# Pixel Super-Resolved Fluorescence Lifetime Imaging Using Deep Learning

arXiv: https://arxiv.org/abs/2512.16266 · HTML: https://mlsanity.com/paper/2512.16266/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 15 of its 52 references that are in the map.
- First posted on arXiv 18 Dec 2025.

## Builds on (most cited first, 15 of 15)

- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [The Unreasonable Effectiveness of Deep Features as a Perceptual Metric](https://mlsanity.com/paper/1801.03924/) (2018)
- [Image-to-Image Translation with Conditional Adversarial Networks](https://mlsanity.com/paper/1611.07004/) (2016)
- [Generative Modeling by Estimating Gradients of the Data Distribution](https://mlsanity.com/paper/1907.05600/) (2019)
- [Conditional Generative Adversarial Nets](https://mlsanity.com/paper/1411.1784/) (2014)
- [Image Super-Resolution via Iterative Refinement](https://mlsanity.com/paper/2104.07636/) (2021)
- [Image Super-Resolution Using Deep Convolutional Networks](https://mlsanity.com/paper/1501.00092/) (2014)
- [Least Squares Generative Adversarial Networks](https://mlsanity.com/paper/1611.04076/) (2016)
- [BBDM: Image-to-image Translation with Brownian Bridge Diffusion Models](https://mlsanity.com/paper/2205.07680/) (2022)
- [Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue](https://mlsanity.com/paper/1803.11293/) (2018)
- [Pixel super-resolved virtual staining of label-free tissue using diffusion models](https://mlsanity.com/paper/2410.20073/) (2024)
- [Resolution enhancement in scanning electron microscopy using deep learning](https://mlsanity.com/paper/1901.11094/) (2019)
- [A robust and scalable framework for hallucination detection in virtual tissue staining and digital pathology](https://mlsanity.com/paper/2404.18458/) (2024)
- [Neural Network-Based Processing and Reconstruction of Compromised Biophotonic Image Data](https://mlsanity.com/paper/2403.14324/) (2024)
- [Virtual Staining of Label-Free Tissue in Imaging Mass Spectrometry](https://mlsanity.com/paper/2411.13120/) (2024)

## Abstract (arXiv)

Fluorescence lifetime imaging microscopy (FLIM) is a powerful quantitative technique that provides metabolic and molecular contrast, offering strong translational potential for label-free, real-time diagnostics. However, its clinical adoption remains limited by long pixel dwell times and low signal-to-noise ratio (SNR), which impose a stricter resolution-speed trade-off than conventional optical imaging approaches. Here, we introduce FLIM_PSR_k, a deep learning-based multi-channel pixel super-resolution (PSR) framework that reconstructs high-resolution FLIM images from data acquired with up to a 5-fold increased pixel size. The model is trained using the conditional generative adversarial network (cGAN) framework, which, compared to diffusion model-based alternatives, delivers a more robust PSR reconstruction with substantially shorter inference times, a crucial advantage for practical deployment. FLIM_PSR_k not only enables faster image acquisition but can also alleviate SNR limitations in autofluorescence-based FLIM. Blind testing on held-out patient-derived tumor tissue samples demonstrates that FLIM_PSR_k reliably achieves a super-resolution factor of k = 5, resulting in a 25-fold increase in the space-bandwidth product of the output images and revealing fine architectural features lost in lower-resolution inputs, with statistically significant improvements across various image quality metrics. By increasing FLIM's effective spatial resolution, FLIM_PSR_k advances lifetime imaging toward faster, higher-resolution, and hardware-flexible implementations compatible with low-numerical-aperture and miniaturized platforms, better positioning FLIM for translational applications.