Improved laser treatment of port wine stains is expected by utilizing higher incident dosages, longer pulse durations, and longer wavelengths than those currently used in clinical settings. However, higher incident dosages also increase the risk of nonspecific thermal injury to the epidermis. Using ex-vivo human skin samples, we investigated the thermal respone of human skin epidermis in different skin types ot 595-nm wavelength laser irradiation at high incident dosages (up to 20 J/cm²) and long pulse durations (1.5 to 40 milliseconds) in conjunction with cryogen spray cooling (CSC). Human skin samples (Fitzpatrick types I-VI) from consenting adult females undergoing trans-rectus abdominis myocutaneoues flap procedures were irradiated at the incident dosages D₀=4, 6, 10, 15, and 20 J/cm², pulse durations τ_laser=1.5, 10, and 40 milliseconds without and with CSC (Refrigerant-134A, spurt duration τ_CSC=100 milliseconds). Thermal injury to the epidermis was evaluated by histological observations. Experimental results showed that thermal injury to the epidermis could not be avoided in skin type VI even at D₀ = 4 J/cm² in conjunction with CSC. However, CSC allowed utilization of high incident dosages (15 - 20 J/cm²) in skin types I-IV. Under the same incident dosage, longer pulse durations led to decreased degree of thermal injury to the epidermis. Threshold values for irradiation parameters that resulted in thermal injury to the epidermis for each skin type were obtained.

In order to enhance the efficacy of photodynamic therapy for skin diseases, we previously demonstrated that the simultaneous application of heating and a laser-induced stress wave (LISW) accelerated skin permeabilization of porfimer sodium (Photofirn) in in-vivo experiments. In this study, to investigate the uptake of Photofrin by cells within skin, we carried out in-vitro experiments using fibroblast-like cells. Immediately after replacing culture medium with 43 degrees C phosphate buffered saline solution of Photofrin in a well, the cells were exposed to a LISW that was generated by irradiation of a nanosecond laser pulse onto a target attached on the back of the well. Uptake of Photofrin within the cells was observed with a confocal laser scanning microscope, while the cells were stained with DAPI (4',6-diamidino-2-phenylindole) to evaluate the survival rate. The largest uptake was observed for the simultaneous application (heating + LISW) with high survival rates (more than 95%). These results suggested that Photofrin was transported into fibroblasts within skin. In this method, irradiation of low-fluence laser was effective to enhance uptake, and therefore optical fiber can be used for laser delivery.

We present our research into a pulsed xenon lamp source for the treatment of psoriasis and other skin disorders. Various filtering techniques, lamp configurations, power supply configurations and delivery systems are discussed. Comparisons are made to existing treatment modalities. Cryogen cooling of the treatment site is discussed.

This study presents a finite element model of a non-ablative RF tissue heating system for dermatological applications. The Thermage ThermaCool TC System consists of a capacitively coupled treatment tip, handpiece, RF generator, and cryogen delivery system. Various electrode geometries were created to generate uniform thermal profiles at specific depths in the tissue. The optimal thermal treatment depth for a clinical indication is influenced by factors such as tissue thickness for a given anatomical location, the desired target for heating in that tissue, and anesthesia factors. Electrodes of ¼, 1, and 1½cm² area were evaluated for depth of treatment. A 3D multi-physics finite element model was developed to simulate RF heating in tissue. The program coupled electrical and thermal models to predict the electric field produced and the consequent heating. The electrical portion of the model was verified using an electric field mapping system. The thermal section of the model was confirmed via thermocouple measurements for cooling and infrared imaging measurements for RF heating. The FEM model produced electrical and thermal predictions that were verified with experimental measurements. The finite element model shows significant potential as a predictive R&D tool to assist in RF electrode design and reduce product development time.

The purpose of this study was to evaluate the ability of single and dual wavelength excitation pulsed photothermal radiometry (SWE- and DWE-PPTR, respectively) to profile port wine stain (PWS) skin. To this end, a numerical optical-thermal model was developed, incorporating a digitized PWS biopsy as the input skin geometry. Both SWE and DWE reconstructed depth profiles were obtained by applying an iterative, nonnegatively constrained conjugate gradient algorithm to the computed PPTR signals. The accuracy of determining the following clinically significant parameters from our reconstructions was determined: (1) average epidermal thickness (Z_epi), (2) maximum epidermal temperature rise (ΔT_epi,max), (3) initial PWS depth (Z_PWS), and (4) depth of maximum PWS temperature rise (Z_PWS,max). In the SWE-PPTR reconstruction, key parameters such as Z_epi and Z_PWS could not be determined. Comparison of the epidermal profiles of the actual and DWE-PPTR profiles revealed a good quantitative match in Z_epi and ΔT_epi,max. Comparison of the PWS profiles revealed that Z_PWS and Z_PWS,max are determined within 25% and 11%, respectively. The results of this study indicate that DWE-PPTR is a viable tool for depth profiling of PWS skin.

The aim of this study is to investigate the feasability of using a needle-free injection gun to inject highly viscous glycerol into porcine skin for the purpose of optical skin clearing. In this study a needle-free injection device DERMO-JET by Robbins Instruments was used to inject glycerol in 100%, 50% and 25% concentration into freshly excised porcine skin. The injection sites were imaged using optical coherence tomography (OCT) amplitude data to determine injection depth. Similar experiments were conducted involving the same device for injection of 100%, 50% and 25% glycerol-water mixtures with trace amounts of rhodamine. Injected tissue was rapidly frozen and sectioned with a keratome to reveal the mixture dispersion with a fluorescence microscope.

In therapy of port wine stain (PWS) birthmarks using pulsed green or yellow lasers, non-specific absorption by epidermal melanin reduces the amount of incident radiation that reaches the target PWS blood vessels. The related epidermal heating can induce blistering, dyspigmentation, or scarring, which limits the applicable radiant exposure, thus adversely affecting the efficacy of treatment in many patients. Our objective was to assess temperature depth profiles induced in PWS skin by a novel Nd:YAG laser emitting simultaneously at 1064 and 532 nm. The results should help determine safe radiant exposures for use in future clinical trials. The underlying hypothesis is that the added 1064 nm radiation may lead to a higher temperature increase in PWS relative to the epidermis, in comparison with a customary KTP/Nd:YAG laser system for vascular treatments (emitting at 532 nm only). The laser induced temperature profiles were determined in vivo using pulsed photothermal radiometry. A PWS test site was irradiated with a sub-therapeutic laser pulse and the transient change of the infrared radiant emission was recorded by a fast infrared camera. The laser-induced temperature profiles were reconstructed by solving the thermal-radiative inverse problem using an iterative minimization algorithm.

High-powered photoselective vaporization of the prostate (PVP) is a relatively new addition in the armamentarium against bladder outlet obstruction due to BPH. With BPH, the prostate undergoes stromal and epithelial hyperplasia, particularly in the transitional zone, mediated by dihydrotestosterone (DHT). This periurethral enlargement can compress the prostatic urethra leading to bladder outlet obstruction and eventually urinary retention. Treatment of uncomplicated symptomatic BPH has evolved from the standard transurethral resection of the prostate (TURP) to multiple medical therapies and the putative minimally invasive surgical procedures. These include microwave ablation, needle ablation, balloon dilation, stents, as well as fluid based thermo-therapy, ultrasound therapy and cryotherapy. Different forms of lasers have been applied to treat BPH with variable short and long term benefits of urinary symptoms. However, the controversy remains about each laser regarding its technical applicability and efficacy.

The urologic management of benign prostatic hyperplasia (BPH) beyond pharmaco-therapy has changed dramatically over the last decade. Open prostatectomy and transurethral resection of the prostate (TURP) have been the mainstays of surgical intervention for BPH. These procedures were initially reserved for patients with obstructive uropathy, prostatic bleeding, or bladder calculi. With improved techniques and lower morbidity, TURP is currently the "gold standard" of treatment for patients with BPH and troubling lower urinary tract symptoms (LUTS), and patients are being treated prior to the development of these adverse sequelae. Nevertheless, TURP is still major surgery, requiring either a spinal or general anesthetic and an inpatient hospital stay. Furthermore, TURP is not uniformly successful. Up to 30% of patients report dissatisfaction from the procedure. Complications have been well described and include bleeding, bladder-neck contracture, erectile dysfunction retrograde ejaculation, urinary incontinence, and fluid/electrolyte imbalance (post-TUR syndrome). The mortality rate for TURP is approx. 2 - 10/1000 cases. Over the past decade, the number of TURPs being performed has been decreasing as minimally invasive therapies, including alpha-adrenergic blockers, are being used as "first-line" management with increasing frequency and success. In addition, urologists no longer just treat ill patients in urinary retention. The treatment paradigm has evolved to include patients with persistently troubling symptoms of bladder-outlet obstruction, prior to the development of such adverse sequelae. Furthermore, patients see the care of a urologist on an elective basis, and they frequently wish to avoid surgery. As described in prior chapters, advancements in our understanding of the pathophysiology of BPH have led toimprovements in its medical management and have delayed or precluded surgery in many patients. However, when pharmacotherapy fails, further treatment options need to be discussed. Minimally invasive therapies for BPH have evolved out of this need to "bridge the gap" between medical and surgical managment. This chapter describes the current modalities of minimally invasive treatment for benign prostatic obstruction caused by prostatic lobar hyperplasia, and their respective roles in our office practice.

From February, 1995 through June, 2002, 68 patients underwent laser incision of the prostate at our clinic. By means of a 23 F cytoscope and a 600 micrometer lateral firing quartz fiber the vesical neck was incised at the 5 and 7 o'clock position at 60 W power. Total energy averaged 13648 J. Operative time did not exceed 15 minutes. General anesthesia was employed in all but one patient. 38 patients remained catheter-free whereas 30 patients were catheterized for two hours. Except for three cases, all patients were discharged on the same day, usually after the first micturition. Anti-inflammatory treatment was administered for two weeks, Cotrimoxazole for 5 days. No serious complications were encountered. Minor side effects included urinary retention (1 pat.), urinary infection (3 pat.) and retrograde ejaculation (1 pat.). Considering a mean follow-up of 21 months, the average Qmax improved enormously (25.4 ml/s versus 10.9 ml/s), as did residual urine volume (35 ml versus 95 ml) and IPSS (7.1 versus 20.5). Three patients required TUR-P 2-3 years after laser surgery and one patient underwent radical retropubic prostatectomy for prostate cancer 2 years later. In conclusion, Nd:YAG laser incision of the prostate is a simple, safe, reliable and cost-effective outpatient procedure.

The number of dialysis patients due to end stage kidney disease is increasing. Finding ways to improve patient outcomes and reduce the cost of dialysis is a challenging task. Dialysis care is complex and multiple factors may influence patient survival. More than 50 parameters may be monitored while providing a kidney dialysis treatment. Understanding the collective role of these parameters in determining outcomes for an individual patient and administering individualized treatments is of importance. Individual patient survival may depend on a complex interrelationship between multiple demographic and clinical variables, medications, and medical interventions. In this research, a data mining approach is used to elicit knowledge about the interaction between these variables and patient survival. Two different data mining algorithms are employed for extracting knowledge in the form of decision rules. Data mining is performed on the individual visits of the "most invariant" patients as they form "signatures" for their decision categories. The concepts introduced in this research have been applied and tested using a data collected at four dialysis sites. The computational results are reported.

Indwelling double J ureteral stents are used for internal urinary diversion for ureteral obstruction and post-surgical drainage of the upper urinary tract. Stent calcification is a serious complication especially in those with forgotten stents. In a retrospective review of 16 patients (10 male and 6 female) we found holmium laser to be highly effective in the management of calcified stents. Encrustations/calcifications were noted on the distal end of the sent in 6 patiens (37.5%), middle and distal portions in 2 patients (12.5%), along the entire length of the stent in 3 patients (18.75%), lower portion of the stent in 4 patients (25%) and at the upper and lower ends of the stent in one patient (6.25%). Cystolitholapaxy, retrograde ureteroscopy (URS) with holmium: YAG (yttrium-aluminum-garnet) laser intracorporeal lithotripsy, percutaneous nephrostolithotomy (PNL) and antegrade URS with holmium: YAG laser intracorporeal lithotripsy were effectively performed without intraoperative complications. Lithotripsy became necessary before stent removal in 11 patients (68.75%). Holmium laser lithotripsy was useful in managing 7 patients (43.75%), and shockwave lithotripsy (SWL) in 6 patients (37.5%). In two patients (12.5%) both holmium and SWL were used before the stent can be removed.

Purpose: To assess the safety and efficacy of ureteroscopy and holmium:YAG (yttrium-aluminum-garnet) laser lithotripsy in the treatment of upper urinary tract calculi in patients with known and uncorrected bleeding diatheses. Materials and Methods: A retrospective chart review from 2 tertiary stone centers was performed to identify patients with known bleeding diatheses who were treated with holmium:YAG laser lithotripsy for upper urinary tract calculi. Twenty-five patients with 29 upper urinary tract calculi were treated with ureteroscopic holmium laser lithotripsy. Bleeding diatheses identified were coumadin administration for various conditions (17), liver dysfunction (3), thrombocytopenia (4), and von Willebrand's disease (1). Mean international normalized ratio (INR), platelet count and bleeding time were 2.3, 50 x 10⁹/L, and > 16 minutes, for patients receiving coumadin or with liver dysfunction, thrombocytopenia, or von Willebrand's disease, respectively. Results: Overall, the stone-free rate was 96% (27/28) and 29 of 30 procedures were completed successfully without significant complication. One patient who was treated concomitantly with electrohydraulic lithotripsy (EHL) had a significant retroperitoneal hemorrhage that required blood transfusion. Conclusions: Treatment of upper tract urinary calculi in patients with uncorrected bleeding diatheses can be safely performed using contemporary small caliber ureteroscopes and holmium laser as the sole modality of lithotripsy. Ureteroscopic holmium laser lithotripsy without preoperative correction of hemostatic parameters limits the risk of thromboembolic complications and costs associated with an extended hospital stay. Avoidance of the use of EHL is crucial in reducing bleeding complications in this cohort of patients.

Objectives: Symptomatic urolithiasis in pregnancy that does not respond to conservative measures has traditionally been managed with ureteral stent insertion or percutaneous nephrostomy (PCN). Holmium:yttrium-aluminum-garnet (YAG) laser lithotripsy using state-of-the-art ureteroscopes represents an emerging strategy for definitive stone management in pregnancy. The purpose of this study was to review the results of holmium laser lithotripsy in a cohort of patients who presented with symptomatic urolithiasis in pregnancy. Methods: A retrospective analysis was conducted at 2 tertiary stone centers from January 1996 to August 2001 to identify pregnant patients who were treated with ureteroscopic holmium laser lithotripsy for symptomatic urolithiasis or encrusted stents. Eight patients with a total of 10 symptomatic ureteral calculi and 2 encrusted ureteral stents were treated. Mean gestational age at presentation was 22 weeks. Mean stone size was 8.1 mm. Stones were located in the proximal ureter/ureteropelvic junction (UPJ) (3), mid ureter (1), and distal ureter (6). Results: Complete stone fragmentation and/or removal of encrusted ureteral stents were achieved in all patients using the holmium:YAG laser. The overall procedural success rate was 91%. The overall stone-free rate was 89%. No obstetrical or urological complications were encountered. Conclusions: Ureteroscopy and holmium laser lithotripsy can be performed safely in all stages of pregnancy providing definitive management of symptomatic ureteral calculi. The procedure can be done with minimal or no fluoroscopy and avoids the undesirable features of stents or nephrostomy tubes.

While 55 - 60% of newly diagnosed bladder cancers are superficial, a significant number recur as higher grade and/or stage tumors. WBPDT has been used to treat some of these recurrent superficial tumors, although its use has been associated with dose-dependent side effects. Preclinical investigation of three sequential WBPDT treatments using lower PDT dose in normal canine bladder resulted in a lack of permanent bladder contracture. Lower dose single PDT treatment has shown less durable tumor response; however, sequential WBPDT treatments with lower dose may result in durable tumor response. Five patients (4 male, 1 female), average age 65.6 (62-72 years), with recurrent or resistant superficial TCC of the bladder received two WBPDT treatments. First treatment occurred at baseline and the second treatment at 6 months. Photofrin (1.5 mg/kg) was given intravenously 48 hours prior to each cystoscopic treatment with laser light (630 nm, Coherent Lambda-Plus laser). Total light treatment doses were 1500 - 2500 Joules at baseline and 1000- 1500 Joules at 6 months. Moderate irritative bladder symptoms occurred in all patients the first week post PDT. No cases of bladder contracture have occurred. 4 of 5 patients showed no evidence of disease during the follow-up period (12 - 18 months post second treatment). One patient had a recurrence at 18 months post second treatment. Mean disease-free interval is 16.2 months. The safety of two sequential WBPDT treatments is suggested by this preliminary data. Assessment of efficacy will be possible wit a large number of patients and a longer follow-up period.

The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

Purpose: Several investigators have demonstrated an approximately 20% higher tumor detection rate by ALA (5-aminolevulinic acid) based fluorescence endoscopy (AFE) compared to standard white light cystoscopy. These data suggest a reduction of residual and recurrent tumor following fluorescence guided transurethral resection (TUR) of bladder carcinoma. The present study was performed to test this hypothesis. Materials and Methods: In a prospective randomized multi-center study, 2 x 51 patients underwent TUR of bladder tumor(s) either with white light (current standard) or assisted by ALA-induced fluorescence. A 2nd look TUR with AFE was performed 6 weeks after the initial operation. Control cystoscopies were performed 3 and 6 months after initial tumor resection. Results: At 2nd look TUR (6 weeks post op) and at control cystoscopies 3 and 6 months following initial TUR in the white light group residual and/or recurrent carcinoma was detected in 20 of 51, in 24 of 48 and in 28 of 48 patients, respectively, and in the AFE group in 8 of 51, in 10 of 47 and in 17 of 47 patients, respectively. The differences were statistically significant (p=0.005, p=0.002 and p=0.01, respectively). Three patients in the white light and four patients in the AFE group were lost to follow up. Conclusions: AFE is a minimally invasive and inexpensive diagnostic procedure that significantly improves bladder tumor detection rates compared to standard white light endoscopy. In the present study AFE reduced the residual/recurrent tumor rate 6 weeks, 3 and 6 months after initial TUR by 59%, 58% and 38%, respectively.

The use of indocyanine green-doped albumin protein solders has been shown to vastly improve the anastomotic strength that can be achieved by laser tissue repair techniques, while at the same time minimizing collateral thermal tissue damage. However, the safety of the degradation products of the chromophore following laser irradiation is uncertain. Therefore, we studied the feasibility of using alternative chromophores in terms of temperature rise at the solder/tissue interface, the extent of thermal damage in the sourrounding tissue, and the tensile strength of repairs. Biodegradable polymer scaffolds of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid), using a solvent-casting and particulate-leaching technique. The porous scaffold acted as a carrier to the traditional protein solder composition of serum albumin and an absorbing chromophore mixed in deionized water. Two commonly used chromophores, indocyanine green and methylene blue were investigated, as well as blue and green food colorings. Temperature rise at the solder surface and at the interface between the solder and tissue were monitored by an IR temperature monitoring system and a type-K thermocouple, respectively, and the extent of thermal damage in the underlying tissue was determined using light microscopy. As expected, temperature rise at the solder/tissue interface, and consequently the degree of collateral thermal tissue damage, was directly related to the penetration depth of the laser light in the protein solder. Optimal tensile strength of repairs was achieved by selecting a chromophore concentration that resulted in a temperature of 66 ± 3°C at the solder/tissue interface.

Laser tissue welding involves the partial denaturing and renaturing of the collagen triple helical structure. Although the mechanisms of laser tissue welding are not well understood, water in tissues plays an important role in the process. High quality welding of human and porcine aorta tissue have been achieved using NIR lasers tuned to the water absorption band around 1450 nm. Fluorescence and Raman spectra from welded and non-welded regions are compared for ex vivo human and porcine aorta tissues. The fluorescence from the outer surface of welded aorta was substantially weaker than the fluorescence from the non-welded region. The Raman spectra from the welded and non-welded tissue regions appeared similar in the energies of the observed vibrational levels but the intensity of the fluorescence wing was considerably greater from the outer surface of the welded region as compared to the non-welded region. For the outer surface of the aorta, the emission intensity from the welded region was larger than for the non-welded region.

The ability to reproduce strong repairs is essential to establishing the reliability of laser-tissue soldering techniques and advancing their use to the clinical setting. While some thermal damage is necessary to achieve a viable solder-tissue bond, excessive thermal damage leads to decreased flexibility and strength of the repair. In addition, if the temperature at the solder/tissue interface is too low, inadequate solder-tissue bonding will occur to provide a strong repair. This suggests the presence of an optimal temperature for laser-tissue repair. The choice of solder material presents another challenge to the reproducibility of strong repairs. The emerging use of chromophore-enhanced solder-doped polymer scaffolds offers numerous advantages over more traditional liquid and solid solders composed of serum albumin and an absorbing chromophore mixed in deionized water. Polymer scaffolds, fabricated from poly(L-lactic-co-glycolic acid) using a solvent casting and particulate leaching technique, are porous enough to absorb serum albumin and can also be doped with various hemostatic and thrombogenic agents to aid in tissue healing. Use of the polymer scaffolds allows one to combine the strength of solid solders and the flexibility of liquid solders without the common “runaway” problems. An in vitro study was performed to correlate tissue temperature with the tensile strength of arterial repairs formed using the chromophore-enhanced solder-doped polymer scaffolds. Laser irradiance was varied and the solder surface and solder/tissue interface temperatures were monitored by an IR temperature monitoring system and a type-K thermocouple, respectively. The solder/tissue interface temperature required for optimized tensile strength was determined to be 67 ± 5°C. This value was in agreement with previous studies using serum albumin solders alone, where the optimal solder/tissue interface temperature was found to be 65°C.

The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

A study was conducted to determine the feasibility of using alternative chromophores in light-activated surgical adhesives. Two commonly used chromophores, indocyanine green (ICG), and methylene blue (MB) were investigated, as well as three different food colorings: red #40, blue #1, and green food coloring consisting of yellow #5 and blue #1. The study consisted of three components. First, the absorption profiles of the five chromophores, both diluted in deionized water and bound to protein, were recorded with a UV-Vis-NIR spectrophotometer. Second, the effect of accumulated thermal dosages on the stability of the absorption profiles was investigated. Third, the stability of the absorption profiles of the chromophore solutions when exposed to ambient light for an extended period of time was investigated. The peak absorption wavelengths of ICG, MB, red #40, and blue #1, were found to be 780 nm, 665 nm, 500 nm, and 630 nm respectively. The green food coloring had two absorption peaks at 417 nm and 630 nm, corresponding to the two dye components comprising this color. The peak absorption wavelength of the ICG shifted to 805 nm when bound to protein. ICG and MB showed a significant decrease in absorbance units with increased time and temperature when heated to temperatures up to 100 degrees C. Negligible change in absorption with accumulated thermal dose was observed for any of the three food colorings investigated. Photobleaching was observed in both ICG and MB solutions with exposure to a white light source. An 88% decrease in absorption was seen in ICG deionized water solution after 7 days of exposure with a corresponding 33% decrease in absorption seen in the MB deionized water solution. A negligible drop in absorption was observed from exposure to ambient light for a 12-week period with the three food colorings investigated.

Ex vivo specimens of human and porcine aorta and skin were welded using either Cr⁴⁺:YAG or Erbium fiber lasers tuned to the water absorption band at 1440-1460 nm. Welding was performed without the use of protein solders or glues. Welding efficacy was monitored by measuring the tensile strength of the welded tissue and the extent of collateral tissue damage. Full thickness tissue bonding with no collateral damage was observed with porcine aorta samples. The optimum tensile strength for porcine and human aorta was 1.33 ± 0.15 kg/cm² and 1.13 ± 0.27 kg/cm² respectively for welding at 1460 nm, while that for porcine and human skin was 0.94 ± 0.15 kg/cm² and 1.05 ± 0.19 kg/cm² respectively achieved with welding at 1455 nm. The weld strength as a function of laser wavelength demonstrated a correlation with the absorption spectrum of native water suggests that absorption of light by water in the tissue plays a significant role in laser tissue welding.

Laser tissue welding with albumin solder/indocyanine green (ICG) dye is an effective technique in surgical reconstruction. This study was carried out in vitro to find optimal ICG concentration and power density (PD) in laser assisted vascular anastomosis (LAVA). Fresh porcine carotid arteries incised into vascular strips (n = 120) were welded by diode laser in end-to-end with 50% albumin solder of 0.01, 0.1, and 1.0 mM ICG and at power density of 27.7, 56.7, and 76.9 W/cm². Direct temperature was measured by inserting thermocouples outside and inside vessel. Tensile strength was tested immediately and histological study was performed. Temperature (both outside and inside vessel) significantly gradually decreasd (p < 0.01) with the increasing of ICG concentration at PD 56.7 W/cm². Tensile strength significantly gradually decreased (p < 0.01) with increasing of ICG concentration at PD 56.7 W/cm². Histological study showed minimal thermal injury limited to adventitia of vessels and no appreciable difference in all groups. We find that ICG concentration within solder is most important factor affecting both tissue temperature and tensile strength during laser vessel welding. The optimal balance between stronger strength and minimal thermal injury of vessel may be achieved primarily by using PD 56.7 W/cm² at 0.01 mM ICG within solder during LAVA.

To develop the catheter-based laser vascular welding device against aortic dissection, we studied fundamental characteristics of the laser vascular welding for aorta dissection model in vitro with the scattering light monitoring to obtain welding proceedings. We employed the laser vascular welding by means of the combination of the diode laser irradiation and indocyanine green (ICG) stain to the dissected vessel surface in a swine aortic dissection model to obtain localized heat generation on the surface. The forward and backward scattering lights of the diode laser from the welding portion were measured during the laser irradiation. The breaking stresses of the welded aortic pieces were measured. The breaking stress of 170gf/cm² obtained with the 425W/cm², 2.4s irradiation may be strong enough to the successful therapy for aortic dissection regarding to the dissecting force caused by blood flow. By analyzing forward and backward scattering lights, we could observe the occurrence of water evaporation in the welding portion, the bleaching of the ICG and the carbonization of the welding portion. Then we could monitor the proceedings of the welding process. The temperature estimation of the welding portion and the microscopic observation revealed that the mechanism of our welding may be basically elastic fiber entwining. We think our vascular welding with the scattering light monitoring of the welding process has the potential to apply catheter-based therapy for aortic dissection.

Background and objectives: Conventional methods for microvascular anastomosis are normally based on suturing, using special thin nylon sutures. These methods suffer from major drawbacks, which include: anastomosis, which is not watertight, and sutures or clips that cause an inflammatory response. In order to obtain better results, we introduced a procedure based on CO₂ laser soldering. We tested the system on arteriotomy incisions in rat blood vessels, in vivo. Materials and methods: We used a fiber optic based laser soldering system, with a temperature control capability. Arteriotomy incisions of lengths 4±1mm were performed on the femoral arteries of 48 wistar rats: 24 rats in the control group (suture) and 24 rats in the test group (laser soldering). We conducted two follow-up periods: 7 days and 21 days after the surgical procedure, for each group. Flow tests and histology examination were done in order to evaluate the quality of the procedures. Results: The patency rate was 84% for both groups, soldered and sutured. The sutured group showed a significant foreign body reaction (p < 0.05), which was not observed in the soldered group. We found no evidence of thermal damage in the soldered blood vessels. Conclusions: We can conclude that laser soldering is a less traumatic procedure, compared with the conventional suturing technique. It is potentially a faster technique and easier to master.

Soldered vascular anastomoses have been reported using several chromophores but little is known of the optimal conditions for microvascular anastomosis. There are some indications of the optimal protein contents of a solder, and the effects of methylene blue on anastomotic strength. The effects of varying laser power density in vivo have also been described, showing a high rate of thrombosis with laser power over 22.9Wcm^-2. However no evidence exists to describe how long the solder remains at the site of the anastomosis. Oz et al reported that the fibrin used in their study had been almost completely removed by 90 days but without objective evidence of solder removal. In order to address the issue of solder re-absorption from the site of an anastomosis we used radio-labelled albumin (I-125) incorporated into methylene blue based solder. This was investigated in both the situation of the patent and thrombosed anastomosis with anastomoses formed at high and low power. Iodine-125 (half life: 60.2 days) was covalently bonded to porcine albumin and mixed with the solder solution. Radio-iodine has been used over many years to determine protein turnover using either I-125 or I-131. Iodine-125 labelled human albumin is regularly used as a radiopharmaceutical tool for the determination of plasma volume. Radio-iodine has the advantages of not affecting protein metabolism and the label is rapidly excreted after metabolic breakdown. Labelling with chromium (Cr-51) causes protein denaturation and is lost from the protein with time. Labelled albumin has been reported in human studies over a 21-day period, with similar results reported by Matthews. Most significantly McFarlane reported a different rate of catabolism of I-131 and I-125 over a 22-day period. The conclusion from this is that the rate of iodine clearance is a good indicator of protein catabolism. In parallel with the surgery a series of blank standards were prepared with a known mass of solder to correct for isotope decay and allow data interpretation in terms of the actual amount of the solder remaining after a particular time. The anastomoses were formed with a known amount of solder and allowed to continue for up to 60 days before being sacrificed. The explanted vessels were then placed into a gamma counter and the amount of solder remaining expressed as a percentage. In this way the proportion of albumin left at the site of the anastomosis could be determined. By changing the power density of the laser it has been shown that the patency of soldered microvascular anastomoses is altered. By doing this it was hoped to determine any effect thrombosis might have on solder re-absorption. In addition the explanted vessels were inspected for inflammation, patency and aneurysm formation.

Completely sutureless end-to-end large bowel anastomoses were successfully performed in New Zealand white rabbits by using 1064 nm, 0.4-W power pulsating Nd:YAG laser to produce welding. Purpose: The aim of this study was to assess the results of our whole experimental data and summarize our experimental work on laser colon anastomosis. Methods: This experimental study investigated integrity of anastomosis, degree of narrowing, macroscopic appearance, microscopic findings, animal body weight change, and collagen concentration of laser colon anastomoses, compared with those of conventional sutured anastomoses up to ninety postoperative days. Results: Bursting pressures of laser anastomoses were at first low and came to be equivalent at seven days, but the laser group exhibited a consistent narrowing tendency. However, laser anastomoses demonstrated fewer and milder adhesions, and animals showed a better recovery of body weight. Histologically, laser anastomoses showed better layer-to-layer reconstitution without foreign body response and with less fibrosis. Difference in collagen concentration did not reach statistical significance. Conclusion: The technique of laser anastomosis presents a promising alternative to suturing in reconstitution of the large bowel.

Introduction: Laparoscopic pyeloplasty is used for the repair of uretero-pelvic junction (UPJ) obstructions. Our aim was to do it using laser tissue soldering. Materials and Methods: We developed a tissue bonding system based on a CO₂ laser, a temperature detector and infrared transmitting optical fibers, to obtain temperature controlled laser soldering of incisions. The system was then adapted for laparoscopic soldering of ureters of pigs. Results: We successfully carried out laparoscopic pyeloplasty in a porcine model, using a procedure based on CO₂ laser soldering. Conclusions: Laparoscopic laser soldering was found to be faster than suturing, it was easier to use and provided watertight bonding. This technique will be useful in other surgical procedures.

Laser activated tissue solders have been used for sutureless anastomosis in various contexts. Solders were initially developed in response to the finding that the use of lasers alone caused vessel damage resulting in aneurysm formation and medical damage. Many reports exist of the use of lasers to perform micro-anastomoses, but little has been reported on the use of laser tissue solder in the formation of medium sized vessel anastomoses or in vivo. This group has recently developed a methylene blue based albumin solder for use in vascular anastomoses. The early work concentrated on a rabbit carotid end-to-end model. More recently this has progressed into its application in medium sized vessels. The use of PTFE is common in clinical practice particularly relating to peripheral vascular reconstruction or vascular access surgery. In these instances conventional surgical techniques applied to PTFE will result in excessive bleeding at the site of the anastomosis. Suture materials commonly used such as polypropylene or polyamide leave holes in such prostheses. To compound the problem patients are often anticoagulated or suffer impaired platelet function, improving the chances of graft survival, but increasing bleeding time, the time required to achieve haemostasis and also the post operative complications related to bleeding such as haematoma formation. It was therefore intended to apply the techniques of soldered vascular anastomoses to such a scenario, by reinforcing the anastomotic suture line of grafts placed in an animal model, with MB based solder. The bleeding times, overall operating times and postoperative complications were then analyzed and compared to sutured controls.

In the past, we have successfully used laser soldering for bonding cuts in the skin of medium and large size animal models. In this work, we have used the same method for bonding cuts on the backs of rabbits and mature pigs model. Cuts were created in dorsally depilated skins of rabbits and mature pigs. 47% bovine serum albumin (BSA) solder was applied onto the approximated edges of each cut, using a special approximation device. An infrared fiberoptic CO₂ laser system was used to heat a spot on the cut, under good temperature control, to 65°C for 10 seconds. Other glued or sutured cuts, served as controls. Immediate tensile strength measurements were done on bonded incisions in rabbit skins. We found that laser soldered incisions exhibited similar strength to one bonded by cayanoacrylate glue. No dehiscence of wound edges was found in both treatments. The laser soldering procedure was 25% faster then suturing. A 14-day follow up of the bonded pig skin incisions was carried out, using punch biopsies. We found better aesthetic appearance of the soldered incisions. We observed better and faster wound repair in the laser-soldered scars, using histological and molecular staining. The temperature controlled laser soldering offers immediate strength similar to that of cyanoacrylate glues and better aesthetic and wound healing properties, in comparison to suturing techniques. We have clearly demonstrated the potential of this novel technique, which will pave thw way for clinical studies.

The history of lasers in otolarygngolgoy-head and neck surgery (ORL) demonstrates the advances seen in the application of laser energies. This paper is the beginning of our review of the five pillars which support the long and mutually-beneficial relationship between laser technologies and ORL: (1) "necessity is the mother of invention" -- organ systems which require innovative approaches for diagnosis and treatment; (2) clinicians who seek and incorporate new technologies; (3) "feedback" effect of technology leading to changes in clinical care which may obviate the need for that technology itself; (4) "right place, right time" -- the close collaboration between corporate, clinical and basic science realms, and (5) financial. These principles provide the context for following the progressive application of laser energy in ORL for ablation, tissue-altering and most recently, sensing.

The aim of this project is the development of a microsurgical laser Doppler (LD) probe that simultaneously monitors blood flow and Electrocochleography (ECochG) from the round window of the ear. The device will prevent neurosensory hearing loss during acoustic neuroma surgery by preventing damage to the internal auditory nerve and to the cochlear blood flow supply. A commercially available 0.5 mm diameter Laser-Doppler velocimetry probe (LaserFlo, Vasamedics) was modified to integrate an ECochG electrode. A tube for suction and irrigation was incorporated into a sheath of the probe shaft, to facilitate cleaning of the round window (RW) and allow drug delivery to the round window membrane. The prototype microprobe was calibrated on a single vessel model and tested in vivo in a rabbit model. Preliminary results indicate that the microprobe was able to measure changes in cochlear blood flow (CBF) and ECochG potentials from the round window of rabbits in vivo. The microprobe is suitable for monitoring cochlear blood flow and auditory cochlear potentials during human surgery.

An optical tweezers system was used to study the mechanical characteristics of outer hair cell (OHC) and human embryonic kidney (HEK) cell plasma membranes. The effect of the cationic amphipath chlorpromazine (CPZ) on the equilibrium tethering force, (F_eq) force relaxation time constant,(τ) and effective membrane viscosity (η_eff) was measured. The F_eq for the OHC lateral wall plasma membrane was ~60 pN and was unchanged by addition of CPZ. A significantly greater τ value was observed in CPZ-treated OHCs (30.5 ± 12.6 s) than in control OHCs (19.0 ± 13.2 s). The F_eq and τ values for control HEK cells were >60% lower than the respective OHC values but increased by ~3 times following CPZ addition. Effective viscosity ranged between 1.49-1.81 pN•s/μm for CPZ-treated OHCs. This represents a decrease from reported control OHC membrane viscosities.

Laser surgical methods as an alternative to conventional surgery for the treatment of recurrent chronic polypous sinusitis have been widely established over the past few years. While feedback-controlled contact laser application causes little disruption to the tissue, the minimal-invasive approach is limited by the accessibility of recurrent polyps. We employ a semi-rigid applicator for the guidance of the laser fiber with an outer diameter of 4 mm, whose tip can be adjusted and fixed in a flexible manner before or while accessing the operative field. In addition to the laser fiber channel, two further integrated channels can be used for laser plume suction and for introducing a flexible micro-endoscope with an outer diameter of 1.3 mm. This new device enables the surgeon to apply laser energy in close proximity to an endoscope and smoke suction channel even in regions with limited accessibility, such as the maxillary sinus bottom or the frontal sinus recess. The single-handed use facilitates maneuvering this device in narrow endonasal cavities. The integrated micro-applicator presented here widens the scope of operative options for endonasal laser surgery. In addition to a better access to all regions of the paranasal sinuses following conventional endonasal sinus surgery, its use for treating locally limited chronic polypous sinusitis via natural drainage pathways as a primary surgical procedure bears considerable potential for further evaluation.

Much interest has been placed on the permanent reshaping of cartilage for facial reconstructive surgery using lasers. An alternate way to reshape cartilage is to heat the tissue in a water bath while maintaining the specimen in mechanical deformation. The objective of this study was to measure the circular bend angle of a cartilage specimen produced by varying the temperature and immersion time in a water bath. Rectangular cartilage specimens (18 x 4 x 1.5 mm) were bent in a semicircular jig (diameter 11 mm) and then immersed in a saline bath at temperatures between 50 - 80°C. The immersion times were 5, 20, 80, 160 and 320 seconds at each temperature. The distance between the ends of each specimen was measured before reshaping and at 15 minutes and 24 hours after immersion in order to calculate the resulting bend angle. The largest bend angle occurred in the specimen immersed in saline at 74°C for 320 seconds, illustrating a definite thermal influence on the physical shape of the cartilage sample. The critical immersion times and bath temperatures where definite shape change occurred were determined.

Dielectric properties of cartilage have received comparatively little interest and few studies have examined the effect of the applying electric currents to mechanically deformed cartilages. The objective of this study was to determine the dependence of shape change on electrode composition during a process we have described as “electroforming.” Porcine nasal septal cartilage specimens (16 x 5 x 2 mm) were mechanically deformed between two semicircular electrodes. Direct current (DC) current was applied to establish charge separation and electrical streaming potential. Voltage (<10 V) and application time (0-6 minutes) were varied, and shape change was measured using analytic representation. Surface features were evaluated using light microscopy. While shape change strongly correlated with voltage and time for all electrode materials, the voltage and application time that produced maximum shape change (curvature of the jig, ~ 160°) varied for each material. Aluminum is more effective for electroforming than gold as it yields the lowest set of plateau values. Surface features indicated that electrodeposition occurs depending upon the voltage and the standard reduction potential of electrodes. The results from this study provide insight into the dependence of shape change on the external electrical environment of cartilage and how optimal shape change can be produced with nominal electrodeposition.

A new non-thermal method of altering the shape of cartilage to create mechanically stable new morphologies was developed using low DC voltage electric fields (electroforming). In cartilage electroforming, voltage is applied to the surfaces of cartilage specimens held in mechanical deformation by a jig made of two large surface area electrodes for 2-5 minutes. Following removal of the specimen from the jig, permanent shape change is observed. Electric resistance and mechanical stress were monitoring during electroforming. Strong correlation between resistance and stress was observed suggesting that the mechanism of stress relaxation is electrically mediated and may provide a mean to monitor electroforming.

Laser irradiation may cause a proliferative response in cartilage leading to new, less invasive treatment modalities for diseases such as osteoarthritis. Our previous studies have shown that laser irradiation causes chondrocytes to proliferate on the periphery of the laser-irradiated region and this effect is dose dependent. In this study, flow cytometry was used for cell counting because the colorimetric assay used previously was relatively insensitive to small proliferative responses. Ex-vivo rabbit nasal septal cartilages were harvested and subjected to one of three treatments: laser irradiation, heating, or mechanical modification. Specimens were irradiated with an Nd:YAG laser (λ=1.32μm, 4-16 sec, 6 W/cm²), heated by immersion in saline or contact heating, and mechanically modified by scoring with a scalpel or crushing with a metal stamp. Specimens were incubated for 7-21 days in growth media containing 10μM Bromodeoxyuridine (BrdU) then chondrocytes were isolated with enzymatic digestion. Cells were incubated with fluorescein conjugated anti-BrdU monoclonal antibody (Roche Diagnostic, Basel, Switzerland) and counterstained with propidium iodide (PI). Fluorescent-activated cell counting was performed by flow cytometry (λ=488 nm, Model BD LSR Flow Cytometer, Becton Dickson) identifying cells with emissions measured at 515 nm (anti-BrdU) and 620 nm (PI). Analysis showed a population of cells in S-phase of the cell cycle indicating these cells had undergone cell division. This provides further evidence that laser irradiation causes a proliferative response in chondrocytes and may lead to new treatments for degenerative articular diseases and disorders.

Osteoarthritis is a heterogeneous disease characterized by progressive loss of cartilage. The earliest biochemical features, which precede gross pathological changes, include non-uniform loss of proteoglycans associated with increase of water content in tissue and finally, fibrillation of the tissue's collagen network. Loss of proteoglycans decreases the ability of cartilage to withstand compressive loading and makes the tissue softer and more susceptible to wear and fibrilation. If the early loss of proteoglycans is detectable by a non-invasive optical technique, progression of the disease may be arrested using, for example, pharmacologic or surgical intervention. When an electric field is applied to cartilage by an electrical stimulator, the current-generated stress gradients are produced and stress deformation occurs. Since differential phase optical coherence tomography is very sensitive to subsurface stress deformation, we propose to stimulate cartilage electrically and detect stress gradients before gross signs of cartilage degeneration appear. Detection of depth-resolved electromechanical stress gradients in cartilage using differential phase optical coherence tomography may be useful to monitor non-invasively cartilage degeneration. Since the streaming potential and other electrokinetic effects in cartilage are directly proportional to proteoglycan density, application of an electric field in cartilage combined with depth-resolved phase sensitive optical measurements may provide a sensitive indicator of cartilage viability on the molecular-level.

The smaller anatomy and limited access to instrumentation pose a challenge to the pediatric airway surgeon. The enhanced precision and ability to photocoagulate tissue while operating with the laser enhances the surgeon’s ability to successfully treat unique pediatric conditions such subglottic hemangiomas, congenital cysts, respiratory papillomatosis, and laryngeal or tracheal stenosis. Due to its shallow tissue penetration and thermal effect, the carbon dioxide (CO2) laser is generally considered the laser of choice for pediatric airway applications. The potential for increased scarring and damage to underlying tissue caused by the greater penetration depth and thermal effect of the Nd:YAG and KTP lasers preclude their use in this population. In this review, we will describe the specific advantages of using lasers in airway surgery, the current technology and where the current technology is deficient.

Composite cartilage grafts were excised from New Zealand rabbit ears. An incision through the perichondrium exposed a 5mm wide strip of cartilage on the posterior auricle surface. Flat specimens were manually deformed with a jig and maintained in this new position during irradiation. The exposed cartilage was irradiated on the concave surface with an Nd:YAG laser (1064 nm, 3 mm spot) at 10W, 15W, 20W. Cryogen spray (CSC) was applied to the convex, non-irradiated surface of the tissue to reduce thermal injury to the graft. The specimens were maintained in a deformation for 15 minutes after irradiation and serially examined for 14 days. Reshaping and acute thermal injury were assessed by photography. For 15 and 20 W, CSC was delivered: (1) continuously (constant delivery of cryogen active through the entire irradiation period) and (2) under control (cryogen released when surface reached 40°C, and (3) a third group received no CSC. 20W with no CSC caused full thickness injury, while 15W with no CSC caused only minor epidermal thermal injury. The specimen exposed to 20W with controlled CSC retained its new shape to the highest degree over all others, and thermal injury was minimal. Although most levels of laser and CSC yielded a high degree of reshaping over an acute time period, after 14 days specimens exposed to 15W or 20W retained shape better than those treated at 10W.

Coblation is a unique method of delivering radiofrequency energy to soft tissue for applications in Otolaryngology (ENT). Using radiofrequency in a bipolar mode with a conductive solution, such as saline. Coblation energizes the ions in the saline to form a localized plasma near the target tissue. The plasma has enough energy to dissociate water molecules from the saline, as well as ionizing the saline salt species, thus forming chemical conditions leading to the breaking of the tissue's molecular bonds. Energetic electrons in the plasma also possess enough energy to directly dissociate tissue chemical bonds. The overall effect results in tissue ablation and localized removal or reduction of tissue volume. The heat dissipated in the process, aided by continual cooling from the surrounding saline solution, produces tissue temperature raises of approximately 45 - 85°C, significantly lower than traditional radio-frequency techniques. Coblation has been used for Otolaryngological applications such as Uvulopalatopharyngoplasty (UPPP), tonsillectomy, turbinate reduction, palate reduction, base of tongue reduction and various Head and Neck cancer procedures. The decreased thermal effect of Coblation has led to less pain and faster recovery for cases where tissue is excised. Several clinical studies have shown the benefits of using Coblation for both extra and intra-capsular tonsillectomy.

Urinary tract symptoms related to benign prostatic hyperplasia affect 70% of men older than 70 years. Complications are common problems and a significant cause of morbidity in this population, placing a considerable burden on health services. In the early 1990s laser treatment of benign prostatic hyperplasia became widely used after the introduction of the side-firing neodym: YAG laser. However, because of technical limitations and inferior results compared to classical transurethral resection of the prostate many Urologists became desinterested in this device. With the introduction of the holmium: YAG laser a new laser generation became available for use in Urology. Beside several other applications the holmium: YAG laser can be used for incision, ablation, resection, and more recently enucleation of the prostate. In this paper we reviewed the current literature regarding the holmium: YAG laser resection and enucleation of the prostate compared to transurethral resection of the prostate and open prostatectomy. The holmium: YAG laser technique is an effective and durable surgical alternative to standard transurethral resection of the prostate. Interestingly, enucleation of the prostate with this device seems to be a safe and effective procedure for large prostatic adenomas, it may become an attractive alternative to open prostatectomy.

Completeness and certainty of tumor detection are very important issues in clinical oncology. Recent technological developments in ultrasound, radiologic and magnetic resonance imaging diagnostics are very promising, but could not improve the detection rate of early stage malignancies. One of the most promising new approaches is the use of 5-aminolevulinic acid, a potent photosensitizer, in photodynamic diagnosis and therapy. 5-aminolevulinic acid is meanwhile a well-established tool in the photodynamic diagnosis of bladder cancer. It has been shown to improve the sensitivity of detection of superficial tumors and carcinoma in situ, which enables to reduce the risk of tumor recurrence related to undetected lesions or incomplete transurethral resection of the primary lesions. The use of 5-aminolevulinic acid is steadily expanding in diagnostics of urological malignancies. First clinical results are now reported in detection of urethral and ureteral lesions as well as in urine fluorescence cytology. Furthermore, due to the selective accumulation in transitional cell carcinoma of the bladder, 5-aminolevulinic acid may be an ideal candidate for photodynamic therapy in superficial bladder cancer. Summarizing the data of multiple clinical trials, 5-aminolevulinic acid is a promising agent in photodynamic diagnostics and treatment of superficial bladder cancer.

Benign prostatic hyperplasia (BPH) is a common disease in males older than 50 years of age. 75-80% of this population is considered to have some degree of BPH causing clinical symptoms and requiring urological treatment. Transurethral resection of the prostate (TUR-P) is currently the standard surgical treatment modality for BPH. In an attempt to minimize the need for hospitalization and the associated perioperative and postoperative morbidity, alternatives have been sought. Various types of Laser techniques such as interstitial Laser cogaulation and side-firing technology have been proposed. Numerous studies have shown that Laser procedures safely and effectively reduce the volume of the prostate. Intra- and postoperative bleeding are nearly unknown complications for Laser procedures, whereas this is the most relevant complication for the TUR-P. Due to significant tissue edema after Laser treatment, patients commonly show delayed time to void adequately, and therefore, catheter drainage is often necessary for 3 to 21 days. Retrograde ejaculation is reported to occur less (0 - 10%) compared to TUR-P (> 60%). Urinary tract infections are very common after interstitial laser coagulation. Although not many long-term clinical data are available, various studies have shown that BPH patients improve in symptom score, flow rate and post-void residual up to 3 years after Laser treatment. This paper presents a concise review of efficacy, advantages and disadvantages of the most frequently used Laser techniques as well as the long-term clinical data compared to TUR-P.

The use of minimally invasive treatments for benign prostatic hyperplasia (BPH) have been introduced into the medical community. Over the last decade several minimally invasive treatment techniques have been approved for use. In particular, interstitial laser coagulation (ILC) has shown pomise as an alternative to the current gold standard, transurethral resection of prostate (TURP). Studies show ILC to have equal efficacy as TURP while causing less side effects. Future technical advances as well as increased physician experience with ILC could lead to the replacement of TURP as the gold standard in trestment of BPH.

Photodynamic Therapy (PDT) using Photofrin has been recently approved by the FDA for the treatment of esophageal cancer and Barrett's esophagus. A major limitation of PDT for Barrett's esophagus is the development of esophageal stricture in up to 53% of patients. Mechanisms of PDT stricture formation have not been elucidated. The major difficulty is the lack of an animal model for PDT-induced stricture. We have used a pig model in which the esophagus is very similar to that of the human esophagus. Two (Scrofa) domestic pigs were injected with Photofrin at dosage of 2 mg/kg 48 hours prior to photoactivation with 630 nm light. Following anesthesia, a laser probe (2.5 cm in length) was passed through the oral cavity to approximately the mid-point of the esophagus via an endoscope. Light energy (400 Joules (J)/cm) was delivered as a single dose in one pig or repeated at 72 hours in the second pig. In this pig model, upper endoscopy, Barium swallow and pathological studies confirmed stricture formation following esophageal PDT exposure of 400 J as one or two fractions. We believe that this is the first animal model created to study esophageal strictures resulting from PDT.

Advances in optical and computer technology have enabled the development of a device that utilizes white-light reflectance spectrophotometry to measure capillary hemoglobin saturation in intestinal mucosa during colonoscopy. Studies were performed using the colon oximeter in anesthetized animals and patients undergoing colonoscopy. Mucosal hemoglobin saturation in the normal colon (mean +/- S.D.) is 72% +/- 3.5%. In an animal model, ischemia via arterial ligation and hypoxemia via hypoxic ventilation each result in a decrease of over 40% in the mucosal saturation. In human patients with colon polyps, ischemia induced by epinephrine injection, stalk ligation using a loop, or clipping of the polyp stalk each result in a decrease of over 40% in the mucosal saturation (p<0.02). In contrast, saline injection does not decrease the mucosal saturation (p=N.S.). A patient who previously underwent partial colectomy with sacrifice of the inferior mesenteric artery had a saturation of 55% in the remaining sigmoid colon, with normal values in the superior mesenteric artery territory (p<0.05). A novel device for measuring capillary hemoglobin saturation in intestinal mucosa during colonoscopy is capable of providing reproducible measurements in normal patients and clearly detects dramatic decreases in saturation with ischemic and hypoxic insults.

X-ray mammography has been the major imaging modality in breast cancer detection for years, despite its high false diagnosis rate for malignant tumors and harmful radiation. In the last decade, optical imaging has been emerging as a promising method for breast cancer detection. Using near infrared (NIR) light ranging from 690 nm to 900 nm, an optical device can measure functional properties of breast tissue, such as total hemoglobin concentration (HbT) and oxygen saturation (SO2). Cancers tend to have higher levels of HbT because of their greater vascularization, and lower SO2 because of greater oxygen consumption, than normal tissue. Thus the NIR technology could be useful in breast cancer detection. In addition, optical detection is totally noninvasive and safe, and can be low cost. Photonify Technologies Inc. has developed an optical device for real-time two-dimensional mapping of HbT and SO2 in breast tissue. The device has been tested in a pilot clinical study for a group of 50 patients at the Department of Radiology of the Masachusetts General Hospital at Harvard Medical School. Preliminary results suggest that contrast-normalized standard deviations in HbT and SO2 might be good indicators for breast cancer detection. A patient may have a higher risk to have cancer in a breast portion where the normalized standard deviation in either HbT or SO2 is greater than 0.3. We demonstrate 92% diagnostic sensitivity and 66% specificity in detecting ductal carcinoma, either invasive or in situ. The device may potentially be used as an adjunctive tool with mammography to reduce unnecessary biopsies.

Early detection and treatment of breast cancer is least costly in terms of dollars, morbidity and mortality. With new early detection x-ray technology, tumors can be found, diagnosed and treated at a much smaller size than is currently possible. This paper proposes the development of a high resolution, high quality imaging system. It is a laser-driven x-ray system with time-gated detection that removes scattering noise in the image and produces resolution on the order of 10 μm. This higher resolution and higher image quality will enable the detection of one or two millimeter tumors hopefully detecting them before metastasis. We also propose that tumor detection should be followed by an immediate needle-directed, optical fiber biopsy to instantly determine if cancer is present and, if present, the tumor should immediately be given a lethal treatment of laser or x-radiation through the same needle using fiber optics or hollow waveguides. This technology will help prevent multiple interventions resulting in both the lowest overall cost and a more efficacious therapy. The approach can be stopped at the first negative (benign) indication and will help forestall repeated examination as well as reduce patient anxiety.

The goal of our study is to develop a time-dependent three-compartment model of beacon delivery to simulate the distribution of Indocynanine Green (ICG) in cancer tissue by using JSIM development environment of model simulation and data analysis. We studied the major factors that contribute to distribution of ICG in our model. The simulation results show that our time-dependent three-compartment model can describe the delivery of ICG injected intravenously into the human subject and assist in breast cancer detection.

A frequency-domain photon migration (FDPM) imager employing an image-intensified CCD camera for fast data acquisition on a large tissue-mimicking phantom (1087 ml) is described. Fluorescence-enhanced imaging is performed employing frequency-domain techniques at 100 MHz in order to obtain the boundary measurements of phase and amplitude and to recover the interior optical maps using the first principles of light propagation. The effect of refractive-index parameter in the boundary condition of the light propagation model is not significant due to the large phantom volume and its curvilinear nature. Initial experiments were performed under perfect (1:0 contrast) and imperfect (100:1 contrast) uptake cases using indocyanine green as the contrast agent. Preliminary 3D image reconstructions using the approximate extended Kalman filter (AEKF) algorithm are presented.

The purpose of these preliminary experiments was to calculate the activation energy and the frequency factor constants of the Arrhenius equation for prediction of the denaturation zone produced by laser interstitial thermotherapy in female breast tissue models. In a first step, pairs of parameters consisting of the activation energy (ΔE) and frequency factor (A) were calculated for different half denaturation times at 50°C and 60°C. Pairs of parameters were eliminated if the calculated time of denaturation at 70°C was excessively short (<0.1s). In a second step, denaturation was calculated over time for each remaining pair of parameters using temperature measurements performed during a laser heating experiment in ex-vivo porcine mammary chain tissue. The zone of denaturation in the tissue after laser heating was 2.0 cm x 3.5 cm. One pair of Arrhenius parameters was chosen whose denaturation plot showed no denaturation outside the experimentally-observed denaturation zone, 50% denaturation at the border of the experimental denaturation zone, and 100% denaturation within the experimental denaturation zone after 1200 seconds. The activation energy and frequency factor which best fit our experimental data were ΔE=3.02x10⁵ J mol^-1 and A=1.18x10⁴⁴ s^-1, respectively. These values fall within the general range given in the literature.

There have been many innovations and technological advancements in balloon angioplasty since its introduction in the late 1970’s, but percutaneous intervention on a totally occluded artery is still a challenge to the vascular interventionalist. Catheter-based intervention that avoids an invasive surgical procedure is a clear and desired advantage for the patient. A total occlusion challenges the interventionalist because the path of the artery can not be seen in the occluded vessel since the flow of the radiopaque contrast media is blocked. Optical coherence reflectometry techniques have been shown to be able to differentiate between artery wall and occlusive materials allowing the lumen of the blocked artery to be seen inside the occlusion. During this past year, a guide wire that uses OCR for forward-looking guidance has received FDA 510(k) clearance and future generation devices that add radio frequency ablation capabilities are in clinical trials. Clinical results show that these new tools are addressing this subset of patients with percutaneous interventions with safety and effectiveness.

Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular spectrofluorimetry. It may also be possible to use macrophage-targeted PDT to therapeutically modify inflammatory cell-laden VPs leading to plaque stabilization and reduction of sudden cardiovascular death.

ELAN is a new method for treating atherosclerotic vessels. Its purpose is to restore wall flexibility by removing arterial wall tissue from the outer arterial layer. This leads to expansion of the narrowed vessel resulting in increased blood flow. We generated cuts in dissected arteries of sheep and pigs by photo-ablation with an ArF-Excimer Laser operating at a wavelength of 193 nm. During the cutting process the vessel diameter was monitored by measuring the running time of the laser induced pressure transients with a pressure transducer lying under the artery. A nearly linear increase of the diameter dependent on the residual wall thickness was found with a maximum increase of vessel diameter about 10%. We also observed that the arterial wall maintains stable to very small residual wall thicknesses i.e. deep cutting. To support the experiments and to test different geometries of tissue removal we performed FEM-Analysis. We simulated vessel deformation and the total strain depending on the depth, width and number of cuts in the outer artieral wall. We also found a significant increase of the "lumen" in a model with atherosclerotic shape obtained from a histological section.

A RF ablation guide wire with an optical coherence reflectometry guidance system has been developed to percutaneously open total occlusions in arteries. The ablation energy does generate heat as does any electrosurgical application of RF energy. Prior histology studies using this device had shown that the heat generated in the total occlusion was not a clinical concern. In this study, a novel fiber-optic based temperature measurement sensor was used to actually measure the temperature rise in an artery in vivo in a porcine model. The optical temperature measurement system is immune to RF emissions and interference and could be delivered in the same catheter as the guide wire. Temperature rises in the occluded arteries in a worst-case scenario were shown to be less than 10°C, localized to the volume adjacent to the ablation tip, and the temperature returned to ambient within a few seconds after the energy was no longer applied. The temperature data is in agreement with the prior histology studies.

The feasibility to detect and characterize vulnerable plaques by Optical Coherence Tomography (OCT) is currently under investigation. It has been shown that in some cases, by using qualitative criteria, the OCT images can be used to differentiate between different types of plaque. However, the quality of the image and the experience of the observer greatly influences the interpretation of the images, which indicates the necessity of a quantitative analysis of the OCT data. As OCT measures the depth resolved backscattering it is possible to calculate the light attenuation coefficient (μ_t) in the different areas in the image and use that to identify the different plaque constituents in the target tissue. In this study, we present in vitro data on μ_t, measured in atherosclerotic lesions.

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) was tested for the treatment of acne vulgaris. Patients with acne were treated with ALA plus red light. Ten percent water solution of ALA was applied with 1,5-2 h occlusion and then 18-45 J/cm² 630 nm light was given. Bacterial endogenous porphyrins fluorescence also was used for acne therapy. Treatment control and diagnostics was realized by fluorescence spectra and fluorescence image. Light sources and diagnostic systems were used: semiconductor laser (λ=630 nm, P_max=1W), (LPhT-630-01-BIOSPEC); LED system for PDT and diagnostics with fluorescent imager (λ=635 nm, P=2W, p=50 mW/cm²), (UFPh-630-01-BIOSPEC); high sensitivity CCD video camera with narrow-band wavelength filter (central wavelength 630 nm); laser electronic spectrum analyzer for fluorescent diagnostics and photodynamic therapy monitoring (LESA-01-BIOSPEC). Protoporphyrin IX (PP IX) and endogenous porphyrins concentrations were measured by fluorescence at wavelength, correspondingly, 700 nm and 650 nm. It was shown that topical ALA is converted into PP IX in hair follicles, sebaceous glands and acne scars. The amount of resulting PP IX is sufficient for effective PDT. There was good clinical response and considerable clearance of acne lesion. ALA-PDT also had good cosmetic effect in treatment acne scars. PDT with ALA and red light assist in opening corked pores, destroying Propionibacterium acnes and decreasing sebum secretion. PDT treatment associated with several adverse effects: oedema and/or erytema for 3-5 days after PDT, epidermal exfoliation from 5^th to 10^th day and slight pigmentation during 1 month after PDT. ALA-PDT is effective for acne and can be used despite several side effects.

An ex vivo study was conducted to compare the tensile strength of tissue samples repaired using three different techniques: (i) application of a scaffold-enhanced light-activated albumin protein solder, (ii) application of a scaffold-enhanced n-butyl-cyanoacrylate adhesive, and (iii) repair via conventional suture technique. Biodegradable polymer scaffolds of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) and salt particles using a solvent-casting and particulate-leaching technique. Group I porous scaffolds were doped with protein solder composed of 50%(w/v) bovine serum albumin solder and 0.5mg/ml indocyanine green dye mixed in deionized water, and activated with an 808-nm diode laser. Group II scaffolds were doped with n-butyl-cyanoacrylate, and required no light-activation. No stay sutures were required for Group I or II experiments. Group III repairs were performed using a single 4-0 suture. Thirteen organs were tested ranging from skin to liver to the small intestine, as well as the coronary, pulmonary, carotid, femoral and splenic arteries. Acute breaking strengths were measured and the data were analyzed by Student’s T-test. Using the protein solder of Group I, repairs formed on the ureter were most successful followed by small intestine, sciatic nerve, spleen, atrium, kidney, muscle, skin and ventricle. The strongest vascular repairs were achieved in the carotid artery and femoral artery. Overall, the tensile strength of Group III repairs performed via suture techniques were equivalent in magnitude to that of Group I repairs, however, a larger variance was observed in the suture repair group. Group II repairs utilizing the cyanoacrylate-doped scaffold all performed extremely well. Bonds formed using the Group II adhesive were approximately 30% stronger than Group I and III organ repairs and approximately 20% stronger than Group I and III vascular repairs. Application of the polymer scaffold assists in tissue alignment and reduces problems associated with adhesive runaway from the repair site. Scaffold-enhanced adhesives could possibly be used as a simple and effective method to join tissue together quickly and effectively in an emergency situation, or as a substitute to mechanical sutures or staples in many clinical applications.

Over the last decade advances in laser and semiconductor technology has allowed the investigation of terahertz region of the electromagnetic spectrum as a potential tool for medical imaging. The terahertz frequency range covers the far infrared wavelengths and is sensitive to librational and vibrational modes of molecules. Terahertz radiation is non-ionizing and is not highly scattered like visible and near infrared light. Terahertz Pulsed Imaging (TPI) has already been demonstrated as an effective tool for differentiating between tissue types in particular normal skin and basal cell carcinoma in vitro. TPI may prove advantageous in distinguishing type, lateral spread and depth of tumors. Here we present recent ex vivo results obtained with a portable TPI system in a clinical setting. It is hoped that this technique could be applied to other epithelial tissues, which give rise to more than 80% of all adult cancers and include common cancers of the skin, oral cavity, breast, colon and prostate.

Objectives: The treatment of female urinary incontinence (UI) is a growing health care concern in our aging society. Publications of recent innovations and modifications are creating expectations. This brief review provides some insight and structure regarding indications and expected outcomes for the different approaches. Materials: Data extraction is part of a Medline data base search, which was performed for "female stress incontinence" from 1960 until 2000. Additional literature search was performed to cover 2001 and 2002. Outcome data were extracted. Results: (1) INJECTION OF BULKING AGENTS (collagen, synthetic agents): The indication for mucosal coaptation was more clearly defined and in the majority of articles limited to ISD. (2) OPEN COLPOSUSPENSION (Burch, MMK): Best long-term results of all operative procedures, to date considered the gold standard. (3) LAPAROSCOPIC COLPOSUSPENSION (different modifications): Long-term success rates appear dependent on operator skills. There are few long-term data. (4) NEEDLE SUSPENSION: (Stamey, Pareyra and modifications): Initial results were equal to Burch with less morbidity, but long-term success rates are worse. (5) SLING PROCEDURES (autologous, synthetic, allogenic graft materials, different modes of support and anchoring, free tapes): The suburethral sling has traditionally been considered a procedure for those in whom suspension had failed and for those with severe ISD. The most current trend shows its use as a primary procedure for SUI. Long-term data beyond 5 years are insufficient. (6) EXTERNAL OCCLUSIVE DEVICES (vaginal sponges and pessaries, urethral insert): Both vaginal and urethral insert devices can be effective in selected patients. (7) IMPLANTABLE ARTEFICIAL URETHRAL SPHINCTERS: Modifications and improvements of the devices resulted in improved clinical results regarding durability and efficacy. CONCLUSION: (1) The Burch colposuspension is still considered the gold standard in the treatment of female genuine SUI. There is a trend for the suburethral sling to be used as the primary procedure for this indication. Early outcome data are encouraging. New concepts such as use of metalic bone anchors and allograft material as well as the Tension free Vaginal Tape are under investigation. (2) Standardization of diagnostic and therapeutic interventions is prerequisite for any meaningful research. Randomized controlled prospective studies are essential to provide objectives regarding risks and benefits of new procedures and materials.