Nonlinear super-resolution signal processing allows intracellular tracking of calcium dynamics.

Traditional quantification of fluorescence signals, such as
∆F/F, relies on ratiometric measures that necessitate a baseline for compar-
ison, limiting their applicability in dynamic analyses. Our goal here is to
develop a baseline-independent method for analyzing fluorescence data that
fully exploits temporal dynamics to introduce a novel approach for dynami-
cal super-resolution analysis, including in subcellular resolution.
Approach: We introduce ARES (Autoregressive RESiduals), a novel method
that leverages the temporal aspect of fluorescence signals. By focusing on
the quantification of residuals following linear autoregression, ARES obviates
the need for a predefined baseline, enabling a more nuanced analysis of signal
dynamics.
Main Result: We delineate the foundational attributes of ARES, illustrat-
ing its capability to enhance both spatial and temporal resolution of calcium
fluorescence activity beyond the conventional ratiometric measure (∆F/F).
Additionally, we demonstrate ARES's utility in elucidating intracellular cal-
cium dynamics through the detailed observation of calcium wave propagation
within a dendrite.
Significance: ARES stands out as a robust and precise tool for the quan-
tification of fluorescence signals, adept at analyzing both spontaneous and
evoked calcium dynamics. Its ability to facilitate the subcellular localiza-
tion of calcium signals and the spatiotemporal tracking of calcium dynam-
ics-where traditional ratiometric measures falter-underscores its potential
to revolutionize baseline-independent analyses in the field.