To deliver better health through laser medicine and surgery the laser industry, at least in the U.S.A., will have to show more interest and support. Also, this interest and concern on the part of industry will help in the more rapid development and more effective laser safety programs as new systems and new applications come. The global current market in laser medicine and surgery should also interest the laser industry.

Lasers have come a long way since the old joke that a laser was a solution searching for a problem. Today lasers pervade all aspects of our lives. There are laser light shows at discos, lasers used medically to preserve vision, lasers used to separate cells to detect potential birth defects, lasers used to weld floor-pans for automobiles and laser drilled cigarette filters. There are military applications from laser guided bombs to proposed earth-based lasers with synchronous mirrors on satellites that bring destruction at the speed of light anywhere in the world. Most of us see only the very surface of these diverse applications. Today I will quickly review what a laser is and how its unique properties make it applicable in the field of medicine. I will then show you some of the many different ways in which lasers are presently used, describe to you the major markets and companies presently engaged in the manufacture of medical lasers, and, importantly, share with you some thoughts about the future of lasers in medicine.

Carbon dioxide laser surgery has been limited to a great extent to surgical application on the integument and accessible cavities such as the cervix, vagina, oral cavities, etc. This limitation has been due to the rigid delivery systems available to all carbon dioxide lasers. Articulating arms (series of hollow tubes connected by articulating mirrors) have provided an effective means of delivery of laser energy to the patient as long as the lesion was within the direct line of sight. Even direct line-of-sight applications were restricted to physical dimension of the articulating arm or associated hand probes, manipulators and hollow tubes. The many attempts at providing straight endoscopic systems to the laser only stressed the need for a fiber optic capable of carrying the carbon dioxide laser wavelength. Rectangular and circular hollow metal waveguides, hollow dielectric waveguides have proven ineffective to the stringent requirements of a flexible surgical delivery system. One large diameter (1 cm) fiber optic delivery system, incorporates a toxic thalliumAbased fiber optic material. The device is an effective alternative to an articulating arm for external or conventional laser surgery, but is too large and stiff to use as a flexible endoscopic tool. The author describes the first highly flexible inexpensive series of fiber optic systems suitable for either conventional or endoscopic carbon dioxide laser surgery. One system (IRFLEX 3) has been manufactured by Medlase, Inc. for surgical uses capable of delivering 2000w, 100 mJ pulsed energy and 15w continuous wave. The system diameter is 0.035 inches in diameter. Surgically suitable fibers as small as 120 um have been manufactured. Other fibers (IRFLEX 142,447) have a variety of transmission characteristics, bend radii, etc.

Progress in the design, fabrication, and characterization of vitreous mid-infrared (IR) optical fibers suitable for medical applications such as surgery, cauterization, thermal imaging, and microanalysis is reviewed. Specifically, we describe the current status and future prospects for chalcogenide glass fibers operating from approximately 2 to 12 microns in the IR; and heavy metal fluoride glass fibers operating from the near-UV to approximately 7 microns in the IR. Results of recent measurements of optical and mechanical characteristics of IR glass fibers will be presented.

Laser instrumentation for the study of immunologic disease and the immune response, as well as for therapy in immunologic associated diseases is still a very new field. The laser nephelometer is the most standard of the instruments now used, because of its ability to exactly measure and quantitate various materials. Fluorescent techniques to help identify various materials including various subsets of lymphocyte population in concert with monoclonal antibodies is a field for further study and development. The therapeutic use of laser, in immunologic and rheumatic diseases, will depend upon in vitro, and in vivo animal and human design studies.

Samples of erythrocytes of different ABO groups, diluted in normal saline, were irradiated with high concentrated low power He-Ne Laser beam during 30 minutes. By microscopic observations made every 5 minutes the crenation time history of the irradiated red cells were determined. Assuming the crenation to have two sequential steps, experimental data of the rate constants for each of two steps of each blood sample were calculated. All these parameters and crenation-time history curves appear different and characteristic for each group of ABO-System. Further work to verify detected sensibility changes in inmunohematological reactions with Laser treated red blood cells is under progress.

Laser Raman spectroscopy was used to investigate cataractogenesis from infrared sources and human senile cataract. Rabbits were exposed to radiation from a ND-YAG laser; Raman spectra were recorded and results correlated with established ultraviolet damage mechanism. Human senile lenses were also examined by Raman spectroscopy. The Raman technique appears suitable for potential clinical diagnosis.*

Lasers have been used for some time now on animals for experimental purposes prior to their use in human medical and surgical fields. However the use of lasers in veterinary medicine and surgery per se is a recent development. We describe the application of high and low intensity laser technology in a general overview of the current uses, some limitations to its use and future needs for future inquiry and development.

With the increasing market in laser medicine and surgery it is well to plan ahead so that there will be increasing production. For the concept of so-called laser biostimulation with various low output laser systems there is much need for well controlled studies to avoid discrediting all of laser medicine. There is great potential for the future in laser instrumentation for heart disease, cancer research, diagnoses and treatment, all fields of surgery, and in perinatology. Also, laser communications and information handling can make for deliverance of better health care. It is well to open up better lines of communication between laser industry and modern medicine.

The effectiveness of hematoporphyrin derivative (HpD) photoradiation therapy (PRT) will depend on (a) the tumor selectivity of HpD, (b) HpD dosage and the delay time between injection and treatment, (c) spectrum of light source, (d) delivered light dose and (e) the optical characteristics of the tissue. Evaluation of the potential useful wavelength of light for HpD-PRT and thier penetration in different tissues have been evaluated. On a theoretical basis, green light (500-520nm) and violet light (400-420nm) will be useful for treating only superficial lesions less than 0.5mm thick while red light (620-640nm) is the light of choice for treatment at depths greater than 0.5mmfor a cat brain tissue.

Clinical trials of photoradiation therapy (PRT) have been carried out in 32 patients with lung cancer, 10 of which are reported here. The aim is the palliative treatment and control of cancer lesions obstructing an airway, whether in the trachea or in a large bronchus leading to a lung or to a lobe of a lung. The objective or patient benefit is the opening up of the lumen of the airway to improve ventilation to relieve shortness of breath, and to prevent the retention of secretions containing bacteria, that cause lung infections. Immediate results (one to several weeks) were uniformly good. Air passageways were opened up as revealed by subsequent bronchoscopy, after clearing away tumor debris. Short-term (several months) observations were limited in number but indicate potentially good results. Future research is directed toward better criteria for patient selection improved patient evaluation that will reveal potential cardiac and pulmonary complications, and the devising of more suitable laser light delivery techniques.

Liver cancer is an aggressively malignant tumor refractory to known therapy. This study investigated the potential of hematoporphyrin (HP) and light energy to selectively photo-necrose experimental hepatoma in rats. Hepatoma cells (106) when inoculated directly into the liver of recipient Wistar rats developed into a rapidly growing neoplasm which simulated human liver cancer. Seventy-two hours following intravenous HP (5-25 mg/kg), the tumor exhibited patchy porphyrin fluorescence on gross examination and on U.V. microscopy. Fluorescence was maximal in areas furthest from blood vessels, and was within cells which morphologically appeared least viable. Liver tissue did not fluoresce but contained HP concentrations 60% of that in fluorescent tumor and 3 times greater than that in non-fluorescent viable tumor. Tumor necrosis produced by light (Tungsten, 600-640 nm, 200 mW/ sq cm, 240 joules) and HP appeared macroscopically complete to a depth of 1.5 cm. Histologically, in necrotic areas, there were islands of surviving tumor enveloping blood vessels. Three weeks after irradiation, tumor volume averaged 2 mm3 compared to 250 mm3 in control operated animals where HP containing neoplasm was exposed to diffuse room light only. Neighboring liver tissue also was necrosed reflecting HP uptake. As the liver behaved in vivo as a tumor, this provided an ideal solid tissue model to study the biology of the photodynamic action of porphyrins. The clearly visible line of demarcation between photonecrosed and living tissue allowed measurement of the depth of necrosis with an accuracy of a fraction of a millimeter. We observed the following: 1) blue light (Xenon, bandwidth 60 nm, 30 mW/sq cm, 360 joules) produced 1/10 depth of necrosis when compared to red light of the same bandwidth and energy. This may relate in part to demonstrated preferential absorption of shorter wavelength (<590 nm) light energy by liver tissue pigments and hemoglobin. 2) The depth of necrosis related to the log of incident light energy (joules/sq cm). 3) The photodynamic effect of red coherent light (545-625 nm) from a tunable dye pulse laser system was no different from that of red light from a continuous noncoherent (Tungsten) source. 4) There was a logarithmic relationship between the dose of HP administered and the depth of liver necrosis. 5) If one interposed a photoopaque shield between the incident laser light and the liver, a considerable back scattering of light caused tissue necrosis behind the shield. However, when the diameter of the shield was greater than 1.3 mm, there always was a surviving island of tissue which escaped destruction. 6) The depth of necrosis in liver (mms) was significantly less than adjacent non-pigment tumor (cms) which suggests that the optical density of the tissue is a major factor in determining effective light penetration. We conclude that measurement of tissue porphyrin, and optical density with reference to the liver, will allow precise calculation potentially of major clinical importance in the treatment of skin and mucosal cancers.

We have developped a device which includes two laser sources (nitrogen laser and dye laser), an optical system, an optical fiber able to transmit ultra-violet, visible and infrared light, photoreceivers and an analog circuit feeding a microcomputer, in order to perform in situ and on line study of NADH/NAD ratio by fluorimetry. The technical description of the device has already been exposed in the SPIE'S Technical Symposium East'81, held in April 81 in Washington DC. We intend now to present the scientific grounds of the method, the technical improvements concerning the propagation of light from the sources to the living tissue as well as from and to the receivers (special processing of the extremities of the optical fiber) and the results of the experiments carried out with several models. Additional information on the non-occurence of the photo-optical artifact and on the considered applications (heart surgery for instance) will be provided.

An important medical laser application is in the emerging field of photoradiation therapy (PRT). PRT is the process in which malignant tissue is destroyed by administration of light to a specific photosensitized site. Filtered arcs, incandescents and dye lasers have been used as sources of activating light. We have carried out light experiments in tissue to study such PRT light distributions. The results of this research have shown that a number of important optical phenomena occurring within illuminated tissue must be accounted for in order to make good predictions of tumor light dosage. Among these are; tissue type, interface effects and anomalies due to composition. These effects substantially influence light levels in PRT and, thus, the therapeutic effect. The uniqueness of tissue as a medium for light transport presents special problems for optics research and instrumentation. Successful solutions necessarily will involve collaboration between the life sciences and optic specialists. Attempts at treatment of human disease using non-ionizing radiation have a history archaeologically traceable to archaic societies (in which the sun's photons were used and often worshipped).1 Western medicine in the past, has used visible light beneficially, albeit empirically, on a few ailments. However, in this century, a significant development in the understanding and in the therapeutic use of this electromagnetic radiation in the UV, visible and IR has occurred, based on scientific study. This utilization of radiation in the visible and ultraviolet can be by two distinct processes. One is through the direct action of the photons which serve as the sole treatment agent. In this case the photon interacts with the cell, or its components, in a single step, to produce a desired effect. An example is the successful use of blue light for treatment of bilirubinemia in newborns. The second process is a biological effect produced through the combination of electromagnetic radiation with a photosensitive drug or naturally occurring compounds. The photo-sensitive molecule (ideally concentrated in the target tissue) serves as a kind of reaction catalyst in the living subject by transferring the photon's energy for the initiation of a biochemical reaction. An example is the use of the photosensitive compound hematoporphyrin derivative (HpD) combined with red light used to initiate a lethal oxidation of tumor tissue in cancer therapy. Dougherty has introduced this process and termed it photoradiation therapy (PRT)2. The current understanding of the PRT mechanism is schematized in Figure 1. A photosensitive compound (PC) at groundstate, concentrated in target tissue, is acted on by a photon of appropriate energy (hv) resulting in PC being raised from its ground state to the short lived, excited singlet state (PCs). In step two, PCs decays to its longer lived triplet state (PCt). In the third step, the excited compound, PCt in the presence of ground state molecular oxygen (02) transfers its energy to the oxygen, thus raising oxygen to a highly reactive singlet oxygen state (02s). PC, through the foregoing transition, is returned to its ground state and may repeat its role on encounter with a second photon. In the last step, 02s reacts with an available tissue substrate (M). Some of this toxic oxidation is thought to occur in membrane structures, with resulting cellular disruption. The damage to this cell component is presumed to be the key to the observed tumor destruction by the

The use of the laser in general surgery is slightly over ten years. Many advances have been made during this time, but many more are needed. In order to understand the poor acceptance of the laser by general surgeons to this period of time, one must first understand the characteristics of the surgeon. Most surgeons are very conservative people, doing surgery only when nothing else will work. Secondly, surgeons are trained to feel the incision or the pressure of the knife and to see the sharp, nice dissection being done and the tissues parting. In addition, he feels a certain amount of insecurity if he is using a device where he's not exactly sure of the depth of the cut. Certainly, new types of lasers will aid the general surgeon to better understand and to use the C02 and other lasers and may eventually give them reason to accept it as a definite modality in surgery.

The greatest advancements in the past three decades in surgery were the development of precision surgical and endosccpic techniques. The introduction of binocular magnification with improved lighting in ear surgery contributed mainly to improve precision techniques in surgery. An order of magnitude improvement in precision was achieved using magnification and delicate instruments. Similarly, endoscopic instrumentation, rigid and flexible, made previously unaccessible areas accessible without major surgical intervention.

Multipurpose surgical CO2 lasers marketed in the USA have been developed to be applicable to a variety of surgical procedures in many surgical fields. They are all suited for endoscopic surgical procedures and can be fitted to all standard surgical microscopes. They all can adjust the focal length of the laser beam to the different standard focal lengths of the surgical microscope which for instance in laryngoscopy is 400 mm and in colposcopy 300 mm. One laser instrument can even change the spot size in a given focal distance which is very advantageous for some microsurgical procedures (Merrimack Laboratories 820). All multipurpose surgical CO2 laser systems provide a multi-articulated surgical arm for free-hand surgery. The surgical arms are cumbersome to use but they are adapted to the surgeons needs with ingenuity. The practicality of the multi-articulated surgical arms depends mostly on the distance of the handpiece from the surgical console which now is also overbridged by the laser tube in most surgical laser system. The spot size of the beam is variable in most handpieces by interchangeable lenses which modify the focal distance of the beam and the power density. Another common feature in all systems is a coaxial He-Ne pilot light which provides a red spot which unfortunately becomes invisible in a bleeding surgical field. Most surgical laser systems have a spacial mode of TEM 00 which is essential for incisional surgery. The continuous mode of beam delivery is used for incisional surgery and also for most endoscopic procedures.

Light Amplification by the Stimulated Emission of Radiation results in a release of electromagnetic energy which is unique in that the light energy thus generated is of a single wave length (monochromatic), and the waves are in synchrony in space and time (coherent). The energy is not dampened by dispersion or interference of conflicting electromagnectic fields. Each substance which can be made to laser (laser medium) emits light energy of a wave length specific to itself. In the spectrum of electromagnetic waves, visible light occupies a narrow band. Light in the far infrared spectrum, produced by the carbon dioxide laser, is invisible and is not absorbed by pigmented materials. It can be focused to a fine point with a selenium-germanium lens. On impact with solid or liquid matter, light energy is converted to heat energy. In living tissue, this results in an instantaneous elevation of intracellular water temperture to the boiling point and explosion of the cell to a cloud of smoke. The speed of the process protects adjacent cells by the leidenfrostche or water jacket effect, which insulates the area of intense heat from its surroundings.

Several investigators have explored the possibility of revascularizing the ischemic myocardium from the ventricular chamber. The high energy laser was investigated as a means to accomplish this based on the finding that the laser beam could produce small channels in the myocardium devoid of debris and scarring. The technique was investigated in four groups of mongrel dogs. In three groups the left anterior descending branch of the coronary artery was ligated and the myocardium exposed to laser treatment. The fourth group was the control, the LAD was ligated but laser channels were not made. In the three groups treated by laser, the myocardium was protected by the channels. In the control group all animals died within 20 minutes of LAD ligation. Animals in the first three groups were subsequently sacrificed at various intervals. Channels were visualized grossly, microscopically they were patent and endothelialized. The results indicate channels made by laser effectively protect the myocardium from acute coronary artery occlusion.