A color-camera-based technique was used for evaluation of reflectance and transmittance of the human hair shafts. The inverse Monte Carlo method was used for estimation of hair optical properties - absorption and reduced scattering coefficients. Hair samples have been obtained from ten volunteers. We have investigated blond, brown, black, light- brown and gray hairs. Obtained differences in absorption and scattering properties correlate with structure- morphological features of hair types. Offered method allows one to provide express-analysis of optical properties of a hair shaft, to determined separately absorption and scattering coefficients and melanin content.

Cutaneous vascular disorders such as port wine stains can now be treated using lasers with a high probability of success. However, the predictability of the outcome, both in terms of satisfactory lesion clearance and risk of side effects, remains a major challenge. The investigators have found evidence that laser coagulation of blood is much more complex process than previously anticipated, involving chemical changes in the hemoglobin molecule, shape changes in the red blood cells, and protein coagulation on at least two different time scales. The optical (scattering and absorption) and thermal properties of blood are therefore time- and temperature-dependent. Thus, modeling using "cold" optical properties of blood may fail to predict experimental results. We have performed several investigations into the laser coagulation ofblood to further elucidate the coagulation mechanisms: - Apump-probe experiment has been used to investigate the optical property changes of coagulating blood in cuvettes at various wavelengths. Measurements have been made of the time-domain integrated reflectance and transmission ofthe samples. - Rapid optical coherence tomography imaging of the coagulation process in cuvettes of blood shows distinct waves of coagulation. - A decrease of the longitudinal spin relaxation time in magnetic resonance imaging is observed in photothermally coagulated blood as compared to native blood.

Knowledge of optical and thermal properties of human tissue is essential for optimization of laser therapy and optical diagnostics. Published data are in general incomplete, and there is very limited information on the temperature dependence of optical properties. The temperature dependence of hemoglobin is important since it is the target chromophore for laser treatment of e. g. port-wine stains. The present study emphasizes the temperature dependence of the hemoglobin absorption. Erythrocyte concentrate was heated in a water bath, hemolyzed with distilled water and centrifuged before absorption spectra were collected. Measurements were performed in the range of 50-80 °C. Penetration depth measurements of the heated erythrocyte concentrate were done at 488 nm, 585 nm, 590 nm and 630 nm. For these measurements the erythrocytes were mixed with a highly scattering material (whole milk). The hemoglobin absorbance demonstrates a characteristic change during heating. This change is partly due to oxidative reactions with formation of met-hemoglobin, and also by protein denaturation. The change in the absorption coeÆcient due to met-hemoglobin has a maximum at approximately 72 °C, where the increase was measured up to 200 % at 630 nm wavelength.

We present experimental results on study of Methylene Blue penetration into skin using a method of digital analysis of color images. Experiments were carried out with a rat skin in vitro. Dependence of the penetration depth of Methylene Blue on dyeing time ofthe tissue was researched. Diffusion coefficients of Methylene Blue within the skin in vitro were estimated.

This study aimed to evaluate the penetration of Methylene Blue (MB)-loaded microspheres into the follicular ducts of rats. MB was incorporated into porous nylon microspheres which have a size of 10 ?m (Orgasol 4000 Nat Cos, Elf-Atochem, France). The microspheres were dispersed into fluid silicone. Male hairless rats (NU, Iffa Credo, France; mutant hairless Sprague Dawley rat) were used to evaluate the penetration of MB into hair follicles. After formulation application, MB diffusion was induced and skin biopsies were realized immediately, 2 hours and 26 hours after MB loaded microspheres application. All samples were snap frozen in liquid nitrogen and processed stored at -80°C before embedded in TissuTek and cryostat-cut. 14?m sections were realized. MB fluorescence was observed with Eclipse E800 microscope (Nikon, Tokyo, Japan) expanded for fluorescence microscopy (with FITC, TRITC and CY5 filters) and penetration depth was quantified using image analysis software (Sigma Pro, Jandel, USA). Autofluorescence was evaluated using FITC and TRITC filter. MB was seen 200?m deep in hair follicles (2 hours after application) and at 600?m (26 hours after application). This galenical approach aims to transport MB into the hair follicle specifically and deeply.

The skin permeability of most of drugs is low, because the stratum corneum works as a solid barrier. It is required, therefore, to enhance the skin permeability for transdermal delivery of drug. To investigate the effects of heating skin and exposing skin to a laser-induced stress wave (LISW) on the drug permeability, we tried to deliver porfimer sodium into rat’s skin. The experiment was performed under the four different skin conditions; exposing to a LISW (case 1); heating (case 2); exposing to a LISW and heating (case 3); control (case 4). It was observed in all cases except the case 4 (control), the drug permeated into the dermis through the epidermis. The deepest penetration was obtained in the case 3 (a LISW plus heating). It was suggested that heating increased the fluidity of the lipid bilayers in the stratum corneum, and therefore the drug permeability might be enhanced.

Cryogen spray cooling (CSC) is an effective method to minimize epidermal damage during laser treatment of various cutaneous anomalies such as port wine stains, excess hair, and facial rhytides. In this study, we investigated the effects of the cryogen film thickness on heat removal, and laser light transmission through the film. Surfactants were added to the cryogen (R-134a) to decrease the film height by reducing the surface tension, and the resulting heat removal from an in vitro skin phantom was estimated using an algorithm that solved an inverse heat conduction problem. Transmission of light through the cryogen film sprayed onto a glass cover slip was measured by an energy meter at wavelengths of 595, 755, 1064, and 1450 nm. Normalized film height was negatively correlated (r < -0.65) to heat removal for relatively short spraying distances (50 mm). Reducing the cryogen film height may offer an approach to increase heat removal. Values of light transmission were in the range of 70 – 95% for the lasers using various durations of cryogen spurts and delays.

The purpose of this study was to investigate the dynamics oflaser light attenuation during cryogen spray cooling (CSC). Two detection schemes were used to approximate col]imated and diffuse light transmittance measurements of continuous-wave (?= 594 nm) and pulsed (?= 585 nm) laser light during application of short (20-100 ms duration) cryogen spurts on a glass substrate. High-speed video images were also obtained during CSC. Collimated light transmittance varied considerably during CSC. Comparison of collimated and total transmitted light detection indicated that the diffuse component was substantial. Light attenuation occurred despite transparency of the liquid cryogen layer. Light scattering by cryogen results in a diverging laser beam incident on the skin surface. Since specular reflectance at the cryogen-skin interface may differ for diffuse light, further study of light scattering during CSC is warranted. Due to the differences in optical properties of glass and skin, experiments on skin need to be performed to extrapolate our results to the clinical scenario. For dermatologic procedures such as laser port wine stain and vascular lesion removal, hair removal, and nonablative skin rejuvenation, recommended ?d are 10-80 ms. This range of td appears to be appropriate, although more studies are required to arrive at a definite conclusion.

Cryogen spray cooling (CSC) offers a means to selectively cool the epidermis during laser therapy and has been used in conjunction with pulsed laser irradiation to treat light skin patients (Fitzpatrick Type I-TV) at moderate radiant exposures (<15 J/cm2). The purpose of this study was to determine the effectiveness of CSC in protecting the human skin epidermis in vivo from thermal injury during high radiant exposures (>15 J/cm2). Normal abdominal skin on twenty anesthetized individuals undergoing transverse rectus abdominis myocutaneous (TRAM) flap procedures with various skin types (Fitzpatrick type I-VT) were irradiated using incident radiant exposures of 8-30 J/cm2 without and with CSC. Assessment of tissue damage was based on histologic analysis. Epidermal damage was observed as basal epidermal cell vacuolization, epidermal basal layer separation, and epithelial cell spindling. For lighter skin patients (Fitzpatrick type IIV) the epidermal damage threshold was increased to as much as 30 J/cm2 when using CSC. However, complete epidermal protection in the darkest skin patients (Fitzpatrick type V-VT) could not be achieved with cryogen spurt durations as long as 300 ms using cunent CSC protocols.

We investigate a novel design of a cryogen-cooled capacitive RF treatment tip (Thermage) designed to volumetrically heat skin while preserving the epidermis. Cryogen R-134a (1,1,1,2-tretrafluoroethane), an environmentally compatible, non-toxic, FDA-approved freon substitute, is sprayed on the back of the treatment tip to induce conductive cooling to the skin surface. The treatment tip is driven by an RF generator at 6 MHz with a typical dosage of 95 J delivered over 2 sec. The purpose of this study was to predict the temperature profiles within human skin due to the RF heating and cryogen cooling through the use of a three-dimensional mathematical model of the temperature distribution within human skin. RF cunent density was determined by measuring the potential field in skin-like saline solution with a custom 3D field mapping system. The three-dimensional bioheat equation was solved using the central finite-difference approximation. Results of this study show that this electrode design induces volumetric heating deep within the skin while still protecting the superficial skin layers from thermal injury. This combination of RF heating and surface cooling may prove beneficial for non-ablative cutaneous thermal therapies.

Phase III multicenter study was conducted in the USA under the FDA approved protocol, to establish the safety and efficacy of High Intensity Focused Ultrasound (HIFU) in the treatment of Benign Prostatic Hyperplasia (BPH) using the Sonablate? system. A total of sixty eight patients have been treated to date in the Phase III study. Transrectal probes capable of real-time ultrasound imaging of the prostate and well as delivering the HIFU energy to the selected region in the prostate gland were used. Probes with different focal lengths were used to treat different size of prostate glands. The patients were treated in one treatment session and were followed up to a period of one year following the treatment. The subjects underwent physical exam, Digital Rectal Examination (DRE), cystoscopy, Transrectal Ultrasound (TRUS), blood work, urine exam and were given standard questionnaires before treatment and during the follow up period. Under this protocol HIFU was found to be safe and effective in reducing the BPH related symptoms and improving the peak urinary flow rate with preservation of sexual function and no permanent side effects.

Surgical vasectomy may lead to complications including bleeding, infection, and scrotal pain. Noninvasive transcutaneous delivery of therapeutic focused ultrasound has previously been shown to thermally occlude the vas deferens. However, skin burns and inconsistent vas occlusion have presented complications. This study uses bioheat transfer simulations and thermocouple measurements to determine the optimal ablation dosimetry for vas occlusion without skin bums. A two-radian ultrasound transducer clip delivered 4 MHz ultrasound energy to the canine vas deferens co-located at the focus between the clip jaws. Chilled, degassed water was circulated through an attached balloon, providing efficient ultrasound coupling into the tissue and applied cooling to prevent skin bums. Temperatures were recorded at the vas, intradermal, and skin surface during ablation. Acoustic powers of 3-7 W and sonication times of 60-120 sec were used on both the left and right vas (n=2) in a total of four dogs (Control, 3W/120s, 5W/90s, 7W/60s). Measurements were compared with bio-heat transfer simulations modeling the effects of variations in power and sonication time on tissue temperatures. Simulations and experiments suggest that a therapeutic window exists in which vas occlusion may be achieved without skin bums (P =5-7 W, SI = 1.4- 1 .9 W/cm2, t = 20-50 sec). This dosimetry will guide future vasectomy experiments using focused ultrasound.

Cold knife incision of urological strictures results in a high rate of stricture recurrence. This study compares Ho:YAG and Er:YAG lasers for precise incision of urethral and ureteral tissues. Laser ablation was performed using Ho:YAG (?=2.1 µm) and Er:YAG (?=2.94 µm) lasers operating in long-pulse mode (?p = 300 µs). Ho:YAG laser radiation was delivered through low-OH fibers while Er:YAG laser radiation was delivered through germanium oxide or sapphire fibers. Ex vivo canine and porcine tissue samples were placed in saline, and perforation thresholds, ablation rates, and histological thermal damage measurements were recorded. Optical fiber damage thresholds during contact ablation were also studied. The Ho:YAG and Er:YAG lasers perforated thick tissue samples at thresholds of 350 J/cm2 and 65 J/cm2, respectively, with peripheral thermal damage zones measuring 290 + 30 µm and 30 + 10 µm, respectively. Germanium oxide fibers were damaged at energies greater than 150 mJ/pulse (80 JIcm2), but no damage to sapphire fibers was observed at energies up to 450 mJ/pulse (3 50 J/cm2). The Er:YAG laser efficiently ablates urethral and ureteral tissues while reducing peripheral thermal damage by an order of magnitude over the Ho:YAG laser. In vivo animal studies for Er:YAG laser incision of strictures are planned with comparison to cold knife incision.

Safety, efficacy and probe flexibility of intracorporal lithotripsy systems are key factors that influence both the treatment outcome and range of indication in the treatment of stone diseases, e.g. urolithiasis. A new shockwave solid-state laser is investigated for its clinical application in that field.

The laser system U100 made by WOM AG, Germany is a newly designed medical laser device espacially for the use in urology for the intra corporal kidney, urethra and bladder stone shockwave lithotripsy as well as for the gestrointestinal surgery to shatter stones in the bile duct. In opposite to other laser systems which usually produces little shockwaves by means of collapsing steam cavities by a rapid and strong heating of the water surrounding the material, the laser energy of the U100 generates a real mechanical shock wave directly on the targeted stone, which leads to a safe and very efficient crushing of the stones. Becase of this non thermal interaction the adjacent tissue remains unaffected. Highly flexible, thin fiber system permit the laser energy to be trensferred to the targets using various methods of access, by means of X-ray control and under the direct endoscopical view with rigid and flexible scopes. We present the background of the FREDDY (Frequency Doubled Double Pulse Nd:YAG) lase technology and discuss the applications in urology, gestrointestinal surgery and other medical fields the U100 has been grented FDA 510k approval for use in urology in November 2001.

5-aminolevulinic acid (ALA)-induced fluorescence diagnosis (FD) allows for a more thorough transurethral resection (TUR) of superficial bladder tumours (BT) compared to conventional white light (WL). A prospective randomized trial was performed to investigate whether residual tumour rate and long-term tumour recurrence can be reduced by means of FD.

The objective of the study was to design, to investigate and to optimize non-contact fiber delivery system for different clinical applications. This system eliminate the main disadvantages both applied contact and non-contact probes, namely surface contamination with further probes thermal deterioration and large beam divergence, respectively. The main part of the proposed non-contact fiber delivery system is probe made in fused silica or synthetic sapphire which produces quasi-collimated beam with specific outside diameter and power distribution along this beam. These probes were designed for different laser clinical applications, especially for interstitial thermotherapy and photodynamic therapy. Five different types of them were manufactured by InnovaQuartz, Inc. (Phoenix, AZ, USA) and Tochpribor (Kharkiv, Ukraine). To provide comparative analysis and optimization of the optical properties of the novel fiber delivery systems with commercially available ones "steady beam distance"; "steady beam ratio" and "power density efficiency" coefficients are proposed. The improved versions of the commercial urologic devices "transurethral optical laser knife" (Mayo Clinic), TULIP (Intrasonics), UroLase (Bard), SideFire (Myriadlase), ADD (Laserscope), UltraLine (Heraeus Lasersonics), ProLase II (Cytocare) are examined. The received results could provide a tool useful to designers of noncontact fiber delivery systems intended for different clinical applications with cw and pulse lasers.

Recently technological advances in optical imaging have shown the promise to provide high-resolution imaging of biotissues. Optical coherence tomography (OCT) enables cross-sectional imaging of highly scattering biological tissues at the axial resolution of 10 micrometers or less and at the depths of up to 2-3 mm, highly desirable for screening various kinds of superficial lesions and the invasion of these lesions. In this study, we applied OCT to examine normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of rat bladder demonstrate the potential of this method to clearly delineating the micro morphological structures of human bladder tissue. Our results show that the micro morphology of rat bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlate with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion, as well as abnormal growth of urothelium. By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. The results suggest the potential of OCT for noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering.

Traditional protein solders composed of serum albumin, an optional absorption chromophore, and water, are soluble in physiological fluids before laser irradiation. This can be problematic for application of the solder to the tissue, as some of the material tends to run away before it is bonded to the tissue. In addition, as the solder is subjected to blood dilution during application, the mechanical properties are altered and consequently, the strength of the repair is compromised. This ultimately leads to poor reproducibility and reliability of the repair technique. Enhancement of these protein solders with a synthetic polymer membrane composed of poly(L-lactic-co-glycolic acid) was investigated as a means for increasing the stability of the solders in physiological fluids prior to irradiation. In addition, predenaturation of both the traditional and membrane enhanced solders in a hot water bath at 75°C was investigated as a means to decrease the solubility of the solders, thus improving their handling characteristics, prior to laser irradiation. A Bradford protein assay was used to measure the solubility of the protein solders prior to thermal denaturation with a laser. To compare these results with the final product of laser tissue repairs, the solubility analysis was also performed on similar specimens after laser irradiation with an 805-nm diode laser. Doping of the solder in a polymer membrane and predenaturation of the solders at 75 °C were found to be advantageous for improving their handling characteristics. Alteration of the mechanical properties of the solders prior to laser treatment was also prevented, thus improving the reproducibility and reliability of the repairs. Finally, the solubility of protein solders of varying composition was correlated with the mechanical strength of arterial repairs formed in an in vitro porcine model. The data suggests that there should be an optimal solubility at which solder/tissue contact is maximized and solder runaway minimized, thus resulting in a superior bond.

An investigation was conducted to assess the feasibility ofusing various synthetic polymers as scaffolds to traditional albumin protein solders with the aim of enhancing the mechanical strength of repairs formed during laser tissue soldering. Biodegradable polymer membranes of controlled porosity were fabricated with either polylactic acid (PLA), polyglycolic acid (PGA), or two different poly(L-lactic-co-glycolic acid) (PLGA) blend ratios, using a solvent-casting and particulate-leaching technique. In addition, membranes were prepared by combining each of the above mentioned polymers with poly(ethylene glycol) (PEG). The porous membranes provided a scaffold into which the traditional protein solder composition of serum albumin and indocyanine green dye mixed in deionized water was readily absorbed. Studies were conducted to assess the influence of various processing parameters on the strength of tissue repairs formed using the new adhesives. These parameters included the polymer type, the polymer/PEG blend ratio, the salt particle size, and the initial albumin weight fraction. No significant difference was observed between the four polymers investigated, however, variation of the polymer type and blend ratio is known to influence the degradation rate of the membranes. The addition of PEG to the films during the casting stage was observed to increase the flexibility of the membranes. Finally, repair strength increased significantly with an increase in the size ofpores present in the membranes and with increased protein concentration.

A new method for tissue soldering using an argon ion beam coagulator (ABC) and human serum albumin is presented. The ABC is widely used in surgery and provides a fast and precise means of achieving hemostasis. In this paper, the mechanical properties of liver and denatured albumin (solder) were measured and the failure methods of liver repaired with albumin were identified. The ultimate tensile strength was measured for healthy liver (N=37) and thermally damaged liver (N=32). The ultimate tensile strength was measured for three concentrations of coagulated albumin (25, 38 and 53%) in a single layer and for two layers of denatured 38% albumin. Failure under tension of argon beam coagulator soldered liver on the parenchymal surface (N=30) with 38% albumin in two layers had a 70% occurrence for tearing at a mean stress of 39 kPa and a 23% occurrence for shearing at a mean stress of 7 kPa. Liver repaired on the interior surface (N=11) failed in tension by tearing (64%) at a mean stress of 34 kPa and by shearing (36%) at a mean stress of 6 kPa. Argon beam coagulator soldering with 38% albumin took 6 s/cm2 for two layers of solder and gave the best balance of usability and strength.

Background: The argon beam coagulator (ABC) is frequently used to control bleeding on parenchymatous organs during surgery. The purpose of this study was to assess whether it improves the efficacy of hemostasis of using the argon beam coagulation with a concentrated human albumin at partial hepatectomy. Methods: Thirty-two domestic swine were randomized and treated with either conventional argon beam coagulation alone (ABC, N=16) or the argon beam coagulation in association with a concentrated human albumin (ABCA, N16) following by wedge resection of left median lobe of the liver using a digital fracture technique. Postoperative followup was up to 90 days for acute parameters and chronic bio-compatibility studies. Results: The ABCA group required fewer repeat applications of argon beam coagulation than ABC alone group (mean 0.5 vs. 1.5, p=0.00'7). The total blood loss of ABCA was significantly less than ABC group (mean 3.83 vs. 8.29, p=O.O49). The post-operative reaction was similar to the both groups, which shows a chronic inflammation response as part of the ongoing normal healing process. Conclusions: We demonstrated that the ABCA is more effective and reliable than ABC alone in hemostasis of hepatic injury. Clinical trials ofusing the ABCA for solid organs injury repair are warranted.

Previous in vitro laser-tissue welding research demonstrated a technique to improve the acute breaking strength of liquid albumin solder using biodegradable polymer film reinforcement. This study’s purpose was to explore what problems could arise in vivo that were not evident in vitro. Full thickness incisions were created on the dorsum of Sprague-Dawley rats. A poly(lactic-co-glycolic acid) (PLGA) film was subcutaneously implanted in the incision (controls had no film). The incisions were closed by laser-tissue welding: albumin solder with Indocyanine Green dye was inserted between the incision edges and coagulated with a diode laser. Specimens were harvested at 0, 3, 7, and 14 days for strength testing and histologic analysis. Histology indicated that the PLGA film was relatively well tolerated by the tissue. Breaking strengths of controls at 0 and 14 days were stronger than specimens with implanted films (t-test, P < 0.05). Difficulty apposing the incision edges due to the film presence probably contributed to low acute strengths. Interference with wound contraction by the films possibly contributed to lower breaking strengths at 14 days. Polymer films for patch reinforcement of solder may be clinically feasible; however, application specific problems can occur and should be considered when developing a clinical technique.

We present a study on welding of ex vivo aorta and skin samples using a tunable Cr4+: yttrium aluminum garnet (YAG) laser to explore the wavelength dependence of the welding efficacy. Welding efficacy was monitored by measuring the tensile strength of the welded tissue and the extent of collateral tissue damage. Tensile strengths were measured using a digital force gauge. Full thickness tissue bonding was observed with both aorta and skin samples. The welding of aorta was so perfect that it was difficult to distinguish the welded sites from the non-welded sites on hematoxylin and eosin staining of the samples under optical microscope. No collateral damage of the aorta samples was observed. Scanning Electron Microscopic study of the welded samples supported the optical microscopy results. Best results for aorta and skin were achieved in the 1455-1460 nm range. The weld strength as a function of wavelength correlates with the absorption spectrum of water. Fluorescence imaging of welded aorta and skin shows no significant change in collagen and elastin signal.

Background and objectives: A feedback temperature controlled laser soldering system was used for bonding cut wounds on the skins of young and mature pigs. This is a step towards clinical implantation of this promising novel technique. Materials and methods: 47% bovine serum albumin (BSA) solder was applied onto cuts created in dorsally d epilated skin on the backs of pigs, weighing 8 -10Kg or 74Kg. A temperature fiberoptic CO2 laser system was used to monitor and control the temperature of a spot on the cut at a desired temperature. For given values of time and temperature, a 28 days follow up of the soldered scars was obtained and compared with standard suturing. Results: Optimal soldering temperature was found to be 65ºC. The tensile strength of laser-soldered cuts was measured after 3-28 days postoperatively and was found similar to that of sutured cuts. Macroscopic and microscopic studies showed better and faster wound healing of soldered scars compared with standard sutures. All soldered scars in the mature pig, demonstrated excellent healing with no signs of dehiscence. Conclusions: Temperature controlled laser soldering of cut wounds in pig skin offers several advantages over standard suturing techniques. This novel method should be tested clinically.

Objectives: To determine the feasibility and reproducibility of laser soldering of cornea using biolog ical solder and a fiberopitc temperature conrolled CO2 laser system. Methods: We developed a system based on IR fiber delivery of CO2 laser radiation, for heating a spot on tissue, a fiberoptic radiometer for non-tactile infrared thermometry of the heated spot, and a computer control of the temperature of the spot.Experiments were performed in vivo in 8 corneas of 12Kg piglets eyes, which had 180°, 6mm diameter corneal trephnation perforating cuts.Soldering was done on some of the cuts at a set temperature of 65°C, with adjuvant 47% albumin solder, and standard suturing was done on other cuts, as control.Macroscopic and histologic evaluation was then carried out. Results: On macroscopic examination, the corneas were centrally clear, with corneal neovascularisation only around the sutures.Histologic examination of piglets corneas one week, one month, two months and five months after soldering revealed stromal lamellae which were organized with a fewer inflammatory reaction, in contrast to marked inflammatory response in the suture controls. Conclusions: The laser soldering technology appears to be reliable for closure of large corneal perforating cuts, and may overcome some of the technical difficulties and disadvantages of conventional corneal suture technique.

An in vivo study was conducted to investigate the feasibility, mechanical function, and chronic biocompatibility of a new range of light-activated surgical adhesives for vascular anastomosis. Porcine carotid arteries (n=12) and femoral arteries (n=12) were exposed, and a 0.3 -0.6cm longitudinal incision was made in the arterial walls. The vessels were divided equally into two groups. Vessels belonging to the first group were repaired using a surgical adhesive, composed of a poly(L-lactic-co-glycolic acid) scaffold doped with the traditional protein solder mix of serum albumin and indocyanine green dye mixed in deionized water. The adhesive was applied across the incision and denatured using an 805-nm diode laser. Vessels belonging to the second group formed part of a control study, and were repaired using conventional suturing techniques. Blood flow was restored to the vessels immediately after the procedure and the incision sites were checked for patency. The strength and hemostatic abilities of the new surgical adhesives were evaluated in the context of arterial pressure, persistence of hemostasis and presence of any inflammatory reaction after 3 days. The adhesive technique compared favorably with the suture technique. Repairs formed with the adhesive technique were achieved more rapidly than suturing, and acute leakage was observed less frequently. Repairs closed by suture did not burst, but leaked at pressures significantly below those of vessels closed with the adhesive material. Finally, the adhesive technique produced better histology than the suture technique, suggesting that it holds great promise as an alternative to suturing.

Photodynamic therapy (PDT) is a potential improvement over conventional therapy for urinary bladder cancer, especially using the pro-photosensitizer 5-aminolevulinic acid (ALA), which is metabolized to its active form, protoporphyrin IX (PpIX), within both normal and neoplastic epithelial tissue. The purpose of this study was to evaluate ALA-based PDT in healthy dogs as a prelude to treating dogs with transitional cell carcinoma of the urinary bladder. Methods: Twelve dogs were given oral ALA at 0, 30, 60, or 90 mg/kg. Four hours later, the dogs were sacrificed and bladder tissue was collected and frozen for low-intensity fluorescence microscopy. Fifteen dogs were given oral ALA at 0, 30, 60, or 90 mg/kg and anesthetized four hours later. The trigone was irradiated with 635 nm laser light. All dogs were necropsied after PDT (48 h or 21 d). Results: PpIX fluorescence was confined to the urinary bladder mucosa with no detectable fluorescence in the muscularis or serosa. Histopathological lesions after PDT were limited to mild inflammation. Conclusions: Oral ALA appears to be well tolerated by healthy dogs at the dosages used. Because PpIX fluorescence was confined to the mucosa, ALA-based PDT may be a useful treatment for canine lower urinary tract neoplasia.

The Ho:YAG laser, used successfully in humans, may be effective for treating canine urolithiasis. The purpose of this study was to determine the in vitro effects of various Ho:YAG laser operating parameters on canine uroliths and a urethra model. Canine uroliths of known composition and cadaveric porcine urethral tissue were irradiated with the Ho:YAG laser. Fragmentation time was analyzed as a function of urolith composition, water weight, Hertz, pulse mode, and energy. All uroliths were completely fragmented with 20 seconds or less of laser irradiation. Calcium oxalate, cystine, and silica uroliths had significantly longer fragmentation times than struvite and urate uroliths. As Hertz rate increased, fragmentation time significantly decreased. No significant differences were noted in fragmentation time or total energy required for fragmentation between single and double pulse mode. Grossly visible urethral damage increased as total energy increased. Urethral damage scores were significantly higher in tissues treated with a 90° incident beam compared to those tissues treated with a 30° incident beam. Likewise, urethral damage scores were significantly higher in contact mode treated tissues compared to non-contact mode treated tissues. Based on these findings, the Ho:YAG laser may be useful for treating clinical cases of canine urolithiasis.

The Neodynium: Yttrium Aluminum Garnet (Nd: YAG) laser has been the most frequently used laser in correcting equine upper respiratory disorders.'4 Evaluation of this laser and several other lasers' ability to penetrate tissues is based on in vitro studies using portions of the arytenoid cartilage and the nasal septum.5 The parameters measured have routinely been the depth and width of the crater created by laser irradiation of the tissue.5 Previous studies, now considered the standard, have used a power output of 200 joules to create a measurable crater in order to make comparisons.5'6 The initial method of measurement consists of standard histological preparation followed by microscopic evaluation. This has been compared to computed tomography which has been determined to be as accurate.5'6 In a more recent study, we compared the 980nm and 810nm diode lasers producing a total power output of 20 watts, to the Nd: YAG laser.7 As demonstrated, both diode lasers can potentially be used as a substitute for the Nd: YAG laser.7 Our study also indicated that intravenous administration of indocyanine green (ICG) greatly enhanced the depth and width of crater formation in equine respiratory tissue with the laser set at 200 joules total power output.7 Intravenous administration of ICG was found to be an expensive protocol, therefore, the current study was devised to determine the penetration parameters of ICG after topical administration. The evaluation consisted of comparing depths and widths of penetration measured by computed tomography technique after ICG was topically sprayed on the tissue with solution concentrations ranging from 0. 1 % to 1%. The study's results demonstrated that topical application of ICG greater than or equal to 0.5% solution produced a depth ofpenetration significantly greater (p>0.05) than that ofthe Nd: YAG laser. The width measurements of craters created by the diode laser irradiation were found to be significantly less than those produced by the Nd: YAG laser. It was concluded that topical administration of ICG was more economical than intravenous administration.

The Neodynium: Yttrium Aluminum Garnet (Nd: YAG) laser was one ofthe first lasers to allow tissue photoablation to be performed transendoscopically in the standing equine patient.1 It became very popular due to the fact that its irradiation can be applied through flexible fiber optic cables. Recently, a number of diode lasers have been marketed to the equine practitioner as replacements for the Nd: YAG laser, specifically the 810nm and 980nm diode lasers. Initially, both of these lasers produced a maximum of 20 watts total power output. Currently, higher power output versions being 50 or 60 watts are available to the practitioner. Producing a high power output means these lasers have the potential to be used in the non-contact configuration, as well as contact, when performing corrections of upper respiratory disorders ofthe horse. Penetration studies have been performed using lower power (20 watt) 810nm and 980nm diode laser which were compared to the depths and widths of penetration produced by the Nd: YAG laser.2,3 The purpose of this investigation was to evaluate the 60 watt 810nm diode lasers penetration delivering 200-600 joules on to equine respiratory tissue. Penetration parameters selected were width and depth of craters and were compared to the Nd: YAG laser set to deliver 200 joules of energy. This study determined that the 810nm diode lasers penetration parameter is close to that of the Nd: YAG laser. As the diode laser power output increased above 200 joules, it significantly penetrated respiratory tissue deeper than the Nd: YAG laser set at 200 joules output. Measurement of the crater depth created by the 810nm diode laser as its output power was increased at 100 joule increments was significantly deeper than the depth of crater formed by the previous power setting. Similarly, the diode laser's crater top and bottom width measurement, at 400 joules and greater, was significantly greater than or equal to that of the Nd: YAG lasers set to deliver 200 joules of energy. This investigation provided evidence that the 60 watt 810nm diode laser produces substantial penetration that can be applied not only in the contact mode successfully, but also in the non-contact mode providing the practitioner with a more versatile laser for transendoscopic application in the equine.

In otolaryngology two novel RF instruments have been developed addressing the shortcomings associated with classic electrosurgery: controlled tissue ablation (Coblation) and temperature controlled radiofrequency total volume reduction (Somnoplasty). Coblation involves placing closely spaced bipolar electrodes in a conductive media in approximation with the tissue of interest. A plasma layer is produced disrupting molecular bonds in the tissue. Resultant debris is washed away during intraoperative irrigation. Since plasma forms in the conductive media, not on the tissue directly, surface temperatures are reduced (40-70°C compared to >400°C) resulting in decreased collateral tissue damage. In Somnoplasty, high frequency RF energy is delivered using a needle inserted into tissue. Resistive heating occurs in the tissue surrounding the electrode leading to heat generation and temperature rise. Temperature change is monitored using integrated thermocouples providing a control signal to a microprocessor permitting modulation of energy delivery rate. Irreversible tissue damage occurs at a threshold temperature. The tissue itself generates heat and not the probe. This presentation will introduce the principles underlying Coblation and Somnoplasty, focusing on their utility in head and neck surgery and addressing how these technologies are used to treat disorders of the head and neck while reducing thermal injury and carbonization.

Saline for enhancement of lesion size has been demonstrated for constant power radiofrequency systems using saline irrigation of the treatment area. The data for temperature-controlled systems and non-irrigation applications of saline are limited. Data from a human clinical trial using a low-power, temperature-controlled radiofrequency system for treatment of the base of tongue demonstrated a correlation between the amount of electrolyte fluid injected into the treatment area and positive treatment outcome. This study investigates the effects of electrolyte solutions on lesion volume and energy delivery time using a low-power, temperature-controlled radiofrequency system in an ex vivo setting. Lesions were formed at set temperature and energy (85ºC, 750 Joules), in bovine tongue. Varying amounts of saline, local anesthetic, or a mixture of the two, were used to simulate the in vivo situation. Lesion volumes increased with the amount of fluid injected, with saline having a greater effect than the local anesthesia or the mixture of the two. Fluid injection had a more variable effect on time. Both saline and local anesthesia alone decreased time with increased volume, but the change was not significant. Comparisons of the similarities and differences between the ex vivo and in vivo data are discussed.

Laser energy has been shown to be effective in skin resurfacing and other dermatologic surgery procedures, but it operates at relatively high temperatures (200-600°C). Lasers produce mid-to far-infrared energy that is absorbed primarily by tissue water and peptide bonds. The resulting localized tissue heating and vaporization produces tissue ablation with a residual thermal injury to the lower dermis. Traditional radiofrequency (RF) devices also use extreme heat (400-600 °C) to abruptly vaporize intracellular and extracellular fluids and cause tissue desiccation. In contrast, a new technology, Coblation®, utilizes a unique method of delivering RF energy for soft tissue removal applications in medicine, including dermatological surgery. Coblation uses bipolar wands to energize the particles in a conductive saline solution surrounding the target tissue to form a plasma field. The plasma has enough energy to break the tissue’s molecular bonds, creating an ablative path with minimal thermal effects (45-90 °C). Collateral tissue damage and tissue healing were investigated in several clinical studies, and compared to those observed with conventional electrosurgery. There was significantly less collateral tissue damage, less inflammation, and faster wound healing in Coblation-treated tissues. In a multicenter clinical study, Coblation was used for skin resurfacing for the treatment of facial wrinkles and provided statistically significant wrinkle improvement. When compared to CO2 laser, the decreased thermal effects of Coblation has led to less pain and faster recovery for most patients, yet the effect was enough to both stimulate new collagen production and to shrink collagen fibers. Coblation has the potential to be applied in most procedures where lasers have been used in the past in cosmetic and dermatological applications.

Traditional radiofrequency devices use extreme heat (400-600 °C) to abruptly vaporize intracellular and extracellular fluids, causing tissue desiccation. On a new front, Coblation presents a unique method of delivering radiofrequency energy for soft tissue removal applications in medicine, including ENT surgery. Coblation involves energizing the ions in conductive fluid (saline), via a bipolar wand, to form a plasma field. The plasma has enough energy to break the tissue’s molecular bonds, creating an ablative path while resulting in minimal thermal penetration (70-90 °C) into surrounding tissue. Epithelial destruction, collateral tissue damage, and wound healing were observed in a rat tongue model. Coblation treated animals had significantly less epithelial destruction and collateral tissue damage, which resulted in less granulation tissue and faster wound healing. Clinical experience with coblation in otolaryngology has been very promising in a variety of situations. Specifically, coblation has been used for tonsillar surgery for total tonsillar excision, subtotal ablation and tonsil channeling with subsequent volume reduction . Clinical studies have shown that coblation has offered significant advantages compared to tradition techniques in each of these applications. In many cases patients operated on using coblation had a reduction of pain and a more rapid return to normal diet and activity. The blend of effective tissue ablation and hemostasis for bleeding that coblation offers may make it useful for most procedures that utilize electrocautery devices at this time.

The use of lasers in otolaryngology has become well established over the last decades. Especially in the treatment of otosclerosis, where precise no-touch fenestration of the stapes footplate is required, lasers provide an attractive alternative to mechanical drilling method. Today, Argon, KTP, CO2 and Er:YAG lasers are clinically used in middle ear surgery. Each laser has its characteristic interaction process with bone gaining specific advantages and disadvantages. Therefore, the conflicting and controversially discussed experimental and clinical reports are not surprising The visible laser radiation has a high optical penetration depth in water and therefore a limited energy absorption in the unpigmented bone. In contrast, infrared radiation by virtue of its strong absorption in water results in an explosive ablation process of high efficiency. The greatest potential risks for the inner ear during laser stapedotomy are the conversion of laser energy into heat in the vestibule, due to direct absorption of laser radiation or heat diffusion, and pressure fluctuations inside the cochlea caused by the explosive ablation process inherent in pulsed laser systems. The purpose of this study is to comprehensively compare the tissue effects of the different laser systems in view of safety and efficacy.

Cochlear implantation provides auditory stimulation for children who are deafened beyond the aid of traditional amplification. While cochlear implantation has been available for nearly twenty years, improvements in surgical technique and device design, and growing evidence regarding the communication and social benefits ofimplantation, have all contributed to wider application and acceptance of this technology. This paper is intended to update a multi-disciplinary audience on (1) the basic science behind auditory stimulation using cochlear implants and (2) technical challenges. Specific technical challenges include implantation of dysplastic cochleas and minimally invasive techniques for implantation.

Laser surgery has been proven a valuable tool in treating recurrent chronic-polypous sinusitis when conservative treatment is ineffective. As thermic ablation is one of the key principles, the question remains whether wound healing in the mucosa is prolonged or results in superficial scarring. After 143 Neodymium:YAG laser procedures for the ablation of recurrent polyps under local anesthesia, 14 biopsies were taken during an interval of 6 days to 2 years from the laser-treated mucosa. All were examined histologically. 16 biopsies were taken from patients after conventional endonasal microscopic sinus surgery. All patients had been followed up by regular endoscop employing a combined anti-inflammatory, anti-allergic drug regime. In the laser-treated group, 5 of 14 cases showed a prolonged inflammatory reaction including submucosal edema, granulocyte infiltration for up to 3 to 4 months, while the control group tended to show submucosal lymphocyte infiltration and formation of collagenous tissue in 6 of 16 cases. The interval of 8 months average, which eventually leads to restitution of respiratory epithelium, is the same in both groups. While wound healing is comparable to conventional surgery, laser surgery has the advantage of being a minimally-invasive out-patient procedure, which helps to avoid extensive conventional revision surgery.

The laser induced ignition of endotracheal tubes is seen as the most dangerous accident during laser surgical treatment. During the years the laser resistance could be improved by various temperature resistant material and sophisticated constructions. Also the testing procedure to determine the laser resistance was standardized. The International Standard ISO/DIS 1 1990 (Draft) "Optics and optical instrumentation — Lasers and laser-related equipment — Determination of laser resistance of tracheal tube shafts" gives clear information about the testing apparatus and the preparation of the test specimen. It states a containment box with specified dimensions and a specified gas environment, i.e. an oxygen flow rate of 1 I/mm through the tracheal tube and an oxygen concentration of (98 ± 2) % outside of the tube and inside of the box. The paper reports on the technical and physical problems which have to be solved to fulfil these conditions. Especially the predicted environmental concentration is difficult to reach and brings the containment box as well as the whole testing apparatus in high risk of ignition.

Many surgical procedures today are performed with lasers. Most medical laser companies produce a variety of lasers units, such as C02, Nd:YAG, Erbium, Excimer, Argon, and others. Each radiates a unique wavelength of light for use in a range of surgical procedures. Many of these wavelengths lie outside the visible spectrum. To allow surgeons to target the invisible beam, medical lasers transmit a secondary, low-power, visible aiming beam coincident with the high-power treatment beam. The laser delivery system's most important characteristic is the precision with which the size arid location ofthe aiming beam coincide with the size and location ofthe treatment beam at the surgical site.

Laser cartilage reshaping has become of clinic interest due to its potential applications for facial plastic surgery. Although the temperature dependent phase transformation oflaser mediated cartilage reshaping has been well described, few studies have examined the reshaping process in an in vivo model and correlated shape change with laser dosimetry in a rigorous fashion. We report preliminary findings of Nd:YAG laser mediated cartilage reshaping ofthe New Zealand White rabbit nasal septum. Four New Zealand white rabbits (3.5 -4.0 kg) underwent submucous resection ofthe nasal septum via a novel surgical approach under anesthesia. The septal cartilage was removed and cut into two equal sized slabs (5 x 1 5 mm); one used as a control, while other was reshaped using an Nd:YAG laser (?=1.32µm, 25W/cm2). Both the control and irradiated cartilages were reimplanted into a subcutaneous pocket in the rabbit's back. All four rabbits survived the submucous resection procedure, with no post-operative complications at 3 months post op. Cartilage reshaping was seen to take place at the thermal range 60-70°C. Further study on the long term viability oflaser reshaped cartilage will be performed by serial biopsies ofthe control and irradiated cartilage grafts at 6 and 12 month intervals for histological and viability assays. The preliminary results are promising thus far, and suggest the feasibility of utilizing the rabbit model in studying laser mediated cartilage reshaping.

We developed a new surgical procedure to correct cartilaginous deformities of the nasal septum using transmucosal laser irradiation without the need for sedation or traditional septoplasty techniques in particular the creation of mucoperichondrial flaps. Since 1988, at the Sechenov Medical Academy of Moscow, 150 patients have underwent laser septal cartilage reshaping using a Holmium:YAG laser. Minimal re-relaxation of shaped septa was observed. Rhinomanometric findings confirmed subjective assessments of improved breathing and relief of nasal obstruction. Laser septoplasty involves photothermal non-destructive heating of the septal cartilage allowing plastic deformation of this tissue. It is performed in an outpatient setting requiring only about ten minutes to complete without the need for sedation or splints. No visible undesirable side effects were observed for all patients underwent to laser reshaping procedure. It is shown that the laser reshaping is a simple bloodless, painless procedure. Potential applications in aesthetic, reconstructive, and pediatric head and neck surgery are discussed.

During laser irradiation, mechanically deformed cartilage undergoes a temperature dependent phase transformation resulting in accelerated stress relaxation. Clinically, laser-assisted cartilage reshaping may be used to recreate the underlying cartilaginous framework in structures such as ear, larynx, trachea, and nose. Therefore, research and identification of the biophysical transformations in cartilage accompanying laser heating are valuable to develop many potential clinical applications. To observe spectral features in quasi-elastic light scattering from cartilage, light emitted from a Nd:YAG laser (? = 1.32?m) was used for a heating source and a Ti:Al2O3 femtosecond laser (? = 850nm) was used for a light scattering source. A spectrometer and infrared detector were used to monitor the backscattered light spectrum and transient temperature changes from cartilage following laser irradiation. A cartilage sample was irradiated by Nd:YAG laser light over a 6 second time period and the transient temperature was simultaneously measured during laser irradiation. The denaturation of macromolecules within cartilage was observed after 4.5 seconds. The obtained spectral data were analyzed by computing a Fast Fourier transform and converted to the optical path length difference domain. The path length difference of a spectral oscillation within cartilaginous framework was also calculated. Although the measured path length differences were different from the expected values, the results will give rise to distinct patterns of the movement of macromolecules within cartilage following laser irradiation.

The lack of adequate cartilage for aesthetic and reconstructive head and neck surgery has prompted intense research in developing methods to stimulate chondrocyte proliferation in cartilage, a terminally differentiated tissue. In this study, we propose that laser heating can stimulate chondrocyte proliferation in rabbit nasal septal cartilage. Ex-vivo rabbit nasal septal cartilage grafts were irradiated using a CO2 laser (?=10.6 um, 5, 10, or 20 W, 0.1 or 0.5 seconds) and then placed in tissue culture for 7-21 days with 10 _M of 5-bromo-2’-deoxyuridine (BrdU), a thymidine analog that is incorporated into DNA during the S phase of the cell cycle. Chondrocytes were then isolated using enzymatic digestion, incubated with fluorescein conjugated anti-BrdU monoclonal antibodies (Roche Diagnostic, Basel, Switzerland) and counterstained with propidium iodide (PI), a DNA intercalater.? Fluorescent-activated cell counting was performed by flow cytometry (excitation wavelength ?=488 nm, Model BD LSR Flow Cytometer, Becton Dickson, Franklin Lakes, NJ) identifying cells with emissions measured at 515 nm (fluorescein labeled anti-BrdU) and 620 nm (PI).? Cellular debris and cell aggregates were gated out of the signal.?Cartilage grafts irradiated approximately 24 times with the CO2 laser were found to have a significant proliferating population by flow cytometry. Chondrocytes incorporating BrdU into their DNA were clearly identified and the signal intensity increased in integral multiples from baseline values indicating these cells had undergone cell division.? This provides further evidence that chondroctyes have a proliferative response to photothermal stimulation, which may be a response to injury to thermal heating by laser irradiation.

Endoscopic ultrasonography provides the endosonographer the best of both worlds. Not only can one visualize structures endoscopically, but also one can see through the gut wall and better define the extent of disease and more effectively plan therapy. Linear array echoendoscopy produces a scanning plane, which is parallel to the the long axis of the endoscope. Hence, endosonography-guided fine needle aspiration biopsy (EUS FNA), endosonography-guided fine needle injection (EUS FNI), duplex endosonography, and endosonography -guided celiac plexus neurolysis (EUS CPN) can be performed. The role of linear array echoendoscopy in cancer staging and management will be critically reviewed.

Endoscopic ultrasound (EUS), as a preoperative procedure, has become an important modality in the asssessment of pancreatic, biliary and ampullary tumors, especially when they are small (<3cm).

In the United States about 50,000 men with organ-confined prostate cancer undergo radiation therapy each year. Depending on the source of the data and the definition of treatment failure, estimates of cancer recurrence after radiation therapy vary widely from 10% up to 50%. Patients who fail radiation have a choice of hormonal treatment, which unfortunately is only palliative, and salvage radical prostatectomy, a procedure that can be very difficult with significant comorbidities. If the patient decides for watchful waiting, tumor progression and metastatic disease are only a matter of time. Due to these clinical problems there is a need for new techniques to provide local salvage therapy. New developments in cryotherapy and endoscopic laser application such as thermocouples and ultrasound monitoring have led to decline in morbidity such as urinary incontinence. This paper presents a concise review of clinical data of salvage therapy in patients with local tumor recurrence after radiation. Only limited studies are available for laser treatment due to problems in tissue penetration and intraoperative monitoring. There is more data available dealing with cryotherapy, where argon-based cryosurgery is most common. Patients with a Gleason score < 8 and a PSA serum level less than 8.0 ng/ml seem to benefit compared to those who did not meet these criteria. Cumulative retrospective data show that with a mean follow-up of 24 months, 60% of the treated patients have a serum PSA nadir of < 0.1 ng/ml and 30% < 4.0. However, the data reviewed are primarily retrospective case series, which are particularly prone to bias. Prospective clinical studies including quality of life data are necessary in order to clarify the clinical relevance of these new techniques in salvage surgery.

Transitional cell carcinoma (TCC) of the bladder has a 40-70% local recurrence rate when treated with transurethral resection (TURBT)1 and carcinoma in situ (CIS) has a 54-83% recurrence rate within 4 years2. Today, the main therapy is intravesical chemotherapy, of which Bacillus Calmette-Guerin (BCG) is the most effective. However, because chemotherapy is only modestly beneficial3 and most bladder carcinomas will not respond to second course of BCG4, an additional treatment modality is being researched. Photodynamic therapy (PDT) combines a photosensitizing dye with laser therapy to destroy cancer cells. Pathologic cells take up the photosensitizing agent and upon activation by visible light (400 - 760 nm) the cancerous cells are destroyed. PDT can be used for focal or diffuse disease. It also can be used to treat recurrent and refractory superficial TCC, in addition to being used as a prophylactic measure. We review the literature (mostly retrospective or nonrandomized studies) that supports the use of PDT for TCC of the bladder. While PDT seems to be a very promising treatment modality, BGC intravesical treatment remains the standard of care for TCC. However if additional randomized trials confirm current data, PDT may soon be a recommendable option.

Photodynamic diagnostic (PDD) using 5-aminolevulenic acid (5-ALA)-induced protoporphyrinIX is now a wellestablished tool in the diagnostics of bladder cancer. 5-ALA is routinely used for diagnosis of the superficial bladder tumors. It was shown to improve the sensitivity of detection for carcinoma in situ and therefore to reduce the risk of recurrence related to undetected cancerous lesions or incomplete TURB. Recent experimental studies showed selective accumulation of 5-ALA in transitional cell carcinoma of the bladder following intravesical or oral administration of the compound. This observation led investigators to propose the use of 5-ALA, a potent photosensitizer, as an agent for selective photodynamic therapy (PDT) of superficial bladder cancer and possible of less sever cases of muscle-invasive carcinoma of the bladder. Here we reviewed up-to-date literature dedicated to the advances in PDT with 5-ALA. Despite recent progress in characterizing the effects of phototoxicity on both cancer and normal cells in vitro little is known about the underlying molecular mechanisms and the extent of cellular damage in vivo. The available data mainly include the results of early clinical studies that point to the possibility of the use of photodynamic therapy both as a single modality treatment, and also as an element of supportive therapy e.g. in classical surgical treatment. These initial clinical results suggest that PDT using topically or orally administered 5-ALA is effective as an organpreserving procedure in treatment of superficial bladder cancer even in patients with resistance to the standard intravesical treatments. PDT of the bladder with 5-ALA is proven to be relatively safe and poses low risk of inducing permanent urological complications. Based on the observations above, this therapeutic method should be further evaluated in clinic in order to optimize differential photodynamic efficacy between tumor and normal urothelial cells.

Determining an individual’s cancer risk is an important step to increase the efficacy of screening procedures. Currently, breast cancer risk can be clinically assessed using tissue density patterns seen on standard x-ray mammography. These patterns reflect the ratio of glandular tissue to adipose tissue within the breast. Increased dense areas of glandular tissue indicate a higher risk category with an odds ratio of approximately 6. Near-infrared optical transillumination spectroscopy has been shown helpful in investigating physiological and anatomical properties of the breast tissue. Similarly the adipose and glandular tissue ratio responsible for the x-ray density pattern together with other optically active tissue chromophores can result in unique optical transillumination spectra. In this study we are considering patients who had standard mammograms and examine their breast tissue by optical transillumination spectroscopy in order to establish a correlation between the two techniques and therefore the ability of using transillumination for risk estimation. The transillumination spectra show haemoglobin, water and lipid absorption characteristics. Correlation between optical transillumination spectroscopy and mammographic density pattern are established through the use of Principal Component Analysis and Linear Discriminant Analysis. Preliminary, results indicate that x-ray dense tissue can be identified with a specificity and sensitivity above 0.87 each, for both post and pre-menopausal women.

Purpose: the purpose of these experiments was to evaluate the temperature and predicted cell kill distribution during LITT of breast tissue phantoms at 940nm and compare with the results of previous experiments ar 830 nm and 980 nm. Material and Methods: A Dornier Medilas D Skinpulse 940 nm diode lase system coupled to a Dornier D-6111-T2 fiber (Dornier Surgical Products, Phoenix, AZ) was used to irradiate the porcine tissue three times at approximately 5 W for 10 minutes. Results: The initial rate of temperature increase at 940 nm for locations 5, 10, and 15 mm from the fiber axis ranged from 0.076 to 0.142 °C/s, 0.027 to 0.041 °C/s, and 0.008 to 0.013 °C/s, respectively, wile the maximum temperature increase ranged from 37.8 to 46.9 °C, 19.3 to 26.1 °C, 8.6 to 13.0 °C, respectively, temperature curves hed lower slopes at 940 nm than at 830 nm and 980 nm. the maximum temperature increase was higher at 940 nm than at 830 nm. Predicted area of 100% cell kill was approximately 2 cm by 2 cm Conclusion: Results of experiments at 940 nm were more comparable to those at 980 nm than at 830 nm.

Laser assisted thrombolysis may be a viable alternative or adjunct to current thrombolytic therapies. However, knowledge of the particulate debris associated with this modality is limited. The objective of this in-vitro study was to evaluate and quantify the particulate generation following ablation of thrombus. Ablation of reconstituted thrombus was conducted in-vitro with an excimer laser operating at 308 nm and multifiber laser catheters. Particulate debris was quantified by weighing filtered particles and light obscuration particle counting. The effect of laser parameters, catheter size, and clot consistency on particulate production and ablation efficiency was investigated. For light obscuration particle counting experiments, the total number and size distribution of particles was similar for all laser parameters. More than 92% and 99% of the particulate generated was less than 10 and 25 microns, respectively. For the filtering experiments, particulate greater than 10 microns amounted for less than 6% of the original clot weight. Increased catheter size, increased laser parameters, and decreased clot consistency produced greater amounts ablated without increasing particulate debris production. The majority of particulate produced by excimer laser ablation of thrombus in-vitro was sub-cellular in size and debris production was not influenced by laser parameters, clot consistency, or catheter size.

The objective of this study was to evaluate the effect of laser fluence, repetition rate and catheter size on the ablation of thrombus by an excimer laser, in-vitro. Ablation of reconstituted thrombus was conducted with a XeCl (308 nm) excimer laser. Fluences of 30 and 45 mJ/mm2, repetition rates of 25 and 40 Hz, and catheters of sizes 0.9, 1.4, and 2.0 mm were used. Ablation efficiency (?g/J*pulse), and mass removal rate (?g/sec) were calculated by measuring the pre- and post-ablation weight of clot blocks (~2x1x1 cm3) placed on a precision scale. Depending on lasing parameters and catheter size, the ablation efficiency ranged from 0.51+/-0.09 to 1.13+/-0.20 ?g/J*pulse (N=12), while the mass removal rate ranged from 105+/-23 to 936+/-146 ?g/sec (N=12). Overall, there was a strong dependence of both quantities on the catheter size. Ablation efficiency was not significantly affected by either the fluence or the repetition rate, while mass removal rate increased with increased fluence and repetition rate. Excimer laser can effectively ablate thrombus in vitro. Catheter size affects both ablation efficiency and mass removal rate, while fluence and repetition rate mainly affect the mass removal rate.

Laser thrombolysis is under investigation as a safe and rapid therapy for arterial recanalization in acute embolic stroke. Clot formation is a complex process affected by many factors that lead to differences in strength and hemoglobin concentration in samples formed from whole blood. The strength of thrombus formed in vivo also varies with age. Laser thrombolysis experiments were performed using a 577 nm 1 sec pulsed dye laser at an energy of approximately 25 mJ and a repetition rate of 4 Hz. Laser ablation and confined compression modulus were measured with three in vitro clot models: gelatin, static clot, and reconstituted clot. Laser ablation studies demonstrate that laser ablation efficiency (µg/mJ/pulse) is not significantly affected by differences in the confined compression modulus of clot. This agrees with previous studies using dye and gelatin. These results provide support for the effective use of this laser thrombolysis system for the removal of clots of varied age and strength.

We have developed an imaging device that provides cross-sectional imaging as well as fluorescence spectroscopy. The first application of this device is to differentiate healthy arterial wall from atherosclerotic plaque. Optical coherence tomography (OCT) provides two-dimensional imaging. OCT images have an imaging length and depth of 1-2 millimeters and 1 5 micron resolution. Laser induced fluorescence (LIF) spectroscopy provides histochemical information. Due to high absorption of excitation wavelengths the fluorescence spectra is integrated from tissue only 200 microns deep. The OCT portion of the device is based on a Michelson interferometer. A superluminescent diode provides light at 1300 nm with 49 nm spectral width, and a galvanometer mounted retroreflector allows the reference arm length to be modulated. A helium cadmium laser provides the excitation source with wavelengths of 325 and 442 nm. In one instrument design, a series of dichroic mirrors is used to combine light from the OCT and LIF systems. In another design, OCT. excitation and emission fibers are combined into the same custom-built catheter for the delivery and collection of light. Preliminary data show that OCT images and LW spectra give complementary information from normal and atherosclerotic portions of arterial wall.

We present theoretical calculations and experimental imaging results that demonstrate the possibility of extending viewing distances through blood simply by selection of an ‘optimal’ illuminating wavelength and use of a camera with appropriate parameters. Based on a simple one-dimensional model of image signal formation and employing Kubelka- Munk theory of light transport in a turbid medium, we derive an analytical expression that describes the effect of optical properties of the medium and camera parameters on image signal. Experimental images of an artificial target placed behind a sample of human blood of different thickness taken in transmission and reflection modes confirm the predicted imaging possibilities. An optical-difference offset technique developed to enhance image contrast is demonstrated as well.

The cyclic micro-deformation of the arterial wall with pulsatile flow was measured to get fundamental data for estimation of the mechanical stress in endothelial cells. The descending aorta (1-2 mm diameter) of an anesthetized rat was exposed under thoracotomy. The displacement measuring system was assembled with the charge coupled devise (CCD) of laser sensor. The movement of laser beam (670 nm wave length) reflected at the vessel wall was calibrated to the movement of the arterial wall. The fluctuating movement was also measured at four points marked on the vessel wall with CCD camera to distinguish the circumferential movement from the longitudinal one. The results showed that the present designed system has enough resolution to measure the arterial vessel wall cyclic-micro-fluctuation, which is 10 percent of diameter in the circumferential direction without deformation in the longitudinal direction with the cardiac beating in vivo.

Cryogen spray cooling is used to prevent epidermal thermal damage during port-wine stain laser therapy, despite the limited understanding of the fluid dynamics, thermodynamics, and heat transfer characteristics of cryogen sprays. In recent studies, it has been suggested that the heat flux through human skin could be increased by changing physical parameters such as nozzle-to-skin distance, nozzle diameter, and/or by depositing cryogen in sequential spurts. These changes affect spray parameters such as droplet diameter, velocity, and spray temperature. Therefore, in order to optimize new nozzle designs, it is necessary to explore the influence that these fundamental spray parameters have on heat extraction. In this paper, various valve/nozzle configurations were characterized. A Phase Doppler Particle Analyzer was used to determine the average diameter, velocity, and droplet concentration of various cryogen sprays. The mass flux delivered by each valve/nozzle configuration was also measured, along with the average spray temperature. A custom-made device consisting of an insulated metallic disk was used to measure the heat extracted by different sprays. The results showed that there are significant differences in the heat extracted by the different valve/nozzle configurations. These variations are proportionally influenced by mass fluxes. Strong correlations were also observed between average droplet velocities and heat extraction. These findings indicate that mass flux has a dominant effect on heat extraction from human skin during cryogen spray cooling. It is also apparent that kinetic and thermal energies are other parameters to be considered when optimizing heat extraction.

Background and Objective: Pulsed CO2 laser resurfacing improves photo-damage and acne scarring by removing abnormal tissue with subsequent regeneration and remodeling of collagen through heat induced collagen contraction. On the other extreme, Normal Mode Er:YAG lasers operate yielding ablative tissue removal with a thermal damage zone that can be limited to fewer then ten microns. This study introduces and evaluates the effectiveness of a new method of Thermo-optical Skin Conditioning (TSC). This method allows the user to induce tissue effects that span the entire range from the purely thermal tissue modification (CO2-like) to the highly mechanical effects induced by dermabrasion and Er:YAG lasers. TSC utilizes an optical energy in conjunction with a highly absorbing substance (HAS) deposited on a thin, thermally conductive intermediate material module (IMM) allowing the user to achieve optical to thermal energy conversion. The thermal energy is allowed specific interaction time determined by the scanning spatial pattern and scanning rate. The total amount of power density deposited in the tissue is a function of laser power, scan rate, spot size, and the synchronized action of the energy removal system (ERS) incorporated and synchronously activated at the end of the interaction period. Materials and Methods: A substance capable of efficiently absorbing laser light was applied to one side of an intermediate medium material to be placed in contact with the target skin. The intermediate medium material was then formed into a tape that was capable of advancing along a flat surface. An 810nm diode laser was used as an energy source. Galvanometer scanners and a lens were used to cover an area of approximately 50 mm2. Different power settings and scan rates determined the maximum power density and fluence at the target area. Following the experiments, the skin was then fixed in 10% Formalin and used for histological section preparations and optical light microscopy evaluation. The samples were then evaluated for histological changes and to measure ablation and thermal damage depth. In addition, measurements of thermal tissue response during and after the interaction were performed using both thermocouples and an infrared thermal camera. Results: Epidermis ablation ranged from as little as 10 ?m per pass, to as much as 50 ?m per pass. The depth of thermal damage decreased with scan frequency and with decreased laser power. Temperature increase ranged from 150C to as much as 900C. ERS temperature control allowed restoration of ambient temperature within less then 250 ms. TSC is shown to be a very effective method for inducing a range of tissue modification effects ranging from highly thermal to mechanical /non-thermal effects.

The objective of this research is to provide a novel approach to the problem of vascular anastomosis. The work subscribes to the idea that if we use a human protein that has adhesive properties, denatures by heat in an irreversible way and forms a semi-hard but flexible matter. Also belongs to the circulatory system, is liquid in its native state , and after denaturing it is not soluble inwater, blood plasma or any other related fluids anymore. Therefore, a pulsed diode laser beam can be used on this protein in order to have a strong welding for vascular anastomosis. It was established in the Oregon Medical Laser Center that the best proteins to be used , as a welding biomaterial, is human albumin. Indocyanine Green was added to provide a compound that absorbs light and transforms it in heat to the denaturing and welding process. Tests with liquid albumin were performed, the results obtained were unreliable due to the following facts: the variation in the liquid film thickness produced pockets of native (non-denatured albumin) underneath the denatured welded crust and bubbles produced by water evaporation. This phenomenon led to a weak welding. After testing different options, it was decided that the manufacturing of asolid thin film of albumin/ICG with a content of water between 37-40% was the best option. It reduces the number of bubbles, and provides a constant thickness between 200-250 ?m. This thin film can be used alone on the vascular surface to be welded , or in combination with an elastin strip to increase strength. To avoid collapsing of the blood vessel while welding, and also keep both edges of the vessel together, an albumin/ICG stent was designed so the configuration of the stent does not allow the vessel to slip away or collapse. The stent is made out of native human albumin with water content between 37-40%. When the weld is completed and the forceps are released, it is expected that the natural flow of blood will dissolve the stent in less than 12 minutes (according with experiments already performed with lukewarm water).

Radio-frequency energy has been used in surgery since the 1920’s, primarily to control bleeding by coagulating blood vessels. While still its major use, other applications have developed. The newer applications in the head and neck area are: 1) Tissue contraction: Creation of a controlled lesion by a needle electrode inserted into tissue, such as the soft palate or tongue, results in later contraction of the tissue. The size of the lesion is controlled by monitoring tissue temperature and impedance and the energy in joules. Contraction of the soft palate and tongue provides improvement in snoring and obstructive sleep apnea while contraction of the nasal turbinates produces improvement in nasal breathing. 2) Destruction of nerves: Radio-frequency ablation of sensory nerves has been used for years to control pain, particularly facial pain. The technique has recently been used on motor nerves to eliminate facial wrinkles. 3) Tightening of skin and soft tissue and surface ablation: RF energy delivered by a monopolar or bipolar electrode can tighten skin or destroy surface tissue on the skin and inside the mouth and nose.

The reported strengths of industrial hot melt adhesives are in the range of 500-1000 psi when assessed gravimetrically, or 3.4-6.9 MPa. The strongest laser welds using ICG/albumin paste as a solder and laser exposures of 20-100 s have breaking strengths in the range of 400 to 600 N/cm2, or 4-6 MPa. The threshold tensile pressure for laser-induced cavitation of body water, which has particulates to act as nucleation sites, is about 10 bar or 1 MPa. For 10% and 20% collagen gels, the threshold tensile pressures for cavitation are about 28 and 46 bar, or 2.8 and 4.6 MPa, respectively. Hypothesis: Tensile-pressure-induced weld failure and laser-induced cavitation share a common mechanism of void initiation and growth, thereby explaining their similar pressure thresholds. Hypothesis for mechanism: Conservation of density and volume requires that solder flows inward radially when the two adjoined surfaces are pulled apart. When the solder cannot flow sufficiently fast to match the rate of surface separation, void volumes form to allow the surfaces to separate. Such void formation is comparable to cavitation that has a known threshold tensile pressure for onset.