LASER beams-used for swashbuckling effect in the movie Star Wars nearly a quarter century ago-are now proving an effective weapon in the war against medical conditions such as stroke and arthritis, as well as in surgical procedures. A critical ally in this battle is LATIS (an acronym for LAserTISsue), a computer code developed at Lawrence Livermore. It is a two-dimensional, time-dependent code that simulates the interaction of laser light with living tissue. LATIS is based on experience gained during 25 years of modeling high-intensity laser-matter interactions for inertial confinement fusion.
Medical researchers from the Department of Energy's national laboratories, as well as from universities and industry, have been turning to LATIS and its new, three-dimensional counterpart, LATIS3D, for help in the design and use of new laser medical tools. LATIS was originally developed by Livermore physicists Richard London, George Zimmerman, David Bailey, and Mike Glinsky (now at Shell Co.). The codes are particularly useful in analyzing novel laser systems used for photothermal, photochemical, and photomechanical applications.
For these medical applications, LATIS explores laser-light propagation, thermal heat transport, material changes such as thermal coagulation and photochemistry, and hydrodynamic motion. "LATIS was originally funded as part of a Laboratory Directed Research and Development project looking at ways to diagnose and treat stroke," London explains. "In developing the code, we leveraged experience, expertise, and technologies already available at the Laboratory in areas such as computational modeling, laser technologies, and precision engineering of laser-matter interaction and radiation hydrodynamics. The results are having an effect on healthcare technologies and economics by making it easier-and less expensive-to develop some of these laser tools."
In the past three years, LATIS codes have simulated a laser system that will break up blood clots in stroke patients and experiments using a tissue "welding" system based on laser light. Current work includes a new technique for easing arthritis.

Attacking Strokes at the Source
Strokes, like heart attacks, usually result from decreased blood flow interrupting the supply of oxygen and nutrients to tissue. Most frequently, the flow is decreased because of a blockage in blood vessels.
In 1995, Livermore's stroke-initiative team began developing optical therapies for breaking up clots in the blood vessels of the brain as well as the laser-tissue interaction modeling that was the beginning of LATIS (for more information see S&TR, June 1997, pp. 14-21). The clot-busting system delivers low-energy laser pulses through a fiber-optic microcatheter positioned close to the cerebral clot. The optical light is converted to acoustic stress waves that break up the clot and restore blood flow in the cerebral arteries.
"With LATIS, we simulated the interaction of the laser beam with fluids (blood, saline solution), the blood clot, and tissue near the end of the fiber. We then compared the results with experiments," London said (Figure 1). "We modeled the generation of acoustic waves near the interaction and the acoustic energy on the blood clot. The results provided direction to researchers on the optimal parameters for laser wavelength, pulse length, and optical fiber diameter. The modeling also helped reduce the number of experiments needed."
LATIS incorporated a number of variables-the size and composition of the clot, strength of the blood-vessel tissue, and buildup and transport of heat during laser clot-busting. The code then numerically simulated the hydrodynamics of the laser-created energy and predicted the energy needed to break up the clots without damaging other tissue.
This clot-busting instrument, now being advanced by Endovasix Inc., is entering clinical tests and should be commercially available within a couple of years.






Modeling Temperatures for Tissue Welding
In another effort spearheaded by Livermore's Medical Photonics Laboratory, researchers, led by Duncan Maitland, designed a system that uses laser light to join tissue, much like sutures. The laser energy activates tissue bonds between surgical surfaces, fusing them together. If there's too much heat, however, the tissue is damaged, and poor healing results. If there's not enough heat, the bonds don't form.
In this case, LATIS helped researchers analyze data from tissue experiments and then design the system. LATIS modeled the heating effects and the heat transport of the laser energy absorbed by the tissue. The researchers made interesting discoveries in this modeling effort. For instance, for a pulse of many seconds to a few minutes, they found that the evaporation of water from the surface of the tissue cools the tissues, much like sweating. Before this, no one had determined quantitatively how important cooling was to the process. They also simulated the temperature profile of the underlying tissue, something that wasn't possible to measure experimentally. The findings had a significant impact on the system's design.
LATIS modeled the in-depth temperature profile for two temperature-control techniques: one, by dripping water on the tissue surface, the other by using a feedback system incorporating an infrared thermometer, developed at the Laboratory, that controls the amount of laser energy delivered to the tissue surface (see S&TR, October 1998, pp. 14-15). Both methods cool the surface of the tissue, but the question was which method better controls the temperature below the surface.
"The modeling predicted that temperatures below the surface would stay more uniform with the feedback system," said London (Figure 2). "The experimental results showed that the welds using the feedback technique were superior in several ways. The only way the techniques differed was in their in-depth temperature profiles."
The resulting tissue-welding system is showing particular promise in heart surgery on newborns, and the Laboratory is collaborating with the University of California's San Francisco Medical Center and Conversion Energy Enterprises on experiments to eventually bring this system to market.





Easing Arthritis
Another medical application for advances of the LATIS code is photodynamic therapy, using light-activated drugs to treat medical conditions including cancer and arthritis.
As part of the Center for Excellence for Laser Applications in Medicine, formed in 1998 by the Laboratory and the University of California at Davis's Medical Center, researchers are developing a treatment for arthritis based on photodynamic techniques. This project correlates with a Laboratory Directed Research and Development project to develop a successor to LATIS-a three-dimensional interactive code called LATIS3D. It is being used to make an accurate calculation of the distribution of laser light in a joint.
"We set up a model of the geometry of a knee joint, which is a very complicated three-dimensional (3D) structure," said London. "Developing a numerical description of the joint required making a three-dimensional numerical mesh, or grid. We are using magnetic-resonance images-MRIs-of knee joints as a basis for our 3D model. We will then define the properties of each tissue in each mesh."
With the model in place, the team uses Monte Carlo probability methods to determine light distribution in the various tissues. "We calculate where the light goes. Combining that with estimates from our collaborators of where the drug is concentrated, we can then calculate how the tissue is affected," said London.
These modeling efforts will help in designing the photodynamic therapy instrument, determining the laser energies needed, and positioning the light source.
For this application, LATIS3D could also be used to develop physician treatment plans. A physician can transfer a patient's MRI data into the model and come up with a plan that includes where to place the fiber, how long to make the exposures, how much energy is needed, and so on.

Powerful Modeling Tool Meets the Medical Future
Developing new instruments and procedures for use in laser medicine typically involves extensive experimental and clinical studies. As London noted, computational modeling codes such as LATIS and LATIS3D can help medical researchers define experimental parameters more narrowly and gain deeper understanding of specific laser medical processes. LATIS will also have a future role in designing patient-specific treatment plans and in training physicians.
"In these ways," said London, "modeling can lead to more rapid development of new medical systems, to the genesis of new ideas, and to more individually tailored treatment plans. All, of course, to the ultimate benefit of patients."
-Ann Parker

Key Words: arthritis, laser surgery, laser-tissue interaction modeling, LATIS code, LATIS3D code, stroke, tissue welding.

For further information contact Rich London (925) 423-2021 (london2@llnl.gov), or see the Livermore Medical Technology Program's Web site at http://lasers.llnl.gov/lasers/mtp/modeling.html.


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