Skip to main content

GENERAL COMMENTARY article

Front. Physiol., 17 October 2022
Sec. Integrative Physiology

Commentary: Multiple laser doppler flowmetry probes increase the reproducibility of skin blood flow measurements

Alicia Guigui,
Alicia Guigui1,2*Jordan Loader,,Jordan Loader1,2,3Alexandre Bellier,Alexandre Bellier2,4Matthieu Roustit,Matthieu Roustit1,2
  • 1University Grenoble Alpes, Inserm U1300, Grenoble, France
  • 2Grenoble University Hospital, Inserm CIC1406, University Grenoble Alpes, Grenoble, France
  • 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • 4Computational and Mathematical Biology Team, TIMC-IMAG UMR 5525, CNRS, University Grenoble Alpes, Grenoble, France

A Commentary on
Multiple laser doppler flowmetry probes increase the reproducibility of skin blood flow measurements

by Luck JC, Kunselman AR, Herr MD, Blaha CA, Sinoway LI and Cui J (2022). Front. Physiol. 13:876633. doi. 10.3389/fphys.2022.876633

Luck et al. (2022) recently reported that the reproducibility of skin blood perfusion measurements with laser Doppler flowmetry (LDF) may be improved by the use of multiple laser Doppler probes at a given region of interest.

Laser Doppler flowmetry is one of several laser-based imaging technologies (e.g., laser Doppler imaging and laser speckle contrast imaging) that can be used to routinely assess skin microcirculation in humans. Additionally, when these laser-based technologies are coupled with tests provocative to the microcirculation (e.g., transdermal iontophoresis of vasoactive substance, local heating or cooling, electrical stimulation etc.), microvascular reactivity and/or function can be explored (Cracowski and Roustit, 2020). However, as highlighted by Luck et al. (2022), LDF is an older technology using a single-point laser, the reproducibility of which is reduced by the variability in the anatomy of the skin microcirculation; more specifically, the variability in the distribution of capillary loops and arteriovenous anastomoses.

To address the spatial limitation in LDF, Luck et al. (2022) used multiple laser Doppler probes concurrently in a single measurement, rather than a single probe as is traditionally implemented. This approach, using multiple, averaged LDF signals via so-called “integrative” probes, was demonstrated previously (Tew et al., 2011). Laser Doppler imaging addressed the spatial limitation in LDF by measuring blood flux over a greater area of the skin microcirculation; essentially averaging out the anatomical variations in the microcirculation (Roustit et al., 2010; Puissant et al., 2013). However, laser Doppler imaging is temporally limited. Developed more recently, laser speckle contrast imaging addresses both spatial and temporal limitations of LDF and laser Doppler imaging, respectively, by recording continuous measurements over larger regions of interest. While LDF equipment costs less than laser speckle contrast imaging, this principal advantage is attenuated by the use of multiple laser Doppler probes in a single measurement; raising serious questions about the relevance of the study when considering the use of LDF in practice.

Methodologically, it must be noted that the authors only focused on resting skin blood flux. Overall, baseline flux has little relevance as a biomarker in disease. A striking example of this is in persons with diabetes, where baseline flux may be increased while reactivity/function is usually impaired (Fredriksson et al., 2010). Indeed, the main application of LDF and other laser-based technologies is to assess changes in microvascular reactivity/function throughout the development of disease or in response to an intervention, requiring that they are coupled with a test that challenges (i.e., dilates or constricts) the microvessels in order to provide data of any real value. It is also worth noting that experiments were performed on the non-glabrous skin of the dorsal forearm. Skin microcirculation and, therefore, the reproducibility of LDF measurements is different between the non-glabrous skin assessed by Luck et al. (2022) and the glabrous skin evaluated by the majority of previous studies (Cracowski and Roustit, 2020).

Given that all experiments were performed in the same volunteer on the same day, the interday reproducibility of the method used by Luck et al. (2022) is unknown. Interday reproduciblity is more relevant than intraday reproducibility when considering patient follow-up or repeated visits in a clinical study. In that context, the necessity to use a semi-permanent marker to ensure replicable placement of the LDF probes does not seem to be suitable for studies requiring follow-up. Additionally, LDF may not be applicable in several conditions, such as surgical interventions, where contact with the wound is generally avoided; further promoting the advantages of non-contact, imaging techniques such as laser speckle contrast imaging.

There were also some errors or inconsistencies that affect the overall quality of the manuscript. While we fully agree that expressing blood flux as cutaneous vascular conductance (CVC) is relevant to account for variations in blood pressure, we question how CVC can be higher than the flux expressed as perfusion units (PU) in Table 3. Indeed, CVC is calculated as the flux (PU) divided by mean arterial pressure (mmHg). Therefore, it is impossible due to the division of a positive number by another positive number ≥1 (CVC = PU/mmHg). In addition, the authors discuss the “mean statistical power” for the intraclass correlation coefficient. The statistical power is the probability that a test correctly rejects the null hypothesis when the alternative hypothesis is true. It is useful to calculate sample size before the study begins, based on one hypothesis. Whether “mean power” is useful is not clear. However, it would be useful to have an indication of the precision of the estimates from this sample size by providing 95% confidence intervals. Although the authors stated that these were calculated, we were unable to find them.

There is also confusion within the manuscript regarding imaging techniques, “laser-Doppler speckle contrast imaging” does not exist. Laser speckle contrast imaging is not based on the Doppler effect, these are two distinct techniques. There is also some inconsistencies in the terminology (flow versus flux). Indeed, these laser-based techniques do not provide a measure of flow (i.e., volume of fluid per unit time), but arbitrary PU, often referred to as flux, which does not permit direct comparisons between technologies.

Overall, Luck et al. (2022) is one of many studies that has introduced a questionable, additional technique using an inferior technology into a field that’s already over-saturated with unstandardized methodologies. Research resources would be better directed to refining techniques that are already known to be superior.

Author contributions

AG and AB wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Cracowski J.-L., Roustit M. (2020). Human skin microcirculation. Compr. Physiol. 10 (3), 1105–1154. Available at:. doi:10.1002/cphy.c190008

PubMed Abstract | CrossRef Full Text | Google Scholar

Fredriksson I., Larsson M., Nystrom F. H., Lanne T., Ostgren C. J., Stromberg T. (2010). Reduced arteriovenous shunting capacity after local heating and redistribution of baseline skin blood flow in type 2 diabetes assessed with velocity-resolved quantitative laser Doppler flowmetry. Diabetes 59 (7), 1578–1584. Available at:. doi:10.2337/db10-0080

PubMed Abstract | CrossRef Full Text | Google Scholar

Luck J. C., Kunselman A. R., Herr M. D., Blaha C. A., Sinoway L. I., Cui J. (2022). Multiple laser Doppler flowmetry probes Increase the reproducibility of skin blood flow measurements. Front. Physiol. 13, 876633. Available at:. doi:10.3389/fphys.2022.876633

PubMed Abstract | CrossRef Full Text | Google Scholar

Puissant C., Abraham P., Durand S., Humeau-Heurtier A., Faure S., Leftheriotis G., et al. (2013). Reproducibility of non-invasive assessment of skin endothelial function using laser Doppler flowmetry and laser speckle contrast imaging. PLoS ONE 8 (4), e61320. Available at: doi:10.1371/journal.pone.0061320

PubMed Abstract | CrossRef Full Text | Google Scholar

Roustit M., Millet C., BlaiSe S., Dufournet B., Cracowski J. L. (2010). Excellent reproducibility of laser speckle contrast imaging to assess skin microvascular reactivity. Microvasc. Res. 80 (3), 505–511. Available at: doi:10.1016/j.mvr.2010.05.012

PubMed Abstract | CrossRef Full Text | Google Scholar

Tew G. A., Klonizakis M., Moss J., Ruddock A. D., Saxton J. M., Hodges G. J. (2011). Reproducibility of cutaneous thermal hyperaemia assessed by laser Doppler flowmetry in young and older adults. Microvasc. Res. 81 (2), 177–182. Available at: doi:10.1016/j.mvr.2010.12.001

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: skin blood flux, laser Doppler, reproducibility, repeatability, microcirculation (skin)

Citation: Guigui A, Loader J, Bellier A and Roustit M (2022) Commentary: Multiple laser doppler flowmetry probes increase the reproducibility of skin blood flow measurements. Front. Physiol. 13:1025905. doi: 10.3389/fphys.2022.1025905

Received: 22 September 2022; Accepted: 06 October 2022;
Published: 17 October 2022.

Edited by:

Joaquin Garcia-Estañ, University of Murcia, Spain

Reviewed by:

James Lang, Iowa State University, United States

Copyright © 2022 Guigui, Loader, Bellier and Roustit. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Alicia Guigui, aguigui@chu-grenoble.fr

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.