Non-ionizing, laser radiation in Theranostics: The need for dosimetry and the role of Medical Physics.

The discovery of coherent laser light in 1960 shifted and expanded the biomedical applications of radiation to the non-ionizing part of the electromagnetic spectrum. As in the case of ionizing radiation, but considering the laser specific features, the effective, safe and ethically acceptable use of biomedical laser technology requires interdisciplinary collaboration between physicists, engineers and physicians. This should extend at the research, preclinical and clinical level, inspiring at this time the dynamic discipline of Medical Physics in new areas. With this work we aim to introduce the interested reader in the need of dosimetry in medical applications of laser radiation, as this field is still unexplored. After some necessary definitions, we give a brief review of the basic biophysical mechanisms of coherent light-matter interactions. The manuscript focuses on biomedical laser applications in diagnosis and therapy (i.e. in Theranostics). From the vast field of laser theranostic applications we have chosen some experimental and theoretical results - examples of quantification of the laser effect, particularly relevant to soft and hard tissue laser ablation, laser induced photodiagnosis and photodynamic therapy of cancer. These topics intend to highlight the important role of Medical Physicists in the optimization of well-established laser based clinical procedures and mainly emerge the necessity of the relevant dosimetry for each application. Finally, we hope that this effort is going to give food for thought and highlight the importance of deep knowledge of the physics behind some everyday medical applications.

Biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy.

Reactive oxygen species (ROS) are usually involved in two opposite procedures related to cancer: initiation, progression and metastasis of cancer, as well as in all non-surgical therapeutic approaches for cancer, including chemotherapy, radiotherapy and photodynamic therapy. This review is concentrated in new therapeutic strategies that take advantage of increased ROS in cancer cells to enhance therapeutic activity and selectivity. Novel biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy are discussed, including optical tweezers and atomic force microscopy. This review highlights how these techniques are playing a critical role in recent and future cancer fighting applications. We can conclude that Biophotonics and nanomedicine are the future for cancer biology and disease management, possessing unique potential for early detection, accurate diagnosis, dosimetry and personalized treatment of biomedical applications targeting cancer.

Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue.

The object of this study was to investigate whether laser-induced skin autofluorescence (LIF) and/or light reflectance spectra could provide a useful contrast between basal cell carcinoma (BCC) tissues and the surrounding healthy skin. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a nitrogen laser (lambda = 337 nm) for excitation of autofluorescence and a tungsten halogen lamp for the reflectance measurements. The ex vivo spectroscopic results were correlated with the histopathology images to distinguish the areas of BCC from those of the surrounding health skin. A simple spectral analysis technique was also applied for better skin diagnosis. In conclusion, it seems that LIF and reflectance spectra could be used to differentiate neoplastic from normal skin tissue using an appropriate classification model analysis.

In vitro fluorescence measurements and Monte Carlo simulation of laser irradiation propagation in porcine skin tissue.

In dermatology, the in vivo spectral fluorescence measurements of human skin can serve as a valuable supplement to standard non-invasive techniques for diagnosing various skin diseases. However, quantitative analysis of the fluorescence spectra is complicated by the fact that skin is a complex multi-layered and inhomogeneous organ, with varied optical properties and biophysical characteristics. In this work, we recorded, in vitro, the laser-induced fluorescence emission signals of healthy porcine skin, one of the animals, which is considered as one of the most common models for investigations related to medical diagnostics of human cutaneous tissues. Differences were observed in the form and intensity of the fluorescence signal of the porcine skin, which can be attributed to the different concentrations of the native fluorophores and the variable physical and biological conditions of the skin tissue. As the light transport in the tissue target is directly influencing the absorption and the fluorescence emission signals, we performed Monte Carlo simulation of the light distribution in a five-layer model of human skin tissue, with a pulsed ultraviolet laser beam.

Study of visible and mid-infrared laser ablation mechanism of PMMA and intraocular lenses: experimental and theoretical results.

Laser-polymer interactions have attracted extensive attention both for understanding the inherent basic ablation mechanism and for development of tissue simulators in several biomedical laser applications such as in human ophthalmology. Ablation experiments were performed on polymethylmethacrylate used as cornea tissue simulator and PMMA intraocular lenses. The polymer-ablation mechanism was examined with two different wavelengths and pulse durations. The experiments were conducted with Nd:YAG and Er:YAG solid-state lasers, and the ablation rates were simulated by a mathematical model in each case. Furthermore, to investigate the role of tissue hydration during laser ablation, we performed a set of experiments in which Er:YAG laser ablation of hydrophilic acrylic intraocular lenses, with different H(2)O and D(2)O concentrations, was studied. The hydrophilic acrylic lenses with the higher concentration of H(2)O gave the most satisfactory results regarding both the ablation efficiency and the quality of the ablated craters.

Laser induced autofluorescence studies of animal skin used in modeling of human cutaneous tissue spectroscopic measurements.

BACKGROUND/PURPOSE: Laser-induced autofluorescence spectroscopy provides excellent possibilities for medical diagnostics of different tissue pathologies including cancer. However, to create the whole picture of pathological changes, investigators collect spectral information from patients in vivo or they study different tumor models to obtain objective information for fluorescent properties of every kind of healthy and diseased tissue. Therefore, it is very important to find the most appropriate, and close to the human skin, animal samples from the fluorescence point of view, which will allow the extrapolation of the animal data to human spectroscopic diagnostics. METHODS: In the present work, we examined the autofluorescence properties of different animal skin tissues, which are considered as the most common skin models. A nitrogen laser was used as an excitation source. Samples of healthy mouse, chicken and pig skin in vivo and/or ex vivo were studied and were compared with results obtained from investigations of healthy human skin in vivo. RESULTS AND CONCLUSION: Specific features of the recorded spectra are discussed and the possible origin of the obtained fluorescence signals is proposed. Quantitative evaluation of data extrapolation for each skin type is also depicted.

Spectroscopic characterisation of carotid atherosclerotic plaque by laser induced fluorescence.

BACKGROUND AND OBJECTIVE: An effort has been made to distinguish the composition of carotid atherosclerotic plaques (CAP) from patients undergoing carotid endarterectomy, by laser induced fluorescence spectroscopy. STUDY DESIGN/MATERIALS AND METHODS: Different excitation wavelengths were used: 476, 488, and 458 nm of a continuous wave krypton/argon ion laser, and 337 nm of a pulsed nitrogen laser. Twenty-three CAP samples from different patients were investigated and several spectra from each plaque were obtained. RESULTS: Results were crossed-examined with conventional histologic techniques, which showed three areas of different composition on the pathologic samples: fibrous tissue, lipid constituents, and calcified plaque. Gaussian fittings were performed to reproduce the fluorescence spectra as a correlation of multiple Gaussian curves. CONCLUSION: The accuracy for discrimination of the heterogeneous composition of the atherosclerotic plaque is still limited, due to superposition of the fluorescence emission of various plaque components.

Modeling tumor growth and irradiation response in vitro--a combination of high-performance computing and web-based technologies including VRML visualization.

A simplified three-dimensional Monte Carlo simulation model of in vitro tumor growth and response to fractionated radiotherapeutic schemes is presented in this paper. The paper aims at both the optimization of radiotherapy and the provision of insight into the biological mechanisms involved in tumor development. The basics of the modeling philosophy of Duechting have been adopted and substantially extended. The main processes taken into account by the model are the transitions between the cell cycle phases, the diffusion of oxygen and glucose, and the cell survival probabilities following irradiation. Specific algorithms satisfactorily describing tumor expansion and shrinkage have been applied, whereas a novel approach to the modeling of the tumor response to irradiation has been proposed and implemented. High-performance computing systems in conjunction with Web technologies have coped with the particularly high computer memory and processing demands. A visualization system based on the MATLAB software package and the virtual-reality modeling language has been employed. Its utilization has led to a spectacular representation of both the external surface and the internal structure of the developing tumor. The simulation model has been applied to the special case of small cell lung carcinoma in vitro irradiated according to both the standard and accelerated fractionation schemes. A good qualitative agreement with laboratory experience has been observed in all cases. Accordingly, the hypothesis that advanced simulation models for the in silico testing of tumor irradiation schemes could substantially enhance the radiotherapy optimization process is further strengthened. Currently, our group is investigating extensions of the presented algorithms so that efficient descriptions of the corresponding clinical (in vivo) cases are achieved.

Factors affecting the specificity of beta-glucosidase from Fusarium oxysporum in enzymatic synthesis of alkyl-beta-D-glucosides.

Fusarium oxysporum beta-glucosidase has been used to catalyze the production of alkyl-beta-D-glucosides from various disaccharides, based on the transglucosylation reaction, in the presence of primary, secondary and tertiary alcohols as glucosyl acceptors. Primary alcohols were found to be the best acceptors. The influence of the glucosyl donor concentration, as well as the enzyme specificity towards the cleaved glucosidic bond and the aglucone part of the donor, have also been investigated. The enzyme does not exhibit regiospecificity and seems to be unspecific towards the aglucone part. The specificity of the beta linkage has been confirmed by proton nuclear magnetic resonance (1H NMR) analysis.

XeCl laser ablation of biocompatible PTFE studied by photothermal beam deflection.

Laser beam deflection is a useful tool for studying the dynamics of the pulsed laser ablation mechanism, and has the advantage of being used as an in situ laser damage monitoring technique for both bulk and thin film polymeric and biological tissue samples. This work employs the photothermal deflection technique to study possible photo-acoustic phenomena during the excimer laser ablation of biocompatible polytetrafluoroethylene (PTFE) and to examine the crater surface quality by video microscopy.Although photo-acoustic phenomena are detected in the laser fluence threshold region, ablation is mainly the result of the photothermal process.