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

Laser induced optical breakdown (LIOB) can produce precise intracellular and intra-tissue effects. LIOB occurs where the breakdown threshold is exceeded, and may be manipulated to target selectively areas within tissues while minimizing damage to surrounding material. 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. 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 LIOB generated shock waves and probe the resulting microbubbles through pulse-echo recordings. Increasing laser pulse fluence and pulse number lengthens bubble lifetime from tens of milliseconds to hundreds of milliseconds, but a bubble of particular stability does not necessarily have to be of a particular size. Bubble behavior is independent of pulse period below a fluence-dependent threshold value, but exhibits stochastic behavior if pulse repetition is too slow. Ultimately, pulse fluence, period and number may be varied to stabilize bubble behavior for a given set of conditions. Stability can be maintained only above a threshold size, however. Our high frequency ultrasonic technique has identified system parameters for controllable LIOB-induced bubble creation in tissue-mimicking phantoms.