Objectives For the development and validation of diagnostic procedures based on microscopic methods, knowledge about the imaging depth and achievable resolution in tissue is crucial. This poses the challenge to develop a microscopic artificial phantom focused on the microscopic instead of the macroscopic optical tissue characteristics. Methods As existing artificial tissue phantoms designed for image forming systems are primarily targeted at wide field applications, they are unsuited for reaching the formulated objective. Therefore, a microscopy- and microendoscopy-suited artificial tissue phantom was developed and characterized. It is based on a microstructured glass surface coated with fluorescent beads at known depths covered by a scattering agent with modifiable optical properties. The phantom was examined with different kinds of microscopy systems in order to characterize its quality and stability and to demonstrate its usefulness for instrument comparison, for example, regarding structural as well as fluorescence lifetime analysis. Results The analysis of the manufactured microstructured glass surfaces showed high regularity in their physical dimensions in accordance with the specifications. Measurements of the optical parameters of the scattering medium were consistent with simulations. The fluorescent beads coating proved to be stable for a respectable period of time (about a week). The developed artificial tissue phantom was successfully used to detect differences in image quality between a research microscope and an endoscopy based system. Plausible causes for the observed differences could be derived based on the well known microstructure of the phantom. Conclusions The artificial tissue phantom is well suited for the intended use with microscopic and microendoscopic systems. Due to its configurable design, it can be adapted to a wide range of applications. It is especially targeted at the characterization and calibration of clinical imaging systems that often lack extensive positioning capabilities such as an intrinsic z-stage.

The influence of inhomogeneities in the emission characteristics of optical fiber diffusers on the light distribution within biological tissue was evaluated by Monte Carlo (MC) simulations and by experiments on optical phantoms. Due to the strong scattering of light within biological tissue, inhomogeneities in the emission profile become blurred within a short light propagation distance, so that the light distribution within the tissue approaches that of a homogeneous diffuser. The degree of feature vanishing in the light distribution is mainly determined by the width of the inhomogeneities. It was shown that the influence of local inhomogeneities on top of a homogeneous light distribution fades away very effectively within 1 mm of tissue depth, which results in a light distribution very close to that for a homogeneously emitting diffuser. Emission profiles composed of multiple narrow peaks distributed over the full diffuser length with a peak-to-peak distance of less than 2 mm result in an almost homogeneous light distribution after approximately 1 mm of tissue depth. While this article is focused on the impact of diffuser inhomogeneities on the light distribution within the tissue, the importance of further investigations on the related thermal effects is also discussed.

Background and ObjectivesLight delivery is an essential part of therapy forms like photodynamic therapy (PDT), laser‐induced thermotherapy, and endovenous laser therapy. While there are approaches to the light application for all three therapies, there is no diffuser that can be used for all three approaches. This diffuser must meet the following criteria: Homogeneous radiation profile over a length of 40 mm, efficient light extraction in the diffuser area, mechanical breakage resistance as well as thermal stability when applying high power.Study Design/Materials and MethodsAn ultrashort pulse laser was used to inscribe inhomogeneities into the core of a fused‐silica fiber core while scanning the laser focus within a linear arrangement of cuboids centered around the fiber axis. The manufactured diffuser was optically and mechanically characterized and examined to determine the maximum power that can be applied in a tissue environment.ResultsBased on the analysis of all examined diffusers, the manufactured diffuser exhibits an emission efficiency ε = (81.5 ± 5.9)%, an intensity variability of (19 ± 5)% between distal and proximal diffuser end, and a minimum bending radius Rb = (15.4 ± 1.5) mm. It was taken advantage of the fact that the outer areas of the fiber core do not undergo any structural changes due to the machining and therefore do not suffer a major loss of stability. Tissue experiments revealed that a maximal power of 15 W was deliverable from the diffuser without harming the diffuser itself.ConclusionsIt could be shown that a diffuser manufactured by ultrafast‐laser processing can be used for low power applications as well as for high power applications. Further tests have to show whether the mechanical stability is still maintained after the application of high power in a tissue environment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC

Photodynamic therapy is a promising method to selectively treat cancer with light. Therefore, the tumour cells have to be illuminated homogeneously by distributing optical fibers with diffuser tips within the tumour tissue. The challenge is to measure and thereby, tailor the irradiation of the diffusers. In this paper, a novel non-imaging, camera-based method to measure the radiation profile is introduced and compared to an established imaging-based method. The radiation profile of a commercial polymer diffuser with radial homogeneous emittance and the profile of an ultrafast-laser surface structured fiber with radially asymmetric emission was evaluated. For the novel method, the diffuser was positioned in close contact to the image sensor. After coupling a LED to the diffuser, images were recorded for various radial positions. The irradiation profiles of the diffusers were also determined using an imaging camera system. The radiation profiles measured with the novel approach stand in good agreement with the existing imaging method using radial homogeneously emitting diffusers. However, the comparison revealed that the novel approach is advantageous, if the radiation profile is radially asymmetric and if the near-field is of special interest. In this case, several details, such as double peaks, were resolved, which were invisible using other methods. The novel approach is of special interest for the development of simulation models to gain further knowledge about the laser-tissue interaction in the near-field of the fiber. Thereby, irradiation profiles of diffusers could be predicted and tailored towards an application specific irradiation.

Thermography is a widespread non-contact imaging method for determining temperature. Its application in medicine, however, has so far been limited and its significance h as n ot b een e xtensively r eviewed i n t his field. Hence the applicability of thermography in laser medicine has been evaluated by determining the corresponding essential parameters. This includes the emissivity of biological tissue, tissue phantoms and cylindrical light diffusers used for interstitial photodynamic therapy (iPDT). The time-dependent surface temperature of light diffusers for iPDT was thermographically recorded in air and compared to thermocouple measurements. Furthermore, laser light was applied via surface-parallel cylindrical light diffusers for iPDT to a tissue phantom and to porcine brain tissue in an iPDT-like setup. In case of the tissue phantom, four light diffusers were positioned at different lateral positions and depths below the surface, in case of the porcine tissue, only one diffuser was used. The temperature distribution at the surface was recorded thermographically and by a thermocouple. The results were compared to Monte Carlo based simulations of the temperature distribution at the surface. In the context of laser medicine, thermography seems useful for the inspection of components for laser light application. To protect tissue from unwanted thermal effects, the surface temperature of light applicators can be examined to localize potential temperature hot spots. Nevertheless limitations of thermography have to be considered, especially the fact that this method provides information exclusively about the temperature distribution at the surface.

Photodynamic Therapy (PDT) is a gentle method to treat cancer through irradiation by light. To guarantee a positive result from the treatment, a complete illumination of the treated malignant volume has to be reached. The technical challenge is to specifically decouple light from a wave guide, inserted into malignant regions. The aim of this study was to measure and simulate the radiation profile of radially emitting diffusers. An ultrafast laser system combined with a rotational axis was used to machine the distal end of optical fibers. Cylindrical and tapered shaped diffusers were produced. A low power diode laser (lambda = 670 nm) was coupled into the fiber to determine the emission profile, which was measured via a camera setup. The measured emission profiles were simulated using a 2D-Matlab model and a 3D-LightTools model. The simulated and measured intensity profile along the cylindrical and the tapered fiber tip is characterized by an intensity maximum at the beginning, constant intensity in the middle, and exponentially decreasing intensity at the end. The studies indicate that fiber diffusers with tailored 3D radiation profile can be manufactured using ultrafast lasers. Further investigations have to be performed to adapt the simulations to the measured data.

The fragmentation efficiency on Bego artificial stones during lithotripsy and the propulsive effect (via video tracking) was investigated for a variety of laser settings. A variation of the laser settings (pulse energy, pulse duration, repetition rate) altered the total application time required for stone fragmentation, the stone break up time, and the propulsion. The obtained results can be used to develop lithotripsy devices providing an optimal combination of low stone propulsion and high fragmentation efficacy, which can then be evaluated in a clinical setting. Additionally, the fluorescence of human kidney stones was inspected endoscopically in vivo. Fluorescence light can be used to detect stone-free areas or to clearly distinguish calculi from surrounding tissue or operation tools.

Knowledge of tissue optical properties, in particular the absorption mu(a) and the reduced scattering coefficient mu(s)', is required for diagnostic and therapeutic applications in which the light distribution during treatment has to be known. As it is generally very difficult to obtain this information with sufficient accuracy in vivo, optical properties are often approximately determined on ex vivo tissue samples. In this case, the obtained optical properties may strongly depend on the sample preparation. The extent of the expectable preparation-dependent differences was systematically investigated in comparative measurements on dissected and homogenized porcine tissue samples (liver, lung, brain, and muscle). These measurements were performed at wavelengths 520, 635, 660, and 785 nm, using a dual-step reflectance device and at a spectral range of 515 to 800 nm with an integrating sphere setup. In a third experiment, the density of tissue samples (dissected and homogenized) was investigated, as the characteristic of the packaging of internal tissue structures strongly influences the absorption and scattering. The standard errors of the obtained absorption and reduced scattering coefficients were found to be reduced in case of homogenized tissue. Homogenizing the tissues also allows a much easier and faster sample preparation, as macroscopic internal tissue structures are destroyed in the homogenized tissue so that a planar tissue sample with well-defined thickness can easily and accurately be prepared by filling the tissue paste into a cuvette. Consequently, a better reproducibility result was obtained when using homogenized samples. According to the density measurements accomplished for dissected and homogenized tissue samples, all types of tissues, except lung, showed a decrease in the density due to the homogenization process. The presented results are in good agreement for mu(s)' regardless of the preparation procedure, whereas mu(a) differs, probably influenced by blood content and dehydration. Because of faster and easier preparation and easier sample positioning, homogenization prior to measurement seems to be suitable for investigating the optical properties ex vivo. Additionally, by means of using the homogenization process, the sample size and thickness do not need to be particularly large, as is the case for most biopsies from the OR. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE)

OBJECTIVES:Ureteroscopic laser lithotripsy is an important and widely used method for destroying ureter stones. It represents an alternative to ultrasonic and pneumatic lithotripsy techniques. Although these techniques have been thoroughly investigated, the influence of some physical parameters that may be relevant to further improve the treatment results is not fully understood. One crucial topic is the propulsive stone movement induced by the applied laser pulses. To simplify and speed up the optimization of laser parameters in this regard, a video tracking method was developed in connection with a vertical column setup that allows recording and subsequently analyzing the propulsive stone movement in dependence of different laser parameters in a particularly convenient and fast manner. MATERIALS AND METHODS:Pulsed laser light was applied from below to a cubic BegoStone phantom loosely guided within a vertical column setup. The video tracking method uses an algorithm to determine the vertical stone position in each frame of the recorded scene. The time-dependence of the vertical stone position is characterized by an irregular series of peaks. By analyzing the slopes of the peaks in this signal it was possible to determine the mean upward stone velocity for a whole pulse train and to compare it for different laser settings. For a proof of principle of the video tracking method, a specific pulse energy setting (1 J/pulse) was used in combination with three different pulse durations: short pulse (0.3 ms), medium pulse (0.6 ms), and long pulse (1.0 ms). The three pulse durations were compared in terms of their influence on the propulsive stone movement in terms of upward velocity. Furthermore, the propulsions induced by two different pulse energy settings (0.8 J/pulse and 1.2 J/pulse) for a fixed pulse duration (0.3 ms) were compared. A pulse repetition rate of 10 Hz was chosen for all experiments, and for each laser setting, the experiment was repeated on 15 different freshly prepared stones. The latter set of experiments was compared with the results of previous propulsion measurements performed with a pendulum setup. RESULTS:For a fixed pulse energy (1 J/pulse), the mean upward propulsion velocity increased (from 120.0 to 154.9 mm · s-1 ) with decreasing pulse duration. For fixed pulse duration (0.3 ms), the mean upward propulsion velocity increased (from 91.9 to 123.3 mm · s-1 ) with increasing pulse energy (0.8 J/pulse and 1.2 J/pulse). The latter result corresponds roughly to the one obtained with the pendulum setup (increase from 61 to 105 mm · s-1 ). While the mean propulsion velocities for the two different pulse energies were found to differ significantly (P < 0.001) for the two experimental and analysis methods, the standard deviations of the measured mean propulsion velocities were considerably smaller in case of the vertical column method with video tracking (12% and 15% for n = 15 freshly prepared stones) than in case of the pendulum method (26% and 41% for n = 50 freshly prepared stones), in spite of the considerably smaller number of experiment repetitions ("sample size") in the first case. CONCLUSION:The proposed vertical column method with video tracking appears advantageous compared to the pendulum method in terms of the statistical significance of the obtained results. This may partly be understood by the fact that the entire motion of the stones contributes to the data analysis, rather than just their maximum distance from the initial position. The key difference is, however, that the pendulum method involves only one single laser pulse in each experiment run, which renders this method rather tedious to perform. Furthermore, the video tracking method appears much better suited to model a clinical lithotripsy intervention that utilizes longer series of laser pulses at higher repetition rates. The proposed video tracking method can conveniently and quickly deliver results for a large number of laser pulses that can easily be averaged. An optimization of laser settings to achieve minimal propulsive stone movement should thus be more easily feasible with the video tracking method in connection with the vertical column setup. Lasers Surg. Med. 50:333-339, 2018. © 2017 Wiley Periodicals, Inc.