An acoustic backscatter-based method for estimating attenuation towards monitoring lesion formation in high intensity focused ultrasound

An experimental study on the stiffness of size-isolated microbubbles using atomic force


INTRODUCTION
Currently, one of the most common and promising noninvasive modality for high-temperature thermal therapy is high intensity focused ultrasound (HIFU).The purpose of monitoring HIFU treatment is to ensure that the target volume is completely treated (thermally damaged), and to ensure the safety of sensitive structures near or outside the target volume.Monitoring should be conducted in real-time and using a closed loop system.X-ray imaging, magnetic resonance imaging (MRI), and ultrasound imaging have all been used as noninvasive methods for monitoring and assessment of tissue thermal damage in HIFU surgeries [1].
In studies conducted on changes in ultrasound tissue attenuation coefficient as a function of temperature or thermal dose [2][3][4], it was observed that as the temperature of tissue rose, and ultimately, as the tissue coagulated, there was a dramatic increase in ultrasound attenuation slope, ȕ, and ultrasound attenuation intercept, Į 0 .This provided the possibility that changes in the frequency dependent ultrasound attenuation as a function of temperature and thermal dose might be exploited for monitoring HIFU procedures, and gaining more information about the location and size of the thermal damage within the tissue [3,[5][6][7][8][9].In monitoring HIFU using ultrasound attenuation estimation, ultrasound attenuation slope and attenuation intercept measurements are directly applied to the region of interest in the tissue through analysis of the RF backscattered ultrasound signal, resulting in differentiation of normal and thermally coagulated regions of the tissue.
In this study, a system capable of acquiring backscattered ultrasound RF data in the pre, during, and post phases of HIFU procedures was designed and developed.In addition, two frequency domain algorithms were developed to estimate attenuation slope and attenuation intercept.The two algorithms were capable of quantitatively estimating changes in tissue attenuation using the acquired backscattered ultrasound RF data.The purpose of the study was to show that changes in the attenuation of HIFU lesions can be estimated with respect to initial attenuation of normal tissue, using the acquired backscattered RF data.Using the two algorithms, the transient characteristics of tissue attenuation coefficient parameters (ǻȕ and ǻĮ 0 ) as a function of HIFU exposure time, at different total acoustic powers in ex vivo porcine muscle tissues, were investigated.Finally, ǻȕ and ǻĮ 0 images (attenuation maps) were generated, and correlated with B-mode images.The HIFU lesion imaging performance of these attenuation maps were compared with each other and with conventional B-mode imaging.

MATERIALS AND METHODS
The experiments were conducted on fresh ex vivo porcine muscle tissues.The muscle specimens were cut and trimmed to 20×80×100 mm, and stored in degassed, deionized water at 5ÛC for 12 hours prior to conducting the experiment.This ensured that most preexisting gas bubbles were transferred from the tissue into the degassed water.The HIFU transducer was installed inside a water tank filled with degassed deionized water at room temperature.The imaging probe was installed confocally through an opening at the center of the HIFU transducer (Fig. 1(f-g)).The specimens were mounted on a tissue holder for HIFU treatment.The tissue in the tissue holder was then submerged in the tank at the focal region such that it would cover the entire focal area.Enough time was allocated for the tissue inside the water tank to reach room temperature.An acoustic absorber was placed at the end of the water tank to absorb acoustic waves, and prevent any reverberations within the water tank.
A single element HIFU transducer (Model 6699A101; Imasonic S. A., Voray sur l'Ognon, France) with a resonant frequency of 1 MHz was used throughout this study.The transducer had a 125 mm diameter of aperture, and a 100 mm geometric focal length (radius of curvature).The measured axial and lateral focal width of the HIFU transducer were 8 mm and 2 mm at full width at half maximum (FWHM), respectively.The radio frequency (RF) signal driving the HIFU transducer was generated by an arbitrary function generator (Model AFG3010; Tektronix, Beaverton, OR, USA).The RF signal was amplified by a class-A broadband RF power amplifier (Model A150; E&I, Rochester, NY, USA).The efficiency of the transducer was measured to be 64% for input electric powers in the range of 0.8 W to 157 W. For total acoustic powers (TAP) of 34, 37, 39, 44, and 49 W, used in this study, the HIFU transducer generated free field (in water) spatially averaged focal intensities (I SA ) of 737, 801, 845, 961, and 1068 W/cm 2 , respectively.
An ultrasound imaging system (SonixRP ® scanner, Ultrasonix Inc., Richmond, BC, Canada) and an endocavity array probe (EC9-5/10, Ultrasonix Inc., Richmond, BC, Canada) with 128 elements, a center frequency of 7 MHz, and bandwidth of 3 MHz, were used for acquisition of B-mode images, and RF backscattered data.In order to acquire RF backscattered data throughout all phases of treatment, a micro-controller (Model M68HC11; Motorola, Inc., Schaumburg, Illinois, USA) was used to synchronize various components of the experimental setup.RF data were acquired pre, during, and post HIFU treatments to estimate the initial, transient, and final  The visualization of lesion formation is directly correlated with the B-mode images formed from the pulse-echo RF data, shown in Fig. 3(a), with the HIFU transducer being on top.Fig. 3(b) shows the corresponding ǻĮ 0 images, and Fig. 3(c) shows the corresponding ǻȕ images generated using the same RF data.Every frame represents a 2-D map of change in attenuation inte im e high intensity regions in the ǻĮ , and ǻȕ images remain visible.To quantitatively compare the pe rcept (ǻĮ 0 ) and least squares attenuation coefficient slope (ǻȕ), respe ly.After the treatment, the bright hyperechoic region in the focal region visible in the B-mode ages gradually fades, and after 10 minutes it is hardly visible.However, after 10 minutes, th ctive 0 rformance of the attenuation slope (ǻȕ) and attenuation intercept algorithms (ǻĮ 0 ) with each other, and further with conventional B-mode imaging, the contrast to speckle ratios (CSR) [11] of all three different modes of generating images in this study are investigated.The CSR is defined as: where, S in is the mean signal measured inside the region of interest, S out is the mean signal measured from same-sized regions outside the region of interest, and ı 2 in and ı 2 out represent the va

CONCLUSIONS
We have obtained preliminary data for the changes in attenuation coefficient induced in ex vivo porcine muscle tissues due to coagulation.Changes in attenuation coefficient slope (ǻȕ) and attenuation coefficient intercept (ǻĮ 0 ) are both potentially reliable indicators of tissue thermal damage.riances of the signal within and outside of the region of interest, respectively [11].Fig. 4 shows CSR values for lesions created at different total acoustic powers for frames acquired less than 10 minutes after the end of HIFU treatment (representing steady state conditions due to the absence of boiling bubbles, and no temperature rise).
The transient characteristics of attenuation coefficient slope and attenuation coefficient intercept were simultaneously investigated in a novel approach.In this new approach, based on a simplified model, ǻȕ and ǻĮ 0 values for any given location were estimated as functions of time and location, with respect to pre-treatment values of ȕ and Į 0 at that same location, before, during and after HIFU treatment at different HIFU powers, using pulse-echo ultrasound RF signals.
The rapid increases in attenuation slope and intercept were generally accompanied by some fluctuations due to rapid rises in temperature and the bubble activities.Violent bubble activities were evident as hyperechoic regions in the B-mode images at the HIFU treatment sites.The performance of the B-mode images relied more on the effects of bubble activities than that of the ǻȕ and ǻĮ 0 images.The dynamic changes of attenuation coefficient parameters (ǻȕ and ǻĮ 0 ) and evaluation of HIFU-induced al tissue damage to the dynamic changes in attenuation coefficient parameters (ǻȕ

FIGURE 2 .
FIGURE 2. (a) Dynamic changes of ǻĮ 0 and (b) Dynamic changes of ǻȕ (spatially averaged in ROI) in ex vivo porcine muscle tissue during HIFU treatment, for monitoring duration of 10 min, duty cycle was 77% for a total HIFU treatment time of 40 s, and TAP values were 34, 37, 39, 44, and 49 W.

Fig. 2 (
Fig. 2 (a-b) show the dynamic changes of attenuation intercept and attenuation slope, respectively, as functions of HIFU treatment time in ex vivo porcine muscle tissue at different input electric powers.These figures provide a quantitative assessment of the changes in Į 0 and ȕ for duration of 10 minutes.The visualization of lesion formation is directly correlated with the B-mode images formed from the pulse-echo RF data, shown in Fig. 3(a), with the HIFU transducer being on top.Fig. 3(b) shows the corresponding ǻĮ 0 images, and Fig. 3(c) shows the corresponding ǻȕ images generated using the same RF data.Every frame represents a 2-D map of change in attenuation inte

FIGURE 3 .
FIGURE 3. Lesion growth in degassed ex vivo porcine muscle tissue in (a) conventional B-mode images (b) ǻĮ 0 images, and (c) ǻȕ images, where the duty cycle was 77%, resulting in TAP of 49 W, and average focal intensity of 1068 W/cm 2 at the HIFU treatment site, for a total HIFU treatment time of 40 s

FIGURE 4 .
FIGURE 4. Comparison of contrast to speckle ratios at various total acoustic powers, less than 10 minutes after the end of HIFU treatment