Saber
Izak Ghasemian
*ab,
Fabian
Reuter
a,
Yuzhe
Fan
b,
Georg
Rose
bc and
Claus-Dieter
Ohl
ab
aInstitute of Physics, Otto-von-Guericke Universität, Magdeburg, Germany. E-mail: saber.izak@ovgu.de
bResearch Campus STIMULATE, Otto-von-Guericke Universität, Magdeburg, Germany
cInstitute of Medical Engineering, Otto-von-Guericke Universität, Magdeburg, Germany
First published on 22nd November 2023
Elastography is a non-invasive technique to detect tissue anomalies via the local elastic modulus using shear waves. Commonly shear waves are produced via acoustic focusing or the use of mechanical external sources, shear waves may result also naturally from cavitation bubbles during medical intervention, for example from thermal ablation. Here, we measure the shear wave emitted from a well-controlled single laser-induced cavitation bubble oscillating near a rigid boundary. The bubbles are generated in a transparent tissue-mimicking hydrogel embedded with tracer particles. High-speed imaging of the tracer particles and the bubble shape allow quantifying the shear wave and relate it to the bubble dynamics. It is found that different stages of the bubble dynamics contribute to the shear wave generation and the mechanism of shear wave emission, its direction and the efficiency of energy converted into the shear wave depend crucially on the bubble to wall stand-off distance.
E = 2ρVs2(1 + ν). | (1) |
A crucial step in shear wave elastography concerns the generation of the shear waves in tissue. A very elegant technique that is widely used is the acoustic radiation force impulse technique.7 There, focused ultrasound push beams is used to create local displacement in the tissue from which a shear wave emerges. Other techniques are external mechanical vibrations,8 in conductive media Lorentz forces,9 and nucleation of bubbles from electrolysis.10 Also, cavitation bubble collapses near a tissue-air boundary have been shown to generate shear waves.11
In the current work, we show that the non-spherical dynamics of a cavitation bubble near a rigid boundary with is expected to occur at a hard tissue or near a bone, also generates shear waves. These cavitation-generated shear waves are measured with high-speed optical imaging of the motion from tracer particles. We then correlate this motion to the bubble dynamics using high-speed imaging. Single bubbles are conveniently generated at a variable distance from a rigid boundary through a pulsed and focused laser beam.
Our interest on the possibility that cavitation bubbles may excite shear waves is motivated by the rather common occurrence of bubble nucleation in a variety of medical procedures such as high intensity focused ultrasound (HIFU),12,13 histotripsy,14,15 laser lithotripsy16,17 and thermal ablation of tumours,18,19 to name a few. Also, cavitation has been reported to occur within the brain following the impact of the skull,20 as well as in synovial fluid during joint cracking.21,22
A sketch of the experimental setup is shown in Fig. 1. A single laser-induced cavitation bubble is created by focusing a collimated laser pulse (Litron Nano series, Q-switched Nd:YAG, 6 ns, wavelength 532 nm) with a microscope objective (Mitutoyo 50×, NA = 0.42, nominal working distance 20.5 mm) through the bottom of the cuvette into the thin, about 1 mm thick, layer of graphite particles. For optical index matching, the microscope objective output aperture and the cuvette are submerged in water for optical index matching. In the focal region of the objective, the bubble is generated through optical breakdown, i.e. by plasma generation.
An important quantity for characterizing the bubble dynamics is the distance of the bubble from the boundary. Here, we normalize this stand-off distance with γ = d/Rmax, where d is the distance of centre of plasma to the solid boundary and Rmax is the bubble radius at maximum expansion. Rmax is measured in the direction perpendicular to the solid, as discussed in ref. 24. The bubble dynamics and the particle motion are recorded with a high-speed camera (Photron, FASTCAM Mini, AX200) equipped with a macro lens (Canon MP-E 65 mm f/2.8 1 − 5× Macro) with a pixel resolution of 6.6 μm per pixel. Additionally, to resolve the much faster bubble dynamics, a Shimadzu HPV-X2 high-speed camera is used at 500000 frames per second. Again, it is equipped with the same macro lens resulting at a pixel resolution of 6.5 μm per pixel. The timing of the laser and the high-speed camera is controlled with a digital delay generator (BNC 525, Berkeley Nucleonics).
Fig. 1b presents a selected image of a cavitation bubble with the axis of symmetry at r = 0. The shear wave generation can be considered symmetric, as shown in Appendix A, thus, here we record and process the shear wave only within the blue window. This allows for camera recordings at higher resolutions to obtain more accurate measurements of the of displacement. The displacement field is obtained using PIVlab which is an open source MATLAB toolbox to perform PIV with image data.25 We use FFT window deformation algorithm with three passes and deforming windows with 64, 24 and 16 interrogation areas with 50% overlap for each window. Sub-pixel estimation is performed using a Gauss 2 × 3 point sub-pixel estimator, which fits a Gaussian function to the integer intensity distribution.26 Prior PIV analysis, the images are inverted and background subtracted with a rolling ball background subtraction (radius of 20 pixels). Once the particle velocity is extracted from the images, we can estimate the kinetic energy density of the propagating shear wave. For this, we have to assume a cylinder symmetry of the displacement field around the axis of symmetry, i.e. r = 0. Then the energy density per cross-sectional area e at point (r, z) is calculated as where ρ = 1000 kg m−3 is the mass density, and Vr and Vz are the horizontal and vertical components of the speed at point (r, z). This way, the entire cylindrical volume is considered.
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Fig. 2 Dynamics of laser-induced cavitation bubbles in a tissue-mimicking material for three different stand-off distances γ, recorded at 500![]() |
The location of the solid boundary of the experiment is indicated with a dashed line at the bottom of each frame, which restricts the deformation of the gelatin sample around the bubble. Each bubble is nucleated at time t = 0. For γ = 1.85 shown in Fig. 2a, the bubble expands spherically to a maximum radius of Rmax = 566 ± 6 μm at t ≈ 47 μs. As the bubble shrinks, its shape becomes increasingly non-spherical and an axial jet towards the solid boundary develops during the collapse. This jet results in the bubble indentation in the axial direction, visible for example in the frame just before the bubble collapse (t = 99 μs). This jetting phenomenon is commonly observed for bubbles collapsing in liquids close to solids.27
Reducing the stand-off distance to γ = 0.97, see Fig. 2b, the bubble expansion is not spherical anymore. The bubble reaches a maximum radius Rmax = 555 ± 6 μm, and collapses at t ≈ 108 μs. The instance of collapse can be determined with a higher precision than the interframe time of 2 μs via backtracking of the shockwave emitted during collapse. The shockwave is clearly imaged with the very short illumination using shadowgraphy. As a result, the collapse occurred at t = 108 μs. Looking at the frame just before the collapse, the bubble indentation in the axial direction is wider than the previous case, suggesting a wider jet flow.
At the smallest stand-off, i.e. γ = 0.11, the bubble reaches a maximum radius of Rmax = 720 ± 6 μm and collapses at t ≈ 116 μs (see the shockwave Schlieren), see Fig. 2c. In this stand-off regime, a considerably different bubble dynamics develops. It results in the formation of a so-called needle jet, as shown for the case of water.28,29 It results from a planar, and initially boundary-parallel jetting flow, see the kink at t = 108 μs. In contrary to the previous cases, the bubble indentation during collapse is not in axial but in the radial direction now, as clearly visible at time t = 110 μs. Once this radial jet impacts on the axis of symmetry, a high speed needle-like jet forms and impacts axially onto the boundary. This is not resolved in Fig. 2c and occurs between t = 110 μs and t = 116 μs.
We have now a look at the shear waves generated from these three cases of far, intermediate and short stand-off distance. Therefore, the graphite particles were added to the samples as described in the experimental section. Fig. 3 depicts the propagation of the energy density associated with the shear wave for the three different stand-off cases. Please note that the stand-offs slightly differ from the previous figure but the dynamics is still representative to the respective cases. The time t = 0 refers to the instance of bubble generation, and we only show frames for t > 474 μs for the first two cases and t > 148 μs for the third case, thus after the bubble collapse. From these times onward, the shear field has propagated sufficiently, such that it can be well-resolved with the present setup. The shock wave is not visible in these series as the speed of sound is about 1483 m s−1, thus much larger than the shear velocity, such that the shock wave has already propagated out of the imaging frame 1.1 μs after its generation at the instance of collapse.
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Fig. 3 Temporal evolution of areal energy density of the shear wave for three different stand-off distances γ, corresponding animations are provided in the ESI† as Movies M4–M6. For each stand-off distance, the location of the shear measurements with respect to the bubble is shown on the left. The bubble is depicted just prior collapse, and the stand-off distance d is indicated. The shear maps are analysed in the blue box, see also Fig. 1b. The Poynting vector of the shear wave indicates the direction of energy flux, and its direction is shown on the first frame of each case. The directions of the Poynting vectors are obtained from the linear motion of the shear wave fronts, see for example the slopes of the dashed lines in Fig. 4b and c. For the large stand-off case, γ = 1.75, the shear wave propagates mostly parallel to the boundary, while for the small stand-off case (γ = 0.15) it propagates mostly in the vertical direction, i.e. perpendicular to the boundary. For the intermediate case, γ = 0.97, a superposition of a boundary-perpendicular and a boundary-parallel wave is observed. We show the vertically propagating shear with “VS” and the horizontally propagating shear wave with “HS” at t = 563 μs. |
For γ = 1.75, a shear wave is emitted in horizontal direction. Its propagation velocity is Vs = 1.84 ± 0.12 m s−1. For the estimation of the uncertainty in the magnitude, we assume that the position of the shear wave front is detected with an uncertainty of 1/3 PIV window size. This velocity is in agreement with previous works using a similar gelatin recipe by Rapet et al.11 who found Vs = 1.8 m s−1. From the propagation velocity, we calculate an elastic modulus of 9.8 kPa for our gelatin sample, using eqn (1) with ρ = 1000 kg m−3 and ν = 0.45.11
Before studying the intermediate distance, we look at the closest distance γ = 0.15 (bottom graph). Here, unlike in the previous case, the shear wave is propagating approximately in the vertical direction and this shear pulse is much more energetic. The total energy amounts for 0.4 μJ in one quadrant, which is 7 times higher than in the γ = 1.75 case. Also, the wave geometries are disparate. While the γ = 0.15 case appears to produce a plane wave, the γ = 1.75 case emits a wave that is partially spherically shaped.
For the intermediate stand-off distance, γ = 0.97, a more complex pattern is found. It can be unraveled as a superposition of two shear waves, namely, one that propagates about parallel to the boundary (HS) and one that propagates about perpendicular to the boundary (VS). This suggests that in the intermediate case both shear wave generation mechanisms occur. Here, they produce shear waves of approximately equal energy. The total shear energy in one quadrant is about 3 times larger than for the γ = 1.75 case.
To further elucidate the origin of the shear wave, we correlate the shear wave emission with the bubble dynamics. First, we track the shear front in space and time. Linear extrapolation of the shear wave trajectory allows following the shear wave back in space and time and localize its origin. Fig. 4 illustrates the propagation of shear waves in space and time for the large (γ = 1.75) and small (γ = 0.15) stand-offs in black and blue, respectively. The time t = 0 denotes the bubble generation, and the coordinate z = 0 denotes the position of the solid wall.
Fig. 4a plots the shear wave trajectories along with the respective bubble shapes at maximum expansion. As the centroid of shear generation must coincide with the linear extrapolations, it follows that in the large stand-off case the shear wave was generated close to the bubble generation region, i.e., the centre of the expanded bubble, while in the small stand-off case the shear was generated much closer to the solid wall and outside the maximum bubble expansion region.
Further insight is provided by Fig. 4b, where the positions z(t) and r(t) are plotted for the large stand-off case. They denote the coordinates of the shear wave trajectory. Again, the centroid of shear wave generation must coincide with the dashed lines. The r(t) trajectory is the more relevant one here, as the shear wave propagates in r-direction. The curve implies that the shear was generated at about the instance of collapse TC = 109 μs, because at this time the trajectory intersects the t-axis and due to the symmetry considerations, negative r coordinates are forbidden. Then, the centroid of shear emission can be read as (r(TC), z(TC)) = (r = 0, z = 1126) μm which is close to the point of bubble generation (r = 0, z = 1098) μm.
This position coincides with the region where the jet forms and penetrates the bubble. The jetting into the bubble is visible from its deformation, see Fig. 2γ = 1.85 and 99 μs ≤ t ≤ 103 μs. Always connected with the jetting is a motion of the bubble towards the rigid wall. The origin of the shear generations suggests that it is the formation of the jet on the upper part of the bubble that launches the shear wave.
The small stand-off case shown in Fig. 4c is more involved. The shear can either be generated at around TC, implying z ≈ 205 μm, or at about the time of bubble generation, t = 0 at z ≈ 0 μm or at both times. To unravel this shear generation dynamics, in Fig. 5 we plot the time evolution of the particles in the potential shear generation region (blue box) in time. One particle is tracked using the dashed line. Sudden changes in the slope of the dashed line indicate shear generation. Thus, shear is mainly generated at the wall and during early expansion already. In addition, some shear seems to be generated during the late collapse stage and after jet impact. Thus, both expansion and collapse contribute to the shear wave.
Thus, the shear wave can be generated during bubble collapse in the jet region for larger γ or during expansion and collapse at the wall for smaller stand-offs and accordingly the shear wave travels either in horizontal or vertical direction, respectively, i.e., the Poynting vector has an angle with respect to the wall that is ideally 0° or 90°, respectively. In Fig. 6 we show the angle of the Poynting vector as function of the γ. To estimate the uncertainty we first take the standard error of the slope30 of the fitted shear wave trajectories. From that, we derive the propagation angle error using error estimation of derived quantities.31 It can be seen that for γ < 0.5 the shear wave is generated in the wall-near generation and for γ > 1 around the jet. The stand-offs between γ = 0.5 and γ = 1.0 represent an intermediate regime where both shear waves are generated. It should be noted, though, that the shear wave that is generated in the wall near region may be underestimated in our measurements because the shear measurement window is in the upper quadrant, which implies a certain propagation distance of the shear wave into the measurement window with respective attenuation.
In the above shear maps of Fig. 3 it was shown that for the smallest stand-off the shear wave energy is largest. Now, we systematically study the efficiency of the shear generation η and plot the ratio of shear energy to bubble energy as function of the stand-off in Fig. 7, i.e., η = USW/Ububble = p0V. The shear wave energy is obtained from the area integral where u is the shear wave energy density shown in Fig. 3 and Ω is the measurement area. The vertically propagating shear wave, once it reaches the quadrant of evaluation, is completely in the measurement window, the horizontal wave, however, needs a special treatment. As it is symmetric with respect to the bottom axis of the evaluation window, we multiply the associated energy by a factor of two for γ > 0.5 cases. The bubble energy is approximated as Ububble = p0V, where p0 = 1 bar is the atmospheric pressure, and V is the maximum bubble volume. To estimate the volume of the non-spherical bubble we use
for γ > 1, for stand-offs smaller than 1, we chose
as discussed by Bußmann et al.32 with Rmax standing for bubble radius in its maximum expansion and d for the bubble seeding distance.
The shear energy fluctuates in time, and we chose to take the energy maximum. To estimate the uncertainty we assume a spatial uncertainty of 1/3 PIV window size for the detection of the shear front.
It can be seen that the shear generation indeed has a maximum for γ → 0 and approaches zero as the bubble dynamics become spherical, i.e., η(γ → ∞) = 0, which is what we expect for spherically oscillating bubbles. We make a phenomenological fit of the shear generation efficiency using the following function: η = aebγ with a = 1.22 and b = −1.87. Extrapolation of the fit suggests that in this configuration, at most η(γ = 0) = 1.22% of the bubble energy can be converted into shear energy for the given material.
Finally, we would like to discuss the condition for shear wave excitation and make a connection with the acoustic emission from laser light absorption, i.e. photoacoustics. There, for the emission of acoustic waves from impulsive laser-induced heating, the heating duration must be shorter than the stress confinement time, i.e. the time for the stress to travel across the heating region as an acoustic pulse.33 Then, stresses can be built up and are released by a strong acoustic emission. This condition is commonly termed as stress confinement. In analogy, if the duration of shear generation is shorter than the transport of the shear out of the volume, shear stress will be confined. Let us quantify this argument in very simple terms. The duration of shear stress generation is of the order of the Rayleigh collapse time, while the shear wave propagates out of this volume of stress generation within a time
. Shear stress confinement is then reached once TC < TSW or
. At maximum expansion the pressure in the bubble is typically almost zero, thus the pressure difference can be estimated as the atmospheric pressure: ΔP = 100 kPa. For the present material of about E ≈ 10 kPa, we obtain a value of TC/TSW ≈ 0.1. Following this argument, shear stress confinement is more difficult to obtain in stiffer materials. Thus, if a tissue becomes stiffer during therapy, e.g. in thermal ablation, the strength of the shear wave should reduce. It may be possible to monitor the strength of the emitted shear waves in thermal procedures and use that value to evaluate the thermal dose of the tissue it has received. For that, it may also be important looking into the shear wave generation as function of tissue properties, in particular the elastic modulus in future works.
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Fig. 8 Shear measured in the left and right quadrant generated here by a cavitation bubble with γ = 0.48. The solid boundary is shown with a dashed line below the frame. |
Footnote |
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3sm01077e |
This journal is © The Royal Society of Chemistry 2023 |