Researchers at Helmholtz Munich and the Technical University of Munich (TUM) have developed a new imaging technology that can noninvasively capture three-dimensional information from capillaries to detect early signs of heart disease. The system is called fast raster-scan optoacoustic mesoscopy (fast-RSOM) and is designed to visualize and quantify through the skin microvascular endothelial dysfunction (MiVED), a biomarker that often precedes dysfunction in larger arteries. The development of this new technology is published in the journal Light Science & Applications.
“With fast-RSOM, we can, for the first time, noninvasively assess endothelial dysfunction at single-capillary and skin-layer resolution in humans,” said the paper’s first author Hailong He, PhD, a group leader at TUM. His co-first author Angelos Karlas, MD, a vascular surgeon at TUM University Hospital added: “Our novel approach offers an unprecedented view of how cardiovascular disease manifests at the microvascular level.”
According to the researchers, evidence is building that MiVED precedes the development macrovascular endothelial dysfunction (ED) and could be an important biomarker of early disease development. Currently, however, most risk assessments focus on larger blood vessels since there are limited options for assessing microvascular function in vivo. Existing optical technologies and Doppler-based methods are capable of measuring blood flow and oxygenation but are not able to provide data on individual capillaries.
Fast-RSOM was developed to overcome these limitations and enable visualization of capillaries. It was built on existing raster-scan optoacoustic mesoscopy (RSOM), an imaging method that uses short pulses of light to generate ultrasound signals from tissue. Absorption of light by blood produces acoustic waves that are detected and then reconstructed into high-resolution images of vascular structures. Previous research had already shown that RSOM could visualize microvascular morphology in dermatology and metabolic disease.
To enable functional imaging at the capillary level, the team modified RSOM to include coaxial illumination and detection, which allows higher laser repetition rates, and by introducing scanning protocols that switch between volumetric scans and rapid line scans. These advances enabled imaging at temporal resolutions of at least 2 Hz, sufficient to capture fast vascular responses.
The system was designed to observe vascular behavior during post-occlusive reactive hyperemia (PORH), which is regularly induced in patients to observe blood flow changes to assess function of the vascular endothelium and microcirculation. Using fast-RSOM, the researchers discovered three MiVED biomarkers, maximum volume change, hyperemia ratio, and time-to-peak, that quantify how individual capillaries and specific skin layers respond during hyperemia. “The definition of such biomarkers was not possible before since no other method is able to retrieve such capillary metrics,” the researchers wrote.
To test fast-RSOM, the team examined healthy volunteers, smokers, and patients with atherosclerotic cardiovascular disease. “Our results show that using fast-RSOM on skin clearly measured the effects of smoking (N = 20) and atherosclerotic CVD (N = 20) on cutaneous endothelial function,” the researchers wrote. These data showed layer-specific impairments, with smoking and cardiovascular disease affecting the sub-papillary dermis differently from the reticular dermis. Importantly, the researchers observed “no substantial structural changes in the microvasculature,” indication that MiVED could be used as an early indicator of disease risk.
If further developed, fastRSOM could find its way to the clinic where it would quantitatively capture functional changes that manifest from smoking or hypertension to guide earlier interventions and provide a means to monitor responses to lifestyle or therapeutic changes. According to the TUM team, the portability and cost of the technology would lend itself to broad clinical adoption.
Building on these findings, the researchers will now validate fast-RSOM biomarkers in larger and more diverse population patient cohort and begin longitudinal studies to assess how well the new biomarkers predict disease onset and progression compared with standard macrovascular assessments. They will also continue to refine the technology to include multi-spectral fast-RSOM to assess oxygen saturation changes as well as expanded scanning to cover larger skin areas.
