An improved method to estimate ultrasonic absorption in agar-based gel phantom using thermocouples and MR thermometry.

In this paper, a novel experimental set-up was developed that measures the absorption coefficient. The proposed system was evaluated in an agar-based gel phantom. The new experimental system provides accurate and fast measurement of the rate of temperature change within the phantom. The rate of temperature change was measured using thermocouple and was confirmed using MR thermometry. An ultrasonic transducer with a broad beam was used in order to reduce the conduction effect. The absorption coefficient of the agar-based phantom was 0.26 dB/cm-MHz using 4% agar, 30% evaporated milk and 4% silica. The absorption coefficient increased by increasing the volume of the evaporated milk, and agar. The absorption coefficient increased at low silica concentration (<4%) and then decreased at higher concentration of silica (>4%). By proper selection of evaporated milk, agar and silica concentration, it is possible to achieve similar coefficient like in soft tissues. Acoustic absorption measurement is considered as a difficult measurement in ultrasonics because obtaining the precise temperature change in the focus is challenging. Due to the quick and accurate placement of the thermocouple at the ultrasonic beam, it is possible with the proposed system to perform absorption measurement is less than one minute.

Evaluation of a small flat rectangular therapeutic ultrasonic transducer intended for intravascular use.

BACKGROUND: The aim of the proposed study was to evaluate the performance of a flat rectangular (2×10mm2) transducer operating at 4MHz. The intended application of this transducer is intravascular treatment of thrombosis and atherosclerosis. METHODS: The transducer's thermal capabilities were tested in two different gel phantoms. MR thermometry was used to demonstrate the thermal capabilities of this type of transducer. RESULTS: Temperature measurements demonstrated that this simple and small transducer adequately produced high temperatures, which can be utilized for therapeutic purposes. These high temperatures were confirmed using thermocouple and MR measurements. Pulsed ultrasound in combination with thrombolytic drugs and microbubbles was utilized to eliminate porcine thrombi. CONCLUSIONS: The proposed transducer has the potentials to treat atherosclerotic lesions using the thermal properties of ultrasound, since high temperatures can be achieved in less than 5s. The results revealed that the destruction of thrombi using pulsed ultrasound requires long exposure time and high microbubble dosage.

Longitudinal imaging of the ageing mouse.

Several non-invasive imaging techniques are used to investigate the effect of pathologies and treatments over time in mouse models. Each preclinical in vivo technique provides longitudinal and quantitative measurements of changes in tissues and organs, which are fundamental for the evaluation of alterations in phenotype due to pathologies, interventions and treatments. However, it is still unclear how these imaging modalities can be used to study ageing with mice models. Almost all age related pathologies in mice such as osteoporosis, arthritis, diabetes, cancer, thrombi, dementia, to name a few, can be imaged in vivo by at least one longitudinal imaging modality. These measurements are the basis for quantification of treatment effects in the development phase of a novel treatment prior to its clinical testing. Furthermore, the non-invasive nature of such investigations allows the assessment of different tissue and organ phenotypes in the same animal and over time, providing the opportunity to study the dysfunction of multiple tissues associated with the ageing process. This review paper aims to provide an overview of the applications of the most commonly used in vivo imaging modalities used in mouse studies: micro-computed-tomography, preclinical magnetic-resonance-imaging, preclinical positron-emission-tomography, preclinical single photon emission computed tomography, ultrasound, intravital microscopy, and whole body optical imaging.

Review of MRI positioning devices for guiding focused ultrasound systems.

BACKGROUND: This article contains a review of positioning devices that are currently used in the area of magnetic resonance imaging (MRI) guided focused ultrasound surgery (MRgFUS). METHODS: The paper includes an extensive review of literature published since the first prototype system was invented in 1991. RESULTS: The technology has grown into a fast developing area with application to any organ accessible to ultrasound. The initial design operated using hydraulic principles, while the latest technology incorporates piezoelectric motors. Although, in the beginning there were fears regarding MRI safety, during recent years, the deployment of MR-safe positioning devices in FUS has become routine. Many of these positioning devices are now undergoing testing in clinical trials. CONCLUSION: Existing MRgFUS systems have been utilized mostly in oncology (fibroids, brain, liver, kidney, bone, pancreas, eye, thyroid, and prostate). It is anticipated that, in the near future, there will be a positioning device for every organ that is accessible by focused ultrasound.

MR compatible positioning device for guiding a focused ultrasound system for the treatment of brain deseases.

BACKGROUND: A prototype magnetic resonance imaging (MRI)-compatible positioning device that navigates a high intensity focused ultrasound (HIFU) transducer is presented. The positioning device has three user-controlled degrees of freedom that allow access to brain targets using a lateral coupling approach. The positioning device can be used for the treatment of brain cancer (thermal mode ultrasound) or ischemic stroke (mechanical mode ultrasound). MATERIALS AND METHODS: The positioning device incorporates only MRI compatible materials such as piezoelectric motors, ABS plastic, brass screws, and brass rack and pinion. RESULT: The robot has the ability to accurately move the transducer thus creating overlapping lesions in rabbit brain in vivo. The registration and repeatability of the system was evaluated using tissues in vitro and gel phantom and was also tested in vivo in the brain of a rabbit. CONCLUSION: A simple, cost effective, portable positioning device has been developed which can be used in virtually any clinical MRI scanner since it can be placed on the table of the MRI scanner. This system can be used to treat in the future patients with brain cancer and ischemic stroke.

Dependence of ultrasonic attenuation and absorption in dog soft tissues on temperature and thermal dose.

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.

Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part I. Analytical model.

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.

Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part II. In vitro study.

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.

MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies.

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.

Histologic effects of high intensity pulsed ultrasound exposure with subharmonic emission in rabbit brain in vivo.

In this study, the threshold for subharmonic emission during in vivo sonication of rabbit brain was investigated. In addition, the histologic effects of pulsed sonication above this threshold were studied. Two spherically curved focused ultrasound transducers with a diameter of 80 mm and a radius of curvature of 70 mm were used in the sonications. The operating frequencies of the transducers were 0.936 and 1.72 MHz. The sonication duration was varied between 0.001 and 1 s and the repetition frequency between 0.1 and 5 Hz. The threshold for subharmonic emission at the frequency of 0.936 MHz was found to be approximately 2000 W cm-2 and 3600 W cm-2 for pulse durations of 1 s and 0.001 s, respectively. The threshold was approximately 1.5-fold as high at a frequency of 1.72 MHz. However, there was considerable variation from experiment to experiment. The multiple pulse experiments at a frequency of 1.72 MHz and an intensity of 7000 W cm-2 showed that the histologic effects ranged from no observable damage of the tissue, to blood-brain barrier breakage, to local haemorrhagia, to local destruction of the tissue, to gross hemorrhage resulting in the death of the animal. The severity of the tissue damage increased as the pulse duration, number of pulses and their repetition frequency increased. The results indicate that the end point of the tissue damage may be controlled by selecting the sonication parameters. Such control over tissue effects can have several different applications when brain disorders are treated.

The usefulness of a contrast agent and gradient-recalled acquisition in a steady-state imaging sequence for magnetic resonance imaging-guided noninvasive ultrasound surgery.

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.

The effect of various physical parameters on the size and shape of necrosed tissue volume during ultrasound surgery.

The purpose of this study was to test the concept of using calculated thermal dose as a predictor for the necrosed tissue volume. A parametric study was conducted where the sonication parameters (pulse duration, power), transducer parameters (frequency, F number) and tissue properties (perfusion rate, attenuation) were varied and their effect on the lesion size was investigated. In vivo experiments where a focused ultrasound beam was used to induce tissue necrosis in thigh muscle of dog and rabbit were also conducted to obtain the reliability of the predictions. The experimental and simulated lesion sizes compared well. From the parametric study the threshold intensity for 1- and 5-s sonications were found to be about 1000 and 400 W/cm2, respectively. It was found that the lesion size was practically perfusion independent for pulses 5 s or shorter. The lesion size increases with increased pulse duration, acoustical power, and F number, but decreases with increased frequency provided that the focal intensity is kept constant. It was found also that the deeper the focus is in the tissue, the smaller the frequency range that causes selective tissue necrosis in the focal zone.

Pulse duration and peak intensity during focused ultrasound surgery: theoretical and experimental effects in rabbit brain in vivo.

The goal of this study was to establish the exposure parameters that will generate predictable thermally induced lesions in brain. In addition, the accuracy of a theoretical model for prediction of the lesion size was tested. To do this, 160 adult rabbits were sonicated (frequency 0.936 and 1.72 MHz) and then sacrificed at various intervals after the sonications. The results showed that predictable thermal lesions could be induced if the exposure durations were between 0.5 and 2 s. Dimensions of the necrosed tissue volume were roughly predictable by the theoretical calculations based on purely thermal effects. Shorter sonications required higher intensities (above 3700 W cm-2 at 1.72 MHz) resulting in mechanical effects with extensive vascular damage. Lesion size varied more at longer exposures (5 and 10 s), perhaps due to the increased effect of tissue perfusion. As a conclusion, focused ultrasound can be used for destruction of tissues deep in brain without causing undesirable mechanical effects, if the exposure parameters are selected properly.

Tissue thermometry during ultrasound exposure.

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.

Focal spacing and near-field heating during pulsed high temperature ultrasound therapy.

It has been proposed that high temperature short duration hyperthermia treatment would be perfusion insensitive and thus, significantly improved thermal exposure uniformity could be achieved. This study investigates the execution of such a treatment, which utilizes single spherically curved transducer and multiple sonications to cover the complete target volume. The spacing of neighboring pulses as a function of the transducer characteristics was studied utilizing computer simulations. In addition, the temperature elevation in front of the focal zone during multiple sonications was evaluated. It was found that significant delays (20 s or longer) between the sonications must be introduced in order to avoid unwanted tissue damage in front of the focal zone. In addition, decreasing the pulse duration and F-number reduced the temperature build-up in front of the focus. The results were verified in vivo in dog's thigh muscle. This study is important not only for hyperthermia but also for ultrasound surgery, and indicates that each sonication system must be carefully evaluated for potential thermal damage outside of the target volume prior to implementation in therapy.

Noninvasive determination of the left ventricular end-systolic pressure.

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.