High-intensity Focused Ultrasound Lesions Research Articles

Integrated HIFU Drive System on a Chip for CMUT-Based Catheter Ablation System.

Conventional High Intensity Focused Ultrasound (HIFU) is a therapeutic modality which is extracorporeally administered. In applications where a relatively small HIFU lesion is required, an intravascular HIFU probe can be deployed to the ablation site. In this paper, we demonstrate the design and implementation a fully integrated HIFU drive system on a chip to be placed on a 6 Fr catheter probe. An 8-element capacitive micromachined ultrasound transducer (CMUT) ring array of 2 mm diameter has been used as the ultrasound source. The driver chip is fabricated in 0.35 μm AMS high-voltage CMOS technology and comprises eight continuous-wave (CW) high-voltage CMUT drivers (10.9 ns and 9.4ns rise and fall times at 20 V pp output into a 15 pF), an eight-channel digital beamformer (8-12 MHz output frequency with 11.25 ° phase accuracy) and a phase locked loop with an integrated VCO as a tunable clock source (128-192 MHz). The chip occupies 1.85 × 1.8 mm 2 area including input and output (I/O) pads. When the transducer array is immersed in sunflower oil and driven by the IC with eight 20 Vpp CW pulses at 10 MHz, real-time thermal images of the HIFU beam indicate that the focal temperature rises by 16.8 °C in 11 seconds. Each HV driver consumes around 67mW of power when driving the CMUT array at 10 MHz, which adds up to 560mW for the whole chip. FEM based analysis reveals that the outer surface temperature of the catheter is expected to remain below the 42 °C tissue damage limit during therapy.

Optical property changes in ex vivo tissues exposed to high‐intensity focused ultrasound

Real-time acousto-optic (AO) sensing has been shown to non-invasively detect changes in ex vivo tissue optical properties during high-intensity focused ultrasound (HIFU) exposures. Baseline changes in optical properties have been previously measured as a function of thermal-dose for tissues exposed to a temperature-controlled water bath (doi:10.1088/0031-9155/59/13/3249). In this work, the wavelength-dependent optical scattering and absorption of ex vivo tissues exposed to HIFU were measured using an integrating sphere spectrophotometric technique employed previously. HIFU-induced spatiotemporal temperature elevations were measured using an infrared camera and used to calculate the thermal dose delivered to a localized region of tissue. We consider the impact of thermal dose, temperature elevation, and heating rate on the formation of HIFU lesions and the resulting changes in tissue optical properties. Recently, reported results (doi:10.1088/0031-9155/59/13/3249) refute the hypothesis that optical propert...

The role of high-intensity focused ultrasound in ablation of atrial fibrillation and other cardiac arrhythmias

Atrial fibrillation is the most prevalent arrhythmia of the heart, originating usually from ectopic atrial activity of the pulmonary veins. Therefore, one of the treatment options is pulmonary vein isolation. Among the novel approaches to pulmonary vein isolation, high- intensity focused ultrasound (HIFU) has been developed. The ultrasound energy can be focused on a specific area and would result in the formation of a lesion similar to that formed with radiofrequency (RF) ablation. Although preclinical studies were promising, clinical studies in patients resulted in lower efficacy and high complication rates in comparison to the standard ablation method, due to collateral damage. Using HIFU for epicardial approach during cardiac surgery and for extracorporeal ablation does seem to have a future role. In this review, we pres- ent the mechanism of HIFU lesion formation and the principal studies.

High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI)

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the −3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p < 0.002 in the 2D HMI system. We demonstrated the feasibility of using this HMI-based technique to localize the HIFU focal spot without inducing thermal changes during the planning phase. The focal spot localization method has also been applied on ex vivo human breast tissue ablation and can be fully integrated into any HMI system for planning purposes.

Multi-Wavelength Photoacoustic Visualization of High Intensity Focused Ultrasound Lesions.

High intensity focused ultrasound (HIFU) thermal therapies are limited by deficiencies in existing image-guidance techniques. Previous studies using single-wavelength photoacoustic (PA) imaging have demonstrated that HIFU lesions generate contrast with respect to native tissues but have not sufficiently assessed lesion extent. The purpose of this study is to demonstrate feasibility of characterization of in vitro HIFU ablation lesion dimensions using 3D multi-wavelength PA imaging. Fresh porcine cardiac and liver tissue samples were embedded in agar phantoms and ablated using a 2.5 MHz small-animal HIFU system. Both 2D and 3D multi-wavelength photoacoustic-ultrasonic (PAUS) scans were performed in the near-infrared (NIR) range to characterize the change in the absorption spectrum of tissues following ablation and were compared to stained gross pathology to assess treatment margins and lesion extent. Comprehensive 2D multi-wavelength PA imaging yielded a spectrum in ablated tissue that did not display the characteristic local maximum in the optical absorption spectrum of deoxy-hemoglobin (Hb) near 760 nm. Two-dimensional tissue characterization map (TCM) images reconstructed from 3D TCM volumes reliably characterized lesion area and showed >70% area agreement with stained gross pathology. In addition, tissue samples were heated via water bath and concurrently interrogated with 2D PAUS imaging. PA signal exhibited an initial amplitude increase across all wavelengths, corresponding to an initial temperature increase, before then exhibiting a spectral change. This study suggests that multi-wavelength PA imaging has potential to obtain accurate characterization of HIFU lesion extent and may be better suited to guide HIFU ablation therapies during clinical treatments than single-wavelength methods.

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.

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.

Transmural Ultrasound Imaging of Thermal Lesion and Action Potential Changes in Perfused Canine Cardiac Wedge Preparations by High Intensity Focused Ultrasound Ablation

Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm2), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43±1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96±0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89±0.01, n = 13) and change of APA (ROC AUC 0.79±0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction.

Dual perfluorocarbon nanodroplets enhance high intensity focused ultrasound heating and extend therapeutic window in vivo

Perfluorocarbon microbubbles are known to enhance high intensity focused ultrasound (HIFU) ablation by cavitation. However, they can result in superficial skin heating, minimizing their clinical translation. Perfluorocarbon nanodroplets activate only at the higher pressures present at the acoustic focus. We hypothesized that a mixed perfluorocarbon nanodroplet formulation would minimize surface heating while still enhancing ablation. Tissue-mimicking phantoms containing microbubbles or nanodroplets were sonicated (1 MHz, 15 W, 60 s) to assess heating and lesion formation in vitro. Microbubbles or nanodroplets were injected into rats (n = 3) and HIFU (1 MHz, 15 W, 15 s) was focused into each liver while under MRI guidance. Temperature throughout the liver was tracked by MR thermometry. In vitro, microbubbles caused excess surface heating during HIFU, whereas nanodroplets did not. In vivo, microbubbles typically circulate for less than 15 min. In comparison, the nanodroplets remained viable in circulation for at least 96 min. HIFU lesions of consistent volume were produced during this time and reached the same maximal temperature rise (Δ550 °C). In the absence of nanodroplets or microbubbles, significantly greater power (25 W) and twice as much time (30 s) was required to generate an ablation lesion in the liver. These results demonstrate the ability of nanodroplets to more safely shorten ablation procedures.

Spatial specificity and sensitivity of passive cavitation imaging for monitoring high-intensity focused ultrasound thermal ablation in ex vivo bovine liver

Passive cavitation images (PCIs) generated from scattered acoustic waves are a potential technique for monitoring lesion formation during high-intensity focused ultrasound (HIFU) thermal ablation. HIFU lesion prediction by PCIs was assessed in ex vivo bovine liver samples (N = 14) during 30-s sonications with 1.1-MHz continuous-wave ultrasound (1989 W/cm2 estimated spatial-peak intensity). Treated samples were sectioned, optically scanned, and the HIFU lesions segmented based on tissue discoloration. During each insonation, a 192-element, 7-MHz linear array (L7/Iris 2, Ardent Sound) passively recorded emissions from a plane containing the HIFU propagation axis oriented parallel to the image azimuth direction. PCIs were formed from beamformed A-lines filtered into fundamental, harmonic, ultraharmonic, and inharmonic frequency bands. Lesion prediction was tested using binary classification of local tissue ablation based on thresholded PCIs, with spatial specificity and sensitivity of lesion prediction quantified by the area under receiver operating characteristic curves (AUROC). Tadpole-shaped lesions were best predicted by harmonic emissions (AUROC = 0.76), prefocal lesions were best predicted by harmonic or ultraharmonic emissions (AUROC = 0.86), and cigar-type focal lesions were best predicted by fundamental and harmonic emissions (AUROC = 0.65). These results demonstrate spatial specificity and sensitivity when predicting HIFU lesions with PCIs. [Work supported in part by NIH grants F32HL104916 and R21EB008483.]

Improving the acousto-optic detection of high-intensity focused ultrasound lesions

Real-time acousto-optic (AO) sensing has been shown to non-invasively detect changes in ex vivo tissue optical properties during high-intensity focused ultrasound (HIFU) exposures. Although proof-of-concept experiments have been successful, the underlying parameters and mechanisms affecting the AO detectability of HIFU lesion formation are not well understood. In this work, a modeling based approach is used to improve the AO sensing of lesion formation during HIFU therapy. The angular spectrum method is used to model the acoustic field from the HIFU source and the temperature field, due to the absorption of ultrasound, is modeled using a finite-difference time-domain solution to the Pennes bioheat equation. Wavelength specific changes in tissue optical properties are calculated using a thermal dose model, calibrated by experimental data. The diffuse optical field is modeled using an open-source graphics processing unit accelerated Monte Carlo algorithm. The Monte Carlo algorithm is modified to account for light-sound interactions, using the acoustic field from the angular spectrum method, and to account for AO signal detection. Results will demonstrate the important roles of optical wavelength selection, and illumination and detection configurations on the detectability of HIFU lesions by optical and AO sensing methods. [Work supported in part by NSF.]

The role of acoustic nonlinearity in tissue heating behind a rib cage using a high-intensity focused ultrasound phased array

The goal of this study was to investigate theoretically the effects of nonlinear propagation in a high-intensity focused ultrasound (HIFU) field produced by a therapeutic phased array and the resultant heating of tissue behind a rib cage. Three configurations of focusing were simulated: in water, in water with ribs in the beam path and in water with ribs backed by a layer of soft tissue. The Westervelt equation was used to model the nonlinear HIFU field, and a 1 MHz phased array consisting of 254 circular elements was used as a boundary condition to the model. The temperature rise in tissue was modelled using the bioheat equation, and thermally necrosed volumes were calculated using the thermal dose formulation. The shapes of lesions predicted by the modelling were compared with those previously obtained in in vitro experiments at low-power sonications. Intensity levels at the face of the array elements that corresponded to the formation of high-amplitude shock fronts in the focal region were determined as 10 W cm−2 in the free field in water and 40 W cm−2 in the presence of ribs. It was shown that exposures with shocks provided a substantial increase in tissue heating, and its better spatial localization in the main focal region only. The relative effects of overheating ribs and splitting of the focus due to the periodic structure of the ribs were therefore reduced. These results suggest that utilizing nonlinear propagation and shock formation effects can be beneficial for inducing confined HIFU lesions when irradiating through obstructions such as ribs. Design of compact therapeutic arrays to provide maximum power outputs with lower intensity levels at the elements is necessary to achieve shock wave regimes for clinically relevant sonication depths in tissue.

Spatial specificity and sensitivity of passive cavitation imaging for monitoring high-intensity focused ultrasound thermal ablation in ex vivo bovine liver.

Passive cavitation images (PCIs) generated from scattered acoustic waves are a potential technique for monitoring lesion formation during high-intensity focused ultrasound (HIFU) thermal ablation. HIFU lesion prediction by PCIs was assessed in ex vivo bovine liver samples (N=14) during 30-s sonications with 1.1-MHz continuous-wave ultrasound (1989 W/cm^2 estimated spatial-peak intensity). Treated samples were sectioned, optically scanned, and the HIFU lesions segmented based on tissue discoloration. During each insonation, a 192-element, 7-MHz linear array (L7/Iris 2, Ardent Sound) passively recorded emissions from a plane containing the HIFU propagation axis oriented parallel to the image azimuth direction. PCIs were formed from beamformed A-lines filtered into fundamental, harmonic, ultraharmonic, and inharmonic frequency bands. Lesion prediction was tested using binary classification of local tissue ablation based on thresholded PCIs, with spatial specificity and sensitivity of lesion prediction quantified by the area under receiver operating characteristic curves (AUROC). Tadpole-shaped lesions were best predicted by harmonic emissions (AUROC=0.76), prefocal lesions were best predicted by harmonic or ultraharmonic emissions (AUROC=0.86), and cigar-type focal lesions were best predicted by fundamental and harmonic emissions (AUROC=0.65). These results demonstrate spatial specificity and sensitivity when predicting HIFU lesions with PCIs.

Modeling acousto-optic sensing of high-intensity focused ultrasound lesion formation

Real-time acousto-optic (AO) sensing has been shown to non-invasively detect changes in tissue optical properties, a direct indicator of thermal damage, during high-intensity focused ultrasound (HIFU) therapy. In this work, a comprehensive model is developed to describe the AO sensing of lesion formation during HIFU therapy. The angular spectrum method is used to model ultrasound propagation, and the temperature field due to the absorption of ultrasound is modeled using a finite-difference time-domain (FDTD) solution to the Pennes bioheat equation. Thermal damage dependent optical properties are calculated based on a probabilistic and calibrated thermal dose model. To simulate light propagation inside of insonified and optically heterogeneous tissue, an open-source graphics processing unit (GPU) accelerated Monte Carlo algorithm is used. The Monte Carlo algorithm is modified to account for light-sound interactions, using input from the angular spectrum method, and to account for AO signal detection. Results will show how wavelength and illumination/detection configurations affect the detectability of HIFU lesions using AO sensing.

Photoacoustic-guided ultrasound therapy with a dual-mode ultrasound array

Photoacoustics has recently been proposed as a potential method to guide and/or monitor therapy based on high-intensity focused ultrasound (HIFU). We experimentally demonstrate the creation of a HIFU lesion at the location of an optical absorber, by use of photoacoustic signals emitted by the absorber detected on a dual mode transducer array. To do so, a dedicated ultrasound array intended to both detect photoacoustic waves and emit HIFU with the same elements was used. Such a dual-mode array provides automatically coregistered reference frames for photoacoustic detection and HIFU emission, a highly desired feature for methods involving guidance or monitoring of HIFU by use of photoacoustics. The prototype is first characterized in terms of both photoacoustic and HIFU performances. The probe is then used to perform an idealized scenario of photoacoustic-guided therapy, where photoacoustic signals generated by an absorbing thread embedded in a piece of chicken breast are used to automatically refocus a HIFU beam with a time-reversal mirror and necrose the tissue at the location of the absorber.

In Vitro Atrial Septal Ablation Using High-Intensity Focused Ultrasound

High-intensity focused ultrasound (HIFU) has been applied clinically as a noninvasive therapeutic tool. Atrial septostomy is a palliative treatment for pulmonary artery hypertension. The purpose of this study was to assess the feasibility of atrial septal ablation invitro using HIFU. Fourteen sections of atrial septum from pig hearts were treated. Focused ultrasound energy was applied with an operating frequency of 5.25 MHz at the nominal focal point intensity of 4.0 kW/cm(2) for 0.4sec in 1-sec intervals. Lesions were created with ultrasonic exposures ranging from 40 to 120 pulses. There were significant relationships between HIFU exposure time and lesion area on the exposed site (R(2)= 0.3389, P < .0001) and lesion volume (R(2)= 0.6161, P < .0001). HIFU has the potential to create focal perforations without direct tissue contact. This method may prove useful for noninvasive atrial septostomy.

Performance Assessment of HIFU Lesion Detection by Harmonic Motion Imaging for Focused Ultrasound (HMIFU): A 3-D Finite-Element-Based Framework with Experimental Validation

Harmonic motion imaging for focused ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on amplitude-modulated (AM) - harmonic motion imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module and an image-formation model. The objective of this study is to develop such a framework to (1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young’s modulus, and the HIFU lesion size with respect to the HIFU exposure time and (2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young’s modulus ratio of 3, 6 and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69 and 5.39 and 1.65, 3.19 and 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28 and 1.78 at 10-s, 20-s and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was found in both simulations (16.2, 73.1 and 334.7 mm 2) and experiments (26.2, 94.2 and 206.2 mm 2). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo.

Real-time monitoring of high-intensity focused ultrasound ablations with photoacoustic technique: Anin vitrostudy

The purpose of this study is to apply photoacoustic imaging (PAI) to monitor high intensity focused ultrasound (HIFU) process in real-time for accurate evaluation of thermal ablation outcomes. A photoacoustic (PA) imaging system was used to monitor HIFU ablation process in this study. Single-element, spherically focused ultrasonic transducers with center frequencies of 5 and 10 MHz were used to generate HIFU lesions and detect PA signals in beef kidney during HIFU treatments, respectively. A 25-μm diameter, T-type thermocouple was used to measure the temperature rise during the treatment as well. Thermal dose, which was used to indicate the coagulation of soft tissue, was calculated with the temperature measured by the thermocouple. Detected PA signals were then related to the coagulation of soft tissue through thermal dose calculations. In addition, PA signals from beef kidney coagulating under a constant temperature was obtained to show the changes of PA signals under a constant temperature during soft tissue coagulation. PA amplitude increases during the HIFU process and tends to have a saturation stage after the soft tissue is completely coagulated, which is indicated by a 240 or more TD(43) minutes. Also, a linear relation between the PA signal amplitude changes and temperature was observed when monitoring the sole effect of temperature. In addition, PA amplitude changes finally reached a constant value during soft tissue coagulation under a constant temperature. Through measurement of the photoacoustic signal, the authors demonstrated that monitoring thermal dose may be a more appropriate method in HIFU treatment than monitoring temperature.

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 mm 2 and 65.2 ± 9.6 mm 2, respectively) in the gel phantom are significantly smaller ( p < 0.05) than those using raster scanning (92.9 ± 11.8 mm 2). 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.

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. The investigators hypothesized that microbubbles generated by ADV could enhance high-intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption. Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W · cm(-2) in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted magnetic resonance imaging. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup. Thermal lesions were sevenfold larger in phantoms containing droplets (3 × 10(5) droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2-second HIFU exposure in droplet-containing phantoms was comparable to that made by a 5-second exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm(3) (n = 4; 5-second exposure) and 0.265 ± 0.005 cm(3) (n = 3; 5-second exposure), respectively, a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by magnetic resonance imaging. ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power and provide ultrasonic imaging feedback of the thermal therapy.