Functional ultrasonography for intraosseous blood circulation assessment – FUIBCA

Intraosseous blood circulation is thought to have a key role in bone growth and remodeling, in fracture healing and in the development of bone disorders. However it is rarely considered in the clinical practice because of the absence of a suitable technique for its in vivo evaluation in humans. Inadequate bone vascularity has been associated with bone disorders (e.g. osteoporosis, osteonecrosis) in animal models, most often with invasive techniques. However evidence in humans is very sparse. There exists no gold standard method for the measurement of intraosseous blood flow in humans. Magnetic resonance imaging (MRI) has been proposed to assess the perfusion of marrow only. Positron emission tomography (PET) and near-infrared optical methods have poor spatial resolution; therefore they do not allow the clear distinction between blood flow in cortical bone, in marrow and in soft tissues surrounding bone. On the other hand, ultrasonography offers higher spatial resolution and has the potential to investigate deeper tissues compared to optical techniques.

We hypothesize that the development of intraosseous functional ultrasonography will enable the non-invasive characterization of intraosseous blood circulation, i.e. blood flow in the cortical bone tissue and in the bone marrow. Our project is organized in four tasks. A first task will be to develop and validate transmission pulsing schemes and methods of image reconstruction in order to relax two major assumptions made in conventional ultrasonography, namely the speed of sound in the human body is assumed to be uniform and the multiple reflections experienced by ultrasound waves in the human body are neglected. The reconstruction of an anatomical image of bone will be performed by an adaptation of time-tested seismic imaging methods and an adaptation of automatic sound speed selection methods developed for ultrasonography in soft tissues or seismic imaging. Ultrasound images of the forearm of healthy volunteers will be validated with gold standard anatomy obtained by high-resolution x-ray computed tomography (CT). Capitalizing on the results of task 1, a second task will aim to develop transmission pulsing schemes and signal processing for intraosseous functional ultrasonography by adapting recent advances in ultrafast ultrasonic assessment of blood flow in soft tissues. The sensitivity of those methods to characterize intraosseous blood flow will be tested in healthy volunteers. The third task will study the added value of using an ultrasound contrast agent (routinely used for conventional contrast-enhanced ultrasound imaging) by developing specific transmission pulsing schemes and signal processing. An injection of contrast agent enhances the echogenicity of blood since contrast agent microbubbles reflect ultrasound much more efficiently than red blood cells. The contrast agent signal can then be used as a surrogate for the blood signal. In this way, we hope to improve the sensitivity of the methods developed in task 2. The goal of the fourth task will be to evaluate the sensitivity of intraosseous functional ultrasonography to physiological variations of intraosseous blood flow in the tibia of healthy volunteers that change position (sitting - head-down tilt), and in patients with bone fracture at the radius or at the tibia.

This scientific project aims to develop and validate a non-invasive and relatively inexpensive way of assessing intraosseous blood circulation in vivo in humans, which is currently unavailable. The success of this work will help to better understand bone physiopathology. It may provide in the long term a clinical tool that misses today, and help in the early diagnosis of bone diseases or the monitoring of bone healing. Besides it will broaden the range of clinical uses of ultrasonography, which fails to image bone so far.