A finite-element-method model with ANSYS 8.0 of a 29 year old human lens during accommodation will be presented. The required data, to draw and calculate a two dimensional, axis-symmetric model of the human lens is inherited from various sources. Furthermore the analysis premises all lens materials to be linear elastic and allows large displacements. A first analysis of a possible method for the treatment of presbyopia by fs-laser induced microcuts is accomplished. Therefore a mechanical analysis of an untreated and a treated lens are compared. As a result an improvement of the flexibility of the lens tissue is found and as its consequence a change of the lens' radii of curvature is established. After a suitable processing of the output data a linear Gaussian ray trace is performed and a minor change in the optical power between the untreated and treaded human lens is perceived. By calculation of the discrete optical power of the anterior and posterior surface on the one hand and the overall optical power on the other hand an interpretation of the effectiveness resulting from the treatment is offered. It is ascertained that the change in optical power of the anterior lens surface is increased while the optical power of the posterior lens surface is decreased, almost compensating each other. A possible explanation for this phenomenon is given and a suggestion of how to increase the effectiveness of the treatment is discussed.

A study was conducted to investigate why 193 nm excimer laser beams of uniform fluence produce corneal ablations that are deeper at the edge than at the center. Enucleated porcine eyes were ablated and measured with an optical profilometer. A dehydrated cornea was also ablated. Enucleated porcine eyes and PMMA were ablated with and without narrow central masks, and ablation plumes were photographed. Characteristic patterns of central underablation were present in the porcine corneas. Ablation craters ranging in diameter from 2.0 to 6.5 mm exhibited increasingly shallower central ablation and nearly constant depth at the edges. There was no significant depth variation in the dehydrated cornea. Masks did not change the depth or shape of craters near the edges of the zone; but depth adjacent to the images of the masks was more than twice that with no mask. The depth adjacent to the mask image was nearly the same as at the edge of the zone, and the rate of change in depth with position was nearly equal in both areas. The area of maximum plume density centered over the entire ablation with or without the mask. Redeposition of plume particles is not the major cause of central underablation; rather, propagating transverse energy from the absorption of photons by the peptide bonds increases pressure on the excited components within the irradiated area, increasing recombination, which in turn raises the ablation threshold.

Selective tissue damage on the cellular level can be achieved due to transient microbubbles around laser-heated intracellular pigments. We investigated bubble dynamics and nucleation mechanisms at microabsorbers in suspensions as well as bubble formation in retinal pigment epithelial cells by fast flash photography and time-resolved probe laser transmission.

Manipulation—that is, inactivation and movement—of subcellular organelles in living cells is important to understand cell dynamics. We review disruption of subcellular organelles in living cells by tightly focusing femtosecond laser pulses inside the cells. Photodisruption of organelles in living cells was experimentally confirmed by restaining of organelles. Femtosecond laser based nanosurgery has the possibility to remove or manipulate organelles in living cells and may lead to elucidation of functional interactions between organelles, protein transportation, and inter-cell communication.

We show sub-micron scale surgery with femtosecond lasers in a tiny living organism. By just cutting few nano-scale nerve connections inside the nematode C. elegans, we can stop the whole worm from moving backwards. This delicate axotomy keeps the surrounding of the severed axons un-damaged so that the axons can regrow back, and the worms recover and can move backwards again. These results demonstrate, for the first time, nerve regeneration in such a tiny organism, in its evolutionarily simplest form. The ability to perform precise sub-micron scale axotomy on such organisms provides tremendous research potential for rapid screening of drugs and discovery of new biomolecules affecting regeneration and development.

We demonstrated that gene can be transfected to various types of cell lines by the use of laser-induced stress waves. The effect of cellular heating was also investigated, showing the different characteristics between nonmalignant cells and malignant cells.

Background: Laparoscopic surgery especially relies on hemostatic dissection. In this study, a new laser scalpel suitable for laparoscopic surgery due to its rapid dissection and adequate hemostatic properties is presented. Methods: A Thulium YAG laser system (λ= 2.01 μm) was used at power levels of 15- 20 W transmitted via 365μm core diameter quartz fiber. Arteries and veins of 0.25-3.2 mm inner diameter were coagulated and transected with the laser scalpel in anesthetized pigs, followed by ex vivo measurement of resistance to pressures up to 375 mmHg. Results: Small vessels (<0.5 mm) were successfully occluded up to 100% (arteries) and 89% (veins), larger vessels (1- 2.3 mm) to 74% (arteries) and 65% (veins). At 375 mmHg, 30% of veins and 35% of arteries stayed closed during external pressure measurement. Conclusion: The laser scalpel proved satisfying hemostatic properties for small vessels, for medium-sized vessels alternative coagulating devices must serve as possible back-up.

Preterm infants have a high incidence of post hemorrhagic or post infectious hydrocephalus often associated with ventricular or arachnoic cysts which carry a high risk of entrapment of cerebrospinal fluid (CSF). In these cases fenestration and opening of windows within the separating membranes are neurosurgical options. In occlusive hydrocephalus caused by aquaeductal stenosis 3rd ventriculostomy is the primary choice of the operative procedures. Although Nd:YAG and diode lasers have already been used in neuroendoscopic procedures, neurosurgeons avoid the use of high energy lasers in proximity to vital structures because of potential side effects. We have used a recently developed diode pumped solid state (DPSS) laser emitting light at a wavelength of 2.0 micron (Revolix TM LISA laser products, Katlenburg, Germany), which can be delivered through silica fibres towards endoscopic targets. From July 2002 until May 2005 22 endoscopic procedures in 20 consecutive patients (age 3 months to 12 years old) were performed. Most children suffered from complex post hemorrhagic and post infectious hydrocephalus, in whom ventriculoperitoneal shunt devices failed to restore a CSF equilibrium due to entrapment of CSF pathways by the cysts. We used two different endoscopes, a 6 mm Neuroendoscope (Braun Aesculap, Melsungen, Germany) and a 4 mm miniature Neuroscope (Storz, Tuttlingen, Germany). The endoscopes were connected to a standard camera and TV monitor, the laser energy was introduced through a 365 micron core diameter bare ended silica fibre (PercuFib, LISA laser products, Katlenburg, Germany) through the endoscope's working channel. The continuous wave laser was operated at power levels from 5 to 15 Watt in continuous and chopped mode. The frequency of the laser in chopped mode was varied between 5 and 20 Hz. All patients tolerated the procedure well. No immediate or long term side effects were noted. In 3 patients with cystic compression of the 4th ventricle, insertion of a shunt device could be avoided. All 3rd ventriculostomies were sufficient for therapy of hydrocephalus, postoperatively MRI scans showed a bright flow void signal. The authors conclude that the use of the new Revolix laser enables safe and effective procedures in neuroendoscopy.

Systematic investigations on ablation of compact bone tissue with different CO₂ laser systems are presented. Main attention is paid to the influence of the laser wavelength and pulse duration on the efficiency of the ablation.

Laser osteoperforation method, initially developed for treatment of osteomyelitis, was successfully applied to 66 patients with osteal and osteoarticular panaritium. The procedure consisted in perforation of the affected phalanx with diode laser radiation (wavelength 970nm; average power 10-12W; pulse mode 100/50 ms), delivered through quartz monofiber. Additional laser induced thermotherapy (power 2-3W; continuous mode) was fulfilled for persistent fistulas. In comparison with conventional surgery, laser osteoperforation provided faster pain relieve, edema dissipation, wound and fistula closure; good functional results; decreasing of disability cases number.

The near-infrared (NIR) laser radiation due to its high penetration depth is widely used in phototherapy and photothermolysis. In application to skin appendages a high selectivity of laser treatment is needed to prevent light action on surrounding tissues. Indocyanine Green (ICG) dye may provide a high selectivity of treatment due to effective ICG uploading by a target and its narrow band of considerable absorption just at the wavelength of the NIR diode laser. The goal of this study is to demonstrate the efficacy of the NIR diode laser photothermolysis in combination with topical application of ICG suggested for treatment of acne vulgaris. Two volunteers with back-located acne were enrolled. Skin sites of subjects were stained by ICG and irradiated by NIR laser-diode light (803 or 809 nm). The individual acne lesions were photothermally treated at 18 W/cm² (803 nm, 0.5 sec) without skin surface cooling or at 200 W/cm² (809 nm, 0.5 sec) with cooling. The results of the observations during a month after the treatment have shown that ICG stained acne inflammatory elements were destructed for light exposures of 0.5 sec.

It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-μm region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (μg/cm²/h) and total penetration amount (μg/cm²) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-μm region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

The results are presented on the study of the damage of melanin granules contained in ex-vivo animal skin specimens under a series of single Nd:glass laser pulses of nanosecond duration, with intensity I ~ 10⁸ W/cm². The mechanism responsible for tissue damage at the given conditions is shown to be a selective photodisruption occurring due to preferential energy absorption by endogenic skin pigment. For such a complicated multicomponent structure as biotissue comprising substructures inhomogeneously distributed in the bulk of it and differing in physical and chemical properties, such a parameter as volume energy density becomes a decisive one for tissue damage. When its magnitude reaches the damage threshold value within the absorption loci it breaks whereas the surrounding tissue remains undisturbed.

Application of intravenous laser irradiation of blood (ILIB) is considered to be the most effective method of laser therapy and its application is expedient pathogenetically in the ischemic disturbances. The aim of this study is to investigate ILIB influence with red helium-neon laser (HNL) with 630 nm wavelength and different powers on blood oxygen transport (BOT), cerebral and dermal microhaemodynamics (MGD), hydro-ion balance in normal rabbits and after modeling of local ischemia of brain (LIB). Experimental cerebral ischemia is characterized by development of BOT disturbance, ionic disbalance and edema in the ischemic brain region. Microcirculation disturbances with worsening of the cerebral and dermal MHD were revealed. ILIB with HNL radiation of 2.5 and 4.5 mW powers provokes dehydratation of brain structure alone with the K⁺, Na⁺ concentration decreasing and hemoglobin-oxygen affinity increasing in intact group of animals. There was not revealed marked changes of cerebral MHD condition here. Using of ILIB in rabbits after LIB contributes for improving function of BOT, normalizing of water content in all cerebral structures compared to operated animals. Preventive ILIB provoked improvement of speckl-optical parameters and marked protective effect on microhaemodynamics processes in superficial brain structures. HNL radiation with 1.0 mW power results in worsening of oxygen transport, cerebral and skin MHD, hydro-ion homeostasis in animals with LIB modeling. Thus, laser haemotherapy contributes for improving of hydro-ion status, blood oxygen transport and cerebral microcirculation in brain ischemia, what allows considering that helium-neon radiation with the pointed regimen is substantiated pathogenetically in brain ischaemia.

Infra-red diode laser with wavelength 1060 nm was used for combined treatment of 163 children aged from 21 days to 13 years with 221 hemangiomas. For interstitial coagulation a power of 1.8-2 W and a power density of 5-90 J/cm³ were used in continuous mode. For distant coagulation pulse mode was applied with pulse/pause duration 30-50/200-250 ms, average power 1.3-2 W, and power density 65-450 J/cm². 197 (89.1 %) hemangiomas were capillary, 7 (3.2 %) cavernous, and 17 (7.7 %) combined (combination of capillary and cavernous hemangiomas). The area of hemangiomas ranged from 6 mm² to 48 cm². For the majority (193, 87.3 %) of hemangiomas one session of photocoagulation was enough to achieve a good cosmetic effect. However, 28 (12.7 %) hemangiomas were treated repeatedly, 11 (5%) of them needed 4-7 sessions. In 8 children with cavernous and combined hemangiomas both distant and interstitial laser coagulation were used. In all, good or excellent results were obtained in 96,3 % of the patients. In 6 (3.7%) patients with extensive combined hematomas the considerable improvement was achieved.

A computer model of blood vessel heating by pulse laser irradiation incident on the upper skin layer (epidermis) is suggested. The model is a multilayered half-infinite structure. The depths, optical (absorption and scattering), mechanical and thermal-optical properties of layers are in agreement with the real properties of epidermis and dermis of skin. The exterior of model object (epidermis) is illuminated by light beam of cylindrical form with homogeneous intensity distribution along the cross section. The blood vessel, situated in dermis, is simulated by infinite circular cylinder. Calculations of the dynamics of temperature field inside blood vessel taking into account an inhomogeneous distribution of volumetric heat release within it under the action of pulse laser irradiation of skin were made.

A genetic algorithm for optimal placement of optical fibers in arbitrary geometries for interstitial photodynamic therapy has been developed. Based on calculated fiber positions, the diffuse light distribution is simulated by solving the diffusion equation by means of the finite element method and the treatment time is calculated. Utilizing an instrument for interstitial photodynamic therapy that is capable of both delivering the therapeutic irradiation and measuring parameters of relevance to treatment monitoring, knowledge has been gained on temporal variations of tissue light absorption, sensitizer photobleaching and tissue oxygenation status. We speculate on how variations in these three parameters can be implemented in a crude pre-treatment dosimetry model for photodynamic therapy.

The effect of non-ideal cylindrical diffusers on the fluence rate distribution is studied in intraluminal and interstitial light delivery settings. Two types of diffuser non-uniformities are modeled: a forward-directed polar emission profile, and a longitudinal emission profile with a peak at the distal tip of the diffuser. These effects were compared with an ideal diffuser constructed via a superposition of isotropic point sources placed along the length of the diffuser. Monte Carlo simulations were run for a wide range of optical properties and the resulting fluence rate distribution were analyzed. Parameters describing the shape of these distributions were defined. The longitudinal profile most strongly influenced the shape of the fluence rate distribution displaying high local fluence rates, high degrees of asymmetry, and deeper penetration into tissue. These characteristics are particularly evident for interstitial illumination. In intraluminal illumination, both non-ideal profiles produced a shift of the fluence rate, but, while remaining largely insensitive to optical properties for the longitudinal diffuser, the position of the peak fluence rate varied to a considerable extent for the polar anisotropic diffuser, particularly as a function of albedo. Measurement of the polar emission profile and its inclusion in treatment planning, based on the tissue optical properties, is recommended for the intraluminal geometry. The longitudinal emission profile should be determined regardless of the application, together with knowledge of the tissue optical properties.

Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m², i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 ± 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm². Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm²) effectively eradicated SAbiofilms within bone. Conclusions: Results support the application of PDT to the treatment of primary or metastatic lesions within bone. Secondly, that ALA-PDT may be useful as a treatment for osteomyelitis. Further studies aim to optimize the parameters of delivering PDT into bone and explore imaging technologies that can be used for clinical PDT.

Photodynamic inactivation (PDI) may be a very promising alternative method for antimicrobial treatment of many localised infections. In the present study we report the activity of three lanthanides (Eu(III), Pr(III), Yb(III)) complexes of Fotolon sensitizer, composed of chlorin e6 and polyvinylpyrrolidone (PVP), against standard E.coli P. aeruginosa, K. pneumoniae and S. aureus ATCC strains. The 160±10mW/cm² of 651 nm laser light was applied for 600 seconds after photosensitiser administration (50μg/ml) and 30 minutes incubation time. Impact of pure Fotolon and pure lanthanides solution was examined as control groups.

In-vitro photodynamic inactivation of Ps. aeruginosa with methylene blue under pulsed light excitation was investigated at different pulse repetition rates. Bacterial suspensions were illuminated with 670-nm nanosecond pulsed light with a peak intensity of 2.0 MW/cm² at pulse repetition rates in the range of 5-30 Hz. Photobactericidal effect increased with increasing pulse repetition rate for the same total light dose; more than two orders in magnitude reduction of bacterial survival fraction was obtained at 30 Hz. Such a positive dependence of photobactericidal effect on pulse repetition rate was inconsistent with our previous results for human lung cancer cells that were photodynamically treated with a lysosomal sensitizer. The reason for the increased photobactericidal effect at the high pulse repetition rate is discussed.

Photodynamic diagnosis of bladder carcinoma based on hypericin fluorescence cystoscopy has shown to have a higher degree of sensitivity for the detection of flat bladder carcinoma compared to white light cystoscopy. The potential of the photosensitizer hypericin-induced fluorescence in performing non-invasive optical biopsy to grade bladder cancer in vivo using fluorescence cystoscopic image analysis without surgical resection for tissue biopsy is investigated in this study. The correlation between tissue fluorescence and histopathology of diseased tissue was explored and a diagnostic algorithm based on fluorescence image analysis was developed to classify the bladder cancer without surgical resection for tissue biopsy. Preliminary results suggest a correlation between tissue fluorescence and bladder cancer grade. By combining both the red-to-blue and red-to-green intensity ratios into a 2D scatter plot yields an average sensitivity and specificity of around 70% and 85% respectively for pathological cancer grading of the three different grades of bladder cancer. Therefore, the diagnostic algorithm based on colorimetric intensity ratio analysis of hypericin fluorescence cystoscopic images developed in this preliminary study shows promising potential to optically diagnose and grade bladder cancer in vivo.

Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes it possible to treat acne with PDT. This initial study investigates the possibility of fluorescence imaging as assessment tool in adjunct to PDT of patients with acne. Twenty-four patients with acne on the cheeks have been treated with PDT with and without mALA. Fluorescence images have been obtained before and after treatment. The clinical acne score was assessed as base line before PDT, and at every follow up visit. Additionally the amount of P.acnes was determined. The clinical evaluation showed a general improvement of acne, even though no difference between treatment with and without mALA was observed. By performing texture analysis and multivariate data analsysis on the fluorescence images, the extracted texture features were found to correlate with the corresponding clinical assessment (67%) and amount of P.acnes (72%). The analysis showed that features describing the highly fluorescent pores could be related to the clinical assessment. This result suggests that fluorescence imaging can be used as an objective assessment of acne, but further improvement of the technique is possible, for example by including colour images.

The clinical results of photodynamic therapy of chronic maxillary sinusitis have been demonstrated. Obtained results show that the photodynamic therapy is effective in comparison with conservative methods of treatment of the disease. Diffusion of Methylene Blue in the mucous tissue has been studied in vitro and value of the diffusion coefficient of Methylene Blue in the tissue has been estimated at 20°C as (4.8±2.9)×10^-7 cm²/sec.

Clinical results of photodynamic therapy (PDT) with a novel natural second generation chlorin-type photosensitizer "Radachlorin", mainly consisting of sodium chlorine e6, are presented. This sensitizer possesses a number of advantages over sensitizers of hematoporphyrin and phthalocyanine types. In particular, Radachlorin is excreted from organism much faster (in 1-2 days), as a result the problem of patient light hypersensitivity for a few months is non-actual for Radachlorin. As light source there was used a 662 nm diode laser specially designed for PDT with Radachlorin. The 5 year clinical results of PDT application to 89 patients with different malignant tumors are summarized and analysed. It is shown in particular that PDT with Radachlorin is a radical high efficient method for treatment of basal cell carcinoma of skin. At intravenous introduction in drug dose 0.5 mg/kg with light fluence 300-350 J/cm2 or in dose 1 mg/kg with fluence 200-250 J/cm2 the method gives full recovery in almost 100% cases with excellent cosmetic effect. The method was successfully combined with surgical operations, laser ablations, radio- and chemotherapy. Preoperative and intraoperative PDT favors improvement of results in complex treatment of malignant tumors. The method has a potential as palliative measure; in a number of incurable cases it allowed us to achieve recanalization of obturated hollow organs, eliminate the inflammatory complications, and as a result to improve life quality.

Photodynamic therapy with saturating of photochemical dose (PD) using three different techniques was studied theoretically. At saturation PD does not depend on the light fluence and is determined by concentration of photosensitizer or oxygen.