Calibrating Doppler imaging of preterm intracerebral circulation using a microvessel flow phantom

Abstract

Introduction: Preterm infants are born during critical stages of brain development, in which the adaptive capacity of the fetus to extra-uterine environment is limited. Inadequate brain perfusion has been directly linked to preterm brain damage. Advanced high-frequency ultrasound probes and processing algorithms allow visualization of microvessels and depiction of regional variation. To assess whether visualization and flow velocity estimates of preterm cerebral perfusion using Doppler techniques are accurate, we conducted an in vitro experiment using a microvessel flow phantom.

Materials and methods: An in-house developed flow phantom containing two microvessels (inner diameter 200 and 700 μm) with attached syringe pumps, filled with blood-mimicking fluid, was used to generate non-pulsatile perfusion of variable flow. Measurements were performed using an Esaote MyLab70 scanner.

Results: Microvessel mimicking catheters with velocities as low as 1 cm/s were adequately visualized with a linear ultrasound probe. With a convex probe, velocities <2 cm/s could not be depicted. Within settings, velocity and diameter measurements were highly reproducible [intra-class correlation 0.997 (95% CI 0.996-0.998) and 0.914 (0.864-0.946)]. Overall, mean velocity was overestimated up to threefold, especially in high velocity ranges. Significant differences were seen in velocity measurements when using steer angle correction and in vessel diameter estimation (p < 0.05).

Conclusion: Visualization of microvessel-size catheters mimicking small brain vessels is feasible. Reproducible velocity and diameter results can be obtained, although important overestimation of the values is observed. Before velocity estimates of microcirculation can find its use in clinical practice, calibration of the ultrasound machine for any specific Doppler purpose is essential. The ultimate goal is to develop a sonographic tool that can be used for objective study of regional perfusion in routine practice.

Keywords: Doppler; calibration; cerebral blood flow; cerebral circulation; cerebral perfusion; flow phantom; microcirculation; preterm brain.

Figure 1

The test setting. Flow phantom with a fixed ultrasound probe. BMF, blood-mimicking fluid.

Figure 2

Ultrasound image of phantom microvessel. Ultrasound image showing a 200 μm flow phantom catheter as depicted by a linear probe in color Doppler mode.

Figure 3

Pump velocity versus measured Doppler velocity. Relation between true velocity (centimeter per second) and velocity measured (centimeter per second) in different settings: (A) with or without steer angle correction, (B) color Doppler versus power Doppler, (C) convex versus linear probe, (D) vessel size. Since applying steer angle correction leads to significant (p < 0.001) overestimation of velocity, velocities in (B–D) are without applying steer angle correction. The dotted line represents the line of equality.

Figure 4

Agreement between true velocity and Doppler velocity. Bland–Altman plot of agreement between true velocity (V_true) and velocity estimated by Doppler measurements (V_measured). The mean difference is 4.12 cm/s (95% CI 3.10–5.15 cm/s), dotted lines represent ± 2 SD borders.

Figure 5

Vessel diameter. Vessel diameter measured (±SD) for the 200 μm vessel and the 700 μm vessel. Note the significant overestimation.