We present a fast and accurate analytical method for fluorescence lifetime imaging microscopy (FLIM), using the extreme learning machine (ELM). We used extensive metrics to evaluate ELM and existing algorithms. First, we compared these algorithms using synthetic datasets. The results indicate that ELM can obtain higher fidelity, even in low-photon conditions. Afterwards, we used ELM to retrieve lifetime components from human prostate cancer cells loaded with gold nanosensors, showing that ELM also outperforms the iterative fitting and non-fitting algorithms. By comparing ELM with a computational efficient neural network, ELM achieves comparable accuracy with less training and inference time. As there is no back-propagation process for ELM during the training phase, the training speed is much higher than existing neural network approaches. The proposed strategy is promising for edge computing with online training.

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 1D 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 1D convolutional neural network (1D 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 1D 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.

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.

We present a deep learning approach to obtain high-resolution (HR) fluorescence lifetime images from low-resolution (LR) images acquired from fluorescence lifetime imaging (FLIM) systems. We first proposed a theoretical method for training neural networks to generate massive semi-synthetic FLIM data with various cellular morphologies, a sizeable dynamic lifetime range, and complex decay components. We then developed a degrading model to obtain LR-HR pairs and created a hybrid neural network, the spatial resolution improved FLIM net (SRI-FLIMnet) to simultaneously estimate fluorescence lifetimes and realize the nonlinear transformation from LR to HR images. The evaluative results demonstrate SRI-FLIMnet’s superior performance in reconstructing spatial information from limited pixel resolution. We also verified SRI-FLIMnet using experimental images of bacterial infected mouse raw macrophage cells. Results show that the proposed data generation method and SRI-FLIMnet efficiently achieve superior spatial resolution for FLIM applications. Our study provides a solution for fast obtaining HR FLIM images.

This study presents a framework for classifying a wooden mannequin’s poses using a single-photon avalanche diode (SPAD) array in dynamic and heterogeneous fog conditions. The target and fog generator are situated within an enclosed fog chamber. Training datasets are continuously collected by configuring the temporal and spatial resolutions on the sensor's firmware, utilizing a low-cost SPAD array sensor priced below $5, consisting of an embedded SPAD array and diffused VCSEL laser. An extreme learning machine (ELM) is trained for rapid pose classification, as a benchmark against CNN. We quantitatively justify the selection of nodes in the hidden layer to balance the computing speed and accuracy. Results demonstrate that ELM can accurately classify mannequin poses when obscured by dynamic heavy fog to 35 cm away from the sensor, enabling real-time applications in consumer electronics. The proposed ELM achieves 90.65% and 89.58% accuracy in training and testing, respectively. Additionally, we demonstrate the robustness of both ELM and CNN as the fog density increases. Our study also discusses the sensor’s current optical limitations and lays the groundwork for future advancements in sensor technology.

SignificanceDiffuse correlation spectroscopy (DCS) is a powerful, noninvasive optical technique for measuring blood flow. Traditionally the blood flow index (BFi) is derived through nonlinear least-square fitting the measured intensity autocorrelation function (ACF). However, the fitting process is computationally intensive, susceptible to measurement noise, and easily influenced by optical properties (absorption coefficient μa and reduced scattering coefficient μs′) and scalp and skull thicknesses.AimWe aim to develop a data-driven method that enables rapid and robust analysis of multiple-scattered light’s temporal ACFs. Moreover, the proposed method can be applied to a range of source–detector distances instead of being limited to a specific source–detector distance.ApproachWe present a deep learning architecture with one-dimensional convolution neural networks, called DCS neural network (DCS-NET), for BFi and coherent factor (β) estimation. This DCS-NET was performed using simulated DCS data based on a three-layer brain model. We quantified the impact from physiologically relevant optical property variations, layer thicknesses, realistic noise levels, and multiple source–detector distances (5, 10, 15, 20, 25, and 30 mm) on BFi and β estimations among DCS-NET, semi-infinite, and three-layer fitting models.ResultsDCS-NET shows a much faster analysis speed, around 17,000-fold and 32-fold faster than the traditional three-layer and semi-infinite models, respectively. It offers higher intrinsic sensitivity to deep tissues compared with fitting methods. DCS-NET shows excellent anti-noise features and is less sensitive to variations of μa and μs′ at a source–detector separation of 30 mm. Also, we have demonstrated that relative BFi (rBFi) can be extracted by DCS-NET with a much lower error of 8.35%. By contrast, the semi-infinite and three-layer fitting models result in significant errors in rBFi of 43.76% and 19.66%, respectively.ConclusionsDCS-NET can robustly quantify blood flow measurements at considerable source–detector distances, corresponding to much deeper biological tissues. It has excellent potential for hardware implementation, promising continuous real-time blood flow measurements.