Reduction of laser-induced pathologic tissue injury using pulsed energy delivery

Continuous-wave (CW) laser irradiation of cardiovascular tissues is characterized by 2 distinctive histologic findings: a superficial zone of coagulation necrosis and a subjacent zone of polymorphous lacunae. The present investigation was designed to determine whether such injury could be eliminated by altering the temporal profile of laser energy delivery. One hundred forty-five myocardial slices were irradiated with an air-tissue interface using CW laser irradiation at wavelengths of 488 to 515 nm (argon), 1,064 nm (Nd-YAG) and 10,600 nm (CO2). Pulsed laser irradiation included 248 nm (excimer); 355, 532 and 1,064 nm (Nd-YAG); and 515 nm (mode-locked argon). Energy profiles in the pulsed mode included a range of repetition rates (1 Hz to 256 MHz), pulse duration (0.2 to 358 ns) and pulse energies (2 nJ to 370 mJ). Resultant average powers were 0.1 to 38 W. Grossly visible charring of myocardial tissue was observed at all laser wavelengths when the laser energy profile was CW or pulsed at high repetition rates (more than 2 KHz) and low pulse energies (less than 3 mJ) independent of the wavelengths used. In contrast, when laser energy was pulsed at low repetition rates (less than 200 Hz) and large pulse energies (more than 10 mJ), neither gross nor histologic signs of thermal injury were observed. Pathologic injury associated with laser-induced tissue ablation may thus be substantially reduced by use of pulsed energy delivery at low repetition rates. Potential advantages of pulsed laser energy include a more benign healing process, a less thrombogenic surface, and improved preservation of structural tissue integrity.     

Fragmentation of biliary calculi with tunable dye lasers

The feasibility of using lasers to fragment biliary calculi was examined in vitro. Flashlamp-pumped tunable dye lasers were coupled to small-diameter flexible quartz fibers that were placed in direct contact with biliary calculi. The minimum laser energy necessary to damage a calculus was measured for wavelengths between 450 and 700 nm and for pulse durations between 0.8 and 360 microseconds. This threshold energy increased with increasing wavelength but was not significantly affected by pulse duration. Cholesterol stones had uniformly higher thresholds than pigmented ones. When a repetitively pulsed laser was used, complete fragmentation required fewer than 500 pulses and fragments were predominantly less than 2 mm. The pulsed dye laser can effectively fragment biliary calculi when transmitted through a small-diameter quartz fiber and may be useful as a tool for fragmenting retained common duct stones.     

The interaction between excimer laser energy and vascular tissue

The effects of XeF1 excimer laser on isolated normal and atherosclerotic aorta were studied. Experiments were performed in flowing water at constant temperature, flow rate, water depth, pulse width (10 nsec), wavelength (351 nm), beam size (1 mm2) and focal length (50 cm). The number of pulses, the pulse energy, and the pulse frequency were varied, and the vascular tissue was studied histologically. The following observations were made: tissue ablation required a minimum threshold pulse energy and was nonlinearly proportional to the number of pulses and the pulse energy delivered; precise tissue ablation occurred at low pulse frequencies, but changes resembling a thermal process were seen as pulse frequency increased; calcified plaque was more photoresistant than atheroma or normal vessel; excimer laser energy was markedly attenuated by blood; and the time interval between pulses and high peak power are related to the precision of ablation by pulsed excimer laser. It is concluded that excimer laser can rapidly and precisely ablate vascular tissue by a photothermal process.     

Laser-induced vascular lesions by cw-NdYAG or pulsed UV lasers during angioplastic procedures

Conventional (NdYAG, Argon and CO2 lasers) laser and pulsed far ultraviolet laser radiation are able to remove arteriosclerotic tissue of the arterial wall. However, there is a striking difference between both systems: The continuous wave of conventional wave-length laser-radiation produces considerable thermal injury to the surrounding tissue, whereas the effect of pulsed far ultraviolet radiation induces less or no thermal damage despite an easily assessable tissue-removing effect. In the following study the potential of far UV laser-radiation for recanalization of occluded vessels is demonstrated in in-vitro experiments on fresh and well preserved atherosclerotic human vessels.     

Effects of different types of continuous emission laser on human atheromatous plaques in vitro

The laser beam is a punctual source of thermal energy which can be used to vaporize human atheroma. The physical characteristics of optimal utilisation (total energy, wave length, continuous or pulsed emission) have not been clearly defined. We carried out in vitro irradiations of human atheromatous material and healthy arterial wall with different combinations of power-emission time and three different wave lengths, using four continuous emission laser beams (Nd-Yag, two CO2 with different lenses, Argon). The beam emitted by the Nd-Yag was absorbed less than the CO2 and Argon lasers, which had comparable effects above a threshold of 2 to 14 joules. The weight of vaporized fibro-atheromatous material was 0.11 mg per joule of optical energy dissipated (CO2). No radical difference was observed in the nature of the effects of the three types of laser studied. The problems of using this technique on the beating heart remain unsolved (ballistics of the emerging ray). Other modes of emission (pulsed) and different wave lengths should be studied.     

Physics of surgery with lasers

The characteristics of the principal lasers used in surgery are summarized in Table 1. Their diverse effects on biologic tissues permit the following generalizations: The CO2 laser is best suited for precise, visually controllable tissue removal by vaporization with minimal marginal damage. Hemostasis is excellent for bleeding from capillary vessels, but difficult for larger ones. The Nd:YAG laser is best suited for the coagulation of larger tissue volumes of the order of 10 mm3 or more. Tissue heating inherently extends for several millimeters, leading to excellent hemostasis. Radiation from this laser is well transmitted through flexible optical fibers and clear fluids. The argon ion laser emits radiation in the visible range and is ideally suited for treating the retina and other tissues in the eye without damage to its transparent structures. Radiation of this laser is strongly absorbed by pigmented tissues, scattered and reflected by others, and transmitted by fluids. Its radiation can be focused to very small spot sizes, leading to high precision and high-power densities. It has hemostatic properties intermediate between those of the CO2 and of the Nd:YAG laser radiations. It is well transmitted through optical fibers and clear fluids. It is used extensively in ophthalmology and dermatology. Selected applications to neurosurgery and otology are being investigated. These lasers have become indispensable adjuncts to the surgical armamentarium of several specialties. The very success of these lasers is leading to a critical examination of their shortcomings and to a search for improved systems. Examples are (1) the ongoing search for optical fibers to transmit the radiation of the CO2 laser; (2) the development of systems for the sequential delivery to tissues of several wavelengths from a single unit (Fig. 14); and (3) investigations of tissue effects of laser beams in the ultraviolet and in the infrared at wavelengths intermediate between those of the Nd:YAG and CO2 lasers. The use of lasers has already contributed to improved medical care in many surgical disciplines. Additional areas of application can be confidently anticipated.     

Endoscopic treatment of idiopathic subglottic stenosis with digital AcuBlade robotic microsurgery system

Herein, we described a novel method as the use of AcuBlade robotic microsurgery system to manage idiopathic subglottic stenosis in a 73‐y‐old lady. Compared to traditional CO2 lasers, AcuBlade facilitated the scar resection by the generation of different shape of beams (straight, curved, or disk). The same setting used for phonomicrosurgery (1‐mm beam length, power of 10 W and pulse duration of 0.05‐s) allowed to obtain fast, long, and uniform cuts. In addition, the reduction of the number of laser passes over the same area prevented injury of adjacent tissue and thus reduced the risk of recurrence.     

Coronary excimer laser angioplasty: reduced complications and indium-111 platelet accumulation compared with thermal laser angioplasty

The relative safety and thrombogenicity of pulsed excimer and thermal laser angioplasty systems were compared in 20 normal coronary artery segments in a total of seven pigs. Using similar over the wire catheter systems and laser delivery periods of 3 to 5 s, thermal laser angioplasty was achieved with a 1.3 mm metal probe heated with 10 W of continuous argon laser energy and excimer laser angioplasty was performed with a 4.5F excimer laser catheter consisting of 13 concentrically arranged 200 microns fiber optics delivering 35 to 40 mJ/mm2 of xenon chloride (308 nm) excimer laser irradiation at a repetition rate of 25 to 30 Hz and a pulse duration of 120 ns. On angiography, the incidence of vessel perforation (1 in 10 versus 3 in 10) and abrupt vessel closure (0 in 10 versus 2 in 10) was less with excimer compared with thermal laser angioplasty. Macroscopically, there was a greater incidence of mural and occlusive thrombus formation after thermal laser than after pulsed excimer laser angioplasty. Histologic examination confirmed that this thrombogenicity was associated with greater charring and coagulation necrosis of the media. Quantitative indium-111-labeled platelet deposition was significantly increased after thermal laser angioplasty (median 87.2 x 10(6)/cm length) compared with excimer-treated (0.4 x 10(6)/cm length) or control (1.2 x 10(6)cm length) segments (p less than 0.001). Thus, excimer laser angioplasty was found to result in fewer complications and, as a consequence, less thrombosis and platelet accumulation than did thermal laser angioplasty.     

Plaque ablation by excimer laser irradiation using a movable energy-transmitting device

During the past 2 years, excimer laser energy has been shown to provide a highly suitable type of atherosclerotic plaque ablation, especially in small-diameter vessels such as coronary or crural arteries. Nevertheless, transmission of far-ultraviolet pulsed laser power has remained a major problem in animal studies and clinical trials. In an attempt to solve this problem, we constructed an energy-transmitting device for use with a Lambdaphysics EMG 102 excimer laser. The transmission system, which was housed in a rigid articulated arm, allowed movement in all directions and rotation along the long axis, thus permitting easy handling and guiding of the laser beam in the operating field. To test whether this device could deliver enough energy to remove atherosclerotic plaques within a period that would meet the requirements for intraoperative use, we obtained fresh human cadaver coronary arteries both with and without atherosclerotic disease, and irradiated them vertically and coaxially. A power meter was used to determine the effective amount of energy delivered at the distal end of each vessel. Energy densities up to 3 J/cm(2)/pulse were obtained, owing to energy focussing within the transmitting device. At 5 Hertz (Hz), tissue ablation consisted of approximately 20 microm/pulse. Areas of normal vascular tissue, as well as fibrohyalinous and lipid plaque components, were promptly ablated. Macroscopically, the "lasered holes" appeared well-circumscribed, with clear-cut surfaces and no carbonization. Light microscopy revealed no thermal damage to the boundary tissue. With this new energy-transmitting device, the surgeon can use excimer laser irradiation intraoperatively. There is no significant loss of energy between the generator and the tip, and energy densities of 3 J/cm(2)/pulse are available for sufficient plaque removal.     

Acute biologic response to excimer versus thermal laser angioplasty in experimental atherosclerosis

Vascular injury and platelet accumulation after balloon angioplasty are two potentially important triggers of the process of restenosis that may be minimized by the use of laser energy to ablate atherosclerotic plaque. The type of laser most suitable to achieve these goals remains unknown. Accordingly, angiographic and histologic studies and quantitative platelet deposition analysis were performed on 27 atherosclerotic rabbit iliac arteries randomized to treatment with excimer laser or thermal laser angioplasty. Excimer laser angioplasty was achieved with 35 to 40 mJ/mm2 of 308 nm xenon chloride irradiation delivered through a 4.5F catheter made of 13 concentrically arranged 200 microns fiber optics, at a repetition rate of 25 to 30 Hz and a pulse duration of 135 ns; thermal laser angioplasty was achieved with a 1.7 mm metal probe heated with 10 W of continuous wave argon laser energy. The baseline and post-laser luminal diameters of excimer laser-treated vessels (0.92 +/- 0.28 and 1.56 +/- 0.48 mm, respectively) were similar to those observed in thermal laser-treated vessels (1.05 +/- 0.44 and 1.61 +/- 0.41 mm, respectively). Perforation occurred in 4 (29%) of 14 thermal laser-treated arteries and in 0 of 13 excimer laser-treated arteries (p = 0.04); spasm was observed in only 1 thermal laser-treated vessel. On the basis of a quantitative histologic grading scheme (damage scores of 0 to 4), greater degrees of injury were measured in thermal versus excimer laser-treated vessels (2.4 +/- 1.0 versus 1.3 +/- 0.4, p = 0.009).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endoscopic pulsed dye laser lithotripsy of gallbladder calculi in vivo.

We have evaluated the efficacy and safety of pulsed dye laser lithotripsy of gallbladder calculi using a percutaneous endoscopic technique in a porcine model. Fragmentation was readily achieved in vivo. Using a combination of laser lithotripsy and saline lavage, complete removal of all stone debris was feasible through a 24 F tract (N = 3). However, the degree of fragmentation required rendered removal through a smaller tract inefficient, a mean 53% of stone mass being retrievable through a 16 F tract (N = 11). Repeated laser activation at 1 mm from the gallbladder mucosa produced minimal injury, regardless of pulse energy. When the laser fiber was pressed against the mucosa, perforation of the gallbladder was possible at therapeutic pulse energy, but this did not lead to clinical sequelae. We conclude that the pulsed dye laser is a safe and effective means of fragmenting gallbladder calculi in vivo.     

Laser tissue interaction in direct myocardial revascularization.

This investigation examines the various laser choices used for transmyocardial laser revascularization (TMLR) with emphasis on the laser-tissue interaction. A series of in vivo (porcine model, n=27) and in vitro experiments were performed to study the effects of CO(2), holmium:YAG, and XeCl excimer lasers on the histological outcome of TMR channels. Computerized histopathological analysis has revealed that the CO(2) and holmium:YAG lasers produce substantial unpredictable thermal damage and differ predominantly in the amount of the mechanical injury or tissue shredding. In comparison, the excimer laser appears to produce the most uniform tissue ablation with the least thermal and shockwave damage.     

The excimer laser: gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease

Excimer lasers are pulsed gas lasers that use a mixture of a rare gas and halogen as the active medium to generate pulses of short wavelength, high energy ultraviolet light. A krypton-fluoride gas mixture was used to achieve an excimer emission at a wavelength of 248 nm. A total of 30 atherosclerotic coronary artery segments were irradiated over a range of pulse energies (250 to 750 mJ), repetition rates (2 to 25 Hz), average powers (1.9 to 18.8 watts) and cumulative exposures (3 to 12 seconds). In no case was there gross, light microscopic or ultrastructural evidence of the pathologic injury typically associated with continuous wave laser irradiation of coronary artery segments. Similar results were achieved after excimer laser irradiation of 30 samples of myocardium. Excimer irradiation of calcified aortic valve leaflets accomplished focal debridement without pathologic tissue injury; when total debridement was attempted, however, gross charring was observed. The paucity of pathologic alterations observed after excimer irradiation of cardiovascular tissue may prove beneficial in precisely controlling laser ablation of pathologic tissue without injury to the surrounding normal tissue. Clinical application of excimer laser irradiation requires resolution of several issues, including the development of suitable fiber optics and laser coupling, evaluation of potential ultraviolet toxicity, and demonstration that ultraviolet light can be transmitted through a blood-filled system.     

In vitro opening of human atheromatous coronary arteries using a pulsed laser

This study was undertaken to assess the respective values of pulsed and continuous laser emission for in vitro recanalisation of very stenosed atheromatous human coronary arteries. The Nd-YAG laser used emitted a 10 Hz 10 ns burst in the infrared band (1 064 microns). Previous spectroscopic studies had shown no specific band of absorption in the spectral field of emission of the usual lasers. The laser beam was focused in the axis of the segment of coronary artery irradiated. The crater or neo lumen obtained usually had irregular walls. No perforation of the arterial wall or macroscopic debris were observed. Histological studies showed minimal burn lesions with sparse coagulation necrosis limited to a few tens of micron thickness. The percentage recanalisation obtained with pulses of 200 mJ attained 50% for a total energy of 450 J delivered in 2 mn. This study confirmed the feasibility of disobliteration of atheromatous coronary arteries by pulsed laser. Our results suggest that ultra short pulsed laser acts more by a mechanical than by a thermal mechanism which may lead to less side effects than observed in vivo with continuous laser emission.     

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers.

BACKGROUND. Recently, laser-heated and radio frequency-heated balloon angioplasty techniques have been proposed as a means to treat or minimize dissection and elastic recoil but have been associated with a high rate of clinical restenosis. Similarly, pulsed laser angioplasty techniques proposed to minimize thermal injury while ablating obstructing atheroma have failed to reduce clinical restenosis. Because "hot balloon" and pulsed laser angioplasty create both mechanical and thermal injury, it has been difficult to discern the cause of the smooth muscle cell (SMC) proliferation resulting in restenosis and whether such magnitude of proliferation is predictable and dose related. This study was undertaken to explore these issues. METHODS AND RESULTS. Localized thermal lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser in nine rabbit aortas, which consistently led to a focal proliferation of SMC that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser irradiation at multiple independent sites of 24 central rabbit ear arteries without ablation led to brief approximately 30 degrees C thermal transients and thermal damage to the artery wall resulting in significant neointimal proliferation by 3 weeks and a mean cross-sectional narrowing of 59 +/- 17% at a dose of 390 mJ/mm2. Acute and chronic responses to varying total energy deposition were studied by histology after the rabbits were killed at 2 hours to 4 weeks. Arterial segments midway between laser injuries were unaffected and served as internal controls. Neointimal proliferation at 3 weeks after laser injury exhibited a clear dose dependence. Mean cross-sectional narrowing increased from 34 +/- 10% to 85 +/- 15% as laser fluence increased from 240 mJ/cm2 to 640 mJ/cm2 (r = 0.84). Similarly, cross-sectional narrowing caused by SMC neointimal proliferation increased from 20 +/- 10% to 77 +/- 17% for a fixed surface irradiation as the depth of the most superficial arterial media decreased from 600 microns to 330 microns (r = 0.94). CONCLUSIONS. Thermal injury to the arterial wall is a potent stimulus for SMC proliferation and may necessitate reduction in laser or thermal energy used for angioplasty. Moreover, a dose-response relation exists between the degree of thermal injury and SMC proliferative response. Hence, this technique could be used as a practical model of restenosis suitable for screening therapies for inhibition of SMC proliferation.     

Experimental air leaks in lung sealed by low-energy carbon dioxide laser irradiation

When a focused carbon dioxide laser beam strikes a surface of tissue, the light energy is converted instantly into thermal energy, causing cells directly in the laser's path to vaporize. Because the carbon dioxide laser's energy is well absorbed by water, this thermal effect is attenuated at a distance of 100 mu. If the laser beam is "defocused," the same thermal energy is dissipated over a larger area, causing only desiccation and melting of tissue without vaporization; however, the depth of injury remains shallow. This modified technique has been used to seal artificially created air leaks in the canine lung. Twelve mongrel dogs were anesthetized, intubated, and ventilated. The lingula was exposed sterilely through a left thoracotomy. A 1 X 3-mm hole was made in the lung at 1 cm from the edge. The created air and blood leaks were sealed with a defocused carbon dioxide laser beam set at 8 W (32 W/sq cm). Each tissue "weld" withstood 40 cm H2O of peak ventilation pressure without leak. At the time of reoperation three weeks later, there was apparent complete healing of the pulmonary surface. No air leaks were present. Histologic examination showed a small zone of amorphous coagulated pleura and lung overlying a zone of minimal atelectasis. Normal lung was present within 150 mu of the laser seal. This new technique was performed safely and easily with currently available carbon dioxide lasers in the laboratory. It is presently undergoing intraoperative trials in a controlled clinical setting.     

Thermal Effects In Vivo from Holmium: YAG Lasing in the Intracoronary Setting

While the thermal effect of laser energy does ablate atheromatous plaque, thermal injury to adjacent tissue produces high rates of arterial thrombosis and spasm. Holmium:YAG lasers use a pulsed laser source to maximize photoblative effects while minimizing thermal effects. These lasers have been utilized clinically to ablate thousands of complex coronary lesions with low rates of spasm and thrombosis, suggesting that little or no thermal injury occurs with these devices. However, we have been able to detect thermal injury in patients angioscopically in coronary arteries after holmium:YAG lasing. Here we report the use of directional coronary atherectomy (DCA) to òbiopsyó arteries in patients following holmium:YAG laser treatment, allowing direct histologic examination of lased tissue. Thirty such lased DCA samples were matched for patient age, gender, target vessel, and lesion characteristics with thirty control DCA samples obtained from patients undergoing DCA without prior lasing. Blinded pathologic examination correctly identified 27/30 control samples but only 18/30 lased samples. Subsequent unblinded analysis, sometimes with recutting and restaining of tissue blocks, resulted in the detection of thermal effects in 27/30 lased samples. The thermal effects seen included edge disruption, charring, coagulation necrosis, and most commonly, vacuolization. We conclude that holmium:YAG lasing does produce detectable thermal effects in tissue in most patients. These effects can be quite subtle or can be extensive, but do not predict poor patient outcome.     

Effects of carbon dioxide, Nd-YAG, and argon laser radiation on coronary atheromatous plaques

Laser radiation has been successfully applied in several areas of medical practice. However, its use in cardiology and specifically its effects on obstructive atherosclerosis have largely been unexplored. To evaluate effects of laser radiation on atherosclerotic plaques 25 fresh necropsy atherosclerotic coronary artery segments were exposed to laser radiation with either a carbon dioxide, Nd-YAG, or argon laser. Split or intact segments were prepared under dry conditions or while immersed in saline solution or blood and exposed to laser radiation as power and duration of exposure varied. All 3 lasers were capable of creating controlled injury to atherosclerotic plaques. In general, the magnitude of injury varied according to the total energy delivered (that is, power times duration of exposure). Calcified and noncalcified plaques were penetrated with similar levels of injury. Histologic examination demonstrated that laser radiation produced a wedge incision in the atherosclerotic plaque which was surrounded by zones of thermal and acoustic injury.     

On the Ablation Behavior of Carbon Fiber-Reinforced Plastics during Laser Surface Treatment Using Pulsed Lasers

This contribution discusses the ablation phenomena observed during laser treatment of carbon fiber-reinforced plastics (CFRPs) with pulsed lasers observed employing laser sources with wavelengths of 355 nm, 1064 nm and 10.6 µm and pulse durations from picoseconds (11 ps) to microseconds (14 µs) are analyzed and discussed. In particular, the threshold fluence of the matrix material epoxy (EP) and the damage threshold of CFRP were calculated. Moreover, two general surface pretreatment strategies are investigated, including selective matrix removal and structure generation through indentation (ablation of both, matrix material and fibers) with a cross-like morphology. The surfaces obtained after the laser treatment are characterized by means of optical and scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy is employed for the analysis of composite and constituent materials epoxy and carbon fibers. As a result, different ablation mechanisms, including evaporation and delamination are observed, depending on the employed laser wavelength and pulse duration. For both 355 nm and 1064 nm wavelength, the laser radiation produces only partial ablation of the carbon fibers due to their higher absorption coefficient compared to the epoxy matrix. Although a selective matrix removal without residues is achieved using the pulsed CO₂ laser. Differently, both constituent materials are ablated with the nanosecond pulsed UV laser, producing indentations. The sum of the investigations has shown that existing theories of laser technology, such as the ablation threshold according to Liu et al., can be applied to composite materials only to a limited extent. Furthermore, it has been found that the pronounced heterogeneity of CFRP mostly leads to an inhomogeneous ablation result, both when creating grooves and during selective matrix removal, where the carbon fibers influence the ablation result by their thermal conductivity, depending on fiber direction. Finally, despite the material inhomogeneity, a scanning strategy has been developed to compensate the heterogeneous ablation results regarding structure depth, width and heat affected zone.     

Experimental coronary angioplasty using a UV-Excimer laser

Both conventional Argon- and NdYAG-lasers in continuous wave or pulsed application and far ultraviolet laser radiation are able to cause a loss of substance of biologic tissue. The thermic and ablative effects of NdYAG-lasers and UV-Excimer lasers at the wavelengths of 193 nm (ArF) and 248 mm (KrF) on inconspicuous and atherosclerotic human and animal coronary vessels were compared by histologic and, in some cases, by scanning electron microscopic examinations. Whereas common lasers generally produce thermal injuries of the surroundings, pulsed far ultra-violet radiation is characterized by a lack of thermic damage. The UV-radiation in vitro cleaned precise defects of substance, and assessable tissue-removing effects were found. These results were influenced by the wavelength used. In general, the removing effect was good in normal and atherosclerotic tissue, whereas massive calcification was very resistant. Excimer lasers seem to be preferable for ablation of atherosclerotic tissue, but still there is a great number of technical problems to be solved until use in the clinical setting can be justified.