Novel Noninvasive Assessment of Microvascular Structure and Function in Humans

Abstract

Introduction Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing in vivo structures at a resolution of ~10 μm. We have developed specialized OCT-based approaches that quantify diameter, speed, and flow rate in human cutaneous microvessels. In this study, we hypothesized that OCT-based microvascular assessments would possess comparable levels of reliability when compared with those derived using conventional laser Doppler flowmetry (LDF). Methods Speckle decorrelation images (OCT) and red blood cell flux (LDF) measures were collected from adjacent forearm skin locations on 2 d (48 h apart), at baseline, and after a 30-min rapid local heating protocol (30°C–44°C) in eight healthy young individuals. OCT postprocessing quantified cutaneous microvascular diameter, speed, flow rate, and density (vessel recruitment) within a region of interest, and data were compared between days. Results Forearm skin LDF (13 ± 4 to 182 ± 31 AU, P < 0.05) and OCT-derived diameter (41.8 ± 6.6 vs 64.5 ± 6.9 μm), speed (68.4 ± 9.5 vs 89.0 ± 7.3 μm·s−1), flow rate (145.0 ± 60.6 vs 485 ± 132 pL·s−1), and density (9.9% ± 4.9% vs 45.4% ± 5.9%) increased in response to local heating. The average OCT-derived microvascular flow response (pL·s−1) to heating (234% increase) was lower (P < 0.05) than the LDF-derived change (AU) (1360% increase). Pearson correlation was significant for between-day local heating responses in terms of OCT flow (r = 0.93, P < 0.01), but not LDF (P = 0.49). Bland–Altman analysis revealed that between-day baseline OCT-derived flow rates were less variable than LDF-derived flux. Conclusions Our findings indicate that OCT, which directly visualizes human microvessels, not only allows microvascular quantification of diameter, speed, flow rate, and vessel recruitment but also provides outputs that are highly reproducible. OCT is a promising novel approach that enables a comprehensive assessment of cutaneous microvascular structure and function in humans.

Optical coherence tomography: a novel imaging approach to visualize and quantify cutaneous microvascular structure and function in patients with diabetes

“… 31 32 In this study we chose a modified local heating protocol which aimed to induce maximal vasodilation and so assess functional and structural aspects of microvascular dilation. 20 The impaired heating responses we observed in the DFU and DNU groups may be due to loss of neurogenic vasodilation and/or reduced synthesis of NO or other local factors. We think it will be possible in future studies, using a combination of OCT assessment and simultaneous microdialysis delivery of specific pathway antagonists, 33–35 to pharmacodissect individual pathways responsible for the regulation of cutaneous microvascular dysfunction/function in health and disease.…”

“…Further details of this image acquisition and analysis are described elsewhere. 20 In brief, the characteristics of the speckle noise are related to blood flow speed, with faster blood flow giving rise to more rapid fluctuations in the speckle noise. Speckle indicating blood vessels is automatically delineated from the surrounding static tissue using standard imaging processing techniques, with the speckle fluctuations providing an estimate of flow speed at each point.…”

“…In our recent studies, we have shown that OCT is capable of providing high-resolution images and accurate quantification of cutaneous microvessel structure and function, both at rest and in response to physiological stimulation (eg, responses to local heating). 20 21 The purpose of this study was to apply OCT in people with diabetes, with and without foot ulceration, and compare these responses to a healthy age and sex-matched control group. We hypothesized that OCT-based parameters would differentiate between control and diabetic subjects in terms of their skin microvascular structure and function.…”

Optical coherence tomography for the investigation of skin adaptation to mechanical stress

“…The utility of OCTA for measuring the cutaneous microvasculature in response to a local heating protocol was recently demonstrated for the first time by Smith et al 24 The researchers imaged the ventral forearm of participants with OCTA while applying heat with a commercially available skin heating probe. While their study did well to introduce the concept of using OCTA with local heating for exercise physiology research, we believe the methods demonstrated in the current study offer several improvements that may help to advance the technique even further.…”

Historical reviews of the assessment of human cardiovascular function: interrogation and understanding of the control of skin blood flow

“…Similar, to laser perfusion imaging, the speckle pattern changes with movement of red blood cells compared to stationary tissue, which allows an estimate of the rate of blood flow. In recent studies from the same laboratory, OCT of the skin in the lower forearm was imaged alongside laser Doppler flowmetry during a 30 min bout of local heating to cause increases in skin blood flow (Carter et al 2016, Smith et al 2019. These studies uniquely demonstrated that the OCT technique can provide in-depth insight into the morphological and functional changes in skin vessels.…”