Christakis Damianou

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.

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 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.

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 dogs 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 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.

Evaluation of accuracy of a theoretical model for predicting the necrosed tissue volume during focused ultrasound surgery

The concept of thermal dose as a predictor for the size of the necrosed tissue volume during high-intensity focussed ultrasound surgery was tested. The sensitivity of the predicted lesion size to the uncertainties in the iso-dose constant, attenuation coefficient, and thermal dose threshold of necrosis was studied. The predicted lesion size appears to be independent of attenuation at some high attenuation values and certain depth in tissue. Thus, for a given target depth, a proper selection of frequency could minimize the lesion size variability due to uncertainty in the tissue attenuation. The predicted lesion size was less dependent on the uncertainties in the iso-dose constant and thermal dose of necrosis. The predictions of the model were compared with experimental data in rabbit muscle, and experimental data in cat and rat brain measured by others. The agreement was found to be good in most of the experiments. Similarly, the model was found to predict well the trends of increasing power and pulse duration.<<ETX>>

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

Hynynen K, Darkazanli A, Damianou CA, Unger E, Schenck JF. 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) TI-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.

Application of the thermal dose concept for predicting the necrosed tissue volume during ultrasound surgery

The concept of calculated thermal dose was used to predict the size of the necrosed tissue volume during high-intensity focused ultrasound surgery. The model presented was verified using experimental data in rabbit muscle and cat brain. The agreement is good and therefore, this model can be used to give guidelines for the sonication prior to clinical ultrasound surgery

In vitro and in vivo ablation of porcine renal tissues using high-intensity focused ultrasound

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.