Picosecond Laser-Induced Photothermal Skin Damage Evaluation by Computational Clinical Trial.

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.

Highly accurate scattering spectra of strongly absorbing samples obtained using an integrating sphere system by considering the angular distribution of diffusely reflected light.

An integrating sphere system has been used to investigate the estimation error in the scattering coefficient for biological tissues. Since the angular distribution of diffusely reflected light from a sample may depend on the sample absorbance, leakage at the entrance port may affect estimates of the scattering coefficient based on measurement of diffuse reflectance. In the present study, the dependence of the angular distribution of the diffusely reflected light on the hemoglobin (Hb) concentration in a sample was investigated. Subsequently, the effect of the entrance port diameter on the error in the scattering coefficient estimated based on diffuse reflectance measurements was evaluated. For a biological tissue phantom, the angular reflectance distribution at a wavelength of 405 nm, at which strong absorption occurred, showed an increasing bias toward specular reflection as the Hb concentration was increased. No such concentration dependence was found at a wavelength of 664 nm, where the absorbance was low. In addition, it was found that the estimation error in the scattering coefficient was reduced for smaller entrance port diameters. Therefore, when attempting to determine the scattering coefficient for strongly absorbing samples, it is necessary to consider both the angular distribution of the diffusely reflected light and the optimal entrance port diameter.

Neu5Acα2,6Gal and Neu5Acα2,3Gal receptor specificities on influenza viruses determined by a waveguide-mode sensor.

To characterize the differences in the receptor-binding specificities of human and avian influenza viruses with glycan chains, the authors performed binding analyses using an evanescent field-coupled waveguide-mode biosensor. The experiments were performed on intact viruses and hemagglutinin proteins, using gold-nanoparticle-conjugated Neu5Acα2,6Gal and Neu5Acα2,3Gal glycan chains. Several influenza viruses belonging to subtypes H3N2 (A/Udorn/307/1972, A/Shandong/9/1993, A/Kiev/301/1994, A/Panama/2007/1999, A/Wisconsin/67/2005 and A/Brisbane/10/2007), H1N1 (A/Brisbane/59/2007 and A/California/07/2009) and H5N1 (A/chicken/India/NIV33487/2006) were used. High levels of glycan-based discrimination were observed with the H3N2 strain A/Brisbane/10/2007 due to its specificity with Neu5Acα2,6Gal, but not with Neu5Acα2,3Gal. Possible amino acid residues responsible for the discrimination of human and avian influenza viruses are discussed. These types of sensor-based discriminatory analyses would be very useful for distinguishing between influenza pandemics, especially during the transition and overlapping periods of human and avian influenza viruses with evolutionary changes.

Ablation of demineralized dentin using a mid-infrared tunable nanosecond pulsed laser at 6 µm wavelength range for selective excavation of carious dentin.

In dental clinic, some lasers have already realized the optical drilling of dental hard tissue. However, conventional lasers lack the ability to discriminate and excavate carious tissue only, and still depend on the dentist's ability. The objective of this study is to develop a selective excavation of carious dentin by using the laser ablation with 6 µm wavelength range. Bovine dentin demineralized with lactic acid solution was used as a carious dentin model. A mid-infrared tunable pulsed laser was obtained by difference-frequency generation technique. The wavelength was tuned around the absorption bands called amide 1 and amide 2. In the wavelength range from 5.75 to 6.60 µm, the difference of ablation depth between demineralized and normal dentin was observed. The wavelength at 6.02 µm and the average power density of 15 W/cm(2), demineralized dentin was removed selectively with less-invasive effect on normal dentin. The wavelength at 6.42 µm required the increase of average power density, but also showed the possibility of selective ablation. In the near future, development of compact laser device will open the minimal invasive laser treatment to the dental clinic.

Biomolecular sensors utilizing waveguide modes excited by evanescent fields.

Properties of evanescent-field-coupled waveguide-mode sensors consisting of a multi-layer structure made of a SiO(2) waveguide, a thin metal layer (Au, Cu, W or Ti), and a high refractive index glass substrate illuminated under the Kretschmann configuration have been theoretically and experimentally investigated. In all cases, reflectivity changes attributed to streptavidin combining to biotinyl groups were observed in close spectral vicinity of the waveguide resonances. The sensors with the Au and the Cu layers show superior sensitivity as compared to those with the W and the Ti layers, whereas the W and Ti layers show better thermal and chemical stability. The results indicate that the materials of thin metal layers should be chosen in accordance with the purpose of sensors and/or environment in which the sensors are used.

Photonic crystal structures in titanium dioxide (TiO2) and their optimal design.

We propose photonic crystal (PhC) structures in titanium dioxide (TiO2) material which is suitable for micro-nano structure optical device engineering and is a good candidate for visible light application. To provide a guideline for designing TiO2 based PhC, the comprehensive optical band gap maps of both the two-dimensional and three-dimensional structures are computed using the planewave expansion method. For 2D structures, besides the ideal infinite high 2D PhC and conventional air-bridge type slab, we also propose a "sandwich-type" PhC for better robustness and easier fabrication. The optimal thicknesses of both types of PhC slabs are investigated. In 3D PhC, we calculate the Yablonovite structure and its reverse which are made possible recently in our fabrication. For the first time to our knowledge, the computation results indicate that the reversed Yablonovite structure also shows a complete band gap characteristic, although it is smaller compared to that of the normal Yablonovite. The dependence of band gap width on the filling ratio and drilling angles for both types of Yablonovite structures are investigated.

Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green.

BACKGROUND/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.

Development of an intravascular laser treatment with an infrared free electron laser. Selective removal of cholesterol ester in carotid atheromatous plaques.

SUMMARY: We have studied to develop an intravascular device with an infrared free electron laser (FEL) to treat occlusive carotid atherosclerotic lesions. In this study, we irradiated the FEL with a wavelength of 5.75 mum on surgical specimens of human atheromatous carotid plaques. After the irradiation on a cholesterol-ester-accumulated portion of the carotid plaques under proper conditions, a microscope transmission FTIR (Fourier Transform Infrared) spectroscopy showed that the peak of a tissue infrared absorption spectrum corresponding to the molecular vibration of cholesterol ester (5.75 mum) disappeared.Tissue damages associated with the irradiation were not histologically noted. This study demonstrated that irradiation of FEL can selectively remove cholesterol ester from the human atheromatous carotid plaques.

Bilirubin calculi crushing by laser irradiation at a molecular oscillating region wavelength based on infrared absorption spectrum analysis using a free-electron laser: an experimental study.

We investigated a new laser technique of crushing bilirubin calculi, our aim being to crush calculi in isolation using a minimally invasive procedure. Infrared absorption spectrum analysis of the bilirubin calculi was conducted, revealing maximum absorption spectrum at a wavelength of the C=O stretching vibration of ester binding that exists within the molecular structure of bilirubin calcium. As an experiment to crush calculi using the free-electron laser, we set the laser at the effective irradiation wavelength of ester binding, and conducted noncontact irradiation of the bilirubin calculi. The calculi began to slowly ablate until the irradiated site had been completely obliterated after 20s of irradiation. Moreover, absorption spectrum analysis of the irradiated site, from a comparison of absorption peak ratios, revealed that absorption peak intensities decreased over time at the absorption wavelength of ester binding. These findings suggest that irradiation of molecular oscillating region wavelengths peculiar to calculi based on infrared absorption spectrum analysis results in the gradual crushing of calculi in isolation by breaking down their molecular structure.

Free electron laser induces specific immobilization of heparin on polysulfone films.

Covalent immobilization of heparin has been developed to reduce the amount of heparin administered systematically during long-term dialysis. Recently, it was doubted partially because of the complexion during immobilization process. In this study, we investigated a novel method for specific immobilization of heparin on polysulfone (PSF) via free electron laser (FEL) irradiation. Laser wavelengths of 6.18 or 6.31 microm, the typical absorption bands of carboxyl groups of heparin and aromatic rings in PSF, respectively, were chosen to irradiate the thin heparin membrane formed on PSF surfaces. The amount of heparin immobilized on PSF was measured by the toluidine blue method. The binding of heparin on PSF was analyzed by X-ray photoelectron spectroscopy (XPS). The immobilization of heparin resulted in a hydrophilic surface on which decreased platelet adhesion was observed. The efficiency differences, depending on laser wavelengths, were discussed from the point of view of structural and environmental differences of light-absorbing groups.

Chemical changes of polymeric surfaces after modification with multi-source cluster deposition.

A new process for surface modification of polymers with multi-source cluster deposition apparatus has been reported in our previous work. The apparatus simultaneously supplies reactant of ammonium sulfamate and activator of energetic Ar(+) ion. In this work chemical changes are analyzed on the basis of XPS spectra and the relations of contact angle and platelet adhesion with chemical changes are discussed. Polymer film, setting on a turning holder, was irradiated by Ar(+) ions during bombardment with ammonium sulfamate clusters. The Ar(+) ion source served for activation of polymer surface and a cluster ion source supplied ammonium sulfamate molecules to react with activated surface. After thorough washing with deionized sterile water, the modified surfaces were evaluated in terms of contact angle of water, elemental composition and binding state on XPS and platelet adhesion with platelet rich plasma (PRP). The modification of polysulfone decreased the contact angle of water on surfaces from 82.6 down to 34.5 degrees. The adhesion number of platelets were decreased to one-tenth of the original surface. Ammonium, amine, sulfate and thiophene combinations were formed on the modified surfaces. The primary studies showed successful modification of polysulfone with ammonium sulfamate by assistance of Ar(+) ion irradiation. The polar groups like N-sulfate were formed on surfaces and contribute to the decrease of surface contact angle and adhesion number of platelets. Since the same process can also be applied to other polymeric materials with various substrates, combining with the features of no solvent and no topographic changes, this method might be developed in a promising way for modification of polymers.

The properties of BCN films formed by ion beam assisted deposition.

A study has been made on the formation and the properties of boron carbonnitride (BCN) thin films. The BCN films were produced by ion beam assisted deposition, in which boron and carbon were deposited by electron beam heating and nitrogen was supplied by ion implantation simultaneously. The mechanical properties of BCN films were measured using a ultra micro hardness tester and a friction tester. The atomic ratio and the structure of BCN thin films were estimated by means of X-ray photoelectron spectroscopy, laser Raman spectroscopy and Fourier transform infrared spectroscopy. As preliminary results, it was found that the BCN films are higher in hardness and lower in friction coefficient than diamond-like carbon (DLC) films. The mechanical properties are discussed with the relation of surface composition and structure.

Selective removal of cholesterol esters in an arteriosclerotic region of blood vessels with a free-electron laser.

BACKGROUND AND OBJECTIVE: In advanced atheromatous atherosclerosis, a large amount of lipids, particularly cholesterol esters, accumulates on the arterial wall. The selective removal of cholesterol esters accumulated in the intracellular or extracellular spaces has clinical significance. In the present work, the authors investigated the removal of cholesterol esters by using a free-electron laser (FEL) in an arteriosclerotic region. STUDY DESIGN/MATERIALS AND METHODS: Thin films of cholesteryl oleate and albumin and the cross section of a rabbit artery were placed on an inverted microscope stage, and the changes caused by the FEL irradiation of 5.75 microm and 6.1 microm, with 1.5-3 mW on average, were monitored continuously by using a CCD camera in real time. RESULTS AND CONCLUSION: FEL irradiation at a wavelength of 5.75 microm, which is a stretching vibrational mode of the ester, was able to ablate cholesterol esters without affecting albumin. It can also remove cholesterol esters from rabbit arteriosclerotic arterial walls.

Clinical applications of ICG Finger Monitor in patients with liver disease.

The indocyanine green (ICG) Finger Monitor system is a non-invasive indication of ICG concentrations in the blood. In this study, significant correlation was found between the sensor signal voltage and plasma ICG concentrations ranging from 0.04 mg/dl to 1.0 mg/dl (r = 0.998, P < 0.001) in vivo. The ICG clearance curve showed an initial sharp rise 20-30 s after bolus injection, followed by a small rise. The concentration then deceased exponentially. In 196 patients with chronic liver disease, there was a close correlation between the KICG (plasma disappearance rate) and R15 (blood retention ratio at 15 min) (r = 0.886, P < 0.001, r = 0.912, P < 0.001) and corresponding values calculated by the conventional ICG method. In 263 cases with chronic liver disease, the plasma disappearance rates calculated using this monitor (mean +/- S.D.) were 0.156 +/- 0.064 (n = 20) in the control group, 0.129 +/- 0.060 (n = 92) in the chronic hepatitis group, 0.048 +/- 0.025 (n = 59) in the cirrhosis group and 0.059 +/- 0.03, (n = 92) in the group with hepatocellular carcinoma. A significant difference in the plasma disappearance rate and blood retention ratios 15 min after injection of ICG using this system was observed between control cases and the chronic hepatitis and cirrhosis groups (P < 0.0001). In 36 cases, the time from injection to the appearance of ICG in the fingertip significantly decreased in the cirrhosis group (P < 0.01). The ICG Finger Monitor system was shown to be useful clinically as well as for research due to its accuracy and non-invasive nature.