A versatile and robust microfluidic device for capillary-sized simple or multiple emulsions production

International audienceUltrasound-vaporizable microdroplets can be exploited for targeted drug delivery. However, it requires customized microfluidic techniques able to produce monodisperse, capillary-sized and biocompatible multiple emulsions. Recent development of microfluidic devices led to the optimization of microdroplet production with high yields, low polydispersity and well-defined diameters. So far, only few were shown to be efficient for simple droplets or multiple emulsions production below 5 microns in diameter, which is required to prevent microembolism after intravenous injection. Here, we present a versatile microchip for both simple and multiple emulsion production. This parallelized system based on microchannel emulsification was designed to produce perfluorocarbon in water or water within perfluorocarbon in water emulsions with capillary sizes (<5 μm) and polydispersity index down to 5 % for in vivo applications such as spatiotemporally-triggered drug delivery using Ultrasound. We show that droplet production at this scale is mainly controlled by interfacial tension forces, how capillary and viscosity ratios influence droplet characteristics and how different production regimes may take place. The better understanding of droplet formation and its relation to applied pressures is supported by observations with a high-speed camera. Compared to previous microchips, this device opens perspectives to produce injectable and biocompatible droplets with a reasonable yield in order to realize preclinical studies in mice

Measuring Image Resolution in Ultrasound Localization Microscopy

The resolution of an imaging system is usually determined by the width of its point spread function and is measured using the Rayleigh criterion. For most system, it is in the order of the imaging wavelength. However, super resolution techniques such as localization microscopy in optical and ultrasound imaging can resolve features an order of magnitude finer than the wavelength. The classical description of spatial resolution no longer applies and new methods need to be developed. In optical localization microscopy, the Fourier Ring Correlation has showed to be an effective and practical way to estimate spatial resolution for Single Molecule Localization Microscopy data. In this work, we wish to investigate how this tool can provide a direct and universal estimation of spatial resolution in Ultrasound Localization Microscopy. Moreover, we discuss the concept of spatial sampling in Ultrasound Localization Microscopy and demonstrate how the Nyquist criterion for sampling drives the spatial/temporal resolution tradeoff. We measured spatial resolution on five different datasets over rodent's brain, kidney and tumor finding values between 11~\mu \text{m} and 34~\mu \text{m} for precision of localization between 11~\mu \text{m} and 15~\mu \text{m}. Eventually, we discuss from those in vivo datasets how spatial resolution in Ultrasound Localization Microscopy depends on both the localization precision and the total number of detected microbubbles. This study aims to offer a practical and theoretical framework for image resolution in Ultrasound Localization Microscopy. ImPhys/Medical Imagin

Ultrasound localization microscopy to image and assess microvasculature in a rat kidney

Abstract The recent development of ultrasound localization microscopy, where individual microbubbles (contrast agents) are detected and tracked within the vasculature, provides new opportunities for imaging the vasculature of entire organs with a spatial resolution below the diffraction limit. In stationary tissue, recent studies have demonstrated a theoretical resolution on the order of microns. In this work, single microbubbles were localized in vivo in a rat kidney using a dedicated high frame rate imaging sequence. Organ motion was tracked by assuming rigid motion (translation and rotation) and appropriate correction was applied. In contrast to previous work, coherence-based non-linear phase inversion processing was used to reject tissue echoes while maintaining echoes from very slowly moving microbubbles. Blood velocity in the small vessels was estimated by tracking microbubbles, demonstrating the potential of this technique to improve vascular characterization. Previous optical studies of microbubbles in vessels of approximately 20 microns have shown that expansion is constrained, suggesting that microbubble echoes would be difficult to detect in such regions. We therefore utilized the echoes from individual MBs as microscopic sensors of slow flow associated with such vessels and demonstrate that highly correlated, wideband echoes are detected from individual microbubbles in vessels with flow rates below 2 mm/s

Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging

International audiencePositron emission tomography–computed tomography (PET–CT) is the most sensitive molecular imaging modality, but it does not easily allow for rapid temporal acquisition. Ultrafast ultrasound imaging (UUI)—a recently introduced technology based on ultrasonic holography—leverages frame rates of up to several thousand images per second to quantitatively map, at high resolution, haemodynamic, biomechanical, electrophysiological and structural parameters. Here, we describe a pre-clinical scanner that registers PET–CT and UUI volumes acquired simultaneously and offers multiple combinations for imaging. We demonstrate that PET–CT–UUI allows for simultaneous images of the vasculature and metabolism during tumour growth in mice and rats, as well as for synchronized multi-modal cardiac cine-loops. Combined anatomical, functional and molecular imaging with PET–CT–UUI represents a high-performance and clinically translatable technology for biomedical research