Enhancing Ultrasound Molecular Imaging: Toward Real-Time RPCA-Based Filtering to Differentiate Bound and Free Microbubbles

Ultrasound molecular imaging (UMI) is an advanced imaging modality that shows promise in detecting cancer at early stages. It uses microbubbles as contrast agents, which are functionalized to bind to cancer biomarkers overexpressed on endothelial cells. A major challenge in UMI is isolating bound microbubble signal, which represents the molecular imaging signal, from that of free-floating microbubbles, which is considered background noise. In this work, we propose a fast GPU-based method using robust principal component analysis (RPCA) to distinguish bound microbubbles from free-floating ones. We explore the method using simulations and measure the accuracy using the Dice coefficient and RMS error as functions of the number of frames used in RPCA reconstruction. Experiments using stationary and flowing microbubbles in tissue-mimicking phantoms were used to validate the method. Additionally, the method was applied to data from ten transgenic mouse models of breast cancer development, injected with B7-H3-targeted microbubbles, and two mice injected with non-targeted microbubbles. The results showed that RPCA using 20 frames achieved a Dice score of 0.95 and a computation time of 0.2 seconds, indicating that 20 frames is potentially suitable for real-time implementation. On in vivo data, RPCA using 20 frames achieved a Dice score of 0.82 with DTE, indicating good agreement between the two, given the limitations of each method.