow-up of Sono-sensitive Liposome Tumor Delivery and Controlled Release After High-Intensity Focused Ultrasound

This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T₂ and T₂*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T₂* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T₁) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T₁.     

Temporal and Spatial Detection of HIFU-Induced Inertial and Hot-Vapor Cavitation with a Diagnostic Ultrasound System

The onset and presence of inertial cavitation and near-boiling temperatures in high-intensity focused ultrasound (HIFU) therapy have been identified as important indicators of energy deposition for therapy guidance. Passive cavitation detection is commonly used to detect bubble emissions, where a fixed-focus single-element acoustic transducer is typically used as a passive cavitation detector (PCD). This technique is suboptimal for clinical applications, because most PCD transducers are tightly focused and afford limited spatial coverage of the HIFU focal region. A Terason 2000 Ultrasound System was used as a PCD array to expand the spatial detection region for cavitation by operating in passive mode, obtaining the radiofrequency signals corresponding to each scan line and filtering the contribution from scattering of the HIFU signal harmonics. This approach allows for spatially resolved detection of both inertial and stable cavitation throughout the focal region. Measurements with the PCD array during sonication with a 1.1-MHz HIFU source in tissue phantoms were compared with single-element PCD and thermocouple sensing. Stable cavitation signals at the harmonics and superharmonics increased in a threshold fashion for temperatures >90°C, an effect attributed to high vapor pressure in the cavities. Incorporation of these detection techniques in a diagnostic ultrasound platform could result in a powerful tool for improving HIFU guidance and treatment. (E-mail: cfarny@bwh.harvard.edu)     

Ex Vivo Characterization of Canine Liver Tissue Viscoelasticity after High-Intensity Focused Ultrasound Ablation

The potential of elasticity imaging to detect high-intensity focused ultrasound (HIFU) lesions on the basis of their distinct biomechanical properties is promising. However, information on the quantitative mechanical properties of the tissue and the optimal intensity at which to determine the best contrast parameters is scarce. In this study, fresh canine livers were ablated using combinations of I_SPTA intensities of 5.55, 7.16 and 9.07 kW/cm² and durations of 10 and 30 s ex vivo, resulting in six groups of ablated tissues. Biopsy samples were then interrogated using dynamic shear mechanical testing within the range of 0.1–10 Hz to characterize the tissue's post-ablation viscoelastic properties. All mechanical parameters were found to be frequency dependent. Compared with unablated cases, all six groups of ablated tissues had statistically significant higher complex shear modulus and shear viscosity. However, among the ablated groups, both complex shear modulus and shear viscosity were found to monotonically increase in groups 1–4 (5.55 kW/cm² for 10 s, 7.16 kW/cm² for 10 s, 9.07 kW/cm² for 10 s, and 5.55 kW/cm² for 30 s, respectively), but to decrease in groups 5 and 6 (7.16 kW/cm² for 30 s, and 9.07 kW/cm² for 30 s, respectively). For groups 5 and 6, the temperature was expected to exceed the boiling point, and therefore, the decreased stiffening could be due to the compromised integrity of the tissue microstructure. Future studies will entail estimation tissue mechanical properties in vivo and perform real-time monitoring of tissue alterations during ablation.     

High-Intensity Focused Ultrasound Attenuates Neural Responses of Sciatic Nerves Isolated from Normal or Neuropathic Rats

Patients with diabetic neuropathy often have neuropathic pain. The purpose of our work was to investigate the effects of high-intensity focused ultrasound (HIFU) on the conduction block of normal and neuropathic nerves for soothing pain. Adult male Sprague–Dawley rats were used, and diabetes was induced by streptozotocin injection. Diabetic neuropathy was evaluated with animal behavior tests. Sciatic nerves of both control and neuropathic rats were dissected from the starting point of the sciatic nerve to the point where the sural nerve ends near the ankle. The nerves were stored in Ringer's solution. The in vitro nerve was placed on a self-developed experimental platform for HIFU exposure. Stimulation and recording of the compound action potentials (CAPs) and sensory action potentials (SAPs) were performed. Control and neuropathic nerves exposed or not exposed to HIFU were submitted to histologic analysis. For the control and neuropathic nerves, suppression of CAPs and SAPs started 2 min post-HIFU treatment. Maximum suppression of SAPs was 34.4 ± 3.2% for the control rats and 11.6 ± 2.0% and 9.8 ± 3.0% for rats 4 wk post-injection and 8 wk post-injection, respectively. Time to full recovery was 25, 70 and 80 min, respectively. Histologic analysis revealed that the nerves in which CAPs and SAPs did not fully recover were damaged thermally or mechanically by HIFU. It is feasible to reversibly block nerves with appropriate HIFU treatment. Diabetic nerves were less suppressed by HIFU and were more vulnerable to permanent damage.     

A Preclinical In Vivo Investigation of High-Intensity Focused Ultrasound Combined with Radiotherapy

This study aims to perform an in vivo investigation evaluating the injury to the pancreas and adjacent tissue of swine resulting with high-intensity focused ultrasound (HIFU) combined with radiotherapy (RT). The protocol was approved by the animal ethics committee at the Peking University First Hospital. A total of 12 domestic swine were divided into four groups: control, HIFU only, RT only and HIFU + RT. The injury to the pancreas, adjacent tissue and tissue within the acoustic path of the HIFU beam was assessed based on gross and histologic findings. For the targeted region of the pancreas, the score of the combined group was higher than that of the HIFU group and there was significant difference. For the acoustic path tissue, there was no significant difference except between the control group and the other groups. HIFU combined with RT increased the injury to the targeted pancreas, without increased injury to tissue outside of the targeted region. (E-mail: xsgao777@hotmail.com)     

Application of High-Intensity Focused Ultrasound to the Study of Mild Traumatic Brain Injury

Though intrinsically of much higher frequency than open-field blast overpressures, high-intensity focused ultrasound (HIFU) pulse trains can be frequency modulated to produce a radiation pressure having a similar form. In this study, 1.5-MHz HIFU pulse trains of 1-ms duration were applied to intact skulls of mice in vivo and resulted in blood-brain barrier disruption and immune responses (astrocyte reactivity and microglial activation). Analyses of variance indicated that 24 h after HIFU exposure, staining density for glial fibrillary acidic protein was elevated in the parietal and temporal regions of the cerebral cortex, corpus callosum and hippocampus, and staining density for the microglial marker, ionized calcium binding adaptor molecule, was elevated 2 and 24 h after exposure in the corpus callosum and hippocampus (all statistical test results, p < 0.05). HIFU shows promise for the study of some bio-effect aspects of blast-related, non-impact mild traumatic brain injuries in animals.     

Cesarean Scar Pregnancy: Comparing the Efficacy and Tolerability of Treatment with High-Intensity Focused Ultrasound and Uterine Artery Embolization

The aim of this study was to investigate the clinical efficacy of high-intensity focused ultrasound (HIFU) for the treatment of a cesarean scar pregnancy compared with uterine artery embolization (UAE) and intra-arterial methotrexate infusion combined with uterine curettage. In this retrospective cohort study, 31 patients were treated with HIFU (HIFU group), and 45 patients were treated with UAE (UAE group). We compared the treatment and recovery of the patients, including follow-up. After UAE treatment, serum levels of the β subunit of human chorionic gonadotropin declined significantly on the first day, and the residual lesions disappeared in 3–17 wk. One patient underwent hysterectomy; intrauterine adhesions were found by hysteroscopic examination after 6 mo in 2 patients, whose menstrual function did not return to normal. The remainder of the 42 patients recovered normal menstrual functioning during the 3- to 18-wk follow-up. In the patients who underwent HIFU treatment, serum β-HCG levels did not decline rapidly; serum β-HCG levels increased in many patients and then declined to normal steadily within 2–12 wk. Lesions detached in 3–14 wk in all patients, and menstrual functioning was recovered in 3–9 wk without uterine curettage. Compared with the UAE group, the HIFU group had less pain and fewer complications; the patients in the HIFU group were not hospitalized or anesthetized and had lower costs. HIFU is an efficient, tolerable and non-invasive treatment.     

Influence of Skin and Subcutaneous Tissue on High-Intensity Focused Ultrasound Beam: Experimental Quantification and Numerical Modeling

High-intensity focused ultrasound (HIFU) enables the non-invasive thermal ablation of tumors. However, numerical simulations of the treatment remain complex and difficult to validate in clinically relevant situations. In this context, needle hydrophone measurements of the acoustic field downstream of seven rabbit tissue layers comprising skin, subcutaneous fat and muscle were performed in different geometrical configurations. Increasing curvature and thickness of the sample were found to decrease the focusing of the beam: typically, a curvature of 0.05 mm⁻¹ decreased the maximum pressure by 45% and doubled the focal area. A numerical model based on k-Wave Toolbox was found to be in very good agreement with the reported measurements. It was used to extrapolate the effect of the superficial tissues on peak positive and peak negative pressure at focus, which affects both cavitation and target heating. The shape of the interface was found to have a strong influence on the values, and it is therefore an important parameter to monitor or to control in the clinical practice. This also highlights the importance of modeling realistic configurations when designing treatment procedures.     

A Comparison of Acoustic Cavitation Detection Thresholds Measured with Piezo-electric and Fiber-optic Hydrophone Sensors

A Fabry-Perot interferometer fiber-optic hydrophone (FOH) was investigated for use as an acoustic cavitation detector and compared with a piezo-ceramic passive cavitation detector (PCD). Both detectors were used to measure negative pressure thresholds for broadband emissions in 3% agar and ex vivo bovine liver simultaneously. FOH-detected half- and fourth-harmonic emissions were also studied. Three thresholds were defined and investigated: (i) onset of cavitation; (ii) 100% probability of cavitation; and (iii) a time-integrated threshold where broadband signals integrated over a 3-s exposure duration, averaged over 5–10 repeat exposures, become statistically significantly greater than noise. The statistical sensitiviy of FOH broadband detection was low compared with that of the PCD (0.43/0.31 in agar/liver). FOH-detected fourth-harmonic data agreed best with PCD broadband (sensitivity: 0.95/0.94, specificity: 0.89/0.76 in agar/liver). The FOH has potential as a cavitation detector, particularly in applications where space is limited or during magnetic resonance-guided studies.     

Gel Phantom Study with High-Intensity Focused Ultrasound: Influence of Metallic Stent Containing Either Air or Fluid

We aimed to investigate whether a cylindrical structure containing either air or fluid and with or without a metallic stent affects the volume and density of cavitation produced by high-intensity focused ultrasound via a gel phantom study. Sixteen tissue-mimicking phantoms based on a polyacrylamide gel mixed with bovine serum albumin with a cylindrical hole 1 cm in diameter and 7.5 cm in length were divided into four groups of four phantoms with air in the holes (group 1), four phantoms with fluid in the holes (group 2), four phantoms with air-containing metallic stents (group 3) and four phantoms with fluid-containing metallic stents (group 4). A pulsed high-intensity focused ultrasound beam (50% duty cycle, 40-Hz pulse repetition frequency) at 75 W of acoustic power was directed perpendicularly to the longitudinal axis of the hole, with its focus at the posterior wall of the hole. The size of the cavitation on the x-, y-, and z-axes was measured, and the volumes of cavitation and coagulation were calculated using the formula for the volume of an elliptical cone. The density of cavitation was measured in the tissue phantom anterior to the hole with a 1 × 1-cm square region of interest. For statistical analysis, the Kruskal–Wallis test and Mann–Whitney U-test were used. The phantoms with air-containing holes (groups 1 and 3) developed larger and denser cavitations anterior to the focus, without unnecessary coagulation posterior to the focus, compared with the phantoms with fluid-containing holes (groups 2 and 4), regardless of the presence of stents. All of the axes and volumes of the anterior cavitations were significantly larger than those of the posterior cavitations in groups 1 and 3 (all p-values <0.05). The results of this study might be applied to maximize cavitation to enhance drug delivery into tumors.     

Real-Time Spatiotemporal Control of High-Intensity Focused Ultrasound Thermal Ablation Using Echo Decorrelation Imaging in ex Vivo Bovine Liver

The ability to control high-intensity focused ultrasound (HIFU) thermal ablation using echo decorrelation imaging feedback was evaluated in ex vivo bovine liver. Sonications were automatically ceased when the minimum cumulative echo decorrelation within the region of interest exceeded an ablation control threshold, determined from preliminary experiments as ?2.7 (log-scaled decorrelation per millisecond), corresponding to 90% specificity for local ablation prediction. Controlled HIFU thermal ablation experiments were compared with uncontrolled experiments employing two, five or nine sonication cycles. Means and standard errors of the lesion width, area and depth, as well as receiver operating characteristic curves testing ablation prediction performance, were computed for each group. Controlled trials exhibited significantly smaller average lesion area, width and treatment time than five-cycle or nine-cycle uncontrolled trials and also had significantly greater prediction capability than two-cycle uncontrolled trials. These results suggest echo decorrelation imaging is an effective approach to real-time HIFU ablation control.