Microvascular flow dictates the compromise between spatial resolution and acquisition time in Ultrasound Localization Microscopy

Vincent Hingot,Mickael Tanter,Line Rahal,Olivier Couture,Baptiste Heiles,Claudia Errico

doi:10.1038/s41598-018-38349-x

Abstract

Medical ultrasound is a widely used diagnostic imaging technique for tissues and blood vessels. However, its spatial resolution is limited to a sub-millimeter scale. Ultrasound Localization Microscopy was recently introduced to overcome this limit and relies on subwavelength localization and tracking of microbubbles injected in the blood circulation. Yet, as microbubbles follow blood flow, long acquisition time are required to detect them in the smallest vessels, leading to long reconstruction of the microvasculature. The objective of this work is to understand how blood flow limits acquisition time. We studied the reconstruction of a coronal slice of a rat’s brain during a continuous microbubble injection close to clinical concentrations. After acquiring 192000 frames over 4 minutes, we find that the biggest vessels can be reconstructed in seconds but that it would take tens of minutes to map the entire capillary network. Moreover, the appropriate characterization of flow profiles based on microbubble velocity within vessels is bound by even more stringent temporal limitations. As we use simple blood flow models to characterize its impact on reconstruction time, we foresee that these results and methods can be adapted to determine adequate microbubble injections and acquisition times in clinical and preclinical practice.

Highlights

With a sub-millimeter precision deep in tissues, medical ultrasound is a widespread preclinical and clinical technique to study organs and blood flows
We explore the link between the slow passage of microbubbles inside the vasculature and the acquisition time for Ultrasound Localization Microscopy
In the course of 4 minutes, 192,000 coronal planes of an in vivo rat brain were acquired with an ultrafast ultrasound scanner during a constant jugular infusion of contrast agents. 6 million microbubbles were localized with interpolation factors ranging from 1 to 15 (Fig. 1A), corresponding to in plane pixel sizes between 100 μm and 5 μm which is the theoretical resolution limit described in (4)

Summary

Introduction

With a sub-millimeter precision deep in tissues, medical ultrasound is a widespread preclinical and clinical technique to study organs and blood flows. Ultrasound Localization Microscopy (ULM) was developed as a transposition of fPALM to ultrasound imaging using clinically-approved gaseous contrast agents, smaller than red blood cells After intravenous injection, these microbubbles, explore the whole vasculature and are eliminated within a few minutes. The precise positions of hundreds of thousands of individual microbubbles are accumulated to form super-resolution images Under these conditions, ULM was able to map vessels smaller than 10 μm with velocities as low as 1 mm.s−1 in the living rat brain and image the microvasculature of the kidney, ear and tumor in animal models. We introduce a model Equation [4] based on blood flow to describe how it drives acquisition time and spatial resolution We apply it to the rat’s brain as it offers a large and multiscale distribution of vessels. We discuss the validity and relevance of this framework and especially how it can serve as a guideline for ULM acquisitions in 2D and eventually 3D, and to accompany the translation to clinical practice

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