Laser Instrument for Malignant-Tumor Therapy
Development of a Medical Laser Instrument for Photochemical and Hyperthermal Therapy of the Malignant Tumors in the Absence of an Exogenous Photosensitizer
Tech Area / Field
- MED-DID/Diagnostics & Devices/Medicine
- PHY-OPL/Optics and Lasers/Physics
3 Approved without Funding
NPO Astrophysica, Russia, Moscow
- FIAN Lebedev, Russia, Moscow\nMedical Radiological Scientific Center, Russia, Kaluga reg., Obninsk\nMoscow State University / International Laser Center, Russia, Moscow
- London Health Science Centre / London Regional Cancer Program, Canada, ON, London\nHumboldt Universität / Charité Universitätsklinikum / Klinik fur Dermatologie, Venerologie und Allergologie, Germany, Berlin\nWills Eye Hospital, USA, PA, Philadelphia\nDrexel University / School of Biomedical Engineering, Science and Health Systems, USA, PA, Philadelphia
Project summaryThe major goal of the project comprises development and trials of a laser instrument to both photochemical and hyperthermal tumor destruction; determination of the optimum laser irradiation doses; development of a computational algorithm for determining depth of tissue lesion depending on its morphology and blood-flow characteristics and, finally, development of a novel method for malignant-tumor treatment.
The project investigates simultaneous hyperthermal and photochemical actions of the specific laser radiation on malignant tumors with the final goal to suppress the tumor growth. Laser treatment is routinely used in the modern oncology practice.
Photochemical action is usually referred to as photodynamic therapy (PDT) implies the use of a photosensitizer. The key stage of the PDT is formation of singlet molecular oxygen inside the living tissue under laser irradiation. The resultant singlet oxygen acts like a cytotoxic agent. On the other hand, the sensitizer toxicity is known as the major PDT drawback.
Results obtained in the course of 1552 ISTC project implementation showed that it is possible to produce substantial amount of singlet oxygen under laser irradiation at wavelength 1268 nm by direct excitation of the optical transition in O2 molecules without using of any exogenous sensitizer. In the experiments conducted in the frames of this project, the quantities of singlet oxygen molecules directly produced in tumors were sufficient to suppress the tumor growth rate in experimental animals, and its inhibition reached about 58%. Based on these results, characteristics of the laser radiation for the direct photochemical tumor destruction have been evaluated.
At the same time the results show that, as compare to photodynamic therapy, in the experiments small effect of the laser irradiation on tumor growth due to low peak-power of the applied radiation level, that doesn’t provide production of such concentrations of singlet-oxygen in the tissues that would be sufficient to suppress both reparative and antioxidant tumor cells protection.
Direct tumor destruction requires laser pulses of high peak power because the efficiency of cell lethal damage is a square function on singlet oxygen concentration. Production of sufficient concentration of singlet oxygen directly in tissues requires a corresponding amount of laser energy which must be delivered to the tumor. Analysis shows that at wavelength 1268 nm semiconductor lasers as well as diode-pumped fiber lasers cannot provide the necessary peak-power levels. They cannot generate megawatt sub-microsecond pulses that are required for production of high concentrations of singlet-oxygen in tissues. An instrument based on a Q-switched Nd-YAG laser pumped forsterite laser can provide solution of the problem. A similar forsterite laser but operating at low peak power was used in the course of 1552 ISTC project.
The hyperthermal laser action is specific of distinctive features. The hyperthermal effect is usually achieved by RF heating or by some other appropriate heat producing method, including laser irradiation. The narrow temperature gap which is allowed for the hyperthermal method is small: it does not exceed 2o C. This requires knowledge of tissue light absorbing and scattering properties and heat transfer characteristics as well. Development of the mathematical model of light and thermal diffusion patterns inside the tissue that takes in account optical properties of various tissues, blood-flow characteristics, and physiology of the thermal regulation can solve the above posed problem: simulate the heat pattern and the pattern of photochemical damage as well. A mathematical model of the laser-induced heating of under-skin layer that accounts for the heat-transfer factor and reactivity of the blood vessels was developed within the framework of 1552 ISTC project. Measurements of temperature in healthy tissues under the laser radiation at several different wavelengths have been performed.
It is suggested that the obtained data can be used for developing the laser instruments and application methods within the framework of the current project. A special unit will be incorporated into the laser instrument for controlling the thermal impact. The suggested laser instrument would perform mapping of the tumor borders and a quality assessment of the therapy procedure, using a special channel of the laser Doppler probing unit.
Simultaneous use of both the laser hyperthermia and photochemical treatment will result in synergetic way, i.e. the both mechanisms disorder transcapillar metabolism within the tumor tissue, and in the result that put in destruction of the tumor. It is expected that the effect from two factors will be more profound than just a sum effect obtained from each of the component applied separately.
The major goal of the current project is development of laser hardware combined with the control instrumentation for tumor destruction and suppression of growth by direct generation in tissues sufficient concentration of singlet oxygen without administrating any exogenous sensitizer, and controlled generation of heat inside the tumor with predicted pattern. This is based on mathematical modeling and numerical simulations of light distribution, singlet oxygen and heat generation in tissue. Hence, the suggested laser hardware with specified characteristics will provide us with the opportunity of implementing the therapy using both photochemical and hyperthermal regimes simultaneously.
The major tasks, which will be solved in the frames of the project, are:
- Development of an advanced mathematical model of simultaneous hyperthermal and photochemical destruction of tumors under laser irradiation;
- Creation of experimental setup and testing the method of laser action in biological objects.
- Development and production of a prototype of the instrument for clinical use.
- Medical trials.
Preliminary studies (including those performed in the framework of the 1552 ISTC project) have revealed prospects of the described treatment method that has been approbated by medical examination. Successful innovative studies within the present project can be developed into commercial production of the laser instrument at the SUE “SPA Astrophysics” which is a successful manufacturer of the medical equipment since ten years. The SUE “SPA Astrophysics has introduced into medical practice and performed production of series of instruments developed at the SUE “SPA Astrophysics”, namely, LAKK-01 - laser analyzer of blood capillary blood flow; MLADA - magnet-laser physiotherapeutic apparatus; SPECL - laser ophthalmology physiotherapeutic instrument; and OGP-1 - haematooximeter. Moreover, new working places can be organized for this production. The authors of the project will be involved in the author follow-on supervision, the method upgrading, and production management.
The proposed instrument can compete with existing PDT instruments and photosensitizer manufacturing. The product predominantly aims at the Russian and CIS markets. The following market advancement envisages expansion to other countries.
Participants of the present project are involved in the investigation of laser action on living objects and development of medical laser apparatus for the last fifteen years. Several laser therapeutic and diagnostics instruments have been designed and developed, and their serial production has been launched. The studies of mechanisms of singlet oxygen production, photochemical destruction of different biological objects, and laser thermodestruction have been performed.
The scope of supplementary innovate activities of the project comprises development of noninvasive optical methods for studying peripheral blood flow and tissue oxygenation, development of laser instruments for medical diagnostics. The project participants have been involved in implementation of the laser Doppler method into biology and medical studies during several decades. The results have been published in scientific journals and conference proceedings, and patented. Several generations of the medical diagnostic hardware have been developed. The instruments passed the clinical tests. The project participants are involved in studies of the biotissue optics, laser Doppler studies of the collective hemodynamic processes in the microcirculatory system, rhythmical processes, and transcapillary exchange. The authors have launched a novel LDF direction, namely, microhemodynamic oxymetry that is covered by the Russian patents.
The project category is applied medical study. The project provides the Russian scientists and specialists who were formerly involved in weaponry research with opportunities of civilian research and promotes integration of the scientists and specialists into the international scientific society. The project implementation will support applied studies and development of civilian and peaceful aims specifically in the area of modern medical hardware industry. The project contributes to the solution of public health problems and assists domestic medical-hardware industry to occupy a fitting place in the international market. Finally, the project contributes to the transfer to the market economy that corresponds to the civilian requirements. The major project activity aims at development and production of a novel medical instrument and comprises preliminary theoretical and experimental studies, development of the models and prototypes of the instruments, service equipment for the instrument certification. The project duration is three years, 6345 person*days.
In accordance with the total work volume in the frames of the project the following cooperation with the foreign institutions is planned:
- Information exchange during the project implementation;
- Provision of comments to the technical reports;
- Crosschecks of the project results;
- Tests and evaluation of the equipment and technologies that will be developed during the project implementation;
- Participation in the technical control of the project activities;
- Assistance to the project participants in participation in the international conferences;
- Joint symposia and workshops.
The project implementation is performed using the technical approaches and methods of laser physics, biomedical optics, experimental biology, and medicine.
The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.
ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.