No abstract

The emergence of ultrafast frame rates in ultrasonic imaging has been recently made possible by the development of new imaging modalities such as transient elastography. Data acquisition rates reaching more than thousands of images per second enable the real-time visualization of shear mechanical waves propagating in biological tissues, which convey information about local viscoelastic properties of tissues. The first proposed approach for reaching such ultrafast frame rates consists of transmitting plane waves into the medium. However, because the beamforming process is then restricted to the receive mode, the echographic images obtained in the ultrafast mode suffer from a low quality in terms of resolution and contrast and affect the robustness of the transient elastography mode. It is here proposed to improve the beamforming process by using a coherent recombination of compounded plane-wave transmissions to recover high-quality echographic images without degrading the high frame rate capabilities. A theoretical model is derived for the comparison between the proposed method and the conventional B-mode imaging in terms of contrast, signal-to-noise ratio, and resolution. Our model predicts that a significantly smaller number of insonifications, 10 times lower, is sufficient to reach an image quality comparable to conventional B-mode. Theoretical predictions are confirmed by in vitro experiments performed in tissue-mimicking phantoms. Such results raise the appeal of coherent compounds for use with standard imaging modes such as B-mode or color flow. Moreover, in the context of transient elastography, ultrafast frame rates can be preserved while increasing the image quality compared with flat insonifications. Improvements on the transient elastography mode are presented and discussed.

Non-invasive imaging deep into organs at microscopic scales remains an open quest in biomedical imaging. Although optical microscopy is still limited to surface imaging owing to optical wave diffusion and fast decorrelation in tissue, revolutionary approaches such as fluorescence photo-activated localization microscopy led to a striking increase in resolution by more than an order of magnitude in the last decade. In contrast with optics, ultrasonic waves propagate deep into organs without losing their coherence and are much less affected by in vivo decorrelation processes. However, their resolution is impeded by the fundamental limits of diffraction, which impose a long-standing trade-off between resolution and penetration. This limits clinical and preclinical ultrasound imaging to a sub-millimetre scale. Here we demonstrate in vivo that ultrasound imaging at ultrafast frame rates (more than 500 frames per second) provides an analogue to optical localization microscopy by capturing the transient signal decorrelation of contrast agents--inert gas microbubbles. Ultrafast ultrasound localization microscopy allowed both non-invasive sub-wavelength structural imaging and haemodynamic quantification of rodent cerebral microvessels (less than ten micrometres in diameter) more than ten millimetres below the tissue surface, leading to transcranial whole-brain imaging within short acquisition times (tens of seconds). After intravenous injection, single echoes from individual microbubbles were detected through ultrafast imaging. Their localization, not limited by diffraction, was accumulated over 75,000 images, yielding 1,000,000 events per coronal plane and statistically independent pixels of ten micrometres in size. Precise temporal tracking of microbubble positions allowed us to extract accurately in-plane velocities of the blood flow with a large dynamic range (from one millimetre per second to several centimetres per second). These results pave the way for deep non-invasive microscopy in animals and humans using ultrasound. We anticipate that ultrafast ultrasound localization microscopy may become an invaluable tool for the fundamental understanding and diagnostics of various disease processes that modify the microvascular blood flow, such as cancer, stroke and arteriosclerosis.

Ultrasonography has been widely used for diagnosis since it was first introduced in clinical practice in the 1970's. Since then, new ultrasound modalities have been developed, such as Doppler imaging, which provides new information for diagnosis. Elastography was developed in the 1990's to map tissue stiffness, and reproduces/replaces the palpation performed by clinicians. In this paper, we introduce the principles of elastography and give a technical summary for the main elastography techniques: from quasi-static methods that require a static compression of the tissue to dynamic methods that uses the propagation of mechanical waves in the body. Several dynamic methods are discussed: vibro-acoustography, Acoustic Radiation Force Impulsion (ARFI), transient elastography, shear wave imaging, etc. This paper aims to help the reader at understanding the differences between the different methods of this promising imaging modality that may become a significant tool in medical imaging.