Ultrasound matrix imaging for transcranial in-vivo localization microscopy

Transcranial ultrasound imaging is usually limited by skull-induced attenuation and high-order aberrations. By using contrast agents such as microbubbles in combination with ultrafast imaging, not only can the signal-to-noise ratio be improved, but super-resolution images down to the micrometer scale of the brain vessels can be obtained. However, ultrasound localization microscopy (ULM) remains impacted by wave-front distortions that limit the microbubble detection rate and hamper their localization. In this work, we show how matrix imaging, which relies on the prior recording of the reflection matrix, can provide a solution to those fundamental issues. As an experimental proof-of-concept, an in-vivo reconstruction of deep brain microvessels is performed on three anesthetized sheeps. The compensation of wave distortions is shown to drastically enhance the contrast and resolution of ULM. This experimental study thus opens up promising perspectives for a transcranial and non-ionizing observation of human cerebral microvascular pathologies, such as stroke.

Optical matrix imaging applied to embryology

High-resolution label-free imaging of oocytes and embryos is essential for in vitro fertilization procedures. Yet conventional microscopy fails in this task because of aberrations and multiple scattering induced by refractive index heterogeneities inside the sample. These detrimental phenomena drastically degrade the images of early embryos particularly in depth. To overcome these fundamental problems without sacrificing the frame rate, optical matrix imaging (OMI) is a suitable tool. Relying on an ultra-fast measurement of the reflection matrix associated with the sample, it can compensate for aberration and forward multiple scattering in post-processing, thereby providing three-dimensional and highly contrasted images of embryos at a confocal resolution. As a first proof-of-concept, bovine oocytes and embryos are imaged at a 300 nm resolution almost in real time. Our system enables visualization of intracellular structures such as lipids and mitochondria in the cytoplasm or the zona pellucida surrounding it. Altogether, we demonstrate that OMI is a promising tool for research in developmental biology and for time-lapse monitoring of oocytes and embryos in assisted reproduction.

Reflection Matrix Imaging for Wave Velocity Tomography

Besides controlling wave trajectory inside complex media, wave velocity constitutes a relevant bio-marker for medical imaging. In a transmission configuration, wave-front distortions can be unscrambled to provide a map of the wave velocity landscape $c(\mathbf{r})$. However, most in-vivo applications correspond to a reflection configuration for which only back-scattered echoes generated by short-scale fluctuations of $c(\mathbf{r})$ can be harvested. Under a single scattering assumption, this speckle wave-field cannot provide the long-scale variations of $c(\mathbf{r})$. In this paper, we go beyond the first Born approximation and show how a map of $c(\mathbf{r})$ can be retrieved in epi-detection. To that aim, a reflection matrix approach of wave imaging is adopted. While standard reflection imaging methods generally rely on confocal focusing operations, matrix imaging consists in decoupling the location of the incident and received focal spots. Following this principle, a self-portrait of the focusing process can be obtained around each point of the medium. The Gouy phase shift exhibited by each focal spot is leveraged to finely monitor the wave velocity distribution $c(\mathbf{r})$ inside the medium. Experiment in a tissue-mimicking phantom and numerical simulations are first presented to validate our method. Speed-of-sound tomography is then applied to ultrasound data collected on the liver of a difficult-to-image patient. Beyond paving the way towards quantitative ultrasound, our approach can also be extremely rewarding for standard imaging. Indeed, each echo can be assigned to the actual position of a scatterer. It allows an absolute measurement of distance, an observable often used for diagnosis but generally extremely sensitive to wave velocity fluctuations.

Three-Dimensional Ultrasound Matrix Imaging

Matrix imaging paves the way towards a next revolution in wave physics. Based on the response matrix recorded between a set of sensors, it enables an optimized compensation of aberration phenomena and multiple scattering events that usually drastically hinder the focusing process in heterogeneous media. Although it gave rise to spectacular results in optical microscopy or seismic imaging, the success of matrix imaging has been so far relatively limited with ultrasonic waves because wave control is generally only performed with a linear array of transducers. In this paper, we extend ultrasound matrix imaging to a 3D geometry. Switching from a 1D to a 2D probe enables a much sharper estimation of the transmission matrix that links each transducer and each medium voxel. Here, we first present an experimental proof of concept on a tissue-mimicking phantom through ex-vivo tissues and then, show the potential of 3D matrix imaging for transcranial applications.