PNR: Physics-informed Neural Representation for high-resolution LFM reconstruction

Light field microscopy (LFM) has been widely utilized in various fields for its capability to efficiently capture high-resolution 3D scenes. Despite the rapid advancements in neural representations, there are few methods specifically tailored for microscopic scenes. Existing approaches often do not adequately address issues such as the loss of high-frequency information due to defocus and sample aberration, resulting in suboptimal performance. In addition, existing methods, including RLD, INR, and supervised U-Net, face challenges such as sensitivity to initial estimates, reliance on extensive labeled data, and low computational efficiency, all of which significantly diminish the practicality in complex biological scenarios. This paper introduces PNR (Physics-informed Neural Representation), a method for high-resolution LFM reconstruction that significantly enhances performance. Our method incorporates an unsupervised and explicit feature representation approach, resulting in a 6.1 dB improvement in PSNR than RLD. Additionally, our method employs a frequency-based training loss, enabling better recovery of high-frequency details, which leads to a reduction in LPIPS by at least half compared to SOTA methods (1.762 V.S. 3.646 of DINER). Moreover, PNR integrates a physics-informed aberration correction strategy that optimizes Zernike polynomial parameters during optimization, thereby reducing the information loss caused by aberrations and improving spatial resolution. These advancements make PNR a promising solution for long-term high-resolution biological imaging applications. Our code and dataset will be made publicly available.

Prostate cancer histopathology with label-free multispectral deep UV microscopy quantifies phenotypes of tumor grade and aggressiveness

Identifying prostate cancer patients that are harboring aggressive forms of prostate cancer remains a significant clinical challenge. To shed light on this problem, we develop an approach based on multispectral deep-ultraviolet (UV) microscopy that provides novel quantitative insight into the aggressiveness and grade of this disease. First, we find that UV spectral signatures from endogenous molecules give rise to a phenotypical continuum that differentiates critical structures of thin tissue sections with subcellular spatial resolution, including nuclei, cytoplasm, stroma, basal cells, nerves, and inflammation. Further, we show that this phenotypical continuum can be applied as a surrogate biomarker of prostate cancer malignancy, where patients with the most aggressive tumors show a ubiquitous glandular phenotypical shift. Lastly, we adapt a two-part Cycle-consistent Generative Adversarial Network to translate the label-free deep-UV images into virtual hematoxylin and eosin (H&E) stained images. Agreement between the virtual H&E images and the gold standard H&E-stained tissue sections is evaluated by a panel of pathologists who find that the two modalities are in excellent agreement. This work has significant implications towards improving our ability to objectively quantify prostate cancer grade and aggressiveness, thus improving the management and clinical outcomes of prostate cancer patients. This same approach can also be applied broadly in other tumor types to achieve low-cost, stain-free, quantitative histopathological analysis.