Generative deep learning-enabled ultra-large field-of-view lens-free imaging

Advancements in high-throughput biomedical applications necessitate real-time, large field-of-view (FOV) imaging capabilities. Conventional lens-free imaging (LFI) systems, while addressing the limitations of physical lenses, have been constrained by dynamic, hard-to-model optical fields, resulting in a limited one-shot FOV of approximately 20 $mm^2$. This restriction has been a major bottleneck in applications like live-cell imaging and automation of microfluidic systems for biomedical research. Here, we present a deep-learning(DL)-based imaging framework - GenLFI - leveraging generative artificial intelligence (AI) for holographic image reconstruction. We demonstrate that GenLFI can achieve a real-time FOV over 550 $mm^2$, surpassing the current LFI system by more than 20-fold, and even larger than the world's largest confocal microscope by 1.76 times. The resolution is at the sub-pixel level of 5.52 $\mu m$, without the need for a shifting light source. The unsupervised learning-based reconstruction does not require optical field modeling, making imaging dynamic 3D samples (e.g., droplet-based microfluidics and 3D cell models) in complex optical fields possible. This GenLFI framework unlocks the potential of LFI systems, offering a robust tool to tackle new frontiers in high-throughput biomedical applications such as drug discovery.

Simultaneous reconstruction and displacement estimation for spectral-domain optical coherence elastography

Optical coherence elastography allows the characterization of the mechanical properties of tissues, and can be performed through estimating local displacement maps from subsequent acquisitions of a sample under different loads. This displacement estimation is limited by noise in the images, which can be high in dynamic systems due to the inability to perform long exposures or B-scan averaging. In this work, we propose a framework for simultaneously enhancing both the image quality and displacement map for elastography, by motion compensated denoising with the block-matching and 4D filtering (BM4D) method, followed by a re-estimation of displacement. We adopt the interferometric synthetic aperture microscopy (ISAM) method to enhance the lateral resolution away from the focal plane, and use sub-pixel cross correlation block matching for non-uniform deformation estimation. We validate this approach on data from a commercial spectral domain optical coherence tomography system, whereby we observe an enhancement of both image and displacement accuracy of up to 33% over a standard approach.

Model-based iterative reconstruction for spectral-domain optical coherence tomography

Spectral domain optical coherence tomography (OCT) offers high resolution multidimensional imaging, but generally suffers from defocussing, intensity falloff and shot noise, causing artifacts and image degradation along the imaging depth. In this work, we develop an iterative statistical reconstruction technique, based upon the interferometric synthetic aperture microscopy (ISAM) model with additive noise, to actively compensate for these effects. For the ISAM re-sampling, we use a non uniform FFT with Kaiser-Bessel interpolation, offering efficiency and high accuracy. We then employ an accelerated gradient descent based algorithm, to minimize the negative log-likelihood of the model, and include spatial or wavelet sparsity based penalty functions, to provide appropriate regularization for given image structures. We evaluate our approach with titanium oxide micro-bead and cucumber samples with a commercial spectral domain OCT system, under various subsampling regimes, and demonstrate superior image quality over traditional reconstruction and ISAM methods.