Multiscale, multidomain analysis of microvascular flow dynamics.

NEW FINDINGS: What is the topic of this review? We describe a range of techniques in the time, frequency and information domains and their application alone and together for the analysis of blood flux signals acquired using laser Doppler fluximetry. What advances does it highlight? This review highlights the idea of using quantitative measures in different domains and scales to gain a better mechanistic understanding of the complex behaviours in the microcirculation. ABSTRACT: To date, time- and frequency-domain metrics of signals acquired through laser Doppler fluximetry have been unable to provide consistent and robust measures of the changes that occur in the microcirculation in healthy individuals at rest or in response to a provocation, or in patient cohorts. Recent studies have shown that in many disease states, such as metabolic and cardiovascular disease, there appears to be a reduction in the adaptive capabilities of the microvascular network and a consequent reduction in physiological information content. Here, we introduce non-linear measures for assessing the information content of fluximetry signals and demonstrate how they can yield deeper understanding of network behaviour. In addition, we show how these methods may be adapted to accommodate the multiple time scales modulating blood flow and how they can be used in combination with time- and frequency-domain metrics to discriminate more effectively between the different mechanistic influences on network properties.

Flow motion dynamics of microvascular blood flow and oxygenation: Evidence of adaptive changes in obesity and type 2 diabetes mellitus/insulin resistance.

An altered spatial heterogeneity and temporal stability of network perfusion can give rise to a limited adaptive ability to meet metabolic demands. Derangement of local flow motion activity is associated with reduced microvascular blood flow and tissue oxygenation, and it has been suggested that changes in flow motion activity may provide an early indicator of declining, endothelial, neurogenic, and myogenic regulatory mechanisms and signal the onset and progression of microvascular pathophysiology. This short conference review article explores some of the evidence for altered flow motion dynamics of blood flux signals acquired using laser Doppler fluximetry in the skin in individuals at risk of developing or with cardiometabolic disease.

Dynamics of microvascular blood flow and oxygenation measured simultaneously in human skin.

OBJECTIVE: To evaluate the dynamics of skin microvascular blood flow (BF) and tissue oxygenation parameters (OXY) measured simultaneously at the same site using a combined non-invasive BF+OXY+temperature probe. METHODS: Skin BF, oxygenated (oxyHb) and deoxygenated (deoxyHb) haemoglobin and mean oxygen saturation (SO2 ) were measured in 50 healthy volunteers at rest and during perturbation of local blood flow by post-occlusive reactive hyperaemia, sympathetic nervous system-mediated vasoconstriction (deep inspiratory breath-hold) and local skin warming. Signals were analysed in time and frequency domains. RESULTS: The relationship between BF and SO2 over the range of flows investigated was described by a non-linear equation with an asymptote for SO2 of 84% at BF >50 PU. SO2 was independently associated with BF, skin temperature, BMI and age, which together identified 59% of the variance in SO2 (p<0.0001). Fourier analysis revealed periodic low frequency fluctuations in both BF and SO2 , attributable to endothelial (~0.01 Hz), neurogenic (~0.04 Hz) and myogenic (~0.1 Hz) flow motion activity. The frequency coherence between the BF and SO2 signals was greatest in the endothelial and neurogenic frequency bands. CONCLUSIONS: The simultaneous evaluation of microvascular blood flow and oxygenation kinetics in healthy skin provides a platform from which to investigate microvascular impairment in the skin and more generally the pathogenesis of microvascular disease.

Vortical flow in human elbow joints: a three-dimensional computed tomography modeling study.

The human elbow joint has been regarded as a loose hinge joint, with a unique helical motion of the axis during extension-flexion. This study was designed to identify the helical axis in the ulnohumeral joint during elbow extension-flexion by tracking the midpoint between the coronoid tip and the olecranon tip of the proximal ulna in a three-dimensional (3D) computed tomography (CT) image model. The elbows of four volunteers were CT-scanned at four flexion angles (0°, 45°, 90°, and 130°) at neutral rotation with a custom-made holding device to control any motion during scanning. Three-dimensional models of each elbow were reconstructed and a 3D ulnohumeral joint at 45°, 90°, and 130° was superimposed onto a fully extended joint (0°) by rotating and translating each 3D ulnohumeral joint along the axes. The midpoints of the olecranon and coronoid tips were interpolated using cubic spline technique and the dynamic elbow motion was plotted to determine the motion of the helical axis. The means and standard deviations were subsequently calculated. The average midpoint pattern of joint motion from extension to flexion was elliptical-orbit-like when projected onto a sagittal plane and continuously translated a mean 2.14 ± 0.34 mm (range, 1.83-2.52 mm) to the lateral side during elbow extension-flexion. In 3D space, the average midpoint pattern of the ulnohumeral joint resembles a vortical flow, spinning along an imaginary axis, with an inconsistent radius from 0° to 130° flexion. The ulnohumeral joint axis both rotates and translates during elbow extension-flexion, with a vortex-flow motion occurring during flexion in 3D model analysis. This motion should be considered when performing hinged external fixation, total elbow replacement and medial collateral ligament reconstruction surgery.

Dysregulated Neurovascular Control Underlies Declining Microvascular Functionality in People With Non-alcoholic Fatty Liver Disease (NAFLD) at Risk of Liver Fibrosis.

BACKGROUND/AIMS: Increasing evidence shows that non-alcoholic fatty liver disease (NAFLD) is associated with dysregulation of microvascular perfusion independently of established cardio-metabolic risk factors. We investigated whether hepatic manifestations of NAFLD such as liver fibrosis and liver fat are associated with microvascular hemodynamics through dysregulation of neurovascular control. METHODS: Microvascular dilator (post-occlusive reactive hyperemia) and sympathetically mediated constrictor (deep inspiratory breath-hold) responses were measured at the forearm and finger, respectively, using laser Doppler fluximetry. Non-linear complexity-based analysis was used to assess the information content and variability of the resting blood flux (BF) signals, attributable to oscillatory flow-motion activity, and over multiple sampling frequencies. RESULTS: Measurements were made in 189 adults (113 men) with NAFLD, with (n = 65) and without (n = 124) type 2 diabetes mellitus (T2DM), age = 50.9 ± 11.7 years (mean ± SD). Microvascular dilator and constrictor capacity were both negatively associated with age (r = -0.178, p = 0.014, and r = -0.201, p = 0.007, respectively) and enhanced liver fibrosis (ELF) score (r = -0.155, p = 0.038 and r = -0.418, p < 0.0001, respectively). There was no association with measures of liver fat, obesity or T2DM. Lempel-Ziv complexity (LZC) and sample entropy (SE) of the BF signal measured at the two skin sites were associated negatively with age (p < 0.01 and p < 0.001) and positively with ELF score (p < 0.05 and p < 0.0001). In individuals with an ELF score ≥7.8 the influence of both neurogenic and respiratory flow-motion activity on LZC was up-rated (p < 0.0001). CONCLUSION: Altered microvascular network functionality occurs in adults with NAFLD suggesting a mechanistic role for dysregulated neurovascular control in individuals at risk of severe liver fibrosis.

Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia.

As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1-19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5-40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after short-term acclimatization. Then again, 1 week is what one needs to get from home to a location at significant altitude.