Photoplethysmography (PPG) is a noninvasive optical method accepted in the clinical use for measurements of arterial oxygen saturation. It is widely believed that the light intensity after interaction with the biological tissue in vivo is modulated at the heartbeat frequency mainly due to pulsatile variations of the light absorption caused by arterial blood-volume pulsations. Here we report experimental observations, which are not consistent with this model and demonstrate the importance of elastic deformations of the capillary bed in the formation of the PPG waveform. These results provide new insight on light interaction with live tissue. To explain the observations we propose a new model of PPG in which pulse oscillations of the arterial transmural pressure deform the connective-tissue components of the dermis resulting in periodical changes of both the light scattering and absorption. These local changes of the light-interaction parameters are detected as variations of the light intensity returned to a photosensitive camera. Therefore, arterial pulsations can be indirectly monitored even by using the light, which slightly penetrates into the biological tissue.

Microcirculatory bed, as part of the whole human vascular system, is the link between blood, lymph, and interstitial space. Laser Doppler flowmetry (LDF) is traditionally used to study blood microcirculation. The aim of the study was to identify the wavelength ranges in which the differences in the reflection coefficient of vessels with different degrees of blood and lymph filling are maximal. The nature of the differences in the reflection coefficient may allow the estimation of the contribution of the blood and lymphatic components to the total reflected signal. Materials and Methods. The reflection coefficient on isolated blood and lymphatic vessels in the wavelength ranges commonly used in existing diagnostic systems has been investigated, the amplitude-frequency parameters of LDF signals characterizing the functional state of the blood and lymph flows have also been analyzed. The experiments were carried out on laboratory male Wistar rats. Static spectral characteristics of blood and lymph have been studied on isolated vessels obtained in the acute experiment using HR4000 spectrometer (Ocean Optics, USA). The portal vein and thoracic lymphatic duct of the living anesthetized rat have been selected as an object for studying LDF characteristics of the blood and lymph flow in vivo. Biopac LDF 100C diagnostic system (Biopac Instruments, USA) with a probe wavelength of 830±10 nm was used for measurements. Results. After the evacuation of blood or lymph in the isolated vessels, significant changes (p=0.0059) in the reflection coefficient in certain wave ranges (700-860 nm for lymphatic and 410-560 nm for blood vessels) have been registered that, in our opinion, allowed us to evaluate the dynamics of filling the probed object with blood or lymph, respectively. During heart contraction, a LDF signal with phase oscillations has been recorded on the thoracic lymphatic duct persisting after cardiac arrest. Its amplitude-frequency spectrum contained the predominant slow-wave harmonics increasing in cardioplegia. Conclusion. The results obtained demonstrate the possibility of the LDF method to record the signal characterizing the change in tissue perfusion due to the lymphatic flow. The spectral reflective properties of the isolated vessels are characterized by a multidirectional change in the reflection coefficient with a decrease in blood and lymph concentration in the studied tissue volume that should be taken into account when choosing a radiation source for LDF studies and developing new techniques of functional tests.

Background and Aims According to various research, vascular complications of type 2 diabetes mellitus are the main reason for patients' mortality. The most specific one, observed in patients with diabetes only, is diabetic microangiopathy, especially diabetic nephropathy. This complication accounts for more than 20% of cases of chronic kidney disease. So, the development of non-invasive methods for the diagnosis of vascular complications of type 2 diabetes mellitus is critically important. There is a perspective method for this problem - Laser Doppler flowmetry (LDF). It is currently used in the diagnosis of diabetic microangiopathy, but the limiting factor is the lack of a unified algorithmic approach to the data interpretation. This work aimed to analyze changes in the amplitude indicators of the low-frequency part of the LDF signal spectrum in patients with chronic kidney disease and type 2 diabetes and to identify their correlations with the glomerular filtration rate. Method The study included 42 patients (20 men and 22 women) with type 2 diabetes mellitus chronic kidney disease (stage C3-C4). The age of patients was 58-77 years (66 years on average). The duration of diabetes was more than 5 years (on average 7 years). All patients had diabetic nephropathy with a decrease in glomerular filtration rate, chronic kidney disease stage C3-C4. Laser Doppler flowmetry was done using the "LAZMA MC-1" system ("Lazma", Russia). Each patient had a 10-minute LDF registration. The sensor was placed on the skin of the rear of the foot. After recording the LDF curve, the special software has calculated amplitudes of endothelial, myogenic, neurogenic, respiratory, and pulse flux motions. Then we assessed the amplitude contribution of every frequency range to the total power of the local flux motion region. The next step was a correlation analysis with the estimated glomerular filtration rate. For statistical analysis, we used the GraphPad Prism 8 (GraphPad Software, USA). Results All examined patients had amplitude peaks in the neurogenic, myogenic, respiratory, and pulse ranges. There were no significant correlations between the glomerular filtration rate and the amplitudes of myogenic and neurogenic flux motions (p>0.05) (Fig. 1). However, there was a significant positive correlation between the contribution of myogenic flux motions to the low-frequency range and glomerular filtration rate (p<0.01), and a negative one – for the contribution of neurogenic flux motions (p<0.01) (Fig. 2). In six observations there was a tendency to a decrease in the contribution of endothelial flux motions as the glomerular filtration rate decreased. Conclusion The results of this study showed that laser Doppler flowmetry has the potential to diagnosis the nature of the dysfunction of individual microcirculation modulation mechanisms. In patients with chronic kidney disease of the C3-C4 stage decreasing the glomerular filtration rate correlated with decreasing the contribution of myogenic flux motions and increasing the contribution of neurogenic flux motions to the total power of the low-frequency part of the LDF signal amplitude-frequency spectrum. These changes can be explained within the framework of the existing understanding of the pathogenesis of diabetic microangiopathy, namely, damage to the smooth muscle layer of the wall of arterioles and venules with damage to myocyte pacemakers and changes of basal vascular tone pattern. It causes an increase in the role of neurogenic modulation of the micro-vascular bloodstream. These data can be an additional argument in favor of the further development of improving laser Doppler flowmetry using for the tasks of early (preclinical) non-invasive diagnosis of microvascular disorders in patients with type 2 diabetes mellitus, as well as for monitoring the effectiveness of the therapy. The reported study was funded by RFBR, project number 19-315-90080.

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