Single-capillary endothelial dysfunction resolved by optoacoustic mesoscopy

Microvascular endothelial dysfunction (MiVED) is implicated in several health conditions, such as hypertension, atherosclerotic cardiovascular disease (CVD), and diabetes. MiVED is considered an early marker of endothelial impairment that often precedes dysfunction in larger arteries. Our study aims to address the lack of suitable technologies for detailed in-vivo MiVED observation by introducing fast raster-scan optoacoustic mesoscopy (fRSOM), which can resolve cutaneous MiVED features at single-capillary resolution.

The scientific hypothesis was that fRSOM could record morphological features and dynamic responses during post-occlusive reactive hyperemia (PORH), providing the most detailed observation of MiVED achieved so far. The study involved assessing the effects of smoking and CVD on cutaneous endothelial function using the skin as a window to MiVED.

fRSOM was shown to clearly measure the effects of smoking habit (N=20) and CVD (N=20) on cutaneous endothelial function. The results showed that these effects are layer-specific, with smoking and CVD affecting the sub-papillary dermis differently than the reticular dermis. Interestingly, the study did not observe substantial structural changes in the microvasculature of smokers and volunteers with CVD, indicating that MiVED may be an earlier marker than morphology-based biomarkers, typically assessed by histological studies.

The scientists explain the fRSOM and PORH procedures: “Forearm PORH tests were conducted, and we compared the fRSOM readouts to laser Doppler flowmetry (LDF) and white-light tissue spectrometry (WLS) measurements. The PORH procedure included three phases of measurements: 2 minutes of baseline, 5 minutes of "cuff on" (inflated cuff at a pressure of at least 40 mmHg above the systolic blood pressure of the subject), and 3 minutes of "cuff off" (deflated cuff). The fRSOM obtained 3D volumetric scans and 2D cross-sectional scans, allowing examination of the response to PORH with high spatial and temporal detail.”

Three MiVED biomarkers were extracted from the fRSOM data: the maximum volume change (MVC), hyperemia ratio (HR), and time-to-peak (TP), at the single-capillary level and as a function of capillary depth. “These biomarkers allowed an in-depth understanding of fRSOM unique capabilities and their relationship to different conditions”, explained the scientists, “we employed these biomarkers to assess the effects of smoking, that is associated with high cardiovascular risk, and CVD on MiVED on a spatially-dependent basis.”

Their results showed that fRSOM could resolve dynamics of individual cutaneous capillaries at 2 Hz temporal resolution, necessary for capturing changes during a PORH test. The study observed MiVED alterations in both the smoker and CVD groups and recorded previously undocumented impairment differences in shallow versus deeper dermal microvessels. They also found that fRSOM provided significantly better inter-day repeatability and reproducibility compared to LDF and WLS.

In conclusion, the study demonstrated that fRSOM is a non-invasive modality that enables the visualization and quantification of skin microvascular structure and function. “This innovative capability bridges a technological gap and has the potential to fill the knowledge void concerning the effects of diseases on MiVED and the prospective utilization of MiVED as an early detection, diagnostic, or theranostic marker”, forecast the scientists.

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