Microbubble contrast agent as a minimally invasive pressure sensor at body temperature and reduced concentrations in an ultrasound flow phantom
Authors: Dockerill C , Faraci A , Christensen-Jeffries K , Alastruey J , Tang M X , Rajani R , Lamata P , Nio A Q X 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): MRC.

Background
Cardiac catheterisation is the gold standard for assessing cardiac pressures. However, this is an invasive and costly procedure. A minimally invasive alternative may be to use the subharmonic signal of microbubble ultrasound contrast agents to estimate pressure using echocardiography (Sub-Harmonic Assisted Pressure Estimation: SHAPE).

Purpose
The aim of this work was to investigate the ability of SHAPE to track dynamic diastolic pressures in a flow phantom at body temperature and at reduced microbubble concentrations.

Methods
A priming dose of 0.4 mL/L of sulphur hexafluoride microbubbles was circulated through a silicone tube using a peristaltic pump at a flow rate of 375 mL/min (generating 376 pressure cycles/min and maximum pressure gradient of 1.9 mmHg/ms; Fig. 1). The ULtrasound Advanced Open Platform (ULA-OP) was used with a cardiac phased array transducer to transmit a pulse-inversion sequence at 2.1 MHz. Radiofrequency data were recorded at five acoustic pressures (71–228 kPa peak-negative). To investigate the effects of temperature, the subharmonic-pressure relationship was measured over 60 min at both room and body temperature (37°C). Microbubble concentration was maintained by regular top-up (0.15 mL/L every 3–5 min). To investigate the effect of lower concentrations on the subharmonic-pressure relationship, a priming dose of 0.4, 0.3 or 0.2 mL/L was administered before a single acquisition was made. The system was immediately purged before testing the next concentration. The subharmonic (1.05 MHz) amplitude of the microbubbles was calculated over a 40% bandwidth. A solid-state catheter recorded ground-truth pressures. Correlation coefficient (r) and sensitivity (dB/mmHg) of the subharmonic signal to the pressure values were calculated.

Results
The mean correlation coefficient (r = 0.91 ± 0.04; Fig. 2) and sensitivity (0.20 ± 0.04 dB/mmHg) at body temperature (n = 20) were significantly greater than those for the same batch of microbubbles at room temperature (r = 0.81 ± 0.07 and 0.14 ± 0.02; n = 18; p &lt; 0.05) at the optimal acoustic pressure (Fig. 2). No significant differences in the subharmonic-pressure relationship were observed between the three different microbubble concentrations (Correlation: r = 0.96 ± 0.00, 0.96 ± 0.01, 0.97 ± 0.01. Sensitivity: 0.26 ± 0.02, 0.26 ± 0.03, 0.28 ± 0.02 mmHg/dB for 0.4, 0.3 and 0.2 mL/L, respectively; n = 3) at the optimal acoustic pressure.

Conclusions
SHAPE can accurately track diastolic pressures five times faster than the average resting heart rate at body temperature and with reduced microbubble concentrations. SHAPE is a potential method for assessing cardiac diastolic pressures using ultrasound in a minimally invasive fashion, being suitable for use in patients with faster microbubble clearance or in the event of delayed acquisition. The use of SHAPE fits into routine clinical procedures and has the potential to improve the diagnosis and monitoring of cardiovascular diseases.