Proceedings Volume 3907

Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems X

R. Rox Anderson M.D., Kenneth Eugene Bartels D.V.M., Lawrence S. Bass M.D., et al.
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Proceedings Volume 3907

Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems X

R. Rox Anderson M.D., Kenneth Eugene Bartels D.V.M., Lawrence S. Bass M.D., et al.
View the digital version of this volume at SPIE Digital Libarary.

Volume Details

Date Published: 17 May 2000
Contents: 12 Sessions, 78 Papers, 0 Presentations
Conference: BiOS 2000 The International Symposium on Biomedical Optics 2000
Volume Number: 3907

Table of Contents

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Table of Contents

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  • Advances in Laser Skin Resurfacing
  • Laser Tissue Welding
  • Optical Diagnosis in Dermatology
  • Poster Session
  • Benign Prostatic Hyperplasia
  • Miscellaneous
  • Tissue Welding
  • Miscellaneous
  • Photodynamic Therapy
  • Miscellaneous
  • Laser Therapies
  • Laser Diagnostics
  • Lasers in Otology
  • Section
  • Miscellaneous
  • Section
  • Lasers in Otology
  • Miscellaneous
  • Advances in Laser Skin Resurfacing
  • Optical Diagnosis in Dermatology
  • Lasers in Otology
  • Section
Advances in Laser Skin Resurfacing
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Subsurface wrinkle removal by laser treatment in combination with dynamic cooling
Dilip Y. Paithankar, James C. Hsia, E. Victor Ross M.D.
Compared to traditional CO2 or Er:YAG laser resurfacing, sub-surface thermal injury to stimulate skin remodeling for the removal of wrinkles is attractive due to the lower morbidity associated with epidermal preservation. We have developed a technique that thermally damages dermal collagen while preserving the epidermis by a combination of infra-red laser irradiation and dynamic cooling of skin. Wound healing response to the thermal denaturation of collagen may trigger synthesis of fresh collagen and result in restoration of a more youthful appearance. The laser wavelength is chosen so as to thermally injure dermis in a narrow band at depths of 150 to 500 microns from the surface of the skin. The epidermis is preserved by a Candela dynamic cooling device (DCDTM) cryogen spray. Three-dimensional Monte Carlo calculations have been done to calculate the light distribution within tissue while taking into account light absorption and scattering. This light distribution has been used to calculate heat generation within tissue. Heat transfer calculations have been done while taking into consideration the cryogen cooling. The resulting temperature profiles have been used to suggest heating and cooling parameters. Freshly excised ex vivo pig skin was irradiated with laser and DCD at these heating and cooling parameters. Histological evaluation of the biopsies has shown that it is possible to spare the epidermis while thermally denaturing the dermal collagen. The modeling and histology results are discussed.
In-vivo experimental evaluation of nonablative skin remodeling using a 1.54-um laser with surface cooling
Serge R. Mordon, Alexandre Capon M.D., Collette Creusy M.D., et al.
Selective dermal remodeling using diode or 1.32 micrometer Nd:YAG lasers has been recently proposed for skin rejuvenation. This new technique consists in inducing collagen tightening and/or neocollagen synthesis without significant damage of the overlying epidermis. Such an approach requires (1) a cooling system in order to target dermal collagen with relatively good protection of the epidermal layer, (2) a specific wavelength for confining the thermal damage into the upper dermis (100 to 400 micrometer). Based on previous studies, demonstrating a better water absorption and a reduced melanin absorption at 1.54 micrometer compared to the 1.32 micrometer, this experimental study aimed to evaluate a new laser (co-doped Yb-Er:phosphate glass material, Aramis, Quantel-France) emitting at 1.54 micrometer. This laser was used in combination with the Dermacool system (Dermacool, Mableton, USA) in order to achieve epidermis cooling before, during and after irradiation. Male hairless rats were used for the study. Pulse train irradiation (1.1 J, 3 Hz, 30 pulses) and different cooling temperatures (+5 degree(s)C, 0 degree(s)C, -5 degree(s)C) were screened with clinical examination and histological evaluation at 1, 3, and 7 days after laser irradiation. The clinical effects showed that pulse train irradiation produced reproducible epidermal preservation and confinement of the thermal damage into the dermis. The different cooling temperatures did not provide detectable differences in terms of size and depth of thermal damage. New collagen synthesis was confirmed by a marked fibroblastic proliferation, detected in the lower dermis at D3 and clearly seen in the upper dermis at D7. This new laser appears to be a promising new tool for the treatment of skin laxity, solar elastosis, facial rhytids and mild reduction of wrinkles.
Simultaneous video and thermal imaging of cryogen spray cooling
Bernard Choi, Ashley J. Welch
In order to understand better the dynamic interaction of cryogen spray cooling of skin, video and thermal images were obtained simultaneously. The cryogen spurt was applied either to skin phantoms (gelatin, 70% water by mass) or in vivo human skin; imaging was performed with a CCD camera (30 frames per second) and a high-speed infrared camera (100 - 850 frames per second). Acquired thermal images were compared to visible images, and a time sequence of different events (ice formation, ice temperature changes, etc.) was developed and used as an input into computer models to provide a more realistic estimation of cryogen spray cooling dynamics. Ice formation, which was present for durations on the order of seconds, had the greatest effect on the theoretical temperature distribution.
Skin thermal response to sapphire contact and cryogen spray cooling: a comparative study based on measurements in a skin phantom
Jorge H. Torres M.D., J. Stuart Nelson M.D., B. Samuel Tanenbaum, et al.
Non-specific thermal injury to the epidermis may occur as a result of laser treatment of cutaneous hypervascular malformations (e.g. port wine stains) and other dermatoses. Methods to protect the epidermis from thermal injury include sapphire contact cooling (SCC) and cryogen spray cooling (CSC). Evaluation of the skin thermal response to either cooling method and better understanding of the heat transfer process at the skin surface are essential for further optimization of cooling technique during laser therapy. We present internal temperature measurements in an epoxy resin phantom in response to both SCC and CSC, and use the results in conjunction with a mathematical model to predict the temperature distributions within human skin. Based on our results, a conductive heat transfer process at the skin interface appears to be the primary mechanism for both SCC and CSC. In the case of CSC, 'film cooling' rather than 'evaporative cooling' seems to be the dominant mode during the spurt duration. Currently, due to the lower temperature of the cryogen film and its shorter time of application, CSC produces larger temperature reductions at the skin surface and smaller temperature reductions at depths greater than 200 micrometer (i.e., higher spatial selectivity) when compared to SCC. However, SCC can potentially induce temperature reductions comparable to those produced by CSC if a sapphire temperature similar to that for a cryogen could be achieved in practice.
Laser Tissue Welding
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Biodegradable polymer thin film for enhancement of laser-assisted incision closure with an indocyanine-green-doped liquid albumin solder
The purpose of this study was to determine if solid material reinforcement of a liquid albumin solder coagulum could improve the cohesive strength of the solder and thus the ultimate breaking strength of the incision repair in vitro. A 50%(w/v) bovine serum albumin solder with 0.5 mg/mL Indocyanine Green (ICG) dye was used to repair an incision in bovine aorta. The solder was coagulated with an 806 nm CW diode laser. A 50 micrometer thick poly(DL-lactic-co-glycolic acid) film was used to reinforce the solder (the controls had no reinforcement). Acute breaking strengths were measured and the data were analyzed by one-way ANOVA (P less than 0.05). Multiple comparisons of means were performed using the Newman- Keuls test. Observations of the failure modes indicated cohesive strength reinforcement of the test specimens versus the controls. At the higher laser powers used in this study (400 and 450 mW), the reinforced solder was consistently stronger than the controls. Reinforcement of liquid albumin solders in laser-assisted incision repair may have mechanical advantages in terms of acute breaking strength over conventional methods that do not reinforce the cohesive strength of the solder.
Solid protein solder-doped biodegradable polymer membranes for laser-assisted tissue repair
Diane E. Hodges, Karen M. McNally-Heintzelman, Ashley J. Welch
Solid protein solder-doped polymer membranes have been developed for laser-assisted tissue repair. Biodegradable polymer films of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) using a solvent-casting and particulate-leaching technique. The films provided a porous scaffold that readily absorbed the traditional protein solder mix composed of bovine serum albumin (BSA) and indocyanine green (ICG) dye. In vitro investigations were conducted to assess the influence of various processing parameters on the strength of tissue repairs formed using the new membranes. These parameters included the PLGA copolymer and PLGA/PEG blend ratio, the salt particle size, the initial bovine serum albumin (BSA) weight fraction, and the laser irradiance used to denature the solder. Altering the PLGA copolymer ratio had little effect on repair strength, however, it influenced the membrane degradation rate. Repair strength increased with increased membrane pore size and BSA concentration. The addition of PEG during the film casting stage increased the flexibility of the membranes but not necessarily the repair strength. The repair strength increased with increasing irradiance from 12 W/cm2 to 15 W/cm2. The new solder-doped polymer membranes provide all of the benefits associated with solid protein solders including high repair strength and improved edge coaptation. In addition, the flexible and moldable nature of the new membranes offer the capability of tailoring the membranes to a wide range of tissue geometries, and consequently, improved clinical applicability of laser- assisted tissue repair.
Improved laser-assisted vascular tissue fusion using solder-doped polymer membranes on a canine model
Newly developed light-activated surgical adhesives have been investigated as a substitute to traditional protein solders for vascular tissue fusion without the need for sutures. Canine femoral arteries (n equals 14), femoral veins (n equals 14) and carotid arteries (n equals 10) were exposed, and a 0.3 to 0.6 cm longitudinal incision was made in the vessel walls. The surgical adhesive, composed of a poly(L-lactic-co-glycolic acid) scaffold doped with the traditional protein solder mix of bovine serum albumin and indocyanine green dye, was used to close the incisions in conjunction with an 805 nm diode laser. Blood flow was restored to the vessels immediately after the procedure and the incision sites were checked for patency. The new adhesives were flexible enough to be wrapped around the vessels while their solid nature avoided the problems associated with 'runaway' of the less viscous liquid protein solders widely used by researchers. Assessment parameters included measurement of the ex vivo intraluminal bursting pressure one to two hours after surgery, as well as histology. The acute intraluminal bursting pressures were significantly higher in the laser-solder group (greater than 300 mmHg) compared to the suture control group (less than 150 mmHg) where four evenly spaced sutures were used to repair the vessel (n equals 4). Histological analysis showed negligible evidence of collateral thermal damage to the underlying tissue in the laser-solder repair group. These initial results indicated that laser-assisted vascular repair using the new adhesives is safe, easy to perform, and contrary to conventional suturing, provides an immediate leak-free closure. In addition, the flexible and moldable nature of the new adhesives should allow them to be tailored to a wide range of tissue geometries, thus greatly improving the clinical applicability of laser-assisted tissue repair.
Liver repair and hemorrhage control using laser soldering of liquid albumin in a porcine model
Yasmin Wadia M.D., Hua Xie M.D., Michio Kajitani M.D., et al.
The purpose of this study was to evaluate laser soldering using liquid albumin for welding liver lacerations and sealing raw surfaces created by segmental resection of a lobe. Major liver trauma has a high mortality due to immediate exsanguination and a delayed morbidity and mortality from septicemia, peritonitis, biliary fistulae and delayed secondary hemorrhage. Eight laceration injuries (6 cm long X 2 cm deep) and eight non-anatomical resection injuries (raw surface 6 cm X 2 cm) were repaired. An 805 nm laser was used to weld 53% liquid albumin-ICG solder to the liver surface, reinforcing it with a free autologous omental scaffold. The animals were heparinized to simulate coagulation failure and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, eight soldering repairs each were evaluated at three hours. A single suture repair of each type was evaluated at three hours. All 16 laser mediated liver repairs were accompanied by minimal blood loss as compared to the suture controls. No dehiscence, hemorrhage or bile leakage was seen in any of the laser repairs after three hours. In conclusion laser fusion repair of the liver is a quick and reliable technique to gain hemostasis on the cut surface as well as weld lacerations.
Optical Diagnosis in Dermatology
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Confocal microscopy of excised human skin using acetic acid and crossed polarization: rapid detection of nonmelanoma skin cancers
Milind M. Rajadhyaksha, Gregg Menaker, Salvador Gonzalez
Moh's micrographic surgery for basal- and squamous-cell cancers (BCCs, SCCs) involves precise excision of the tumor with minimal damage to the surrounding normal skin. Precise excision is guided by histopathologic examination for tumor margins; typically, 2 - 4 slices of skin are excised, and there is a waiting time of 15 - 45 minutes for the surgeon and patient while each slice is being processed for histopathology. We can avoid the processing by using a confocal reflectance microscope; confocal detection of BCCs and SCCs is possible after staining the nuclei in the excised skin with 5% acetic acid, and imaging in crossed polarization. The cancerous nuclei appear bright against the dark surrounding normal dermis. The contrast is due to increased back-scattering as well as increased depolarization from the intra-nuclear structure relative to that from the surrounding normal dermis. As in conventional histopathology, the tumors are first detected at low resolution (section thickness 20 micrometer) in a wide field (1-2 mm); nuclear morphology is then viewed at high resolution (section thickness 2 micrometer) in a small field (0.25 - 0.50 mm). Mosaics of images are assembled to produce confocal maps of the BCCs or SCCs within large excised tissue. Rapid detection (within minutes) is possible.
Noninvasive in-vivo near-infrared vibrational spectroscopic study of lipid and aqueous phases of skin and near-surface tissues
Joseph Chaiken, William F. Finney, Karen P. Peterson, et al.
We report the use of near infrared vibrational spectroscopy to noninvasively probe the in-vivo lipid and aqueous phases of skin and near surface tissues under conditions of thermal and chemical modulation. We demonstrate thermally induced order- disorder transitions in lipids that can be directly compared to well known behavior of in-vitro samples of phospholipid bilayers and bulk fatty acids. We show reversible chemical modification of aqueous phase proteins which are also directly comparable to well known phenomena involving in-vitro proteins. The results of these studies demonstrate the capacity for noninvasively probing live human tissues on the molecular level using near infrared vibrational spectroscopy. This capacity suggests numerous potential applications ranging from assessing the efficacy of cosmetics, skin care treatments and transdermal therapeutic agents/treatments to serving as a diagnostic of various skin ailments, e.g. melanoma.
Use of osmotically active agents to alter optical properties of tissue: influence on the detected fluorescence signal from a subsurface target
In this study, we used a technique that alters the optical properties of tissue to study the effects of tissue scattering on the detected fluorescence from a target placed under the tissue sample. By using hyper-osmotic solutions of glycerol or dimethyl sulfoxide, scattering in tissue samples was reduced substantially. A fluorescent film was placed underneath in vitro and in vivo samples of hamster skin. Excitation of the fluorescent film was achieved through the tissue and the fluorescent signal from the film monitored over time as an osmotically active agent was added to the tissue. The film had an absorption peak at 542 nm and an emission peak at 585 nm. The reduction in tissue scattering caused by the optical clearing agents led to an increase in the detected fluorescent signal (up to double the original signal). The increase was greater for 14 M dimethyl sulfoxide than for 13 M glycerol, and greater for in vivo skin than for in vitro skin. The study serves as a demonstration of the benefits of optical tissue clearing by osmotically active agents to the detected signal in an optical application. Temporary reduction of scattering in tissue will be useful in therapeutic and diagnostic applications that can benefit from an increase in the penetration depth of light.
Optical coherence tomography in differential diagnosis of skin pathology
Natalia D. Gladkova, Galina P. Petrova, Elena Derpaluk, et al.
The capabilities of optical coherence tomography (OCT) for imaging in vivo of optical patterns of pathomorphological processes in the skin and use of their optical patterns in clinical practice for differential diagnosis of dermatoses are presented. Images of skin tissue 0.8 - 1.5 mm deep were acquired with a resolution of 5, 12 and 20 micrometer using three compact fiber OCT devices developed at the Institute of Applied Physics RAS. The acquisition time of images of skin regions 2 - 6 mm in length was 2 - 4 s. The OCT capabilities were analyzed based on the study of 50 patients with different dermatoses. OCT images were interpreted by comparing with parallel histology. It is shown that OCT can detect in vivo optical patterns of morphological alterations in such general papulous dermatoses as lichen ruber planus and psoriasis, a capability that can be used in differential diagnosis of these diseases. Most informative are OCT images obtained with a resolution of 5 micrometer. The results of our study demonstrate the practical importance of OCT imaging for diagnosis of different dermatoses. OCT is noninvasive and, therefore, makes it possible to perform frequent multifocal examination of skin without any adverse effects.
Classification of infrared spectra from skin tumors
Laura M. McIntosh, James R. Mansfield, A. Neil Crowson, et al.
The clinical differential diagnosis of skin tumors is an often-challenging task, to which the probing of skin with mid- and near-infrared (IR) light may be contributory. The development of objective methods for the analysis of IR spectra remains a major hurdle to developing clinically useful applications. The authors highlight different processing methods for IR spectra from skin biopsies and in-vivo skin tumors. Spectroscopic maps of biopsies of basal cell, squamous cell and melanocytic neoplasms were objectively grouped into distinct clusters that corresponded with tumor, epidermis, dermis, follicle and fat. Normal and abnormal skin components were located within maps using a search engine based upon linear discriminant analysis (LDA). In all instances, areas of tumor were distinct from normal tissue in biopsies. In-vivo, near-IR spectroscopy and LDA allowed discrimination between benign and malignant skin lesions with a high degree of accuracy. We conclude that IR spectroscopy has significant diagnostic promise in the skin cancer arena. The analytical methods described can now be used to create a powerful classification scheme in which to detect skin tumor cells within biopsied and living skin.
Selective photocoagulation of cutaneous blood vessels: evaluation of vessel damage by color Doppler optical coherence tomography
Gracie Vargas, Mathieu G. Ducros, Susan Dozier M.D., et al.
This study investigates the threshold radiant exposures required to irreversibly damage cutaneous blood vessels using a pulsed dye laser (PDL) operating at 585 nm. Evaluation of blood vessel damage and blood flow stoppage was achieved using Doppler imaging in a color Doppler optical coherence tomographic (CDOCT) system. Hamster dorsal skin flap window vessels were irradiated with radiant exposures ranging from 2.5 - 8 J/cm2. A 5 mm spot size and 360 microsecond pulse duration were used. Irradiation sites were imaged with CDOCT prior to, immediately after, and a minimum of 24 hours after delivery of laser energy. Magnitude and color Doppler images provided information such as approximate vessel size, depth, and changes in blood flow velocity. Vessel stenosis, temporary occlusion, permanent occlusion, hemorrhaging, and changes in flow velocity were frequent results of laser irradiation visualized with CDOCT and video imaging. Probit analysis was used to estimate the 50% probability that a blood vessel of given size and type will be destroyed by a given radiant exposure. In most instances, arterioles required higher radiant exposures to be irreversibly damaged than venules of the same size. However, arteriole/venule pairs required approximately the same radiant exposures for visible damage to occur. Vessels of larger diameter required higher radiant exposures to coagulate than vessels of smaller diameter.
Determination of absorption coefficient of skin melanin in visible and NIR spectral region
By assuming a wavelength independent scattering coefficients for different skin layers and using the known wavelength dependence of the absorption coefficient of oxy- and deoxy- hemoglobin and water, we have simulated the reflection spectra from skin with various level of blood oxygen saturation. Comparison of the simulation results with experimental measurements made in vivo make it possible to estimate the absorption coefficient of skin melanin in the visible and near-infrared regions. Quantitative results are presented.
Achromatic handpiece and laser delivery device for cutaneous medical application
A fiber handpiece developed for dermatological and vascular medical applications is discussed in detail. The handpiece can be zoomed such that it can deliver output spot diameters ranging from 2 mm to 10 mm when connected to a fiber optic with a 365 micrometer diameter core size. The spot diameter is invariant at the treatment plane over a continuous wavelength spectrum between 532 nm to 1064 nm and exhibits a spot diameter variation of less than 10% over the depth of focus of plus or minus 5 mm at each spot size setting. In these regards, the handpiece can be considered 'achromatic' and 'telecentric.' Details of the optical design, the design process, and important delivery device considerations will be discussed.
Poster Session
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Laser applications in skin diagnosis
Yulia M. Proshina, Nina A. Razumikhina, Valery V. Tuchin
Various possibilities of laser application in skin diagnosis are overviewed. The method of determination of skin state through measuring the scattering properties of the tissue is proposed. The scattering coefficient of biological tissue depends on many uncontrollable factors, which include the concentration of interstitial water, the density of structural fibers, and the shapes and sizes of cellular structures. A spatially resolved two fibers measuring system of back reflectance at 830 nm was used. Immersion and temperature treatment are used as a controlling parameters of the skin under study.
Photomatrix LED therapy of extensive cutaneous pathology
Vladimir P. Zharov, Yulian A. Menyaev, I. Z. Zharova, et al.
Standard sources of radiation have not sufficient efficiency at treating spatially extended pathology, especially when pathologic areas involve opposite sides of the human being's body or when they are uneven in shape. The typical examples of such pathology are extensive burns, oedema, inflammatory processes, infectious wounds, actinic keratosis, psoriasis, arthritis and neurological diseases. Superbright LEDs gathered in a matrix and grasping the area of irradiation are the most suitable sources of radiation. This article presents the result of investigation of the effectiveness of various types of the blue-to-infrared spectrum range LED array that allow irradiating a surface with an area from several cm2 to several thousand cm2 including the whole human being's body with the intensity varying from 1 to 100 mW/cm2. Besides the matrixes, composed of separate light diodes, modular systems with separate monolithic hybrid chips with a high density of positioning the sources of radiation are considered. The peculiarities and results of applying such systems to treat oedema, cancer, weight regulation, neurological diseases, different infections diseases in combination with PDT, stomatitis and paradontosis are analyzed. The parameters of the photomatrix LED for different spectral regions and different geometry from flat shape to semispherical and cylindrical are presented. The perspective combination photomatrix LED with another therapeutical devices including photovacuum and photomagnetic therapy are considered.
Leg veins with diameter between 1 and 3 mm: flash-lamp-pulsed dye laser, alexandrite laser, invasive Nd:YAG laser treatment, or sclerotherapy?
Roman Smucler M.D., Jiri Mazanek, Marta Moidlova
After unrealistic laser expectations we can see renaissance of 'golden standard' -- sclerotherapy in leg veins treatment. Every laser specialist knows difference between facial and leg veins now. Combination of flash lamp pulsed dye laser /PDL/ and sclerotherapy can be new 'golden standard' but patients are dissatisfied with this procedure which include 'needle medicine.' We presented our way to solve this problem partially-invasive laser treatment with Nd:YAG laser last year. Another trend is introduction of new modifications of near infrared lasers. GentleLASE/Candela, MA/ with dynamic cooling is one of them. We treat veins from 0 - 1 mm in diameter very successfully with PDL/ScleroPlus, Candela, MA/, bigger veins we recommend for minimal invasive or classical surgery. Combination of lasers is we think only one possibility for successful laser treatment. Aim of our work is comparison of sclerotherapy with combinated treatments with PDL, near infrared laser and invasive Nd:YAG laser for veins in diameter between 1 - 2 mm. Results show that combination of lasers offer same results with comparable side effects like sclerotherapy that is cheaper and most common of course. Patients prefer pure laser therapy with combination of pulsed dye laser and alexandrite laser. We think that isn't one best method, decision is one the doctor and patient.
Benign Prostatic Hyperplasia
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Cleveland Clinic experience with interstitial laser coagulation of the prostate
James C. Ulchaker M.D., Christopher S. Ng, David Palone M.D., et al.
Transurethral resection of the prostate (TURP) has long been considered the gold standard therapy for benign prostatic hyperplasia (BPH). The problems associated with the TURP, which have been extensively described, include significant bleeding, TUR syndrome, incontinence, stricture, bladder neck contracture, and sexual dysfunction. The desire for simpler, less morbid alternative therapies to TURP has led to an eruption of research and development in the last decade. This is fueled by the continued research for more economical alternatives in our current high cost health care system.
Noninvasive surgery of prostate tissue by high-intensity focused ultrasound: an updated report
Narendra T. Sanghvi, J. Syrus, Richard S. Foster M.D., et al.
High Intensity Focused Ultrasound (HIFU) has been clinically used for the treatment of benign prostatic hyperplasia (BPH) and it is experimentally applied for the treatment of localized prostate caner (PC). Recent advances in the transducer material and technology have permitted to combine the ultrasound visualization capability and HIFU on the same ceramic crystal. Also, the transducer efficiency has increased to a level that a smaller size intracavity probe can be made to produce sufficient acoustic power required for the focused ultrasound surgery of the prostate. Using this technology, 4 MHz mechanically scanning transrectal ultrasound probes has been designed. The transrectal probes are used with Sonablate (SB-200, manufactured by Focus Surgery, Inc., Indianapolis, IN) device. The SB-200 produces both transverse and longitudinal images of the prostate. The transverse and longitudinal images are used for selection of tissue volume, treatment planning and monitoring of tissue during the HIFU treatment cycle. The paper reviews the present operation of the device and recent clinical protocol that has improved efficiency, efficacy and safety of the device. The two years follow-up clinical results from the multi-site US Pilot Study (USPS) and The Male Health Centre are compared with the Kitasato-study (Kitasato School of Medicine, Sagamihara, Japan).
Multiple interstitial ultrasound applicators for conformal heating of the prostate during thermal therapy
Implant strategies using multiple catheter-cooled interstitial ultrasound applicator were investigated for the ability to conform temperature distributions and thermal coagulation within a targeted tissue volume for either hyperthermia or high temperature thermal therapy in the prostate. Multi- element ultrasound applicators were fabricated using cylindrical piezoceramic transducers sectored to 220 degrees to provide angular directional heating, and in non-directional configurations. The applicators were designed to be inserted into standard 13 or 14 gage brachytherapy catheters integrated with water-cooling. Measurements of acoustic power output, and beam profile distributions were obtained in degassed water. Thermal lesions were formed in fresh in vitro beef muscle, and in vivo pig thigh muscle. Axial and radial temperature distributions were monitored using multi-junction thermocouple probes. Thermal lesions measuring 4 cm diameter were produced in vitro within 4 minutes of heating with 5 W applied electrical power delivered to 6 applicators with an angular spacing of 60 degrees. In vivo thermal lesions generated in pig thigh muscle using only 4 directional applicators were confined to a target volume of 3 cm diameter by 3 cm long. Temperatures measured in the center of the target volume reached 85 degrees Celsius during heating, while temperatures outside the target volume remained below 45 degrees Celsius. Results from these studies indicated the ability to control thermal coagulation within the targeted tissue while protecting surrounding tissue from thermal damage.
Miscellaneous
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Transurethral electrolaser complex therapy to treat chronic prostatitis
According to the world statistics, from 30 to 60 percent of elderly male population suffer from chronic prostatitis in different countries. This disease has a number of consequences such as urino-genital inflammation, dysuria, perineal pain, reduction in the physiological activity of smooth muscles, blockage of the anus passages with micro-organism vital activity products, appearance of stagnant zones and low blood circulation complicated by disorders of the sexual function. Most of these features make it difficult to use standard drug therapies with antibiotics or immunocorrectors. For that reason, the objective of this study is to develop and to investigate a novel combined electrolaser therapy which improves drug delivery in the prostate gland and simultaneously provides an independent physiotherapeutic effect. The main feature of this therapy is the utilization of two diode lasers emitting in the red (0.67 micrometer, 10 mW) and in the infrared (0.85 micrometer, 1 W) spectrum ranges in combination with transurethral electrostimulation. An electrolaser catheter containing both hollow cylindrical electrodes and an axial optical fiber to deliver laser radiation was brought along the urethra to the seminal vesicles. The red laser in combination with a photosensitizer ('Photosens,' Russia) was used to realize the antibacterial treatment of the urethra. The infrared laser was employed to heat the prostate gland and to stimulate the blood perfusion without thermal damage of tissues. The laser heating of the prostate at a local tissue temperature of 41 degrees Celsius in combination with the electrostimulation provided approximately a 4.5-fold increase in the blood flow. The realization of an additional mode of photovacuum therapy inside the urethra together with the electrostimulation made it possible to 'clean' the anus passages and to improve the DNA diagnosis reliability in respect of the urogenital infectious remainder. The clinical data obtained in 980 patients, who had been undergoing the treatment since 1994 till 1999 in accordance with the electrolaser method in Russia, are analyzed.
Tissue Welding
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Unpredictable long-term tissue effects in laser-assisted vasovasostomy
Peter T. O. Gilbert
Macroscopic Nd:YAG laser-assisted vasovasostomy was introduced to clinical practice as an attractive alternative to conventional microsurgical suture techniques. In this simple procedure the approximated vasal ends are welded by 0.5 sec laser pulses of 10 W power. The anastomosis is secured by two superficial seromuscular 5 - 0 PDS sutures placed on diametrically opposed sites of the vasal circumference. To date, 17 patients have undergone macroscopic laser-assisted vasovasostomy. In each case the operation was carried out under general anesthesia. There were no serious intra- or postoperative complications. Twelve patients were available for long-term followup (4 years). Sperm counts were obtained two months following surgery and from then on every two years. Whereas patency rate reached 75% at the first control examination, it dropped to 33% after two years. After that period no further deterioration was observed. Probably the main reason for this phenomenon is sperm leaking through mucosal defects at the anastomosis with subsequent formation of intramural sperm granuloma and delayed stenosis of the vasal lumen. This tissue reaction may also occur in the different suture techniques thus accounting for the well- established discrepancy of patency and pregnancy rates in microsurgical vasovasostomy.
Laser welding with an albumin stent: experimental ureteral end-to-end anastomosis
Hua Xie M.D., Brian S. Shaffer, Scott A. Prahl, et al.
Porcine ureters were anastomosed using an albumin stent and diode laser in vitro. The albumin stent provided precise apposition for an end to end anastomosis and enhanced welding strength. The anastomosis seam was lasered with an 810 nm diode laser using continuous wave and pulse light through a hand-held 600 micrometer noncontact optical fiber. Tensile strength, burst pressures, operative times, total energy and thermal damaged were measured in this study. The results demonstrated that using an albumin stent to laser weld ureteral anastomoses produces strong weld strengths. The liquid albumin solder also provided satisfactory welding strength. There were no significant differences of tissue thermal damage between the albumin stent alone, liquid solder alone and both combination groups. Thermal damage to tissue depended on laser setting and energy. This study determined the appropriate laser setting parameters to perform in vivo ureteral end to end anastomosis.
Miscellaneous
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Laser-induced thermotherapy of renal cell carcinoma in man: dosimetry, ultrasound, and histopathologic correlation
J. Chandler Williams M.D., Peter N. Swischuk, Patricia M. Morrison, et al.
Laser-induced thermoterapy (LITT), is the interstitial application of laser energy to achieve tissue coagulation by a thermal process. This is achieved by implanting the laser delivery fiber directly into the target tissue and firing the laser. LITT is being investigated and evaluated clinically as a treatment for renal tumors. The objective of this study was to determine if ultrasound could be used as a real-time monitoring modality of LITT during the coagulation process. Ultrasound characterization was correlated with histopathologic changes and dosimetry. In addition, temperature was monitored and correlated as well.
Photodynamic Therapy
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Computer model for photodynamic therapy of the prostate
Jerzy Jankun, Amjad Zaim, Monika Jankun-Kelly, et al.
Photodynamic therapy (PDT) is an emerging minimally invasive treatment that can be employed in many human diseases including prostate cancer. This treatment of human prostate cancer depends on the localization of a drug (photosensitizer) into the prostate. The photosensitizer is activated by high- energy laser light and the active drug destroys cancerous tissue. The success of PDT depends on precise placement of light diffusers in the prostate. Since the prostate is irregular in shape, with different dimensions, a transurethral light delivery that is circular in distribution cannot be used in most cases of carcinoma of the prostate. Sources of light and their spatial distribution must be tailored to each individual patient. More uniform, therapeutic light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. For this reason, we are developing a computer program that can calculate the distribution of energy depending on the number of light sources placed in the prostate, their position in the gland, the dimension of the prostate, and the attenuation coefficient. A patient's three-dimensional prostate model is built based on ultrasound images. Then the program is being designated to predict the best set of parameters and position of light diffusers in space, displays them in graphical form or in numerical form. The program is amenable for interfacing with robotic treatment systems.
Miscellaneous
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Proteus mirabilis viability after lithotripsy of struvite calculi
Sabitha Prabakharan, Joel M. H. Teichman M.D., Scott S. Spore, et al.
Urinary calculi composed of struvite harbor urease-producing bacteria within the stone. The photothermal mechanism of holmium:YAG lithotripsy is uniquely different than other lithotripsy devices. We postulated that bacterial viability of struvite calculi would be less for calculi fragmented with holmium:YAG irradiation compared to other lithotripsy devices. Human calculi of known struvite composition (greater than 90% magnesium ammonium phosphate hexahydrate) were incubated with Proteus mirabilis. Calculi were fragmented with no lithotripsy (controls), or shock wave, intracorporeal ultrasonic, electrohydraulic, pneumatic, holmium:YAG or pulsed dye laser lithotripsy. After lithotripsy, stone fragments were sonicated and specimens were serially plated for 48 hours at 38 C. Bacterial counts and the rate of bacterial sterilization were compared. Median bacterial counts (colony forming units per ml) were 8 X 106 in controls and 3 X 106 in shock wave, 3 X 107 in ultrasonic, 4 X 105 in electrohydraulic, 8 X 106 in pneumatic, 5 X 104 in holmium:YAG and 1 X 106 in pulsed dye laser lithotripsy, p less than 0.001. The rate of bacterial sterilization was 50% for holmium:YAG lithotripsy treated stones versus 0% for each of the other cohorts, p less than 0.01. P. mirabilis viability is less after holmium:YAG irradiation compared to other lithotripsy devices.
Laser Therapies
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Transcutaneous laser-induced interstitial thermotherapy of nodular goiter
Valeriy A. Privalov, Oleg V. Seliverstov, Jean A. Revel-Muroz, et al.
In the experiment on 41 dogs the possibilities of Nd:YAG (1064 nm) and diode lasers (805 nm) usage for thermotherapy of thyroid gland was grounded. We founded the regimes of laser irradiation causing local destruction of thyroid glands without damage of surrounding organs and tissues. An intratissue dynamic thermometry control in the thyroid and surrounding tissues and their histological analysis were used for determination of the operating mode. The thermometry was performed with the help of an original setup, specimens for the analysis were taken in the period from 1 - 3 to 130 days after the laser irradiation. The results of the experiments gave occasion to the use of intrathyroid local laser hyperthermia in the treatment of 15 patients with recurrent nodal and multinodal euthyroid goiter and 2 patients with inoperable (incurable) medullary thyroid cancer. The laser thermotherapy was fulfilled transcutaneously with ultrasonic control. No complications were registered during the irradiation and the nearest postoperative period. The dynamic ultrasonic examination of the patients carried out for 3 - 18 months showed a positive effect in all cases.
Stress relaxation of porcine septal cartilage during radio-frequency-generated heating
Michael W. Keefe M.D., Brian Jet-Fei Wong M.D., Roger Crumley M.D.
Alteration of the cartilaginous framework within the face and upper airway is a focus of intense clinical research. In this study, radiofrequency (RF) heating was used to induce stress relaxation and reshape mechanically deformed porcine nasal septal cartilage. After RF heating and rehydration, the previously straight cartilage specimens were reshaped into new curved configurations. Two commercial RF devices were used in this study: (1) a 460 kHz device with a series of integrated microthermocouples within the electrode, which allowed monitoring cartilage temperature and (2), a 2.8 MHz device with variable power settings. RF heating duration was determined by measuring the denaturation of albumin to simulate thermal alteration of the cartilage matrix. In cartilage, changes in diffuse transmittance from a diode laser ((lambda) equals 650 nm) during RF heating were measured using a lock-in detection technique, as this correlates with stress relaxation. Alterations in diffuse transmittance were observed during RF generated heating and cartilage was successfully reshaped using both devices, which were objectives of this preliminary study.
Laser reshaping of nasal septum cartilage: clinical results for 40 patients
Clinical results on sparing laser reshaping of nasal septum cartilage are reported for the first time. Forty patients have been treated with holmium laser to correct a deformed cartilage. The laser reshaping is a bloodless, painless procedure which takes few minutes to straighten nasal septum. The stability of the new shape and possible side effects have been examined during twelve months. The headache and other negative symptoms have disappeared, as a result of laser treatment for the most of patients. Rhinoscopic examination show an excellent long-term reshaping effects for nasal septum of 23 patients, and, also, good results for other 12 patients. For 5 patients only a little effect takes place. Our rhinomanometric examinations demonstrate a pronounced improvement of the breathing for 35 patients. No visible undesirable side effects were observed for all patients underwent to laser reshaping procedure.
Surgical management of laryngomalacia: update 2000
Laryngomalacia is the most common cause of inspiratory stridor in children. This disease of excess tissue collapse most often does not require surgical correction. Surgery when necessary is best performed with the aid of the carbon dioxide (CO2) laser, delivered through a mirrored-arm micromanipulator- controlled system, while the supraglottis is exposed using a bivalved laryngoscope. This paper reviews the details of surgical technique used for the safe alleviation of airway distress due to larnyngomalacia.
Coblation technology: plasma-mediated ablation for otolaryngology applications
Jean Woloszko, Charles Gilbride
Coblation is a unique method of delivering radio frequency energy to soft tissue for applications in Otolaryngology (ENT). Using radio frequency in a bipolar mode with a conductive solution, such as saline, Coblation energizes the ions in the saline to form a small plasma field. The plasma has enough energy to break the tissue's molecular bonds, creating an ablative path. The thermal effect of this process is approximately 45 - 85 degrees Celsius, 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 anecdotally has led to less pain and faster recovery for cases where tissue is excised. In cases where Coblation is applied submucosally to reduce tissue volume (inferior turbinate, soft palate), the immediate volume reduction may lead to immediate clinical benefits for the patient. Coblation is currently being tested in various clinical studies to document the benefits for otolaryngological applications.
Plasma-mediated ablation for the management of obstructive sleep apnea
Robert Puchalski, Udayan K. Shah M.D.
Plasma-mediated ablation (PMA) removes tissue by developing an electrically induced plasma layer between the instrument and target tissue. Charged particles within the plasma field then accelerate toward the tissue, breaking the molecular bonds within the top layer of tissue. Thermal damage to collateral tissue is minimal, resulting in the moniker, 'cold' ablation, for this method. Recently, instrumentation has been developed to permit application for soft tissue resection in Otolaryngology. Presentation of the theory, as well as the benefits and disadvantages associated with CoblationTM technology will be followed by examples of its use. A brief videotape will demonstrate the application of PMA for UPPP, tonsillectomy and nasal turbinate reduction. Preliminary experience from our institution, including eighteen children treated with tonsillectomy and followed for at least one month post-operatively, has provided an initial cohort for comparing the risks and benefits of the approach. The advantage of CoblationTM technology identified thus far, that of less thermal damage, is balanced against a decreased level of hemostasis (compared to MES) and an increased cost.
Laser Diagnostics
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Fluorescence detection of oral squamous cell carcinoma using Hyperflav
A novel hypericin-based drug HyperflavTM has been evaluated for light-induced fluorescence detection of oral cancer. Squamous cell carcinoma was induced with carcinogenic agent in right pouches of forty hamsters (20/20 males/females). Solution of HyperflavTM was sprinkled into stomach with a single dose 0.2 - 4 mg of pure hypericin per kg b.w. and 4 - 8 hours before fluorescence analysis. In two animal groups with cancer symptoms the autofluorescence and hypericin-induced fluorescence were taken under 442 nm excitation. The buccal mucosa and adjacent areas were measured fiberoptically in-vivo and in-vitro using orange/green ratio (610/540). The in-vivo fluorescence imaging of malignant areas was conducted to assist the biopsy guidance and to compare with white-light images. Histological and morphological analyses were performed from biopsies. Oral squamous cell carcinoma in its early stage demonstrated specific higher 610/540 ratio for 37 tested hamsters. Advanced state involved another higher fluorescence maximum around 640 nm that in our opinion caused by strong porphyrin-induced native fluorescence. Such deformation of fluorescence spectra may lead to inadequate perception of diseased tissue area. To avoid this problem the autofluorescence spectra & images were added. HyperflavTM application is promising for demarcation of early oral cancer when combined with autofluorescence measurements.
Use of flow cytometry to assess chondrocyte viability after laser reshaping of cartilage
Alexandre Rasouli, Charlton C. Kim, Reshmi Basu, et al.
Lasers have been shown to cause permanent shape change in cartilage via photothermally induced mechanical stress relaxation. While the biophysical properties of cartilage during laser irradiation have been studied, tissue viability following laser irradiation has not been fully characterized. In this study, cell viability staining and flow cytometry were used to determine chondrocyte viability following photothermal stress relaxation. Porcine septal cartilage slabs (10 X 25 X 1.5 mm) were irradiated with light from a Nd:YAG laser ((lambda) equals 1.32 micrometer, 25 W/cm2) while surface temperature, stress relaxation, and diffuse reflectance were recorded. Each slab received one, two, or three laser exposures (respective exposure times of 6.7, 7.2, 10 s), determined from measurements of diffuse reflectance, which correlate with mechanical stress relaxation. Irradiated samples were then divided into two groups analyzed immediately and at five days following laser exposure (the latter group was maintained in culture). Chondrocytes were isolated following serial enzymatic digestion with hyaluronidase, protease, and collagenase II for a total of 17 hours. Chondrocytes were then stained using SYTOR/DEAD RedTM (Molecular Probes; Eugene, OR) wherein live cells stained green (530 nm) and dead cells stained red (630 nm) when excited at 488 nm. A flow cytometer (FACScan, Becton Dickinson, Franklin Lakes, NJ) was then used to detect differential cell fluorescence; size; granularity; and the number of live cells, dead cells, and post irradiation debris in each treatment population. Nearly 60% of chondrocytes from reshaped cartilage samples isolated shortly after irradiation, were viable as determined using flow cytometry while non- irradiated controls were 100 percent viable. Specimens irradiated two or three times with the laser demonstrated increasing amounts of cellular debris along with a reduction in chondrocyte viability: 31 percent following two laser exposures, and 16 percent after three laser exposures. In those samples maintained in culture medium and assayed 5 days after irradiation, viability was reduced by 28 to 88 percent, with the least amount of deterioration in untreated and singly irradiated samples. Functional fluorescent dyes combined with flow cytometric analysis successfully determines the effect of laser irradiation on the viability of reshaped cartilage. The flow cytometric approach to viability is accurate, fast, and can handle large sample numbers and sizes. Most importantly, since the method reveals that a single laser exposure of 6.7 s (sufficient for sustained shape change) causes less than 40 percent acute reduction in viability, photothermal reshaping of cartilage may be further researched as a clinical alternative to conventional techniques.
In-vitro bacterial identification using fluorescence spectroscopy with an optical fiber system
Brian C. Spector, Jay A. Werkhaven M.D., Dana Smith, et al.
Acute otitis media (AOM) remains a source of significant morbidity in children. With the emergence of antibiotic resistant strains of bacteria, tympanocentesis has become an important method of bacterial identification in the setting of treatment failures. Previous studies described a prototype system for the non-invasive fluorescence identification of bacteria in vitro. We demonstrate the addition of an optical fiber to allow for the identification of a specimen distant to the spectrofluorometer. Emission spectra from three bacteria, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were successfully obtained in vitro. This represents a necessary step prior to the study of in vivo identification of bacteria in AOM using fluorescence spectroscopy.
Recoil momentum induced by laser ablation: risk for laser middle ear surgery?
Laser ablated material escapes from the surface with high velocities up to the speed of sound. Due to the conservation of momentum, the same amount of momentum which is in the ablated material is also transferred to the remaining tissue. The effect of this recoil momentum is like a force which accelerates the tissue. In the case of the tiny middle ear bones, the acceleration may be so large that it harms structures of the inner ear. Laser Doppler vibrometry was used to measure the recoil momentum induced by infrared lasers like Holmium, Erbium and CO2 laser. This paper focuses on the effect of repetitive laser pulses of a short pulse CO2 laser.
Lasers in Otology
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Preliminary investigation of CTH:YAG laser for cochlear implantation
Udayan K. Shah M.D., Bruce R. Pawel, William P. Potsic
Cochlear implantation is a treatment for deafness that requires the surgical placement of electrodes within the cochlea, using a high-speed drill. While the drill is effective, the tip of the drill or the drill shaft may damage critical adjacent structures, such as the facial nerve. In addition, the narrow working spaces involved in this surgery make the drill a relatively cumbersome tool for such delicate work. The use of a flexible fiber to deliver the laser energy may make the surgery easier by allowing a more maneuverable instrument to access the region, while reducing the risk of injuring adjacent structures. We report our preliminary investigation of fiber delivery of CTH:YAG energy ((lambda) equals 2091 nm) for the purpose of bony ablation. A 550 micron diameter low-OH silica fiber was used to drill through up to 2.5 mm thick human temporal bone specimens. An average of 14 pulses was required for 1 mm thick bones, and an average of 33 pulses required to ablate 2 mm of bone. The holes drilled were precise, and showed limited adjacent tissue effect by gross and histopathologic evaluation. This work demonstrates the effective fiberoptic delivery of CTH:YAG energy for bone ablation. Further work is warranted to explore the clinical possibilities offered by this technique for precise bony ablation with limited adjacent tissue effect.
980-nm diode laser for middle ear surgery
C. Gaelyn Garrett M.D., Lou Reinisch
We used a 980 nm diode laser at 15 W in the continuous wave mode, delivered through a 200 micrometer optical fiber to perform in vitro laser stapedotomies in a model system. We could measure the temperature increase of the perilymph after the laser had penetrated the footplate. More than 0.5 mm away from the footplate the temperature increase was 3 degrees Celsius or less. However, a measurable amount of the laser light penetrated more than 4 mm in our model perilymph system. There was no evidence of acoustic waves and the optical fiber was easy to use. We anticipate that this laser is safe and effective for laser stapedotomies.
Laser tissue interactions: an update for otolaryngology
Lou Reinisch
We review the laser, characteristics of laser light, the delivery of laser light, pulse lengths and laser tissue interactions. We review these parameters and how they have changed over the history of the laser and how we expect them to change in the future. This survey of laser use is targeted to the otolaryngologist. Very little background in lasers is necessary to follow the discussion. This is intended to introduce and reintroduce laser technology.
Measurement of the elastic modulus of porcine septal cartilage specimens following Nd:YAG laser treatment
Mark D. Gaon, Brian Jet-Fei Wong M.D.
In this study we measured the mechanical properties of porcine septal cartilage before and after Nd:YAG laser ((lambda) equals 1.32 micrometer, 21.22 W/cm2) radiation using parameters and conditions encountered during laser-mediated cartilage reshaping. During laser irradiation, specimens were linearly translated at constant velocity while surface temperature was monitored radiometrically with a thermopile sensor. Irradiation was terminated when surface temperature reached approximately 70 degrees Celsius. Force versus displacement curves were generated in cantilevered specimens using a calibrated thin beam load cell and a single motorized micropositioner (velocity equals .762 mm/sec). Measurements were determined immediately before and after laser irradiation, and then following hydration in saline solution (40 minutes, 25 degrees Celsius). Elastic modulus was calculated using a model assuming linear viscoelastic behavior. Specimens boiled in saline (one hour, 100 degrees Celsius and then re-hydrated) were also evaluated as these tissues are completely denatured. The calculated moduli before and after irradiation were 4.86 plus or minus .145 and 1.166 plus or minus .055 Mpa respectively. Following re-hydration in saline, the modulus returned to near-baseline values (5.119 plus or minus .163 Mpa). In contrast, elasticity remained lower in specimens boiled and re-hydrated (3.25 plus or minus .130 Mpa). These findings suggest that cartilage matrix properties have not been significantly altered following laser irradiation and that the mechanical properties of the tissue are maintained.
Section
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Endoscopic ultrasonography in the management of esophageal cancer
Precise tumor-staging is critical in the management of early esophageal caner. Endoscopic ultrasound (EUS) allows the endoscopist a view beyond the esophageal wall which opens the door to a variety of new gastroenterologic techniques. Endoscopic mucosal resection, laser photoablation and photodynamic therapy may be successfully employed in early esophageal cancer management. Combination radiation therapy and chemotherapy have shown better responses in advanced cancer. Expandable metallic stents may also provide palliation with inoperable esophageal cancer. The efficacy of EUS in the management of esophageal cancer is critically reviewed.
ED50 determination and histological characterization of porcine dermal lesions produced by 1540-nm laser radiation pulses
Pedro J. Rico, Michael A. Mitchell, Thomas E. Johnson, et al.
The military and industry are using 1540 nm laser systems for which current consensus safety standards are misleading. Threshold, ED50, exposure data, along with mechanisms of laser-tissue interaction need to be more accurately determined. Recent studies within our group indicate the Yucatan mini-pig is a more applicable animal model for laser induced skin injury investigators. Laser delivery is accomplished using an Er:Glass system producing 1540 nm of light at millisecond exposure times and in the range of 17 to 77 J/cm2. Dermal lesion development is evaluated for acute, 1 hour, and 24 hour post exposure presentation. Preliminary data obtained from dermal exposures indicate a difference in ED50 for Yorkshire and Yucatan pigs. In the Yucatan mini-pig erythematous lesions are formed acutely while in the Yorkshire, lesions are seen at 24 hours. Preliminary data indicates that lesion development occurs at or near the basal layer of the epidermis causing nuclear pyknosis, cellular swelling and loss of cellular detail. Contrary to the theory that water absorption is the primary mechanism of dermal tissue damage observed from 1540 nm laser exposures, skin chromophores appears to play a role in lesion development.
Role of laser photoablative therapy and expandable metal stents in colorectal carcinoma
Raja S. Chennupati, Eugene A. Trowers M.D.
Metallic stents are effective in relieving colorectal obstruction in more than 80% of cases. Self expanding metallic stents allow for decompression of the proximal colon and preoperative bowel cleansing. Hence, emergent surgery for large bowel obstruction with its associated high morbidity and mortality might be avoided. Endoscopic laser photoablation and stent placement may successfully palliate inoperable colorectal cancer patients by maintaining luminal patency and avoiding the need for a colostomy. Major complications associated with metallic stents include pressure necrosis, perforation, bleeding and migration. The effectiveness of expandable metallic stents in obstructive colorectal carcinoma is critically reviewed. The authors present a concise review of the effectiveness of endoscopic laser photoablation and expandable metal stent placement.
Efficacy of laser photoablative therapy and expandable metal stents for esophageal carcinoma
Gowra Balachandar, Eugene A. Trowers M.D.
Malignant dysphagia is a serious condition in which 70% of patients die within one year, regardless of the treatment received. It provokes a rapid deterioration of a patient's physical condition and a significant worsening of quality of life. The surgical treatment of dysphagia is frequently complicated with technical difficulties, and often the tumors cannot be excised because of extensive invasion into adjacent structures. Furthermore, many patients are considered inoperable due to advanced age, associated diseases and malnutrition. Laser photoablative therapy coupled with expandable metal stents restores luminal patency in more than 80% of patients allowing them to eat liquids and soft foods. The efficacy of laser photoablative therapy and expandable metal stents for the palliation esophageal carcinoma will be critically reviewed.
Photodynamic therapy (PDT) with endoscopic ultrasound for the treatment of esophageal cancer
Timothy A. Woodward M.D., Herbert C. Wolfsen
In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.
Design of a protocol for combined laser hyperthermia-photodynamic therapy in the esophagus
Richard A. London, Juergen P. Eichler, Jochen Liebetruth, et al.
Photodynamic laser therapy (PDT) for esophageal cancer has recently been studied in animal and clinical trials. In several animal experiments a synergetic effect was found by simultaneously applying PDT and hyperthermia (HT). In this paper an optical fiber system is described which can be used in the esophagus for combined PDT with a 1 W dye laser and HT with a 15 - 40 W Nd-YAG laser. Phantoms were developed to simulate the geometry of the esophagus using cow muscle. The spatial-temporal temperature field during HT was measured. The results were compared with calculations using a coupled Monte Carlo laser transport/finite difference heat transport model using the LATIS computer program. Measurements and calculations yield a realistic description of the temperature distribution during HT under various experimental conditions. The LATIS program allows the prediction of the effects of blood perfusion for in-vivo situations. The results show that the perfusion has considerable influence on the temperature field, which must be considered for in-vivo applications.
Autonomous device for photostimulation of the gastrointestinal tract immunity
Sergey A. Naumov, Vladimir N. Dyrin, Sergey M. Vovk, et al.
A very small optoelectronic device emitting light in the red and green band has been developed as a small capsule consisting of two semispheres connected with light-transmitted coupling. The device -- a phototablet permits to irradiate all parts of the gastro-intestinal tract (GIT) including the immunocompetent formations of the small intestine -- Peyer's patches responsible for production of secretory immunoglobulins A (IgA). The main mechanisms of realizing endogenic phototherapy using a phototablet begin functioning when irradiating both the walls of the GIT organs and its contents. The results of clinical trials of the phototablet testify to a favorable effect of endogenic therapy on the human organism in asthenic syndrome, some types of deficiency in the immunity function, in dysbioses, the syndrome of large intestine irritation, duodenostasis, etc. After endogenic phototherapy the patients had an increased level of lysozyme, leukocytes, a number of lactobacteria. There were no side effects when using a phototablet. Indications and contraindications for endogenic phototherapy were represented. Thus, the method of endogenic phototherapy allows us to have an effective and direct influence on the immunocompetent cells of GIT organs without medicamental agents and antigens that makes it possible to use the phototablet in medicine on a large scale.
Optical coherence tomography in diagnosing cervical cancer
Irina A. Kuznetzova, Natalia M. Shakhova, Tatiana S. Kachalina, et al.
Cervical cancer remains one of the most significant problem in oncogynecology. It tends towards treatment approaches that provide termination of pathological processes along with preservation of the patient's life quality. There is a need in earlier and more accurate diagnosis of pathological states, objective assessment of physiological processes, and adequate monitoring of the course of treatment. In our previous publications we have reported unique capabilities of the Optical Coherence Tomography (OCT) to image in vivo the mucosa structure of the cervix and to monitor various physiological and pathological alterations. In this report, we present results of OCT application to diagnose different stages of cervical cancer and to control its treatment at early stages. We have performed OCT-colposcopy in 11 female patients with cervical cancer to derive OCT criteria of this disease, to provide exact demarcation of a pathological area, and to determine a real size of a tumor. We have found that, in general, borders of a tumor, defined visually and detected with OCT by violation of the basement membrane in exocervix, do not coincide. The mismatch depends on a stage of cancer and can be as much as several millimeters. This information is especially important for evaluation of linear dimension of tumors with 3 - 5 mm invasion and also for differential diagnosis between the T1 and T2 stages with cancer extension onto vagina.
Pilot study: intravenous use of indocyanine green as an enhancer for 808-nm diode laser application in the equine
Lloyd P. Tate V.D.M., Anthony T. Blikslager, Mark G. Papich
The 808-nm diode laser, delivering 20 - 40 watts of power, has been produced for medical applications by several manufacturers over the past 10 years. This laser's power output is less than most Neodymium:yttrium aluminum garnet (Nd:YAG) lasers and other high power cutting lasers that use fiberoptic delivery systems. The 808-nm diode laser has not gained popularity in equine transendoscopic laser surgery. Indocyanine green (ICG) is absorbed at 810-nm of light which when concentrated in tissue should be an excellent absorber for the energy produced by the 808-nm diode laser. This study compares the depths and widths of penetration achieved with the 808-nm diode laser after intravenous injection of ICG in equine respiratory tissue. Indocyanine green was administered at two doses: 1.5 mg/kg and 3 mg/kg. The 808-nm diode laser was set to deliver 200 joules of energy. The depths and widths of penetration were also compared to the Nd:YAG laser applied at the same energy setting.
IR fiber optics for biomedical applications
Jasbinder Singh Sanghera, L. Brandon Shaw, David B. Talley, et al.
The availability of low loss and high strength chalcogenide fibers is enabling many applications, including biomedical. We report the use of chalcogenide fibers for IR laser power delivery for surgery, biomedical spectroscopy (tissue analysis) and scanning near field IR microscopy (SNIM). For example, lateral resolution of 20 nm and optical resolution of about 100 nm have been demonstrated for SNIM.
Corneal equivalents: a replacement model for in-vivo 1540-nm laser exposure studies
David J. Fletcher D.V.M., Thomas E. Johnson, Michael A. Mitchell, et al.
We investigate the use of in-vitro corneal equivalents as a replacement model for in-vivo rabbit corneas used in laser damage threshold studies. In-vitro corneal equivalents (CE) were exposed to 0.8 millisecond (ms), 1540 nanometer (nm) single laser light pulses ranging from 124 J/cm2 to 58 J/cm2. After exposure, CE's were evaluated opthalmoscopcopically, imaged using confocal microscopy and examined histologically to investigate the mechanisms of laser induced damage. Preliminary results indicate that the 50% damage threshold for CE's, ED50, is approximately 70 J/cm2 with a 0.5 mm diameter spot size. Additional data points are required to determine a statistically significant ED50. Preliminary exposures of in-vivo rabbit corneas using the same laser parameters as the CE's are also reported. Comparisons between the in-vivo and in-vitro models are presented. Histopathological images from both models show remarkable similarities in the location and extent of damage throughout the full thickness of each tissue.
Fluorescence spectroscopy of Foscan induced feline tissues
Samuel James Rhoades IV, James P. Wicksted, A. Y. Hamad, et al.
Abstract not available.
New technique for feline carbon dioxide laser onychectomy by resection of the redundant epidermis of the ungual crest
William Phillip Young D.V.M.
A new technique for feline carbon dioxide laser onychectomy can further minimize postoperative pain and complications in any age animal. This procedure is accomplished by resection of the redundant epidermis over the ungual crest. Resection of the redundant epidermis allows complete dissection and removal of the claw from a strictly cranio-dorsal approach, thereby minimizing trauma to the surrounding tissues and post- operative complications. The laser setting is preferred at four to six watts continuous power. The epidermis of the ungual crest is resected in a circumferential manner at its most distal edge. This tissue is pushed proximally over the ungual crest. A second circumferential incision is made 3 mm proximal to the first incision. Deeper subcutaneous fascia is also pushed proximally over the ungual crest. An incision of the extensor tendon is made at its insertion on the ungual crest keeping the redundant epidermis proximal to this incision. The incision through the extensor tendon is continued deeper to the synovium of PII and PIII. Gentle traction in a palmar direction will disarticulate the joint space between PII and PIII. Incisions into the lateral and medial collateral ligaments from a cranio-dorsal origin in palmar direction further disarticulate the joint. Care must be exercised to preserve all epidermal tissue lying immediately adjacent to the collateral ligaments. Continual palmar traction will expose the base of PIII and the insertion of the flexor tendon. A dorsal incision is made into the flexor tendon in a palmar direction. Extreme palmar rotation of PIII will allow the dissection of the subcutaneous tissue of the pad from PIII. The redundant epidermal tissue will now cover the majority of the onychectomy site. No sutures or tissue adhesive are advised.
Laser use in avian and exotic animal medicine
Terri Parrott
The use of lasers in clinical avian and exotic animal practice has increased the types of surgical procedures available to the veterinarian. Tissue injury and blood loss can be minimized with both the CO2 and Diode laser. The physical properties of these lasers give them direct advantages over other types of lasers for small animal and avian surgical patients. Routine salpingohysterectomy, castration and mass removal can be accomplished with the CO2 laser. Power, pulse settings and tip diameters for the various tissues make the CO2 laser a versatile instrument in surgery. Endoscopic surgery in the avian patient has been revolutionized with the use of the Diode laser. The use of the flexible fiber system makes it amendable to both rigid and flexible scopes.
Effect of laser irradiation for healing of the skin-muscle wounds of animals
Victoria Alkseyevna Lapina, Eduard I. Veremei, Evgeniy A. Pancovets
The purpose of our investigation was to study the medical effect of low-intensity laser influence on healing of skin- muscle wounds of agricultural animals. We used the laser radiation of low intensity for cub's therapy: to sucking-pigs after herniotomy and castration, to cattle cubs after skin- muscle wounds. The animals were kept under clinical observation up to their recovery. The recuperation dynamic was observed by changing of blood quotients, leukograms, sizes of inflammatory edema, general behavior of animals. The positive dynamic of blood quotients of the experimental animal groups was really higher than that in control. The analysis of wound healing after laser influence shows that wound surface of experimental group was to a great extent smaller in comparison with control group of animals. So, these facts testify about anti-inflammatory action of laser radiation, which hastens regenerative and rehabilitative processes. Analysis of the obtained experimental data has revealed the positive influence of laser irradiation on the dynamics of wound adhesion of agricultural animals.
Laser-induced activation of regeneration processes in spine disc cartilage
Emil N. Sobol, Natalia N. Vorobjeva, Alexander P. Sviridov, et al.
The effect of laser radiation on the regeneration processes in spine disk cartilage has been studied in-vivo. We used rabbits as a model and a Holmium (2.09 micrometer) and an Erbium fiber (1.56 micrometer) lasers for irradiation the discs which were preliminary opened to remove annulus fibrosus and the nucleus pulposus of the intervertebral disc. The irradiated zone has been examined using an optical coherent tomography in one month after the operation and conventional histological technique in two months after the laser operation. It has been shown that laser radiation promotes the growth of the new cartilaginous tissue of fibrous and hyaline types.
Miscellaneous
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Use of high-intensity focused ultrasound in the treatment of both benign and malignant prostatic disease
Kenneth M. Kernen, Brian J. Miles M.D.
Prostate cancer, the most common malignancy in men in the United States, accounts for more than 29% of all male cancers diagnosed and 13% of all cancer deaths. This translates into approximately 200,000 men diagnosed and 37,000 men who will die from the disease this year in this country. A significant number of patients ultimately choose external beam radiation or interstitial radioactive implants (brachytherapy) combined with external beam radiotherapy as their primary treatment. Approximately 25 - 35% of external beam irradiation patients and 20 - 30% of interstitial implants combined with external beam radiotherapy will fail within 10 years. The treatment options for patients with localized radiorecurrent disease include watchful waiting, endocrine therapy, salvage radiotherapy, and salvage radical prostatectomy, cryotherapy and now high intensity focused ultrasound therapy (HIFU). Although some studies regarding watchful waiting demonstrated comparable results to formal treatment for early prostate cancer, other studies have shown metastatic and mortality rates that are significantly higher, and that radiorecurrent patients would have even greater rates of metastasis and progression to death. Prostate cancer cure by means of endocrine therapy is highly unlikely and its role is still one of palliation with a side effect profile which includes hot flashes, osteoporosis, fatigue, loss of muscle mass, anemia, loss of libido and potency. The role of salvage radiotherapy may offer local control, however long term efficacy has yet to be determined. In a recent series, only 50% of the patients were controlled for a mean of four years with salvage radiotherapy. Salvage prostatectomy has the advantage of providing excellent local control and even a cure if the cancer is confined to the prostate or within the surrounding periprostatic tissue. Historically, salvage prostatectomy is technically demanding and fraught with higher complications. In one large series, investigators found rectal injuries in up to 15%, anastomotic strictures in 27% and urinary incontinence in approximately 58%, as well as an overall higher estimated blood loss, transfusions, and hospital stay greater than that of a standard radical retropubic prostatectomy. Cryotherapy also has a significant complication rate with incontinence (73%), impotence (72%), and prolonged dysuria in 67%. In this report, biopsies were negative in 77% but biochemical failure occurred in 58% of patients. High intensity focused ultrasound (HIFU) therapy is a relatively new treatment modality and is being applied transrectally for the treatment of both benign prostatic hyperplasia and adenocarcinoma of the prostate. The therapy is also under evaluation at multiple centers in the United States for the treatment of radiorecurrent prostate cancer. In Europe, it not only being evaluated as treatment for radiorecurrent prostate cancer, but is also being evaluated and offered as a minimally invasive primary therapy for prostate cancers localized to the gland. The technique of HIFU generation has been previously described in detail. The ablation device is comprised of a patient treatment table, main computer, an oscillator, power amplifier, power measurement system, probe movement system, endorectal probe with built-in ultrasound scanner and treatment transducer, and reprography equipment. The patient is administered either a spinal or general anesthesia, positioned on the treatment table on his side with the legs flexed, the endorectal probe is then inserted. The ultrasound imaging is used to detect the contours of the prostate and the target volume to be treated is then calculated. Under computer control, the HIFU device position and then successively repositions the endorectal probe, delivering the high intensity focused ultrasound according to the treatment blocks defined by the surgeon. This sequence then repeats until all sectors of the prostate have been treated. HIFU is generated by high power acoustic transducers, which produce focused ultrasound waves, that generate high temperatures to achieve coagulative necrosis of the target tissue. The ultrasound waves are emitted in discrete, timed bursts with a duration of several seconds. At the focal point of the ultrasound, the temperatures achieved are approximately 85 degrees Celsius, thereby ablating the prostate tissue. An attractive advantage of HIFU is its low risk of morbidity, due to the sudden, short bursts of the intensely focused ultrasound, which, along with the heat generated, are quickly absorbed by the target tissue, thereby protecting the surrounding tissues from damage.
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Imaging of atherosclerotic plaques by optical coherence tomography (OCT)
Jop Perree, Ton G. J. M. van Leeuwen, Gerard Pasterkamp, et al.
Optical Coherence Tomography (OCT) is an imaging technique that measures the intensity of light back scattered from sub- surface tissue structures with a very high resolution. This report describes the qualitative and quantitative correlation of OCT and histology measurements for plaque presence and thickness of caps overlying atherosclerotic plaques, respectively. Imaging of samples (n equals 12) was performed from the luminal side with 1300 nm 1 mW or 10 mW light sources, with coherence lengths of 21 and 16 micrometer, respectively. Samples were histologically processed and stained with H&E, EvG and picro-sirius red (PSR) and histological and OCT images were matched. For each sample, the presence of plaque was assessed and the minimal cap thickness was measured by means of histomorphometry and OCT. We found a sensitivity of 6/6 and a specificity of 5/6 for detection of plaques with OCT. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements (R2 equals 0.968). Thus, OCT is a sensitive method for detection of plaques, is quantitatively comparable to histology and holds promise as a high-resolution diagnostic tool for visualization of plaque cap thickness.
OCT-guided TMR
Transmyocardial revascularization (TMR) has been investigated as a means of reperfusing ischemic heart tissue by introducing channels in the myocardium. In percutaneous TMR (P TMR), the channels are made from within the left ventricle by introducing an excimer laser catheter via the femoral artery. There is currently no means of determining the limits of ablation in P TMR so that the epicardium is not perforated. We used an optical coherence tomography (OCT) signal to detect the epicardial surface during excimer laser ablation of the myocardium in porcine hearts. A XeCl excimer laser operating at 308 nm with a pulse duration of 125 - 200 ns and a pulse energy of 21/mJ at 25 Hz was used to ablate channels in porcine hearts ex vivo. The OCT system was connected to an optical fiber guidewire that was introduced coaxially with the ablation fiber. The OCT signal was monitored on a computer during the ablation process. The epicardial surface was detected within 600 micrometer of perforation.
Navigating a guide wire through total occlusions: clinical experience
John M. Neet, Thomas R. Winston M.D., Allan D. Hedrick, et al.
One of the last remaining frontiers in angioplasty interventions is successfully recanalizing arteries containing total occlusions. The primary limiting condition is the inability to pass a guide wire safely across the total occlusion to facilitate therapeutic interventions. The operator has to perform the intervention without the assistance of x-ray imaging to define the vessel's path since the contrast media flow is blocked by the occlusion. To overcome this limitation, a guide wire system has been developed that transmits low coherence near-infrared light through an optical fiber internal to the guide wire and illuminates the tissue adjacent the distal end. Differences in the scattering of near-infrared light by the normal arterial wall and occluding tissues are detected by optical coherence reflectometry (OCR) techniques. Through a real-time monitoring system and display, the physician is warned if the guide wire approaches the normal arterial wall, allowing the guide wire to be redirected to prevent perforating the vessel. The system has been used in clinical coronary angioplasty cases demonstrating the ability to cross 10 out of 11 total occlusions without any perforations or dissections. The OCR guide wire system has demonstrated clinical potential and will require additional testing for clinical efficacy claims.
Linear lesions in heart tissue using diffused laser radiation
Nathaniel M. Fried, Albert C. Lardo, Ronald D. Berger, et al.
Transmural, continuous, and linear lesions may be necessary for successful catheter ablation of cardiac arrythmias such as atrial fibrillation. Laser ablation was studied as an alternative to radiofrequency ablation, which is noted to produce superficial and discontinuous lesions as well as tissue charring and vaporization. Samples of canine myocardium were placed in a saline bath and irradiated with an 1.06- micrometer Nd:YAG laser operated in either pulsed or continuous mode. For pulsed mode, the laser pulse duration was 10 s with 10 s cooling between pulses. Laser radiation was delivered radially through diffusing optical fiber tips oriented parallel to the endocardial surface. In CW mode, transmural (6-mm-deep), linear (16-mm-long), and continuous lesions were produced using a laser power of 30 W and an irradiation time of 180 s. Peak tissue temperatures measured 51 plus or minus 1 degree Celsius at the endocardial surface, 61 plus or minus 6 degrees Celsius in the mid-myocardium, and 55 plus or minus 6 degree Celsius at the epicardial surface. There was no evidence of tissue charring or vaporization. Pulsed laser irradiation produced comparable lesion depths to CW irradiation with more uniform heating of the subsurface myocardium, but at the expense of longer operation times. Further in vivo study of laser ablation is warranted for possible clinical applications.
Mechanism of neoangiogenesis development after transmyocardial laser revascularization
Gennady K. Popov, Elena S. Golovneva
Pathophysiological mechanisms of transmyocardial laser revascularization (TLMR) remain insufficiently clear. Since the laser transmyocardial channels soon after their formation are closed and then substituted by the connective tissue, the laser effect is caused by neoangiogenesis in the place of injury. We have carried out TLMR in 250 Vistar rats with the help of Nd:YAG laser. In the point of lesion the development of inflammatory process with feebly marked, exudation reaction was registered. A connective tissue scar have been forming in the place of the lasers channel. The substantial growth of small vessels number is shown morphometrically in this place. The number of mast cells in have been increasing since the first hours after operation. The most part of the mast cells were degranulated, that indicates the release of bioactive substances into the extracellular space. The signs of activation of fibroblasts in the place of myocardium damage (abrupt hyperplasia of granular endoplasm reticulum on the electron microphotographs) were evident by the 5 - 6 day. At the first hours and days the platelets in the laser damaged vessels aggregated and the number of (alpha) granules decreased. It also points at the presence of bioactive substances, secreted by platelets. Zymography showed, that the activity of collagenase have been sharply increasing, with its peak on the 10 day after operation. Thus, the activation of noncontracting elements of myocardium during TMR may be the source of growth factors and proteases necessary for neoangiogenesis.
Cardiovascular photodynamic therapy: state of the art
Kathryn W. Woodburn, Stanley G. Rockson
Photodynamic therapy (PDT) has been used traditionally for oncologic and ophthalmic indications. In addition, the enormous potential for the use of PDT agents in cardiovascular diseases is currently being translated into reality. Preclinical studies with various photosensitizers have demonstrated reduction in atheromatous plaque and prevention of intimal hyperplasia. With recent advances in light-based vascular devices and laser diode technology, the clinical use of cardiovascular photodynamic therapy is even more likely. Two photosensitizers, 5-aminolevulinic acid (ALA) and AntrinR (motexafin lutetium) Injection, are under clinical evaluation with many other agents in preclinical testing. Here, preclinical studies are reviewed and the clinical viability of cardiovascular photodynamic therapy is discussed.
Photoangioplasty: new applications of photodynamic therapy in atherosclerosis
Stanley G. Rockson
Atherosclerosis has traditionally held appeal as a pathologic entity in which photodynamic therapy might arrest or reverse the manifestations of disease. Earlier attempts to bring photodynamic therapy to the human clinical arena were hampered by the limitations of the photosensitizers under investigation, including the propensity to phototoxic manifestations and light-induced trauma to surrounding, normal vascular tissues. Many of these inherent limitations may be circumvented by newer photosensitizers that are activated at longer, more optimal wavelengths of light energy. Advances in fiberoptic catheter design for the endovascular delivery of light have also contributed to the greater applicability of photodynamic therapy to human atherosclerosis. Initial experiences with one family of photosensitizers, the texaphyrins, indicate that photodynamic therapy of human peripheral arterial atherosclerosis is feasible, safe, and well-tolerated. Photodynamic therapy of atherosclerosis holds promise for the treatment of de novo atherosclerosis and may have future applicability in the treatment, and perhaps prevention, of restenosis.
Laser thrombolysis in an in-vitro model
Abram D. Janis, Lisa A. Buckley, Kenton W. Gregory M.D.
Stroke is the leading cause of disability and is the third leading cause of morbidity in the United States. Approved therapies are limited. A novel therapy utilizing laser energy delivered through a fluid core catheter in the ablation of embolic thrombus in acute stroke is currently being tested in a clinical trial. In order to optimize the efficiency of clot removal by this system, an in vitro method to measure the effects of varying the laser parameters on the efficiency of clot removal was developed. Included in this model is a new reconstituted clot target that has reproducible mechanical and optical properties which allow reliable spectrophotometric measurement of the mass ablated. In this study the parameters of energy and repetition rate were adjusted while the average power remained constant at approximately 100 mW. The energy levels and repetition rates tested were 36 mJ at 3 Hz, 25 mJ at 4 Hz, 20 mJ at 5 Hz, 15 mJ at 7 Hz, and 12.4 mJ at 8 Hz. We demonstrate that the efficiency of clot removal achieved at higher pulse energies and low repetition rates can be maintained at a lower energy and higher repetition rate. These results are in agreement with previous studies using gel phantoms. This study demonstrates the reproducibility of the reconstituted clot and supports the use of this model as a clinically relevant method to investigate the efficiency of laser thrombolysis.
Optical biopsy: in-vivo diagnosis of breast cancer using elastic scatter spectroscopy
David Christopher O. Pickard, Gavin M. Briggs, Christobel Saunders, et al.
Elastic scattering or diffuse reflectance spectroscopy offers the possibility of distinguishing between cancerous and non- cancerous tissue in the breast with a relatively simple optical measurement. The measurement of the relative reflection of light has previously been shown to be sensitive to both the size and distribution of intra and inter-cellular structures as well as absorption from chromophores, which are present in the tissue. Coupling a white light source and spectrometer to optic fibers makes it possible to construct probes that can be inserted percutaneously or used intra- operatively to take in-vivo spectra from breast tissue or ex- vivo spectra from excised sentinel nodes. This 'optical biopsy' is correlated with a conventional histopathological specimen obtained at the same point. Spectra are reported from a large number of patients with benign and malignant lesions. Some of the differences that appear in these spectra are outlined and the uses and limitations of this technique for in-vivo diagnosis are discussed. It is shown that to a relatively high degree of sensitivity and specificity it is possible to distinguish between malignant tumors, benign lesions and normal tissue.
Edge response function in optical imaging by time-resolved laser transillumination
Maria Lepore, Rosario Esposito, Pietro Luigi Indovina
The image quality in optical imaging is actually under intense investigation in order to ultimately define the role of optical techniques for medical diagnosis purposes. In this work we have investigated the spatial resolution, noise and contrast parameters by using edge response function measurements with masks having well-controlled optical properties. The experimental set-up mainly consisted of an Argon pumped Titanium-Sapphire laser working in femtosecond regime and a streak camera with a few picosecond of temporal resolution. The investigated samples were solutions of Intralipid 10% with distilled water in order to approximate optical properties of biological tissues. The experimental data were analyzed with different imaging algorithms and compared with theoretical predictions about the above- mentioned image quality parameters. The use of spatial resolution, contrast and signal-to-noise ratio allowed us in identifying the best working conditions for optical imaging systems and in evaluating the efficiency of different image reconstruction algorithms.
Uptake and distribution of fluorescently labeled cobalamin in neoplastic and healthy breast tissue
Michelle J. Cannon, James M. McGreevy, Joseph A. Holden, et al.
Fluorescent analogs of cobalamin (vitamin B12) have been developed as diagnostic markers of cancer cells. These compounds are recognized by transcobalamin, a cobalamin transport protein, with high affinity, as shown by surface plasmon resonance. The cellular sequestration and gross distribution of fluorescent cobalamin bioconjugates in breast tissue is being examined by epifluorescence microscopy. The distribution of each compound is being evaluated in proliferative and non-proliferative tissue, i.e. normal tissue and breast carcinoma. The results of preliminary studies suggest that fluorescent analogs of cobalamin may be a useful tool in therapeutic breast operations to define tumor margins and to distinguish neoplastic breast tissue from healthy breast tissue.
Phototherapeutic treatment of lymphedema and other complications after mastectomy
Vladimir P. Zharov, Konstantin L. Kalinin, Andrei A. Borisov, et al.
One of the possible consequences of mastectomy is lymphedema of soft tissues of upper extremities on the side of ablated breast as result of cutting and trauma of multiple nerves, lymphatic and blood vessels. This phenomenon is often accompanied by deterioration of blood and lymphatic microcirculation, increasing of stagnation and aggregation ability of thrombocities, limitation of humeral and ulnar joint activity, severe pain and decreasing of myotonus. The developing of new phototherapeutic method based on using of light-emitting diodes (LED) arrays is attempted. This method is just directed on improvement of patient's condition in combination with other traditional methods such as drug therapy, pressure bandaging etc. The main parameters of LED arrays fixed inside cylindrical tube covering pathology region are: wavelength -- 660 nm, intensity range -- 0.5 mW/sm2. To control and study efficiency of phototreatment ultrasonic dopplerography, thermography, electromyography and viscosimetry have been used. During clinical trials in oncology department of Moscow State University of Medicine and Dentistry 128 patients have been treated with following results: patients felt complete disappearance of pain and weightiness sensation in arm, restoration of skin sensitivity and muscle strength. There were statistically proved amelioration of excitation spreading velocity on radial nerve, decreasing of blood viscosity, increasing of blood velocity in main arteries of shoulder and symmetry of temperature distribution.
Development of a tissue phantom for experimental studies on laser interstitial thermotherapy of breast cancer
Nelson Salas Jr., Fabrice Manns, Pascal F. Chapon, et al.
A tissue phantom for experimental studies in Laser Interstitial ThermoTherapy (LITT) for the treatment of small breast tumors was developed and evaluated. The tissue phantom consists of a polyacrylamide/acrylate hydrogel matrix containing various concentrations of an absorber (Nigrosin) and a scatterer (Intralipid 10% solution), allowing the optical properties to be varied in accordance to experimental need. Temperature measurements in the phantom were performed with a thermocouple array placed symmetrically around the fiber axis during laser irradiation for different output powers, treatment duration, and different concentrations of absorber. A 980 nm diode laser system was used in conjunction with an REM LightStic 360 diffusing tip fiber. The polyacrylamide/acrylate matrix tissue phantom remained stable during laser irradiation and produced reproducible results. The behavior of the temperature curves produced by the phantom during laser irradiation was similar to the behavior of the temperature curves in ex-vivo tissue. Therefore, this tissue phantom can be used as a model for the thermal response of tissue during laser interstitial thermotherapy. The phantom will be used as an experimental model to determine a set of optimum laser treatment parameters for laser interstitial thermotherapy of breast cancer.
Lasers in Otology
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Two-photon excitation laser scanning microscopy of porcine nasal septal cartilage following Nd:YAG laser-mediated stress relaxation
Charlton C. Kim, Vincent P. Wallace, Alexandre Rasouli, et al.
Laser irradiation of hyaline cartilage result in stable shape changes due to temperature dependent stress relaxation. In this study, we determined the structural changes in chondrocytes within porcine nasal septal cartilage tissue over a 4-day period using a two-photon laser scanning microscope (TPM) following Nd:YAG laser irradiation (lambda equals 1.32 micrometer) using parameters that result in mechanical stress relaxation (6.0 W, 5.4 mm spot diameter). TPM excitation (780 nm) result in induction of fluorescence from endogenous agents such as NADH, NADPH, and flavoproteins in the 400 - 500 nm spectral region. During laser irradiation diffuse reflectance (from a probe HeNe laser, (lambda) equals 632.8 nm), surface temperature, and stress relaxation were measured dynamically. Each specimen received one, two, or three sequential laser exposures (average irradiation times of 5, 6, and 8 seconds). The cartilage reached a peak surface temperature of about 70 degrees Celsius during irradiation. Cartilage denatured in 50% EtOH (20 minutes) was used as a positive control. TPM was performed using a mode-locked 780 nm Titanium:Sapphire (Ti:Al203) beam with a, 63X, 1.2 N.A. water immersion objective (working distance of 200 mm) to detect the fluorescence emission from the chondrocytes. Images of chondrocytes were obtained at depths up to 150 microns (lateral resolution equals 35 micrometer X 35 micrometer). Images were obtained immediately following laser exposure, and also after 4 days in culture. In both cases, the irradiated and non-irradiated specimens do not show any discernible difference in general shape or auto fluorescence. In contrast, positive controls (immersed in 50% ethanol), show markedly increased fluorescence relative to both the native and irradiated specimens, in the cytoplasmic region.
Miscellaneous
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Perspectives of transurethral robotic laser resection of the prostate: vaporization and coagulation effects with the Nd:YAG laser
Gideon Ho, Ming Yeong Teo, Chee Keong Kwoh, et al.
A longer operating time and steeper learning curve in mastering the techniques for transurethral laser resection of the prostate are the main problems faced by surgeons compared to standard transurethral resection of the prostate (TURP). However, these disadvantages can be solved with the introduction of a treatment modality designed and developed based on an integrated system of computer, robotics and laser technology. In vitro experiments were carried out to determine variables affecting the vaporization and coagulation lesions, in order to identify the parameters that could optimize this modality. Human cadaveric prostate and fresh chicken breast tissues were irradiated with different parameters using continuous wave Nd:YAG laser fiber in contact with the tissue. The effects of irrigant flowrate, fiber/tissue angle of inclination, number of passes, direction, speed and power of lase on the volume of tissue vaporized and coagulated, were assessed. A non-contact optical coordinate measuring machine was used to measure the depth and width of the vaporized and coagulated lesion. Results reveal that for each directional vaporization path (forward, clockwise and counter-clockwise), power and speed of lase are the most significant parameters influencing the volume of the vaporized and coagulated lesion. Optimized values of the power and speed of lase at 100 W and 1 - 3 mm/s respectively were obtained from the experiments when the tissues were irradiated in the forward, clockwise and counter-clockwise directions. It was concluded from our study to quantify tissue removal and damage, optimized values of irradiation power and speed could be obtained and implemented in the procedure of transurethral robotic laser resection of the prostate.
Advances in Laser Skin Resurfacing
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Dynamics of cryogen deposition relative to heat extraction rate during cryogen spray cooling
Goal is to investigate how delivery nozzle design influences the cooling rate of cryogen spray as used in skin laser treatments. Cryogen was sprayed through nozzles that consist of metal tubes with either a narrow or wide diameter and two different lengths. Fast-flashlamp photography showed that the wide nozzles, in particular the long wide one, produced a cryogen jet (very small spray cone angle) rather than a spray (cone angles of about 15 degrees or higher) and appeared to atomize the cryogen less finely than the narrow nozzles. We measured the cooling rate by spraying some cryogen on an epoxy-block with thermocouples embedded. The heat extraction rate of the wide nozzles was higher than that of the narrow nozzles. The results suggest that finely atomized droplets produced by the narrow nozzles do not have enough kinetic energy to break through a layer of liquid cryogen accumulated on the object, which may act as a thermal barrier and, thus, slow down heat extraction. Presumably, larger droplets or non- broken jets ensure a more violent impact on this layer and therefore ensure an enhanced thermal contact. The margin of error for the heat extraction estimate is analyzed when using the epoxy-block. We introduce a complementary method for estimating heat extraction rate of cryogen sprays.
Optical Diagnosis in Dermatology
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Pulsed photothermal profiling of hypervascular lesions: some recent advances
Boris Majaron, Wim Verkruysse, B. Samuel Tanenbaum, et al.
Pulsed photothermal radiometry (PPTR) can be used for non- invasive depth profiling of port wine stain (PWS) birthmarks, aimed towards optimizing laser therapy on an individual patient basis. Reconstruction of laser-induced temperature profile from the experimentally obtained radiometric signal involves the skin absorption coefficient in the infrared detection band. In the commonly used 3 - 5 micrometer detection band (InSb), the absorption coefficient varies by two orders of magnitude, while assumed to be constant in the reconstruction algorithms used thus far. We discuss the problem of choosing the effective absorption coefficient value to be used under such conditions. Next, we show how to account explicitly for the strong spectral variation of the infrared absorption coefficient in the image reconstruction algorithm. Performance of such improved algorithm is compared to that of the unaugmented version in a numerical simulation of photothermal profiling. Finally, we analyze implementation of a bandpass filter which limits the detection band to 4.5 - 5 micrometer. This reduces the absorption coefficient variation to a level that permits the use of unaugmented algorithm. An experimental test of the latter approach for in vivo characterization of the depth of PWS lesion and epidermal thickness will be presented, including a novel technique that uses two laser excitation wavelengths in order to separate the epidermal and vascular components of the radiometric signal.
Lasers in Otology
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Characterization of micromanipulators for CO2 laser surgery in head and neck: comparison of reflective and refractive optical systems
Kenneth K. H. Chao, Eric Cheung, William B. Armstrong, et al.
Laser micromanipulators deliver laser energy to difficult to access regions within the head and neck allowing surgeons to perform high precision microsurgical procedures. In this study, the laser spot sizes (as a function of power) produced by a two micromanipulators of different optical design were compared. A CO2 laser and operating microscope (400 mm focal length) was coupled to either a reflective (Cassegrain- like) (Unimax 2000, Reliant Technologies, Inc., Foster City, CA) or refractive micromanipulator (Microslad 719, Sharplan Lasers Inc. Allendale, NJ). The laser spot size was determined by measuring the region of ablation following laser irradiation of dry tongue blades, exposed photopaper, and agar gel using optical micrometry. Laser power was varied from 0.5 to 20 W for pulse durations of 0.1 and 0.5 seconds. A logarithmic relationship between spot size (diameter) and laser power on wood and photopaper was observed for both devices. In agar samples a discontinuity in spot size was observed at 9 W due to the formation of a large ablation crater on the surface of the agar. For a given laser power, the micromanipulator with reflective optics demonstrated overall smaller spot sizes and lower incremental change in spots size with increasing power. These results suggest the reflective micromanipulator tested in this study produced a smaller spot size at all powers tested, and with increasing power the spot size increased more slowly than with the conventional refractive optical device tested.
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Endovascular photodynamic therapy inhibits intimal hyperplasia after PTA in a rat model
Edward E. Gabeler M.D., Richard van Hillegersberg, R. G. Statius van Eps, et al.
Background: Vascular restenosis due to intimal hyperplasia (IH) and negative vascular remodeling (shrinkage) attenuates long-term patency of interventions like bypass procedures, endarterectomies and PT(C)As. Endovascular photodynamic therapy (PDT) may be an adjuvant approach based on intracellular photoactivation of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PP IX) resulting in local cytotoxicity. Aim: To prevent restenosis by inhibiting IH with endovascular PDT. Methods: Male Wistar rats (n equals 33) were subdivided into two groups; one experimental group; the PTA + PDT group (N equals 18), in which illumination with either 0, 12.5, 25 and 50 J/cm diffuser length was applied at 100 mW/cm diffuser length; one control group; the PTA group in which IH was induced after balloon denudation of the right iliacal artery (n equals 15). Results: Morfometric analysis showed that IH developed from 0.02 plus or minus 0.02 mm2 at 1 week to 0.13 plus or minus 0.04 mm2 at 4 weeks in the PTA group. In the PTA + PDT-group with 50 J/cm diffuser length still no IH (0.002 plus or minus 0.003 mm2) developed after 4 weeks. Conclusion: Endovascular PDT prevents formation of IH measured 4 weeks post PTA. An optimal light dosimetry of 50 J/cm diffuser length at 3 hours after ALA application was found in this IH model. Therefore, endovascular PDT is a promising therapy to prevent restenosis after vascular interventions.