用深度学习将荧光寿命成像分辨率提升5倍,加快成像速度。
Pixel Super-Resolved Fluorescence Lifetime Imaging Using Deep Learning
- 基于条件生成对抗网络,从大像素数据重建高分辨图像。
- 在真实肿瘤组织上实现5倍超分辨率,空间带宽积提升25倍。
- 适合临床快速成像,尤其适用于低数值孔径和微型设备。
荧光寿命成像显微镜(FLIM)是一种能提供代谢与分子对比的定量技术,具有无标记、实时诊断的强转化潜力。但其临床应用受限于长像素采集时间和低信噪比(SNR),导致分辨率与速度的权衡更严苛。本文提出FLIM_PSR_k,一种基于深度学习的多通道像素超分辨率(PSR)框架,可将像素尺寸增大至5倍时仍重建出高分辨率图像。模型采用条件生成对抗网络(cGAN),相比扩散模型,推理时间更短、重建更鲁棒,利于实际部署。在未参与训练的患者来源肿瘤组织样本上盲测显示,该方法稳定实现超分辨率因子k=5,输出图像空间带宽积提升25倍,揭示了低分辨率输入中丢失的精细结构,且在多项图像质量指标上均有显著提升。该方法提升了FLIM的有效空间分辨率,推动其向更快、更高分辨率、硬件灵活的实现方式发展,兼容低数值孔径与微型化平台,更有利于临床转化。
原文摘要 · Abstract (English)
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.
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