Lab Develops New Method to Monitor Endothelial Function

Lawrence Berkeley National Laboratory (Berkeley Lab) has created a new non-invasive method employing cuff-based measurement of flow-mediated dilation to detect preclinical cardiovascular disease. The technology is now available for licensing.

Endothelial function, like blood pressure, is a powerful predictor of heart attack and stroke; emerging studies have linked the COVID-19 virus to endothelial dysfunction. The new method will enable the accurate, inexpensive, and routine detection and monitoring of preclinical cardiovascular disease via both endothelial function and endothelium-independent vasodilation. The novel method is the only noninvasive vasorelaxation assessment technique to achieve the previously unprecedented accuracy of invasive methods such as ultrasonic imaging.
 
Studies on human subjects have verified that the new method is 37 percent more sensitive to arterial relaxation than brachial artery imaging. In addition, the apparatus costs one-fifteenth as much as an ultrasonic imager, minimizes the possibility of human operating error, and eliminates the need for an ultrasound technician.
 
The current state-of-the-art technology, flow-mediated dilation (FMD), measures the change in diameter in the brachial artery before and after shutting off blood flow. FMD requires the use of an ultrasound scanner or expensive systems, making the current technology unsuitable for frequent testing or continuous monitoring. In addition, the measurements by some FMD systems are based on microvascular tone, which can be compromised by factors such as sympathetic nervous activation. The Berkeley Lab invention developed by Biosciences Area scientists Jonathan Maltz and Thomas Budinger overcomes these challenges to achieve more convenient patient testing.
 
Maltz also invented a way to calibrate the cFMD measurements with those of ultrasound-based flow-mediated dilation (uFMD). This allows health providers to take advantage of existing research on the effect of cardiovascular health factors (diet, physical activity, medical interventions, etc.), typically assessed using uFMD. The novel uFMD calibration technology can be used in nearly every setting, may be applied to arteries in the arms and legs, and is compatible with existing technologies and other dilation measurement systems.
 
The Berkeley Lab method works by inducing an artificial pulse at the superficial radial artery via a linear actuator. A natural pulse is not used because it changes the properties of the artery wall and its edge is not as sharp and easy to measure. An ultrasonic Doppler stethoscope detects the pulse 10-20 cm upstream from the initial pulse. The delay between pulse application and detection provides the pulse transit time (PTT). PTT is measured before and after five minutes of BA occlusion and reactive hyperemia. The Berkeley Lab instrumentation includes a cuff occlusion system but other means of stimulating endothelial mediated compliance changes are possible.
 
As the blood flow increases after occlusion, the endothelial cells that line the inner wall of the artery sense the increased friction and chemical composition of the blood and release relaxing agents into the artery’s smooth muscle. The healthier the arterial system, the better the endothelial layer functions and the greater the difference will be between the pre-and post-occlusion measurements.
 
The rise time of the artificial pulse used in the Berkeley Lab method is more than an order of magnitude shorter than that of a natural pulse. The ability to calculate PTT from artificial pulses makes the Berkeley Lab technique much more precise than other noninvasive procedures.