Zero-Shot Denoising for Fluorescence Lifetime Imaging Microscopy with Intensity-Guided Learning

Abstract: Multimodal and multi-information microscopy techniques such as Fluorescence Lifetime Imaging Microscopy (FLIM) extend the informational channels beyond intensity-based fluorescence microscopy but suffer from reduced image quality due to complex noise patterns. For FLIM, the intrinsic relationship between intensity and lifetime information means noise in each channel is a multivariate function across channels without necessarily sharing structural features. Based on this, we present a novel Zero-Shot Denoising Framework with an Intensity-Guided Learning approach. Our correlation-preserving strategy maintains important biological information that might be lost when channels are processed independently. Our framework implements separate processing paths for each channel and utilizes a pre-trained intensity denoising prior to guide the refinement of lifetime components across multiple channels. Through experiments on real-world FLIM-acquired biological samples, we show that our approach outperforms existing methods in both noise reduction and lifetime preservation, thereby enabling more reliable extraction of physiological and molecular information.