Towards novel compact laser sources for non-invasive diagnostics and treatment

An important field of application of lasers is biomedical optics. Here, they offer great utility for diagnosis, therapy and surgery. For the development of novel methods of laser-based biomedical diagnostics careful study of light propagation in biological tissues is necessary to enhance our understanding of the optical measurements undertaken, increase research and development capacity and the diagnostic reliability of optical technologies. Ultimately, fulfilling these requirements will increase uptake in clinical applications of laser based diagnostics and therapeutics. To address these challenges informative biomarkers relevant to the biological and physiological function or disease state of the organism must be selected. These indicators are the results of the analysis of tissues and cells, such as blood. For non-invasive diagnostics peripheral blood, cells and tissue can potentially provide comprehensive information on the condition of the human organism. A detailed study of the light scattering and absorption characteristics can quickly detect physiological and morphological changes in the cells due to thermal, chemical, antibiotic treatments, etc [1-5]. The selection of a laser source to study the structure of biological particles also benefits from the fact that gross pathological changes are not induced and diagnostics make effective use of the monochromatic directional coherence properties of laser radiation

Biophotonics approach for the study of leukocyte activation

Leukocytes are the main cells of immune system, but also contribute to other systems and participate in pathogenesis of different diseases. In particular, leukocytes are involved in the progression of diabetic retinopathy due to their hyperactivation in diabetes. However, a connection between diabetes and the dysfunction of leukocytes is poorly understood. For a more complete picture, studies of the leukocytes activation under the influence of various substances are necessary. Arachidonic acid (AA) and its metabolites are the strongest activating factors of leukocytes. However, the studies involving AA are complicated because it is water-insoluble. Here we describe the method to study activation using photolabile analogs of AA

Multimodal optical diagnostics of the microhaemodynamics in upper and lower limbs

The introduction of optical non-invasive diagnostic methods into clinical practice can substantially advance in the detection of early microcirculatory disorders in patients with different diseases. This paper is devoted to the development and application of the optical non-invasive diagnostic approach for the detection and evaluation of the severity of microcirculatory and metabolic disorders in rheumatic diseases and diabetes mellitus. The proposed methods include the joint use of laser Doppler flowmetry, absorption spectroscopy and fluorescence spectroscopy in combination with functional tests. This technique showed the high diagnostic importance for the detection of disturbances in peripheral microhaemodynamics. These methods have been successfully tested as additional diagnostic techniques in the field of rheumatology and endocrinology. The sensitivity and specificity of the proposed diagnostic procedures have been evaluated.<br/

Verification of NADH content measurements by portable optical diagnostic system in living brain tissue

The overall aim of this study was verification of the possibility to register the change of NADH fluorescence in live tissue by a portable diagnostical laser system with fibre optical probe output and excitation by compact semiconductor UV light source. The measurements were conducted in fresh brain tissue slices of Wistar rat pups. The fluorescence measurements were conducted simultaneously at intervals of 5 s by the microscopic system with excitation at 360 nm and registering of the emitted fluorescence light at 455 nm and by the tested diagnostical system equipped with the fibre optical probe with excitation at 365 nm and registration of the fluorescence spectrum by the inbuilt spectroscopic subsystem. To modulate the mitochondrial function in the living cells, in the chamber sequentially were added 1 μM FCCP and 1 mM NaCN. The comparisons between the curves registered by the methods allowed us to find well agreement between the microscopic measurements and measurements by the fibre optical probe. The obtained results prove that the tested diagnostic system is capable of sensing the changes in brain metabolic activity associated with the NADH content alterations within the physiological range

Non-invasive biomedical research and diagnostics enabled by innovative compact lasers

For over half a century, laser technology has undergone a technological revolution. These technologies, particularly semiconductor lasers, are employed in a myriad of fields. Optical medical diagnostics, one of the emerging areas of laser application, are on the forefront of application around the world. Optical methods of non- or minimally invasive bio-tissue investigation offer significant advantages over alternative methods, including rapid real-time measurement, non-invasiveness and high resolution (guaranteeing the safety of a patient). These advantages demonstrate the growing success of such techniques. In this review, we will outline the recent status of laser technology applied in the biomedical field, focusing on the various available approaches, particularly utilising compact semiconductor lasers. We will further consider the advancement and integration of several complimentary biophotonic techniques into single multimodal devices, the potential impact of such devices and their future applications. Based on our own studies, we will also cover the simultaneous collection of physiological data with the aid a multifunctional diagnostics system, concentrating on the optimisation of the new technology towards a clinical application. Such data is invaluable for developing algorithms capable of delivering consistent, reliable and meaningful diagnostic information, which can ultimately be employed for the early diagnosis of disease conditions in individuals from around the world

Bifurcation in blood oscillatory rhythms for patients with ischemic stroke:a small scale clinical trial using laser Doppler flowmetry and computational modelling of vasomotion

We describe application of spectral analysis of laser Doppler flowmetry (LDF) signals to investigation of cerebrovascular haemodynamics in patients with post-acute ischemic stroke (AIS) and cerebrovascular insufficiency. LDF was performed from 3 to 7 days after the onset of AIS on forehead in the right and left supraorbital regions in patients. Analysis of LDF signals showed that perfusion in the microvasculature in AIS patients was lower than that in patients with cerebrovascular insufficiency. As a result of wavelet analysis of the LDF signals we obtained activation of the vasomotion in the frequency range of myogenic oscillation of 0.1 Hz and predominantly nutritive regime microcirculation after systemic thrombolytic therapy of the AIS patients. In case of significant stroke size, myogenic activity and nutritive pattern microhaemodynamics were reduced, in some cases non-nutritive pattern and/or venular stasis was revealed. Wavelet analysis of the LDF signals also showed asymmetry in wavelet spectra of the LDF signals obtained in stroke-affected and unaffected hemispheres in the AIS patients. A mechanism underlying the observed asymmetry was analysed by computational modelling of vasomotion developed in (Arciero &amp; Secomb, 2012). We applied this model to describe relaxation oscillation of arteriole diameter which is forced by myogenic oscillation induced by synchronous calcium oscillation in vascular smooth muscle cells. Calculation showed that vasomotion frequency spectrum at the low-frequency range (0.01 Hz) is reciprocally modulated by myogenic oscillation (0.1 Hz) that correlates with experimental observation of inter-hemispheric variation in the LDF spectrum

Novel measure for the calibration of laser Doppler flowmetry devices

The metrological basis for optical non-invasive diagnostic devices is an unresolved issue. A major challenge for laser Doppler flowmetry (LDF) is the need to compare the outputs from individual devices and various manufacturers to identify variations useful in clinical diagnostics. The most common methods for instrument calibration are simulants or phantoms composed of colloids of light-scattering particles which simulate the motion of red blood cells based on Brownian motion. However, such systems have limited accuracy or stability and cannot calibrate for the known rhythmic components of perfusion (0.0095-1.6 Hz). To solve this problem, we propose the design of a novel technique based on the simulation of moving particles using an electromechanical transducer, in which a precision piezoelectric actuator is used (e.g., P-602.8SL with maximum movement less than 1 mm). In this system, Doppler shift is generated in the layered structure of different solid materials with different optical light diffusing properties. This comprises a fixed, light transparent upper plane-parallel plate and an oscillating fluoroplastic (PTFE) disk. Preliminary studies on this experimental setup using the LDF-channel of a "LAKK-M" system demonstrated the detection of the linear portion (0-10 Hz with a maximum signal corresponding to Doppler shift of about 20 kHz) of the LDF-signal from the oscillating frequency of the moving layer. The results suggest the possibility of applying this technique for the calibration of LDF devices

Singlet oxygen luminescence detector based on low-cost InGaAs avalanche photodiode

Molecular oxygen excited to singlet state (Singlet oxygen, 1O2) becomes highly reactive and cytotoxic chemical. 1O2 is commonly generated by photoexcitation of dyes (photosensitizers), including the photodynamic therapy and diagnostics of cancer. However, the formation of singlet oxygen is often unwanted for various light-sensitive compounds, e.g. it causes the photobleaching of fluorescent probes. In either case, during a development of new photosensitive chemicals and drugs there is a need to evaluate the amount of 1O2 formed during photoexcitation. The direct approach in measuring the amount of singlet oxygen is based on the detection of its luminescence at 1270 nm. However, this luminescence is usually weak, which implies the use of highly sensitive single-photon detectors. Thus the existing instruments are commonly complicated and expensive. Here we suggest an approach and report a device to measure the 1O2 luminescence using low-cost InGaAs avalanche photodiode and simple electronics. The measurements can be performed in stationary (not time-resolved) mode in organic solvents such as tetrachloromethane (CCl4), ethanol and DMSO. In particular, we performed spectral-resolved measurements of the singlet oxygen luminescence in CCl4 with the device and demonstrated high complementarity to literature data. The simple setup allows to evaluate the efficiency (or speed) of singlet oxygen generation and hence facilitates the development and characterization of new photosensitizers and other photosensitive chemicals

Computational model of bladder tissue based on its measured optical properties

Urinary bladder diseases are a common problem throughout the world and often difficult to accurately diagnose. Furthermore, they pose a heavy financial burden on health services. Urinary bladder tissue from male pigs was spectrophotometrically measured and the resulting data used to calculate the absorption, transmission, and reflectance parameters, along with the derived coefficients of scattering and absorption. These were employed to create a "generic" computational bladder model based on optical properties, simulating the propagation of photons through the tissue at different wavelengths. Using the Monte-Carlo method and fluorescence spectra of UV and blue excited wavelength, diagnostically important biomarkers were modeled. Additionally, the multifunctional noninvasive diagnostics system "LAKK-M" was used to gather fluorescence data to further provide essential comparisons. The ultimate goal of the study was to successfully simulate the effects of varying excited radiation wavelengths on bladder tissue to determine the effectiveness of photonics diagnostic devices. With increased accuracy, this model could be used to reliably aid in differentiating healthy and pathological tissues within the bladder and potentially other hollow organs