Fluorescence lifetime imaging (FLIM) is a powerful tool that provides unique quantitative information for biomedical research. In this study, we propose a multi-layer-perceptron-based mixer (MLP-Mixer) deep learning (DL) algorithm named FLIM-MLP-Mixer for fast and robust FLIM analysis. The FLIM-MLP-Mixer has a simple network architecture yet a powerful learning ability from data. Compared with the traditional fitting and previously reported DL methods, the FLIM-MLP-Mixer shows superior performance in terms of accuracy and calculation speed, which has been validated using both synthetic and experimental data. All results indicate that our proposed method is well suited for accurately estimating lifetime parameters from measured fluorescence histograms, and it has great potential in various real-time FLIM applications.

This paper reports a bespoke adder-based deep learning network for time-domain fluorescence lifetime imaging (FLIM). By leveraging the l1-norm extraction method, we propose a 1-D Fluorescence Lifetime AdderNet (FLAN) without multiplication-based convolutions to reduce the computational complexity. Further, we compressed fluorescence decays in temporal dimension using a log-scale merging technique to discard redundant temporal information derived as log-scaling FLAN (FLAN+LS). FLAN+LS achieves 0.11 and 0.23 compression ratios compared with FLAN and a conventional 1-D convolutional neural network (1-D CNN) while maintaining high accuracy in retrieving lifetimes. We extensively evaluated FLAN and FLAN+LS using synthetic and real data. A traditional fitting method and other non-fitting, high-accuracy algorithms were compared with our networks for synthetic data. Our networks attained a minor reconstruction error in different photon-count scenarios. For real data, we used fluorescent beads’ data acquired by a confocal microscope to validate the effectiveness of real fluorophores, and our networks can differentiate beads with different lifetimes. Additionally, we implemented the network architecture on a field-programmable gate array (FPGA) with a post-quantization technique to shorten the bit-width, thereby improving computing efficiency. FLAN+LS on hardware achieves the highest computing efficiency compared to 1-D CNN and FLAN. We also discussed the applicability of our network and hardware architecture for other time-resolved biomedical applications using photon-efficient, time-resolved sensors.

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