We propose an ultrasound approach which provides, with one single examination and one single device, access to three bone biomarkers: anatomy, tissue quality and blood flow. It unlocks ultrasound imaging inside bone by accounting for ultrasound wave speed heterogeneity and anisotropic wave refraction. This study reports the first in vivo evaluation with a comparison to peripheral Quantitative Computed Tomography (pQCT) and modulations of blood flow. Anatomical multi-layer bone-corrected reconstruction was validated at the tibia of healthy volunteers against pQCT and showed agreement on bone cortex interfaces. Estimation of axial and radial ultrasound wave speeds in cortical bone tissue (i.e. along the tissue symmetry axis and normal to it) demonstrated good reproducibility and positive correlation with bone mineral density measured by pQCT. Pulsatile blood flow was mapped and quantified in cortical and medullary regions. A directional ray selection method was developed to enhance blood signal extraction by reducing strong specular reflections originating from the outer and inner surfaces of the bone cortex. Physiological and non-physiological modulations of blood flow, namely head-up/head-down tilt table maneuvers and arterial occlusions, demonstrated the method sensitivity to blood flow variations. For the first time, reactive hyperemia was observed inside bone cortex. These results demonstrate the feasibility of a portable, non-ionizing, and quantitative ultrasound approach for structural, anatomical, and vascular characterization of bone tissue. This approach may offer new diagnostic capabilities for bone disorders, for instance osteoporosis, delayed fracture healing or osteonecrosis.

Dynamic elastography uses an imaging system to visualize the propagation of elastic waves, the speed of which is directly related to the elasticity felt by palpation. Very few studies have focused on X-ray elastography because of the technical challenges it poses: a planar image of an integration volume at a very slow sampling rate. We demonstrate that tracking a slow elastic wave guided along a one-dimensional structure could provide a possible solution. The recently discovered flexural pulse wave, which is naturally generated by heartbeats and propagates along arteries, is the perfect candidate for X-ray elastography. As it reflects the cardiovascular health of patients, arterial elasticity is a biomarker of high clinical interest. We first validate the method by measuring the elasticity in artery phantoms using X-ray. We then move on to data obtained in vivo on coronary arteries during a routine angiography examination. During coronary angiography, a catheter is used to inject an X-ray contrast dye into the patient’s aorta. X-rays are then taken as the dye spreads through the coronary arteries. It shows the movement of the coronary arteries for a few seconds and provides an opportunity to follow the natural flexural pulse waves. The obtained Young’s moduli for two patients are E = 38 ± 30 kPa and E = 36 ± 28 kPa, respectively. These preliminary results are expected to pave the way for X-ray elastography.

Perfectly diffuse wave fields are the underlying assumption for noise-correlation tomography in seismology, nondestructive testing, and elastography; however, perfectly diffuse fields are rarely encountered in real-world applications. We show that homogeneously distributed magnetic microparticles allow instantaneous generation of a diffuse wave field, which can be imaged using a clinical probe connected to a fully programmable ultrasound scanner. The particles are placed inside a bilayered hydrogel and act as elastic-wave sources on excitation by a magnetic pulse. Using ultrafast ultrasound imaging coupled to phase tracking, the diffuse elastic wave field is imaged. This allows the local wave velocity to be measured everywhere on the image using noise-correlation algorithms inspired by seismology. Thanks to this instantaneous diffuse wave field, a very short acquisition time is sufficient to retrieve the wave speed contrast of a bilayered phantom. The correlation time window can be shrunk down to three time samples, which we show in a numerical simulation mimicking the experimental conditions. Our experimental and numerical results are consistent with theoretical predictions made by information theory, and they pave the way for real-time elasticity imaging. This is of particular interest for monitoring of medical treatments through real-time tissue-elasticity assessment, and it is also applicable in related fields such as seismology and nondestructive testing.

Arteriosclerosis is a major risk factor for cardiovascular disease and results in arterial vessel stiffening. Velocity estimation of the pulse wave sent by the heart and propagating into the arteries is a widely accepted biomarker. This symmetrical pulse wave propagates at a speed which is related to the Young's modulus through the Moens Korteweg (MK) equation. Recently, an antisymmetric flexural wave has been observed in vivo. Unlike the symmetrical wave, it is highly dispersive. This property offers promising applications for monitoring arterial stiffness and early detection of atheromatous plaque. However, as far as it is known, no equivalent of the MK equation exists for flexural pulse waves. To bridge this gap, a beam based theory was developed, and approximate analytical solutions were reached. An experiment in soft polymer artery phantoms was built to observe the dispersion of flexural waves. A good agreement was found between the analytical expression derived from beam theory and experiments. Moreover, numerical simulations validated wave speed dependence on the elastic and geometric parameters at low frequencies. Clinical applications, such as arterial age estimation and arterial pressure measurement, are foreseen.