Monitoring of the central blood pressure waveform via a conformal ultrasonic device

Abstract

Continuous monitoring of the central-blood-pressure waveform from deeply embedded vessels, such as the carotid artery and jugular vein, has clinical value for the prediction of all-cause cardiovascular mortality. However, existing non-invasive approaches, including photoplethysmography and tonometry, only enable access to the superficial peripheral vasculature. Although current ultrasonic technologies allow non-invasive deep-tissue observation, unstable coupling with the tissue surface resulting from the bulkiness and rigidity of conventional ultrasound probes introduces usability constraints. Here, we describe the design and operation of an ultrasonic device that is conformal to the skin and capable of capturing blood-pressure waveforms at deeply embedded arterial and venous sites. The wearable device is ultrathin (240 μm) and stretchable (with strains up to 60%), and enables the non-invasive, continuous and accurate monitoring of cardiovascular events from multiple body locations, which should facilitate its use in a variety of clinical environments.

Figure | 1

Design and working principle of the stretchable ultrasonic device. a, Schematics of the stretchable ultrasonic device, where key components are labeled. The high-performance 1–3 composite with periodic piezoelectric rods embedded in an epoxy matrix suppresses shear vibration modes and enhances longitudinal ultrasonic penetration into the skin. The vertical interconnect access (VIA) is used connect the top and bottom electrodes, allowing the co-planar anisotropic conductive film (ACF) bonding to the electrodes to enhance the robustness of the device. When mounted on the human neck, the device enables monitoring of CBP by capturing the pulsating vessel diameter of carotid artery, internal jugular vein (int jugular), and external jugular vein (ext jugular) using the pulse-echo method, as illustrated as the bottom left graph. The device can locate the dynamic anterior (ant) and posterior (post) walls of the vessel using high-directivity ultrasonic beam, as bottom middle graph shows. The corresponding shifting echo radio frequency signals reflected from the anterior and posterior walls appear in the bottom right. b, The device conforming to complex surfaces and under mixed modes of stretching and twisting, demonstrating the mechanical compliance and robustness of the device. The large contact angle of the water droplet on the device in the left panel shows the hydrophobic properties of silicone encapsulation materials that can be used as a barrier to moisture/sweat.

Figure | 2

Electrical, mechanical, acoustical, and biocompatibility characterizations of the conformal ultrasonic device. a, Impedance and phase angle spectra of the 1–3 composite, showing the excellent piezoelectricity. The resonant and anti-resonant frequency ranges are labeled in shaded circles. The left inset is the equivalent RLC circuit diagram of the piezoelectric transducer. At the resonant frequency, the impedance of the equivalent circuit is at the minimum, which will be the most power efficient. At the anti-resonant frequency, the impedance of the equivalent circuit is at the maximum, and the transducer will have the largest damping. b, Ultrasonic receiving signals on the ulnar artery, with two clear echo peaks from the anterior (ant) and posterior (post) vessel walls. Inset is a schematic diagram representing the transducer and the ulnar artery to show echo peaks aligned with the ant and post vessel walls. Tx represents the transducer. c, Time and frequency domain characterization of the signal in b (post-wall peak), showing excellent signal quality and bandwidth (dashed line), indicating the high sensitivity of the transducer. d, Simulated acoustic emission profile of a piezoelectric material size of 0.9 × 0.9 mm² (inset) with excellent beam directivity and penetration depth (>4 cm). e, Bi-axial tensile test of the device with stretchability up to 60% in the x-direction and 50% in y-direction without fracture. The zoomed-in image of the dashed box shows the slight plastic deformation when biaxial strain is larger than 30% in the x-direction. f, Fluorescent images of the fibroblast cells before (left panel) and after 16 hours (right panel) continuous exposure to the ultrasound generated by the conformal ultrasonic device. The 100% survival rate of the cells prove the excellent bio-compatibility of the conformal ultrasonic device.

Figure | 3

Comparison between the conformal ultrasound (US) sensor and the commercial tonometer, exercise hemodynamics monitoring, and central arterial and venous pulse measurements. a, Continuous measurements of radial pulse waveforms by both US sensor (top) and the commercial tonometer (bottom) under the same condition. b, Comparison of applied pressure levels to the skin during the measurement. Inset figures show the skin irritation brought by the tonometer and the conformal US sensor. Dots represent all data points. Error bars represent ± s.d. (N=4). c, Comparison of the BP waveforms measured continuously when wrist is bent at a rate of ~15°/s, showing the robust performance of the conformal device. Different postures from 0° to 30° are labeled in different shades. d, Autocorrelation of the waveforms in c, showing the conformal US device can maintain stable measurements in motion. e, Pulse waveforms on the radial artery before (bf) and after (aft) exercise, showing the changes in absolute pressure values and waveform morphologies. f, Pulse waveforms averaged from 10 continuous periods and normalized to the same diastolic and systolic pressure values to demonstrate the change in morphologies caused by vasodilation. g, Illustration of the US sensor measurement locations marked with arrows: the left carotid artery (CA), external jugular vein (Ext JV) and internal jugular vein (Int JV). The right jugular vein and carotid artery are also highlighted. h, A typical pulse waveform measured from the carotid artery, directly correlated to the left atrial and ventricular events. Different phases and characteristic morphologies are marked. i, A typical pulse waveform from the internal jugular vein, directly correlated to right atrial and ventricular activities. Different phases and characteristic morphologies are marked.

Figure | 4

BP measurements from the central to peripheral arteries and validation using the commercial tonometer. Measurement positions (top row), collected arterial pressure waveforms (middle row), and the BP waveform of one period compared with results from the tonometer (bottom row). From the 1^st column to 4^th column are carotid artery (CA), brachial artery (BA), radial artery (RA), and pedal artery (Dorsalis pedis), respectively, showing an increase of the amplification effect by progressive vascular resistance, a longer interval time between systolic peak and dicrotic notch (illustrated by the grey area), a higher systolic pressure value, and a higher upstroke gradient (the slope of the BP waveform at the beginning of the upstroke).

Figure | 5

ECG correlation based PWV calculation to evaluate the arterial stiffness. a, Illustration of the measurement positions of the three cases from the central to the peripheral arteries, with simultaneous ECG measurements. BP waveforms are normalized based on the systolic pressure. b, Case 1: simultaneous measurement of ECG and BP at the BA. c, Case 2: simultaneous measurement of ECG and BP at the RA. d, Case 3: simultaneous measurement of ECG and BP at the pedal artery (Dorsalis pedis). The graphs on the right panel of b, c, and d show the PAT, as indicated by the grey area, for each case. e, PAT results compared between the conformal device and the tonometer. Dots represent all data points. Error bars represent ± s.d. (N=10).