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Background and objectives In this study, the threshold fluences for disrupting the melanosomes for pigmented skin lesion treatment were determined using a 755-nm picosecond laser for clinical use. Based on the melanosome disruption thresholds, incident fluences corresponding to the target lesion depths were evaluated in silico for different laser spot sizes. Study design/materials and methods Melanosome samples were isolated from porcine eyes as alternative samples for human cutaneous melanosomes. The isolated melanosomes were exposed to 755-nm picosecond laser pulses to measure the mean particle sizes by dynamic light scattering and confirm their disruption by scanning electron microscopy. The threshold fluences were statistically determined from the relationships between the irradiated fluences and the mean particle sizes. Incident fluences of picosecond laser pulses for the disruption of melanosomes located at different depths in skin tissue were calculated through a light transport simulation using the obtained thresholds. Results The threshold fluences of 550- and 750-picosecond laser pulses were determined to be 2.19 and 2.49 J/cm2 , respectively. The numerical simulation indicated that appropriate incident fluences of picosecond laser pulses differ depending on the depth distribution of the melanosomes in the skin tissue, and large spot sizes are desirable for disrupting the melanosomes more deeply located within the skin tissue. Conclusion The threshold fluences of picosecond laser pulses for melanosome disruption were determined. The incident fluence analysis based on the thresholds for melanosome disruption provides valuable information for the selection of irradiation endpoints for picosecond laser treatment of pigmented skin lesions. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Since 2000, Federation Dentaire Internationale has advocated for “minimal intervention” dental treatments. The dental field has demanded less-invasive caries treatment methods. However, recent caries treatments using a microsecond-pulsed free-running Er:YAG laser with a pulse duration of 200–300 μs have issues with non-selectivity for caries due to the thermal effect caused by the laser. To improve the selectivity by reducing the thermal effect, the ablation characteristics of a nanosecond-pulsed Er:YAG laser are investigated. A Q-switched Er:YAG laser with a rotating mirror Q-switching system attached to a flash lamp-pumped Er:YAG laser and a free-running Er:YAG laser were used. The pulse duration of the Q-switched Er:YAG laser was 80–130 ns, while that of the free-running Er:YAG laser was around 200 μs. The pulse repetition rate of the free-running Er:YAG laser was constant at 10 Hz, but that of the Q-switched Er:YAG laser fluctuated between 10 and 23 Hz. The fluence was 6, 10, or 14 J/cm2. The samples were bovine sound dentin slices and caries models. Caries models were prepared by immersing sound dentin slice samples into a 0.1-M lactic acid solution for 24 h at 37 °C. The samples were irradiated with the two lasers horizontally without water spray for 1, 2, or 4 s. Laser irradiation experiments indicate that the selectivity towards caries occurs at the fluence of 6 J/cm2 without water spray. The ablation depth of a demineralized dentin slice by the Q-switched Er:YAG laser is about three times that by the free-running Er:YAG laser at the fluence of 10 J/cm2. In addition, the Q-switched Er:YAG laser suppresses the thermal effect reducing the range of the thermal melting area. Caries dentin may be selectively removed without water spray using the Q-switched Er:YAG laser with suppressing dental pulp necrosis because the temperature increase is below 5 °C. The ablation depths by the Q-switched Er:YAG are about three times larger than those using the free-running Er:YAG laser.

The possibility of using photoacoustic imaging for functional diagnosis has attracted much attention especially in the clinical field. Among such imaging systems, a system, which offers real-time imaging using compact and low-priced LEDs as a light source, has appeared. Compared to solid state lasers, the LED pulse energy was extremely small, so it had been thought that imaging would be extremely difficult, but by adding a pre-amplifier, real time photoacoustic imaging became possible. However the signal-to-noise ratio (SNR) and the amplifier gain needed for making real time imaging possible have remained unclear. The present study was designed to clarify these data. The results showed that, using a tissue phantom and human fingers, an SNR > 4 and amplifier gain > 80dB were required, and demonstrated why making an image without a pre-amplifier had proved difficult.

Endoscopic submucosal dissection (ESD) has been at the forefront of international attention as a less invasive treatment for early gastrointestinal cancer. Currently, ESD involves the use of an electrosurgical knife for mucosal incision and subsequent submucosal dissection. However, it has been reported that perforation occurs in approximately 5% of cases. To enhance tissue selectivity with this modality, we focused on applying a laser to ESD (laser ESD). A CO2 laser was chosen as the surgical knife because the saline or sodium hyaluronate solution injected into the submucosal layer during the current ESD procedure has a high absorption coefficient at the wavelength of the CO2 laser. Thus, the purpose of this study is to quantitatively clarify the safety and efficacy of laser ESD for the colon. First, we validated a porcine colon as a model of the human colon in terms of optical and thermal properties. Next, ex vivo experiments on the safety and efficacy of laser ESD were performed. In ex vivo experiments using extracted porcine colon tissue, an incision depth of 0.5–1.0 mm was obtained without thermal damage to the muscle layer when the power density was set at 17, 22, or 28 W/mm2. In addition, less thermal damage was observed in tissue incised with this method compared with electrosurgical knives. These results might be explained by the strong absorption of the CO2 laser by the saline injected into the submucosa. Therefore, laser ESD is expected to be a safer method for the treatment of early colon cancer.

In picosecond laser treatments for pigmented skin lesions, selective optical absorption by melanin particles packaged in cutaneous melanosomes results in producing treatment effects. The treatment effects have been numerically analyzed by simulating light propagation and thermal diffusion at a tissue scale. During picosecond laser irradiation, cutaneous melanosomes are disrupted by explosive vaporization through optical absorption by melanin particles. A multiscale modeling of picosecond laser skin treatments is required for the quantitative evaluation of picosecond therapeutic laser devices. By the multiscale modeling, the treatment effects can be evaluated based on the interactions with picosecond laser pulses at each scale of molecule, organelle, cell, and tissue. For the multiscale modeling, the purpose of this study is to investigate a response of melanin particles to picosecond laser pulses at a molecular scale. Homogeneous melanin suspensions were prepared to irradiate 550-picosecond laser pulses at a wavelength of 755 nm. As a result of comparing morphological characteristics between unirradiated melanin particles and melanin particles irradiated by picosecond laser pulses with a scanning electron microscope and a particle size analyzer using dynamic light scattering, almost no significant change was found. The results suggested that melanin particles do not change the structures and are involved as a heat source to cause damage on lipid bilayer membranes within melanosomes in picosecond laser treatments for pigmented skin lesions.

Photoacoustic imaging is expected to be a next-generation diagnostic modality. However, systems using a solid state laser (SSL) are expensive, large in size and poor in operability of probes. In addition, protective goggles are required because of laser light. Therefore, we have adopted the LED technology and improved the signal-to-noise-ratio (SNR) of the LED-based system, which had been 1 / 2.3 million of the SSL, to the same level with four innovative technologies. These innovative technologies include a) High power and high density LED array technology: Use of high power LED chips with luminous efficiency comparable to laser diode, high density mounting of LED chips on Aluminum base and compact design, b) Giant and ultra-short-pulse drive circuit technology: High speed on-and-off by low-resistance Metal Oxide Semiconductor Field Effect Transistor (MOSFET), and position separation of high-voltage drive circuit from ultrasonic probe (USP) by series connection of LEDs, c) Optical pulse generation technology optimum for frequency response characteristic of USP, d) Noise reduction technology for faint signals using ultra-amplification: Minimization of quantization noise of Analog-digital-converter (ADC) by wide band ultra-amplification of 86 dB, and noise reduction by averaging of

Photothermal damages in laser skin treatments were evaluated computationally to analyze differences between ethnic groups. Our results revealed the seriousness of photothermal damage was varied between the ethnic groups even on the same irradiation conditions.

BACKGROUND AND OBJECTIVES: Computational clinical trial (CCT) in the field of laser medicine promotes clinical application of novel laser devices, because this trial carried out based on numerical modeling of laser-tissue interactions and simulation of a series of treatment process. To confirm the feasibility of the computational clinical trial of skin treatment with a novel picosecond laser, this paper presents an evaluation method of the safety. STUDY DESIGN/MATERIALS AND METHODS: In this method, the light propagation and thermal diffusion process after ultrashort light pulse irradiation to a numerical skin model is calculated and the safety based on the photothermal damage is evaluated by computational modeling and simulation. As an example, the safety of a novel picosecond laser device was examined by comparing with several laser devices approved for clinical use. RESULTS: The ratio of the maximum thermal damage induced by picosecond laser irradiation was 1.2 × 10(−2) % at the epidermis, while that caused by approved laser irradiation was 99 % at the capillary vessels. The numerical simulation demonstrated that less thermal damage was observed compared with the approved devices. The results show the safety simulated by photothermal damage calculation was consistent with the reported clinical trials. CONCLUSIONS: This computational clinical trial shows the feasibility of applying computational clinical trials for the safety evaluation of novel medical laser devices. In contrast to preclinical and clinical tests, the proposed computational method offers regulatory science for appropriately and quickly predicting and evaluating the safety of a novel laser device.

Interstitial photodynamic therapy (iPDT), which uses optical fibers to excite photosensitizers in PDT, is a promising approach in the treatment of internal tumors. To enhance the treatment efficacy, the placement of the inserted optical fibers should be optimized from the photosensitizer distribution in the affected area. Here, we propose a method to obtain a fluorescence distribution of photosensitizers during iPDT. The inserted optical fibers for iPDT can be also used for detection of the fluorescence from the photosensitizer in the tissue. In the proposed method, fluorescence signals from the photosensitizers are collected by changing the combination of the inserted optical fibers for excitation and detection. The detected fluorescence signals are modeled by using excitation light distribution, fluorescence detection efficiency, and photosensitizer distribution. The excitation light distribution and the fluorescence detection efficiency distribution are obtained by calculating light propagation in the tissue. The photosensitizer distribution is reconstructed from the detected signals with a compressive sensing algorithm with a sparsity constraint. As a demonstration, we performed numerical simulations to obtain a photosensitizer distribution in a biological tissue by inserting several optical fibers for excitation and detection. In the numerical simulation, we verified the spatial distribution of the photosensitizers in a biological tissue can be reconstructed from the fluorescence signals detected by inserting the optical fibers.

An in silico method is proposed to evaluate thermal skin damage caused by picosecond laser irradiation. The results show the temperature rise and the thermal damage are noninferiority to a conventional nanosecond domain laser device.

Cholesteryl esters are the main components of atherosclerotic plaques, and they have an absorption peak at the wavelength of 5.75 µm. To realize less-invasive ablation of the atherosclerotic plaques using a quasi-continuous wave (quasi-CW) quantum cascade laser (QCL), the thermal effects on normal vessels must be reduced. In this study, we attempted to reduce the thermal effects by controlling the pulse structure. The irradiation effects on rabbit atherosclerotic aortas using macro pulse irradiation (irradiation of pulses at intervals) and conventional quasi-CW irradiation were compared. The macro pulse width and the macro pulse interval were determined based on the thermal relaxation time of atherosclerotic and normal aortas in the oscillation wavelength of the QCL. The ablation depth increased and the coagulation width decreased using macro pulse irradiation. Moreover, difference in ablation depth between the atherosclerotic and normal rabbit aortas using macro pulse irradiation was confirmed. Therefore, the QCL in the 5.7-µm wavelength range with controlling the pulse structure was effective for less-invasive laser angioplasty.

Since the increase in the overall mortality rate in patients with colon cancer is remarkably high in recent years, early treatment is required. For this reason, endoscopic submucosal dissection (ESD) has been at the forefront of international attention as a low invasive treatment for early digestive cancer. In current ESD procedure, an electrosurgical knife is used for mucosal incision and subsequent submucosal dissection. However, the perforation has been reported to occur by approximately 5%. Thus, to enhance the tissue selectivity of this modality, we focused on the application of laser for ESD. A carbon dioxide laser was chosen as a surgical knife because the saline or a sodium hyaluronate solution injected into the submucosal layer in current ESD procedure has a high absorption coefficient at the wavelength of the carbon dioxide laser. In this research, ex vivo experiment was performed at the output power of 3–7 W and discuss the optimum irradiation power of laser. As a result of ex vivo experiment using extracted porcine colon tissues, mucosal incision and submucosal dissection were safely and less invasively performed in every output power, without reaching the thermal damage to a muscular layer. This is because a carbon dioxide laser is strongly absorbed by saline injected into submucosa. ESD using a carbon dioxide laser is a safer method for the treatment of early colon cancer. We are planning to measure and compare the optical and thermal properties of porcine colon with those of human colon.

Due to the characteristic absorption peaks in the IR region, various molecules can be used as a matrix for infrared matrix-assisted laser desorption/ionization (IR-MALDI). Especially in the 6–7 µm-band IR region, solvents used as the mobile phase for liquid chromatography have absorption peaks that correspond to their functional groups, such as O–H, CO, and CH3. Additionally, atmospheric pressure (AP) IR-MALDI, which is applicable to liquid-state samples, is a promising technique to directly analyze untreated samples. Herein we perform AP-IR-MALDI mass spectrometry of a peptide, angiotensin II, using a mid-IR tunable laser with a tunable wavelength range of 5.50–10.00 µm and several different matrices. The wavelength dependences of the ion signal intensity of [M + H]+ of the peptide are measured using a conventional solid matrix, α-cyano-4-hydroxycinnamic acid (CHCA) and a liquid matrix composed of CHCA and 3-aminoquinoline. Other than the O–H stretching and bending vibration modes, the characteristic absorption peaks are useful for AP-IR-MALDI. Peptide ions are also observed from an aqueous solution of the peptide without an additional matrix, and the highest peak intensity of [M + H]+ is at 6.00 µm, which is somewhat shorter than the absorption peak wavelength of liquid water corresponding to the O–H bending vibration mode. Moreover, long-lasting and stable ion signals are obtained from the aqueous solution. AP-IR-MALDI using a 6–7 µm-band IR tunable laser and solvents as the matrix may provide a novel on-line interface between liquid chromatography and mass spectrometry. Copyright © 2015 John Wiley & Sons, Ltd.

Background and aims Endovenous laser ablation (EVLA) has been well-reported as a minimally invasive method to deal with varices of the lower extremities. The lasers used fall into two categories: pigment, i.e., hemoglobin-specific lasers in the visible and near-infrared (near-IR) wavebands and longer wavelength mid-infrared lasers where the chromophore is water. The fiber used to deliver the laser energy is also important, and not enough attention has been paid to this element of EVLA. The present study was therefore designed to compare EVLA delivered through two specific fiber types coupled with a near-IR laser wavelength where water was the major chromophore. Materials and methods A laser diode system at the wavelength of 1470 nm was used as the laser energy source near a peak in the water absorption spectrum. Laser energy was delivered with two specific types of optical fiber, a Radial™ fiber and a Radial 2ring™ fiber (CeramOptec, Germany), and EVLA was evaluated using a computer simulation model taking light transport into account based on the Monte Carlo method and temperature distribution with the heat conduction equation. Results and conclusions It was confirmed from both the simulation model and a previously published ex vivo experiment that carbonization and sticking during EVLA caused by excess temperature rise can be minimized by using the Radial 2ring fiber compared with the Radial fiber, coupled with the 1470 nm wavelength. In the future, lasers with different wavelengths or optical fibers with differing irradiation modes may appear as candidate systems for EVLA. It is important to evaluate safety and efficacy carefully using the methods in the present study before moving to in vivo indications in human subjects.

Background and Aims: Laser vaporization of the prostate is expected as a less invasive treatment for benign prostatic hyperplasia (BPH), via the photothermal effect. In order to develop safer and more effective laser vaporization of the prostate, it is essential to set optimal irradiation parameters based on quantitative evaluation of temperature distribution and thermally denatured depth in prostate tissue. Method: A simulation model was therefore devised with light propagation and heat transfer calculation, and the vaporized and thermally denatured depths were estimated by the simulation model. Results: The results of the simulation were compared with those of an ex vivo experiment and clinical trial. Based on the accumulated data, the vaporized depth strongly depended on the distance between the optical fiber and the prostate tissue, and it was suggested that contact laser irradiation could vaporize the prostate tissue most effectively. Additionally, it was suggested by analyzing thermally denatured depth comprehensively that laser irradiation at the distance of 3 mm between the optical fiber and the prostate tissue was useful for hemostasis. Conclusions: This study enabled quantitative and reproducible analysis of laser vaporization for BPH and will play a role in clarification of the safety and efficacy of this treatment.

Recently, endoscopic submucosal dissection (ESD) has been performed to treat early gastric cancer. The en bloc resection rate of ESD has been reported to be higher than that of conventional endoscopic mucosal resection (EMR), and ESD can resect larger lesions than EMR. However, ESD displays a higher complication rate than conventional EMR. Therefore, the development of devices that would increase the safety of ESD is desired. Lasers have been extensively studied as a possible alternative to electrosurgical tools. However, laser by itself easily resulted in perforation upon irradiation of the gastrointestinal tract. We hypothesized that performing ESD using a CO2 laser with a submucosal laser absorber could be a safe and simple treatment for early gastric cancer. To provide proof of concept regarding the feasibility of ESD using a CO2 laser with submucosally injected laser absorber solution, an experimental study in ex vivo and in vivo porcine models was performed. Five endoscopic experimental procedures using a carbon dioxide (CO2) laser were performed in a resected porcine stomach. In addition, three endoscopic experimental procedures using a CO2 laser were performed in living pigs. In the ex vivo study, en bloc resections were all achieved without perforation and muscular damage. In addition, histological evaluations could be performed in all of the resected specimens. In the in vivo study, en bloc resections were achieved without perforation and muscular damage, and uncontrollable hemorrhage did not occur during the procedures. Endoscopic submucosal dissection using a CO2 laser with a submucosal laser absorber is a feasible and safe method for the treatment of early gastric cancer.

A novel technique of lithotripsy was investigated with a mid-infrared tunable pulsed laser using difference-frequency generation (DFG). Human gallstone samples obtained from 24 patients were analyzed with their infrared absorption spectra. It was found that the principal components of the gallstones were different for the different patients and that the gallstone samples used in this research could be classified into four groups, i.e., mixed stones, calcium bilirubinate stones, cholesterol stones, and calcium carbonate stones. In addition, some gallstone samples had different compositions within the single stone. The mid-infrared laser tunable within a wavelength range of 5.5 - 10 μm was irradiated to the cholesterol stones at two different wavelengths of 6.83 and 6.03 μm, where the cholesterol stones had relatively strong and weak absorption peaks, respectively. As the result, the cholesterol stones were more efficiently ablated at the wavelength of 6.83 μm with the strong absorption peak. Therefore, it is suggested that the gallstones could be efficiently ablated by tuning the wavelength of the laser to the strong absorption peak of the gallstones. The higher efficiency of the ablation using the characteristic absorption peaks should lead to the safer treatment without damage to the surrounding normal tissues. In order to identify the composition of the gallstones in the patients, endoscopic and spectroscopic diagnosis using the DFG laser and an optical fiber probe made with two hollow optical fibers and a diamond attenuation total reflection prism should be useful. The absorption spectrum of the gallstones in the patients could be measured by measuring the energy of the DFG laser transmitted through the optical fiber probe and by scanning the wavelength of the DFG laser.

Cholesteryl esters are main components of atherosclerotic plaques and have an absorption peak at the wavelength of 5.75 μm originated from C=O stretching vibration mode of ester bond. Our group achieved the selective ablation of atherosclerotic lesions using a quantum cascade laser (QCL) in the 5.7 μm wavelength range. QCLs are relatively new types of semiconductor lasers that can emit mid-infrared range. They are sufficiently compact and considered to be useful for clinical application. However, large thermal effects were observed because the QCL worked as quasicontinuous wave (CW) lasers due to its short pulse interval. Then we tried macro pulse irradiation (irradiation of pulses at intervals) of the QCL and achieved effective ablation with less-thermal effects than conventional quasi-CW irradiation. However, lesion selectivity might be changed by changing pulse structure. Therefore, in this study, irradiation effects of the macro pulse irradiation to rabbit atherosclerotic plaque and normal vessel were compared. The macro pulse width and the macro pulse interval were set to 0.5 and 12 ms, respectively, because the thermal relaxation time of rabbit normal and atherosclerotic aortas in the oscillation wavelength of the QCL was 0.5–12 ms. As a result, cutting difference was achieved between rabbit atherosclerotic and normal aortas by the macro pulse irradiation. Therefore, macro pulse irradiation of a QCL in the 5.7 μm wavelength range is effective for reducing thermal effects and selective ablation of the atherosclerotic plaque. QCLs have the potential of realizing less-invasive laser angioplasty.

Since numerous characteristic absorption lines caused by molecular vibration exist in the mid-infrared (MIR) wavelength region, selective excitation or selective dissociation of molecules is possible by tuning the laser wavelength to the characteristic absorption lines of target molecules. By applying this feature to the medical fields, less-invasive treatment and non-destructive diagnosis with absorption spectroscopy are possible using tunable MIR lasers. A high-energy nanosecond pulsed MIR tunable laser was obtained with difference-frequency generation (DFG) between a Nd:YAG and a tunable Cr:forsterite lasers. The MIR-DFG laser was tunable in a wavelength range of 5.5–10 μm and generated laser pulses with energy of up to 1.4 mJ, a pulse width of 5 ns, and a pulse repetition rate of 10 Hz. Selective removal of atherosclerotic lesion was successfully demonstrated with the MIR-DFG laser tuned at a wavelength of 5.75 μm, which corresponds to the characteristic absorption of the ester bond in cholesterol esters in the atherosclerotic lesions. We have developed a non-destructive diagnostic probe with an attenuated total reflection (ATR) prism and two hollow optical fibers. An absorption spectrum of cholesterol was measured with the ATR probe by scanning the wavelength of the MIR-DFG laser, and the spectrum was in good agreement with that measured with a commercial Fourier transform infrared spectrometer.

Matrix-assisted laser desorption and ionization by infrared laser (IR-MALDI) is expected to be an effective methods for soft-ionization of high-molecular weight proteins and intracellular proteins. IR-MALDI is not widely used because its low sensitivity, complexity, high cost, and as it does not work well on commercial MALDI time-of-flight mass spectrometers (TOFMSs). We employed a tunable mid-infrared (MIR) laser as a light source for MALDI to investigate the IR-MALDI. The laser wavelength can be tuned within a range from 5.5 to 10.0 μm, and included several biomaterial group vibration modes. We evaluated the wavelength dependence of ionization in IR-MALDI for four matrices: succinic acid, urea, 3,5-dimethoxy-4-hydroxycinnamic acid (sinapic acid) and 2,5-dihydroxybenzoic acid (DHB). These matrices contained various groups of vibration modes, and absorbed an infrared (IR) energy at a specific wavelength. The mass spectra of angiotensin II was obtained at a specific wavelength corresponding to the C O stretching and benzene ring vibration mode. In IR-MALDI, we considered the strong molecular bond attracting an electron from a neighboring hydrogen atom, possibly protonating the hydrogen atom.

Matrix-assisted laser desorption/ionization (MALDI) using a mid-infrared (MIR) laser is a promising technique for the study of biomolecules. We achieved the measurement of an insoluble protein under strong denaturing conditions using two lasers, a UV laser and a free electron laser (FEL). The FEL is a powerful tool for the IR-MALDI; however, it is expensive and difficult to operate. We developed a MIR-MALDI time-of-flight mass spectrometer combined with a tunable MIR nanosecond pulsed laser, which was developed by the Institute of Physical and Chemical Research (RIKEN; Wako, Japan) and Kawasaki Heavy Industries, Ltd. (Tokyo, Japan). We evaluated the advantages of MIR-MALDI using this MIR nanosecond pulsed laser with a urea matrix and compared the results with that from previous study using the FEL. The molecular mass of insulin with urea was obtained at wavelength between 5.8 and 6.2 mum, which corresponds to the >C=O stretching vibration mode. In particular, a high SNR was observed at a wavelength of 5.9 mum. This technique produced a better SNR than that of a previous study that used the FEL.

A new type of cell-cultivation system based on laser processing has been developed for the on-chip cultivation of living cells. Here we introduce a “laser cell-chip“. A sheet prepared from epoxy re...

Atherosclerotic plaques mainly consist of cholesteryl esters. Cholesteryl esters have an absorption peak at the wavelength of 5.75 μm originated from C=O stretching vibration mode of ester bond. Our group achieved making cutting difference between atherosclerotic lesions and normal vessels using a quantum cascade laser (QCL) in the 5.7 μm wavelength range. QCLs are relatively new types of semiconductor lasers that can emit mid-infrared range. They are sufficiently compact and have recently achieved their high-power emission. However, large thermal damage was observed because the QCL worked as a quasi-continuous wave laser due to its short pulse interval. To realize less invasive ablation by the QCL, reducing thermal effects to normal vessels is needed. In this study, we tried improving the thermal effects by changing the pulse structure. First, irradiation effects to rabbit atherosclerotic aortas by macro pulse irradiation (irradiation of pulses at intervals) and conventional continuous pulse irradiation were compared. The macro pulse width and the macro pulse interval were set to 0.54 and 12 ms, respectively, because the thermal relaxation time of rabbit normal and atherosclerotic aortas in the oscillation wavelength was 0.54-12 ms. As a result, ablation depth became longer and coagulation width became shorter by the macro pulse irradiation. In addition, cutting difference between rabbit normal and atherosclerotic aortas was observed by the macro pulse irradiation. Therefore, the macro pulse irradiation achieved the improvement of thermal effects by the QCL in the 5.7 μm wavelength range. The QCL has the potential of realizing less-invasive laser angioplasty.

Endoscopic submucosal dissection using carbon dioxide laser is a promising treatment of early digestive cancer because it can avoid the risk of perforation. Although a hollow optical fiber transmitting mid-infrared light has been used, it was observed that the irradiation effect was influenced by bending a gastrointestinal gastrointestinal endoscope due to the change in transmittance by the bending loss. Therefore, we quantitatively evaluated the change in the irradiation effect by bending the hollow optical fiber in the gastrointestinal endoscope and proposed a correction method to stabilize the irradiation effect. First, the relationship between the irradiated laser energy density and the incision depth for porcine stomach was measured by bending the head of the gastrointestinal endoscope. Next, the relationship between the bending angle of the head of the gastrointestinal endoscope and the temperature rise of the hollow optical fiber in the head of the gastrointestinal endoscope was measured during the laser irradiation. As a result, the laser energy density and the incision depth decreased as the bending angle increased, and linear correlation between the laser energy density and the incision depth was observed. It was found that the bending angle can be estimated by the ratio of the setting laser power to time derivative of the temporal profile of the temperature of the hollow optical fiber. In conclusion, it is suggested that the correction of the laser energy density and stabilization of the incision capability is possible by measuring the temporal profile of the temperature of the hollow optical fiber.

Spectroscopic techniques have been researched for intravascular diagnostic imaging of atherosclerotic plaque. Nearinfrared (NIR) light efficiently penetrates of biological tissues, and the NIR region contains the characteristic absorption range of lipid-rich plaques. The objective of this study is to observe atherosclerotic plaque using a NIR multispectral angioscopic imaging. Atherosclerotic plaque phantoms were prepared using a biological tissue model and bovine fat. For the study, we developed an NIR multispectral angioscopic imaging system with a halogen light, mercury-cadmiumtelluride camera, band-pass filters and an image fiber. Apparent spectral absorbance was obtained at three wavelengths, 1150, 1200 and 1300 nm. Multispectral images of the phantom were constructed using the spectral angle mapper algorithm. As a result, the lipid area, which was difficult to observe in a visible image, could be clearly observed in a multispectral image. Our results show that image-enhanced observation and quantification of atherosclerotic plaque by NIR multispectral imaging at wavelengths around 1200 nm is a promising angioscopic technique with the potential to identify lipid-rich plaques.

Atherosclerosis is a primary cause of critical ischemic diseases like heart infarction or stroke. A method that can provide detailed information about the stability of atherosclerotic plaques is required. We focused on spectroscopic techniques that could evaluate the chemical composition of lipid in plaques. A novel angioscope using multispectral imaging at wavelengths around 1200 nm for quantitative evaluation of atherosclerotic plaques was developed. The angioscope consists of a halogen lamp, an indium gallium arsenide (InGaAs) camera, 3 optical band pass filters transmitting wavelengths of 1150, 1200, and 1300 nm, an image fiber having 0.7 mm outer diameter, and an irradiation fiber which consists of 7 multimode fibers. Atherosclerotic plaque phantoms with 100, 60, 20 vol.% of lipid were prepared and measured by the multispectral angioscope. The acquired datasets were processed by spectral angle mapper (SAM) method. As a result, simulated plaque areas in atherosclerotic plaque phantoms that could not be detected by an angioscopic visible image could be clearly enhanced. In addition, quantitative evaluation of atherosclerotic plaque phantoms based on the lipid volume fractions was performed up to 20 vol.%. These results show the potential of a multispectral angioscope at wavelengths around 1200 nm for quantitative evaluation of the stability of atherosclerotic plaques.

Matrix-assisted laser desorption/ionization (MALDI) combined with time-of-flight mass spectrometry (TOFMS) is a powerful yet robust tool for protein identification, due to its high sensitivity and theoretically unlimited detectable mass range. A large part of functional proteins, such as membrane proteins, are insoluble as native forms in a matrix solution without a strong denaturing condition, hence are not amenable to the conventional MALDI–TOFMS analysis. Aiming at overcoming this difficulty, we have developed a novel MALDI technique (UV/FEL-MALDI). An infrared free electron laser (IR-FEL) has a wide tunability in a mid-IR range and is quite attractive as a source of selective vibrational excitation. The FEL wavelength can be tuned to activate a denaturant, which impedes the conventional MALDI process, without an excess heating of analyte molecules. This scheme lets a dense denaturant to be used for the MALDI sample preparation of insoluble proteins. A simultaneous use of the FEL with a nitrogen pulse laser for MALDI achieves spatially and temporally defined desorption, which is essential to TOFMS detection, while specificity and selectivity owing to an FEL wavelength can be conserved. Some attractive features of the protein clustering have been found in the application of UV/FEL-MALDI to hair keratins, which was chosen as a model of insoluble proteins.

Backgrounds/aims: To evaluate treatment with high peak power pulse energy by femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800 nm wavelength for corneal neovascularisation using photodynamic therapy (PDT) mediated by indocyanine green (ICG). Methods: Using a gelatin solid as an in vitro corneal model, the safety of laser power was studied to determine if it degenerated gelatin with or without ICG. The authors then induced corneal neovascularisation in rabbit eyes by an intracorneal suturing technique. Fluorescein angiography was used to evaluate occlusion before PDT and 0, 1, 3, and 10 days after PDT. The authors performed light microscopy with haematoxylin eosin staining and transmission electron microscopy to determine thrombosis formation in the neovascular regions. Results: The threshold of peak laser power density ranged from 39 to 53 W/cm 2 . Laser irradiation was started 30 seconds after a 10 mg/kg ICG injection, and all irradiated segments were occluded at 0, 1, 3, and 10 days at 3.8 J/cm 2 . Light and electron microscopy documented thrombosis formation in the neovascular region. Conclusion: Femtosecond pulse laser enhanced by ICG can be used for PDT. Because of effective closure of corneal neovascularisation at a low energy level, the high peak power pulse energy of the femtosecond pulse laser might be more efficacious than continuous wave laser for use with PDT.

For low-invasive laser treatment, stable absorption properties of tissue during laser treatment are essentially needed, which enable us to predict irradiation effect (ablation depth, thermally-altered depth) using them. There are water and proteins as main absorber in the mid-infrared range. During laser treatment, the absorption properties of soft tissue are changed due to laser-induced temperature rise and leading to the induction of unexpected irradiation effects. We have proposed and demonstrated a novel, low-invasive laser surgery with 6.1-μm-light irradiation. 6.1-μm-light can resonantly excite both OH bending (water) and amide-I (proteins). The absorption properties of soft tissue during laser treatment would be come considerably stable because they do not remarkably depend on the surrounding temperature and the water concentration. We examined the gelatin ablation properties by λ=6.1-μm irradiation using a tunable mid-infrared Free-Electron Laser and showed that λ=6.1-μm irradiation is one of the candidates for a low-invasive soft tissue incision. Gelatins were used as a model substrate for soft tissue. From these experiments, it was found as follows. (1) Enhanced gelatin ablation occurred near λ=6.1-μm, but not λ=6.45-μm (Amide II of proteins). (2) The gelatins were removed due to water vaporization, which is reflected in the static absorption properties of the gelatin before laser irradiation. Thus, we showed the applicability of λ=6.1-μm -light for a new light source to realize a low-invasive soft tissue incision.

Surface modification of root dentin by mid-infrared (MIR) pulsed-laser irradiation is one of the candidates for a novel, non-invasive treatment to prevent root surface caries. To modify root dentin effectively and non-invasively it is essential to estimate quantitatively and qualitatively the laser parameters, such as the wavelength and the power density, required for surface modification. The key aspect is to bring about effective surface modification of root dentin while minimizing the unwanted removal of the underlying dentin. Using a tunable, MIR Free Electron Laser (FEL) in the wavelength region of 8.8-10.6 μm, we have investigated macroscopically the extent of surface modification (morphological and chemical changes) of root dentin. We have obtained experimental results related to the ablation depth, the MIR absorption spectrum, and the elemental chemical composition of the irradiated dentin. The observations showed that the surface modification of root dentin was inclined toward well-recrystallized, HAp-like material, leading to an increase in the acid resistance and dentinal tubule sealing. The laser parameters, at which efficient surface modification without enhanced ablation occurred, were estimated to be at λ= - 9.0 μm or - 9.7 μm and in the average power density region of - 10-20 W/cm2 (resulting in energy density per macropulse and peak power density regions of - 1-2 J/cm2 and - 66.7-133.3 kW/cm2). Thus, it was found that the surface modification of root dentin strongly depends on the laser conditions applied. We conclude that the optimum laser wavelengths for (1) root surface caries treatment without restorative procedure and (2) hard tissue ablation without water irrigation are around (1) λ= 9.0 μm or 9.7 μm and (2)λ= 9.0 μm in the absorption bands due to P-O stretching, respectively.

Effects of bunch length fluctuation on FEL output are studied experimentally and numerically. The FEL energy drops quasi-periodically in the saturation regime except for certain detuning. The observation of the change in bunch length reveals that the elongation of the bunch length causes these dips. A one-dimensional numerical simulation can reproduce the effect of the elongation of bunch length on the FEL output qualitatively.

BACKGROUND AND OBJECTIVES Surface modification of root dentin by mid-infrared (MIR) pulsed-laser irradiation is one of the candidates for a novel, non-invasive treatment to prevent root surface caries. To modify root dentin effectively and non-invasively it is essential to estimate quantitatively and qualitatively the laser parameters, such as the wavelength and power density, required for surface modification. The key aspect is to bring about effective surface modification of the root dentin while minimizing the unwanted removal of the underlying dentin. STUDY DESIGN/MATERIALS AND METHODS Using a tunable, MIR Free Electron Laser with lambda = 8.8-10.6 microm, we have investigated macroscopically the extent of the surface modification (morphological and chemical changes) of root dentin. We have obtained experimental results related to the ablation depth, the MIR absorption spectrum, and the elemental chemical composition. RESULTS The observations showed that the surface modification of root dentin was inclined toward well-recrystallized HAp-like material, leading to an increase in the acid resistance and dentinal tubule sealing. The laser parameters, at which efficient surface modification without enhanced ablation occurred, were estimated to be approximately in the wavelength region around lambda = approximately 9.0 or approximately 9.7 microm and in the average power density region of approximately 10-20 W/cm2 (resulting in total energy density and peak power density regions of approximately 1-2 kJ/cm2 and approximately 0.67-1.2 kW/cm2). CONCLUSIONS The surface modification of root dentin strongly depends on the laser parameters applied. We conclude that the optimum wavelengths for laser treatment of root surface caries are lambda = approximately 9.0 or approximately 9.7 microm, corresponding to the absorption peak due to P-O stretching.

Various treatment procedures have been proposed to prevent decalcification and loss of dental substance on tooth surfaces, as these occur in dental cavities. One of the most promising methods is an improvement of the tooth surface using laser irradiation to render it resistant to acid. Tuning a laser wavelength to the stretching vibration of specific biomolecules has some advantages in ablation of hard tissues and surface modification induced by the photothermal or photomechanical interaction. The radiation can be realized by the Er:YAG laser, CO 2 laser, and Free Electron Laser in the infrared region. This procedure has been used widely for multiple purposes, and its clinical outcome has been assessed. In this paper, the summary of the basis of laser–tissue interaction of the surface phenomena of dentine and some new aspects of dental laser is described.

A time-of-flight mass spectrometric apparatus was built for infrared matrix-assisted laser desorption/ionization (IR-MALDI) experiments using a free-electron laser (FEL). Preliminary experiments were carried out with a CO2 laser at 9.5 μm and a FEL at 10.6 μm. These mid-IR wavelengths were shown to produce light atomic ions from solid samples. The detected ion peaks were broadened by the FEL macropulse with 15 μs width. Applying a delayed extraction pulse to FEL-generated ions brought about a small improvement on the mass resolution. By chopping a flux of ions at exit of the ion source region, the ion peak width became narrower by a factor of more than 10.

In order to estimate the optimum laser conditions for efficient dissociation of cholesterol ester in an arterio-sclerotic region of blood vessels, we have investigated the relationship between the laser parameters and cholesterol ester dissociation using a MIR free electron laser (FEL). In this study, cholesteryl oleate, a typical cholesterol ester found in arteriosclerotic regions, was irradiated with 5.75-μm-FELs, which is known to cause vibration of ester bonds. The following results were obtained. (1) Ester dissociation depended upon the absorption coefficient. The macropulse duration was shorter than the thermal relaxation time, showing that the ester bonds dissociated into carboxylic acid and cholesterol by macropulse-induced thermal effects without accompanying thermal diffusion. (2) Using a wavelength of 5.75 μm, the maximum ester dissociation ratio was achieved under the optimum laser conditions of a macropulse energy density greater than 0.4 J/cm2. (3) 5.75-μm-FEL was estimated to dissociate cholesterol ester under endothelial cells without thermal damage.

Low-power, near-infra-red laser irradiation has been used to relieve patients from various kinds of pain, though the precise mechanisms of such biological actions of the laser have not yet been resolved. To investigate the cellular mechanisms by near-infra-red laser on the nervous system, we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area, whereas the adenosine diphosphate (ADP) content showed no significant difference. Laser irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the tissue was increased by 4.4-4.7 degrees C during the irradiation of both wavelengths. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from a specific effect of the laser operated at the 830-nm wavelength.

A Free Electron Laser (FEL) holds potential for various biotechnological applications due to its characteristics such as flexible wavelength tunability, short pulse and high peak power. We could successfully introduce the Green Fluorescent Protein (GFP) gene into tobacco BY2 cells by IR-FEL laser irradiation. The irradiated area of the solution containing BY2 cells and plasmid was about 0.1 mm2. FEL irradiation at a wavelength of 5.75 and 6.1 μm, targeting absorption by the ester bond of the lipid and the amide I bond of the protein, respectively, was shown to cause the introduction of the fluorescent dye into the cell. On the other hand, transient expression of the GFP fluorescence was only observed after irradiation at 5.75 μm. The maximum transfer efficiency was about 0.5%.

Tuning a laser wavelength to the stretching vibration of specific biomolecules has some advantages in ablating hard tissue and for surface modification induced by the photothermal or the photomechanical interaction. A tunable pulsed transversely excited atmosphere CO2 laser was tuned to 9.45 μm, which is the stretching vibration of phosphoric acid in hydroxyapatite. Dried cow dentine was irradiated at 36 W/cm2. The infrared absorption spectra of the bovine dentine sample were measured using a microscopic Fourier-transform infrared (FTIR). After laser irradiation, x-ray fluorescence of elements contained in a 300 μm×300 μm irradiated area was measured by energy dispersive x ray (EMAX-5770). This laser irradiation reduced the peak wavelength of the dentine surface from 9.76 to 8.93 μm. The atomic ratio of Ca/P was changed from 1.4 to 1.9 as measured with x-ray diffraction. These results show the potential for application of a 9.45μm CO2 laser to ablation and modification of the dentine surface as measured b...

A novel way for specific immobilization of heparin on polysulfone (PSF) via laser irradiation is summarized. Free Electron Laser (FEL) wavelengths tuned to 6.18 and 6.31 µm, the typical absorption band of carboxyl group of heparin and stretching absorption of aromatic rings in polysulfone respectively, were chosen to illuminate thin heparin film formed on PSF surfaces. The modification at the wavelength of 6.18 µm resulted in surface hydrophilicity and resistance to platelet adhesion. Surface elemental analysis on XPS implied the bounding of heparin on polymer surface. On the contrary, the modification at the wavelength of 6.31 µm showed no statistical difference with controls in terms of hydrophilicity as well as elemental composition. This effect of variation in laser wavelengths is considered as coming from the structural and environmental differences of light-absorbing groups.

We observed and discussed the effects of Free Electron Laser (FEL) irradiation to cholesterol accumulated in the regions of arteriosclerosis in the human carotid artery, by an Infrared micro spectroscopy (FT-IR). As a result of this study, we found that we could selectively remove cholesterol only without effects to normal parts of the human body, in irradiating 5.75 μm-FEL that come from a ester bond of cholesterol ester, under the condition that average power is 5 mW, power density is ∼16 W/cm2 and irradiation time is 30∼180 sec.

Low-power, near-infrared laser irradiation has been used to relieve patients of various kinds of pain, but the precise mechanisms of this biological action by a laser have not yet been clarified. To investigate the cellular mechanisms induced by a near-infrared laser on the nervous system, we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat brain. A diode laser was applied for 15 min with irradiance of 4.8 W/cm2. Tissue ATP content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area. Laser irradiation at another wavelength (652 nm) had no effect on ATP content. The temperature increase of the tissue during irradiation did not depend on the wavelength. These results suggest that the increase in tissue ATP content did not result from the thermal effect but from a specific effect of the laser operated at 830-nm wavelength.

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