Acoustic detection of controlled bubble creation by liob in tissue-mimicking gelatin phantoms

Laser induced optical breakdown (LIOB), based on nonlinear absorption, can produce precise intracellular and intra-tissue effects. LIOB occurs only where the breakdown threshold is exceeded, and has the potential to be manipulated both geometrically and biochemically to selectively target areas within tissues while minimizing thermal and mechanical damage to surrounding material. Furthermore, the measurable effects of localized breakdown, shock wave emission and microbubble formation, signal targeted areas and generate an object for sensitive acoustic detection and potential manipulation. In this study, we show that by varying laser pulse fluence, number, and period, the size and stability of LIOB bubbles may be independently controlled, demonstrating the utility, of these bubbles as site-activated ultrasound contrast agents. To monitor breakdown in tissue-mimicking, collagen gel phantoms, we use a high-frequency (> 50MHz) ultrasound microscopy system to detect shock wave generation at the focus of an ultrafast pulsed laser source and simultaneously probe resulting microbubbles through pulse-echo recordings. While both increases in pulse fluence and pulse number over the ranges studied lengthen bubble lifetime from tens of milliseconds to hundreds of milliseconds, a bubble of particular stability did not necessarily have to be of a particular size. For instance, at a pulse repetition rate of 4 kHz, a 695 ms lifetime bubble created at 2.8 J/cm(2) and stabilized by 100 additional pulses had 4dB reduced maximum integrated backscatter (i.e. reduced size) as compared with an identical lifetime bubble created and stabilized at 4.8 J/cm(2) with 20 pulses. Furthermore, while bubble behavior is independent of pulse period below a fluence-dependent threshold value, it exhibits stochastic behavior if pulse repetition is too slow. Ultimately, pulse fluence, period and number may be varied to deposit energy in a specific temporal manner, affecting and balancing the natural bubble dissolution rate and stabilizing bubble behavior for a given set of conditions. Stability can be maintained only above a threshold size, however, below which dissolution rate rapidly increases, causing bubble collapse. In short, our high frequency ultrasonic technique has identified system parameters for controllable LIOB-induced bubble creation in tissue-mimicking phantoms.