High-Intensity Laser Pulses for Oncology
Study of Ablation Processes and Potential Hazard to DNA in Pathological Biotissue Irradiated by High-Intensity Visible and Near IR Laser Pulses for Application in Oncological Practice
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
- PHY-OPL/Optics and Lasers/Physics
3 Approved without Funding
TRINITI, Russia, Moscow reg., Troitsk
- Cancer Research Center, Russia, Moscow\nVNIIEF, Russia, N. Novgorod reg., Sarov
- University Health Network, Canada, ON, Toronto\nUniversity of California / Center for Biophotonics Science and Technology, USA, CA, Sacramento\nNational Defense Medical College Research Institute, Japan, Tokorozawa\nFachhochschule Aalen / Institute of Applied Research / Group of Biophotonics, Germany, Aalen\nLawrence Livermore National Laboratory / Laser Science and Technology, USA, CA, Livermore\nLawrence Livermore National Laboratory, USA, CA, Livermore
Project summaryGoal: The goal of this project is to work out a laser tool for medicine providing new capabilities for surgery in removing pathological formations in soft tissue, in particular, skin.
Our research is directed towards the study of:
- interaction mechanisms of high-intensity short laser pulses of visible and near IR radiation with biological tissue inducing not a superficial but volume (deep) tissue ablation,
- the possibility to control the structure of laser wound modifying the irradiation condition depending on the pursued therapeutic objective,
- the consequences of laser treatment including cytotoxicity, mutagenicity and the change of cell proliferation potential.
As a result, it is supposed to define and develop optimum parameters and irradiation conditions for laser treatment from the viewpoint of high ablation efficiency and removal rate, least traumaticity, mutagenicity and post-operative complications, hence, good rates of healing up. The ways of beam delivery to the site of treatment will be also the subject of consideration. The chosen laser sources and beam delivery systems will be tested in vitro and then used for clinical trials. A therapeutic result will be, undoubtedly, a decisive criterion for applicability.
State of the art in the field.
In the last decade, in serious physical and medical journals an increasing number of studies on laser application for tissue ablation have appeared. Data is presented for various types of tissue such as skin, myocardium, bone, corneal, brain and others as well as for different laser types. However, even for a particular laser - tissue interaction the data is often sparse and contradictory. It is not surprising: the object of study is a very complicated, multi-component, multi-parametric matter – living tissue. In addition, there is lack of reliable data on tissue physical properties. This data is fragmentary and nonsystematic. In spite of a large number of papers on laser application for medicine, only a limited number of studies could be found in literature on the influence of temporal characteristic of high-intensity laser pulses on living object response including its cytotoxicity, mutagenicity and cell proliferation potential. Besides, detailed models describing laser-tissue interaction are still under debate. Different authors apply different models and, thus, simulation codes to describe tissue response under destructive laser treatment.
However, application of laser sources to medical practice leaves far behind a scientific comprehension of processes occurring in biotissue and thus, is not always justified. This refers as well to the potential hazard to DNA under short high-intensity laser pulses used in ophthalmology, neurosurgery and other fields. Therefore, the necessity arises in serious investigation of how high-intensity destructive pulses affect the structure and vital functions of living biological objects.
To study the processes and mechanisms of photo destruction under short high -intensity laser pulses in
- model targets,
- blood solutions containing culture of fission cells,
- biotargets in vitro,
- living objects in vivo,
- clinical trials
by measuring and analyzing
- morphology and size,
- healing-up dynamics
of the laser wounds produced under different irradiation conditions.
To develop the needed laser sources, its' regimes and characteristics, to work out systems of optical beam delivery to the treatment site, systems of measuring, control over laser parameters and monitoring of ongoing biotarget response in the course of treatment.
Expected Results and Their Application.
As a result of project implementation, a comprehensive study will be performed of laser-tissue interaction under short high-intensity pulses (108 – 1011 W/cm2) and the optimum irradiation conditions will be applied for pathological tissue removal in dermato-oncology and dermato-surgery. Our efforts will be focused on the influence of not only the wavelength but also temporal characteristics (pulse length and shape, repetition rate). The latter characteristics are extremely important because they influence the mechanism of ablation and therefore, tissue response. In addition, as a result of ablation mechanism detailed study, a method of choosing an effective tool will be proposed that may be applied to other types of soft tissue. Particular attention will be paid to safety issues: cytotoxicity, potential hazard to DNA and the change of cell proliferation potential. After the Project is terminated a stage of choosing a commercially produced laser tool is supposed with its subsequent modification. A design firm is supposed to be recruited for this purpose. Further production and promoting to the medicine market are anticipated.
Impact of the proposed project on the progress in this field.
Destruction is not a nice word, all the more, destruction of the living tissue. Progress in destruction sounds even more absurd. However, unfortunately, medicine can’t still prevent tumor origination and growth. Hence, the problem of safe, cardinal, and effective removal of pathological tissue remains urgent.
Laser is one of the rapidly developing promising tools for removal. Study of various aspects of laser destruction of biological tissue will shed the light on the processes taking place under high-intensity radiation. Under conditions of gradually widening laser sources’ application to medical practice, not always justified, comprehension of these processes is extremely important since it will prove the validity of using a laser for a particular surgery problem. Study of a living object response to irradiation of a laser will reveal its merits and drawbacks compared to traditionally used tools, its effectiveness and, what is more important, its safety. It is no secret that lasers of UV-optical range are used in medical practice, for example, for transmyocardial laser revascularization (TMLR), cataract removal etc., although there is data in literature reporting that as a result of photochemical reactions taking place in DNA molecule having absorption bands in UV optical range, the hazard arises of mutations and cancerogenic effect. Moreover, there is no unequivocal opinion on the influence of overheating on cell viability. On the one hand, there is a method destroying tumors called thermotherapy; on the other hand, it is reported that heating the tissue by several degrees is cancerogenic itself.
We expect that as a result of the accomplished study, optimal laser sources will be determined as the tools for pathological tissue removal in soft biotissue, namely the skin. The influence will be revealed of laser parameters and irradiation condition on the morphology of the formed wound and on the effects induced in biological tissue during volume ablation. The possibility will be analyzed to reduce the thickness of thermal coagulation zone in order not to traumatize the adjacent vital structures or, on the contrary, to enhance it in order to stop bleeding. The question will be answered whether short high-intensity laser pulses may bring the hazard of cytotoxicity and mutagenicity at definite irradiation condition. Note that radiation of visible and near-IR optical spectrum is traditionally considered to be safe.
The project results will allow elaborating the criteria of choosing a laser tool for a particular medical application and provide physicians and patients with a possibility to evaluate the consequences of treatment.
Competence of the project team and meeting ISTC Goals and Objectives.
There are 56 persons going to take part in the project, 22 of whom (including 1 Doctor of Science Degree, Professor and 8 Candidates of Science Degree) were earlier involved in weapon development. All participant institutions will be completely reoriented to the project tasks that are of great social importance and deeply humane by essence. The participants are highly qualified and skilled specialists possessing a significant scientific and clinical background, rich experimental and theoretical professionalism and are well equipped with technical, measuring and diagnostic resources (data processing systems, operating experimental arrangements in TRINITI, RONC and VNIIEF). High scientific level of the personnel involved in the Project will undoubtedly provide a successful implementation of the proposed research.
Under the conditions of continuously worsening environment, increasing level of solar radiation, growing number of oncological diseases the present project is of particular importance. The proposed work meets ISTC goals and objectives since its realization will contribute to switching the priorities of R&D from weapon development to humanistic values such as public health and life quality improvement. Project activity will promote gaining the experience in cooperation within different fields: science, medical care, business. It will help integrating scientists into international scientific community and create new opportunities to build in market economy.
Countries financing the Project will get the access to the obtained results first and can use them for medical purposes.
Scope of Activities.
Project will take 2 years. Total scope of activity on Project is 351 men-months, including 180 men-months that are specialists, earlier engaged in weapon development.
Role of Foreign Collaborators.
All collaborators will routinely receive scientific-technology information on the results of Project stages implementation. Each collaborator will be given an opportunity to use methods and apparatus worked out in the course of Project for their research activity and medical practice. Joint seminars and workshops will be held to discuss the obtained results and their application for medicine. In addition, joint research work and open publications of the results are assumed.
Technical approach and methodology.
The response of biotargets of different types versus varying laser parameters and irradiation conditions will be studied using absorption-transmission analysis, optical-calorimetric, optical-acoustic methods and laser fluorescent analysis. The irradiation samples will be analyzed using optical and electronic equipment in order to examine the size and morphology of the produced damage. Based on this analysis, a conclusion will be made of destruction mechanisms. Laser characteristics and irradiation condition will be controlled providing treatment to be most precise and effective, cardinal and fast but least traumatic for surrounding healthy tissue. At the terminal stage the experiments on objects in vivo and then clinical trials will be carried out. Only living objects may be used to study necrosis and healing-up dynamics, antibacterial effect, post-operative complications and side effects.
To evaluate the damage in DNA molecules, a method will be used called “comet assay” which is one of the most sensitive and quick methods. High sensitivity of the method to detecting various defects in DNA molecules, its comparative low cost and fast response make it preferable and perspective for gene toxicology study and biological monitoring. The assessment of cell proliferation ability will be carried out on lymphocytes of peripheric blood based on which one may judge about cell immunity.
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