1. Introduction

High-intensity pressure waves have found numerous biomedical applications. The targeted ablation of tissue and drug delivery is particularly interesting since the treatment can be localized within a volume of less than a cubic millimeter situated relatively deep under its surface. This is particularly important in medical procedures, where damage to the surrounding tissue is highly undesirable. One possible way to achieve such an effect is with a superposition of appropriate pressure waves, focused onto the targeted subsurface tissue, where they culminate into a desired destructive impact.

The conventional method of high-intensity enhanced ultrasonic wave generation using mechanical ultrasonic transducers set in a concave shape is known as a high-intensity focused ultrasound (HIFU) [1–3]. It can generate acoustic cavitation which can be loosely defined as the process by which small nano or micro-sized gas bubbles already present in a liquid pulsate, grow, split, or interact due to pressure wave oscillations [3–6]. Such phenomena are used in medicine, among others, for tumor ablation [1,4,7,8], and for kidney stone fragmentation [8–10]. The use of high-intensity pressure waves is also promising in thrombolysis [11], arterial occlusion [12], cancer [13], or hemorrhage treatments [14], and in targeted brain activity modulation [15]. In these treatments, the destruction occurs in limited tissue regions at high enough intensities of enhanced pressure waves due to three main mechanisms: shock scattering, boiling, and intrinsic threshold histotripsy [16]. However, the affected zone is at least a few millimeters in size, representing one of the fundamental restrictions of HIFU [3,17].

On the other hand, the using of very short laser pulses (a few nanoseconds) together with an optoacoustic lens [18] enables the generation of much higher frequency (>15 MHz) [19] and higher pressure wave amplitudes (>50 MPa) comparing to HIFU using a thermoelastic or ablative mechanism [4]. Such laser generation of enhanced ultrasound is known as a laser-generated focused ultrasound (LGFU) [20,21]. Along with the considerably better spatial accuracy of laser-generated focused pressure waves in comparison with the HIFU method (up to 1000 times smaller affected volume), the advantages of the laser method are also in a much smaller size of the optoacoustic lens, which allows using a smaller contact area and better access to specific body regions. This is due to laser light absorption in an optoacoustic lens that quickly thermally expands due to energy absorption and launches pressure waves that propagate in the substrate. Recent results of using an optoacoustic lens made of Ti/black-TiOx [22] have shown that this material essentially acts as a great optoacoustic transducer for a broad spectrum of incident light.

The LGFU method uses a single laser pulse to induce the pressure wave. Yet a further way of enhancing the micro destruction phenomena is possible with a precise temporal combination of multiple successive pressure waves where the arrival of the next wave must be synchronized with the dynamics of the cavitation bubbles caused by the previous laser pulse. With such an approach, the amplitude of the pressure waves and the connected ablative effects can be larger due to resonance phenomena, which was demonstrated using the conventional HIFU method [23,24]. However, laser multi-pulse generation of pressure waves has not been reported yet. The closest to it was the research where the accelerated collapse of cavitation bubbles achieved with a precise delay of the second laser pulse was used in a model of a dental root canal [25–29]. However, the laser system operated in a free-generation regime with much longer pulses (tens of microseconds) and without any acoustic lens.

Here we report the use of multiple consecutive nanosecond laser pulses, which are synchronized to enhance the generation of pressure waves and acoustic cavitation in the focal area of the optoacoustic lens. For that reason, we employed a state-of-the-art Q-switched Nd:YAG laser source capable of providing multiple high-energy laser pulses (up to 4 pulses with 400 mJ/pulse) with delays in the range from 50 µs to 400 µs. The amplification of the pressure waves and corresponding cavitation phenomena are characterized by high spatial and temporal resolution using a high-speed camera and needle hydrophone.

2. Methods

The experimental setup is schematically shown in Fig. 1. A titanium optoacoustic (OA) lens with a diameter of 9 mm and acoustical focal length of F = 4.5 mm was placed in a glass bath (size of 10 × 18 × 25 cm) filled with distilled water. The lens was irradiated underwater with multiple laser pulses (N ≈ 300, 5 ns pulse duration, wavelength 1064 nm, fluence 2 J/cm², to form a film of hydrogenated (or black) TiOx. Photo-oxidation and passivation of the target with TiOx were promoted by the interaction between the dissociated water (close to the surface of the lens) and the Ti atoms ejected via hot-plasma formation. The transformation of Ti into black TiOx is extensively described and characterized in [30]. In our case, this transformation and Ti-O bounds are corroborated by Raman spectroscopy, SEM/EDS analysis, and UV–Vis spectroscopy in [22]. We used the passivation layer of hydrogenated TiOx (black color) as an absorbing medium to achieve ∼85% absorption in the visible/near-infrared range at 1064 nm. The lens was fully submerged and placed 5 mm below the water surface to ensure the constant replenishment of the water during the experiment.

 

Fig. 1. Experimental setup.

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Pulsed Q-switched Nd:YAG laser (StarWalker, Fotona d.o.o.) was used as an excitation source with pulse duration t_p = 5 ns full width at half maximum (FWHM) and with wavelength λ = 1064 nm. Laser light was delivered through an articulated arm with a handpiece (Fotona, R28). The laser pulse energy was held constant at the exit of the laser system (E_p = 600 mJ). It was then further adjusted by a variable attenuator using a half-waveplate and polarizer. This assures the constant temporal and spatial profile of laser pulses irrespective of the energy. The beam diameter measured on the upper side of the OA lens was d = 8 mm. The laser system enables a burst of pulses with an adjustable delay between them. Within each burst, individual pulses can be delayed from t_d = 50 µs up to 400 µs, and the maximal frequency of bursts was f_b = 20 Hz.

The estimated acoustic gain of our system was G = 9, defined as the ratio of the pressure in focus compared to the pressure close to the OA lens surface. For this specific lens, the f-number was 0.56, and central frequency of induced pressure waves was 0.9 MHz. Details are shown in Supporting Information, section 4.

A strong recoil pressure wave is generated [22] after each laser pulse, which propagates through the water with the speed of sound. Characterization and visualization of these waves and corresponding cavitation phenomena were performed with a needle hydrophone (Precision Acoustic LTD, 60 MHz bandwidth) with a 0.2 mm aperture mounted on an (X, Y, Z) manipulator and with a high-speed camera (Fastcam SA-Z, Photron) with 1:2 magnification lens (Sigma APO Macro, f = 180 mm, F2.8). Both measuring devices were simultaneously triggered on the first laser pulse using a trigger photodiode (Thorlabs, DET10A) connected to an oscilloscope (LeCroy, US, 600 MHz Wave Runner 64MXi-A) together with a hydrophone signal.

The hydrophone needle tip was positioned away from the focal region of the OA lens (h + F = 30 mm), where the probability of cavitation and consequential damage to the tip was negligible. We measured positive (P_pos), negative (P_neg), and peak-to-valley (P_p-v) amplitudes of pressure waves after each laser pulse.

The image sequences from the high-speed camera were recorded on a personal computer and post-processed to measure the sizes of the acoustic cavitation cloud around the focal region and the size of the bubbles formed by a laser-induced breakdown on the upper metal surface of the OA lens. The term “shroud cloud” is used for this phenomenon. The sizes of both clouds were measured as a cumulative area of all detected bubbles within each region of interest. See a more detailed description of image processing in Supporting Information.

3. Results and discussion

Figure 2 shows the phenomena during double laser pulse (2 × 355 mJ) ablative excitation of TiOx OA lens. The absorbed energy of each laser pulse is transformed into heat, causing a rapid expansion of a thin vaporized layer of TiOx and surrounding fluid. Fast heating and expansion induce an intense ablative thrust, resulting in the formation of a shroud cloud on the upper side of the lens (see Fig. 2(a) - shroud cloud are bubbles above the red dashed line) and the formation of a pressure wave (red signal in Fig. 2(b)) that propagates downwards, through the focal region of the OA lens. Acoustic cavitation is induced immediately after the passage of the pressure wave due to rapid compression and decompression of the exposed fluid. As shown in Fig. 2(a), the highest cavitation density appears in the vicinity of the OA lens focus due to significant pressure wave gain in that region and a small radius of curvature (4.5 mm).

 

Fig. 2. Typical dynamics around an OA lens using double-pulse excitation (E_p = 355 mJ and t_d = 280 µs). (a) The image sequence shows acoustic cavitation below the OA lens and shroud cloud above at various characteristic times (Visualization 1 shows the entire sequence). (b) The pressure waveform shows two waves with corresponding estimators (P_pos, P_neg, and P), emitted after the 1^st and 2^nd laser pulse (marked with a yellow line. (c) Area of the acoustic cavitation for each time interval (green line) and the shroud cloud (blue line). The maximal amplitude of the acoustic cavitation area after each laser pulse is marked as A₁ and A₂. (d) Magnified pressure waves of the 1^st (blue) and 2^nd (red) laser pulse. (e) Frequency spectrum of the signals shown in (d).

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The second laser pulse is triggered just after the collapse of the shroud cloud, which can be seen in Fig. 2(c) (blue line). The most interesting is that the size of acoustic cavitation after the second pulse (A₂) is significantly larger than the first pulse (A₁). By comparing images 2 and 6 in Fig. 2(a), acoustic cavitation appears at approximately the same positions. However, at 2^nd pulse, the bubbles are bigger and clustered. Figure 2(d) shows the zoom of the measured pressure waves where the time scale is aligned with the first and second laser pulse. Blue and red lines present waveforms of the first and the second wave respectively. The frequency spectra (see Fig. 2(e)) show a primary peak around 0.9 MHz and the bandwidth of the signal around 4 MHz (a frequency range that includes 95% of the total energy of the signal). Both graphs (time and frequency domain) show similar shapes of the first and the second pressure wave and the same arrival times.

Since the ablative regime of the pressure wave generation can induce much stronger amplitudes than the thermoelastic regime, the deformation of the OA lens is in principle possible. However, any macroscopic deformation of the lens would cause a change in the shape of the pressure wave and its frequency spectrum, which we didn’t observe (see Fig. 2). During our previous investigation [22], the lens was exposed to a broad range of laser fluence from 0.1 J/cm² to an extreme value of 2 J/cm², and the shape of the focused pressure was preserved. We observed a linear trend of the pressure amplitude; thus the expected maximum pressure in focus is >200 MPa at 2 J/cm² (see Pressure measurement extrapolation in Supporting Information); however, the fluence above 1.5 J/cm² causes perforation of the metal lens after approximately 2000 laser pulses. Hence, in contrast to the thermoelastic regime, where the maximal fluence depends on the ablation threshold of the absorption layer, in the ablative regime, the maximal fluence depends on the expected lifetime of the lens. Particularly, on the rate of the phase change into TiOx. Higher is the fluence faster the suboxide will penetrate deep into the lens structure, increasing the absorption of high laser energy until perforation.

3.1 Single-pulse excitation

Figure 3(a) shows in more detail the dynamics of growth, collapse, and rebound of the shroud cloud after the first laser pulse. Figure 3(b) shows the averaged oscillation time (<T_osc> ) of the shroud cloud increasing proportionally to E_p, representing the duration from cloud occurrence to its collapse and relating to its potential energy. It is worth mentioning that the shroud cloud is made up of an ensemble of a multitude of bubbles of different sizes, so collapses do not happen simultaneously. As a result, it also does not occur that the shroud cloud would disappear entirely, but it reaches the local minimum temporally. This population of bubbles mainly origin from laser-induced breakdown, shock wave emission, and bubbles formation on the upper surface of the lens. The linear dependency of <T_osc> on the laser energy remarks a similar behavior observed for a single bubble created by laser breakdown in water. The bubble’s potential energy is linear with E_p and relates to the T_osc through the maximum radius [31].

 

Fig. 3. (a) Typical dynamics of shroud size above the OA lens after the first laser pulse for three different laser energies. (b) Measured oscillation times (T_osc) of the shroud cloud reveal linear relation with laser pulse energy (E_p). (c) Temporal development of acoustic cavitation size below the OA lens after the first laser pulse. (d) Acoustic cavitation probability within the focal region of the OA lens after the first laser pulse versus laser pulse energy (E_p).

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The second population of bubbles refers to the acoustic cavitation process that takes place in a free field after the propagation of the pressure wave within a focal area beneath the OA lens. The nature of this process is generally stochastic. The dynamic at different E_p (after the first laser pulse) is shown in Fig. 3(c). The oscillation time of the acoustic cavitation cloud is significantly shorter (between 10 µs and 40 µs) compared to the shroud’s lifetime, suggesting a smaller dimension of these bubbles. In principle, one could try to synchronize the next laser pulse with this oscillation time to amplify the pressure wave, as it was demonstrated in the case of endodontics using Er:YAG pulses [25]. But besides providing adequately short delays between the laser pulses, which is the limitation of our laser system, the oscillation time of the shroud cloud should be equal to or shorter than the acoustic cavitation to achieve efficient energy conversion.

The probability of acoustic cavitation inception at different E_p is evaluated in terms of the distribution of the bubbles within the cloud when it reaches maximal size. Figure 3(d) shows the probability of acoustic cavitation as a function of the laser energy. The predicted curve resembles the first part of an S-shaped function already shown in a previously published work [22]. A cavitation threshold (defined as a 50% cavitation probability) was observed at 1.2 ± 0.2 J/cm² for a similar lens configuration, which is comparable to our observation, where the threshold fluence is 1 ± 0.2 J/cm². However, we limited the maximal fluence since our primary research goal was to study the multiple pulse regime where T_osc (of the shroud cloud) is smaller than the maximal achievable delay between consecutive laser pulses (<400 µs).

The results presented in Fig. 3(d) show the relation between the laser energy and cavitation probability. However, the cavitation threshold in terms of pressure is also important to compare the measurements with other techniques. As we explained, the needle hydrophone was positioned below the focal point of the OA lens to prevent its damage. To extrapolate the measured values to the focal region, we measured pressure waves at different distances from the focus with 0.5 mm increments at fluences below the cavitation threshold. The ratio between the pressure at the focal region and the pressure measured at the hydrophone location was 35 ± 3 (see Supporting Information, section 5. Pressure measurement extrapolation). The extrapolated negative pressure in the focal region when the acoustic cavitation occurred was, therefore in the range between -21 MPa and -25 MPa, which is in agreement with previous reports [32,33]. The corresponding mechanical index (MI), which is a unitless measure of acoustic-driven non-thermal bioeffects, such as cavitation [34], is MI = 24 ± 2 (central peak frequency is 0.9 MHz, as can be seen from Fig. 2(e)). For comparison, an MI of 1.9 represents the upper limit for diagnostic ultrasounds.

3.2 Double-pulse excitation

This section presents the dynamics when the OA lens is excited with two laser pulses. The effects of the second laser pulse at delay t_d are depicted in Fig. 4. The pressure wave amplitude due to the second pulse is P_p-n.2 and the acoustic cavitation size is A₂. The horizontal brown bands represent the amplitudes after the first pulses (P_p-n.1 and A₁), while vertical green bands indicate oscillation times (T_osc) of the shroud cloud at applied energies. Figure 4(a) to 4(c) show the changes of P_p-n.2 with a considerable attenuation (P_p-n.2 << P_p-n.1) in the region where t_d < T_osc, and it gradually weakens as t_d approaches T_osc. This attenuation is mainly related to the shroud cloud’s presence, which prevents the effective transformation of the optical energy into the energy of the pressure wave. This energy conversion, hence the recoil effect, is expected to be significantly higher when water is in contact with the lens, as presented in a study of laser propulsion of metal rods [35].

 

Fig. 4. Influence of delay on the pressure wave amplitudes (top row) and acoustic cavitation size (bottom row) after the 2^nd laser pulse for three laser energies (259, 355, and 407 mJ). Green vertical bands indicate oscillation times of the shroud cloud (T_osc), while brown horizontal bands indicate pressure wave amplitude (P₁) and acoustic cavitation size (A₁) after the 1^st laser pulse.

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When t_d ≈ T_osc, the P_p-n.2 exceeds the P_p-n.1 at higher E_p (see Fig. 4(b) and 4(c)). The amplification of the pressure wave is most likely due to a reduced dimension of the shroud cloud and the higher temperature of the lens due to the pre-heating from the first pulse. As a consequence of the increasing temperature, the ablative effect is higher and generates a stronger recoil when the second laser pulse impinges on the OA lens. Considering the temperature relaxation time of Ti after ns laser excitation of the order of a few ms [36], the combined effect of the thermodynamic condition and a time-dependent dimension of the shroud cloud determines the amplification condition for t_d ≥ T_osc. In the case when t_d > T_osc, the P_n-p.2 remains constant (Fig. 4(b)) or even starts decreasing at higher E_p (see Fig. 4(c)). The reason for this decrease is the rebounded shroud cloud, which is more pronounced at higher E_p (see Fig. 3(a)). The apparent size of the rebounded shroud drags off the pressure value leading to an evident peak pressure for time delay equal to T_osc.

Hence, the scenario described above could be seen as a result of three different and competitive phenomena: (i) Screening effect of the second pulse due to the dimension of the shroud cloud that reduces the water contact and depends on the laser energy, (ii) Temperature increasing with long relaxation time, greater than the time scale of the shroud cloud dynamics, and (iii) Resonance effect that could appear when the second pulse is temporally delivered at the collapses of the shroud cloud, that could lead to an extra amount of mechanical energy transfer. The latter should generate emission of shock waves that would not be possible to detect with the hydrophone in the far-field due to the high-frequency attenuation.

The changes of acoustic cavitation size A₂ as a function of t_d (Fig. 4(d) to 4(f)) follow a similar trend of the pressure amplitude P_p-n.2. The correlation between the pressure amplitude and the increasing acoustic cavitation is discussed in Supplement 1 (2^nd section). At t_d ≥ T_osc, the acoustic cavitation size follows the increase of the pressure amplitude, reaching the peak at the highest E_p (Fig. 4(f)). The acoustic cavitation size A₂ is nearly constant and slightly exceeds A₁ for the two lower E_p (Fig. 4(d) and 4(e)). The increasing of the pressure amplitude could not explain alone the amplification of the acoustic cavitation. Indeed, for t_d < T_osc, the pressure amplitude of the second pulse is damped below the reference one (1^st pulse) due to the shroud’s screening, which could lead to a reduction of A₂. In this regard, the formation of invisible nano/micro-bubbles after the first pulse that is not yet fully reabsorbed back into the liquid could explain the presence of a sizeable acoustic cavitation cloud. We discuss this aspect in the following subsection, where four-pulse excitation is investigated.

Therefore, the largest relative changes in pressure amplitudes and acoustic cavitation size occur at the highest energies. By choosing an appropriate delay of the second pulse, equal to or greater than the oscillation time of the shroud clod (T_osc), the maximal achievable gain for the pressure and cavitation is around two-fold.

3.3 Four-pulse excitation

The results from the excitation using four laser pulses with E_p = 325 mJ at two different extreme delays are presented in Fig. 5. On the left panel (Fig. 5(a), 5(c), and 5e), the delay is significantly shorter than the shroud cloud oscillation time (t_d = 60 µs and T_osc = 250 µs), while on the right panel (Fig. 5(b), 5(d), and 5f) t_d equals T_osc. The image sequences (Fig. 5(a) and 5(b)) show the moments after each laser pulse when the acoustic cavitation reaches its maximum size. Figure 5(c) and 5(d) show the induced pressure waves (the time scales are the same). For t_d << T_osc, all subsequent pressure waves are significantly weaker than the first one (Fig. 5(c)), while all amplitudes are approximately equal in the case of t_d ≈ T_osc (Fig. 5(d)). The intense pressure damping at the shorter delay resembles the behavior observed in the case of double-pulse excitation, with the shroud cloud influencing the optodynamic conversion. Further on, Fig. 5(e) and 5(f) show the dynamics of the shroud cloud and acoustic cavitation. As can be seen, the acoustic cavitation remains about the same size if t_d << T_osc, while for t_d ≈ T_osc its size increases by approximately 10-fold after the fourth pulse. This amplification is definitively higher if compared with double-pulse excitation.

 

Fig. 5. (a) Typical dynamics around OA lens using four consecutive laser pulses (E_p = 325 mJ) with two different delays (t_d = 60 µs on the left sub-images, and t_d = 250 µs on the right sub-images). (a and b) Image sequences at times when maximal acoustic cavitation appears after each laser pulse (Visualization 2 and Visualization 3 in supporting material show the entire sequences). (c) High attenuation of pressure waves is evident at a shorter delay. (d) Relatively constant pressure waves appear when t_d ≈ T_osc. (e) The acoustic cavitation increases slowly when the short delay is used. (f) The acoustic cavitation size increases significantly after each laser pulse when t_d ≈ T_osc. (g) Remaining micro-bubbles after the major cavitation events. Timestamps are marked with violet dots in figure f.

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The average pressure attenuation PA(dB) of three successive pulses decreases when t_d approaches the shroud cloud oscillation time and converges to zero at t_d = T_osc. Contrary, the average increase of the acoustic cavitation after each laser pulse (cavitation amplification CA), estimated from the linear regression slope in Fig. 5(f), increases until t_d = T_osc (See details in the Supporting Information, 3^rd section). This trend is preserved for all E_p used in the experiment and demonstrates how multiple laser pulses lead to increasing acoustic cavitation that depends on the delay time and laser fluence.

The correlation between the acoustic cavitation sizes and the tensile strength induced by the pressure wave is insufficient to explain these observations. Indeed, the presence of a damped pressure wave at lower t_d (Fig. 5(c)) and their nearly constant amplitudes at higher t_d (Fig. 5(d)) reveals sizeable acoustic cavitation. Even amplification in the second case could not be explained by considering the pressure wave itself. However, the formation of invisible nano/micro-bubbles could probably be responsible for reducing the cavitation threshold. These bubble nuclei can be long-lived ∼400 ms, and they have a dimension that can vary from 100 nm to 10 µm [37]. Figure 5 g shows a magnified image of the focal region after each laser pulse. The presence of a bubble population, almost confined in the proximity of the focal region, is visible after the collapse of the primary cloud for a recording time up to 900 µs. Note that the lifetime of these bubbles could be longer and that the last frame is related to our experimental window. We did not observe the presence of these bubbles at lower E_p but only at higher when they form clusters. This does not exclude their presence, however other techniques, such as dynamic light scattering [38], should be employed to unveil it. A possible mechanism for the formation of the cavitation nuclei is discussed below.

During the acoustic cavitation cycle, the bubble growth is governed by the rectified diffusion and bubble-bubble coalescence processes [39]. During the collapse, they initiate sonochemical reactions through the formation of radicals [40]. The collapses eventually generate bubble nuclei that initiate a new cycle. The rectified diffusion and the bubble-bubble coalescence were indicated as the main mechanisms of the bubble growth over several acoustics cycles in experiments employing a classical ultrasonic transducer. In the rectify diffusion during the expansion phase, gases and molecules diffuse into the bubble through the surface area. Successively, during the compression phase, the material diffuses outside of the bubble. Since the collapse occurs in a time shorter than the expansion and less surface area is available for the gas transport, the amount of material that diffuses outside is less than the one that diffuses into the bubble during the expansion phase. In [41] is defined as the area effect and is responsible for the growth of the acoustic cavitation over time. This relates directly to our observations and becomes more visible at higher E_p, where the starting bubble population is higher, and clusters of bubble nuclei are created, living on the ms timescale.

The importance of the remaining micro-bubbles can also be seen in the Fig. S-3(d-e) in the Supporting Information. It is evident that CA is positive for the entire range of investigated delays and laser energies, which means the acoustic cavitation size is always growing, just the CA differs from 0.1 to 2.7 per pulse. The micro-bubbles, therefore, reduce the cavitation threshold, which results in bigger acoustic cavitation. If the number of laser pulses could be unlimited, the cavitation bubbles would grow until they finally reach the resonance size range [41], when their oscillation time equals the frequency of laser pulses.

Figure 6 shows the average spatial distribution of acoustic cavitation for two different laser energies and after four-pulse excitations. The time interval is chosen when the acoustic cavitation reaches its maximum size. The dimension of the acoustic cavitation increases with the laser energy, and it is confined along the axial lens direction and in the proximity of its focal region, where the pressure amplitude is the highest. Interesting to see is a certain degree of localization of the bubbles. This could also be seen in Fig. 5(a) and 5(b), where, beyond the stochastic events, a part of those clusters repeats in the same position after each laser pulse. This corroborated the presence of the nano/micro-bubbles that form after the first pressure wave and act as cavitation nuclei. This quasi-deterministic creation of acoustic cavitation due to consecutive laser-induced pressure waves could have implications for the ablation of soft tissue. In fact, the laser parameters (E_p and t_d) and the amount of initial impurity of gas bubbles could be used to shape and localize the bubble cluster, hence the damage induced by the collapses.

 

Fig. 6. Average spatial distribution of acoustic cavitation for different laser energies (275 mJ and 325 mJ) and four-pulse excitation regime: growing the cavitation area around the focal region with increasing energy.

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3.4 Potential biomedical applications

We already showed the possibility of tailoring the shape of the spatial distribution of the acoustic cavitation by tuning the laser energy, from a more localized volume smaller than 1 mm³ to a denser and deeper distribution of ∼ 8 mm along the axial direction of the lens [22]. Although the pressure can reach high amplitude, the acoustic cavitation, shock waves, and their mutual interaction can be equally important secondary ablative effects [42,43]. The pressure wave amplitude due to the collapse of the bubbles can be on the order of 10³ MPa and can be spatially circumscribed as well.

In our experiment, acoustic cavitation occurs near the OA lens (representing a concave boundary). This type of geometry is known to induce additional cavitation-related phenomena. For instance, Požar et al. [44] describe the generation of aggregates of secondary cavities near the acoustic focal volume specific for optically generated bubbles near concave surfaces. Tomita et al. [45] describe a lengthening of the bubble oscillation period near concave boundaries as well as the appearance of liquid jets and pronounced bubble migration. These effects, although relevant are beyond the scope of the present study.

Localized damage of the soft tissue is an important aspect of ablation therapy. In this study, we provide a possible assessment for the usage in medical applications. We used an inexpensive OA lens with a short focal distance that could be used at the skin interface for local medical therapy. Localized focused ultrasound has been recently shown to be a good candidate for tattoo removal [46], inducing necrosis of the outer dermis and removal of color pigments that are difficult to treat with commercially available laser wavelengths. In this wavelength-independent approach, the electronic counterpart of the HIFU apparatus could be minimized by using an OA lens instead. However, due to modus operandi in the ablative regime, a more engineered solution should be adopted to isolate the ablative side of the OA lens in a separate water-filled transparent chamber. This will enable the placement of the lens in any orientation. And since the chamber above the lens constrains the expansion of the shroud cloud, its oscillation time will be shorter, enabling usage of shorter delay between consecutive laser pulses.

Among different medical diseases, cutaneous melanoma could represent a good case for further investigation of a photoacoustic approach. Besides surgical excision and chemotherapy, researchers have shown that microbubbles destruction induced by ultrasound waves (1 MHz) can be an alternative or additional therapeutic tool to eliminate or limit the tumor progression [47]. Another potential application involving ultrasound and cavitation bubbles at the skin interface is the transdermal drug delivery. It is commonly used at different frequencies ranging from a few tens of kHz to 3 MHz, depending on the purpose of the therapy. During this process, cavitation bubbles of a few tens of micron or more in size, larger than the skin voids, occur near the skin surface, enhancing the skin permeability. Particularly, the oscillating bubbles and the asymmetry in bubble collapse pressure near the skin interface often generate microjets. This microjet penetration into the skin surface or microjet collapse near the skin surface causes skin perturbation during the ultrasound treatment [6]. In our specific case, a water-based coupling medium and a non-contact OA lens could, in principle provide a similar effect described above. Moreover, the efficient amplification of the acoustic cavitation with synchronized delivery of laser pulses could enhance the skin permeability over an area equal to the size of cavitation clouds and provide a novel platform to study more efficient drug penetration.

4. Conclusion

Amplification of high-intensity pressure waves and related cavitation in water was investigated using multi-pulsed laser excitation of the black-TiOx optoacoustic lens. Laser energies were chosen above the ablation threshold of the OA lens, which leads to the generation of intense pressure waves, acoustic cavitation below the lens, and the shroud cloud above the lens. Results show that the shroud cloud dynamics significantly influence the multi-pulse excitation efficiency. If the time delay t_d between consecutive pulses is shorter than the oscillation time T_osc of the shroud cloud, the laser energy conversion into mechanical is significantly attenuated due to the presence of the shroud cloud. On the other hand, when t_d ≥ T_osc, the amplifications of pressure waves and acoustic cavitation were measured. There are two major contributing phenomena. The first is the screening effect of the shroud cloud, and the second is the growth of the nano/microbubbles during the acoustic cavitation cycle, which reduces the cavitation threshold at the next laser pulse. The results show that acoustic cavitation size increases 10-fold after the fourth laser pulse, while the pressure wave amplitude increases by more than 75%.