Two-Phase Greedy Pursuit Algorithm for Automatic Detection and Characterization of Transient Calcium Signaling

Ca²⁺ plays an important role in the regulation of cellular functions. Local calcium events, e.g., calcium sparks, not only bring insights into Ca²⁺ signaling but also contribute to the understanding of various cellular processes. However, it is challenging to detect calcium sparks, due to their transient properties and high level of nonstationary noises in microscopic images. Most of existing algorithms tend to have limitations for the detection of calcium sparks, e.g., empirically defined hard thresholds or poor applicability to nonstationary conditions. This paper presents a novel two-phase greedy pursuit (TPGP) algorithm for automatic detection and characterization of calcium sparks. In Phase I, a coarse-grained search is conducted across the whole image to identify the predominant sparks. In Phase II, adaptive basis function model is developed for the fine-grained representation of detected sparks. It may be noted that the proposed TPGP algorithms overcome the drawback of hard thresholding in most of previous approaches. Furthermore, the morphology of detected sparks is effectively modeled with multiscale basis functions in Phase II, thereby facilitating the analysis of physiological features. We evaluated and validated the TPGP algorithms using both real-word and synthetic images with multiple noise levels and varying baselines. Experimental results show that TPGP algorithms yield better performances than previous hard-thresholding approaches in terms of both sensitivities and positive predicted values. The present research provides the community a robust tool for the automatic detection and characterization of transient calcium signaling.