Contrast enhanced ultrasound is a radiation-free imaging modality which uses encapsulated gas microbubbles for improved visualization of the vascular bed deep within the tissue. It has recently been used to enable imaging with unprecedented subwavelength spatial resolution by relying on super-resolution techniques. A typical preprocessing step in super-resolution ultrasound is to separate the microbubble signal from the cluttering tissue signal. This step has a crucial impact on the final image quality. Here, we propose a new approach to clutter removal based on robust principle component analysis (PCA) and deep learning. We begin by modeling the acquired contrast enhanced ultrasound signal as a combination of a low rank and sparse components. This model is used in robust PCA and was previously suggested in the context of ultrasound Doppler processing and dynamic magnetic resonance imaging. We then illustrate that an iterative algorithm based on this model exhibits improved separation of microbubble signal from the tissue signal over commonly practiced methods. Next, we apply the concept of deep unfolding to suggest a deep network architecture tailored to our clutter filtering problem which exhibits improved convergence speed and accuracy with respect to its iterative counterpart. We compare the performance of the suggested deep network on both simulations and in-vivo rat brain scans, with a commonly practiced deep-network architecture and the fast iterative shrinkage algorithm, and show that our architecture exhibits better image quality and contrast.

Abstract-Ultrasound super-localization microscopy techniques presented in the last few years enable non-invasive imaging of vascular structures at the capillary level by tracking the flow of ultrasound contrast agents (gas microbubbles). However, these techniques are currently limited by low temporal resolution and long acquisition times. Super-resolution optical fluctuation imaging (SOFI) is a fluorescence microscopy technique enabling sub-diffraction limit imaging with high temporal resolution by calculating high order statistics of the fluctuating optical signal. The aim of this work is to achieve fast acoustic imaging with enhanced resolution by applying the tools used in SOFI to contrast-enhance ultrasound (CEUS) plane-wave scans. The proposed method was tested using numerical simulations and evaluated using two in-vivo rabbit models: scans of healthy kidneys and VX-2 tumor xenografts. Improved spatial resolution was observed with a reduction of up to 50% in the full width half max of the point spread function. In addition, substantial reduction in the background level was achieved compared to standard mean amplitude persistence images, revealing small vascular structures within tumors. The scan duration of the proposed method is less than a second while current superlocalization techniques require acquisition duration of several minutes. As a result, the proposed technique may be used to obtain scans with enhanced spatial resolution and high temporal resolution, facilitating flow-dynamics monitoring. Our method can also be applied during a breath-hold, reducing the sensitivity to motion artifacts.

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In traditional optical imaging systems, the spatial resolution is limited by the physics of diffraction, which acts as a low-pass filter. The information on sub-wavelength features is carried by evanescent waves, never reaching the camera, thereby posing a hard limit on resolution: the so-called diffraction limit. Modern microscopic methods enable super-resolution, by employing florescence techniques. State-of-the-art localization based fluorescence subwavelength imaging techniques such as PALM and STORM achieve sub-diffraction spatial resolution of several tens of nano-meters. However, they require tens of thousands of exposures, which limits their temporal resolution. We have recently proposed SPARCOM (sparsity based super-resolution correlation microscopy), which exploits the sparse nature of the fluorophores distribution, alongside a statistical prior of uncorrelated emissions, and showed that SPARCOM achieves spatial resolution comparable to PALM/STORM, while capturing the data hundreds of times faster. Here, we provide a detailed mathematical formulation of SPARCOM, which in turn leads to an efficient numerical implementation, suitable for large-scale problems. We further extend our method to a general framework for sparsity based super-resolution imaging, in which sparsity can be assumed in other domains such as wavelet or discrete-cosine, leading to improved reconstructions in a variety of physical settings.