Ultrasound matrix imaging for 3D 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 also be obtained. However, ultrasound localization microscopy (ULM) remains affected by wavefront distortions that limit the microbubble detection rate and hamper their localization. In this work, we show how ultrasound matrix imaging, which relies on the prior recording of the reflection matrix, can provide a solution to these fundamental issues. As an experimental proof of concept, an in vivo reconstruction of deep brain microvessels is performed on three anesthetized sheep. The compensation of wave distortions is shown to markedly enhance the contrast and resolution of ULM. This experimental study thus opens up promising perspectives for a transcranial and nonionizing observation of human cerebral microvascular pathologies, such as stroke.