Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling
A diagram of the experimental setup that was used to produce HIFU lesions and monitor cavitation and boiling bubbles in transparent polyacrylamide gel and ex vivo tissue.
In situ HIFU waveforms at different power outputs, modeled (thin line) and measured by the FOPH behind a 12-mm-thick layer of bovine heart tissue (thick line). The corresponding intensity and power levels are listed in Table I (exposures 1, 2, and 3 in the heart). High amplitude shock fronts are evident in the waveforms at higher outputs (2 and 3). The pressure waveform is distorted at the lowest output power used in this study but shocks are not fully developed (1).
Determination of the nonlinear parameter β* in ex vivo heart tissue samples by comparing the spectra of the focal waveform measured in tissue (black dots) and derated from the modeling. The spectra correspond to the waveform 1 shown in Fig. 2. The best match was obtained when using β* = 4.
High-speed images of HIFU pulsing in a transparent 7% BSA polyacrylamide gel during the first (on the left) and fifth (on the right) pulses. The frames were recorded at 20 000 frames per second (fps) with a 4 μs shutter speed; the frame taken at 0 ms corresponds to the start of each pulse. The HIFU source was on the left. The exposure parameters were: 2.158 MHz HIFU frequency, 10 ms pulse length, 1 Hz pulse repetition rate (PRF), MPa and MPa (Table I). The start of boiling within each pulse is evident by the large millimeter-sized bubble that appears at the focus after 3.9 ms in the first pulse and in 2.7 ms in the fifth pulse. The shorter boiling time in the fifth pulse is likely due to an increased ambient temperature from the applied pulses relative to the first pulse. The images in the bottom row are enlarged versions of the white boxes that show cavitation bubbles moving through and beyond the focus (left) and a multi-layered cavitation bubble cloud forming in front of the boiling bubble due to reflection of the shock wave from the bubble surface (right). Bubble layers are spaced at approximately half the HIFU wavelength (0.35 mm) as indicated by the arrows at the bottom of the frame (Ref. 24).
High-speed camera images of lesion evolution in a polyacrylamide gel during pulsed HIFU exposures with 10 ms pulses and a 0.01 duty factor (same parameters as in Fig. 2). Images were recorded at 9.5 ms of each 10 ms pulse (left column) and 1 s after each pulse, immediately prior to the subsequent pulse (right column). A large boiling bubble forms during each 10 ms pulse (as shown in Fig. 2), but dissolves in the one second interval between pulses. Several smaller (tens of microns) residual bubbles remain between pulses and are evident in the frames on the right. These bubbles are largely pushed beyond the focus and away from the acoustic axis by the start of the subsequent pulse, collecting at the periphery of the lesion. The residual void of eroded gel is outlined in the right column for better visibility. Explosive growth of the bubble itself and also generation of high negative pressures caused by reflection of the shock wave from the bubble can contribute to tearing of the gel and lesion growth. The images were enhanced by zooming and altering the lighting to enhance the appearance of the residual void (bottom image), which contained gel pieces and infiltrated liquid and was no longer intact gel.
B-mode images in a gel phantom at different time points during a pulsed exposure with the same parameters as used in Figs. 4 and 5: (a) 40 ms after the first pulse; (b) immediately prior to the second pulse; (c) 40 ms after the 10th pulse; (d) 40 ms after the 50th pulse. The needle in the lower right corner of the images was used for alignment purposes. A larger scale photo inset on the top (a) was taken at 10 ms and corresponds to the very end of the first HIFU pulse. The image shows the boiling bubbles at the focus and cavitation bubbles scattered throughout the hour-glass shape of the beam that creates a slight echogenicity on B-mode images but which disappeared shortly after the pulse (within 100–400 ms). Although no large boiling bubbles were evident between HIFU pulses in Fig. 3, the B-mode images showed a persistent echogenic region that continued to grow over 50 pulses (b–d). The second photo inset (on the bottom) confirms that the source of persistent echogenicity is the remnants of boiling bubbles pushed to the back and to the sides of the focus. The residual void is outlined for better visibility.
(a) Selected frames of ultrasound B-mode images of ex vivo bovine heart tissue recorded during pulsed HIFU sonication (exposure 3 in Table I). Similar to images in gel (Fig. 6), echogenicity in tissue appears with the very first pulse as boiling bubbles are induced by HIFU. (b) Recording of the transducer voltage during the first pulse of exposure gives further evidence that bubble activity is specifically boiling: fluctuations in the signal occurred at 4 ms during the 10 ms pulse, in agreement with theoretical estimations of the time-to-boil. (c) The lesions produced by four consecutive independent exposures were voids that were almost identical in size and shape, filled with liquefied tissue (evacuated from the voids in the photo), with no visible signs of thermal denature. The tadpole shape of the lesions was similar to the echogenic region observed in B-mode images (a).
(Color online) Types of lesions produced by different HIFU pulsing schemes in ex vivo bovine heart tissue. (a) Type 1: void with no signs of thermal damage filled with liquefied tissue (top photo) that can be poured out (bottom photo). With an increase of pulse duration and/or duty factor, the lesion transforms into (b) type 2: void with coagulated edges, filled with white paste (top photo), that can be easily removed (bottom photo). With a further increase in pulse duration and/or duty factor, the result is (c) type 3: a solid thermal lesion with an evaporated core.
(Color online) Cross section in the axial plane of lesions induced in bovine heart using 50 HIFU pulses of 10 ms duration, 1 Hz PRF, and increasing power to the HIFU source (from left to right). In situ HIFU waveforms for the lesions 1, 2, and 3 are shown in Fig. 1 and details of the exposure parameters are listed in Table I with the same numbering. No lesions were produced when the focal waveform corresponded to 1 (Fig. 2), as the heating rate was not sufficient to initiate boiling within each pulse as shocks were not yet formed at the focus. At higher outputs (cases 2, 3, and in between them grouped under “A”), shocks were present at the focus (see Fig. 1), boiling was induced within each pulse, and emulsified lesions were produced. The peak negative pressure changed only slightly between exposures 1, 2, and 3; therefore, cavitation activity was only minimally altered. The results from this experiment thus demonstrate that liquefied voids were only observed when shocks and boiling were present.
(Color online) Axial cross-sections of liquefied lesions obtained in ex vivo bovine liver using HIFU transducers of the same geometry but operating at different frequencies: (a) 1.1 MHz, (b) 2.158 MHz, and (c) 3.4 MHz. To balance the comparison, the transducer f-number = 1, the in situ focal pressure ( MPa, MPa), duty factor (0.01), and total HIFU on time (500 ms) were the same for all three exposures. In addition, pulse lengths were approximately three times longer than the time-to-boil for each frequency: 20 ms, 10 ms and 5 ms, respectively. Larger lesions were obtained with lower frequencies and the total lesion size followed the dimensions of the heated focal region for each transducer.
Summary of exposure parameters in gel and in bovine heart tissue.a
Effect of pulse duration and duty factor on the type of lesion produced in ex vivo heart samples: type 1—void filled with liquefied tissue with no signs of thermal denaturation in the filling or tissue surrounding the void; type 2—void with coagulated edges, filled with white paste that represents partially coagulated, emulsified tissue; type 3—solid thermal lesion with a vaporized core.
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