Whole-organ 3D ultrasound micro-flow imaging: from basics physics to clinical proof-of-concept on cardiac and cerebral diseases

Introduction

Blood circulation is essential to organ functions and occurs through a complex network of vessels with diameters varying from several millimeters for large arteries to only a few microns for small capillaries. Dysfunctions in the microcirculation are early markers of many diseases, which are however diagnosed at a later stage, when observable symptoms become visible at larger scales.

Importance of Mapping Blood Flows

Mapping blood flows across several spatial scales at depth in organs is therefore crucial for early diagnosis and monitoring of diseases, but it remains a major challenge in clinical medical imaging.

Ultrasound Localization Microscopy (ULM)

Our laboratory, Physics for Medicine Paris, has introduced in 2015 ultrasound localization microscopy (ULM), a non-invasive method to map and quantify blood flows at depth in organs down to a micron scale resolution, opening avenues for medical imaging.

Challenges in 2D ULM

However, 2D ULM is highly operator-dependent because probe positioning is critical to view the appropriate cross-section. Imaging the whole organ in 3D is therefore crucial for clinical practice and for a comprehensive investigation of organ functions.

Challenges in Ultrasound Imaging

Capturing large 3D volumes through the bones, such as the skull or the rib cage, is a further challenge in ultrasound imaging. Acoustic energy losses due to reflection and distortion of ultrasound waves at the bone interface significantly reduce the imaging sensitivity.

Project Objective

The objective of MicroflowLife is to develop ultrasensitive 3D ULM through bones for mapping the microcirculation of the whole heart and the whole brain.

Methodology

Our approach relies on the development of novel ultrasonic multi-lens probes, combined with new acquisition sequences and processing methods.

Validation and Clinical Translation

Our technology and methods will be first validated in vitro and in vivo, and then translated clinically in first-in-human studies.

Applications

Feasibility of cardiac and cerebral applications will be assessed in two morbid diseases associated with microcirculation alteration:

1. Coronary microvascular dysfunction
2. Brain glioblastoma tumors