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Femtosecond pulsed laser beams can induce precise photodisruption in tissue and tissue-like materials. Both geometrical and biochemical manipulation of laser-induced optical breakdown (LIOB) produces highly localized photodisruption without residual damage to surrounding tissue. Measurable effects associated with LIOB are shock wave emission and microbubble formation. In previous work, we presented techniques for monitoring site-targeted, LIOB microbubbles with high-frequency (>50MHz) ultrasonic imaging. In this study, we used these techniques to study the stability of LIOB-induced bubbles in water-based gelatin. Successive recordings taken before, during, and after laser exposure illustrated bubble creation and stability. Bubbles with a range of lifetimes (20 - 400 ms) and dissolution behaviors were produced by varying either laser fluence (0.7 - 2.1 J/cm2/pulse) or total number of laser pulses delivered (30 - 500 pulses at 18kHz repetition rate). While both increases in pulse fluence and pulse number lengthened bubble lifetime by an order of magnitude and decreased the rate of bubble dissolution, bubble stability was nonlinearly related to total laser exposure. A few pulses at high laser fluence created initially large bubbles with long lifetimes and slow dissolution rates. In contrast, pulses at near-threshold laser fluence created initially smaller, shorter lifetime bubbles that were stabilized with subsequent pulses. Increased stability could be maintained only above a threshold bubble size. Below that critical size, dissolution rate rapidly increased, causing bubble collapse. Ultimately, these results demonstrated an ability to control the size, lifetimes, and stability of laser-induced microbubbles with various optical parameters, increasing their utility as site-activated contrast agents that can be sensitively monitored with high-frequency ultrasound.
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