This PDF file contains the front matter associated with SPIE Proceedings Volume 9542 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

Photodynamic cancer therapy (PDT) had already proved its effectiveness in vitro but the search for more effective photosensitizers is encouraged and ongoing. Gold nanoparticles (AuNPs), have been shown to be good drug delivery agents, but in this work AuNPs were investigated as photodynamic agents for PDT. AuNPs were synthesized and characterized by means UV-Vis spectroscopy and transmission electron microscopy (TEM). Photodynamic effects of AuNPs in MCF-7 cells were evaluated using trypan blue, adenosine triphosphate (ATP) luminescence and lactate dehydrogenase (LDH) membrane integrity for cell viability, proliferation and cytotoxicity, respectively. AuNPs had a peak absorption at 540 nm, spherical in shape and were successfully taken up by MCF-7 cells. As a result of light activation or not, cell damage was observed and AuNPs modified into dendrimer-entrapped gold nanoparticles (AuDENPs), which only yielded effects in a light dependent manner. AuNPs is not a suitable photodynamic agent but its modified AuDENPs can be essential in improving the efficiency of PDT.

Diagnosis improvement by means of metal nanoparticles possibilities is studied. Set of experiments to reveal their presence in deeper layers of multilayered biological tissue on optical properties is performed. Spectra in the optical range were collected on several distances, from several thicknesses of the first layer. Results are being discussed.

The prodrug 5-aminolevulinic acid (ALA) and its ester derivatives have been used in photodynamic therapy (PDT) in dermatology worldwide. In China, ALA-PDT was first used to treat urethral condylomata acuminata and non-melanoma skin cancers in 1997. A powder formulation of ALA hydrochloride was approved by the Chinese Food and Drug Administration for the treatment of condylomata acuminata in 2007. Large successful experience of treating condylomatas was accumulated compared with Western countries. Meanwhile, numerous clinical studies as well as off-label use of ALAPDT have been carried out in China. To reflect the progress of ALA-PDT in China, several major Chinese and English databases were searched and published data were reviewed in this article.

Photobiomodulation (PBM) is a promising approach to treat Parkinson’s disease (PD) symptoms in cellular or animal models. Unfortunately, little information is available on the optical parameters playing a role in the light dosimetry during PBM. We conducted a study to determine the effective attenuation coefficient μ_eff of PD-relevant human deep brain tissues at 671 and 808 nm, using a multichannel fluence rate-meter comprising sub-millimeter isotropic detectors. The first step involved measurements of tissue modifications induced by postmortem situation and tissue storage on rabbit brains. The parameter μ_eff was measured using various tissue conditions (in vivo, immediately after sacrifice, after six weeks’ storage at −20°C or in 10 % formaldehyde solution) on eight female New Zealand white rabbits. In the second step, fluence rate was measured at various locations of a frozen human deep brain when the deep brain was illuminated from the sphenoidal sinus. The results were processed by an iterative Monte-Carlo algorithm to generate sets of optical parameters, and results collected on rabbit brains were used to extrapolate the μ_eff value that would be observed in human deep brain tissues in vivo. Under all tissue conditions, the value of μ_eff at 808 nm was smaller than that at 671 nm. After long-term storage for six weeks at −20°C, μ_eff decreased, on average by 15 to 25 % at all wavelengths, while it increased by 5 to 15 % at all wavelengths after storage in formaldehyde. Therefore, a reasonable estimate of in vivo human deep brain μ_eff values at 671 and 808 nm can be obtained by multiplying the data we report by 120 %.

Stereotactic biopsy procedure is performed to obtain a tissue sample for diagnosis purposes. Currently, a fiber-based mechano-optical device for stereotactic biopsies of brain tumors is developed. Two different fluorophores are employed to improve the safety and reliability of this procedure: The fluorescence of intravenously applied indocyanine green (ICG) facilitates the recognition of blood vessels and thus helps minimize the risk of cerebral hemorrhages. 5- aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence is used to localize vital tumor tissue. ICG fluorescence detection using a 2-fiber probe turned out to be an applicable method to recognize blood vessels about 1.5 mm ahead of the fiber tip during a brain tumor biopsy. Moreover, the suitability of two different PpIX excitation wavelengths regarding practical aspects was investigated: While PpIX excitation in the violet region (at 405 nm) allows for higher sensitivity, red excitation (at 633 nm) is noticeably superior with regard to blood layers obscuring the fluorescence signal. Contact measurements on brain simulating agar phantoms demonstrated that a typical blood coverage of the tumor reduces the PpIX signal to about 75% and nearly 0% for 633 nm and 405 nm excitation, respectively. As a result, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy.

Several forms of Chlorin e6 and its derivatives are reported as efficient photosensitizers (PS) studied in Photodynamic Therapy (PDT) for oncologic applications. Fotolon® is a pure form of Chlorin e6 trisodium salt developed by Apocare Pharma.

Our laboratory is studying experimental thulium fiber laser (TFL) as a potential alternative lithotripter to the clinical gold standard Holmium:YAG laser. Safety studies characterizing undesirable Holmium laser-induced damage to ureter tissue have been previously reported. Similarly, this study characterizes TFL induced ureter and stone basket damage. A TFL beam with pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rates of 150-500 Hz was delivered through a 100-μm-core, low-OH, silica optical fiber to the porcine ureter wall, in vitro. Ureter perforation times were measured and gross, histological, and optical coherence tomography images of the ablation zone were acquired. TFL operation at 150, 300, and 500 Hz produced mean ureter perforation times of 7.9, 3.8, and 1.8 s, respectively. Collateral damage averaged 510, 370, and 310 μm. TFL mean perforation time exceeded 1 s at each setting, which is a greater safety margin than previously reported during Holmium laser ureter perforation studies.

Objective: Several studies indicate that ELT using wavelengths of high water absorption showed advantages compared to conventional ELT. Thulium–Lasers emit nearby the local absorption maximum of water at 1940nm. In this clinical study the effectiveness, safety and the feasibility of 1940nm-ELT is proven. Materials and Method: A single centric, prospective observational study was performed. 1940nm-laserenergy was applied using radial emitting fibres with continuous pullback (1mm/s). Treatment was performed under anesthesia (general, spinal, tumescent) thus simultaneous miniphlebectomy and ligation of perforators could be applied. Patient and technical details were systematically collected. Evaluation included: standardized questionnaire, clinical examination, color-duplex ultrasonography preoperatively, 3d, 4w, 6m postoperatively, statistic. Results: The 1940nm-ELT study include 55 patients (female/men=34/21, mean age 55y, range 23-90y) treating n=72 vessels. The mean maximum diameter of great saphenous veins (GSV, n=59) was 7.5mm (range 3.7–11.3mm) and of small saphenous veins (SSV, n=13) was 5.3mm (3.0-10.0mm). The mean applied longitudinal endovenous energy density (LEED) was 64.3J/cm (40.3-98.2J/cm) in GSVs and 51.0J/cm (37.6-72.7J/cm) in SSVs. Complete occlusion of the vein without sign of reflux was achieved in 100%. The mean length of non-occluded stump at the sapheno-femoral junction was 6.0mm (1.0-20.0mm). Postoperative reduction of the diameter of GSV was 1.6mm (21.3%) and 2.0mm (37.7%) in SSV. One (1.4%) endovenous heat induced thrombus (EHIT) was observed. Further adverse events were: paresthesia 10/72 (13.9%), ecchymosis 1/72 (1.4%), lymphocele 1/72 (1.4%), hyperpigmentation 1/72 (1.4%). The mean postoperative pain intensity was 1.3 and 1.8 single doses of analgesics were administered. Normal physical activity was reached after 3d (1-21d). Conclusion: 1940nm-ELT using radial light application effectively eliminates the reflux in insufficient saphenous veins by a significant diameter reduction. The risk profile correlates with other endothermal treatment options. Low postoperative pain and analgesic requirements with rapid convalescence indicate a high level of patient comfort.

We revealed that after exposure of scarified cornea of rabbits to low-intensity pulsed terahertz radiation 0.1 to 1.8 THz a positive effect on epithelization triggered within the first hours was higher compared to non-irradiated cornea. However, while elevating power of terahertz radiation up to 60.8 nW it resulted in retarding epithelialization process. At that, irradiation did not affect timeframe of complete corneal epithelialization. During experiments it was found that terahertz radiation was well tolerated, exhibited no toxic and allergic reactions or resulted in pathohistological changes in the eye tissues. Also, low-intensity terahertz radiation did not affect normal physiological functions of the eyes and facilitated to re-epithelialization of scarified eyes in rabbits.

A faster healing process was observed in superficial skin wounds after irradiation with the EMOLED photocoagulator. The instrument consists of a compact handheld photocoagulation device, useful for inducing coagulation in superficial abrasions. In this work we present the results of an in vivo study, in a murine model. Two superficial wounds were produced on the back of 12 mice: one area was left untreated, the other one was treated with EMOLED. Healthy skin was used as a control. The animals were sacrificed 3 hours, 12 hours, 1 day, 6 day after treatment. The treatment effects on back skin was monitored by visual observations, histopathological analysis, immuno-histochemical analysis, and nonlinear microscopic imaging performed at each follow up time, finding no adverse reactions and no thermal damage in both treated areas and surrounding tissues. In addition, a faster healing process, a reduced inflammatory response, a higher collagen content, and a better-recovered skin morphology was evidenced in the treated tissue with respect to the untreated tissue. These morphological features were characterized by means of immuno-histochemical analysis, aimed at imaging fibroblasts and myofibroblasts, and by SHG microscopy, aimed at characterizing collagen organization, demonstrating a fully recovered aspect of dermis as well as a faster neocollagenesis in the treated regions. This study demonstrates that the selective photothermal effect we used for inducing immediate coagulation in superficial wounds is associated to a minimal inflammatory response, which provides reduced recovery times and improved healing process.

Lasers have been used in combination with applied cooling methods to preserve superficial skin layers (100's μm's) during cosmetic surgery. Preservation of a thicker tissue surface layer (millimeters) may also allow development of other noninvasive laser procedures. We are exploring noninvasive therapeutic laser applications in urology (e.g. laser vasectomy and laser treatment of female stress urinary incontinence), which require surface tissue preservation on the millimeter scale. In this preliminary study, four lasers were compared for noninvasive creation of deep subsurface thermal lesions. Laser energy from three diode lasers (650, 808, and 980 nm) and a Ytterbium fiber laser (1075 nm) was delivered through a custom built, side-firing, laser probe with integrated cooling. An alcohol-based solution at -5 °C was circulated through a flow cell, cooling a sapphire window, which in turn cooled the tissue surface. The probe was placed in contact with porcine liver tissue, ex vivo, kept hydrated in saline and maintained at ~ 35 °C. Incident laser power was 4.2 W, spot diameter was 5.3 mm, and treatment time was 60 s. The optimal laser wavelength tested for creation of deep subsurface thermal lesions during contact cooling of tissues was 1075 nm, which preserved a surface layer of ~ 2 mm. The Ytterbium fiber laser provides a compact, low maintenance, and high power alternative laser source to the Neodymium:YAG laser for noninvasive thermal therapy.

In this paper we report on our recent achievement in application of conventional and cross-polarization OCT (CP OCT) modalities for in vivo clinical diagnostics in different medical areas including gynecology, dermatology, and stomatology. In gynecology, CP OCT was employed for diagnosing fallopian tubes and cervix; in dermatology OCT for monitoring of treatment of psoriasis, scleroderma and atopic dermatitis; and in stomatology for diagnosis of oral diseases. For all considered application, we propose and develop different image processing methods which enhance the diagnostic value of the technique. In particular, we use histogram analysis, Fourier analysis and neural networks, thus calculating different tissue characteristics as revealed by OCT’s polarization evolution. These approaches enable improved OCT image quantification and increase its resultant diagnostic accuracy.

Results of nevus, papilloma, dermatofibroma, and basal cell skin cancer removal by a 980±10 nm diode laser with "blackened" tip operating in continuous (CW) mode and automatic power control (APC) mode are compared. It was demonstrated that using APC mode decreases the width of collateral damage at removing of these nosological neoplasms of human skin. The mean width of collateral damage reached 0.846±0.139 mm for patient group with nevus removing by 980 nm diode laser operating in CW mode, papilloma - 0.443±0.312 mm, dermatofibroma - 0.923±0.271 mm, and basal cell skin cancer - 0.787±0.325 mm. The mean width of collateral damage reached 0.592±0.197 mm for patient group with nevus removing by 980 nm diode laser operating in APC mode, papilloma - 0.191±0.162 mm, dermatofibroma - 0.476±0.366 mm, and basal cell skin cancer - 0.517±0.374 mm. It was found that the percentage of laser wounds with collateral damage less than 300 μm of quantity of removed nosological neoplasms in APC mode is 50%, that significantly higher than the percentage of laser wounds obtained using CW mode (13.4%).

Endoscopic laser surgery provides an advantageous alternative to Argon Plasma Coagulation, endoscopic tweezers or electro-ablation in gastroenterology that facilitates a selective ablation of stomach tumors with an additional hemostatic effect in the surrounding tissue. This coagulation effect can also be employed for the treatment of gastric ulcers. It is mandatory to control the laser parameters regardless of the desired effect, either cancerous tissue ablation or coagulation to prevent ulcerous bleeding, in order to avoid stomach wall perforation or an insufficient therapeutic outcome. Dosimetric models constitute an attractive tool to determine the proper light dose in order to offer a customized therapy planning that optimizes the treatment results. In this work, a model for Nd:YAG laser surgery is applied to predict both the coagulation zone in gastric ulcers and the removal in adenocarcinomas under different laser setups. Results show clear differences in the effective zone of the gastric malignancy affected by both coagulation and ablation. Therefore the current model could be employed in the clinical practice to plan the optimal laser beam parameters to treat a certain type of pathologic stomach tissue with variable morphology and without risk of perforation or undertreated parts.

The optical properties of normal fibroblasts and fibroblasts cultured with cancer cells were studied in the frequency range of 0.2 - 1.0 THz. The results show the possibility to distinguish healthy cells from corrupted ones using their optical parameters.

Current diagnostic techniques in dentistry rely predominantly on X-rays to monitor dental caries. Terahertz Pulsed Imaging (TPI) has great potential for medical applications since it is a nondestructive imaging method. It does not cause any ionization hazard on biological samples due to low energy of THz radiation. Even though it is strongly absorbed by water which exhibits very unique chemical and physical properties that contribute to strong interaction with THz radiation, teeth can still be investigated in three dimensions. Recent investigations suggest that this method can be used in the early identification of dental diseases and imperfections in the tooth structure without the hazards of using techniques which rely on x-rays. We constructed a continuous wave (CW) and time-domain reflection mode raster scan THz imaging system that enables us to investigate various teeth samples in two or three dimensions. The samples comprised of either slices of individual tooth samples or rows of teeth embedded in wax, and the imaging was done by scanning the sample across the focus of the THz beam. 2D images were generated by acquiring the intensity of the THz radiation at each pixel, while 3D images were generated by collecting the amplitude of the reflected signal at each pixel. After analyzing the measurements in both the spatial and frequency domains, the results suggest that the THz pulse is sensitive to variations in the structure of the samples that suggest that this method can be useful in detecting the presence of caries.

Holmium lasers are nowadays the gold standard for endoscopic laser lithotripsy. However, there is a risk of damaging or perforating the ureter or kidney tissue when the vision is poor. An automatic tissue/stone differentiation would improve the handling and safety of the procedure. To achieve this objective, an easy and robust real-time discrimination method has to be found which can be used to realize a feedback loop to control the laser system. Two possible approaches have been evaluated: White light reflectance and fluorescence spectroscopy. In both cases, we use the treatment fiber for detection and evaluate the possibility to decide whether the fiber is placed in front of tissue or calculus by the signal that is delivered by the surface in front of it. White light reflectance spectroscopy uses the standard light source for endourologic surgeries: Radiation of a Xenon light source is coupled to the ureteroscope via a liquid light guide. The part of the white light that is reflected back into the fiber is spectroscopically analyzed. In a clinical proof of concept study reflection signals were measured in vivo in 8 patients. For differentiation of stone and tissue via autofluorescence, excitation as well as detection was done via the treatment fiber. A suitable excitation wavelength was chosen with in vitro measurements (UV / visible) on several human renal calculi and porcine tissues. For verification of the positive results with green excitation in a clinical proof of concept study, a measurement set-up was realized which allows the recording of fluorescence signals during an endourological intervention.

Laser surgery is an established clinical procedure in dental applications, soft tissue ablation, and ophthalmology. The presented experimental set-up for closed-loop control of laser bone ablation addresses a feedback system and enables safe ablation towards anatomical structures that usually would have high risk of damage. This study is based on combined working volumes of optical coherence tomography (OCT) and Er:YAG cutting laser. High level of automation in fast image data processing and tissue treatment enables reproducible results and shortens the time in the operating room. For registration of the two coordinate systems a cross-like incision is ablated with the Er:YAG laser and segmented with OCT in three distances. The resulting Er:YAG coordinate system is reconstructed. A parameter list defines multiple sets of laser parameters including discrete and specific ablation rates as ablation model. The control algorithm uses this model to plan corrective laser paths for each set of laser parameters and dynamically adapts the distance of the laser focus. With this iterative control cycle consisting of image processing, path planning, ablation, and moistening of tissue the target geometry and desired depth are approximated until no further corrective laser paths can be set. The achieved depth stays within the tolerances of the parameter set with the smallest ablation rate. Specimen trials with fresh porcine bone have been conducted to prove the functionality of the developed concept. Flat bottom surfaces and sharp edges of the outline without visual signs of thermal damage verify the feasibility of automated, OCT controlled laser bone ablation with minimal process time.

Several investigations of dental tissue ablation with ultrashort pulsed lasers suggest that these lasers enable precise and selective material removal and reduce the formation of micro cracks and thermal effects, when compared to ns-pulses. In this study, two damage mechanisms are presented occurring during ablation of dentin using a laser emitting pulses of a duration of 380 fs at a wavelength of 1040 nm. First, it was found that nano cracks appear around the craters after single fs-pulse ablation. These cracks are directed to the crater and cross the dentinal tubules. Transient investigation of the single fs-pulse ablation process by pump-probe microscopy suggest that the driving mechanism could be a pressure wave that is released after stress confinement. Second, squared ablation holes were created by moving the laser focus at scan speeds between 0.5 mm/s and 2.0 m/s and fluences up to 14 J/cm². It was found that deep cracks appear at the edges of the squared holes, if the scan speed is about 0.5 m/s. The fluence has only a minor impact on the crack formation. The crack propagation was investigated in the depth using x-ray micro tomography and optical coherence tomography. It was found that these cracks appear in the depth down to the dental pulp. These findings suggest that fast scanning of the laser beam is the key for damage free processing using ultrashort pulse lasers. Then, ablation rates of about 2.5 - 3.5 mm³/min/W can be achieved in dentine with pulse durations of 380 fs.

The use of ultrafast lasers (pulsed lasers with pulse lengths of a few picoseconds or less) offers the possibility for minimally invasive removal of soft ophthalmic tissue. The potential for using pico- and femtosecond pulses for modification of scleral tissue has been reported elsewhere [1-6] and has resulted in the introduction of new, minimally invasive, procedures into clinical practice [3, 5-10]. Our research is focused on finding optimal parameters for picosecond laser machining of scleral tissue without introducing any unwanted collateral damage to the tissue. Experiments were carried out on hydrated porcine sclera in vitro, which has similar collagen organization, histology and water content (~70%) to human tissue. In this paper we present a 2D finite element ablation model which employs a one-step heating process. It is assumed that the incident laser radiation that is not reflected is absorbed in the tissue according to the Beer-Lambert law and transformed into heat energy. The experimental setup uses an industrial picosecond laser (TRUMPF TruMicro 5x50) with 5.9 ps pulses at 1030 nm, with pulse energies up to 125 μJ and a focused spot diameter of 35 μm. The use of a scan head allows flexibility in designing various scanning patterns. We show that picosecond pulses are capable of modifying scleral tissue without introducing collateral damage. This offers a possible route for minimally invasive sclerostomy. Many scanning patterns including single line ablation, square and circular cavity removal were tested.

Corneal therapeutic molecules delivery represents a promising solution to maintain human corneal endothelial cells (HCECs) viability, but the difficulty is transport across cell membrane. A new delivery method published recently consists in ephemerally permeabilizing cell membranes using a photo-acoustic reaction produced by carbon nanoparticles (CNPs) and femtosecond laser (FsL). The aim of this work is to investigate the size of pores formed at cell membrane by this technique. To induce cell permeabilization, HCECs were put in contact with CNPs and irradiated with a 500 μm diameter Ti:Sa FsL focalized spot. Four sizes of marker molecules were delivered into HCECs to investigate pore sizes: calcein (1.2 nm), FITC-Dextran 4kDa (2.8 nm) and FITC-Dextran 70kDa (12 nm) and FITC-Dextran 2MDa (50 nm). Delivery of each molecule was assessed by flow cytometry, a technique able to measure their presence into cells. We showed that the delivery rate was dependent of their size. Calcein was delivered in 56.1±8.2% of HCECs, FITC-Dextran 4kDa in 42.2±3.5%, FITC-Dextran 70 kDa in 21.5±2.7% and finally FITC-Dextran 2MDa in 12.9±2.0%. It means that a large number of pores in the size ranging from 1.2 to 2.8 nm were formed. However, 12 nm and larger pores were almost half more infrequent. Pore sizes formed at cell membrane by the technique of cell permeabilization by FsL activated CNPs was investigated. The results indicated that the pore sizes are large enough for the efficient delivery of small, medium and big therapeutics molecules on HCECs by this technique.

Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

The knowledge of the light fluence rate distribution inside a biological tissue irradiated by a Laser (or LED) is fundamental to achieve medical treatments. In this paper, we present a semi-analytical model based on the 2-D Fourier Transform of the diffusion equation. This method can be applied to any irradiation source (cylindrically symmetric or not) at the surface of the tissue. Two particular beam shapes are studied: planar irradiation and flat beam with finite radius. The total fluence rate along the depth in tissues was computed by adding the collimated and the diffuse components. The analytical solution was also used to study the effect of the beam radius on the light attenuation. Measurements were performed using a tank filled with a liquid-simulating medium (Milk), illuminated with a LED array (660 nm, 100mm×100mm). Several circular diaphragms were used to obtain uniform circular beams with well defined radii. An optical fibre (with an isotropic tip) was used to measure the fluence rate inside the medium. Preliminary experimental results are in agreement with theoretical predictions.

The goal of this work is to quantify impact of in vivo photochemical treatment using indocyanine green (ICG) or encapsulated ICG and NIR laser irradiation through skin of rat with obesity by the follow up tissue sampling and histochemistry. After 1 hour elapsed since 1-min light exposure samples of rat skin with subcutaneous tissue of thickness of 1.5-2.5 mm were taken by surgery from rats within marked 4-zones of the skin site. For hematoxylin-eosin histological examination of excised tissue samples, fixation was carried out by 10%-formaldehyde solution. For ICG and encapsulated ICG subcutaneous injection and subsequent 1-min diode laser irradiation with power density of 8 W/cm², different necrotic regions with lipolysis of subcutaneous fat were observed. The obtained data can be used for safe layer-by-layer laser treatment of obesity and cellulite.

Identification and preservation of the cavernous nerves (CNs) during prostate cancer surgery is critical for post-operative sexual function. Electrical nerve stimulation (ENS) mapping has previously been tested as an intraoperative tool for CN identification, but was found to be unreliable. ENS is limited by the need for electrode-tissue contact, poor spatial precision from electrical current spreading, and stimulation artifacts interfering with detection. Alternatively, optical nerve stimulation (ONS) provides noncontact stimulation, improved spatial selectivity, and elimination of stimulation artifacts. This study compares ENS to pulsed/CW ONS to explore the ONS mechanism. A total of eighty stimulations were performed in 5 rats, in vivo. ENS (4 V, 5 ms, 10 Hz) was compared to ONS using a pulsed diode laser nerve stimulator (1873 nm, 5 ms, 10 Hz) or CW diode laser nerve stimulator (1455 nm). Intracavernous pressure (ICP) response and nerve compound action potentials (nCAPs) were measured. All three stimulation modes (ENS, ONS-CW, ONS-P) produced comparable ICP magnitudes. However, ENS demonstrated more rapid ICP response times and well defined nCAPs compared to unmeasurable nCAPs for ONS. Further experiments measuring single action potentials during ENS and ONS are warranted to further understand differences in the ENS and ONS mechanisms.

The interaction of light with biological materials, such as fruits and vegetables, is a complex process which involves both absorption, and scattering events at different scales. Measuring the optical properties of a fruit allows understanding the physical and chemical characteristics. In this paper, an optical bench based on the use of a continuous laser source and a CCD camera was developed to study the light diffusion inside apple tissue structures. The method refers to the well-known steady-state spatially resolved method. First, the optoelectronics system was tested with a tissue phantom in order to show the optimal sensing range required to obtain the best estimated optical properties. Second, experimental results were obtained using peeled and unpeeled apples as interrogated tissues. The data were confronted with a diffusion model in order to extract the optical properties at two wavelengths of 633, and 852 nm. To better understand the effect of the apple tissue structures, investigations into the propagation of light through a half cut apple were also performed.

Two innovative approaches for intraocular illumination during vitreoretinal surgery by application of white LEDs are being developed. Both techniques are less harmful to the patient, more convenient for the surgeon and smaller and cheaper compared to conventional illumination by Xenon light sources and optical fibers. These two novel approaches are: I) The miniature LED chandelier endoilluminator consisting of a single white LED with a “light probe” on top of the LED housing that fits in a small incision in the wall of the eye. II) The alternative transscleral LED endoilluminator is integrated into an eye speculum that presses the flat LED top against the eye. The intraocular space is only illuminated by light transmitted through the sclera. In contrast to conventional illumination techniques for vitreoretinal surgery no incision is necessary. Both approaches are evaluated with regard to potential photochemical and thermal risks for the patient´s retina and they are tested on porcine eyes.

Endoluminal surgery for the treatment of early stage colorectal cancer is typically based on electrocautery tools which imply restrictions on precision and the risk of harm through collateral thermal damage to the healthy tissue. As a potential alternative to mitigate these drawbacks we present laser machining of pig intestine by means of picosecond laser pulses. The high intensities of an ultrafast laser enable nonlinear absorption processes and a predominantly nonthermal ablation regime.

Laser ablation results of square cavities with comparable thickness to early stage colorectal cancers are presented for a wavelength of 1030 nm using an industrial picosecond laser. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue. The depth of the ablation can be controlled precisely by means of the pulse energy. Overall, the application of ultrafast lasers to ablate pig intestine enables significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional techniques.

Photodynamic therapy (PDT) is a clinically approved treatment that can exhibit onsite cytotoxic activity toward tumor cells. One of the main factors limiting PDT efficiency is tissue hypoxia derived from photodynamic action. PDT with pulse mode irradiation at the same peak fluence rates as in continuous wave (CW) mode and with appropriate irradiation parameters could be more effective in the potency of ¹O₂ generation and the cytotoxic effect enhancement by tissue reoxygenation. In this study, we demonstrated theoretically that the main parameter of pulse mode irradiation is the intermittency factor, which makes it possible to maintain the intended ³O₂ concentration and to regulate the efficiency of ¹O₂ generation. We also showed experimentally that photodynamic treatment with pulse mode irradiation has congruent cytotoxicity to CW mode but induces preferable cell apoptosis. We assume that not only is cumulative 1O2 concentration is important in photodynamic cytotoxicity, but so is the temporal distribution of ¹O₂ generation, which determines the types of cell death.