19 Complexity-Based Analysis of Microvascular Blood …
293
More recently, the regularity and the randomness of blood flow within microvascular networks has been explored using non-linear methods such as entropy and
complexity techniques [40, 53, 75, 83, 85]. Studies in humans at risk or with
CVD have shown a reduced complexity of the blood flux signal using Lempel-Ziv
complexity algorithms [18] and altered microvascular haemodynamics associated
with diminished chaotic ischaemic flow [34]. In rodent models of cardiovascular
and metabolic disease, chaotic network attractor analysis has revealed a declining
adaptability of microvascular flow patterns [30] and altered spatial heterogeneity and
temporal stability of network perfusion to limit the adaptive ability of the microvasculature and so compromise its function [74]. However, the relevance of these nonlinear indices to the diagnosis and treatment of human cardiovascular disease (CVD)
has yet to be determined.
19.2 Assessment of Microvascular Blood Flow
The microvasculature comprises the small resistance arteries, arterioles, capillaries
and venules with diameter less than 200 μm that lie within the tissue parenchyma.
The primary role of the microcirculation is the optimal exchange of gases, nutrients, water, and metabolites between the blood and surrounding tissues. Regulation
of microvascular perfusion is predominately achieved through changes in network
conductance, modulated at a local level by endothelial, neurogenic and myogenic
regulatory activity [74]. Together these activities determine the cyclic oscillations of
arteriolar diameter (vasomotion) [20, 77] that are related to changes in blood flow
distribution in the microvascular networks (flow motion) [65].
Microcirculatory blood flow has been non-invasively investigated using techniques such as laser Doppler flowmetry (LDF) [67] laser speckle contrast imaging
[11, 70], peripheral arterial tonography [28], diffuse correlation spectroscopy [3],
side-stream dark field [31] and orthogonal polarisation spectral cameras [80], and
nailfold capillaroscopy [89]. The microcirculation of the skin offers an accessible
site in which to study the physiological mechanisms involved in the regulation of
tissue perfusion [36, 67] and LDF, based on the Doppler Effect, first described by
Christian Doppler in 1842 and applied by Buys Ballot in 1845 to sound waves [35],
is currently the most widely used method for continuous, non-invasive monitoring
of skin microcirculation under physiological and pathological conditions [24]. The
LDF signal shows vigorous temporal and spatial variability and measures of this variability (and/or increased stability) can provide a rich source of information relating to
the flexibility/responsiveness of the system. As LDF provides only a relative index of
microvascular perfusion in the time domain it is frequently used in conjunction with
a reactivity test to allow investigation of the mechanisms underlying local control
of vascular tone. Reactivity tests include post occlusive reactive hyperaemia, local
thermal warming and pharmacological tools such as iontophoresis of vasoactive
agents. Skin microvascular responses in the time domain to these provocations are
293
More recently, the regularity and the randomness of blood flow within microvascular networks has been explored using non-linear methods such as entropy and
complexity techniques [40, 53, 75, 83, 85]. Studies in humans at risk or with
CVD have shown a reduced complexity of the blood flux signal using Lempel-Ziv
complexity algorithms [18] and altered microvascular haemodynamics associated
with diminished chaotic ischaemic flow [34]. In rodent models of cardiovascular
and metabolic disease, chaotic network attractor analysis has revealed a declining
adaptability of microvascular flow patterns [30] and altered spatial heterogeneity and
temporal stability of network perfusion to limit the adaptive ability of the microvasculature and so compromise its function [74]. However, the relevance of these nonlinear indices to the diagnosis and treatment of human cardiovascular disease (CVD)
has yet to be determined.
19.2 Assessment of Microvascular Blood Flow
The microvasculature comprises the small resistance arteries, arterioles, capillaries
and venules with diameter less than 200 μm that lie within the tissue parenchyma.
The primary role of the microcirculation is the optimal exchange of gases, nutrients, water, and metabolites between the blood and surrounding tissues. Regulation
of microvascular perfusion is predominately achieved through changes in network
conductance, modulated at a local level by endothelial, neurogenic and myogenic
regulatory activity [74]. Together these activities determine the cyclic oscillations of
arteriolar diameter (vasomotion) [20, 77] that are related to changes in blood flow
distribution in the microvascular networks (flow motion) [65].
Microcirculatory blood flow has been non-invasively investigated using techniques such as laser Doppler flowmetry (LDF) [67] laser speckle contrast imaging
[11, 70], peripheral arterial tonography [28], diffuse correlation spectroscopy [3],
side-stream dark field [31] and orthogonal polarisation spectral cameras [80], and
nailfold capillaroscopy [89]. The microcirculation of the skin offers an accessible
site in which to study the physiological mechanisms involved in the regulation of
tissue perfusion [36, 67] and LDF, based on the Doppler Effect, first described by
Christian Doppler in 1842 and applied by Buys Ballot in 1845 to sound waves [35],
is currently the most widely used method for continuous, non-invasive monitoring
of skin microcirculation under physiological and pathological conditions [24]. The
LDF signal shows vigorous temporal and spatial variability and measures of this variability (and/or increased stability) can provide a rich source of information relating to
the flexibility/responsiveness of the system. As LDF provides only a relative index of
microvascular perfusion in the time domain it is frequently used in conjunction with
a reactivity test to allow investigation of the mechanisms underlying local control
of vascular tone. Reactivity tests include post occlusive reactive hyperaemia, local
thermal warming and pharmacological tools such as iontophoresis of vasoactive
agents. Skin microvascular responses in the time domain to these provocations are