Effect of force on ablation depth for a XeCl excimer laser beam delivered by an optical fiber in contact with arterial tissue under saline.

The effect of force applied to a 430 micron single fiber, delivering 60 pulses of 308 nm XeCl laser radiation at 20 Hz, on the ablation depth in porcine aortic tissue under saline has been investigated. Energy densities of 8, 15, 25, 28, 31, 37, and 45 mJ/mm2 were used. Force was applied by adding weights from 0 to 10 grams to the fiber. The fiber penetration was monitored by means of a position transducer. At 0 grams, the ablation depth increased linearly with incident energy density, but the fiber did not penetrate the tissue; with any weight added, the fiber penetrated the tissue at energy densities above 15 mJ/mm2. The fiber did not penetrate during the first several pulses, possibly due to gas trapped under the fiber. After these first pulses, a smooth linear advancement of the fiber began, which lasted until the pulse train stopped. The ablation depth increased with increasing energy densities and weights. This effect was largest above 25 mJ/mm2 where the ablation efficiencies (unit mm3/J), with weights added to the fiber, were substantially larger than values found in 308 nm ablation experiments described in the literature, which were conducted with either a focused laser beam or a fiber without additional force. The results imply that in 308 nm excimer laser angioplasty, force must be applied to the beam delivery catheter for efficient recanalization, and that experiments performed with a focused beam or without actual penetration of the fiber do not represent the situation encountered in excimer laser angioplasty.     

An experimental study of excimer laser angioplasty]

An excimer laser, which is a pulsed ultraviolet laser and ablates tissue precisely with no thermal injury, is expected to coronary laser angioplasty. We transmitted XeCl excimer laser (308 nm) via a 400 microns fused silica fiber. In the first experiment, we studied about excimer laser ablative effects to normal canine arteries and atherosclerotic rabbit aortas, and about healing responses following excimer laser irradiation in both models. Surfaces after excimer laser ablation were slightly rough but no thermal injury was found in the media. And for healing process of normal canine arteries, endothelial cells appeared at 3 weeks and completely covered surfaces with fibrointimal ingrowth at 3 months. In the rabbit aortas, at 3 weeks there was reconstruction of the surface. At 2 months no accelerated atherosclerotic or aneurysmal changes were observed. In the second, with this excimer laser (short pulse) and 400 microns fused silica fibers (distal fiber-end power: 3-6 mJ/pulse), we performed transluminal laser angioplasty to recanalize totally occluded canine femoral arteries under an angioscopic guidance. We cold recanalize 8 of 9 totally occluded arteries with no thermal injury of adjacent tissue, though perforations were observed in 7 of 9 arteries. In the third, we used a newly-developed long pulse excimer laser, with which distal fiber-end energy was about 3 to 4 times as much as the short pulse one, to recanalize totally occluded canine arteries. In result, recanalization was performed in 6 of 8 arteries rapidly with little thermal injury. However, we observed perforations in 6 of 8 arteries like the short pulse one. Multifiber catheter ("over the wire system") coupled with this long-pulse excimer laser was used to reconstruct stenotic iliac arteries of atherosclerotic rabbit models. The procedure was successful in all the 5 rabbits. In conclusion, our preliminary results suggested that further developments of a more powerful and longer pulse-duration excimer laser, optic delivery system and guidance system would make excimer laser angioplasty safer and more effective method in the near future.     

Percutaneous recanalization of arteries: Status and prospects of laser angioplasty with modified fibre tips

Percutaneous balloon dilatation of arterial stenoses is a firmly established non-surgical treatment of ischaemic disease. The number of percutaneous transluminal coronary angioplasties performed per year in the USA approaches the number of coronary artery bypass graft operations. A great number of novel percutaneous recanalization schemes address the major problems of balloon angioplasty: failure to cross the stenosis (occlusion), failure to dilate effectively (15–20%), acute complications (5%) and re-stenosis within six months (30–40%). Laser energy can effectively evaporate atheromatous plaque, but delivery by an unmodified bare fibre creates only a small channel and carries a high risk of vessel-wall perforation in the coronary arteries. It appears impossible to maintain an axial position in small, tortuous and moving arteries with multiple side-branches. Coronary lesions are anatomically and structurally heterogeneous. Reduction of the perforation risk is being approached by four strategies: (a) optimization of the power source; (b) enhancement of laser-light absorption by plaque relative to artery wall; (c) improvement of plaque recognition; and (d) modification of the delivery system, which is discussed in detail. Recanalization of occluded femoropopliteal arteries with the 2.0-mm metal laser probe has proved to be safe and effective in more than 100 patients. The 2.2-mm rounded sapphire contact probe has been used with success in the peripheral arteries of over 30 patients. The recanalization mechanism of both probes is not yet fully understood. Closed-chest attempts at recanalization of coronary arteries by the 1.7-mm metal laser probe have been reported in 13 patients, with success in the majority. There were no complications requiring emergency surgery. The possible occurrence of embolism or spasm in three cases warrants a cautious approach to application of the metal laser probe in the coronary catheterization room. The primary benefit of laser recanalization with modified fibre tips is the possible transformation of a candidate for surgery into a candidate for balloon angioplasty. It remains to be established whether prior laser debulking of the atheroma will reduce the incidence of acute complications of balloon dilatation and will reduce restenosis in the subsequent year. In the past two years an avalanche of laser and non-laser recanalization schemes have been developed. In peripheral arteries, early results of most methods have shown an acceptably low incidence of acute perforations or other complications. The human arterial wall can take a heavy beating, both mechanically and thermally. In the next decade, catheter intervention techniques will progressively contribute to the treatment of peripheral and coronary artery disease.     

Excimer laser irradiation of non-calcified and calcified human atheroma (248 and 308nm wavelengths)

In order to develop a system of peripheral arterial angioplasty, we carried out an in vitro study to define the quantitative, thermal and morphological characteristics of human-atheroma ablation by excimer laser. A multigas ‘Sopra’ laser was used. The study was performed by using 248nm, krypton fluoride (KrF), then 308nm, xenon chloride (XeCl) wavelengths. The delivered energy was up to 150 mJ pulse⁻¹, pulse duration was 25ns, and the repetition rate could be adjusted to up to 20Hz. Irradiated tissue segments of the superficial femoral and external iliac arteries were obtained in man during surgical procedures and were both calcified and non-calcified atherosclerotic lesions. Quantitative measurements showed a linear increase of ablated tissue mass depending on the energy delivered. For the same energy, the loss of mass was greater with the 248nm wavelength than with the 308nm. The maximum temperature rise measured at the site of irradiation was 6°C at 248nm and 25°C at 308nm. Histological analysis of the irradiated segments revealed neat and precise ablation without thermal injury of adjacent tissue. At 248nm, this phenomenon was observed for calcified as well as non-calcified atheromas. It is concluded that quantitative, thermal and morphological characteristics of in vitro ablation of calcified and non-calcified human atheroma by excimer laser are compatible to clinical requirements. The results observed at 248nm were experimentally more satisfactory.     

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     

Current multicentre studies with the excimer laser: design and aims

. Excimer laser ablation to remove atherosclerotic plaque has been used for over a decade as a methodology to treat cardiovascular disease. Improvements in the technique and technology of excimer laser angioplasty, coupled with the recognition of new clinical opportunities for this treatment modality, have resulted in a resurgence of interest in the laser. Three clinical trials are now being conducted to explore potential applications, including the LARS trial of excimer laser versus balloon angioplasty to treat in-stent restenosis, the PELA trial of excimer laser angioplasty in occluded superficial femoral artery disease, and the LACI trial of excimer laser angioplasty in limb-threatening ischaemia. This article describes the rationale and objectives of these new approaches to some of the more challenging problems in cardiovascular disease.     

Laser induced removal of meniscus cartilage and tendines

This study examines the potential of Nd-YAG lasers with the wavelength 1064 nm or 1320 nm and an Excimer XeCl laser for endoscopic removal of meniscus cartilage and tendon tissue. In vitro irradiation of freshly isolated bovine menisci and tendines with laser light, induced a tissue vaporization and tissue ablation with a highly significant relation to the applied laser energy density. In contrast to the treatment of tissue with the Excimer laser the use of the Nd-YAG laser with both wavelengths provoked carbonization of the lesion surface. Thermic induced changes of tissue integrity as examined by histology and scanning-electron-microscopy were for the Nd-YAG laser with wavelength 1320 nm>Nd-YAG laser with wavelength 1064 nm> Excimer XeCl laser. Due to the smaller thermic induced side effects and the smoother tissue surface after irradiation the pulsed Excimer XeCl laser is favoured for cutting and ablation in meniscus and tendon surgery.     

The effects of laser energy on the arterial wall

Laser energy has been proposed as a method of resecting atherosclerotic plaque since the mid 1960s. However, only over the past several years have we come to understand some of the unique interactions of the laser with cardiovascular tissue. In laser angioplasty a major challenge has been choosing the optimal laser and duration of laser exposure to achieve adequate resection of plaque, while minimizing such complications as thrombosis, perforation, embolization, aneurysm formation, and accelerated atherosclerosis. Ultimately we must develop a more selective laser that resects plaque while leaving adjacent arterial wall uninjured. This review describes the physics of laser energy, the different lasers available for use in the cardiovascular system, laser-arterial wall interactions, and some of the limitations of laser angioplasty.Section Editor - Bruce L. Gewertz, MD, (Chicago, Illinois)     

Excimer laser revascularisation: current indications, applications and techniques

. The ultraviolet pulsed excimer laser (308 nm wavelength) is currently the only laser approved by the FDA for percutaneous intervention in patients with ischemic coronary artery disease. The clinical presentation of the treated patients varies from stable and unstable angina to acute myocardial infarction. Potential advantages of excimer laser revascularisation in acute coronary syndromes and in ischaemic obstructive peripheral vascular disease include concomitant plaque debulking and thrombus removal; absence of systemic lytic state; shortened thrombus clearing time and facilitation of adjunct balloon angioplasty and stenting. Improved understanding of laser–tissue interactions and positive clinical outcomes through the use of safe lasing techniques have led to expansion of indications/applications for laser angioplasty. These include stent restenosis, complex lesions and thrombotic stenoses, bifurcation lesions, balloon failure, total occlusions, focal saphenous vein graft lesions and peripheral arterial obstructions. The excimer laser can be effectively utilised in patients with depressed left ventricular ejection fraction and does not require implantation of a temporary pacemaker as no-reflow phenomenon and severe arrhythmias are rarely encountered. Careful case selection, proper utilisation of equipment and incorporation of efficient lasing techniques play a crucial role in effective and safe cardiovascular laser applications.     

Excimer laser for revascularisation of saphenous vein grafts

Coronary artery bypass grafting has been a major advance in cardiovascular medicine over the past 30 years. Saphenous venous bypass grafts, however, are prone to develop atherosclerotic disease within several years of the procedure. Unfortunately, percutaneous interventional techniques in saphenous venous bypass grafts are associated with significant risks of distal embolisation and resultant non-Q wave myocardial infarction. Preliminary results suggest excimer laser angioplasty may significantly reduce this complication. This article summarises the results of percutaneous interventions in spahenous venous bypass grafts, emphasising the potential role of excimer laser angioplasty in this group of patients.     

Laser dentistry: a new application of excimer laser in root canal therapy

We report the first study of the application of excimer lasers in dentistry for the treatment of dental root canals. High-energy ultraviolet (UV) radiation emitted by an XeCl excimer laser (308 nm) and delivered through suitable optical fibers can be used to remove residual organic tissue from the canals. To this aim, UV ablation thresholds of dental tissues have been measured, showing a preferential etching of infiltrated dentin in respect to healthy dentin, at laser fluences of 0.5-1.5 J/cm2. This technique has been tested on extracted tooth samples, simulating a clinical procedure. Fibers of decreasing core diameters have been used to treat different sections of the root canal down to its apical portion, resulting in an effective, easy, and fast cleaning action. Possible advantages of excimer laser clinical applications in respect to usual procedures are also discussed.     

Percutaneous transluminal excimer laser angioplasty in total peripheral artery occlusion in man

Laser angioplasty and laser-assisted angioplasty have become a clinical reality. Producing sharply defined borders of the ablated area with minimal adjacent thermal damage, excimer lasers offer several proven and some potential advantages over conventional systems. To evaluate the feasibility of excimer laser angioplasty, we have treated one patient using 308-nm radiation via a bare fiber in direct contact with the total occlusion of a right femoral artery. The lesion was successfully recanalized, thus allowing easy passage of the balloon catheter and subsequent dilatation. This percutaneous laser recanalization of an occluded peripheral artery is one of the first to be done in man using excimer laser radiation, thus demonstrating that the technique is feasible and the system is potentially useful.     

Vascular contractile function following experimental excimer laser angioplasty

The aim of this study was to determine the vasomotor response to in vivo excimer laser irradiation with regard to laser-induced tissue effects. Transfemoral excimer laser angioplasty was performed in the right carotid artery of 11 New Zealand white rabbits. In four additional rabbits (sham group), the procedure was performed without the application of laser energy. Angiography documented vessel dissection in five laser-treated animals. Perforation occurred in one animal. Rings of the treated artery and controls of the contralateral artery were investigated in a contraction chamber. The passive stress-strain relation (PSS) and the maximum contraction force (MCF) after stimulation with noradrenaline, serotonin and potassium chloride were determined. The treated vessels had a higher PSS than the control (p=0.05). The MCF was lower in the treated vessels (p<0.05). The contraction force of the sham-operated vessels was higher, although statistically not significant, compared to the laser-irradiated segments. In a subset analysis, performed to compare vessels with moderate and severe trauma, MCF was significantly reduced in vessels with severe laser-induced injury. Experimental in vivo excimer laser angioplasty in this model resulted in heterogeneous structural changes, including dissections and perforation. Post-mortem assessment of vasomotor response showed no significant difference between laser-treated and sham-operated animals. However, the contractile function of the target vessel seems to be reduced following extensive laser-induced vessel injury.     

Lasers in medicine

Since its discovery, the laser has been intensively investigated and used in medicine, first in ophthalmology then in ear, nose and throat surgery, gynaecology, neurosurgery etc. Development spans from the ruby and argon lasers in outpatient eye surgery to the carbon dioxide and Nd:YAG lasers in the operating theatres and further on to the PDT-dye lasers, excimer and solid state angioplasty lasers or flash lamp pumped "gallstone cracker" lasers. The CO2-Nd: YAG laser combination will be described as the state-of-art surgical laser. This simultaneous, coaxial and coherent combination laser offers a new possibility to cut and coagulate effectively at the same time. Operating times are shortened and bleeding volumes minimised. The CO2-Nd: YAG laser represents a new type of interaction between laser and tissue, laser enhanced tissue absorption, which will be described.     

The paradox of thermal ablation without thermal injury

Previous investigations have demonstrated in vitro that the excimer laser may be used to accomplish cardiovascular tissue ablation without causing thermal injury to boundary sites. Initial investigations suggested that results achieved with the excimer laser were related to photochemical breaking of molecular bonds, rather than thermal degradation. More recent investigations, however, have suggested that the mechanism of excimer tissue ablation may not be unique. Results indistiguishable from those accomplished with the excimer laser have been reproduced using both visible and infrared wavelengths. Experiments utilizing gas chromatography have indicated that the vapour-phase photoproducts liberated during excimer laser tissue ablation are indistinguishable from those observed following continuous wave laser irradiation or flame torching of cardiovascular tissue. While photoemission spectroscopic analysis has identified free radicals released in gas phase during excimer laser ablation, electron paramagnetic resonance spectroscopy has similarly identified free radicals released in solution during continuous wave laser ablation; while these two techniques may detect different types of radicals with different kinetic behaviour, these results indicate, that the finding of free radical photoproducts per se during laser ablation does not necessarily exclude a non-thermal mechanism. Finally, plasma-mediated photodisruption represents a third alternative to explain pulsed laser ablation; experiments are required, however, to define whether plasma generated during pulsed laser irradiation is central to the ablation process, or represents an epiphenomenon. However it is done, it is certain that a beam of heat is the essence of the matter. H.G. WellsThe War of the Worlds (1)     

Laser-assisted fluorescence detection of plaque

Selective fluorescence-marking of plaque offers new possibilities in cardiovascular diagnosis and therapy. Angioscopic investigations and spectrometry-assisted laser angioplasty will be simplified and more effective as compared with methods of today. It might help to make laser angioplasty a further promising interventional method to overcome, at least partially, the problems caused by atheromatous or atherosclerotic changes in the cardiovascular system.Fluorescence detection and imaging of markers is usually limited by the intrinsic fluorescence of tissue. Optical differential methods in combination with two-wavelength laser excitation and computer-assisted image processing, however, allow for discrimination of background-related signals and enable plaque detection and imaging at a high contrast.Plaque consists of either fibrotic, lipoid, or calcified depositions and is rather bradytrophic. For that reason in vitro experiments on human specimens post mortem seem to be justified and of clinical evidence. Due to intrinsically different fluorometric properties of plaque and normal vascular tissue imaging of marker-free plaque areas is possible. Additionally the specimens have been incubated with a haematoporphyrin-containing fluorescence marker at concentrations of 10–40g ml^–1 and incubation times of 60 min in order to obtain a corresponding increase in contrast. Lipoid depositions show the highest contrast because of lipophilic properties of the marker, while fibrotic and calcified plaque is slightly less effectively marked. The results, however, so far obtained indicate that fluorescence detection of plaque promises further progress in diagnosis and therapy of cardiovascular diseases.     

Improved results of coronary excimer laser angioplasty by the use of advanced transmission devices

Excimer laser angioplasty is an alternative method for the treatment of obstructive coronary lesions. Initial clinical results demonstrated the safety and feasibility of the procedure. However, efficacy was limited by low catheter flexibility and unreliable energy transmission. Advanced transmission devices were used in 80 interventions in 79 patients. The catheter diameter is 1.3, 1.5 or 1.8 mm, the catheters consist of 20, 30 or 35 quartz fibres (100 m) respectively. The mean energy density was 55 ±18 mJ mm^–2, mean loss of energy transmission was 20%. The pulse width was 60 ns and 115 ns in 40 interventions each. The target vessel was the LAD in 53, the LCX in 6 and the RCA in 21 interventions.Failure of laser angioplasty occurred in 10 patients due to failed guidewire placement (N=6), failed catheter placement (N=3) or impossibility to cross the lesion with the catheter (N=1). Stand-alone laser angioplasty was performed in 43/70 procedures. Additional balloon angioplasty was necessary due to an unsatisfactory result (N=10) or due to complications (N=17) in 27 patients. Vessel occlusion occurred in 18 patients (25%) and could be successfully resolved by balloon dilatation (N=16) or additional laser angioplasty (N=1) in 17 patients. Two early occlusions were found at the 24-h control angiography. The incidence of myocardial infarction and in-hospital death (N=1) was 1.4%.Conclusion: The use of an advanced energy delivery system with trusted energy transmission and higher energy density increased the primary success rate of stand-alone excimer laser angioplasty. However, further improvement of catheter flexibility and reduction of dead space at the catheter tip is necessary to optimize ablation efficacy.     

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.     

Ultrafast imaging of tissue ablation by a XeCl excimer laser in saline.

To determine the temporal evolution of laser induced tissue ablation, arterial wall specimens with either hard calcified or fatty plaques and normal tissue were irradiated in a 0.9% saline solution using a XeCl excimer laser (wavelength 308 nm, energy fluence 7 J/cm2, pulse width 30 ns) through a 600 microns fused silica fiber pointing perpendicular either at a 0.5 mm distance or in direct contact to the vascular surface. Radiation of a pulsed dye laser (wavelength 580 nm) was used to illuminate the tissue surface. The ablation process and the arising bubble above the tissue surface were recorded with a CCD camera attached to a computer based image-processing system. Spherical cavitation bubbles and small tissue particles emerging from the irradiated area have been recorded. The volume of this bubble increased faster for calcified plaques than for normal tissue.