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Background: Due to the heating in the pre-focal field the delay between successive movements in high intensity focused ultrasound (HIFU) are sometimes as long as 60s, resulting to treatment time in the order of 2-3h. Because there is generally a requirement to reduce treatment time, we were motivated to explore alternative transducer motion algorithms in order to reduce pre-focal heating and treatment time., Materials and Methods: A 1 MHz single element transducer with 4 cm diameter and 10 cm focal length was used. A simulation model was developed that estimates the temperature, thermal dose and lesion development in the pre-focal field. The simulated temperature history that was combined with the motion algorithms produced thermal maps in the pre-focal region. Polyacrylimde gel phantom was used to evaluate the induced pre-focal heating for each motion algorithm used, and also was used to assess the accuracy of the simulation model., Results: Three out of the six algorithms having successive steps close to each other, exhibited severe heating in the pre-focal field. Minimal heating was produced with the algorithms having successive steps apart from each other (square, square spiral and random). The last three algorithms were improved further (with small cost in time), thus eliminating completely the pre-focal heating and reducing substantially the treatment time as compared to traditional algorithms., Conclusions: Out of the six algorithms, 3 were successful in eliminating the pre-focal heating completely. Because these 3 algorithms required no delay between successive movements (except in the last part of the motion), the treatment time was reduced by 93%. Therefore, it will be possible in the future, to achieve treatment time of focused ultrasound therapies shorter than 30 min. The rate of ablated volume achieved with one of the proposed algorithms was 71 cm(3)/h. The intention of this pilot study was to demonstrate that the navigation algorithms play the most important role in reducing pre-focal heating. By evaluating in the future, all commercially available geometries, it will be possible to reduce the treatment time, for thermal ablation protocols intended for oncological targets., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The aim of the proposed study was to conduct a feasibility study using a flat rectangular (3 mm × 10 mm) MRI compatible transducer operating at 5.3 MHz for destroying calcified material in an in vitro model. The proposed method can be used in the future for treating atherosclerosis plaques of the coronary, carotid or peripheral arteries., Methods: The system was tested initially on calcium rods. Another test was performed in a hydroxyapatite-polylactide model., Results: A parametric study was performed where the mass of calcified material removed was studied as a function of intensity, pulse repetition frequency (PRF), duty factor (DF) and presence of bubbles., Conclusions: The amount of calcified material removed is directly related to the intensity, PRF and DF. It was found that the presence of bubbles accelerates the removal of calcified material. In order to ensure that pure mechanical mode ultrasound was used, the protocols were designed so that the temperature does not exceed 1 °C.

Objective: Develop a magnetic resonance imaging (MRI) compatible head phantom with acoustic attenuation closely matched to the human attenuation, and suitable for testing focused ultrasound surgery protocols., Materials and Methods: Images from an adult brain CT scan were used to segment the skull bone from adjacent cerebral tissue. The segmented model was manufactured in a 3-D printer using (Acrylonitrile Butadiene Styrene) ABS plastic. The cerebral tissue was mimicked by an agar-evaporated milk-silica gel (2% w/v-25% v/v-1.2% w/v) which was molded inside a skull model., Results: The measured attenuation of the ABS skull was 16 dB/cm MHz. The estimated attenuation coefficient of the gel replicating brain tissue was 0.6 dB/cm MHz. The estimated agar-silica gel's T1 and T2 relaxation times in a 1.5 Tesla magnetic field were 852 ms and 66 ms respectively. The effectiveness of the skull to reduce ultrasonic heating was demonstrated using MRI thermometry., Conclusion: Due to growing interest in using MRI guided focused ultrasound (MRgFUS) for treating brain cancer and its application in sonothrombolysis, the proposed head phantom can be utilized as a very useful tool for evaluating ultrasonic protocols, thus minimizing the need for animal models and cadavers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: A prototype magnetic resonance image (MRI)-conditional robot was developed for navigating a high-intensity focused ultrasound (HIFU) system in order to treat prostate cancer transrectally., Materials and Methods: The developed robotic device utilizes three PC-controlled axes: a linear axis for motion along the rectum, an angular axis for rotation in the rectum, and a linear axis to lift the robot up and down. Experiments with the system were performed in a 1.5-T MRI system using gel phantoms., Result: The robot was successfully operated in a 1.5-T clinical MRI system. The effect of piezoelectric motors and optical encoders was quantified based on the reduction of signal to noise ratio. Discrete and overlapping lesions were created accurately by moving the HIFU transducer with the robotic device., Conclusion: An MRI-conditional HIFU robot was developed which can create controlled thermal lesions under MRI guidance. The intention is to use this robot transrectally in the future for the treatment of prostate cancer.

Background: The aim of the proposed study was to conduct a feasibility study using a flat rectangular (3 × 10 mm(2)) transducer operating at 5 MHz for removing atherosclerotic plaque in an in vivo model. The proposed method can be used in the future for treating atherosclerotic plaques in humans., Methods and Results: The plaque in the rabbits was created using high cholesterol diet for 4 months. The amount of plaque removed was studied as a function of intensity, with a fixed pulse repetition frequency (PRF), and duty factor (DF)., Conclusions: The amount of plaque removed is directly related to the acoustic intensity. It was found that the presence of bubbles accelerates the removal of plaque. In order to ensure that pure mechanical mode ultrasound was used, the intensity used does not produce temperatures that exceed 1°C.

Background: The potential of a magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) system combined with thrombolytic drugs to dissolve clots is investigated using in vitro and in vivo models., Methods: Two spherically focused transducers of 5 cm diameter focusing at 10 cm and operating at either .5 or 1 MHz were used. Doppler ultrasound was used to measure the blood flow during the in vivo experiments., Results: The effect of ultrasound intensity, transducer beam area, and frequency on the dissolved volume was investigated. The goal was to maintain a temperature increase of less than 1°C (called safe temperature) at the clot during the application of pulsed ultrasound and at the same time achieve efficient thrombolysis., Conclusions: The MRgFUS technique was proven successful in dissolving clots in vitro and in vivo. It was found that the volume of dissolved clot increases with acoustic intensity and beam size and decreases with frequency. With this system, it was possible to push ultrasound through a plastic phantom skull using a .5 MHz transducer. The beam of ultrasound through the phantom skull was monitored using the MRI technique of fast spoiled gradient. Finally, the thrombus in the in vivo model (ear artery) was successfully destroyed with the therapeutic protocols investigated in the in vitro models. This study shows that FUS using a single element MR-compatible transducer has the potential to treat clots in synergy with thrombolytic drugs. More advanced MRgFUS systems, such as phased arrays, will have a greater impact in sonothrombolysis., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: High-intensity focused ultrasound (HIFU) is a promising treatment method for many common cancers, including prostate cancer. Magnetic resonance image (MRI) guidance of HIFU permits targeting and monitoring of therapy. A prototype MRI-compatible positioning device that navigates a HIFU transducer was designed, fabricated and tested., Materials and Methods: The positioning device has two PC-controlled and one manually driven stage that allow endorectal access to the prostate. The positioning device was constructed using a 3-D rapid prototype manufacturing device. Software was developed that controls the motion of the positioning device and enables activation of a HIFU transducer. In vitro testing of the system was performed in a 1.5T MRI scanner using ex vivo turkey tissue. Optical encoders were employed to enhance the accuracy of this positioning device., Result: The positioning device was successfully tested for MRI compatibility. The movement error of the positioning device is approximately 20 [Formula: see text]m. The robot has the ability to accurately move the transducer for creation of discrete and overlapping lesions., Conclusion: An MRI-compatible HIFU positioning system was developed that has the ability to create thermal lesions with MRI guidance for endorectal treatment of prostate cancer.

The potential of magnetic resonance imaging-guided focused ultrasound (MRgFUS) combined with the thrombolytic drug recombinant tissue plasminogen activator (rt-PA) to dissolve clots in the carotid of a New Zealand rabbit in vivo is evaluated. A spherically focused transducer of 5-cm diameter, focusing at 10 cm and operating at 1 MHz, was used. A pulsed ultrasound protocol was used that maintains a tissue temperature increase of less than 1 °C in the clot (called safe temperature). MRgFUS has the potentials to dissolve clots that are injected in the carotid of rabbits in vivo. It was found that the time needed for opening the carotid artery using ultrasound and rt-PA was decreased compared with just using rt-PA. The time needed for opening the artery decreases with increasing acoustic intensity. With an intensity of 20 W/cm2 (spatial average temporal average), which is not causing artery heating, the time needed to completely open the artery was 70 minutes. The proposed protocol was monitored using magnetic resonance angiography every 1 minute., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate a flat rectangular (3×10mm(2)) MRI compatible transducer operating at 5MHz. The main task was to explore the feasibility of creating deep lesions in heart at a depth of at least 15mm. The size of thermal necrosis in heart tissue was estimated as a function of power and time using a simulation model. The system was then tested in an excised lamb heart. In this study, we were able to create lesions of 15mm deep with acoustic power of 6W for an exposure of approximately 1min. The contrast to noise ratio (CNR) between lesion and heart tissue was evaluated using fast spin echo (FSE). The CNR value was approximately 22 using T1W FSE. Maximum CNR was achieved with repetition time (TR) between 300 and 800ms. Using T2W FSE, the corresponding CNR was approximately 13 for the 14 in vivo experiments. The average lesion depth was 11.93mm with a standard deviation of 0.62mm. In vivo irradiation conditions were 6W for 60s. The size of the lesion in the other two dimensions was close to 3×10mm(2) (size of the transducer element)., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In this paper, we studied the effect of interfaces during the application of high intensity focused ultrasound (HIFU) ablation in rabbit kidney in vivo. In kidney ablation, mainly two types of interfaces are encountered: these are muscle-kidney and fat-kidney. It was observed that the intensity for which the probability of cavitation (POC) is one was decreased when HIFU penetrated through interfaces, meaning that an interface is a potential site of cavitation. We utilized the concept of scanning the area to be treated in two dimensions (rectangular grid) by applying low intensity ultrasound (diagnostic scan). When all the points of the grid show decrease of signal in T1-weighted fast spoiled gradient (FSPGR) which indicated heating, complete necrosis was observed in the targeted area during the application of HIFU (therapeutic scan). If ultrasound goes through an interface that includes air spaces, the diagnostic scan indicates spaces with poor ultrasound penetration and as a result, during the application of the therapeutic scan, some sites remain untreated. The muscle-kidney and fat-kidney interfaces cause reflection of ultrasound, which prevents the penetration of ultrasound. Microscopic bubbles in the interface may initiate cavitation, especially at high intensities. However, sometimes these types of interfaces do not include any bubbles and therefore the propagation of ultrasound is not inhibited.

The effectiveness of magnetic resonance imaging (MRI) to monitor therapeutic protocols of high-intensity focused ultrasound (HIFU), in freshly excised pig kidney cortex is investigated. For high quality imaging, the pulse sequence fast spin echo (FSE) T1- and T2-weighted, and proton density were evaluated. For fast imaging, the pulse sequence T1-weighted fast spoiled gradient (FSPGR) was used. The main goal was to evaluate the MRI detection of large lesions (bigger than 1 cm x 1 cm x 1 cm) that is achieved by moving the transducer in a predetermined pattern. The contrast between lesion and kidney tissue is excellent with either T1-weighted or T2-weighted FSE. With T1-weighted FSE, the best contrast is observed for recovery time (TR) between 200 ms and 400 ms. With T2-weighted FSE best contrast can be achieved for echo time (TE) between 16 and 32 ms. T2-weighted FSE was proven as the best pulse sequence to detect cavitational activity. This advantage is attributed to the significant difference in signal intensity between air spaces and necrotic tissue. Air spaces appear brighter than thermal lesions. Therefore, for therapeutic protocols created using cavitational mode, T2-weighted FSE may be the optimum pulse sequence to use. The proton density pulse sequence does not provide any advantage over the T1- and T2-weighted pulse sequences. Using T1-weighted FSPGR, acquisition time as low as 5 s could be achieved. Good contrast and signal-to-noise ratio (SNR) are achieved with TR = 100 ms and flip angle between 75 to 90 degrees. The above techniques were very successful in detecting large lesion volumes.

The aim of this paper is to present issues regarding the thermal ablation of porcine renal tissues in vitro and in vivo using high-intensity focused ultrasound (HIFU). Production of lesions in the cortex in vitro is consistent, whereas lesions in the medulla are created whenever there are no air spaces in the medulla. Typically, the lesion length at 2000 W/cm2 and 5-s pulse duration is around 20 mm and the corresponding width around 3 mm. Lesioning of a large volume was achieved by moving the transducer in a grid formation. Lesioning through a fat layer is possible provided that there are no air spaces between the fat and kidney interface. It was found that, above 3200 W/cm2 with 5-s pulse duration at 4 MHz, cavitation activity occurred in most of the lesions created.

The effect of temperature and thermal dose (equivalent minutes at 43 degrees C) on ultrasonic attenuation in fresh dog muscle, liver, and kidney in vitro, was studied over a temperature range from room temperature to 70 degrees C. The effect of temperature on ultrasonic absorption in muscle was also studied. The attenuation experiments were performed at 4.32 MHz, and the absorption experiments at 4 MHz. Attenuation and absorption increased at temperatures higher than 50 degrees C, and eventually reached a maximum at 65 degrees C. The rate of change of tissue attenuation as a function of temperature was between 0.239 and 0.291 Np m-1 MHz-1 degree C-1 over the temperature range 50-65 degrees C. A change in attenuation and absorption was observed at thermal doses of 100-1000 min, where a doubling of these loss coefficients was observed over that measured at 37 degrees C, presumably the result of changes in tissue composition. The maximum attenuation or absorption was reached at thermal dosages on the order of 10(7) min. It was found that the rate at which the thermal dose was applied (i.e., thermal dose per min) plays a very important role in the total attenuation absorption. Lower thermal dose rates resulted in larger attenuation coefficients. Estimation of temperature-dependent absorption using a bioheat equation based thermal model predicted the experimental temperature within 2 degrees C.

Time shifts in echo signals returning from a heated volume of tissue correlate well with the temperature changes. In this study the relationship between these time shifts (or delays) and the tissue temperature was investigated in excised muscle tissue (turkey breast) as a possible dosimetric method. Heat was induced by the repeated activation of a sharply focused high-intensity ultrasound beam. Pulse echoes were sent and received with a confocal diagnostic transducer during the brief periods when the high-intensity ultrasonic beam was inactive. The change in transit time between echoes collected at different temperatures was estimated using cross-correlation techniques. With spatial-peak temporal-peak intensities (ISPTP) of less than 950W/cm2, the delay versus temperature relationship was fit to a linear equation with highly reproducible coefficients. The results confirmed that for spatial-peak temperature increases of approximately 10 degrees C, temperature-dependent changes in velocity were the single most important factor determining the observed delay, and a linear approximation could produce accurate temperature estimations. Nonlinear phenomena that occurred during the high-intensity irradiation had no significant effect on the measured delay. At ISPTP of 1115-2698 W/cm2, the delay-temperature relationship showed a similar monotonically decreasing pattern, but as the temperature peaked its slope gradually increased. This may reflect the curvilinear nature of the velocity-temperature relationship, but it may also be related to irreversible tissue modifications and to the use of the spatial-peak temperature to experimentally characterize the temperature changes. Overall, the results were consistent with theoretical predictions and encourage further experimental work to validate other aspects of the technique.

Temperature changes in tissue, caused by high-intensity focused ultrasound, cause time shifts in the echoes that traverse the heated tissue. These time shifts are caused by thermally induced changes in the distribution of the velocity of sound and by thermal expansion within the tissue. Our analytical model relates these shifts to changes in temperature distribution. It is proposed that these relationships can be used as a method for the noninvasive estimation of temperature within the tissue. The model shows that the echo shifts depend mostly on changes in the mean velocity along the acoustical path of the echoes and that no explicit information about the shape of the velocity distribution is required. The effects of the tissue thermal expansion are small in comparison, but may be significant under certain conditions. The theory, as well as numerical simulations, also predicts that the time shifts have an approximately linear behavior as a function of temperature. This suggests that an empirical linear delay-temperature relationship can be determined for temperature prediction. It is also shown that, alternatively, the distribution of temperature in the tissue can be estimated from the distribution of echo delays along the acoustical path. In the proposed system, low-level pulse echoes are sampled during brief periods when the high-intensity ultrasonic irradiation is off, and thus linear acoustic behavior is assumed. The possibility of nonlinear aftereffects and other disturbances limiting this approach is discussed.

Rationale and Objectives: The ability of magnetic resonance imaging to detect small temperature elevations from focused ultrasound surgery beams was studied. In addition, the value of a contrast agent in delineating the necrosed tissue volume was investigated., Materials and Methods: Gradient-recalled acquisition in a steady state (GRASS) T1-weighted images were used to follow the temperature elevation and tissue changes during 2-minute sonications in the thigh muscles of 10 rabbits. The effects of the treatment on the vascular network was investigated by injecting a contrast agent bolus before or after the sonication., Results: The signal intensity decreased during the sonication, and the reduction was directly proportional to the applied power and increase in temperature. The signal intensity returned gradually back to baseline after the ultrasound was turned off. Injection of the contrast agent increased the signal intensity in muscle, but not in the necrosed tissue. The dimensions of the delineated tissue volume were the same as measured from the T2-weighted fast-spin-echo images and postmortem tissue examination., Conclusions: These results indicate that magnetic resonance imaging can be used to detect temperature elevations that do not cause tissue damage and that contrast agent can be used to delineate the necrosed tissue volume.

In order to quantify ultrasound therapy it is important to measure the tissue temperature during the treatment. Invasive probes induce several artifacts in ultrasound fields. The magnitude of these artifacts is probe dependent. Several different probes were evaluated for hyperthermia purposes in this study. An alternative noninvasive method to evaluate the temperature elevations and tissue damage is to use magnetic resonance imaging. The fast imaging sequences used in this study are marginally useful for monitoring hyperthermia. However, these imaging sequences can be utilized to guide and monitor ultrasound surgery.

To find a noninvasive method for estimating left ventricular end-systolic pressure, 40 patients were studied during cardiac catheterization. Arterial pressure was taken directly from the ascending aorta. Carotid pulse tracing and measurement of blood pressure by cuff sphygmomanometry were taken simultaneously. The tracings were calibrated and left ventricular end-systolic pressure was estimated directly and indirectly. Simple linear regression analysis gave the equations: (1) left ventricular end-systolic pressure direct = 0.56 left ventricular end-systolic pressure indirect + 43.8 (r = 0.61, P = 0.00004), and (2) left ventricular end-systolic pressure direct = 0.39 systolic arterial pressure indirect + 48.8 (r = 0.62, P = 0.00002). To test the accuracy of the technique the study was continued in 40 patients. Left ventricular end-systolic pressure was also estimated by the 2 equations. Left ventricular end-systolic pressure direct was correlated with left ventricular end-systolic pressure estimated by the 2 equations and there was no statistical difference. This noninvasive technique is a bedside method for clinical measurement of left ventricular end-systolic pressure.