Laser Doppler Oximeter for Medical Microhemodynamic Tomography
Designing a Medical Laser Doppler Device for Tomographic Measurement of Blood Oxygenation in the Microcirculation System
Tech Area / Field
- MED-DID/Diagnostics & Devices/Medicine
- INS-MEA/Measuring Instruments/Instrumentation
- PHY-OPL/Optics and Lasers/Physics
3 Approved without Funding
NPO Astrophysica, Russia, Moscow
- Moscow State University / International Laser Center, Russia, Moscow
- University of Oulu, Finland, Oulu\nUniversity of Twente / Faculty of Applied Physics, The Netherlands, Enschede\nUniversity of Kent at Canterbury, UK, Canterbury\nVTT Electronics, Finland, Oulu\nHumboldt Universität / Charité Universitätsklinikum / Klinik fur Dermatologie, Venerologie und Allergologie, Germany, Berlin\nUniversity of Exeter / School of Physics, UK, Exeter\nHeinrich Heine Universität Düsseldorf / Institut für Lasermedizin, Germany, Düsseldorf
Project summaryOne of the major parameters of tissue vital activity is the level of its saturation with oxygen that reveals the tissue capacities for producing sufficient metabolic energy in ATP form in response to metabolic demands. The metabolic misbalance between ATP production and demand can result in immediate and acute consequences for cell and organ functioning because ATP is a universal molecule used in all energy-consuming cell responses. The level of metabolic energy production strictly depends on the level of blood saturation with oxygen bound to hemoglobin. Low oxygen level in relation to the superior metabolic demand causes a fast drop in the level of oxidized haemoglobin in capillary vessels due to its transformation into reduced form. Monitoring the level of deoxyhemoglobin can give assessment of the level of oxygen supply and energy state of the tissues.
The partial pressure of oxygen in tissues (pO2) is routinely measured using the invasive polarography method. Noninvasive pO2 assessments are usually performed using transcutaneous methods (TpO2). The above methods ensure high-accuracy measurements, but are poorly applicable to clinical monitoring and do not allow for separate monitoring the concentration of oxygen in either arterial blood inflowing to the organs or venous reflux from them. The idea of “optical oximetry” emerged in the beginning of the XX century after the absorption spectra of oxidized and reduced hemoglobin were investigated. The concentration of oxidized hemoglobin SO2 that is measured by this technique is expressed in percentage units that can be calculated into pO2 if the blood temperature and its pH are known. Whereas this and other optical techniques were successful in vitro, non-invasive methods did not ensure the measurement accuracy necessary for applied medicine. Because various concentrations of melanin and other skin pigments distorted the result of spectroscopy assessments, deriving the reliable data became a complex problem. In addition, it was difficult to choose the transmitter position that would ensure probing the blood inside a specific type of blood vessels separately without detecting a mixture of responses from both venous and arterial blood. Pulse oximetry (PO), which appeared in 1970-ies, has allowed achieving acceptable measurement accuracy. The method proved to be so successful, that nowadays all modern clinics, operating and diagnostic centers in developed countries are equipped with pulse oximeters. The volume of the world market of these devices exceeds 500 million US dollars.
The basic idea of pulse oximetry comprises measurement of pulse oscillations amplitudes of the tissue absorbance at two different wavelengths. The pulse oscillations are stipulated by cardiac activity and to a greater extent become apparent in the arteries. Therefore this method measures the oxygenation of the arterial blood SAO2.
However, of highest scientific and clinical importance is the examination of oxygen transport directly inside the microcirculation system and the study of transcapillary exchange. At the moment, there is no method permitting non-invasive solution of this problem.
The microcirculation system is a key part of the blood circulation system, supplying the tissues of an organism with oxygen, water, and nutrients, and providing excretion of the metabolic products by means of their transport with the blood flow and transcapillary exchange with surrounding tissues. Disorders of blood flow and transcapillary exchange are symptoms of a large number of diseases, including cardiovascular, oncology, diabetic, hematologic, and many others. Knowledge of pathological alterations at the microvascular level can be implemented for early diagnostics of diseases at those stages when treatment can be performed using sparing and preventive methods.
By this time, various methods for studying the microcirculation system based on different physical principles have been designed. Considerable scientific and clinical achievements are obtained using direct optical visualization of microvessels with the computer-assisted intravital microscopy (capillaroscopy), confocal microscopy, and fluorescent microangiography. Laser Doppler flowmetry (LDF) allows for studying haemodynamics in large tissue volumes, which is important in many clinical applications. LDF is now widely used for assessment of relative alterations in perfusion of tissues and organs and in the microcirculation system. However, LDF is not widely used for examining the transcapillary exchange. Other optical techniques, designed for the studies of haemodynamics, including laser Doppler- and speckle- microscopies and optical coherence Doppler tomography (OCDT) – are being rapidly developed but, however, are not approved so far as methods envisaging clinical use.
Optical coherent tomography provides means for microvessel visualization and assessment of blood-flow velocities in them at a depth not higher than one millimeter, which is not sufficient for studying deep layers of the skin microcirculation system. Laser Doppler microscopy (LDM) allows measuring blood-flow velocities in separate microvessels, however, LDM is limited by specific microvessel deposit depths in skin. None of the above-mentioned methods provides quantitative assessment of oxygen saturation of capillary blood. Hence, no uniform methodological approach has been so far developed for studying microcirculation system throughout entire skin thickness and analyzing its major functions - transcapillary exchange and saturation of the tissues with oxygen.
Besides the above techniques focused at microcirculation studies, different approaches were developed for functional imaging and monitoring of blood oxygenation in human tissues, e.g. brain, by means of time- and spatially resolved near-infrared reflectance spectroscopy. However, these techniques do not provide information on the in-depth distribution of oxygen saturation and cannot distinguish different compartments of the microcirculation system.
In the developed device, it is proposed to measure blood saturation with oxygen separately in arterioles and venules. Similarly to PO, this is achieved by probing a volume of studied tissue at two wavelengths. One of them is close to maximum difference in absorption coefficients between oxidized and reduced hemoglobin whereas the second wavelength coincides with the isobestic point. In contrast to PO, the probing is performed with coherent laser radiation that allows detecting the Doppler signal containing the information on the velocities of particles in the microvessels. In arterioles the blood flows faster than in venules. This enables to design a new algorithm of LDF. In comparison to traditional ones this algorithm provides frequency filtration and selection of signals, formed as a result of light scattering on red blood cells flowing in microvessels of different types. Besides, signal processing includes a correlation algorithm, which accounts for different haemodynamic rhythms in arterioles and venules. The correlation processing and background signal subtraction are similar to those used in PO.
These measurements will be performed layer by layer (tomographically). This will be achieved by using a multichannel detection system with an appropriate aperture function. One of the underlying ideas is based on the dependence of the studied tissue volume on the spacing between the probing and detecting apertures.
The present project aims at development of such an approach and at its practical implementation in instrument prototypes. The method allows studying rhythmic processes in the microcirculation system more efficiently in order to perform long-term monitoring.
The core ideas of the project comprise laser probing, Doppler frequency filtration, and selection of haemodynamic rhythms. The project implementation requires theoretical and experimental research of haemodynamics of different skin layers and microvessel types. Development of new instrument referred to as tomographic microhaemodynamic oximeter (TMO) includes design and experimental works, and medical approbation of the device.
Successful implementation of the proposed project will offer new opportunities and prospects for developing standard methods of LDF. As a result of the project implementation, physiologists and physicians will get new means for noninvasive studies of the microcirculation system.
Our confidence in the feasibility of the proposed method and device is based on the results of our preliminary studies, namely:
– blood-flow velocities and Doppler-signal spectral width are different in various compartments of the microcirculation system;
– rhythmical vasomotions are specific of each type of microvessels;
– information about the haemodynamics processes in various layers of the microcirculation system can be effectively selected by choosing special parameters of the receiving-transmitting system and weight coefficients for each of its elements;
– simultaneous laser probing at several wavelengths allows measuring the oxygenation level in blood circulating in microvessels with the accuracy specific of the pulse oximetry.
The TMO instrument will find clinical application in functional diagnostics; that is why its development has a commercial outcome. The instrument advantages are (1) layer-by-layer analysis of the oxygenation; (2) separate gauging of the blood oxygenation in the blood vessels of the microcirculation system, namely, arterioles and venules, and (3) determination of a specific levels of the oxygen consumption in tissues.
Participants of the proposed project are engaged in application of laser Doppler methods for biological and medical studies for many years. A number of novel research results and data have been harvested and then reported in books, papers, presented at the largest international conferences (including plenary and invited reports); series of patents have been received; several generations of medical diagnostic instruments, which successfully passed clinical trials, have been designed. Some preliminary outcomes on Doppler techniques for studying capillary blood flow have been obtained during successful implementation of the ISTC project #1552.
The project provides Russian scientists and experts involved in weaponry development with the opportunities of civilian activities, encourages integration of scientists in the international scientific society.
As a result, the project implementation promotes transfer to the market economy, matching the public demands.
The foreign collaborators have opportunities for:
– information exchange during the project implementation;
– cross-validation of the results obtained during the project implementation;
– testing and evaluating the equipment and technologies developed during the project implementation;
– participation in collateral workshops and working seminars.
To study the physiological processes in biological tissues the methods of biomedical optics, quantum physics, and computer-information processing will be used. The engineering approach is based on laser, fiber-optics, and numerical techniques, spectral temporal and spatial selection, and signals processing.
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.