Changes within the microcirculation can provide an early indication of the onset of a plethora of ailments. Various techniques have thus been developed that enable the study of microcirculatory irregularities. Correlation mapping optical coherence tomography (cmOCT) is a recently proposed technique, which enables mapping of vasculature networks at the capillary level in a noninvasive and noncontact manner. This technique is an extension of conventional optical coherence tomography (OCT) and is therefore likewise limited in the penetration depth of ballistic photons in biological media. Optical clearing has previously been demonstrated to enhance the penetration depth and the imaging capabilities of OCT. In order to enhance the achievable maximum imaging depth, we propose the use of optical clearing in conjunction with the cmOCT technique. We demonstrate in vivo a 13% increase in OCT penetration depth by topical application of a high-concentration fructose solution, thereby enabling the visualization of vessel features at deeper depths within the tissue.
The microcirculation plays a critical role is maintaining organ health and function by serving as a vascular are where
trophic metabolism exchanges between blood and tissue takes place. To facilitate regular assessment in vivo, noninvasive
microcirculation imagers are required in clinics. Among this group of clinical devices, are those that render
microcirculation morphology such as nailfold capillaroscopy, a common device for early diagnosis and monitoring of
microangiopathies. However, depth ambiguity disqualify this and other similar techniques in medical tomography where
due to the 3-D nature of biological organs, imagers that support depth-resolved 2-D imaging and 3-D image
reconstruction are required. Here, we introduce correlation map OCT (cmOCT), a promising technique for
microcirculation morphology imaging that combines standard optical coherence tomography and an agile imaging
analysis software based on correlation statistic. Promising results are presented of the microcirculation morphology
images of the brain region of a small animal model as well as measurements of vessel geometry at bifurcations, such as
vessel diameters, branch angles. These data will be useful for obtaining cardiovascular related characteristics such as
volumetric flow, velocity profile and vessel-wall shear stress for circulatory and respiratory system.
Collagen and elastin fibers are generally arranged in parallel bundles within the dermis. These bundles are oriented such
that they can most efficiently resist the stress and strain that normally occurs on the skin during movement. The pattern
of these fiber bundles establishes the lines of cleavage of the skin. Knowledge of the orientation of these is of key
importance for surgical procedures. When incisions are cut parallel to the cleavage line orientation the incision will heal
better and produce less scaring.
In this work we report a novel application of Optical coherence tomography for the determination of cleavage line
orientation in in-vivo human skin. The technique operates by pressing a small circular indenter onto the skin to deform
the skin. This is then imaged using optical coherence tomography. Analysis of the resulting deformation can be seen to
have an ellipsoidal shape which is related to the cleavage line orientation. We demonstrate that the technique can be used
to map the cleavage line orientation in-vivo.
The use of microneedles as a method of circumventing the barrier properties of the stratum corneum is receiving much attention. Although skin disruption technologies and subsequent transdermal diffusion rates are being extensively studied, no accurate data on depth and closure kinetics of microneedle-induced skin pores are available, primarily due to the cumbersome techniques currently required for skin analysis. We report on the first use of optical coherence tomography technology to image microneedle penetration in real time and in vivo. We show that optical coherence tomography (OCT) can be used to painlessly measure stratum corneum and epidermis thickness, as well as microneedle penetration depth after microneedle insertion. Since OCT is a real-time, in-vivo, nondestructive technique, we also analyze skin healing characteristics and present quantitative data on micropore closure rate. Two locations (the volar forearm and dorsal aspect of the fingertip) have been assessed as suitable candidates for microneedle administration. The results illustrate the applicability of OCT analysis as a tool for microneedle-related skin characterization.
The use of laser Doppler perfusion imaging (LDPI) and laser speckle perfusion imaging (LSPI) is well known in the noninvasive investigation of microcirculatory blood flow. This work compares the two techniques with the recently developed tissue viability (TiVi) imaging system, which is proposed as a useful tool to quantify red blood cell concentration in microcirculation. Three systems are evaluated with common skin tests such as the use of vasodilating and vasoconstricting drugs (methlynicotinate and clobetasol, respectively) and a reactive hyperaemia maneuver (using a sphygmomanometer). The devices investigated are the laser Doppler line scanner (LDLS), the laser speckle perfusion imager (FLPI)-both from Moor Instruments (Axminster, United Kingdom)-and the TiVi imaging system (WheelsBridge AB, Linköping, Sweden). Both imaging and point scanning by the devices are used to quantify the provoked reactions. Perfusion images of vasodilatation and vasoconstriction are acquired with both LDLS and FLPI, while TiVi images are acquired with the TiVi imager. Time acquisitions of an averaged region of interest are acquired for temporal studies such as the reactive hyperaemia. In contrast to the change in perfusion over time with pressure, the TiVi imager shows a different response due its measurement of blood concentration rather than perfusion. The responses can be explained by physiological understanding. Although the three devices sample different compartments of tissue, and output essentially different variables, comparisons can be seen between the three systems. The LDLS system proves to be suited to measurement of perfusion in deeper vessels, while FLPI and TiVi showed sensitivity to more superficial nutritional supply. (Cont'd.)
We review methods applied to imaging and assessment of the microcirculation and document the
recent progress. Visible and near-infrared light, particularly in the wavelength region of 600 nm
to 1100 nm, offer a window into human and animal tissues due to reduced scattering and
absorption. Laser Doppler perfusion imaging (LDPI) and laser speckle perfusion imaging (LSPI)
are used in the non-invasive investigation of the microcirculation. This paper compares the two
techniques with the recently developed Tissue Viability (TiVi) imaging system, which is
proposed as a useful tool to quantify red blood cell concentration in the microcirculation. Both
imaging and point scanning by the devices were used to quantify microvascular reactivity. The
responses can be explained by physiological understanding and subtle differences by technophysiological
knowledge. The resolution, penetration depth and acquisition rate of each
instrument should be taken into account when choosing a system for a particular clinical
measurement.
Biomedical optics and photomedicine applications are challenged by the turbid nature of most biological tissue systems.
This nature limits the penetration depth of light into the tissue. Optical clearing improves the penetration depth of light
by the application of optical clearing agents which produce an equalization of refractive indices between tissue
components and causes a decrease in tissue scattering, and thus increase in optical transmittance. In this paper we
examine the effects of optical clearing agents on ex vivo porcine skin using the immersion method. We develop a simple
model that can be used to compare different aspects of optical clearing agents such as the rate at which the clearing
agents enters the tissue and also the reduction in scattering achieved. We examine the change in the reflected light
spectrum over time as the clearing agent enters the skin. This is examined via point probe measurements and also a wide
field imaging technique with a consumer-end digital camera. The consumer-end digital camera offers a cheap and
simple method for analyzing optical clearing agents over a wider field, overcoming the limitations of single point
measurements.
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