skip to main content

Attention:

The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 11:00 PM ET on Thursday, October 10 until 2:00 AM ET on Friday, October 11 due to maintenance. We apologize for the inconvenience.


Title: Investigation of multiple scattering in space and spatial-frequency domains: with application to the analysis of aberration-diverse optical coherence tomography

Optical microscopy suffers from multiple scattering (MS), which limits the optical imaging depth into scattering media. We previously demonstrated aberration-diverse optical coherence tomography (AD-OCT) for MS suppression, based on the principle that for datasets acquired with different aberration states of the imaging beam, MS backgrounds become decorrelated while single scattering (SS) signals remain correlated, so that a simple coherent average can be used to enhance the SS signal over the MS background. Here, we propose a space/spatial-frequency domain analysis framework for the investigation of MS in OCT, and apply the framework to compare AD-OCT (using astigmatic beams) to standard Gaussian-beam OCT via experiments in scattering tissue phantoms. Utilizing this framework, we found that increasing the astigmatic magnitude produced a large drop in both MS background and SS signal, but the decay experienced by the MS background was larger than the SS signal. Accounting for the decay in both SS signal and MS background, the overall signal-to-background ratio (SBR) of AD-OCT was similar to the Gaussian control after about 10 coherent averages, when deeper line foci was positioned at the plane-of-interest and the line foci spacing was smaller than or equal to 80 µm. For an even larger line foci spacing of 160 µm, AD-OCT resulted in a lower SBR than the Gaussian-beam control. This work provides an analysis framework to gain deeper levels of understanding and insights for the future study of MS and MS suppression in both the space and spatial-frequency domains.

 
more » « less
Award ID(s):
1752405
NSF-PAR ID:
10307362
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Optical Society of America
Date Published:
Journal Name:
Biomedical Optics Express
Volume:
12
Issue:
12
ISSN:
2156-7085
Format(s):
Medium: X Size: Article No. 7478
Size(s):
Article No. 7478
Sponsoring Org:
National Science Foundation
More Like this
  1. Multiple scattering is a major barrier that limits the optical imaging depth in scattering media. In order to alleviate this effect, we demonstrate aberration-diverse optical coherence tomography (AD-OCT), which exploits the phase correlation between the deterministic signals from single-scattered photons to suppress the random background caused by multiple scattering and speckle. AD-OCT illuminates the sample volume with diverse aberrated point spread functions, and computationally removes these intentionally applied aberrations. After accumulating 12 astigmatism-diverse OCT volumes, we show a 10 dB enhancement in signal-to-background ratio via a coherent average of reconstructed signals from a USAF target located 7.2 scattering mean free paths below a thick scattering layer, and a 3× speckle contrast reduction from an incoherent average of reconstructed signals inside the scattering layer. This AD-OCT method, when implemented using astigmatic illumination, is a promising approach for ultra-deep volumetric optical coherence microscopy.

     
    more » « less
  2. Abstract

    Optical coherence tomography (OCT) is a widely used non-invasive biomedical imaging modality that can rapidly provide volumetric images of samples. Here, we present a deep learning-based image reconstruction framework that can generate swept-source OCT (SS-OCT) images using undersampled spectral data, without any spatial aliasing artifacts. This neural network-based image reconstruction does not require any hardware changes to the optical setup and can be easily integrated with existing swept-source or spectral-domain OCT systems to reduce the amount of raw spectral data to be acquired. To show the efficacy of this framework, we trained and blindly tested a deep neural network using mouse embryo samples imaged by an SS-OCT system. Using 2-fold undersampled spectral data (i.e., 640 spectral points per A-line), the trained neural network can blindly reconstruct 512 A-lines in 0.59 ms using multiple graphics-processing units (GPUs), removing spatial aliasing artifacts due to spectral undersampling, also presenting a very good match to the images of the same samples, reconstructed using the full spectral OCT data (i.e., 1280 spectral points per A-line). We also successfully demonstrate that this framework can be further extended to process 3× undersampled spectral data per A-line, with some performance degradation in the reconstructed image quality compared to 2× spectral undersampling. Furthermore, an A-line-optimized undersampling method is presented by jointly optimizing the spectral sampling locations and the corresponding image reconstruction network, which improved the overall imaging performance using less spectral data points per A-line compared to 2× or 3× spectral undersampling results. This deep learning-enabled image reconstruction approach can be broadly used in various forms of spectral-domain OCT systems, helping to increase their imaging speed without sacrificing image resolution and signal-to-noise ratio.

     
    more » « less
  3. We present a general theory of optical coherence tomography (OCT), which synthesizes the fundamental concepts and implementations of OCT under a common 3Dk-space framework. At the heart of this analysis is the Fourier diffraction theorem, which relates the coherent interaction between a sample and plane wave to the Ewald sphere in the 3Dk-space representation of the sample. While only the axial dimension of OCT is typically analyzed ink-space, we show that embracing a fully 3Dk-space formalism allows explanation of nearly every fundamental physical phenomenon or property of OCT, including contrast mechanism, resolution, dispersion, aberration, limited depth of focus, and speckle. The theory also unifies diffraction tomography, confocal microscopy, point-scanning OCT, line-field OCT, full-field OCT, Bessel beam OCT, transillumination OCT, interferometric synthetic aperture microscopy (ISAM), and optical coherence refraction tomography (OCRT), among others. Our unified theory not only enables clear understanding of existing techniques but also suggests new research directions to continue advancing the field of OCT.

     
    more » « less
  4. For many clinical applications, such as dermatology, optical coherence tomography (OCT) suffers from limited penetration depth due primarily to the highly scattering nature of biological tissues. Here, we present a novel implementation of dual-axis optical coherence tomography (DA-OCT) that offers improved depth penetration in skin imaging at 1.3 µm compared to conventional OCT. Several unique aspects of DA-OCT are examined here, including the requirements for scattering properties to realize the improvement and the limited depth of focus (DOF) inherent to the technique. To overcome this limitation, our approach uses a tunable lens to coordinate focal plane selection with image acquisition to create an enhanced DOF for DA-OCT. This improvement in penetration depth is quantified experimentally against conventional on-axis OCT using tissue phantoms and mouse skin. The results presented here suggest the potential use of DA-OCT in situations where a high degree of scattering limits depth penetration in OCT imaging.

     
    more » « less
  5. Objective: Multicellular tumor spheroids (MCTs) are indispensable models for evaluating drug efficacy for precision cancer therapeutic strategies as well as for repurposing FDA-approved drugs for ovarian cancer. However, current imaging techniques cannot provide effective monitoring of pathological responses due to shallow penetration and experimentally operative destruction. We plan to utilize a noninvasive optical imaging tool to achieve in vivo longitudinal monitoring of the growth of MCTs and therapeutic responses to repurpose three FDA-approved drugs for ovarian cancer therapy. Methods: A swept-source optical coherence tomography (SS-OCT) system was used to monitor the volume growth of MCTs over 11 days. Three inhibitors of 2-Methoxyestradiol (2-ME), AZD1208, and R-Ketorolac (R-keto) with concentrations of 1, 10, and 25 µM were employed to treat ovarian MCTs on day 5. Three-dimensional (3D), intrinsic optical attenuation contrast, and degree of uniformity were applied to analyze the therapeutic effect of these inhibitors on ovarian MCTs. Results: We found that 2-ME, AZD1208, and R-keto with concentration of 10 and 25 µM significantly inhibited the volume growth of ovarian MCTs. There was no effect to necrotic tissues from all concentrations of 2-ME, AZD1208, and R-keto inhibitors from our OCT results. 2-ME and AZD1208 inhibited the growth of high uniformity tissues within MCTs and higher concentrations provided more significant inhibitory effects. Conclusion: Our results indicated that OCT was capable and reliable to monitor the therapeutic effect of inhibitors to ovarian MCTs and it can be used for the rapid characterization of novel therapeutics for ovarian cancers in the future. 
    more » « less