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Abstract Laser ablation is a minimally invasive therapeutic technique to denature tumors through coagulation and/or vaporization. Computational simulations of laser ablation can evaluate treatment outcomes quantitatively and provide numerical indices to determine treatment conditions, thus accelerating the technique’s clinical application. These simulations involve calculations of light transport, thermal diffusion, and the extent of thermal damage. The optical properties of tissue, which govern light transport through the tissue, vary during heating, and this affects the treatment outcomes. Nevertheless, the optical properties in conventional simulations of coagulation and vaporization remain constant. Here, we propose a laser ablation simulation based on Monte Carlo light transport with a dynamic optical properties (DOP) model. The proposed simulation is validated by performing optical properties measurements and laser irradiation experiments on porcine liver tissue. The DOP model showed the replicability of the changes in tissue optical properties during heating. Furthermore, the proposed simulation estimated coagulation areas that were comparable to experimental results at low-power irradiation settings and provided more than 2.5 times higher accuracy when calculating coagulation and vaporization areas than simulations using static optical properties at high-power irradiation settings. Our results demonstrate the proposed simulation’s applicability to coagulation and vaporization region calculations in tissue for retrospectively evaluating the treatment effects of laser ablation.

Accurate determination of the optical properties of biological tissues enables quantitative understanding of light propagation in these tissues for optical diagnosis and treatment applications. The absorption ([Formula: see text]) and scattering ([Formula: see text]) coefficients of biological tissues are inversely analyzed from their diffuse reflectance (R) and total transmittance (T), which are measured using a double integrating spheres (DIS) system. The inversion algorithms, for example, inverse adding doubling method and inverse Monte Carlo method, are sensitive to noise signals during the DIS measurements, resulting in reduced accuracy during determination. In this study, we propose an artificial neural network (ANN) to estimate [Formula: see text] and [Formula: see text] at a target wavelength from the R and T spectra measured via the DIS to reduce noise in the optical properties. Approximate models of the optical properties and Monte Carlo calculations that simulated the DIS measurements were used to generate spectral datasets comprising [Formula: see text], [Formula: see text], R and T. Measurement noise signals were added to R and T, and the ANN model was then trained using the noise-added datasets. Numerical results showed that the trained ANN model reduced the effects of noise in [Formula: see text] and [Formula: see text] estimation. Experimental verification indicated noise-reduced estimation from the R and T values measured by the DIS with a small number of scans on average, resulting in measurement time reduction. The results demonstrated the noise robustness of the proposed ANN-based method for optical properties determination and will contribute to shorter DIS measurement times, thus reducing changes in the optical properties due to desiccation of the samples.

Abstract A miniaturized endoscopic laser system with laser steering has great potential to expand the application of minimally invasive laser treatment for micro-lesions inside narrow organs. The conventional systems require separate optical paths for endoscopic imaging and laser steering, which limits their application inside narrower organs. Herein, we present a novel endoscopic image-guided laser treatment system with a thin tip that can access inside narrow organs. The system uses a single fiber bundle to simultaneously acquire endoscopic images and modulate the laser-irradiated area. The insertion and operation of the system in a narrow space were demonstrated using an artificial vascular model. Repeated laser steering along set targets demonstrated accurate laser irradiation within a root-mean-square error of 28 $$\mu$$ μ m, and static repeatability such that the laser irradiation position was controlled within a 12 $$\mu$$ μ m radius of dispersion about the mean trajectory. Unexpected irradiation on the distal irradiated plane due to fiber bundle crosstalk was reduced by selecting the appropriate laser input diameter. The laser steering trajectory spatially controlled the photothermal effects, vaporization, and coagulation of chicken liver tissue. This novel system achieves minimally invasive endoscopic laser treatment with high lesion-selectivity in narrow organs, such as the peripheral lung and coronary arteries.

A quantitative analysis method of CO2 laser treatments promotes laser treatment performance and rapid clinical application of novel treatment devices. The in silico clinical trial approach, which is based on computational simulation of light-tissue interactions using the mathematical model, can provide quantitative data. Although several simulation methods of laser tissue vaporization with CO2 laser treatments have been proposed, validations of the CO2 laser wavelength have been insufficient. In this study, we demonstrated a tissue vaporization simulation using a CO2 laser and performed the experimental validation using a hydrogel phantom with constant physical parameters to evaluate the simulation accuracy of the vaporization process. The laser tissue vaporization simulation consists of the calculation of light transport, photothermal conversion, thermal diffusion, and phase change in the tissue. The vaporization width, depth, and area with CO2 laser irradiation to a tissue model were simulated. The simulated results differed from the actual vaporization width and depth by approximately 20% and 30%, respectively, because of the solubilization of the hydrogel phantom. Alternatively, the simulation vaporization area for all light irradiation parameters, which is related to the vaporization amount, agreed well with the actual vaporization values. These results suggest that the computational simulation can be used to evaluate the amount of tissue vaporization in the safety and effectiveness analysis of CO2 laser treatments.

Recently, combined therapy using chemotherapy and photodynamic therapy (PDT) has been proposed as a means of improving treatment outcomes. In order to evaluate the efficacy of combined therapy, it is necessary to determine the distribution of the anticancer drug and the photosensitizer. We investigated the use of imaging mass spectrometry (IMS) to simultaneously observe the distributions of an anticancer drug and photosensitizer administered to cancer cells. In particular, we sought to increase the sensitivity of detection of the anticancer drug docetaxel and the photosensitizer protoporphyrin IX (PpIX) by optimizing the ionization-assisting reagents. When we used a matrix consisting of equal weights of a zeolite (NaY5.6) and a conventional organic matrix (6-aza-2-thiothymine) in matrix-assisted laser desorption/ionization, the signal intensity of the sodium-adducted ion of docetaxel (administered at 100 μM) increased about 13-fold. Moreover, we detected docetaxel with the zeolite matrix using the droplet method, and detected PpIX by fluorescence and IMS with α-cyano-4-hydroxycinnamic acid (CHCA) using the spray method.

A continuous flow atmospheric pressure laser desorption/ionization technique using a porous stainless steel probe and a 6–7-µm-band mid-infrared tunable laser was developed. This ion source is capable of direct ionization from a continuous flow with a high temporal stability. The 6–7-µm wavelength region corresponds to the characteristic absorption bands of various molecular vibration modes, including O–H, C=O, CH3 and C–N bonds. Consequently, many organic compounds and solvents, including water, have characteristic absorption peaks in this region. This ion source requires no additional matrix, and utilizes water or acetonitrile as the solvent matrix at several absorption peak wavelengths (6.05 and 7.27 µm, respectively). The distribution of multiply-charged peptide ions is extremely sensitive to the temperature of the heated capillary, which is the inlet of the mass spectrometer. This ionization technique has potential for the interface of liquid chromatography/mass spectrometry (LC/MS).

Molecules such as water, proteins and lipids that are contained in biological tissue absorb mid-infrared (MIR) light, which allows such light to be used in laser surgical treatment. Esters, amides and water exhibit strong absorption bands in the 5–7 μm wavelength range, but at present there are no lasers in clinical use that can emit in this range. Therefore, the present study focused on the quantum cascade laser (QCL), which is a new type of semiconductor laser that can emit at MIR wavelengths and has recently achieved high output power. A high-power QCL with a peak wavelength of 5.7 μm was evaluated for use as a laser scalpel for ablating biological soft tissue. The interaction of the laser beam with chicken breast tissue was compared to a conventional CO2 laser, based on surface and cross-sectional images. The QCL was found to have sufficient power to ablate soft tissue, and its coagulation, carbonization and ablation effects were similar to those for the CO2 laser. The QCL also induced comparable photothermal effects because it acted as a pseudo-continuous wave laser due to its low peak power. A QCL can therefore be used as an effective laser scalpel, and also offers the possibility of less invasive treatment by targeting specific absorption bands in the MIR region.

Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.

In a previous study, we developed a novel fingerprint optical sensor that can detect fingerprint patterns within the skin of a finger without considering the effect of surface condition, and the illumination position of our sensor was optimized experimentally. When a light source irradiated the root of a nail, the output image was bright without saturation. Therefore, the fingerprint image was clear, and a large area of the fingerprint pattern was clear. The aim of the present study was to clarify by experiments the mechanism underlying these results, and we hypothesized that light is scattered throughout the bone and less scattered in the muscle. Thus, the output image is strongly shaded when the nail-side position is irradiated with light. To test the hypothesis and clarify the shading mechanism, we constructed a simple simulation model that consisted of only bone and muscle and used the Monte Carlo method to simulate optical scattering in the tissue. The simulation results were in good agreement with the experimental results, which, in turn, proved our hypothesis. This study contributes to improving our fingerprint sensor, for example, by improving verification performance for use in a wide range of applications. Furthermore, our study contributes to the development of various optical sensors for use with biological tissues. [ABSTRACT FROM AUTHOR]

The optical properties of human brain tumor tissues, including glioblastoma, meningioma, oligodendroglioma, and metastasis, that were classified into "strong," "vague," and "unobservable" fluorescence by a neurosurgeon were measured and compared. The optical properties of the tissues were measured with a double integrating sphere and the inverse Monte Carlo technique from 350 to 1000 nm. Using reasons of ex-vivo measurement, the optical properties at around 420 nm were potentially affected by the hemoglobin content in tissues. Significant differences were not observed between the optical properties of the glioblastoma regions with "strong" and "unobservable" fluorescence. Sections of human brain tumor tissue with "strong" and "unobservable" fluorescence were stained with hematoxylin and eosin. The cell densities [mean ± standard deviation (S.D.)] in regions with "strong" and "unobservable" fluorescence were 31 ± 9 x 10² per mm² and 12 ± 4 x 10² per mm², respectively, which is a statistically significant difference. The higher fluorescence intensity is associated with higher cell density. The difference in cell density modified the scattering coefficient yet it does not lead to significant differences in the reduced scattering coefficient and thus does not affect the propagation of the diffuse fluorescent light. Hence, the false negatives, which mean a brain tumor only shows "unobservable" fluorescence and is hence classified incorrectly as nontumor, in using 5-ALA for detection of human glioblastoma do not result from the differences in optical properties of human brain glioblastoma tissues. Our results suggest that the primary cause of false negatives may be a lack of PpIX or a low accumulation of PpIX. [ABSTRACT FROM AUTHOR]

Herein, the optical adequacy of a tumor model prepared with tumor cells grown on the chorioallantoic membrane (CAM) of a chicken egg is evaluated as an alternative to the mouse tumor model to assess the optimal irradiation conditions in photodynamic therapy (PDT). The optical properties of CAM and mouse tumor tissues were measured with a double integrating sphere and the inverse Monte Carlo technique in the 350- to 1000-nm wavelength range. The hemoglobin and water absorption bands observed in the CAM tumor tissue (10 eggs and 10 tumors) are equal to that of the mouse tumor tissue (8 animals and 8 tumors). The optical intersubject variability of the CAM tumor tissues meets or exceeds that of the mouse tumor tissues, and the reduced scattering coefficient spectra of CAM tumor tissues can be equated with those of mouse tumor tissues. These results confirm that the CAM tumor model is a viable alternative to the mouse tumor model, especially for deriving optimal irradiation conditions in PDT. [ABSTRACT FROM AUTHOR]

No previous reports have observed inside the root canal using both optical coherence tomography (OCT) and x-ray microcomputed tomography (μCT) for the same sample. The purpose of this study was to clarify both OCT and μCT image properties from observations of the same root canal after resin core build-up treatment. As OCT allows real-time observation of samples, gap formation may be able to be shown in real time. A dualcure, one-step, self-etch adhesive system bonding agent, and dual-cure resin composite core material were used in root canals in accordance with instructions from the manufacturer. The resulting OCT images were superior for identifying gap formation at the interface, while μCT images were better to grasp the tooth form. Continuous tomographic images from real-time OCT observation allowed successful construction of a video of the resin core build-up procedure. After 10 to 12 s of light curing, a gap with a clear new signal occurred at the root-core material interface, proceeding from the coronal side (6 mm from the cemento-enamel junction) to the apical side of the root. [ABSTRACT FROM AUTHOR]

Less invasive methods for treating dental caries are strongly desired. However, conventional dental lasers do not always selectively remove caries or ensure good bonding to the composite resin. According to our previous study, demineralized dentin might be removed by a nanosecond pulsed laser operating at wavelengths of around 5.8 µm. The present study investigated the irradiation effect of the light on carious human dentin classified into "remove," "not remove," and "unclear" categories. Under 5.85-µm laser pulses, at average power densities of 30 W/cm² and irradiation time of 2 s, the ablation depth of "remove" and "not remove," and also the ablation depth of "unclear" and "not remove," were significantly different (p < 0.01). The ablation depth was correlated with both Vickers hardness and Ca content. Thus, a nanosecond pulsed laser operating at 5.85 µm proved an effective less-invasive caries treatment. [ABSTRACT FROM AUTHOR]

Coronal tooth lesions, such as caries, enamel cracking, and composite resin restoration cavities, have been observed by optical coherence tomography (OCT). This pilot study was performed to verify whether OCT could reveal details of root canals filled with resin core build-up. A dual-cure, one-step, self-etch adhesive system-bonding agent (Clearfil Bond SE ONE, Kuraray Noritake Dental) and dual-cure resin composite core material (Clearfil DC Core Automix ONE, Kuraray Noritake Dental) were used according to the manufacturer's instructions in root canals. OCT was performed at three stages of the core build-up: after the post space preparation, after bonding application, and after resin core fabrication. The cementum was removed in the cementum absent group and the root was left untreated in the cementum present group. Bubbles were observed in the resin cores and gaps formed between the resin core and dentin. In the cementum absent group, the internal structure of the root could be visualized clearly compared with the cementum present group. The root internal structure could be observed by OCT and the image became clearer when cementum was removed. [ABSTRACT FROM AUTHOR]

AbstractBackground Data and Objective:Mesenchymal stem cells (MSCs) are multipotent cells present in adult bone marrow that replicate as undifferentiated cells and can differentiate to lineages of mesenchymal tissues. Homeostatic control of bone remodeling maintains bone mass by ensuring that bone resorption and bone formation occur sequentially and in a balanced manner. As most homeostatic functions occur in a circadian manner, a circadian clock could control bone mass. Here we show that laser irradiation can direct the extracellular calcification of mouse MSCs by altering the intracellular localization of the circadian rhythm protein cryptochrome 1 (CRY1). Materials and Methods:MSCs were irradiated with a blue laser (wavelength 405 nm) for 180 sec via a fiber attached to the bottom of the culture dish. After laser irradiation, the MSCs were incubated in osteogenic differentiation medium for 5 d. After laser irradiation, circadian rhythm protein CRY1 was immunostained and histochemical staining for extracellular calcification was observed. Results:Laser irradiation promoted extracellular calcification of MSCs, induced the translocation of CRY1 protein from the cytoplasm to the nucleus, and decreased CRY1 mRNA levels quantified by real-time PCR. Since the timing of nuclear accumulation of clock proteins constitutes an important step in the transcription-translation feedback loop driving the circadian core oscillator, laser irradiation could provide a simple and effective technology for clock protein localization and turnover. Our results also indicate that CRY1 is a master regulator of circadian rhythm that regulates the extracellular calcification of MSCs. Conclusion:Laser irradiation could provide a simple and effective means of controlling the fate of MSCs as a therapeutic strategy, and act as a “molecular switch” of regulatory proteins by suppressing CRY transcription. Furthermore, this model system may be useful for exploring the cross-talk between circadian rhythm and cell function. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaques consist mainly of cholesteryl esters, and the C=O stretching vibration mode of cholesteryl esters strongly absorbs radiation at a wavelength of 5.75 µm. For clinical application of less-invasive laser angioplasty with 5.75 µm, a compact laser is required. Quantum cascade lasers (QCLs) are semiconductor lasers that can emit radiation in the mid-IR range. In this study, the potential of the QCL for less-invasive laser angioplasty was evaluated. At the average power density of 180 W/cm2, the atherosclerotic aorta was ablated for the irradiation time of 1 s or more, whereas the normal aorta was ablated for more than 10 s. This demonstrates that selective ablation of the atherosclerotic aorta was achieved. However, strong coagulation and carbonization were observed. For reducing thermal effects, improving the pulse structure is required. In conclusion, the QCL achieved the selective ablation of the atherosclerotic lesions, which indicates the potential of the QCL. [ABSTRACT FROM AUTHOR]

A novel stigmatic mass microscope using laser desorptionionization and a multi-turn time-of-flight mass spectrometer, MULTUM-IMG, has been developed. Stigmatic ion images of crystal violet masked by a fine square mesh grid with a 12.7 m pitch as well as microdot patterns with a 5 m dot diameter and a 10 m pitch made with rhodamine B were clearly observed. The estimated spatial resolution was about 3 m in the linear mode with a 20-fold ion optical magnification. Separating stigmatic ion images according to the time-of-flight, i.e., the mass-to-charge ratio of the ions was successfully demonstrated by a microdot pattern made with two different dyes, crystal violet and methylene blue. Stigmatic ion images of a microdot pattern made with crystal violet were observed after circulation in MULTUM-IMG, and the pattern of the ion image was maintained after ten cycles in MULTUM-IMG. A section of a mouse brain stained with crystal violet and methylene blue was observed in the linear mode, and the stigmatic total ion image of crystal violet and methylene blue agreed well with the optical microphotograph of the hippocampus for the same section. [ABSTRACT FROM AUTHOR]

An infrared technique for molecular alignment control of discotic columnar liquid crystals is described. The liquid crystal domain change was induced in hexagonal columnar mesophase by infrared irradiation with a vibrational excitation of the chemical bonds in the triphenylene mesogen. In the new domain a uniform alignment of molecules was attained and the behaviour is essentially related to the polarisation of the incident beam. Also the new domain is quite stable, though depending on temperature. However, such a new domain formation was not observed in the discotic nematic phase. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are multipotent cells present in adult bone marrow that replicate as undifferentiated cells and can differentiate to lineages of mesenchymal tissues. Homeostatic control of bone remodelling maintains bone mass by insuring that bone resorption and bone formation occur sequentially and in a balanced manner. As most homeostatic functions occur in a circadian manner, a circadian clock could control bone mass. Here, we show that laser irradiation can direct the osteogenesis and adipogenesis of mouse MSCs by altering the intracellular localization of the circadian rhythm protein Cryptochrome 1 (mCRY1). After laser irradiation (wavelength: 405 nm) to MSCs, circadian rhythm protein, mCRY1 and mPER2, were immunostained and histochemical stainings for osteogenic or adipogenic differentiation were observed. Laser irradiation promoted osteogenesis and reduced adipogenesis of MSCs, induced the translocation of mCRY1 and mPER2 protein from the cytoplasm to the nucleus, and decreased mCRY1 mRNA levels quantified by real-time PCR. Since the timing of nuclear accumulation of clock proteins constitutes an important step in the transcription-translation feedback loop driving the circadian core oscillator, laser irradiation could provide a simple and effective technology for clock protein localization and turnover. Our results also indicate that mCRY1 is a master regulator of circadian rhythm that regulates the differentiation of MSCs. Laser irradiation could provide a simple and effective means of controlling the fate of MSCs as a therapeutic strategy and act 'molecular switch' of regulatory proteins by suppressing CRY transcription. Furthermore, this model system may be useful for exploring the crosstalk between circadian rhythm and cell differentiation.