Real-time volumetric MRI thermometry of focused ultrasound ablation in vivo: a feasibility study in pig liver and kidney

MR thermometry offers the possibility to precisely guide high-intensity focused ultrasound (HIFU) for the noninvasive treatment of kidney and liver tumours. The objectives of this study were to demonstrate therapy guidance by motion-compensated, rapid and volumetric MR temperature monitoring and to evaluate the feasibility of MR-guided HIFU ablation in these organs. Fourteen HIFU sonications were performed in the kidney and liver of five pigs under general anaesthesia using an MR-compatible Philips HIFU platform prototype. HIFU sonication power and duration were varied. Volumetric MR thermometry was performed continuously at 1.5 T using the proton resonance frequency shift method employing a multi-slice, single-shot, echo-planar imaging sequence with an update frequency of 2.5 Hz. Motion-related suceptibility artefacts were compensated for using multi-baseline reference images acquired prior to sonication. At the end of the experiment, the animals were sacrificed for macroscopic and microscopic examinations of the kidney, liver and skin. The standard deviation of the temperature measured prior to heating in the sonicated area was approximately 1 °C in kidney and liver, and 2.5 °C near the skin. The maximum temperature rise was 30 °C for a sonication of 1.2 MHz in the liver over 15 s at 300 W. The thermal dose reached the lethal threshold (240 CEM(43) ) in two of six cases in the kidney and four of eight cases in the liver, but remained below this value in skin regions in the beam path. These findings were in agreement with histological analysis. Volumetric thermometry allows real-time monitoring of the temperature at the target location in liver and kidney, as well as in surrounding tissues. Thermal ablation was more difficult to achieve in renal than in hepatic tissue even using higher acoustic energy, probably because of a more efficient heat evacuation in the kidney by perfusion.     

In vivo characterization of tissue thermal properties of the kidney during local hyperthermia induced by MR-guided high-intensity focused ultrasound

The purpose of this study was to evaluate quantitatively in vivo the tissue thermal properties during high-intensity focused ultrasound (HIFU) heating. For this purpose, a total of 52 localized sonications were performed in the kidneys of six pigs with HIFU monitored in real time by volumetric MR thermometry. The kidney perfusion was modified by modulation of the flow in the aorta by insertion of an inflatable angioplasty balloon. The resulting temperature data were analyzed using the bio-heat transfer model in order to validate the model under in vivo conditions and to estimate quantitatively the absorption (α), thermal diffusivity (D) and perfusion (w(b)) of renal tissue. An excellent correspondence was observed between the bio-heat transfer model and the experimental data. The absorption and thermal diffusivity were independent of the flow, with mean values (± standard deviation) of 20.7 ± 5.1 mm(3) K J(-1) and 0.23 ± 0.11 mm(2) s(-1), respectively, whereas the perfusion decreased significantly by 84% (p < 0.01) with arterial flow (mean values of w(b) of 0.06 ± 0.02 and 0.008 ± 0.007 mL(-1) mL s(-1)), as predicted by the model. The quantitative analysis of the volumetric temperature distribution during nondestructive HIFU sonication allows the determination of the thermal parameters, and may therefore improve the quality of the planning of noninvasive therapy with MR-guided HIFU.     

Ultrasonography-based 2D motion-compensated HIFU sonication integrated with reference-free MR temperature monitoring: a feasibility study ex vivo

Magnetic resonance imaging (MRI) and ultrasonography have been used simultaneously in this ex vivo study for the image-guidance of high intensity focused ultrasound (HIFU) treatment in moving tissue. A ventilator-driven balloon produced periodic and non-rigid (i.e. breathing-like) motion patterns in phantoms. MR-compatible ultrasound (US) imaging enabled near real-time 2D motion tracking based on optical flow detection, while near-harmonic reference-free proton resonance frequency shift (PRFS) MR thermometry (MRT) was used to monitor the thermal buildup on line. Reference-free MRT was applied to gradient-echo echo-planar imaging phase maps acquired at the frame rate of 250 to 300 ms/slice with voxel size 1.25×1.25×5 mm(3). The MR-US simultaneous imaging was completely free of mutual interferences while minor RF interferences from the HIFU device were detected in the far field of the US images. The effective duty-cycle of the HIFU sonication was close to 100 % and no off-interval was required to temporally decouple it from the ultrasonography. The motion compensation of the HIFU sonication was achieved with an 8 Hz frame rate and sub-millimeter spatial accuracy, both for single-focus mode and for an iterated multi-foci line scan. Near harmonic reference-less PRFS MRT delivered motion-robust thermal maps perpendicular or parallel to the HIFU beam (0.7 °C precision, 0.5 °C absolute accuracy). Out-of-plane motion compensation was not addressed in this study.     

Towards optimized MR thermometry of the human heart at 3T

Catheter ablation using radio frequency (RF) has been used increasingly for the treatment of cardiac arrhythmias and may be combined with proton resonance frequency shift (PRFS) ?based MR thermometry to determine the therapy endpoint. We evaluated the suitability of two different MR thermometry sequences (TFE and TFE‐EPI) and three blood suppression techniques. Experiments were performed without heating, using an optimized imaging protocol including navigator respiratory compensation, cardiac triggering, and image processing for the compensation of motion and susceptibility artefacts. Blood suppression performance and its effect on temperature stability were evaluated in the ventricular septum of eight healthy volunteers using multislice double inversion recovery (MDIR), motion sensitized driven equilibrium (MSDE), and inflow saturation by saturation slabs (IS). It was shown that blood suppression during MR thermometry improves the contrast‐to‐noise ratio (CNR), the robustness of the applied motion correction algorithm as well as the temperature stability. A gradient echo sequence accelerated by an EPI readout and parallel imaging (SENSE) and using inflow saturation blood suppression was shown to achieve the best results. Temperature stabilities of 2 °C or better in the ventricular septum with a spatial resolution of 3.5 × 3.5 × 8mm³ and a temporal resolution corresponding to the heart rate of the volunteer, were observed. Our results indicate that blood suppression improves the temperature stability when performing cardiac MR thermometry. The proposed MR thermometry protocol, which optimizes temperature stability in the ventricular septum, represents a step towards PRFS‐based MR thermometry of the heart at 3 T. Copyright © 2011 John Wiley & Sons, Ltd.     

MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh

In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumour coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5 T) guidance with one of two eight-sector, spherically curved piezoelectric transducers. The transducer, either a 1.1 or 1.7 MHz array, was driven by a multi-channel RF driving system. The transducer was mounted in an MRI-compatible manual positioning system and the rabbit was situated on top of the system. An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. Focused ultrasound surgery exposures were delivered to the thighs of seven New Zealand while rabbits. The experimental, gas-bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W or 21 W continuous wave exposure for 19.5 s. The respective control sonications were 20 s exposures of 14 W, 21 W and 28 W. During the exposures, MR thermometry was obtained from the temperature dependency of the proton resonance frequency shift. MRT2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble-enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise within the first 4 s and higher overall temperatures than the sonications without bubble formation. The spatial temperature maps and the thermal dose maps derived from the MRI thermometry closely correlated with the resulting lesion as examined by T2-weighted imaging. The lesions created with the gas-bubble-enhanced heating exposures were 2-3 times larger by volume, consistently more spherical in shape and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo. MRI thermometry techniques were successfully used to monitor the thermal effects mediated by the bubble-enhanced exposures.     

基于磁共振温度图的高强度聚焦超声治疗热剂量研究

本实验研究基于磁共振T-Map的HIFU损伤组织的热剂量与实际凝固性坏死的关系。运用磁共振导航高强度聚焦超声治疗系统,使用1 MHz、焦距为150 mm、直径150 mm的聚焦超声换能器,定点辐照深度为20 mm的新鲜离体牛肝脏,辐照过程中用磁共振的测温序列采集各体素随时间变化的温度值并计算各体素的Eq43值,比较计算结果与发生凝固性坏死的Eq43参考阈值,判断该体素是否发生坏死。最后比较通过等效热剂量积分法得到的凝固性坏死面积和组织实际发生坏死的情况。结果表明基于磁共振T-Map的等效热剂量积分法得到的凝固性坏死的面积值能很好的反应实际发生凝固性坏死的情况,为HIFU治疗提供了一种新的判断凝固性坏死发生的方法,这种方法可以实时地反馈控制超声辐照剂量,提高了治疗的安全性。     

Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues

FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 degrees C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 microm degrees C(-1)(r=0.93, p<.005). After sustained heating, the tissue became irreversibly stiffer, followed by an associated decrease in the HMI displacement (-0.79 microm degrees C(-1), r=-0.92, p<0.001). Repeated experiments showed a reproducible pattern of the HMI displacement changes with a temperature at a slope equal to 0.8+/-0.11 and -0.79+/-0.14 microm degrees C(-1), prior to and after lesion formation in seven bovine liver samples, respectively. This technique was thus capable of following the protein-denatured lesion formation based on the variation of the HMI displacements. This method could, therefore, be applied for real-time monitoring of temperature-related stiffness changes of tissues during FUS, HIFU or other thermal therapies.     

Curvilinear transurethral ultrasound applicator for selective prostate thermal therapy

Thermal therapy offers a minimally invasive option for treating benign prostatic hyperplasia (BPH) and localized prostate cancer. In this study we investigated a transurethral ultrasound applicator design utilizing curvilinear, or slightly focused, transducers to heat prostatic tissue rapidly and controllably. The applicator was constructed with two independently powered transducer segments operating at 6.5 MHz and measuring 3.5 mm x 10 mm with a 15 mm radius of curvature across the short axis. The curvilinear applicator was characterized by acoustic efficiency measurements, acoustic beam plots, biothermal simulations of human prostate, ex vivo heating trials in bovine liver, and in vivo heating trials in canine prostate (n=3). Each transducer segment was found to emit a narrow acoustic beam (max width <3 mm), which extended the length of the transducer, with deeper penetration than previously developed planar or sectored tubular transurethral ultrasound applicators. Acoustic and biothermal simulations of human prostate demonstrated three treatment schemes for the curvilinear applicator: single shot (10 W, 60 s) schemes to generate narrow ablation zones (13 x 4 mm, 52 degrees C at the lesion boundary), incremental rotation (10 W, 10 degrees/45 s) to generate larger sector-shaped ablation zones (16 mm x 180 degrees sector), and rotation with variable sonication times (10 W, 10 degrees/15-90 s) to conform the ablation zone to a predefined boundary (9-17 mm x 180 degrees sector, 13 min total treatment time). During in vivo canine prostate experiments, guided by MR temperature imaging, single shot sonications (6 W/transducer, 2-3 min) with the curvilinear applicator ablated 20 degree sections of tissue to the prostate boundary (9-15 mm). Multiple adjacent sonications ("sweeping") ablated large sections of the prostate (180 degrees) by using the MR temperature imaging to adjust the power (4-6.4 W/transducer) and sonication time (30-180 s) at each 10 degrees rotation such that the periphery of the prostate reached 52 degrees C before the next rotation. The conclusion of this study was that the curvilinear applicator produces a narrow and penetrating ultrasound beam that, when combined with image guidance, can provide a precise technique for ablating target regions with a contoured outer boundary, such as the prostate capsule, by rotating in small steps while dynamically adjusting the net applied electrical power and sonication time at each position.     

Simulations and measurements of transcranial low-frequency ultrasound therapy: skull-base heating and effective area of treatment

Measurements of temperature elevations induced by sonications in a single intact cadaver skull filled with soft-tissue mimicking phantom material were performed using magnetic resonance thermometry. The sonications were done using a clinical transcranial ultrasound therapy device operating at 230 kHz and the measurements were compared with simulations done using a model incorporating both the longitudinal and shear wave propagation. Both the measurements and simulations showed that in some situations the temperature increase could be higher in the phantom material adjacent to the skull-base than at the focus, which could lead to undesired soft-tissue damage in treatment situations. On average the measurements of the sonicated locations, as well as the comparative simulations, showed 32 ± 64% and 49 ± 32% higher temperature elevations adjacent to the skull-base than at the focus, respectively. The simulation model was used to extend the measurements by simulating multiple sonications of brain tissue in five different skulls with and without correcting the aberrations caused by the skull on the ultrasound. Without aberration correction the closest sonications to the skulls that were treatable in any brain location without undesired tissue damage were at a distance of 19.1 ± 2.6?mm. None of the sonications beyond a distance of 41.2 ± 5.3?mm were found to cause undesired tissue damage. When using the aberration correction closest treatable, safe distances for sonications were found to be 16.0 ± 1.6 and 38.8 ± 3.8?mm, respectively. New active cooling of the skull-base through the nasal cavities was introduced and the treatment area was investigated. The closest treatable distance without aberration correction reduced to 17.4 ± 1.9?mm with the new cooling method. All sonications beyond a distance of 39.7 ± 6.6?mm were found treatable. With the aberration correction no difference in the closest treatable or the safety distance was found in comparison to sonications without nasal cavity cooling. To counteract undesired skull-base heating a new anti-focus within solid media was developed along with a new regularized phasing method. Mathematical bases for both the methods and simulations utilizing them were presented. It was found that utilizing the anti-focus in solid media and regularized phasing, the fraction of temperature increase of the brain tissue at the focus and the peak temperature increase adjacent to the skull-base can be increased from 1.00 to 1.95. This improves the efficiency of the sonication by reducing the energy transfer to the skull-base.     

An MR-compliant phased-array HIFU transducer with augmented steering range, dedicated to abdominal thermotherapy

A novel architecture for a phased-array high intensity focused ultrasound (HIFU) device was investigated, aiming to increase the capabilities of electronic steering without reducing the size of the elementary emitters. The principal medical application expected to benefit from these developments is the time-effective sonication of large tumours in moving organs. The underlying principle consists of dividing the full array of transducers into multiple sub-arrays of different resonance frequencies, with the reorientation of these individual emitters, such that each sub-array can focus within a given spatial zone. To enable magnetic resonance (MR) compatibility of the device and the number of output channels from the RF generator to be halved, a passive spectral multiplexing technique was used, consisting of parallel wiring of frequency-shifted paired piezoceramic emitters with intrinsic narrow-band response. Two families of 64 emitters (circular, 5 mm diameter) were mounted, with optimum efficiency at 0.96 and 1.03 MHz, respectively. Two different prototypes of the HIFU device were built and tested, each incorporating the same two families of emitters, but differing in the shape of the rapid prototyping plastic support that accommodated the transducers (spherical cap with radius of curvature/aperture of 130 mm/150 mm and, respectively, 80 mm/110 mm). Acoustic measurements, MR-acoustic radiation force imaging (ex vivo) and MR-thermometry (ex vivo and in vivo) were used for the characterization of the prototypes. Experimental results demonstrated an augmentation of the steering range by 80% along one preferentially chosen axis, compared to a classic spherical array of the same total number of elements. The electric power density provided to the piezoceramic transducers exceeded 50 W cm(-2) CW, without circulation of coolant water. Another important advantage of the current approach is the versatility of reshaping the array at low cost.     

Comparative study of temperature measurements in ex vivo swine muscle and a tissue-mimicking material during high intensity focused ultrasound exposures

Tissue-mimicking materials (TMMs) can provide a convenient, stable, and reproducible means for testing high intensity focused ultrasound (HIFU) devices. When TMMs containing thermal sensors are used to measure ultrasound-induced temperature rise, it is important that measurement results reasonably represent those that occur in biological tissue. Therefore the aim of this paper is to compare the thermal behavior of the TMM under HIFU exposure to that of ex vivo tissue. This was accomplished using both a previously developed TMM and fresh ex vivo swine muscle that were instrumented with bare 50 μm thin wire thermocouples. HIFU at 825 kHz was focused at the thermocouple junction. 30 s exposures of increasing peak negative pressure (1 to 5 MPa) were applied and the temperature profile during and after sonication was recorded. B-mode imaging was used to monitor bubble activity during sonication. If bubble formation was noted during the sonication, the sonication was repeated at the same pressure levels two more times at 20 min intervals. Temperature traces obtained at various pressure levels demonstrated similar types of heating profiles in both the tissue and TMM, the exact nature of which depended on whether bubbles formed during the HIFU exposure. The onset of bubble activity occurred at lower ultrasonic pressures in the TMM, but the basic temperature rise features due to HIFU exposure were essentially the same for both materials.     

The feasibility of MRI-guided whole prostate ablation with a linear aperiodic intracavitary ultrasound phased array

Over the past decade, numerous minimally invasive thermal procedures have been investigated to treat benign prostate hyperplasia and prostate cancer. Of these methods, ultrasound has shown considerable promise due to its ability to produce more precise and deeper thermal foci. In this study, a linear, transrectal ultrasound phased array capable of ablating large tissue volumes was fabricated and evaluated. The device was designed to be compatible for use with MRI guidance and thermometry. The intracavitary applicator increases treatable tissue volume by using an ultrasonic motor to provide a mechanical rotation angle of up to 100 degrees to a 62-element 1D ultrasound array. An aperiodic array geometry was used to reduce grating lobes. In addition, a specially designed Kapton interconnect was used to reduce cable crosstalk and hence also improve the acoustic efficiency of the array. MRI-guided in vivo and ex vivo experiments were performed to verify the array's large-volume ablative capabilities. Ex vivo bovine experiments were performed to assess the focusing range of the applicator. The array generated foci in a 3 cm (2 to 5 cm from the array surface along the axis normal to the array) by 5.5 cm (along the long axis of the array) by 6 cm (along the transverse axis of the array at a depth of 4 cm) volume. In vivo rabbit thigh experiments were performed to evaluate the lesion producing capabilities in perfused tissue. The array generated 3 cm x 2 cm x 2 cm lesions with 8 to 12 half-minute sonications equally spaced in the volume. The results indicate that transrectal ultrasound coagulation of the whole prostate is feasible with the developed device.     

Proton spectroscopic imaging of the human prostate at 7 T

The sensitivity of proton MR Spectroscopic Imaging (¹H‐MRSI) of the prostate can be optimized by using the high magnetic field strength of 7 T in combination with an endorectal coil. In the work described in this paper we introduce an endorectal transceiver at 7 T, validate its safety for in vivo use and apply a pulse sequence, optimized for three‐dimensional (3D) ¹H‐MRSI of the human prostate at 7 T. A transmit/receive endorectal RF coil was adapted from a commercially available 3 T endorectal receive‐only coil and validated to remain within safety guidelines for radiofrequency (RF) power deposition using numerical models, MR thermometry of phantoms, and in vivo temperature measurements. The ¹H‐MRSI pulse sequence used adiabatic slice selective refocusing pulses and frequency‐selective water and lipid suppression to selectively obtain the relevant metabolite signals from the prostate. Quantum mechanical simulations were used to adjust the inter‐pulse timing for optimal detection of the strongly coupled spin system of citrate resulting in an echo time of 56 ms. Using this endorectal transceiver and pulse sequence with slice selective adiabatic refocusing pulses, 3D ¹H‐MRSI of the human prostate is feasible at 7 T with a repetition time of 2 s. The optimized inter‐pulse timing enables the absorptive detection of resonances of spins from spermine and citrate in phase with creatine and choline. These potential tumor markers may improve the in vivo detection, localization, and assessment of prostate cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process.     

Thermal dosimetry of a focused ultrasound beam in vivo by magnetic resonance imaging.

Magnetic resonance imaging (MRI) thermometry has been utilized for in vivo evaluation of thermal exposure induced by a focused ultrasound beam. A simulation study of the focused ultrasound beam was conducted to select imaging parameters for reducing the error due to the spatial and temporal averaging of MRI. Temperature imaging based on the proton resonance frequency shift was utilized to obtain the temperature distribution during sonication in the skeletal muscle of eight rabbits. MRI-derived temperature information was then used to calculate the thermal dose distribution induced by the sonication and to estimate the coagulated tissue volume. The tissue changes were also evaluated directly by taking the T2-weighted and the contrast agent enhanced T1-weighted MR images. Errors in the temperature and thermal dose measurements were found to be minimal using the following parameters: slice thickness = 3 mm, voxel dimension = 0.6 mm, and scan time per image = 3.4 s. The estimated dimensions of the coagulated tissue volume were in good agreement with the tissue damages seen on the contrast agent enhanced T1-weighted images. The tissue damage seen on the histology was closely matched to the ones seen on the T2-weighted images. This study showed that MRI thermometry has significant potential for both monitoring the thermal exposure and evaluating the tissue damage. This would allow real-time control of the sonication parameters to optimize clinical treatments.     

Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation

Organic/inorganic, hybrid, multifunctional, material-based platforms combine the merits of diverse functionalities of inorganic nanoparticles and the excellent biocompatibility of organic systems. In this work, superparamagnetic poly(lactic-co-glycolic acid) (PLGA) microcapsules (Fe(3)O(4)/PLGA) have been developed, as a proof-of-concept, for the application in ultrasound/magnetic resonance dual-modality biological imaging and enhancing the therapeutic efficiency of high intensity focused ultrasound (HIFU) breast cancer surgery in vitro and in vivo. Hydrophobic Fe(3)O(4) nanoparticles were successfully integrated into PLGA microcapsules by a typical double emulsion evaporation process. In this process, highly dispersed superparamagnetic Fe(3)O(4)/PLGA composite microcapsules with well-defined spherical morphology were obtained with an average diameter of 885.6 nm. The potential of these microcapsules as dual contrast agents for ultrasonography and magnetic resonance imaging were demonstrated in vitro and, also, preliminarily in vivo. Meanwhile, the prepared superparamagnetic composite microcapsules were administrated into rabbits bearing breast cancer model for the evaluation of the in vivo HIFU synergistic ablation efficiency caused by the introduction of such microcapsules. Our results showed that the employment of the composite microcapsules could efficiently enhance ultrasound imaging of cancer, and greatly enhance the HIFU ablation of breast cancer in rabbits. In addition, pathological examination was systematically performed to detect the structural changes of the target tissue caused by HIFU ablation. This finding demonstrated that successful introduction of these superparamagnetic microcapsules into HIFU cancer surgery provided an alternative strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy of cancer.     

Rapid motion correction in MR‐guided high‐intensity focused ultrasound heating using real‐time ultrasound echo information

The objective of this study was to evaluate the feasibility of integrating real‐time ultrasound echo guidance in MR‐guided high‐intensity focused ultrasound (HIFU) heating of mobile targets in order to reduce latency between displacement analysis and HIFU treatment. Experiments on a moving phantom were carried out with MRI‐guided HIFU during continuous one‐dimensional ultrasound echo detection using separate HIFU and ultrasound imaging transducers. Excellent correspondence was found between MR‐ and ultrasound‐detected displacements. Real‐time ultrasound echo‐based target tracking during MR‐guided HIFU heating is shown with the dimensions of the heated area similar to those obtained for a static target. This work demonstrates that the combination of the two modalities opens up perspectives for motion correction in MRI‐guided HIFU with negligible latency. Copyright © 2010 John Wiley & Sons, Ltd.     

MR guided focused ultrasound: technical acceptance measures for a clinical system

Magnetic resonance (MR) guided focused ultrasound (MRgFUS) is a hybrid technique which offers efficient and safe focused ultrasound (FUS) treatments of uterine fibroids under MR guidance and monitoring. As a therapy device, MRgFUS requires systematic testing over a wide range of operational parameters prior to use in the clinical environment. We present technical acceptance tests and data for the first clinical MRgFUS system, ExAblate 2000 (InSightec Inc., Haifa, Israel), that has been FDA approved for treating uterine fibroids. These tests characterize MRgFUS by employing MR temperature measurements in tissue mimicking phantoms. The coronal scan plane is empirically demonstrated to be most reliable for measuring temperature elevations resulting from high intensity ultrasound (US) pulses ('sonications') and shows high sensitivity to changes in sonication parameters. Temperatures measured in the coronal plane were used as a measure of US energy deposited within the focal spot for a range of sonication parameters used in clinical treatments: spot type, spot length, output power, sonication duration, US frequency, and depth of sonication. In addition, MR images acquired during sonications were used to measure effective diameters and lengths of available sonication spot types and lengths. At a constant 60 W output power, the effective spot type diameters were measured to vary between 4.7 +/- 0.3 mm and 6.6 +/- 0.4 mm; treatment temperatures were found to decrease with increasing spot diameter. Prescribing different spot lengths was found to have no effect on the measured length or on measured temperatures. Tests of MRgFUS positioning accuracy determined errors in the direction parallel to the propagation of the US beam to be significantly greater than those in the perpendicular direction; most sonication spots were erroneously positioned towards the FUS transducer. The tests reported here have been demonstrated to be sufficiently sensitive to detect water leakage inside the FUS transducer. The data presented could be used for comparison by those conducting acceptance tests on other clinical MRgFUS systems.     

An image-guided high intensity focused ultrasound device for uterine fibroids treatment

A high intensity focused ultrasound (HIFU) device was developed for treating uterine fibroid tumors. This prototype device enables image-guided therapy by aligning a commercially available abdominal ultrasound image probe to a vaginal HIFU transducer so the HIFU focus is in the image plane. The device was designed based on anatomical constraints of the female pelvic structures. HIFU was generated using a 3.5 MHz PZT-8 crystal, 25.4 mm in diameter, bonded to an aluminum lens. Computer simulations were performed to ensure that effective focusing was achievable at a fixed focal depth of 40 mm. Transducer efficiency was empirically determined to be 58%, and the half pressure maximum focal dimensions were 11 mm in length and 1.2 mm in width. A water-filled latex condom surrounding the transducer provided acoustic coupling, a stand-off, and allowed water circulation for transducer cooling. In vitro experiments in a tissue-mimicking gel phantom and in turkey breast demonstrated ultrasound image-guided lesion formation, or tissue necrosis, at the focus due to HIFU induced thermal and cavitation effects. The HIFU treatment site appeared as a hyperechoic spot on the ultrasound image at intensities above 1250 W/cm2. The results of in vitro experiments and in vivo ergonomic testing in six human volunteers indicated that the device has the potential of providing a nonsurgical approach for uterine fibroid treatment. Future in vivo studies in large animal models and fibroids patients are planned.     

A novel strategy to increase heating efficiency in a split-focus ultrasound phased array

Focus splitting using sector-based phased arrays increases the necrosed volume in a single sonication and reduces the total treatment time in the treatment of large tumors. However, split-focus sonication results in a lower energy density and worse focal-beam distortion, which limits its usefulness in practical treatments. Here, we propose a new heating strategy involving consecutive strongly focused and split-focus sonications to improve the heating efficiency. Theoretical predictions including linear and thermal-dose-dependent attenuation change were employed to investigate potential factors of this strategy, and ex vivo tissue experiments were conducted to confirm its effectiveness. Results showed that the thermal lesions produced by the proposed strategy could be increased when comparing with the previous reported strategies. The proposed heating strategy also induces a thermal lesion more rapidly, and exhibits higher robustness to various blood perfusion conditions, higher robustness to various power/heating time combinations, and superiority to generate deep-seated lesions through tissues with complex interfaces. Possible mechanisms include the optimization of the thermal conduction created by the strongly focused sonication and the temperature buildup gained from thermally induced tissue attenuation change based on the theoretical analysis. This may represent a useful technique for increasing the applicability of split-focus and multiple-focus sonication techniques, and solve the obstacles encountered when attempting to use these methods to shorten the total clinical treatment time.