Ultrasensitive Photonic Microsystem Enabling Sub-micrometric Monitoring of Arterial Oscillations for Advanced Cardiovascular Studies.

Rosalía Rodríguez-Rodríguez,Xavier Munoz-Berbel,Andreu Llobera,Ulf Simonsen,Vladimir Matchkov,Tobias Nils Ackermann,Jose Antonio Plaza

doi:10.3389/fphys.2019.00940

Abstract

Cardiovascular diseases are the first cause of death globally. Their early diagnosis requires ultrasensitive tools enabling the detection of minor structural and functional alterations in small arteries. Such analyses have been traditionally performed with video imaging-based myographs, which helped to investigate the pathophysiology of the microvessels. Since new vascular questions have emerged, substantial modifications are necessary to improve the performance of imaging and tracking software, reducing the cost and minimizing the microvessel cleaning and manipulation. To address these limitations, we present a photonic microsystem fabricated in polydimethylsiloxane and integrating micro-optical elements and a lightguide-cantilever for sub-micrometric analysis of small arteries (between 125 and 400 μm of basal diameter). This technology enables simultaneous measurement of arterial distension, stiffness, vasomotion, and heartbeat and without the need for advanced imaging system. The microsystem has a limit of detection of 2 μm, five times lower than video imaging-based myographs, is two times more sensitive than them (0.5 μm/mmHg), reduces variability to half and doubles the linear range reported in these myographs. More importantly, it allows the analysis of intact arteries preserving the integrity and function of surrounding tissues. Assays can be conducted in three configurations according to the surrounding tissue: (i) isolated arteries (in vitro) where the surrounding tissue is partially removed, (ii) non-isolated arteries (in vivo) with surrounding tissue partially removed, and (iii) intact arteries in vivo preserving surrounding tissue as well as function and integrity. This technology represents a step forward in the prediction of cardiovascular risk.

Highlights

Cardiovascular diseases (CVDs) are the first cause of death globally: more people die annually from CVDs than from any other cause1
Small blood vessels analysis has been for a long time limited to myographs (Mulvany and Aalkjaer, 1990; Buus et al, 2013), which developed to answer specific questions related to the regulation of vascular diameter in small-size arteries (Halpern et al, 1984)
In the base of the latter, we present a photonic microsystem fabricated in the low cost elastomer polydimethylsiloxane (PDMS) and integrating micro-optic elements and a lightguidecantilever for ultrasensitive analysis of intact small arteries in vivo

Summary

Introduction

Cardiovascular diseases (CVDs) are the first cause of death globally: more people die annually from CVDs than from any other cause (www.who.int). Some of new research questions are related to the bidirectional interaction of neighboring tissues (e.g., perivascular adipose tissue and arterial wall (Costa et al, 2018) These new questions require modifications of the original systems as well as substantial variations in the tools used to measure artery diameter and additional properties of the blood vessel (Lawton et al, 2019). Some interesting contributions have been recently performed, including intravital microscopy combined to laser speckle imaging (Nyvad et al, 2017) and advanced tracking software, such as VasoTracker (Lawton et al, 2019) Even considering these advantages, it becomes increasingly accepted that the early detection of arterial disorders before clinical conditions are manifested requires new specific strategies and tools for sensitive analysis of small artery structure and function

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