Medical use of lasers and photonics in Russia – Therapeutic applications

The topics “clinical biophotonics” and “laser-assisted therapy” are of worldwide interdisciplinary interest as has been clear from the many conferences, that have taken place such as the BiOS (part of SPIE Photonics West), European Conferences on Biomedical Optics (ECBO), and TPB 2013 – Topical Problems in Biophotonics together with their special exhibitions at Photonics West and LASER World of PHOTONICS [1–3]. Such events are essential for anyone seeking information about the latest trends in optical technologies and may serve to bridge the gap between theory and practice, basic science and clinical application, not forgetting, bench to bedside.

The health industry is one of the fastest growing industries in the industrialized nations. It includes the pharmaceutical industry, biotechnology and medical technology as well as provision of medical services. The Federal Government in Germany is not only actively promoting the innovation potential of the health industry but also working to speed up the translation of research results into practical applications. New ways of knowledge and technology transfer are being tested and efforts are being made to ensure that the legal framework conditions facilitate research and innovation. Biophotonics is a key enabling technology, which is used to identify the cause of diseases and to treat them with high specificity.

This is the second issue of Photonics & Lasers in Medicine (PLM) to contain contributions and results from some of our Russian colleagues. Clinical biophotonics has a major priority in the Russian biophotonics community [4–6]. This issue contains four original contributions supplemented by four preliminary research reports and an additional congress report, thus reflecting the wide field of topics from diagnostics to therapeutics and laser safety aspects.

Tumor diagnostics and differentiation of both benign and malignant tissue, with a maximum of specificity and sensitivity, is one of the major interests of research groups investigating new technologies for clinical diagnostics. As autofluorescence techniques suffer from poor specificity, current research activities have their focus on the development and evaluation of exogenous fluorophores [7]. However only a two fluorophores can be used for clinical purposes. These are fluorescein and indocyanine green (including their derivatives), which are mainly vascular-targeted substances. Although exogenous porphyrins were used in the past for diagnostic purposes, 5-ALA-induced protoporhyrin IX is currently the photosensitizer (PS) of choice for fluorescence diagnostic procedures in urology, dermatology, pulmology, and gastroenterology [8] as well as for intra-operative guidance of resection in urology and neurosurgery [9, 10]. As nearly all kinds of photosensitizer have so far suffered from potential chemical and surrounding light toxicity, new PSs have been investigated with particular emphasis on these aspects. Ivanov et al. [11] describes the development of an innovative low-toxic Yb-2,4-dimethoxyhematoporphyrin IX (Yb-DMHP) and its potential for application in fluorescence-assisted diagnostics of tumors. The basic photophysical properties and the pharmacokinetics of Yb-DMHP were investigated and followed by comparison of the preliminary toxicological effects observed in in-vivo experiments with those of the clinically approved photosensitizer chlorin e6 (“Photoditazin”). It could be shown that Yb-DMHP molecules are promising low-toxic markers for the luminescence diagnostics of tumors as these substances do not exhibit the phototoxicity typical of conventional porphyrins and provide relatively high luminescence contrast and selective tumor accumulation [11].

Photodynamic therapy (PDT) is currently a topic with unique worldwide interest and exhibits a variety of scientific and clinical approaches [12–14]. Compared to fluorescence diagnostics, PDT is used to selectively destroy pre-malignant and malignant tissue during which the healthy tissue around the target tissue remains largely unscathed. Consequently, for therapeutic use, PSs are required which are highly selective and achieve a high phototoxicity. Aksenova et al. [15] investigated the enhancement of the photodynamic activity of chlorin PSs using polymers with different structures. It was shown that the photodynamic impact on tumor cell lines in the presence of some polymers increases significantly, thus allowing the therapeutic dosage of PS used to be decreased by more than 10-fold [15].

Laser application in dentistry serves as a diagnostic as well as therapeutic tool. There is considerable interest in laser technologies for the treatment of hard tissues, such as enamel and dentin. Such treatment is localized, easy to handle and less painful due to a lack of vibration, as well as being relatively bloodless and antiseptic [16]. Dental erosion is recognized as being an important cause of tooth tissue loss. As lasers can be used successfully for the modification of biological tissue, studies were performed to investigate the modification of the mechanical and chemical properties of dental enamel [17] and to study light-assisted preventive effects on dentin erosion [18]. Belikov et al. [17] found that sub-ablative YLF:Er-laser irradiation modifies intact enamel and is associated with an increase in its microhardness, which leads to an improved resistance to mechanical abrasion and etching. De-Melo et al. [18] investigated whether low intensity diode laser light (660 and 808 nm) or blue emitting diode light (∼455 nm), combined with fluoride application, resulted in an inhibition of dentin erosion. It was found that all treatments were able to reduce the loss of dentin hardness, but there is no synergistic effect by adding fluoride application to the treatment [18].

On-line monitoring of laser-induced processes is important from the aspect of light dosimetry. Such feedback-sensor techniques are useful for examining the quality and durability of the application system [19] as well as for the control of tissue effects. As optical temperature sensors are often prone to self-heating by absorption of the treatment energy, the interference of the treatment light with the sensor signal is a potential challenge to be overcome [20, 21]. Tissue effects due to heat induction can be detected by changes in the remission intensity [22, 23]. Based upon the analysis of backscattered radiation, Grachev and Loschenov [24] developed a method and a device for measuring backscattered radiation power with the aim to use this method to determine the time and temperature ranges realized in radiation procedures such as PDT and hyperthermia.

Spectroscopic applications for medical purposes are widely represented in the field of biophotonics [25]. Rogatkin et al. [26] present an overview of selected studies in Russia concerning non-invasive spectrophotometry using the “LAKK-M”-system, which uses a combination of various methods such as fluorescence spectroscopy, laser Doppler flowmetry, and tissue reflectance oximetry in in-vivo applications. The authors see great potential of the method, inter alia, in predicting the treatment results of gastro-intestinal tract ulcers and malignant oral neoplasms, in assessing the influence of the type of microcirculation on the outcome of therapeutic applications and in monitoring prescribed pharmaceutical drug dynamics in human and animal organisms [26].

Clinically there is a variety of techniques for interstitial ablation of liver tissue. With respect to the applied energy sources, radiofrequency [27, 28] and interstitial laser therapy [29, 30] as well as microwave ablation [31] are in use, whereas treatment-planning models are still a matter of debate. Hu et al. [32] report on an effective ablation volume model for microwave ablation in liver tissue. This simulation model, based upon the Pennes bioheat transfer equation, was developed and compared with tissue experiments to assess its accuracy and effectiveness and can be regarded as being an important step in the pre-operative treatment planning of microwave ablation.

The treatment of intervertebral disc prolapses as a disease with a worldwide impact is of widespread interest. The purpose of the study by Ali et al. [33] was to assess the clinical effectiveness of percutaneous laser disc decompression (PLDD) for patients suffering from pain caused by disc hernia. This large cohort study summarizes the clinical outcome of more than 4000 PLDD applications in Bangladesh and shows the method to be effective and minimally invasive with almost no side effects or complications, with the added advantage of it being performed under local anesthetic [33].

It is indisputable that laser light applications for diagnostic and therapeutic purposes require special attention and care not only by medical doctors but also by nursing staff. Additionally special care must be taken for the patients’ safety. This requires the observation of the official regulations, both by the laser manufacturing industry and the user. The biennially held International Laser Safety Conference (ILSC^®), which was held this year in Orlando, USA, included the newest developments and aspects from this broad field, which are summarized for PLM by Wöllmer [34].

As can be seen from the reports presented in this issue, German-Russian cooperation in the area of clinical biophotonics has a long and successful tradition. The German-Russian Cooperation Network Biotechnology was launched in April 2005 and is jointly funded and financed by the German Federal Ministry of Education and Research and the participating Federal States, together with the Russian Ministry of Science and Education. The first aim of the network is to support scientific and industrial cooperation between Russian regions of innovations such as Moscow, St. Petersburg, Novosibirsk, Voronezh, and others, and German research centers and clusters.

In 2008, the A.N. Bach Institute of Biochemistry of the Russian Academy of Science was appointed the Russian coordinator of the network. At the same time, the institute acts as the Russian National Contact Point (NCP) for the 7th Research Framework Program of the European Union in “Food, Agriculture, Fisheries and Biotechnology”. As of January 2011, the East-West-Science Centre (OWWZ) at the University of Kassel, Germany, has taken over as the German Coordinator. Within the network, CLIB²⁰²¹ is the coordinating body for R&D cooperation between enterprises whilst the OWWZ coordinates the cooperation in the academic research field [35].

Other German partners are the University of Bielefeld, Faculty of Technology – Bioinformatics Department (spokesman for “Systems Biology and Bioinformatics”), the Laser-Forschungslabor at the University Hospital of Munich (spokesman for “Clinical Research”), the BioCon Valley^® GmbH, Greifswald (spokesman for “Life Sciences/Health Care”) and the Johann Heinrich von Thünen-Institut (vTI) (spokesman for “Bio-Economy”).

The project Light4LIFE focuses on marketing for Germany as the center of innovation in the area of biophotonics, e.g., optical coherence tomography. Based on this German-Russian collaboration, networking and public relations, promotion of training and service and advice are intensified, thus, the partners of Light4LIFE are contributing to improve German-Russian contributions in clinical biophotonic applications and to making these even more visible internationally. We hope that with these two issues we have given you an insight into the research activities of both the diagnostic and therapeutic applications of medical lasers and biophotonics in Russia.