Formation of pressure waves during in vitro excimer laser irradiation in whole blood and the effect of dilution with contrast media and saline

Pressure waves during excimer laser ablation of vascular tissue may be responsible for complications of coronary excimer laser angioplasty. In this experimental study, pressure waves were measured during excimer laser irradiation in blood and contrast media using a polyvinilidenefluoride hydrophone. At a distance of 4 mm lateral to the tip of a 1.7 mm multifiber laser catheter, excimer laser irradiation in blood resulted in a linear increase of peak pressures from 1,365 ± 165 kPa at 30 mJ/mm² to 2,866 ± 404 kPa at 60 mJ/mm². In contrast media, peak pressure increased from 3,172 ± 573 kPa (30 mJ/mm²) to 5,763 ± 467 kPa (60 mJ/mm²). Contrast media and saline were added to blood. At a concentration of 60% contrast in blood, a 3.4 fold increase of peak pressures was documented as compared to pure blood. Further increase of the concentration did not result in higher pressure waves. Concentrations of saline in blood of 90% and 96% reduced the peak pressures by 16% and >50%, respectively, as compared to pure blood. © 1994 Wiley-Liss, Inc.     

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)     

Effects of pulsed lasers on agar model simulation of the arterial wall

Coronary laser angioplasty is limited by a high rate of dissection and the occurrence of abrupt closure and perforation. The aim of this study was to visualize the mechanical effects of pulsed lasers on two chamber in vitro models. These models consisted of 1 or 2 agar layers and calcium carbonate inclusions (1-layer model) or lipid (2-layer model) simulating lipid or calcified tissue. The inclusions were irradiated with a holmium-yttrium-aluminum-garnet (Ho-YAG) laser or a xenon chloride excimer laser. The Ho-YAG laser demonstrated dissection-like expansions of the target and perforation-like cracks. The size of dissection was obtained using an the empirical formula of energy (E) and the maximal expansion distance (Dmax) of the targets, Dmax = 0.15E^0,87-1,17. The excimer laser showed rare and short perforation-like cracks and little dissection-like expansion of the gaseous products originating from the ablation of material. Ho-YAG laser ablation is likely to induce target tissue dissections and/or perforations. Excimer laser ablates targets with less traumatic effects than Ho-YAG laser. © 1993 Wiley-Liss, Inc.     

Early and late arterial healing response to catheter-induced laser, thermal, and mechanical wall damage in the rabbit

Pulsed lasers are being promoted for laser angioplasty because of their capacity to ablate obstructions without producing adjacent thermal tissue injury. The implicit assumption that thermal injury to the artery is to be avoided was tested. Thermal lesions were produced in the iliac arteries and aorta of normal rabbits by a) electrical spark erosion, b) the metal laser probe, and c) continuous wave neodymium-yttrium aluminum garnet (Nd-YAG) laser energy through the sapphire contact probe. High-energy doses were used to induce substantial damage without perforating the vessel wall. Thermal lesions (n = 77) were compared with mechanical lesions (n = 22) induced by oversized balloon dilation. Medial necrosis was induced by all four injury methods. Provided no extravascular contrast was observed after the injury, all damaged segments were patent after 1 to 56 days. The progression of healing with myointimal proliferation was remarkably similar for all injuries. At 56 days, the neointima measured up to 370 microns. In conclusion, provided no perforation with contrast extravasation occurred, the normal rabbit artery recovered well from transmural thermal injury. The wall healing response is largely nonspecific.     

Acute biological response to laser balloon angioplasty in the atherosclerotic rabbit

Laser balloon angioplasty with Nd:YAG energy has been proposed as a method to seal intimal dissection and prevent elastic recoil after balloon angioplasty. To better define the vessel response to laser balloon angioplasty, its effects on luminal diameter, Indium-111 labelled platelet deposition, and histology were studied in 10 atherosclerotic rabbits. Balloon angioplasty was performed in both iliac arteries and was followed by laser balloon angioplasty in only one iliac artery. The nonlased artery served as a control. Single (15–35 W for 20 sec) or repetitive laser pulses (12–25 W for 20 sec × 3) were used. Platelet deposition was quantified 2 hr after the intervention. Lumen diameter (mm) increased following balloon angioplasty from 0.99 ± 0.47 (mean ± SD) to 1.92 ± 0.43 and 0.89 ± 0.46 to 1.99 ± 0.57 in the balloon and laser-treated arteries, respectively (P < 0.001 for both groups for comparisons to baseline, P = NS for between groups comparison). Laser balloon angioplasty resulted in a further increase in luminal diameter to 2.42 ± 0.53 (P < 0.02) when compared to the post balloon angioplasty diameter. Platelet deposition (10⁶/cm vessel) was higher following laser balloon angioplasty (26.9, 10.2–189; median range) than after balloon angioplasty (10.6, 3.4–30), P < 0.001. Histologic evidence of laser “sealing” was present in only one artery. Thus although laser balloon angioplasty results in an improved lumen diameter, it is accompanied by increased platelet deposition. In the atherosclerotic rabbit model, abolition of vascular recoil rather than “sealing” seems to be the most important advantage of laser balloon angioplasty over conventional balloon angioplasty. © 1994 Wiley-Liss, Inc.     

Reflectance during pulsed holmium laser irradiation of tissue

Although generally ignored in considerations of laser ablation of tissue, reflectance of laser light from tissue during laser-induced ablation is a potentially important factor in determining ablation efficiency because it determines the amount of laser light coupled into the target. To determine the significance of reflectance changes induced by laser irradiation, we examined the reflectance of liver samples during pulsed holmium laser ablation by placing the target at one focus of an ellipsoidal reflector and a detector at the other focus. The temporal behavior, total reflectance, and effect of multiple pulses were examined. Tissue reflectance as large as 50% was observed during holmium laser irradiation but depended upon laser radiant exposure and number of laser pulses. These measurements suggest that changes in the optical properties of the target during ablation are important and should be considered in detailed modeling of the ablation process.     

Temperature response of biological materials to pulsed non-ablative CO2 laser irradiation.

This paper presents surface temperature responses of various tissue phantoms and in vitro and in vivo biological materials in air to non-ablative pulsed CO2 laser irradiation, measured with a thermocamera. We studied cooling off behavior of the materials after a laser pulse, to come to an understanding of heat accumulation and related thermal damage during (super) pulsed CO2 laser irradiation. The experiments show a very slow decay of temperatures in the longer time regime. This behavior is well predicted by a simple model for one-dimensional heat flow that considers the CO2 laser radiation as producing a heat flux on the material surface. The critical pulse repetition frequency for which temperature accumulation is sufficiently low is estimated at about 5 Hz. Although we have not investigated the ablative situation, our results suggest that very low pulse frequencies in microsurgical procedures may be recommended.     

Effects of laser sources (argon, Nd:YAG, CO2) on the elastic resistance of the vessel wall: histological and physical study

The function of elastic elements of the vessel wall is to produce a tension suitable to resist the distension strength made by blood pressure. By producing a modification in the morphologic and structural configuration of such elastic elements, it is possible to obtain changes of the elastic resistance of the wall. The paper reports the histological and physical modifications of blood vessel walls irradiated with different laser sources.     

Intravasular ultrasound can be used to evaluate pulsed laser ablation of arterial tissue

Background and Objective: Intravascular ultrasound (IVUS) has been used successfully to detect intravascular lesions. This study evaluates the ability of IVUS to detect acoustic damage to the arterial wall following high power, pulsed laser ablation. Study Design/Materials and Methods: Arterial ablation and disruption were performed in necropsy bovine aorta with a Ho:YAG laser using energy ranging from 140–720 mJ/pulse at 5 Hz. Laser energy was delivered with 2 mm diameter, multifiber over-the-wire catheters. A 20-MHz IVUS catheter was used to image the arterial damage prior to tissue fixation and morphometry. Results: IVUS images revealed ablation craters surrounded by high acoustically backscattering zones. By histology, the arteries revealed ablation craters lined with thermal coagulation surrounded by a region of dissection and vacuolization. The depth and width of the highly backscattering zones on IVUS images correlated strongly with the corresponding morphometric measurements of tissue dissection (r = 0.92, P = 0.0001 and r = 0.80, P = 0.0001, respectively). Morphometric measurements of the ablation crater depth correlated strongly with laser energy (r = 0.90, P= 0.0001), whereas crater width was not correlated with laser energy (r = 0.27, P = 0.09). Conclusion: This study demonstrates that IVUS can detect and measure the extent of arterial damage following pulsed laser ablation. This may provide a means of detecting the extent of tissue disruption and help develop approaches to reduce or prevent extensive tissue damage. © 1995 Wiley-Liss, Inc.     

Comparison of different lasers in terms of thrombogenicity of the laser-treated vascular wall

The thrombogenic properties of the laser-treated vascular wall are reported as quantitatively assessed on the basis of 33 experiments with peripheral canine vessel segments. Three types of surfaces, namely, 1) intact, 2) mechanically de-endothelized, and 3) postlaser, have been simultaneously exposed to platelet-enriched plasma in a sequentially organized artificial circulation system. Then the adherent platelets have been counted on the treated surfaces, and the relative thrombogenicity index has been calculated according to the equation T = (A1 - Aint)/(Ad - Aint), where Aint, Ad, A1 = the adherent platelet counts on intact, mechanically de-endothelized, and laser-treated surfaces, respectively. The following lasers have been evaluated: 1) Nd-YAG, 1,060 nm, continuous wave, 4W; 2) argon-ion, 480 and 514 nm and argon-ion, 350 nm, continuous-wave, 1 W and 400 mW [corrected], respectively; 3) excimer XeCl, 308 nm, pulsed, 30 mJ per pulse, repetition rate 10 Hz [corrected]; and also 4) the laser-heated metal probe (2 mm diameter, Trimedyne, Nd-YAG) 1,060 nm, 8 W. The thrombogenicity index values obtained were 83 +/- 7, 72 +/- 8, 57 +/- 9, 63 +/- 7, and 82 +/- 9%, respectively. The differences between these values were statistically insignificant. The data are suggestive of the essential requirement of, at least, anticoagulant therapy after laser angioplasty irrespective of the laser type.     

High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur

 Low-energy laser irradiation has positive effects on bone fracture healing, osteoblast proliferation, bone nodule formation, and alkaline phosphatase activity. However, the mechanism by which low-energy laser irradiation affects bone is not clearly known. It was recently found that light at a low radiation dosage is absorbed by intracellular chromophores. High-intensity pulsed laser irradiation can produce acoustic waves in the target surface by rapidly heating the tissue. We considered that the acoustic waves induced by high-intensity pulsed laser irradiation, in addition to the photochemical effects that are induced, accelerate bone formation. To clarify whether high-intensity pulsed laser irradiation accelerates bone formation, we investigated bone formation in the irradiated femur of rat, using histomorphometric analysis. Rat femurs were irradiated with a Q-switched Nd: YAG laser, which has a wavelength of 1064 nm, under two conditions: once a day, with the average fluence rate set at 100 mW/cm² (LA1), and twice a day, i.e., every 12 h, with the average fluence rate set at 50 mW/cm² (LA2). The mean bone volume and mineral apposition rate in the LA1 group were significantly higher than those in the nonirradiated group (control). These values were highest for the LA2 group, and were about 1.52 and 1.25-fold those of the control, respectively. These data demonstrated that the number of pulses, rather than the intensity of the laser irradiation, affects bone formation. Thus, this study indicated that high-intensity pulsed laser irradiation accelerates bone formation in the metaphysis. This bone formation induced by high-intensity pulsed laser irradiation might be due to laser-induced pressure waves. Received: May 3, 2002 / Accepted: August 8, 2002 Offprint requests to: T. Ninomiya     

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     

Effect of blood upon the selective ablation of atherosclerotic plaque with a pulsed dye laser

Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques.     

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.     

Studies of acoustical and shock waves in the pulsed laser ablation of biotissue

Quantitative studies are conducted into the absolute pressure values of the acoustical and shock waves generated and propagating in a biotissue under pulsed (τ_P = 50 ns) UV (λ = 308 nm) laser irradiation (below and above the ablation threshold). Powerful (several hundreds of bars in pressure) high-frequency (f ? 10⁷ Hz) acoustic compression and rarefaction pulses are found to be generated in the biotissue. The amplitudes and profiles of the acoustic pulses developing in atherosclerotic human aorta tissues and an aqueous CuCl₂ solution under laser irradiation are investigated as a function of the laser pulse energy fluence. The results obtained point to the absence of the cold spallation of the objects of study by rarefaction waves. Based on experimental data, the rise rates, pressure gradients, and propagation velocities of shock waves in the biotissue are calculated. The experimental data are found to agree well with the theoretical estimates. © 1993 Wiley-Liss, Inc.     

The arterial wall response to intimal injury in an experimental model

Repair of occult arterial injuries is advocated to prevent thrombosis, arteriovenous fistula, and pseudoaneurysm formation. However, recent clinical series describe the healing of arterial intimal injuries and recommend nonoperative therapy. To investigate the arterial wall response to intimal injury, we created intimal flaps in 46 canine femoral arteries. The intimal flaps were imaged by arteriography, angioscopy, and intravascular ultrasound acutely, and at one and three weeks and five months post-injury. Lumen area was measured using caliper techniques (arteriography) and computerized video planimetry (angioscopy, intravascular ultrasound). Intimal and medial thickness were measured by intravascular ultrasound prior to harvest for histologic evaluation by light microscopy. Analysis of 32 patent arteries was performed after exclusion of 14 thrombosed arteries. Residual lumen area (mm²) correlated closely among the imaging modalities at one week (8.7±1.1, 7.3±2.0, 6.9±1.8), three weeks (4.2±0.9, 2.9±1.0, 2.7±0.8), and five months (5.3±0.9, 5.0±0.5, 5.0±0.9). Maximal intimal and medial thickness occurred three weeks post-injury, coincident with the maximal reduction in lumen area. Although intimal injuries can cause acute and delayed arterial thromboses, observation may be appropriate in selected cases. The evaluation of those patients chosen for nonoperative therapy should extend beyond three weeks, as this is the time of maximal arterial wall response with a continued potential for adverse clinical events.Presented at the 16th Annual Meeting of the Peripheral Vascular Surgery Society, June 2, 1991, Boston, Massachusetts.     

Percutaneous peripheral laser angioplasty with a pulsed Nd-YAG laser and sapphire tips

Percutaneous transluminal laser angioplasty with a pulsed Nd-YAG laser (1064 nm wavelength, 100s pulse duration, up to 0.4 J per pulse, 10 Hz repetition rate) coupled to optical fibres with sapphire tips of 1.8 and 2.2 mm diameter was performed under experimental conditions and then in 30 chronic occlusions of femoral and popliteal arteries in 22 patients.The experimental study in 11 human cadaverous arteries revealed that this laser system was effective in the recanalization of seven femoropopliteal occlusions, but the relative rigidity of the sapphire-tipped contact probe prevented its access to two infrapopliteal vessels. Two perforations occurred after the recanalization of 18 and 15 cm, respectively.Clinically the procedure was successful in 17 out of 25 sessions (68%). The probe formed a primary channel of at least 2.0 mm width which was further dilated by conventional balloon catheter. Ankle/brachial systolic pressure index (ABPI) increased from 0.43±0.13 to 0.79±0.21 after the procedure. In eight cases complications occurred. Two reocclusions were treated by Streptokinase infusion, two procedures were repeated 2 months later, one patient was referred to elective bypass surgery, and three patients were treated conservatively. Six patients were followed-up for more than 6 months. In one patient claudication of 400 m reappeared. ABPI showed a moderate decrease from 0.84±0.20 to 0.69±0.19.These first results are encouraging and it is likely that this method could become an important adjunct to balloon angioplasty.     

Characteristics of 308 nm excimer laser activated arterial tissue photoemission under ablative and non-ablative conditions

The present study was designed to assess the characteristics of tissue photoemission obtained from normal and atherosclerotic segments of human postmortem femoral arteries by 308 nm excimer laser irradiation of 60 ns pulsewidth. Three ablative (20, 30, and 40 mJ/pulse) and three non-ablative (2.5, 5, and 10 mJ/pulse) energy fluences were employed. Both the activating laser pulses and the induced photoemission were guided simultaneously over one and the same 1,000 micron core optical fiber that was positioned in direct tissue contact perpendicular to the vascular surface. The spectral lineshape of normal arterial and noncalcified atherosclerotic structures was characterized by a broad-continuum, double-peak emission of relevant intensity between wavelengths of 360 and 500 nm, with the most prominent emission in the range of 400-415 (407 nm peak) and 430-445 nm (437 nm peak). Fibrous and lipid atherosclerotic lesions, however, exhibited a significantly reduced intensity at 437 nm compared to normal artery layers (P less than 0.001), expressed as a 407/437 nm ratio of 1.321 +/- 0.075 for fibrous and 1.392 +/- 0.104 for lipid lesions. Normal artery components presented with approximately equal intensity at both emission peaks (407/437 nm ratio: intima, 1.054 +/- 0.033; media, 1.024 +/- 0.019; adventitia, 0.976 +/- 0.021). Comparison of spectral lineshape obtained under various energy fluences within a group of noncalcified tissues disclosed no substantial difference using the 407/437 nm ratio (P greater than 0.05). In contrast, calcified lesions revealed high-intensity multiple-line (397, 442, 461, and 528 nm) emission spectra under ablative energy fluences, whereas a low-intensity broad-continuum, single-peak spectrum resulted from irradiation beyond the ablation threshold. Thus, these findings suggest fluorescence phenomena for broad-continuum spectra, and plasma emission for multiple-line spectra as an underlying photodynamic process. Regardless of the activating energy fluence, spectral analysis of 308 nm activated photoemission provides accurate information about the laser target under standardized in vitro conditions. It is demonstrated that direct contact ablation and simultaneous spectral imaging of the target tissue via the same optical fiber is feasible.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ultrastructural study of arterial wall repair after argon laser micro-anastomosis

A carotid end-to-end anastomosis was performed in 50 Wistar rats by means of a Coherent 900 argon laser. The vessel sealing was obtained with laser shots (average 19) of 300 mW power and 5-second duration, the beam being focused in a spot of 150 micron diameter (1,700 W/cm2). From day 0 to day 120, 25 specimens underwent semithin and electron microscopic examinations. The results showed the immediate sealing effect of the argon laser owing to protein denaturation and collagen fusion of the media and adventitia 100 micron in width. Re-endothelialization of the anastomotic line began by day 3, while myofibroblast proliferation was observed in the media by day 10. By day 20 media scar was still occupied by numerous myofibroblasts and surrounded by abundant collagen and elastic fibres. At long term the endothelial repair was complete and the anastomotic strength was assured by medial collagenous network.