A. Control of Precision 636 B. Control of Thermal Side Effects 636 C. Control of Mechanical Side Effects 637 D. Maximizing the Ablated Mass 637 E. Selective Ablation 637 XII. Outlook and Challenges 638 XIII. Acknowledgment 639 XIV. References 639 Alfred Vogel studied physics and sociology, receiving the University degree for high school teaching and the Ph.D. degree in physics from the Georg-August University of Göttingen, Germany. Later, he earned the degree of Habilitated Doctor of Physics from the University of Lübeck. In 1988, he joined the laser laboratory of the Eye Hospital of the Ludwig-Maximilians University Munich, and in 1992, he moved to the Medical Laser Center Lübeck, where he has been Vice-Chairman since 1999. His research interests include laser−tissue interactions in biomedical applications of photodisruption, pulsed laser ablation, and photocoagulation as well as laser-induced plasma formation, cavitation, and stress waves. Vasan Venugopalan received his B.S. degree in mechanical engineering from the University of California, Berkeley, and S.M. and Sc.D. degrees in mechanical engineering from MIT. He held postdoctoral positions at

Time-resolved imaging was used to examine the use of pulsed laser microbeam irradiation to produce cell lysis. Lysis was accomplished through the delivery of 6 ns, lambda=532 nm laser pulses via a 40x, 0.8 NA objective to a location 10 microm above confluent monolayers of PtK2 cells. The process dynamics were examined at cell surface densities of 600 and 1000 cells/mm2 and pulse energies corresponding to 0.7x, 1x, 2x, and 3x the threshold for plasma formation. The cell lysis process was imaged at times of 0.5 ns to 50 micros after laser pulse delivery and revealed the processes of plasma formation, pressure wave propagation, and cavitation bubble dynamics. Cavitation bubble expansion was the primary agent of cell lysis with the zone of lysed cells fully established within 600 ns of laser pulse delivery. The spatial extent of cell lysis increased with pulse energy but decreased with cell surface density. Hydrodynamic analysis indicated that cells subject to transient shear stresses in excess of a critical value were lysed while cells exposed to lower shear stresses remained adherent and viable. This critical shear stress is independent of laser pulse energy and varied from approximately 60-85 kPa for cell monolayers cultured at a density of 600 cells/mm2 to approximately 180-220 kPa for a surface density of 1000 cells/mm2. The implications for single cell lysis and microsurgery are discussed.

Although thermal relaxation times of cutaneous port-wine stain microvessels have been calculated and used to formulate laser selective photothermolysis, they have never been measured. A scheme to do so was devised by measuring the skin response to pairs of 585-nm dye laser pulses (250-360 microseconds each) as a function of the time interval between the two pulses, in five volunteers with port-wine stains. After a pump pulse delivering 80% of the fluence necessary for causing purpura, the fluence of a second probe pulse necessary to cause purpura was determined and was found to increase with the interval between the two pulses, in a manner consistent with thermal diffusion theory. Biopsy specimens were obtained from four of the five subjects to examine the nature and extent of vessel damage and to measure the port-wine stain vessel diameters. Using diffusion theory, the thermal relaxation time was calculated based on the measured vessel diameters. These calculated values are consistent with the increase in radiant exposure (fluence) of the probe pulse necessary to induce purpura for longer time delays. Two simple models for thermal relaxation of port-wine stain vessels are presented and compared with the data. The data and histologic assessment of the vessel injury strongly suggest that pulse durations for ideal laser treatment are in the 1-10-millisecond region and depend on vessel diameter. No dermatologic lasers presently used for port-wine stain treatment operate in this pulse width domain.

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