Speed-resolved Perfusion Research Articles

Microvascular dysfunction in women with a history of hypertensive disorders of pregnancy: A population-based retrospective cohort study.

To evaluate microvascular function in women with previous hypertensive disorders of pregnancy (HDP). Retrospective population-based cohort study. Linköping, Sweden. Women aged 50-65 years, participating in the Swedish CArdioPulmonary bioImage Study (SCAPIS) at one site (Linköping) 2016-18, who underwent microcirculatory assessment (N = 1222). Forearm skin comprehensive microcirculatory assessment was performed with a PeriFlux PF6000 EPOS (Enhanced Perfusion and Oxygen Saturation) system measuring oxygen saturation and total speed resolved perfusion. Obstetric records were reviewed to identify women with previous HDP. Data on cardiovascular risk factors, comorbidities, medication, lifestyle, anthropometric data, and biochemical analyses were obtained from SCAPIS. The microcirculatory data were compared between women with and without previous HDP. Skin microcirculatory oxygen saturation and total speed resolved perfusion at baseline and post-ischaemic peak. Women with previous pre-eclampsia displayed impaired post-ischaemic peak oxygen saturation compared with women with normotensive pregnancies (88%, interquartile range [IQR] 84-89% vs 91%, IQR 87-94%, p = 0.001) 6-30 years after pregnancy. The difference remained after multivariable adjustment (β -2.69, 95% CI -4.93 to -0.45). The findings reveal microvascular dysfunction at long-term follow up in women with previous pre-eclampsia and strengthen the possible role of endothelial dysfunction as a link to the increased risk of cardiovascular disease in women with HDP.

Workload and sex effects in comprehensive assessment of cutaneous microcirculation.

Workload and sex-related differences have been proposed as factors of importance when evaluating the microcirculation. Simultaneous assessments with diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) enable a comprehensive evaluation of the microcirculation. The aim of the study was to compare the response between sexes in the microcirculatory parameters red blood cell (RBC) tissue fraction, RBC oxygen saturation, average vessel diameter, and speed-resolved perfusion during baseline, cycling, and recovery, respectively. In 24 healthy participants (aged 20 to 30years, 12 females), cutaneous microcirculation was assessed by LDF and DRS at baseline, during a workload generated by cycling at 75 to 80% of maximal age-predicted heart rate, and recovery, respectively. Females had significantly lower RBC tissue fraction and total perfusion in forearm skin microcirculation at all phases (baseline, workload, and recovery). All microvascular parameters increased significantly during cycling, most evident in RBC oxygen saturation (34% increase on average) and perfusion (9-fold increase in total perfusion). For perfusion, the highest speeds (>10mm/s) increased by a factor of 31, whereas the lowest speeds (<1mm/s) increased by a factor of 2. Compared to a resting state, all studied microcirculation measures increased during cycling. For perfusion, this was mainly due to increased speed, and only to a minor extent due to increased RBC tissue fraction. Skin microcirculatory differences between sexes were seen in RBC concentration and total perfusion.

Speed-resolved perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning.

Laser speckle contrast imaging (LSCI) gives a relative measure of microcirculatory perfusion. However, due to the limited information in single-exposure LSCI, models are inaccurate for skin tissue due to complex effects from e.g. static and dynamic scatterers, multiple Doppler shifts, and the speed-distribution of blood. It has been demonstrated how to account for these effects in laser Doppler flowmetry (LDF) using inverse Monte Carlo (MC) algorithms. This allows for a speed-resolved perfusion measure in absolute units %RBC × mm/s, improving the physiological interpretation of the data. Until now, this has been limited to a single-point LDF technique but recent advances in multi-exposure LSCI (MELSCI) enable the analysis in an imaging modality. To present a method for speed-resolved perfusion imaging in absolute units %RBC × mm/s, computed from multi-exposure speckle contrast images. An artificial neural network (ANN) was trained on a large simulated dataset of multi-exposure contrast values and corresponding speed-resolved perfusion. The dataset was generated using MC simulations of photon transport in randomized skin models covering a wide range of physiologically relevant geometrical and optical tissue properties. The ANN was evaluated on in vivo data sets captured during an occlusion provocation. Speed-resolved perfusion was estimated in the three speed intervals 0 to , 1 to , and , with relative errors 9.8%, 12%, and 19%, respectively. The perfusion had a linear response to changes in both blood tissue fraction and blood flow speed and was less affected by tissue properties compared with single-exposure LSCI. The image quality was subjectively higher compared with LSCI, revealing previously unseen macro- and microvascular structures. The ANN, trained on modeled data, calculates speed-resolved perfusion in absolute units from multi-exposure speckle contrast. This method facilitates the physiological interpretation of measurements using MELSCI and may increase the clinical impact of the technique.

Vasomotion analysis of speed resolved perfusion, oxygen saturation, red blood cell tissue fraction, and vessel diameter: Novel microvascular perspectives.

Vasomotion is the spontaneous oscillation in vascular tone in the microcirculation and is believed to be a physiological mechanism facilitating the transport of blood gases and nutrients to and from tissues. So far, Laser Doppler flowmetry has constituted the gold standard for in vivo vasomotion analysis. We applied vasomotion analysis to speed-resolved perfusion, oxygen saturation, red blood cell tissue (RBC) tissue fraction, and average vessel diameter from five healthy individuals at rest measured by the newly developed Periflux 6000 EPOS system over 10 minutes. Magnitude scalogram and the time-averaged wavelet spectra were divided into frequency intervals reflecting endothelial, neurogenic, myogenic, respiratory, and cardiac function. Recurrent high-intensity periods of the myogenic, neurogenic, and endothelial frequency intervals were found. The neurogenic activity was considerably more pronounced for the oxygen saturation, RBC tissue fraction, and vessel diameter signals, than for the perfusion signals. In a correlation analysis we found that changes in perfusion in the myogenic, neurogenic, and endothelial frequency intervals precede changes in the other signals. Furthermore, changes in average vessel diameter were in general negatively correlated to the other signals in the same frequency intervals, indicating the importance of capillary recruitment. We conclude that vasomotion can be observed in signals reflecting speed resolved perfusion, oxygen saturation, RBC tissue fraction, and vessel diameter. The new parameters enable new aspects of the microcirculation to be observed.

Normative data and the influence of age and sex on microcirculatory function in a middle-aged cohort: results from the SCAPIS study

The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs), and speed-resolved perfusion. Furthermore, to examine the influence of age and sex on microcirculatory function. Measurements were performed using a noninvasive probe-based system, including diffuse reflectance spectroscopy and laser-Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1,765 men and women aged 50-65 yr from the Linköping general population. Normative values are given at baseline, at the end of a 5-min occlusion of the brachial artery and during hyperemia after occlusion release. We found a consistent age distribution, in which the oldest individuals had the lowest peak oxygen saturation (P < 0.001) and the highest baseline low-speed perfusion (P < 0.001). Women had higher peak oxygen saturation (P < 0.001), lower RBC tissue fraction, in general (P < 0.001), lower baseline perfusion in all speed regions (P = 0.01), and lower peak high-speed perfusion at hyperemia (P < 0.001). The normative data can be used as reference values in future studies of disease-specific populations. The results show that age and sex are important aspects to consider in studies of microvascular function. Women and younger age were factors associated with higher peak oxygen saturation after ischemia. This is a novel parameter that reflects overall microcirculatory function associated with vascular dilation capacity.NEW & NOTEWORTHY This study expands experimental microcirculatory research to clinical use by providing normative values on microcirculatory function in a large population-based cohort. Women and younger age were factors associated with higher peak oxygen saturation after ischemia, which implies that age and sex are important aspects to consider in studies of microvascular function. This study is the first step toward using microcirculatory assessment as a tool to improve diagnosis, prognosis, and treatment in disease-specific populations.

Validation of speed-resolved laser Doppler perfusion in a multimodal optical system using a blood-flow phantom.

.The PeriFlux 6000 EPOS system combines diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) for the assessment of oxygen saturation (expressed in percentage), red blood cell (RBC) tissue fraction (expressed as volume fraction, %RBC), and perfusion () in the microcirculation. It also allows the possibility of separating the perfusion into three speed regions (0 to 1, 1 to 10, and ). We evaluate the speed-resolved perfusion components, i.e., the relative amount of perfusion within each speed region, using a blood-flow phantom. Human blood was pumped through microtubes with an inner diameter of 0.15 mm. Measured DRS and LDF spectra were compared to Monte Carlo-simulated spectra in an optimization routine, giving the best-fit parameters describing the measured spectra. The root-mean-square error for each of the three speed components (0 to 1, 1 to 10, and , respectively) when describing the blood-flow speed in the microtubes was 2.9%, 8.1%, and 7.7%. The presented results show that the system can accurately discriminate blood perfusion originating from different blood-flow speeds, which may enable improved measurement of healthy and dysfunctional microcirculatory flow.

Exploring the relationship between the speed-resolved perfusion of blood flux and HRV following different thermal stimulations using MSE and MFE analyses.

Our previous study employed the classic laser Doppler flux (LDF) to explore the complexity of local blood flow signals and their relationship with heart rate variability (HRV). However, microcirculation blood flow is composed of different velocity components. To investigate the complexity of local speed-resolved perfusion and HRV following stimulation with different temperatures in healthy subjects, multiscale entropy (MSE) and multiscale fuzzy entropy (MFE) were used to measure the complexity of local speed-resolved perfusion signals. MSE was also used to evaluate the complexity of HRV. The results indicated that thermal stimulation increased all components of local speed-resolved perfusion and that stimulation with different temperatures resulted in different changes in the complexity area index. However, the same stimulation had no effect on the MSE of HRV. Further research showed that 44°C thermal stimulation resulted in a weak correlation between the composite speed-resolved perfusion and the HRV complexity. The current study provides a new approach for studying the relationship between speed-resolved perfusion signals and cardiac function.

Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms.

.A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (), oxygen saturation (), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source–detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The root-mean-square (RMS) deviations for for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter () was . In conclusion, the skin microcirculation parameters and , as well as, and are estimated with reasonable accuracy.

Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment

We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0–1mm/s, 1–10mm/s and above 10mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20–28years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.

Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry

The tissue fraction of red blood cells (RBCs) and their oxygenation and speed-resolved perfusion are estimated in absolute units by combining diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF). The DRS spectra (450 to 850 nm) are assessed at two source-detector separations (0.4 and 1.2 mm), allowing for a relative calibration routine, whereas LDF spectra are assessed at 1.2 mm in the same fiber-optic probe. Data are analyzed using nonlinear optimization in an inverse Monte Carlo technique by applying an adaptive multilayered tissue model based on geometrical, scattering, and absorbing properties, as well as RBC flow-speed information. Simulations of 250 tissue-like models including up to 2000 individual blood vessels were used to evaluate the method. The absolute root mean square (RMS) deviation between estimated and true oxygenation was 4.1 percentage units, whereas the relative RMS deviations for the RBC tissue fraction and perfusion were 19% and 23%, respectively. Examples of in vivo measurements on forearm and foot during common provocations are presented. The method offers several advantages such as simultaneous quantification of RBC tissue fraction and oxygenation and perfusion from the same, predictable, sampling volume. The perfusion estimate is speed resolved, absolute (% RBC×mm/s), and more accurate due to the combination with DRS.