Bubble dynamics plays a key role in many medical procedures including Laser Thrombolysis (L-T), acoustic and laser lithotripsy, interocular laser surgery, photoacoustic drug delivery, and perhaps ultrasonic imaging. We are investigating the effect that interfaces of different materials, especially biological and biomedical materials, have on the dynamics of nearby bubbles. Collapsing bubbles often become nonspherical, resulting in spectacular directed motion with potentially both beneficial and undesirable consequences. This directed motion may explain L-T mass removal and some types of laser-induced tissue damage.

Mass removal experiments have been performed at the Oregon Medical Laser Center with 10 to 100 mJ 1 microsecond laser pulses at optical wavelengths. Above the energy threshold for bubble formation, the laser mass ablation efficiency ((mu) g/mJ) for removal of gel surrogate thrombus is nearly constant for a given experimental geometry and gel absorption coefficient. The efficiency in 'contact' experiments, in which the optical fiber delivering the energy is in close proximity to the absorbing gel, is approximately three times that of 'non-contact' experiments, in which the optical fiber is approximately 1 mm from the gel. Mass removal occurs hundreds of microseconds after the laser deposition. Experimental data and numerical simulations are consistent with the hypothesis that jet formation during bubble collapse plays a dominant role in mass removal. This hypothesis suggests a model in which the mass removed scales linearly with the maximum bubble volume and explains the distinctive features, including the magnitude, of the mass removal.

Vascular smooth muscle cells (VSMC) are known to be important in restenosis and photodynamic therapy (PDT) has been shown experimentally to deplete the VSMC population in small animal studies. We aimed to investigate the pharmacokinetics of 5- aminolaevulinic acid (5-ALA) and to see if endovascular PDT was feasible in a large animal model. Large White pigs (15 - 20 Kg) were photosensitized with 5-ALA at a concentration of 60 and 120 mg/Kg. Arterial biopsies were taken at intervals between 30 mins and 24 hours and snap frozen in liquid nitrogen. Frozen sections were analyzed using a CCD camera and PpIX activity assessed by computing pixel counts for intima, media and adventitia at each time point. Based on the above results 8 pigs were treated with PDT at 1.5, 2.5 or 6 hours following 5-ALA administration. Iliac segments were then illuminated with 50 J/cm², 635 nm wavelength light via a 4 mm transparent PTA balloon. Animals were culled at 3 days and the above segments pressure perfused in situ with 4% formyl saline, before being excised and fixed. Fluorescence peaked in the adventitia at 1.5 hours, was minimal at 2.5 hours and peaked in the media at 6 hours post 5-ALA. Of the second series of 8 pigs, all animals survived to culling and all treated arteries remained patent. Histological sections stained with H&E were examined and medial VSMC's counted in 4 individual high power fields per section. The mean VSMC count per HPF for PDT treated segments was 16, 51 and 12 at 1.5, 2.5 and 6 hours respectively. VSMC counts in ALA alone controls and light alone controls were 115 and 103 respectively (p less than 0.0001). Endovascular delivery of light to 5-ALA sensitized animals is therefore feasible and was not associated with any complications.

ANTRIN^TM photosensitizer, a lutetium texaphyrin-containing drug, is currently being evaluated in the clinic as a phototherapeutic agent for the treatment of peripheral vascular disease using photodynamic therapy, a procedure which has been designated as photoangioplasty. In order to better understand light delivery/timing, disease indication, and the features necessary in the design of light delivery devices, studies were carried out to measure the effect of hematocrit and photosensitizer concentration on the transmission of 732 nm light in rabbit blood and plasma. In blood, light transmission decreased exponentially with increasing hematocrit. An increase of 10 in the hematocrit (e.g., 35 to 45) resulted in a 40% decrease in the amount of transmitted light. In plasma, high concentrations of Antrin^TM were observed 3 and 5 hours post administration (31.8 plus or minus 9.3 (mu) M and 14.3 plus or minus 8.3 (mu) M, respectively) compared to 24 hours after administration of the sensitizer (2.5 plus or minus 1.4 (mu) M). Increased plasma sensitizer levels correlated with decreased light transmission through plasma due to absorption of light by lutetium texaphyrin. An increase in the delivered light fluence would therefore be expected upon irradiation 24 hours versus 3 or 5 hours post administration of Antrin^TM. However, other factors, such as drug uptake by plaque, would need to be considered in order to optimize the time interval between injection and irradiation.

Patients receiving heart or other organ transplants usually require some level of anti-rejection drug therapy, most commonly cyclosporine. The rejection status of the organ must be monitored to determine the optimal anti-rejection drug therapy. The current method for monitoring post-transplant rejection status of heart transplant patients consists of taking biopsies from the right ventricle. In this work we have developed a system employing optical and signal-processing techniques that will allow a cardiologist to measure spectral changes associated with tissue rejection using an optical catheter probe. The system employs time gated illumination and detection systems to deal with the dynamic signal acquisition problems associated with in vivo measurements of a beating heart. Spectral data processing software evaluates and processes the data to produce a simple numerical score. Results of measurements made on 100 excised transplanted isograft and allograft rat hearts have demonstrated the ability of the system to detect the presence of rejection and to accurately correlate the spectroscopic results with the ISHLT (International Society for Heart and Lung Transplantation) stage of rejection determined by histopathology. In vivo measurements using a pig transplant model are now in process.

Laser prostatectomy shows an improvement in peak urinary flow rates, in post-void residual urine volumes and also a symptomatic improvement when compared to the transurethral resection of the prostate (TUR-P). Time to achieve symptomatic improvement is delayed with many established laser procedures compared to standard resection. However, this disadvantage can be solved with a new resection technique using a pulsed holmium laser. Nevertheless, this advanced technique shows a few problems in a first clinical trial. Besides this clinical study, in vitro experiments were carried out in order to determine the optimal irradiation parameters with respect to resection rate, incision/ablation quality and handling. Prostate tissue of radical prostatectomies and chicken breast as model were irradiated with a pulsed holmium-laser in vitro with different laser parameters using a bare fiber in contact to tissue. The incision quality (depths and coagulation/vaporization effects) was analyzed with regard to pulse energy (speed of incision, angle of incision) and fiber diameter. Fast flash photography was performed to analyze thermo-mechanical side-effects. Fast flash photography reveals cavitation bubble up to 7 mm length in water and dissections in tissue. The ablation rate increases proportional to the laser pulse energy. The Holmium Laser Resection of the Prostate (HOLRP) in humans with available instrumentation right now shows equieffective results compared to the transurethral resection, no need for transfusion, no transurethral resection syndrome, short time for catheterization. Further technical approvement may significantly improve holmium laser prostate resection. We present a new application system for the laser resection.

HoLRP is a technique which produces a defect in the prostatic fossa analogous to TURP but does so with significantly less blood loss. The perioperative outcome was assessed in a randomized clinical trial. The patients in the HoLRP arm (61 patients) had a longer resection time when compared to the TURP group (59 patients) but had less nursing contact time, shorter catheter time and a shorter hospital stay. Four patients in the TURP arm (6.8%) required blood transfusion compared to none in the HoLRP arm. Postoperative dysuria was similar in the two groups. Overall, the perioperative morbidity of HoLRP is less than that of TURP.

To reduce morbidity and costs of transurethral incision of the prostate in cases with bladder neck obstruction and insignificant prostatic hyperplasia, a Nd:YAG laser, wavelength 1064 nm, was used for endoscopic tissue vaporization. Twenty seven patients suffering from severe urinary obstructive symptoms due to a high-riding vesical neck, were operated on under general anesthesia. Under endoscopic control and by means of a 600 micrometer lateral- firing quartz fiber two incisions were performed, starring at the 7 o'clock and 5 o'clock position, respectively, of the bladder neck and following the floor of the prostatic urethra to either side of the verumontanum. Vaporization was achieved with the fiber in permanent tissue contact and the laser working at 60 W power in continuous mode. Total energy averaged 10,000 J. No catheter was inserted and all patients were discharged on the same day after the first micturition. Anti-inflammatory agents were administered for two weeks. No serious complications were encountered postoperatively. Results were evaluated by means of clinical examination, uroflowmetry, sonographic measurement of residual urine and the International Prostate Symptom Score (IPSS) questionnaire. Considering a mean follow up of 15 months, all patients experienced considerable improvement of their obstruction, their urinary peak flow averaging 21 ml/s and their IPSS score 6.7 (preoperatively 12.2 ml/s and 21.8, respectively). As compared to the Collings knife, laser-incision of the prostate carries no risk of bleeding, thus obviating the need of catheterization. It can safely be done in an outpatient setting, probably as well under local as under general anesthesia.

Laser treatment of BPH as minimally invasive therapy has found wide employment in the last few years. The objective here was to study the effects of combined technique of coagulation and vaporization with an Nd:YAG/KTP laser on BPH compared to TURP. Thirty-eight patients presenting symptomatic BPH were randomized and treated either by a laser coagulation/vaporization using an ADD fiber at settings of 40 - 60 W for the Nd:YAG and of 36 W for the KTP alike in 21 cases or by TURP in 17 cases. Symptom score, uroflow and residual urine were assessed preoperatively at 1, 3, 6 and 12 months. No transfusion in any group. Similar postoperative catheterization time. Treatment failure in 2 TURP patients and in 2 laser patients. Comparing AUA score, Qmax and residual urine, both forms of treatment were similar at 1 year. Nd:YAG/KTP laser is equivalent to TURP at 1 year for around 40 g prostates.

Motivation: Recently, new applicators have been designed for laser-induced interstitial thermo-therapy to induce large (greater than 25 mm in diameter) tissue lesions. These systems combine laser-induced tissue heating with cooling of areas adjacent to the optical fiber. The resulting complex tissue temperature profiles, however, require an adequate temperature monitoring during therapy. Aim of the study: Evaluation of a new MR-sequence to determine the temperature distribution in laser-irradiated tissue. Materials and Methods: A fresh sample of bovine liver was irradiated (Nd:YAG laser, (lambda) equals 1064 nm, cw, 15 min, 11.8 W) under MRI control uscg a specially designed cooled laser applicator. The MR sequence used is based on the measurement of the temperature-dependent shift of the proton resonance frequency. To increase the sensitivity, a standard TurboFLASH sequence (slice thickness 6 mm, flip angle 5 degrees, TR/TE equals 10/3 ms, matrix 128 by 128) has been modified. The gradient scheme used leads to a total dephasing of the primary echo resulting in an effective echo time of T_E(eff) equals T_E plus T_R. Results: Temperature maps were obtained every minute during laser irradiation. Regions with maximum temperatures were located in a radial distance of 5 to 10 mm from the cooled applicator representing the typically induced temperature distribution. Conclusion: Echo shifted TurboFLASH sequences based on the determination of the temperature dependent shift of the proton resonance frequency allow an adequate monitoring of the complex heating patterns induced by cooled LITT- applicators.

Our goal was to investigate whether an open 0.5T MR-system with integrated frameless stereotactic guidance tools can provide sufficient intraoperative monitoring of interstitial laser therapy (ILT). Temperature-sensitive T1-weighted Fast- Spin-Echo (FSE)- or Spoiled Gradient-Echo sequences (SPGR) were applied and various image processing techniques (pixel- subtraction, phase mapping, optical flow computation) developed in order to control the thermal energy deposition during ILT in patients with brain- and liver tumors. While images from T1-weighted FSE- or SPGR sequences were acquired within 5 - 13 seconds, ILT lasted 2 to 26 minutes. Pixel subtraction or optical flow computation of T1-weighted images was performed within less than 110 msec. Alternating, phase- mapping of real- and imaginary components of SPGR sequences was performed within 220 msec. Pixel subtraction of T1- weighted images identified thermal changes in liver and brain tumors but could not evaluate the temperature values as chemical-shift based imaging, which was however, more affected by susceptibility effects and motion. Optical flow computation displayed the predicted course of thermal changes and revealed that the rate of heat deposition can be anisotropic, which may be related to heterogeneous tumor structure and/or vascularization.

The holmium laser has become accepted as a versatile instrument for urological applications, such as prostate resection, urethrotomy, tumor coagulation and lithotripsy. Presently, more powerful lasers have become available generating pulses up to 4 J at 80 W. The necessity of these high power systems in urology is ambiguous. In this study, the dosimetry as to efficacy and especially safety was investigated for various applications. The holmium laser ((lambda) equals 2.1 micrometer) emits its energy in 350 microsecond pulses which instantly turn water into vapor. Using high-speed photography explosive vapor bubbles with diameters over 10 mm were captured. The mechanical force of these bubbles, effectively fragments stones but may dilate and rupture a small lumen like the ureter. After implosion of the bubble, the energy of vaporization turns into heat. Depending on pulse energy and pulse repetition rate, tissue can be thermally affected up to 5 mm. For soft tissue applications, e.g., urethrotomy, prostatectomy or tumor coagulation, pulse energies of 0.5 - 1.5 J were applied at a high repetition rate (20 - 40 Hz) to provide sufficient coagulative and hemostatic effects. At higher pulse energies, the fiber tip was vibrating vigorously and the tissue was ripped to pieces decreasing hemostasis and visibility. For hard tissue applications, bursts of 0.5 J pulses at 5 Hz, proved to be sufficient to fragment all types of stones (including cystine) in the ureter and the bladder without mechanical or thermal damage to surrounding tissue. At higher settings, targeting the stone was less controlled and effective due to 'jumping' of the fiber tip with resulting mechanical and thermal trauma to the surrounding tissue. The holmium laser can be used effectively to coagulate and cut soft tissue and fragment stones at relatively low energy and power settings, thus minimizing the risk of complications.

While the role of endoscopy was initially diagnostic, the advent of improved endoscopes and working instruments have increased its therapeutic applications. One of the most recent advances is the holmium laser. It has a broad range of urological applications due to its ability to fragment all urinary calculi and its soft tissue effects. This laser is based on laser energy delivered in a pulsatile fashion at 2100 nm. The purpose of this study is to report our experience with the holmium laser. A retrospective study of patients undergoing endourological procedures with the holmium laser was performed. One hundred and forty patients underwent 157 procedures. The holmium laser was used for the treatment of urinary calculi in 122 patients. Stone location included 61 renal, 64 ureteral, and 17 bladder stones. Renal stone burden was 17 mm (range 3-50), ureteral stone size averaged 10 mm (range 3 - 35), and mean bladder stone size was 31 mm (range 10 - 60). Other uses included treatment of transitional cell carcinoma of the renal pelvis, ureter, and bladder, incision of ureteral strictures, ureterocele, and prostate, and ablation of renal hemangiomas. Intraoperative and post operative complications were noted. Follow-up for calculi consisted of a plain film of the abdomen at one week and an ultrasound or intravenous pyelogram at six to eight weeks post procedure. No ureteral perforations or strictures occurred. The Holmium laser was capable of fragmenting all urinary calculi in this study. No complications were directly attributable to the Holmium laser. In our initial experience, the Holmium laser is safe and effective in the treatment of urinary pathology. It is the most effective lithotrite available and is able to incise and coagulate soft tissue as well. This combination allows the urologist to treat a variety of urinary pathology using a single modality. Its main limitation is the ability to access lower pole lesions in the upper urinary tract due to the fiber's stiffness. Use of laser fibers larger than 200 microns occasionally limit deflection into a lower pole or dependent calyx.

Although the overall incidence of bladder calculi has been decreasing, it is still a significant disease affecting adults and children. Prior treatment options have included open cystolitholapaxy, blind lithotripsy, extracorporeal shock wave lithotripsy, and visual lithotripsy with ultrasonic or electrohydraulic probes. The holmium laser has been found to be extremely effective in the treatment of upper tract calculi. This technology has also been applied to the treatment of bladder calculi. We report our experience with the holmium laser in the treatment of bladder calculi. Twenty- five patients over a year and a half had their bladder calculi treated with the Holmium laser. This study was retrospective in nature. Patient demographics, stone burden, and intraoperative and post-operative complications were noted. The mean stone burden was 31 mm with a range of 10 to 60 mm. Preoperative diagnosis was made with either an ultrasound, plain film of the abdomen or intravenous pyelogram. Cystoscopy was then performed to confirm the presence and determine the size of the stone. The patients were then taken to the operating room and given a regional or general anesthetic. A rigid cystoscope was placed into the bladder and the bladder stone was then vaporized using the holmium laser. Remaining fragments were washed out. Adjunctive procedures were performed on 10 patients. These included transurethral resection of the prostate, transurethral incision of the prostate, optic internal urethrotomy, and incision of ureteroceles. No major complications occurred and all patients were rendered stone free. We conclude that the Holmium laser is an effective and safe modality for the treatment of bladder calculi. It was able to vaporize all bladder calculi and provides a single modality of treating other associated genitourinary pathology.

Preliminary animal model experiments have been performed to test the feasibility of a new treatment for snoring. Current surgical treatments for snoring at the palatal level involve either excision of tissue to shorten the palate, or interstitial ablation of the palate to induce fibrosis and stiffening. Both shortening and stiffening of the palate are believed to be effective in reducing snoring. Mucosal surface damage and delayed tissue sloughing are the cause of considerable pain for the patient. In the new treatment proposed here, palatal stiffening with mucosal preservation is accomplished by combining evaporative cooling at the tissue surface with laser irradiation to heat subsurface tissue layers. The surface is cooled using a timed spray of tetrafluoroethane immediately prior to each pulse from a 1.54 micrometer erbium glass laser. In vivo experiments demonstrate that the technique causes significant shrinkage and decreased elasticity in hamster skin, with no tissue sloughing. In vitro experiments with canine soft palates show that laser-induced thermal damage zones ranged from approximately 0.75 to 1.75 mm below the surface, depending on laser parameters. These results suggest that the noninvasive laser technique may produce palatal stiffening with protection of the mucosal surface, for treatment of snoring with minimal morbidity.

Laryngomalacia is the most common cause of newborn stridor. Management can usually be accomplished without surgery. When surgery is necessary, the carbon dioxide (CO₂) laser plays an essential role in enabling precise, hemostatic dissection. The authors present their application of the CO₂ laser with microspot control for laser correction of laryngomalacia, with emphasis upon the use of the Boston University suspension system to achieve external suspension of the larynx and the bivalved laryngoscope to achieve tissue distension. Review of indications, technique and results is shared to detail the utility of the CO₂ laser in supraglottoplasty.

Vascular targeting is a recent approach to cancer therapy that aims at damaging tumor vasculature to induce tumor cell hypoxia and subsequent cell death. Squamous cell cancer arises in the superficial mucosal and cutaneous epithelial layers, and tumor microvasculature therefore may be particularly well suited for targeting by selective photothermolysis. An initial evaluation of the effect of selective eradication of microvasculature on tumor development was undertaken here using the chemically-induced hamster cheek pouch model and a 585 nm pulsed dye laser. In a first group of 6 hamsters, progression of premalignant mucosal lesions was compared between control and laser treatment groups, and laser-induced regression of established tumors was evaluated. In a second group of 12 hamsters, the number of laser treatments required to produce complete regression of tumors of the buccal mucosa was determined. The effect of the laser on tumors appearing on the skin in these animals was also investigated. These experiments showed that laser treatment inhibited tumor development and caused complete regression of established tumors 10 mm³ or smaller. Photothermal microvascular targeting may be useful in treating dyplasia and early tumors of the upper aerodigestive tract and skin, with fewer adverse sequelae than existing modalities.

In this study, we attempted to determine the critical temperature [T_c] at which accelerated stress relaxation occurred during laser mediated cartilage reshaping. During laser irradiation, mechanically deformed cartilage tissue undergoes a temperature dependent phase transformation which results in accelerated stress relaxation. When a critical temperature is attained, cartilage becomes malleable and may be molded into complex new shapes that harden as the tissue cools. Clinically, reshaped cartilage tissue can be used to recreate the underlying cartilaginous framework of structures such as the ear, larynx, trachea, and nose. The principal advantages of using laser radiation for the generation of thermal energy in tissue are precise control of both the space-time temperature distribution and time- dependent thermal denaturation kinetics. Optimization of the reshaping process requires identification of the temperature dependence of this phase transformation and its relationship to observed changes in cartilage optical, mechanical, and thermodynamic properties. Light scattering, infrared radiometry, and modulated differential scanning calorimetry (MDSC) were used to measure temperature dependent changes in the biophysical properties of cartilage tissue during fast (laser mediated) and slow (conventional calorimetric) heating. Our studies using MDSC and laser probe techniques have identified changes in cartilage thermodynamic and optical properties suggestive of a phase transformation occurring near 60 degrees Celsius.

In earlier experiments it was shown that the laser resistance of a composite tube (Rusch, Lasertubus) is high enough to withstand power densities of up to 10⁶ W/cm² for exposure times up to 120 seconds, while the metallic tube ('Laser-Flex^TM', Mallinckrodt) got destroyed within some seconds at several 1000 W/cm². The reason for the high laser resistance of the composite tube was explained by a cooling mechanism due to vaporization water stored in the moistened foam which covers the outside of this tube. This model was checked by measuring the laser induced temperatures of the tubes by an IR camera and compare these results with model calculation carried out by the method of finite elements.

Recurrent respiratory papillomatosis (RRP) is a viral disease characterized by the growth of benign tumors on the vocal cords. Standard management of RRP currently consists of CO₂ laser microsurgical ablation of the papillomas. Because of the recurrent nature of this disease, patients are often faced with significant cumulative risk of soft tissue complications such as vocal cord scarring. As a minimally traumatic alternative to management of RRP, we have investigated the use of the 585 nm pulsed dye laser (PDL) to cause regression of the papillomas by selective eradication of the tumor microvasculature. Three patients have been treated with the PDL at fluences of 6 J/cm² (double pulses per irradiated site), 8 J/cm² (single pulses), and 10 J/cm² (single pulses), at noncritical areas within the larynx, using a specially designed micromanipulator. Lesions on the true cords were treated with the CO₂ laser. Clinical examination showed that PDL treatment appeared to produce complete regression of papillomas. Unlike the sites of lesions treated by the CO₂ laser, the epithelial surface at the PDL treatment sites was preserved intact. The presumed mechanism for papilloma regression following PDL treatment involves acute or chronic localized hypoxia caused by loss of tumor microvasculature.

We have investigated wound healing of incisions in the buccal mucosa of a canine model created with the Vanderbilt Free Electron Laser tuned to 6.1, 6.45 and 6.8 microns. We have also used a carbon dioxide laser, continuous wave and with a short-pulse structure (100 microseconds) to access wavelength and pulse structure components to wound healing from laser incisions. The tissue was evaluated histologically and with tensiometry acutely and at post operative days 3, 7, and 14. The data indicate that shorter laser pulse durations create less lateral thermal injury and wounds with greater tensile strength, resulting in earlier wound healing. Wound healing was only slightly dependent upon the wavelength of the laser. These results demonstrate that surgical carbon dioxide lasers with a short-pulse structure of approximately 100 microseconds or less could offer more prompt wound healing while maintaining the advantages of a 10.6 micron wavelength laser.

Membrane-damaging action of laser irradiation comparing with membranotoxic activity of model xenobiotics (Novocain and Acrylamide) has been evaluated in our experiments using Rosette-Forming Ability test (RFA) on rat blood lymphocytes, thymocytes, splenocytes for the assessment of membrane- mediated and receptor-mediated immune cells interactions. Infra-red laser irradiation (80 and 1500 Hz, 0.89 mkM) in vivo induced 2-fold increase of lymphocytes capable to form specific rosettes with xenogenous erythrocytes. T-lymphocytes were greatly sensitive to the laser influence. Acute laser exposure (128 sec) induced changes similar to Novocain action (1/2 LD₅₀). Five-fold increase of the laser exposure time (especially for low frequency regime) resulted in more prominent changes in intercellular communication which were found to be similar to the action of Acrylamide (1/2 LD₅₀). B-lymphocytes and splenocytes have been assumed as target cells for the action of laser with the frequency of 1500 Hz. Course application of IR or He-Ne laser induced decrease of RFA for all immune cells tested, and for blood lymphocytes, respectively. Thus, laser-induced changes in immune cells interaction may be connected with reversible injury of cell surface membrane followed by the dysregulation of cellular communication. Based on experimental data, the optimal regime of IR laserotherapy (0.89 and 0.63 micrometer) was chosen for the treatment of 200 patients with chronic decompensated tonsillitis. Efficiency of laser application was confirmed by cytological analysis of lacunes, laserodopplerofluometria, vegetative nervous system evaluation etc. and was found to be dependent on membranotropic activity of laser irradiation.

In this study, we examined the effect of variation of pH environment on the thermal, mechanical and optical response of cartilage to laser-mediated heating. Our previous studies have demonstrated that cartilage undergoes accelerated stress relaxation during laser irradiation at fluences below the ablation threshold. Characteristic changes in integrated backscattered light intensity, radiometric surface temperature and internal stress are consistently observed during irradiation at physiologic pH. A peak in integrated backscattered light intensity occurs when surface temperature reaches approximately 65 degrees Celsius. Internal stress increases, plateaus, and subsequently decreases in a similar manner. In this study, porcine nasal septal cartilage specimens were immersed for 24 hours in physiologic buffer solution titrated to pH 1.1., 7, and 11. Cartilage samples were then irradiated (equals 1.3 micrometer, 4 W, spot size 4 - 5 mm) and integrated backscattered light intensity, radiometric surface temperature and internal stress were recorded. While specimens at pH 7 and 11 demonstrated qualitatively similar behavior, notable differences at pH 1.1 were observed, including: (1) temporal decoupling of the internal stress and light scattering responses; (2) rapid increases in integrated backscattered light intensity measurements during the early phases of laser irradiation; and (3) prolonged elevation in integrated backscattered light intensity and internal stress following laser irradiation. In addition, during successive laser irradiation to the same specimen, we observed a temporal decoupling between integrated backscattered light intensity and internal stress at pH 7 and 11. This was not observed at pH 1.1. These observations are discussed in the context of cartilage structure and chemical interactions within the extracellular matrix. Mechanisms for the observed differences are proposed, including interactions by the cartilage proteoglycan moieties, which are sensitive to changes in the pH environment and provide cartilage tissue with its characteristic viscoelastic properties.

Laser Doppler vibrometry is well established in hearing research, since this technique enables to monitor tiny motions in a touch free mode. The sensitivity to measure the amplitude of vibrations is at 0.5 nm at 100 Hz and 0.05 nm at 1 kHz. Even when laser Doppler vibrometry is a technique with a high potential of application in ENT, its use in clinical routine is rare so far. Beside other reasons this is due to the mechanical dimensions and the weight of the interferometer of a vibrometer. Here an optical set-up is presented which combines an operating microscope and a fiber guided laser Doppler vibrometer. The system is easy to handle and fulfills the conditions for sterility.

A novel infrared (IR) transparent optical fiber coupled to a hand held otoscope and a radiometer was constructed and used to measure the temperatures of the tympanic membrane (TM) and to distinguish between diseased and healthy middle ears. A greater temperature difference between TM readings was found when Acute Otitis Media (AOM) existed in one of the ears examined. This supports the hypothesis that acute inflammation of the middle ear will result in elevated local temperature when measured in such a way that the reading is taken only from the TM without interference of the external canal. The use of an optical fiber enabled temperature measurements of the TM with high spatial resolution eliminating the external ear canal interference. A small patient population was examined and the initial results were statistically significant. In the hands of the primary care physician, this tool would prevent misdiagnosis of AOM preventing indiscriminate use of antibiotics and avoiding complications by early diagnosis.

Laryngeal videostroboscopy (LVS) allows the physician to examine the vibratory free edge of the vocal fold providing direct visualization of the vocal fold surface and indirect visualization of the substance of the vocal fold. Previously in dog LVS, electrical stimulation of the superior and recurrent laryngeal nerves or painful stimuli in the lightly anesthetized animal provided the impetus for glottic closure. In this paper we present a new technique for LVS in the dog model that involves mechanical traction on arytenoid adduction sutures to achieve vocal fold adduction. This method is safe, effective, and reproducible, and the potential applications are numerous.

A laser Doppler vibrometer was used in a pendulum experiment to measure the recoil momentum induced in hard tissue by pulsed infrared laser exposure. A Holmium:YAG laser was irradiated at bone and a superpulsed CO₂ laser irradiated at dentin. Since the masses of the samples were known and the ablated masses were measured, this method allowed an indirect determination of the velocity of the ablated particles. In a second experiment performed with the CO₂ laser the velocities of the ablated particles were measured directly by the time of flight detected by the laser beam of the vibrometer. The results of both methods are in good agreement; at a mean power of 0.5 Watt of the CO₂ laser the velocity was 50 - 60 m/s increasing at higher mean powers.

The Erbium:YAG laser ((lambda) equals 2.94 micrometer) has been suggested for use in dental, orthopedic, and middle ear surgery due to decreased thermal trauma, precise ablation characteristics, and potential fiber optic delivery. While there has been much focus on the thermal and photoacoustic events that occur during pulsed laser ablation of hard tissue, there are few studies that examine the acoustic energy generated by these devices during ablation from an audiologic standpoint. In this study, the porcine otic capsule, nasal bone, and teeth were irradiated with an Erbium:YAG laser. Frequencies of 5 and 10 Hz shot repetition rate were used with .5 to 4 W average power. Additionally, a burst mode consisting of three pulses was used with .2 to 1.4 J total energy. During ablation, acoustic measurements were made using a sound level meter held 20 mm away from the target site. A constant spot size of 500 micrometer was maintained for each laser blast. With each set of laser parameters, the sound intensity (dB SPL) exceeded 70 dB. Peak intensity measurements of 95 dB were measured. The clinical significance of these findings is discussed and the acoustical aspects of middle ear function and noise trauma are reviewed.

Previous skin welding studies have used continuous wave (CW) delivery of radiation. However, heat diffusion during irradiation prevents strong welds from being achieved without creating large zones of thermal damage to surrounding tissue. This damage may prevent normal wound healing. Strong welds and minimal thermal damage can be achieved by introducing a dye and delivering the radiation in a pulsed mode. Two-cm-long, full-thickness incisions were made in guinea pig skin. India ink was used as an absorber, and egg white albumin was used as an adhesive. A 5-mm-diameter spot of CW, 1.06-micrometer Nd:YAG laser radiation was scanned over the weld site, producing 100 millisecond pulses. The cooling time between scans and number of scans was varied. Thermal damage zones were measured using a transmission polarizing microscope to identify birefringence changes in tissue. Tensile strengths were measured using a tensiometer. For pulsed welding and long cooling times, weld strengths of 2.4 kg/cm² were measured, and thermal damage to the epidermis was limited to approximately 500 micrometers. With CW welding, comparable weld strengths resulted in approximately 2700 micrometer of thermal damage. CW laser radiation weld strengths were only 0.6 kg/cm² when thermal damage in the epidermis was limited to approximately 500 micrometers.

We conducted in vitro laser fusion experiments of bovine aorta using successive accumulation of solder droplets. The solder was composed of serum albumin, sodium hyaluronate and Indocyanine Green dye. After depositing 0.2 (mu) L of the solder onto an aorta incision with a micro-pipette, we used a diode laser at 808 nm with fixed energy parameters to coagulate the solder droplet. A solder strip was formed from 10 droplets photocoagulated to increase the solder-tissue contact area and coagulum volume. Repair of aorta incision was achieved with both a single solder strip and double solder strips. For half of the welded specimens, tensile measurement was performed immediately following solder experiments. Tensile strength was measured in the rest of the specimens after soaking in saline for 24 hours. Scanning electron microscopy was performed on selected specimens. The average ultimate tensile strengths for the single strip group were 261 N/cm² for acute, and 81 N/cm² after 1 day of saline immersion. The average ultimate tensile strengths for the double strip group were 253 N/cm² for acute, and 77 N/cm² after soaking is saline for 1 day. We also measured native aorta ultimate tensile strength, which was 76 N/cm². This study demonstrated the feasibility of using micro droplets of solder to increase tensile strength.

Collagen is believed to play a major role in laser tissue welding. Furthermore, the fundamental fusion mechanism(s) may include thermal denaturation of the collagen fibers. An in vitro investigation of the effect of laser heating (1.9 micrometer diode laser) on collagen conformation was performed. Fourier transform infrared (FTIR) spectra of native and heated porcine cornea were obtained. A low-frequency shift in the amide A band of collagen around 3320 cm^-1 indicated that conformational changes associated with denaturation occurred. Samples heated using a temperature feedback controlled 1.9 micrometer diode laser showed a gradual decrease in the amide A peak frequency with increasing temperature, as did samples heated in a water bath. Complete denaturation was achieved at temperatures above 85 degrees Celsius for both heating protocols. Water loss induced by laser heating may have reduced the mobility of the collagen polypeptide chains, and contributed to the elevated denaturation temperature.

Variations in laser irradiance, exposure time, solder composition, chromophore type and concentration have led to inconsistencies in published results of laser-solder repair of tissue. To determine optimal parameters for laser tissue soldering, an in vitro study was performed using an 808-nm diode laser in conjunction with an indocyanine green (ICG)- doped albumin protein solder to weld bovine aorta specimens. Liquid and solid protein solders prepared from 25% and 60% bovine serum albumin (BSA), respectively, were compared. The effects of laser irradiance and exposure time on tensile strength of the weld and temperature rise as well as the effect of hydration on bond stability were investigated. Optimum irradiance and exposure times were identified for each solder type. Increasing the BSA concentration from 25% to 60% greatly increased the tensile strength of the weld. A reduction in dye concentration from 2.5 mg/ml to 0.25 mg/ml was also found to result in an increase in tensile strength. The strongest welds were produced with an irradiance of 6.4 W/cm² for 50 s using a solid protein solder composed of 60% BSA and 0.25 mg/ml ICG. Steady-state solder surface temperatures were observed to reach 85 plus or minus 5 degrees Celsius with a temperature gradient across the solid protein solder strips of between 15 and 20 degrees Celsius. Finally, tensile strength was observed to decrease significantly (20 to 25%) after the first hour of hydration in phosphate-buffered saline. No appreciable change was observed in the strength of the tissue bonds with further hydration.

5To assess the potential of optical spectroscopy and imaging for improving the detection and evaluation of early skin cancer, we have been studying autofluorescence properties of various skin diseases. In this paper, the autofluorescence properties of basal cell carcinoma (BCC) under 442 nm excitation will be presented. Three different spectroscopy and imaging tools have been used in this study: (1) a portable fiber optic spectrometer for in vivo spectral measurements in an outpatient clinic; (2) a CCD imaging system for cutaneous autofluorescence imaging in vivo; and (3) a fiber optic microspectrophotometer system for frozen tissue section examination of in vitro microscopic fluorophore distribution and spectroscopy. Autofluorescence spectra from 109 BCC lesions characteristically showed decreased fluorescence intensity for BCC as compared to the surrounding normal skin. Of 109 biopsy-proven BCC lesions, 104 showed a decreased fluorescence signal. Decreased autofluorescence in BCC has also been corroborated by in vivo autofluorescence imaging of BCC lesions. Microscopic data from histologic frozen sections mirror the in vivo measurements, with decreased autofluorescence observed within and immediately around basal cell tumor nests. An optical model of basal cell carcinoma is under construction.

Current Ruby lasers or Flashlamp light sources for non- invasive removal of unwanted hairs are limited to a treatment speed of approximately 25 cm²/minute. Although adequate for facial treatments, that speed is too slow for treatment of backs and legs. We present an 18-month study of the use of a 5 pps Alexandrite laser (755 mm wavelength) operated at 20 - 40 J/cm². The 2-millisecond pulse duration laser was used on over 200 patients. Results show less than 5 - 10% regrowth 3 months after the last treatment in over 90% of patients. The average number of necessary full area treatments is two followed by 1 - 4 touch-ups at intervals of 11/2 - 3 months, depending on the body site. Treatment speed is 20 minutes for a back and less than 15 minutes per leg.

The efficacy of laser treatment of port wine stains (PWS) has been shown to be highly dependent on the patient-specific structure of vascular lesions. To improve the accuracy of PWS numerical models, an optical-thermal model simulating an arbitrarily complex, three dimensional tissue geometry has been developed. In this model, the distribution of absorbed radiant energy -- determined using a modified Monte Carlo technique -- is used as the source term in a finite difference thermal model that predicts transient temperature rise. The Arrhenius rate process integral is then used to calculate thermal damage. Simulations based on a tomographic reconstruction of a PWS biopsy were performed for laser pulse durations of 0.5, 5.0 and 50.0 ms and a wavelength of 585 nm. Irradiances that produced maximum tissue temperatures of 120 degrees Celsius were used. The simulations indicated that energy deposition in blood is primarily a function of depth in skin. Thermal diffusion effects increased with longer pulse duration, leading to collateral damage observed at 5.0 and 50.0 ms. A pulse duration of 0.5 ms resulted in confinement of thermal damage to blood regions. Clusters of small vessels tended to behave similarly to larger vessels, reaching higher temperatures and creating more damage in the surrounding dermis than isolated vessels. The incorporation of realistic geometry into an optical-thermal model represents a significant advance in computer modeling of laser surgery.

Laser resurfacing have been used for treatment of photoaged facial skin since 1994. Very few long-term follow-up studies regarding the effectiveness and side effects of the laser resurfacing exist. We investigated the long-term effectiveness and side effects of laser resurfacing in our patients who underwent this procedure since our pioneering invention.

Qualitative and quantitative histopathologic procedures were used to study the chronology of healing and mechanism(s) of wrinkle removal using pulsed CO2 laser irradiation. Lesions placed on 'Fuzzy' rat skin were examined pathologically at 0, 2 and 10 days and 2, 4, 8 and 12 weeks. Re-epithelialization began before 2 days and was complete by 10 days. Lethal thermal damage of the epidermis and superficial dermis led to necrosis and slough of the necrotic tissue. Fibrous dermal scar formation was well established at 10 days and, over the next 10 weeks the scar matured and contracted. The proposed mechanisms of wrinkle removal are (1) lethal thermal damage to the upper layers of the skin, (2) slough of the necrotic tissue and (3) re-epithelialization and (4) fibrous scar formation producing a smooth skin surface.

Surface temperature measurements and CCD video imaging were performed during multiple pulse irradiation on in vivo rat skin. A TruPulse laser (100-microsecond pulsewidth, 3 mm X 3 mm spot size) was used at radiant exposures of 2.4 J/cm² and 3.9 J/cm² for all experiments. Temperatures were recorded with a thermal camera. During multiple pulse irradiation, one pulse per second was applied to a single site. A total of fifteen pulses were applied to a single spot. Irradiating with 2.4 J/cm² pulses led to a slow temperature rise that reached steady state at approximately 200 degrees Celsius. Carbonization onset occurred after pulses 5 - 8. With a higher radiant exposure of 3.9 J/cm², carbonization occurred after the third pulse; after the tenth pulse, focal tissue burning was visible, and the temperature oscillated around 350 degrees Celsius. Surface temperatures were measured during clinical scans. Areas of 3 cm X 3 cm were treated by the laser, which was moved across the tissue in a raster scan with 8 pulses per second. Each area was treated three times. From analysis of histological sections, the thermal damage as a function of pass number and radiant exposure was noted. Contrary to previous reports, the epidermis was not removed after the first pass. Indeed, after three passes, the epidermis was still present (H_o equals 2.4 J/cm²) or was severely fragmented (H_o equals 3.9 J/cm²).

A method for imaging the superficial epidermal and papillary dermal layers of the skin is needed when assessing many skin lesions. We have developed an imaging modality using a video camera whose mechanism of contrast is the reflectance of polarized light from superficial skin. By selecting only polarized light to create the image, one rejects the 95% of diffusely reflected light from the deeper dermis. The specular reflectance (or glare) from the skin surface is also avoided in the setup. The resulting polarization picture maximally accents the details of the superficial layer of the skin and removes the effects of melanin pigmentation from the image. Fore example, freckles simply disappear and nevi lose their dark pigmentation to revel the details of abnormal cellular growth. An initial clinical study demonstrated that the polarization camera could identify the margins of sclerosing basal cell carcinoma while the eye of the doctor underestimated the margin estimate. The camera identified an 11-mm-diameter lesion while the unaided eye identified a 6-mm- diameter lesion.

Feasibility of deep coagulation of skin with superficially absorbed Er:YAG lasers is investigated using a numerical model. Unlike most previous models, the skin is treated as a two-component material: water trapped in spherical cavities inside an infinite elastic medium. In describing the interaction of mid-IR laser light with skin, thermodynamic behavior of pressurized hot water and steam is combined with elastic response of the surrounding medium. A one-dimensional treatment of heat diffusion and the Arrhenius model of the protein denaturation process are also included in the model. Temperature evolution, profile and coagulation depth are analyzed as a function of the pulse duration, number of applied pulses and repetition frequency of the sequence. The results indicate that the depth of coagulated layer, which amounts to 15 - 40 micrometer with a single free-generated Er:YAG laser pulse, can be extended up to 200 micrometer with no surface ablation by using a repetitive pulse sequence of suitable single-pulse fluence, repetition frequency and duration.

Exposure ofradiation ulcers in rats to a low-power JR laser radiation (LPLR) (wavelength of890 nm, pulse power of6 W, frequency range of 80-600 Hz, time of exposure - 10 mm, during 10-20 days) considerably accelerates the ulcer healing, reduces the exudative processes, increases the number of specialized cells and connective elements in wound. A prophylactic LPLR application extends the time of formation of the acute radiation ulcer and reduces its size. Keywords: rats, laser, radiation alcer, healing, connective tissue

Use of holmium laser energy for vaporization/coagulation of the nucleus pulposus in canine intervertebral discs has been previously reported and is currently being applied clinically in veterinary medicine. The procedure was originally developed in the canine model and intended for potential human use. Since the pulsed (15 Hz) holmium laser energy exerts photomechanical and photothermal effects, the potential for extrusion of additional disc material to the detriment of the patient is possible using the procedure developed for the dog. To reduce this potential complication, use of diode laser (805 nm - CW mode) energy, coupled with indocyanine green (ICG) as a selective laser energy absorber, was formulated as a possible alternative. Delivery of the ICG and diode laser energy was through a MicroJet device that could dispense dye interactively between individual laser 'shots.' Results have shown that it is possible to selectively ablate nucleus pulposus in the canine model using the device described. Acute observations (gross and histopathologic) illustrate that accurate placement of the spinal needle before introduction of the MicroJet device is critically dependent on the expertise of the interventional radiologist. In addition, the success of the overall technique depends on consistent delivery of both ICG and diode laser energy. Minimizing tissue carbonization on the tip of the MicroJet device is also of crucial importance for effective application of the technique in clinical veterinary medicine.

The Nd:YAG laser is a frequently used laser in correcting equine upper respiratory disorders. Evaluation of this laser and several other lasers ability to penetrate tissue has been based on in vitro studies using portions of the arytenoid cartilage. The parameters measured have routinely been depth and width of crater created from irradiation of tissue. This investigation was performed on cadaver acquired tissue with anticipation of developing a model to conduct future in vivo studies of a similar nature to evaluate and compare different lasers. To perform this power setting, tissue selection and means of acquiring measurements needed to be standardized. Due to its accessibility and anatomic similarity to the arytenoid used in previous studies the rostral nasal septum was chosen as the second tissue for comparison with the arytenoid. Evaluation of the selected energies delivered to the tissues by the Nd:YAG laser were evaluated to set a standard by determining depth and top and bottom diameters of the area ablated. Methods of measurement consisting of standard histologic preparation followed by microscopic evaluation was compared to computer tomography acquired determinations. Statistical analysis supported the hypothesis that the nasal septum is a viable substitute for the arytenoid cartilage for future in vivo studies. It is also easily accessible compared to the arytenoid and evaluation of laser induced lesion parameters either in situ or separate from the animal should not be detrimental to the animal.

Hospital records reviewed over a 12-year period determined that 6 horses had been presented for guttural pouch mycosis. All had a history of epistaxis and several had accompanying neurologic signs, including dysphagia. Initially, conformation of the disease was obtained by radiographic and endoscopic examinations. Surgical treatment was directed at controlling and preventing additional hemorrhage by occluding the arterial source of the hemorrhage. Direct treatment of the mycotic plaque present within the guttural pouch was conducted using transendoscopic technique to direct irradiation from the Nd:YAG laser. The protocol described for the laser application was successful in resolving the lesions and was less complicated and stressful than previously reported topically applied chemical protocols.

Current methods for in vivo evaluation of digital hemodynamics in the horse include angiography, scintigraphy, Doppler ultrasound, electromagnetic flow and isolated extracorporeal pump perfused digit preparations. These techniques are either non-quantifiable, do not allow for continuous measurement, require destruction of the horse orare invasive, inducing non- physiologic variables. In vitro techniques have also been reported for the evaluation of the effects of vasoactive agents on the digital vessels. The in vitro techniques are non-physiologic and have evaluated the vasculature proximal to the coronary band. Lastly, many of these techniques require general anesthesia or euthanasia of the animal. Laser Doppler flowmetry is a non-invasive, continuous measure of capillary blood flow. Laser Doppler flowmetry has been used to measure capillary blood flow in many tissues. The principle of this method is to measure the Doppler shift, that is, the frequency change that light undergoes when reflected by moving objects, such as red blood cells. Laser Doppler flowmetry records a continuous measurement of the red cell motion in the outer layer of the tissue under study, with little or no influence on physiologic blood flow. This output value constitutes the flux of red cells and is reported as capillary perfusion units. No direct information concerning oxygen, nutrient or waste metabolite exchange in the surrounding tissue is obtained. The relationship between the flowmeter output signal and the flux of red blood cells is linear. The principles of laser Doppler flowmetry will be discussed and the technique for laminar capillary blood flow measurements will be presented.

Normal non-pigmented bovine eyelids in two Hereford cows under general anesthesia were treated with diode laser (805 nm) in a power range of 3 - 6.5 watts. Tissue temperatures were measured in areas infiltrated with 0.25% indocyanine green (ICG) solution and in non-infiltrated areas. Targeted tissue was laser treated at post-injection time intervals of 1 to 60 minutes. Temperatures were measured with a computerized temperature sensing program using hypodermic needle thermistors. Trial objectives were to establish power/chromophore concentration/time parameters to create tumor and peri-tumor tissue temperatures of 50 degrees Celsius without causing epidermal vaporization. Tissue temperature of 50 degrees Celsius has been established as the temperature producing coagulative necrosis of squamous cell carcinoma tumor tissue in 30 seconds. This temperature was produced in chromophore-enhanced tissue bit without repeatable confidence. Bovine ocular squamous cell carcinoma (BOSCC)-affected eyes and eyelids have been successfully treated with carbon dioxide focused and defocused laser with and without chromophore enhanced diode laser (805 nm) energy. The need for tumor staging and procedure standardization requires further investigation to determine laser power/chromophore concentration, and issue exposure times.

The major cause of treatment failure in human and veterinary cancer patients is tumor invasion and metastasis. The inability of local therapy (surgery, radiation, photodynamic therapy) to eradicate a metastatic cancer presents a challenge in the therapy of residual or micrometastatic disease. Because of its local therapy limitations, chromophore-enhanced selective photothermal laser treatment has been augmented with a superimposed laser-induced systemic photobiological reaction, laser immunotherapy. Laser immunotherapy is a novel cancer treatment consisting of: (1) a laser in the infrared wavelength range (i.e. 805 nm solid state laser); (2) a photosensitizer of the corresponding absorption peak [i.e. indocyanine green (ICG)]; and (3) an immunoadjuvant [i.e. glycated chitosan gel (GCG)]. The intratumor injection of the photosensitizer (ICG) and immunoadjuvant (GCG) solution is followed by noninvasive laser irradiation. The laser energy causes tumor cell destruction by photothermal interaction to reduce the tumor burden and at the same time exposes tumor antigens. The immunoadjuvant concomitantly stimulates the host to mount a systemic anti-tumor immune response against the remaining cells of the tumor and to induce a long-term, tumor-specific immunity. This study investigates the feasibility of utilizing laser immunotherapy as an adjunctive therapy for the control of feline fibrosarcoma in future.

For soft tissue sarcomas with high local recurrence rates following seemingly adequate surgical excision, intraoperative photodynamic therapy (IOPDT) provides a treatment strategy to eradicate microscopic, residual disease. Six Fischer 344 rats were given bilateral subcutaneous syngeneic 9L gliosarcoma tumors. When tumors reached 1.0 cm³, the rats were given 200 mg/kg ALA by intraperitoneal injection. Four hours later the rats were anesthetized, both tumors were incompletely excised and one surgical field was treated with 635 nm laser light (75 mW/cm², 100 J/cm²). The surgical sites were then closed and the rats were monitored for local recurrence of the tumor. Low intensity fluorescent microscopic images captured with a cooled CCD camera confirmed that the tumors converted ALA into PpIX. Post-IOPDT swelling of the treated leg lasted 48 hours. An 80% local recurrence rate was observed in both groups 14 days following treatment. There was no difference in wound healing between IOPDT-treated sites and sites treated with surgery alone. Recurrent tumors were smaller in IOPDT sites than those treated with surgery alone. Additionally, the IOPDT recurrences were at the margin of the treatment field, suggesting a photoirradiation 'geographical miss.' These preliminary results, although disappointing, suggest that with further refinement IOPDT is a promising treatment modality for traditionally difficult to treat tumors.

Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

Claims of different effects of cold laser (CL) irradiation may be attributable to the competition of different reaction channels activated by CL and/or the unreproducibility of irradiation conditions. This study is concerned about reproducibility of the conditions of irradiation. We present a comparative analysis of the correlation between irradiation characteristics and biostimulation parameters, and show that the leading cause of treatment unreproducibility is the discrepancy of therapeutical and true irradiation doses. We analyze different approaches of true dose determination, influence of blood content and microcirculation on dosage and describe principles of true doses generating. It is shown that only on-line regulation of both parameters of dosage, CL power and temporal mode of irradiation, allows the determination of individual true dose. Problems of designing CL with feedback for on-line regulation of dosage parameters are also described.

Based on the mechanisms of sequential two-photon absorption in biological molecules, a theoretical model is proposed for the absorption of light in melanin. To test this model, melanin samples were studied using the collinear photothermal deflection spectroscopy (PDS), with an He-Ne laser and an Argon-Krypton ion laser to provide two simultaneously exciting wavelengths. It is found that melanin samples have a strong decay in amplitude of the photothermal signal, in contrast to a reference India ink whose photothermal signal is stable. The power dependence of the amplitude of the photothermal signal is also found to exhibit a departure from linearity at higher power densities for a melanin sample. Simultaneous exposure of the same sample to He-Ne and Argon-Krypton ion laser irradiation produces a signal which is significantly less than that expected from the sum of the signals obtained from using each laser alone. These results are explained with a modification of the sequential two-photon absorption process, which involves a conversion of the photon energy to a non- thermal form such as photochemical energy.

Restenosis after balloon angioplasty is caused by both intimal hyperplasia and arterial shrinkage (constrictive remodeling). Previous studies have indicated the inhibitory effect of photodynamic therapy on intimal hyperplasia development after angioplasty. The potential of a photoactivation regime (Psoralen + UVA irradiation: PUVA), which does not cause unwanted systemic side effects, for the prevention of both intimal hyperplasia formation and constrictive remodeling following balloon dilation was explored in the present study. In the rabbit iliac artery, balloon dilation followed by PUVA- therapy at a radiant exposure of 1 J/cm² was performed (n equals 10). Control balloon dilation was performed in the contralateral arteries (n equals 10). After 4 weeks of survival, angiographic lumen renarrowing was determined in terms of intimal hyperplasia and constrictive remodeling. Late loss, but not intimal hyperplasia, was significantly larger in the PUVA group as compared to the control group (p less than 0.05). This difference in angiographic lumen loss can only be attributed to the difference in constrictive remodeling (arterial shrinkage). Thus, PUVA-therapy did not prevent intimal hyperplasia following balloon dilation. PUVA-therapy even enhanced luminal narrowing by augmented constrictive arterial remodeling.

Skin aging caused from chronological and photodamage processes results in many alterations in skin appearance. In many circumstances, patients who pursue CO₂ laser resurfacing for facial rejuvenation are also concerned with other photoaging alternations that are beyond the efficacy of the CO₂ laser. We demonstrated an approach to aged facial skin by using combined treatments of appropriate lasers.

The promising clinical potential for laser welding of tissues has generated a growing interest in this field. As improved laser welding system was constructed in this work. It was based on IR transmitting AgClBr fibers for laser power delivery and for temperature control. The fiberoptic system was used to transmit CO₂ laser power for tissue heating and for non contact (radiometric) temperature monitoring and control. Bladder opening (cystotomy) was performed in 38 rats and 33 of the animals underwent laser welding. In 5 rats (control group) the bladder wound was closed with one layer continuous 6-0 dexon sutures. The rats were sacrificed on days 2, 10 and 30 for histological study. The temperature control of the upper tissue surface was set at 70 plus or minus 5 degrees Celsius. Bladder closure using laser welding was successful in 31/33 (94%) of the animals. The quality of the weld was examined immediately after the operation, revealing a water tight closure of the bladder wall. The histological examination showed an excellent welding and healing of the tissue. These results demonstrate the potential of temperature controlled CO₂ laser welding.

Improvements of endoscopic techniques have renewed the interest of urologists in laser lithotripsy in recent years. Laser energy can be easily transmitted through flexible fibers thereby enabling different surgical procedures such as cutting, coagulating and lithotripsy. The Ho:YAG laser offers multiple medical applications in Urology, among them stone fragmentation. However, the present knowledge of its fragmentation mechanism is incomplete. The objective was therefore to analyze the fragmentation process and to discuss the clinical implications related to the underlying fragmentation mechanism. The stone fragmentation process during Ho:YAG laser lithotripsy was observed by time resolved flash video imaging. Possible acoustic transient occurrence was simultaneously monitored with a PVDF-needle hydrophone. Fragmentation was performed on artificial and cystine kidney stones in water. We observed that though the fragmentation process is accompanied with the formation of a cavitation bubble, cavitation has only a minimal effect on stone fragmentation. Fragment ejection is mainly due to direct laser stone heating leading to vaporization of organic stone constituents and interstitial water. The minimal effect of the cavitation bubble is confirmed by acoustic transients measurements, which reveal weak pressure transients. Stone fragmentation with the Holmium laser is the result of vaporization of interstitial (stone) water and organic stone constituents. It is not due to the acoustic effects of a cavitation bubble or plasma formation. The fragmentation process is strongly related with heat production thereby harboring the risk of undesired thermal damage. Therefore, a solid comprehension of the fragmentation process is needed when using the different clinically available laser types of lithotripsy.

Primary ureteropelvic junction obstruction (UPJO) today is mainly treated by antegrade endopyelotomy. Ureteroscopic retrograde endopyelotomy using a KTP-laser is a new and promising treatment modality for primary UPJO. A semi-rigid Ch. 9.5 continuous flow ureteroscope (Storz) is used. Lateral incision is performed at a power setting of 5 to 20 W with a 0.4 mm bare fiber or a Ch. 3.6 side-firing device (Laserscope). An endopyelotomy stent is left in place for 6 weeks. Evaluation is usually done with a urogram pre- and postoperatively. Eight patients (2m/6f) with a mean age of 29.5 years have been treated so far. In 6/8 cases the incision was successful. Prolonged stenting occurred in one and laparoscopic division of a crossing vessel because of a persistent obstruction in another patient. In 2/8 patients retrograde endopyelotomy was not possible owing to large lower pole vessels and so open pyeloplasty was performed. Our preliminary results suggest retrograde KTP laser endopyelotomy as a safe and efficient procedure. A first attempt to laser endopyelotomy seems to be justified even in case of crossing vessels and/or large pyelocaliceal volume.

The ultrasonic aspirator is essentially a vibrating tip whose ultrasonic frequencies fragment soft tissues, before aspirating it away from the surgical field. In the case of skin, the softer epidermis absorbs the vibrating tip's impact force so as to fragment it, whereas the more elastic and collagenous dermis reflects it. Understanding this, a chronic study to compare a skin resurfacing laser (Coherent, Palo Alto, CA) and an ultrasonic surgical aspirator (CUSA) (Valleylab Inc., Boulder, CO) as a skin resurfacing tool was performed using an in-vivo pigmented porcine model. Gross and histopathologic evaluations were made of the lesions removed at 0, 1, 3, 6, 11, 21, and 56 days post procedure. The laser parameters utilized constant power (60 W) and spot size but the number of passes was varied from 1 to 4 passes. This simulated typical minimal to maximal clinical laser treatments. CUSA parameters were then chosen so as to imitate the various laser passes. On sacrifice gross evaluations showed similar levels of healing, using lesion color and scab formation as the method of evaluation. Histological analysis showed evidence of thermal effects with both devices and that some but not all CUSA settings were comparable to the laser. In short, ultrasonic technology may have the potential to provide a controlled method of selectively removing the epidermal skin layer during resurfacing.

Purpose: The purpose of the study was to determine the optimal indocyanine green dye (ICG) concentration and laser power density (PD) for tissue soldering using an 808-nm diode laser. Methods: Temperature profiles in vitro and in vivo were obtained using the ICG/albumin solder. [ICG] ranged from 0.31 mg/mL to 20 mg/mL while PD ranged from 3.2 to 63.7 W/cm². Solder color and textural changes were noted. Eighteen rats were subjected to 1.5 cm incisions (N equals 128) created on the dorsal skin followed by closure with LTS at varying PD and [ICG]. Tensile strength profiles using rat skin were taken immediately and 10 days postoperatively. Histological examination was performed at the time of sacrifice. Results: Temperature profiles of the ICG/albumin solder did not differ with varying [ICG], but showed statistically significant variability at different laser PD. Using solder color change as a subjective endpoint, average peak solder temperature ranged from 69 degrees Celsius at a PD of 8.0 W/cm², 105 degrees Celsius to 120 degrees Celsius at PD 15.9 to 31.8 W/cm², and greater than 200 degrees Celsius at PD greater than or equal to 47.7 W/cm². Peak intradermal temperatures remained below 50 degrees Celsius at all PD. The broadest range of color change in the solder was observed at [ICG] of 2.5 mg/mL. Immediate tensile strength data showed a trend towards greater strength at higher [ICG]. The greatest immediate tensile strength was reached at a PD of greater than or equal to 31.8 W/cm² for all [ICG]. At 10 days an inverse trend existed only between PD (not ICG) and tensile strength, however this was not statically significant. Histologic analysis showed poorer healing and thermal injury to tissue soldered at a PD greater than or equal to 23.9 W/cm². Conclusions: Based on these findings, optimal laser tissue soldering occurs with an [ICG] of 2.5 mg/ml and a PD of 15.9 W/cm².

Purpose: The purpose of this study was to evaluate laser tissue soldering using an 808 nm diode laser and wavelength- matched human albumin solder for urethral surgery in children. Methods: Currently, 30 boys, ages 3 months to 8 years were randomized to standard suturing (n equals 22) or 'sutureless' laser hypospadias repair (n equals 18). Laser soldering was performed with a human albumin solder doped with indocyanine green dye (2.5 mg/ml) using a laser power output of 0.5 W, pulse duration of 0.5 sec, and interval of 0.1 sec. Power density was approximately 16 W/cm². In the laser group, sutures were used for tissue alignment only. At the time of surgery, neourethral and penile lengths, operative time for urethral repair, and number of sutures/throws were measured. Postoperatively, patients were examined for complications of wound healing, stricture, or fistula formation. Results: Mean age, severity of urethral defect, type of repair, and neourethra length were equivalent between the two groups. Operative time was significantly faster for laser soldering in both simple (1.6 plus or minus 0.21 min, p less than 0.001) and complex (5.4 plus or minus 0.28 min, p less than 0.0001) hypospadias repairs compared to controls (10.6 plus or minus 1.4 min and 27.8 plus or minus 2.9 min, respectively). The mean number of sutures used in the laser group for simple and complex repairs (3.3 plus or minus 0.3 and 8.1 plus or minus 0.64, respectively) were significantly (p less than 0.0001) less than for controls (8.2 plus or minus 0.84 and 20 plus or minus 2.3, respectively). Followup was between 3 months and 14 months. The overall complication rate in the laser group (11%) was lower than the controls (23%). However, statistical significance (p less than 0.05) was achieved only for the subgroup of patients undergoing simple repairs (LTS, 100% success versus suturing, 69% success). Conclusions: These preliminary results indicate that laser tissue soldering for hypospadias repair may be performed in a nearly sutureless fashion and in a more rapid manner than for conventional suturing. The trend towards a decreased rate of complications in the laser group at this time indicates that laser soldering may be an improved method of tissue closure for hypospadias repair. We continue to accrue patients to this study.

We developed a fiber optic pressure catheter which has the potential to exceed the performance and cost-effectiveness of any currently available pressure measurement system in cardiovascular applications. Our design is based on a movable metallic ribbon, which works as a reflector, to transform the pressure into a light signal. The sensor has a diameter of 0.8 mm and is covered by medical grade polyurethane. In the laboratory tests, our sensors consistently showed high sensitivity and low noise (about 1 mmHg) over the pressure range of 0 to 300 mmHg. The time constant of the sensor, which is limited by the current software is about 20 mseconds (50 Hz). Using a mechanical heart simulator to generate pressure pulses, the pressure reading was independent of temperature change over a 30 degree Celsius range, and the drift was minimal during the 72-hour pressure pulse tests. A preliminary animal test was carried out with our sensors inserted into the artery of a dog. The comparison with an external reference sensor showed basic sensor performance. The sensor can also be used in brain, lung, and bladder pressure measurement applications.