Hyperplasia suppression by Ho:YAG laser intravascular irradiation in rabbit

The proliferation of smooth muscle cells (SMCs) was suppressed in denudated rabbit aorta by holmium–yttrium–aluminum–garnet (Ho:YAG) laser intravascular irradiation. This study was dedicated to determine the applicability of the Ho:YAG laser irradiation on chronic restenosis after balloon angioplasty. The proliferation of SMCs in denudated rabbit aortas was suppressed in vivo 6 weeks after the laser irradiation of 20 pulses with 60 mJ per pulse. To investigate the mechanisms of this in vivo effect, the death of SMCs by the Ho:YAG laser-induced bubble collapse pressure was studied in vitro. No significant cell death attributed to this pressure was found. We conclude that the suppression of the proliferation of SMCs in vivo might not be caused by a reduction in density of SMCs induced by the collapse in pressure. We submit that the suppression of SMC proliferation in vivo could be caused by the bubble expansion pressure and/or heat induced by the laser irradiation.     

低功率YAG激光凝堵输精管——初步实验报告

我们试用100mW～100mW低功率Nd:YAG激光分别在离体和活体动物内照射凝堵输精管。在离体标本测定不同激光功率和照射时间所致的阈损(伤设定1/2输精管管壁被穿透)及输精管外膜温度。在活体内,通过套管针插入直径200μm光导纤维对8只(16侧输精管)家兔行输精管腔内照射。功率800mW和1000mW,照射时间相应为24″和16″,术后3～4周输精管管腔完全闭塞。作者认为今后可望采用经皮输精管穿刺插入光导纤维腔内照射作为绝育手术,唯尚需更多实验研究以便应用于临床。     

Low power interstitial Nd-YAG laser photocoagulation in normal rabbit brain

The safe, effective, clinical application of interstitial laser irradiation to destroy brain tumour tissue requires a knowledge of the relation of the extent of laser-induced (thermal) necrosis to the delivered laser power and total energy, and to time post-irradiation. We have conducted experiments to determine these relationships in normal rabbit brain. Irradiation by a Nd-YAG laser (1064 nm), at powers of 0.5–3.0 W and exposures of 200–1333 s produced well-defined necrotic lesions whose size increased with both the power and the total energy delivered. Lesions of 6 mm diameter made by 0.75 W for 1000s were well tolerated by animals allowed to recover from anaesthesia following irradiation. The diameter of the lesion was greatest at 48 h after irradiation. Following evolution of a characteristic healing response to necrosis in brain, the residual damage at 4 weeks was no greater in volume than that of the acute lesion. The results suggest that low power interstitial Nd-YAG laser photocoagulation in brain can be reliably and safely effected.     

Characterization of pulsed-dye laser-mediated vasodilatation in a rabbit femoral artery model of vasoconstriction

Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 μm core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic Vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed- dye laser energy has potential clinical application and warrants further investigation. © 1993 Wiley-Liss, Inc.     

Subsurface tissue lesions created using an Nd:YAG laser and a sapphire contact cooling probe

BACKGROUND AND OBJECTIVES: This study investigates deep laser coagulation of tissue in combination with contact cooling of the tissue surface for potential use in noninvasive procedures in urology. STUDY DESIGN/MATERIALS AND METHODS: A laser probe was designed and tested for simultaneous Nd:YAG laser irradiation and sapphire contact cooling of liver and skin tissue samples, ex vivo. Gross and histologic examination was used to quantify thermal lesion dimensions. RESULTS: Liver lesions measured 5.5 +/- 0.3 mm in diameter, while preserving the tissue surface to a depth of 2.1 +/- 0.2 mm (n = 5). Skin lesions measured 4.3 +/- 0.9 mm in diameter, while preserving the skin surface to a depth of 1.1 +/- 0.2 mm (n = 6). There were no statistical differences in lesion diameter and layer of preserved tissue between contact (sapphire) cooling and prior non-contact (cryogen spray) cooling results for a given tissue type (P > 0.05). CONCLUSIONS: Noninvasive laser procedures targeting tissue structures for thermal coagulation within a few millimeters of the tissue surface are feasible and may expand the use of combined laser/cooling techniques for applications in urology and general surgery. In vivo animal studies are currently in development to optimize the laser and cooling parameters for potential clinical applications.     

Histopathological features of liver damage induced by laser ablation in rabbits

BACKGROUND AND OBJECTIVE: Possible mechanisms that promote or interfere with the effects of laser ablation of the liver have not been clarified. The aim of this study was to define the chronological alterations in the normal rabbit liver at early stages after laser ablation. STUDY DESIGN/MATERIALS AND METHODS: Rabbit livers were ablated with a laser via an optical fiber and then analyzed histopathologically by immunostaining for heat shock protein 70 (HSP70) and by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. RESULTS: The lesions increased in size progressively over the 24 h that followed ablation and the area of the lesion coincided with the area that had been heated above 43 degrees C. TUNEL-positive hepatocytes were surrounded, at some distance, by HSP70-positive hepatocytes were surrounded, at some distance, by HSP70-positive hepatocytes at 6 h, and such cells were in contact with each other at 24 h. CONCLUSIONS: Injury to hepatocytes induced by laser ablation increases for 24 h and dying cells express nuclear HSP70, with subsequent fragmentation of DNA.     

Histological study of vas deferens following intravasal laser irradiation

Aim: To study the histologic changes of the vas deferens following Nd: YAG laser irradiation. Methods:Intravasal laser irradiation was given to (i) 52 segments of rabbit (laser dosage: 2 seconds at 40W～50W) and 16 segments of human (3 seconds at 45W～55W) vas deferens in vitro, (ii) 25 rabbit vasa (2 seconds～2.5 seconds at 40W～45W) in vivo and (iii) 2 human vasa (3 seconds at 55W) in vivo. Segments of vasa were removed from the in vivo irradiated vasa deferentia 15 days ～ 180 days (rabbit) or 15 days (man) after the exposure. All vas segments were embedded in methacrylate resin. Serial sections (thickness 25μm～30μm) were obtained and observed under a light microscope. Results: (i) Laser-induced damage reached the muscularis layer in 27% and 94% of the rabbit and human vas segments in vitro, respectively. (ii) Fourteen of the 25 in vivo rabbit vasa were completely occluded by fibrous tissue and the longer the time interval after treatment, the more likely was the vas occluded. Those unoccluded vasa had either a normal histology or a mucosal damage. (iii) One in vivo human vas was almost completely occluded by the fibrous tissue but the other had a relatively large lumen packed with sperm granulomatous tissue and partial destruction of the smooth muscle layer. Conclusion: Laser irradiation can induce long-term vas occlusion; for rapid occlusion, laser doses just completely destroying the mucosal layer will be advisable.     

In vivo laser-induced interstitial thermotherapy of pig liver with a temperature-controlled diode laser and MRI correlation.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of a new temperature-controlled Diode laser to generate in vivo tissue coagulations with laser-induced interstitial thermotherapy (LITT) in pig liver and MRI-correlation of these necroses. STUDY DESIGN/MATERIALS AND METHODS: Each of four animal subjects received eight treatments at four different constant temperatures (70, 80, 90, and 100 degrees C) and at two out of three different intervals (3, 6, 9 minutes), resulting in a total of 32 lesions. After sacrificing, the liver was examined in an open MRI (0.35T). Tissue necrosis was measured macroscopically and compared with the size measured by MRI. RESULTS: The size of the necrosis was energy dependent with the largest extent at 100 degrees C at 9 minutes (2.1 cm). The correlation between macroscopic lesion size and MRI findings was significant (P > 0.036). Histological workup excluded carbonization in every case. CONCLUSIONS: LITT carried out with the Diode laser provides reproducible necroses of pig liver in vivo. MR-imaging results compared favorably with those obtained by pathologic specimens.     

Excimer laser ablation of fibrocartilage: an in vitro and in vivo study

To date, lasers have found only limited applications in orthopedics. We employed a 308 nm XeCl excimer laser for ablation of fibrocartilage, in order to investigate the feasibility of excimer laser assisted meniscectomy. Experiments were conducted both in vitro and in vivo. For the in vitro study, human menisci, obtained during surgery and autopsy, were irradiated via a 600 microns core fiber at radiant exposures ranging between 20 mj/mm2 and 80 mj/mm2, at 20 Hz. Ablation rate measurements and histological analysis of the samples were performed. The ablation rates were found to range from 3 microns/pulse to 100 microns/pulse depending on the radiant exposure and/or the applied pressure on the fiber delivery system. Thermographic analysis was also performed during pulsed excimer as well as CW Nd:Yag and CW CO2 laser irradiation. Temperatures were lower for excimer laser (Tmax less than 65 degrees) than CW ND: Yag (Tmax less than 210 degrees) or CW CO2 (Tmax less than 202 degrees) laser. For the in vitro study, medial meniscectomy was performed in 15 rabbits with the excimer laser and a CW Nd:Yag laser in the right and left knee respectively. Excimer laser irradiation was performed at 70 mj/mm2. Nd:Yag irradiation was performed via a 600 microns core fiber at power outputs between 20 to 40 W for 10 and 20 seconds duration. The healing response to injury was investigated by histological analysis of the menisci after 1 day, 1, 2, 4, and 8 weeks following the laser procedure. Excimer laser treated menisci showed less inflammatory reaction and noticeable repair with minimal inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endoscopic laser coagulation through an optical laser balloon

An endoscope was equipped with a saline-filled latex rubber balloon at its tip to displace contaminating blood, bile, or gastric contents during operative portoscopy, biliary endoscopy, or upper gastrointestinal endoscopy. A fiber with its tip inside the balloon transmitted energy from an Nd:YAG laser for coagulation of tumors in one bile duct cancer, in six portal vein growths from primary liver cancers, and in a superficially growing stomach cancer. The balloon increased the precision of irradiation by making lesions easier to identify through displacement of bile or blood and by keeping the fiber tip at a fixed position relative to the lesion. The technique, basic experimental studies, and clinical experiences are reported.     

Laser-induced thermal injury to dermal blood vessels: analysis of wavelength (585 nm vs. 595 nm), cryogen spray cooling, and wound healing effects

BACKGROUND AND OBJECTIVES: Successful laser treatment of cutaneous hyper-vascular lesions requires appropriate laser irradiation parameters for selective photothermolysis of ectatic dermal blood vessels as well as appropriate cooling parameters for epidermal protection based on an individual patient basis. Using the rabbit ear as an in vivo model for dermal vasculature, we investigated the influences of laser wavelength (585 nm vs. 595 nm) and cryogen spray cooling with various spurt durations on the laser-induced thermal injury to dermal blood vessels. Wound healing response was also evaluated in 2 hours and 4 days. STUDY DESIGN/MATERIALS AND METHODS: Flashlamp-pumped pulsed dye laser ScleroPlus (operated at the wavelength of 585 or 595 nm) was used for the comparison between the influences of two wavelengths (585 nm vs. 595 nm). R134-a cryogen spurts with the durations from 50 to 300 milliseconds were sprayed onto the sites to be irradiated and terminated 20 milliseconds before the onset of the laser pulses. In vivo rabbit ear was used as the model for cutaneous hyper-vascular lesions. Totally 10 New Zealand Albino white rabbits were experimented and in each rabbit ear six to seven sites were irradiated. Five animals were sacrificed 2 hours after the irradiation, and the remaining five sacrificed 4 days after the irradiation. Thermal injury to the blood vessel was assessed by hematoxylin and eosin stained histological sections and confirmed by an apoptosis assay. RESULTS: When the radiant exposures were above 10 J/cm2, 595 nm wavelength induced equivalent or more severe thermal injury to dermal blood vessels than 585 nm. Cryogen spray cooling with the spurt durations above 100 milliseconds resulted in increased depth of the most superficial thermal injury to dermal blood vessels than without cooling, indicating that superficial blood vessels were non-specifically cooled by the cryogen spurts applied at these parameters. Laser-induced thermal injury was significantly healed in the rabbit ear vasculature at 4 days post irradiation. CONCLUSIONS: Given sufficient radiant exposure, 595 nm wavelength can induce equivalent or more severe vascular injury compared with 585 nm. Cryogen spray cooling with the spurt durations above 100 ms may impair the photocoagulation of superficial blood vessels. Irreversible thermal injury to blood vessel can be achieved only when the basement membrane of blood vessel wall is irreversibly damaged.     

Enhancement of tissue lesion depth by dual wavelength irradiation with the Nd-YAG/KTP laser: Perspectives for laser prostatectomy

The Nd-YAG/KTP laser coagulates and vaporizes prostate tissue. The objective of this study was to investigate the combined effects of both wavelengths and to determine the irradiation parameters allowing the largest lesion volume. Chicken breast tissue was irradiated ex vivo. Consecutive 1064 and 532 nm Nd-YAG/KTP laser irradiations were performed for different combinations (30 W/10 W, 20 W/20 W, 10 W/30 W) with variable total fluence (1200 J, 2400 J, 3600 J) and compared to isofluent single wavelengths at 40 W irradiation. The depths, diameters and volumes of the total lesion as well as the vaporization effects of the 532 nm wavelength on normal and on priorly coagulated tissue were analysed. Maximum total lesion depths (p< 0.001) were found under combined Nd-YAG/KTP (20 W/20 W) irradiation conditions. Ablation efficacy of the 532 nm wavelength was reduced after prior 1064 nm irradiation, but crater depths were increased. Dual wavelength irradiation with the Nd-YAG/KTP laser induces a specific denaturation process. This may represent a new approach to increase the depth of coagulation necrosis, and thus the treated volume, thereby improving long-term results.     

Pulsed versus continuous wave Nd-YAG laser-induced necrosis: Comparison in the rat liver in vivo

It is assumed that a pulsed Nd-YAG laser will avoid heat diffusion in tissue and thus produce more predictable and less deep lesions. The aim of this study was to compare lesions induced in an homogeneous tissue by the pulsed wave (PW) and the continuous wave (CW) modes of the Nd-YAG laser. Single laser shots were delivered to the liver surface of anaesthetized rats after laparotomy, in vivo. In experiment 1, the quartz fibre was handled close to the liver surface. Energies of 10, 20, 40 J were applied. In experiment 2, the quartz fibre was fixed at a distance from the liver and the laser beam was focused through a handpiece, to obtain a spot of 3 mm in diameter at the liver surface. Energies of 20, 40, 80 J were applied. In both studies, four or five shots were performed for each parameter with each laser mode. After excision of the liver, the maximal depth and width of the crater, the necrotic area and the total affected tissue were measured for each lesion. In experiment 1, there was no difference in any dimension of lesion between the two modes. In experiment 2, the only statistical difference was observed at the fluence of 566 J cm^–2 where the necrotic area as well as the total lesion were deeper with the pulsed mode. This difference was not observed for the crater. In this experimental model depths and widths of the different layers of the lesion induced by the PW mode were comparable to those obtained with the CW mode. This PW mode of Nd-YAG laser does not prevent heat diffusion in tissue.     

MRI guided interstitial laser therapy in a rat malignant glioma model

We have used MR monitoring to guide and evaluate the effects of the Nd:YAG interstitial laser on a well-characterized rat brain tumor model (C6). MRI was used to determine the tumor size, verify the location of the interstitial probe, and evaluate the size and location of the laser–induced lesion during and after treatment. During laser irradiation, an irreversible loss of signal intensity at the fiber tip and a reversible decrease in signal intensity around it were observed with MRI. None of the treatment protocols affected mean rat survival significantly. Although MRI-guided interstitial laser therapy appears to be safe and easy, it does not provide a curative treatment for spatially disseminated gliomas where a “target volume” cannot be adequately defined. Better results can be expected, especially in well-defined tumors, with improvements of both the imaging techniques and the laser treatment protocol. © 1993 Wiley-Liss, Inc. © 1993 Wiley-Liss, Inc.     

Morphologic changes correlating to different sensitivities of Escherichia coli and enterococcus faecalis to Nd:YAG laser irradiation through dentin

BACKGROUND AND OBJECTIVE: Previous studies demonstrated the disinfecting potential of Nd:YAG laser irradiation on the root canal system from an overall quantitative viewpoint. The aim of this study was to evaluate the specific effect of irradiation through dentin on gram-negative and gram-positive bacteria with regard to their cell structure. STUDY DESIGN/MATERIALS AND METHODS: Sterile dentin samples of standardized size were divided into two sets of four groups with eight samples each. The first set was inoculated with Escherichia coli as the gram-negative test strain, the second set was inoculated with Enterococcus faecalis, which served as the gram-positive test organism. The samples were then irradiated on the bacteria-free side in contact mode under constant scanning movement at an angle of 10 degrees by use of the fiber optic of the Nd:YAG laser. Upon laser treatment they were critical point dried and subjected to SEM investigation. Another two sets of samples were prepared and irradiated in the same manner and evaluated by standard microbiological procedures to verify whether the observed morphologic alterations correlated to cell death. RESULTS: SEM investigations revealed damage pattens that increased with the amount of energy applied. Whereas the gram-negative test organism showed immediate structural injury, the gram-positive test organism required repeated application of irradiation. The microbiological examination showed reduction of both bacterial strains, yet to different extents. CONCLUSION: Our study demonstrates the different morphologic impact of Nd:YAG laser irradiation through dentin on representatives of the two main groups of bacteria. It shows that the construction of the cell wall is crucial for their individual sensitivity to laser treatment.     

Histologic signatures of thermal injury: applications in transmyocardial laser revascularization and radiofrequency ablation

BACKGROUND AND OBJECTIVE: Cardiac treatments such as transmyocardial laser revascularization and radiofrequency ablation cause thermal injury. We sought to provide quantitative histologic methods of assessing such injury by using the inherent birefringence of cardiac muscle and collagen; specifically, to exploit the connection between thermal injury and the loss of birefringence. STUDY DESIGN/MATERIALS AND METHODS: We quantified tissue birefringence changes in vitro for temperatures up to 130 degrees C. This information was used to assess thermal injury associated with myocardial channels made in vitro. We then measured in vivo cardiac injury 30 minutes and 3 days after radiofrequency exposure. RESULTS: Birefringence decreased above 60 degrees C for muscle and above 70 degrees C for collagen. Temperatures above 80 degrees C were associated with collagen fiber straightening and above 95 degrees C with little muscle birefringence. Injury adjacent to laser channels was greatest parallel to cell orientation. In vivo, muscle with reduced birefringence was surrounded by cells exhibiting focal birefringence increases (contraction bands). Early injury assessment marked by birefringence changes corresponded to lesion size at 3 days. CONCLUSION: Polarized light revealed histologic temperature signatures corresponding to irreversible muscle injury and collagen denaturation.     

Photocoagulation with a copper vapour laser in rabbit liver: A comparative study between the 510 nm and the 578 nm wavelengths

The coagulation effect, penetration depth and healing process of the 510.6 nm (green) and 578.2 nm (yellow) wavelengths of copper vapour laser (CVL) were compared in vivo in rabbit liver (n=15). A pulsed CVL, the Cu 15 from Oxford Laser—pulse repetition 10 kHz, peak-power 70 kW, pulse width 25 ns, and average maximal power 16W—was used connected to a dichroic system. The beam was transmitted through a 1000 μm quartz fibre and focused with a handpiece providing a 2 mm diameter spot size. By means of this delivery system 270 focused lesions are achieved at a power output of 2.65 W (power density 80 W cm⁻²) with irradiation times of 3, 5 and 10 s. The operative and microscopic verifications were achieved at 0 hour, and on days 3, 10, 20 and 30. Immediately after laser application, the lesions were triangular, well demarcated, and characterized by a central vaporization surrounded by four peripheral zones: carbonization; coagulation; oedema; and transition. The penetration depth was noticeably bigger in the yellow wavelength than with green wavelength, evidenced on day 10 by superior size of yellow wavelength photocoagulations and coagulation necrosis. Fibrosis appeared by day 3 and was gaining ground quickly and intensively after yellow wavelength while the fibrotic reaction was delayed on day 10 after green wavelength. The more penetrating effect of yellow wavelength advocates for its use in liver tumour destruction and photoradiation therapy while the green wavelength, inducing less aggressive effect on the surrounding tissue, seems more suitable for liver resection.     

Simplified treatment planning for interstitial laser thermotherapy by disregarding light transport: a numerical study.

BACKGROUND AND OBJECTIVE: The objective was to investigate the effect of light transport on the temperature distribution and the coagulated volume under conditions relevant to interstitial laser thermotherapy (ILT) of tumors in the human liver. STUDY DESIGN/MATERIALS AND METHODS: Temperature distributions and coagulated volumes produced with a diffusing laser fiber or a conductive heat source, at equal output power, were numerically calculated for tissue with different optical penetration depths. Four irradiation times (5, 10, 20, and 30 min) were studied. A three-dimensional finite-element model was used to calculate the temperature distribution during heating with four conductive heat sources (no light emission). Results were compared with measured temperature distributions during laser irradiation in a gel phantom with known optical properties. RESULTS: Numerical calculations showed that the influence of light transport on the coagulated volume was negligible in tissue with optical penetration depths below 3-4 mm at all studied irradiation times. The phantom experiment indicated good agreement with the calculated temperature distribution, both with a single diffusing laser fiber and with four fibers. CONCLUSION: Light transport influences coagulated volumes only slightly under conditions presented in this work, which is relevant to ILT of tumors in the human liver.     

The influence of Nd:YAG laser irradiation on Fluoroptic® temperature measurement: an experimental evaluation

The aim of this study was to experimentally evaluate temperature monitoring with a Fluoroptic® temperature probe in the presence of laser irradiation from a Nd:YAG laser, which is mainly used for clinical MR-guided laser-induced interstitial thermotherapy. Temperature measurements were performed using a Fluoroptic® probe in comparison to a thermocouple probe in a gel phantom and an ex vivo pig liver at distances of 6.5 to 14 mm to the laser applicator (laser energy of 30.8 W). To evaluate the artifacts in the temperature measurement, the laser was turned on and off three times during the entire experiment. A comparison of the fiber-optic measurements with MR thermometry was also performed in pig liver by means of the proton resonance frequency method at a distance of 6 mm. Depending on the distance, the temperature measured by the fiber-optic probe deviated from the thermocouple probe temperature. The phantom deviations of 0.4 to 34.3 % were observed. The differences in the liver were smaller and ranged from 1.6 to 5.2 %. The Bland–Altman mean of differences between MR and fiber-optic temperature measurements was 0.02 °C and the 95 % limits of agreement value was ±2.25°C. During laser application, considerable artifacts occurred in the Fluoroptic® measurements in short distances which was induced by laser energy absorption by the probe coating. No artifacts were verifiable at a distance of 14 mm in both mediums. The good conformity with MR thermometry resulted from the shorter turn-on times of the laser since the laser irradiation had only a minor effect on the measurements.     

Cerebrovascular and metabolic effects on the rat brain of focal Nd:YAG laser irradiation

To investigate the effects of focal neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation (lambda = 1060 nm) on regional cerebral blood flow, cerebral protein synthesis, and blood-brain barrier permeability, the parietal brain surface of 44 rats was irradiated with a focused laser beam at a constant output energy of 30 J. Survival times ranged from 5 minutes to 48 hours. Laser irradiation immediately caused well-defined cortical coagulation necrosis. Within 5 minutes after unilateral irradiation, 14C-iodoantipyrine autoradiographs demonstrated severely reduced blood flow to the irradiation site and perilesional neocortex, but a distinct reactive hyperemia in all other areas of the forebrain. Apart from a persistent ischemic focus in the vicinity of the cortical coagulation necrosis, blood flow alterations in remote areas of the brain subsided within 3 hours after irradiation. Autoradiographic assessment of 3H-tyrosine incorporation into brain proteins revealed rapid onset and prolonged duration of protein synthesis inhibition in perifocal morphologically intact cortical and subcortical structures. Impairment of amino acid incorporation proved to be completely reversible within 48 hours. Immunoautoradiographic visualization of extravasated plasma proteins using 3H-labeled rabbit anti-rat immunoglobulins-showed that, up to 1 hour after irradiation, immunoreactive proteins were confined to the neocortex at the irradiation site. At 4 hours, vasogenic edema was present in the vicinity of the irradiation site and the subcortical white matter, and, at later stages (16 to 36 hours), also extended into the contralateral hemisphere. Although this was followed by a gradual decrease in labeling intensity, resolution of edema was still not complete after 48 hours. Analysis of sequential functional changes in conjunction with morphological alterations indicates that the evolution of morphological damage after laser irradiation does not correlate with the time course and spatial distribution of protein synthesis inhibition or vasogenic edema. Although the central coagulation necrosis represents a direct effect of radiation, the final size of the laser-induced lesion is determined by a delayed colliquation necrosis due to persistent perifocal ischemia. Extent and severity of ischemia in a zone with initial preservation of neuroglial cells can be explained by the optical properties of the Nd:YAG laser; extensive scattering of light within brain parenchyma associated with a high blood-to-brain absorption ratio selectively affects blood vessels outside the irradiation focus.