Disparate absorption of argon laser radiation by fibrous versus fatty plaque: implications for laser angioplasty

The thermal response of white fibrous atheromatous plaque to argon laser irradiation was compared with the thermal response of yellow fatty plaque and normal aortic wall to the same type of radiation. Samples of normal aorta, fibrous, and fatty plaque were irradiated in air with 3.5 Watts of laser power on a 2 mm spot for 5 and 10 seconds. Heterogeneous foci, each covering normal aorta and either fibrous or fatty plaque, were additionally irradiated with 7 Watts on a 1 cm spot for 30 seconds to 2.5 minutes. Tissue surface temperature was monitored during laser irradiation via a 3-5 micron infrared camera. For the 2 mm spot and 5 second exposure time, argon laser irradiation of normal aorta produced popping and surface tearing at a peak temperature of 145 +/- 10 degrees C. Irradiation of fatty plaque produced popping and crater formation at a peak temperature of 200 +/- 10 degrees C. However, fibrous plaque was nonablatively discolored by the same dose of laser radiation with a peak temperature of only 85 +/- 10 degrees C. Irradiation for 10 seconds caused crater formation and carbonization in the fatty plaque but failed to produce ablation in the fibrous plaque. Irradiation of the heterogeneous foci confirmed the disparity in the temperature attained by these two types of plaque and their degree of damage. Therefore, this study suggests that the ablation threshold for soft atheroma is strongly dependent on the optical properties of the particular type of tissue. Yellow fatty plaque preferentially absorbs argon laser radiation, but white fibrous plaque absorbs this radiation less readily than normal aortic wall.     

The pulsed dye laser and atherosclerotic vascular disease

The use of a pulsed dye laser to ablate atheromatous tissue obtained from post-mortem human aortic specimens is reported. Laser energy was delivered with a 600 micron quartz fibre, at a wavelength of 504 nm and a pulse length of 1 microseconds. Pulse energy was varied from 30-140 mJ, producing peak pulse powers of the order of 100 kW. With these parameters the laser ablated fatty, fibrous and calcified plaques. At this wavelength atheroma is vaporized but there is minimal damage to normal vessel wall, due to preferential absorption of the laser light. Light microscopy shows that by microsecond pulsing, thermal damage to surrounding tissues associated with continuous wave lasers is avoided. Transmission electron micrographs reveal a sharp demarcation between a laser crater and the adjacent vessel wall with little ultrastructural disruption. Scanning electron micrographs show the crater walls to be smooth. The pulsed dye laser may therefore be effective in the treatment of occlusive peripheral vascular disease without undue risk of vessel perforation.     

Arterial response to excimer and argon laser irradiation in the atherosclerotic swine

Injury associated with laser-induced tissue ablation may be reduced by using pulsed energy delivery at low repetition rates, as opposed to using continuous wave energy delivery. This study was designed to examine the similarities and differences between these two systems as regards the healing process, and to examine whether one is superior to the other. In order to test this postulate, the healing response of normal and atherosclerotic aorta were examined after exposure in vivo to argon and excimer (XeCl 308 nm) laser radiation in hypercholesterolemic swine. Swine were fed hyperlipidemic diets for eight months following balloon denudation of the descending aorta. Following general anaesthetic, the descending aorta was isolated and laser burns were made on both normal and atherosclerotic intima using a continuous wave argon laser delivered through a 50 diameter quartz fibre, and a XeCl excimer laser carried through a 1 mm diameter fibre. Energy levels of 3 to 5 J were applied with the argon laser. The pulse duration for the excimer laser was 30 ns and craters were produced using 10 to 60 pulses at a repetition rate of 20 Hz and an energy density of 2 J cm^–2.Forty-eight hours after laser application, craters created by both lasers were filled with thrombus material. Argon burns were surrounded by thermal and acoustic injury which was not seen with excimer burns. Three weeks after laser application all crater surfaces were reconstituted. Unlike the excimer burns, argon craters demonstrated necrosis well beyond the crater margins and were characterized by multinucleate giant-cell reaction surrounding char debris. By nine weeks both excimer and argon laser burns were covered by fibrous tissue but could be distinguished by the fact that char debris and subjacent tissue injury arose with the argon burns.The results suggest that both lasers can be used to remove focal atherosclerotic plaque from arteries without inducing excessive thrombogenicity. Rapid healing is observed with both; however, damage to surrounding tissue is significantly greater with a continuous energy delivery laser as opposed to pulsed energy delivery.Work supported in part by: Heart and Stroke Foundation of Ontario, Grant-in-Aid No. 5-17     

Acute effects of a copper vapour laser on atheroma

The acute histological effects of a commercially available copper vapour laser (CVL) on normal and atherosclerotic arterial wall were studied. The multi-cyclic CVL produces a quasi continuous wave output at 511 nm (green) and 578 nm (yellow) [green/yellow ratio 21]. Tissue craters were produced in segments of normal and atherosclerotic human femoral artery using a maximum of 8 J of laser energy delivered with a bare 1 mm quartz fibre in contact and perpendicular to the tissue. Crater dimensions and ablation volumes were determined histologically using an optical graticule. Ablation of atheroma was almost three times more efficient than ablation of normal arterial wall (p<0.001). A narrow zone of vacuolization and coagulative thermal damage lined the crater margins suggesting a predominantly photothermal ablative mechanism. In conclusion, selective ablation of atheroma using low power copper vapour laser light is possible. The CVL is an attractive alternative to the argon ion laser because of its low running costs and applicability to other medical disciplines. Therefore, its potential application in laser angioplasty merits further study, preferably using a modified optical fibretip delivery system.     

Arterial response to laser operation for removal of atherosclerotic plaques

The cellular response of normal and atherosclerotic aortic intima after exposure in vivo to a 0.9 mm diameter carbon dioxide laser was examined in hypercholesterolemic swine with light and electron microscopy to evaluate tissue damage, thrombosis, and healing. At energy levels of greater than 5 joules, laser burns appeared as craters less than 1 mm in depth and 2 mm in diameter. Two days after the operation, craters were filled with platelet-fibrin thrombi that did not protrude above the level of adjacent endothelium. The internal elastic lamina was exposed 1 to 2 mm around the crater. This area was surrounded by a ring of densely packed leukocytes at the edge of the normal endothelium. Two weeks after the operation, the depressed crater surface was mostly reendothelialized with small, closely packed endothelial cells. The subjacent thrombus contained numerous phagocytic cells with inclusion of fibrin, erythrocytes, and membranous debris. Proliferative invaginations containing medial smooth muscle cells, mitotic figures, and collagen extended into the pit from the lateral aspects. Eight weeks after the operation, the burned area was still depressed and therefore less occlusive than adjacent lesion areas, and a fibrous cap had formed over the remaining necrotic area. The results suggest that a focused, low-energy carbon dioxide laser can be used to remove focal atherosclerotic plaques from arteries without inducing excessive thrombogenicity. Rapid healing, including reendothelialization and intimal fibrous scarring, with minimal damage to surrounding tissue, was observed.     

The role of pulse length in limiting distant damage to vascular tissue caused by the Nd-YAG laser

The total damage caused by equivalent doses of energy given to human cadaver vascular tissue over the same time scale from three Nd-YAG lasers of different pulse lengths is quantified. The continuous wave (c.w.) laser produces vacuolation and coagulation around a vaporized crater; the 100 μs pulsed laser produces less surrounding damage and the 10 ns pulsed laser none at all. The areas of damage in five craters made with 10 J energy were measured from histology slides using a digitising platten, and it was found that in each case the total amount of damage was the same, even though the depth of the craters made varied. The dose response for vaporization of the 10 ns pulsed laser was the greatest at 35 μm/J and that of the c.w. laser was least at 8 μm/J. A pulse length of 100 μs may not be the optimum for limiting surrounding tissue damage during laser angioplasty but it produces much less damage than a c.w. laser and unlike the 10 ns pulses is easily transmissible down an optical fibre.     

Arterial healing in the dog after intraluminal delivery of pulsed Nd-YAG laser energy

The application of laser energy to percutaneous recanalization of diseased blood vessels is of interest to vascular surgeons and radiologists. We have examined the effect of pulsed infrared light from a 100 microseconds pulsed Nd-YAG laser on the dog aorta in order to determine the dose response, perforation thresholds and healing properties in vascular tissue. We used 100 microseconds pulses of 0.5 J energy at 10 Hz repetition rate via a 400 micron optical fibre to make 205 craters in 10 dogs at total energies of 5-25 J. The perforation threshold was 15 J in six animals and 20 J in four. The dose response was linear at 10 micron tissue vaporized per Joule delivered. Animals were killed immediately and at intervals of 24 h, 4, 7 and 10 days, 2, 3 and 6 weeks, and 3 and 6 months. Material was retrieved for histology and examined by light and scanning electron microscopy. The tissue exhibited features of laser damage that were less marked than those seen with continuous wave lasers; there was less heat damage surrounding the craters which healed well, even after perforation. This laser is likely to be suitable for human laser angioplasty provided the energy is given in increments of 15 J or less.     

Excimer laser angioplasty: Quantitative comparison in vitro of three ultraviolet wavelengths on tissue ablation and haemolysis

The effects of three ultraviolet excimer laser wavelengths on normal and atheromatous human cadaver aortic wall are presented. Ultraviolet radiation successfully ablates vessel wall; the dose response is greatest at 249 nm followed by 193 nm and 351 nm, where the effect is negligible for the equivalent energy dose. Wavelengths 249 and 193 nm have a selective effect on fibrous atheroma; ablation proceeds at a higher rate in this tissue. Non-linear effects observed at 249 nm may be due to thermal as well as photoablative mechanisms. In addition, blood samples were exposed to all three wavelengths and potassium concentrations were measured; the dose of energy required to produce tissue ablation may also produce significant haemolysis and hyperkalaemia at 249 and 193 nm but not with 351 nm. This finding may be important for coronary angioplasty but less so for peripheral work. The wavelength that produces the strongest dose response is 249 nm; this is the wavelength for which a fibre-optic delivery system should be developed.     

Early and late healing responses of normal canine artery to excimer laser irradiation

Acute in vitro histologic studies have shown that the pulsed xenon chloride excimer laser causes precise microablation without the surrounding thermal tissue injury associated with frequently used continuous-wave lasers such as the argon, carbon dioxide, and neodymium:yttrium aluminum garnet lasers. However, the in vivo healing response of artery wall to excimer laser injury is not known. Accordingly, a xenon chloride excimer laser (308 nm, 40 nsec pulse width, 39 mJ/mm2/pulse) was transmitted via a 600 micron fused silica fiber to create 420 craters of varying depths (30 to 270 micron) in 21 normal canine femoral and carotid arteries. At 2 hours, 2 days, 10 days, and 42 days after excimer laser ablation, the artery segments were perfusion fixed in situ and analyzed by light, scanning, and transmission electron microscopy. At 2 hours, craters were covered by a carpet of platelets and entrapped red blood cells. Fibrin and exposed collagen fibers were seen at the crater base. There was a sharp demarcation of the crater-artery wall interface without lateral laser tissue injury. At 2 days, adherent platelets persisted with thrombus covering the base of the craters. Early healing responses were present, consisting of polymorphonucleated leukocytes and new endothelial cells, which extended over the crater rims. At 10 days, no thrombi were seen, and healing continued with almost complete reendothelialization. Macrophages, fibroblasts, fibrin, and entrapped red blood cells were present below the reendothelialized surface. At 42 days, healing was complete with obliteration of the craters by fibrointimal ingrowth. The surface was completely covered by a smooth monolayer of axially aligned endothelial cells. There were no aneurysms or surface hyperplastic responses. These favorable healing responses in normal canine arteries suggest that pulsed lasers with high tissue absorption coefficients, such as the xenon chloride excimer laser, may be suitable energy sources for clinical laser angioplasty procedures. However, further studies in atherosclerotic animals are required before human clinical responses can be accurately predicted.     

In vitro Alexandrite laser angioplasty: A study on fibre conduction and tissue effects

Pulsed ultra-violet excimer laser radiation is capable of tissue ablation with only minimal thermal injury of adjacent tissue structures. Since difficult fibre optic coupling of energy was observed, alternative Q-switched laser sources capable of ablation of atherosclerotic plaque are under current investigation. To evaluate tissue effects of Alexandrite laser radiation, 160 arterial segments with macroscopic evidence of atherosclerotic disease were treated. The laser light was transmitted via silica based quartz fibres with different diameters. Using the Q-switched Alexandrite laser at the fundamental wavelength (748 nm) with a pulse duration of 300 ns the energy density threshold for tissue ablation was found to be in the range of 63 to 126 J cm^–2 using a 300m fibre. On macroscopic examination only limited thermal and acoustic injury was found in crater adjacent tissue structures. Crater edges were even and did not reveal signs of crater charring or debris in the crater lumen. However, the histological cross-sections revealed thermal injury extending from 100 up to 200m lateral into adjacent tissue. The crater margins revealed fissuring as a result of shock wave injury. Thermal damage was most evident if irradiation of atherosclerotic tissue was performed in blood.     

The histological measurement of laser-induced thermal damage in vascular tissue using the stain picrosirius red F3BA

A histological technique for the measurement of laser-induced thermal tissue damage is described using the stain picrosirius red F3BA. This stain enhances the birefringence of normal collagen when viewed in polarized light. Areas of (thermally) denatured collagen, however, have no optical activity and can be measured directly by optical micrometry. The technique has been applied to experimental studies on both laser angioplasty and laser vascular anastomosis.The tissue ablation characteristics of various 2.2 mm diameter rounded sapphire laser angioplasty probes were compared by lasing (at 1064 nm) segments of porcine aorta under blood in vitro. A marked difference was observed between probes from different manufacturers, the Surgical Laser Technologies probe producing significantly greater forward tissue ablation with less associated lateral thermal damage.The relative degree of thermal damage caused by argon (488/514 nm) and Nd-YAG lasers during in vitro arteriotomy repair was also investigated. No difference was seen between the two wavelengths. However, the use of absorption-enhancing chromophore dyes as an aid to laser welding significantly reduced damage, particularly for the argon laser.In conclusion, we suggest that this histological technique is of considerable value in the investigation of the thermal effects of continuous-wave lasers.     

The argon contact laser scalpel: a study of its effect on atherosclerosis

A new argon laser scalpel (ALS) that delivers radiation to tissue by direct contact was used to perform endarterectomies on atherosclerotic rabbit aortas in vivo. The resultant effects were compared to those induced by CO2 laser (CO2) and conventional surgical endarterectomy (END) to determine whether this instrument might be useful in the treatment of occlusive cerebrovascular disease. Light microscopy of the treated aortic segments revealed significantly more atheroma removed and less damage to the underlying media in the ALS segments compared to the CO2 segments. Electron microscopy showed that the ALS surface and distal intima-media interface were smoother and more even than those of the CO2 or END groups. Prostacyclin synthesis, as measured by 6-keto-prostaglandin F1a levels, was significantly reduced in the ALS compared to the END and control segments. These results indicate that the ALS is superior to CO2 in performing open laser endarterectomies, but such treatment places the atherosclerotic blood vessel at greater risk for thrombotic complications during the early postoperative period that does surgical endarterectomy. It is conceivable that a contact laser may be useful in the smooth welding of the distal edge of an atheroma (i.e., during carotid endarterectomy) and for the transcatheter ablation of surgically inaccessible obstructions of the cerebral circulation.     

Various effects of the CO2-, the neodymium-YAG-, and the argon-laser irradiation on bladder tissue

Application of lasers as cutting or coagulation instruments is based on the conversion of light energy into heat in the irradiated tissue. The extent and degree of the thermal action depends on the beam geometry and the energy of the incident light, as well as on the optic and thermal properties of this tissue. The extinction behavior in the tissue differs for the various laser systems employed in medicine. A comparison of the effects on bladder tissue of rats and rabbits is made with Neodymium-YAG laser and the argon and CO2 lasers to demonstrate the advantages of the Neodymium-YAG laser, especially for the therapeutic irradiation of bladder tumors.     

Hyperthermia from interstitial laser irradiation in normal rat brain

This study examined both the effect of variations in optical fiber tip and in light wavelength on laser-induced hyperthermia in rat brain. Normal rat brains were exposed to argon laser light (454-514.5 nm) delivered through an intracerebral end-emitting (bare-tipped) or a diffusion-emitting (sapphire-tipped) optical fiber probe. Interstitial thermistor probes recorded temperatures after thermal equilibration at varying distances from the emitting source. The end-emitting fiber produced significantly (P less than 0.05) higher elevations in tissue temperature than the diffusion-emitting fiber at the same laser power output. This is due to the smaller surface area (1.2 mm2 versus 7.8 mm2) of the end-emitting fiber, which results in a greater rate of energy delivery to tissue adjacent to the fiber tip. Changes in intracerebral temperature measurements were also recorded at similar distances from a diffusion-emitting fiber at a continuous total laser power output of 150 mW for light wavelengths of 454-514.5 nm, 700 nm, and 750 nm and at a total laser output of 1.1 W for 1,060 nm. Variations in brain tissue temperature with distance from the laser emission source were compared for each laser group with the tissue temperature profile generated by a radiofrequency (wavelength 600-625 m) interstitial probe. Similar temperature changes were found for all visible wavelengths near the probe, suggesting that the thermal response of brain adjacent to an interstitial laser fiber is primarily dependent upon the rate of energy delivery and not upon wavelength. The thermal profile versus distance from the light source depends mostly upon the level of temperature rise near the interstitial laser fiber tip and not the wavelength of laser light used. These results have important implications in interstitial applications of laser for hyperthermia and photochemotherapy.     

Effect of low energy laser on the growth and regeneration of capillaries

Laser light of low energy is discussed to have an accelerating effect on wound healing. The aim of the present study was to proof whether HeNe laser irradiations have a positive effect on regeneration of capillaries.For this purpose aluminium chambers were implanted in the dorsal skin flap of Syrian hamsters. After coagulation of blood vessels by means of an argon laser the tissue was irradiated daily with the low energy light of a HeNe laser. Regeneration of capillaries was studied by means of intravital microscopy.The results of the study revealed a positive effect of low dose HeNe laser irradiation on the regeneration of capillaries at day 5 after the coagulation. The measurable part of the capillaries was about 27% higher for the irradiated animals compared to controls.     

Microvasculature Can Be Selectively Damaged Using Dye Lasers: A Basic Theory and Experimental Evidence in Human Skin

Basic theoretical considerations of the optical and thermal transfer processes that govern the thermal damage induced in tissue by lasers are discussed. An approximate, predictive model and data are proposed for the purpose of selecting a laser that maximizes damage to cutaneous blood vessels and minimizes damage to the surrounding connective tissue and the overlying epidermis. The variables of wavelength, exposure duration, and incident energy density are modeled, and a flashlamp-pumped dye laser operating at or near the 577 nm absorption band of HbO₂, with a pulsewidth (0.3 μsec) less than the estimated, approximately 1 millisecond, thermal relaxation times for microvessels is chosen for experimental exposures of normal Caucasian skin. Highly specific laser-induced damage to blood vessels is demonstrated both clinically and histologically. This is in striking contrast to the previously reported widespread, diffuse necrosis caused by other lasers. The incident energy and preliminary observations of wavelength and temperature dependence for vascular damage thresholds are consistent with theoretical predictions. Whereas typically 20 joules/cm² of argon laser irradiation (514 and 488 nm, ～100 msec) is required to induce widespread thermal damage, the pulsed dye laser requires only about 2 joules/cm² to induce highly specific vascular damage. The potential usefulness of dye laser-induced selective vascular damage as a treatment modality for portwine stain hemangiomas and other vascular lesions is discussed. In addition to possible treatment applications, the dye laser or other sources meeting the requirements for producing such damage may also offer a useful experimental tool for inducing predictable damage to microvas-culature. Histopathologic and clinical studies related to these possibilities are in progress.     

Mechanical and thermal effects in striated muscle irradiated by ns-laserpulses

The therapeutic application of laser light is required to minimize defects in the non-irradiated tissue. The primary mechanism of interaction is determined by the duration of laser action. In the case of continuous wave laser light a tissue layer surrounding the irradiated volume is thermally affected. With the pulses of a Q-switched laser (duration some ns) tissue cutting will be obtained by the laser-induced breakdown. To be able to distinguish between thermal and mechanical effects by histological examination, experiments were performed with laser pulse durations of 8ns and 100μs under the same conditions with a Nd-YAG laser at 1064nm. The beam was focused through air below the tissue surface. The beam geometry in the focal region was identical for both cases. The defective region after irradiation could be divided into four zones surrounding a crater. In the μs-experiments the zones corresponded to the temperature distribution in the tissue, so the changes were all classified as thermal. In the ns-experiments, in general larger craters were found. Increasing the number of pulses to 200 the picture is similar to that produced with μs-pulses. These results show that a few ns-pulses suffice to form a crater. Additional ns-pulses lead to heat accumulation and produce thermal lesions like those of the μs-case.     

Effect of argon laser and Photofrin II on murine neuroblastoma cells.

Laser-induced fluorescence (LIF) of photosensitizers is used to detect cancer. The effect of argon laser light with an average irradiance of 31 mW cm-2 and Photofrin II (Dihematoporphyrin ether, DHE) at concentrations of 1.0 and 5.0 micrograms ml-1 on C1300 murine neuroblastoma cells (MNB, NB41A3) in vitro was investigated. Growth curves and cell viability (trypan blue dye exclusion) were determined at 1, 24, 96, and 144 hr post-irradiation. Light doses of 1.8 and 9.0 J cm-2 combined with 5.0 micrograms DHE ml-1 decreased both cell numbers and viability, immediately and up to 144 hr postirradiation. Argon laser light alone at a fluence of 9.0 J cm-2 caused reversible injury to the cells. This in vitro study shows that both low energy argon laser light and low dose DHE are cytocidal to C1300 MNB cells. LIF promises to aid in the detection and destruction of neuroblastoma. Surgeons should be aware that tissue irreversible damage is likely to occur when performing LIF detection of neuroblastoma. The doses of laser light and of Photofrin II found to be toxic to neuroblastoma cells in culture may provide guidelines for photodynamic therapy ablation of neuroblastoma clinically.     

Assessment of a new device for laser angioplasty

Experimental work has shown that a transparent laser device delivering pulsed energy to an artery results in a smaller area of surrounding damage than does an opaque device with a continuous wave laser. The combination of a transparent ball-tipped device with a pulsed Nd-YAG laser has been investigated. The system delivers pulses of 100 microseconds at a rate of 10 Hz and average energy of 0.5 J per pulse with an energy loss of 5-10% between the output at the laser rail and the fibre tip. The dose/response was measured and showed that on normal aorta under saline the device produces craters with a depth of 5 microns/J and 1.5 mm radius. There is a 100% increase in dose response with diseased aorta and a 50% increase when exposure is carried out under blood. The effect of a varying angle of incidence upon the arterial wall has been measured. Angulation of the device at 10 degrees from the perpendicular reduces the crater depth to 50%, as compared with a 50% reduction at 60 degrees using a bare fibre. As estimated with a thermal camera in air, the device heats up to a maximum of 50 degrees C during a 50 J exposure, compared to 110 degrees C after 5 J for the sapphire device. Artificial circulation experiments were carried out using diseased femoral vessels occluded by a ligature. The new system recanalised 100% of occlusion in straight vessels, and 40% of occlusions in curved vessels at a radius of 2.5 cm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulsed ultraviolet lasers and the potential for safe laser angioplasty

Endoscopic laser ablation of atheroma using continuous wave lasers is limited by imprecise control of thermal ablation, resulting in a crater that expands in width and depth, with thermal damage to adjacent normal tissue. We compared the gross and histologic effects of pulsed 308 mm excimer irradiation to continuous-wave Nd:YAG and Argon Ion laser irradiation, and pulsed 1,060 nm, 532 nm, 355 nm, and 266 nm laser irradiation in 205 atherosclerotic aortic segments. In contrast to the continuous-wave Nd: YAG, Argon Ion, and pulsed 1,060 nm, 532 nm, and 355 nm laser irradiation, which produced gross and histologic evidence of uncontrolled ablation, the 308 nm and 266 nm pulsed lasers induced incisions that conformed precisely to the beam configuration without gross evidence of thermal injury. The incision edges from these two lasers were histologically smooth and comparable to a scalpel incision. Our histologic findings suggest that rapid, precise endoscopic ablation of vascular and nonvascular tissue can be performed at these shorter pulsed wavelengths with very high precision with relatively little damage or risk to adjacent tissue.