Overcoming the Multiple Scattering Limit in Optical Coherence Tomography

克服光学相干断层扫描中的多重散射限制

• 批准号: 10634673
• 负责人: Steven Graham Adie
• 金额: $ 34.64万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634673
• 关键词: 3-Dimensional; Address; Algorithms; Attention; Ballistics; Big Data; Biological; Brain; Creativeness; Data Set; Development; Ensure; Event; Feedback; Fiber; Floor; Freedom; Geometry; Goals; Human; Image; Imaging technology; Knowledge; Length; Light; Lighting; Measurement; Methods; Microscopic; Microscopy; Modality; Motivation; Mus; Noise; Optical Coherence Tomography; Optics; Performance; Phase; Photons; Publishing; Research; Resolution; Sampling; Scheme; Shapes; Signal Transduction; Skin; Skin Tissue; Speed; Spottings; System; Techniques; Thick; Time; Tissues; adaptive optics; brain tissue; clinical application; data acquisition; deep field survey; experimental study; fundamental research; imaging capabilities; imaging science; in vivo; meter; multiphoton microscopy; novel strategies; optical imaging; parallel processing; processing speed; programs; success; titanium dioxide

Extending imaging depth is one of the grand challenges in optical microscopy, and many creative approaches are under development to mitigate the detrimental impact of the phenomenon of ‘optical scattering’ and enable deeper optical imaging in scattering media. Light propagating in dense tissue undergoes scattering events that scramble the phase of the propagating optical wavefront, and thus disrupts the constructive interference needed to focus/spatially localize the light to a diffraction-limited focal spot. Consequently, microscopic resolution is typically only available in the so-called ‘single-scattering’ (SS) or ‘ballistic’ light regime. OCT is one of the leading modalities in the field of deep microscopy, with maximum imaging depths typically 1–2 mm in scattering tissues. However, the incredible success of OCT has in some ways led to lower motivation than in other optical imaging fields to develop new approaches to address the problem of multiple scattering (MS). This is also a great opportunity – by building upon its already deep imaging capabilities, OCT has the opportunity to once again be at the forefront of research on pushing the imaging depth limits of optical microscopy. We propose an integrated approach that combines (1) long-wavelength OCT (1700 nm window, lower scattering coefficient supporting deeper imaging), (2) spectral-domain OCT (SD-OCT) in the conjugate imaging configuration to enhance the deep OCT signal by 2-3 orders of magnitude relative to the standard imaging configuration, (3) hardware adaptive optics (HAO) to correct tissue-induced aberrations and thereby boost the ballistic signal deep within tissue, and (4) aberration-diverse OCT (AD-OCT) for suppressing MS. Our recently-developed AD-OCT approach combines the advantages of a fiber-based OCT system with the principle behind the highly promising coherent accumulation of single scattering (CASS) method. The CASS method coherently accumulates SS from multiple illumination angles (plane wave illumination in full-field imaging geometry), whereas AD-OCT coherently accumulates SS arising from illuminating the sample with different known aberration states, and leveraging computational adaptive optics (CAO) to circumvent the resolution penalty normally associated with these aberrations. Aim 1 will develop a method to overcome the aberration-diversity saturation limit, implement high- speed GPU-based processing to address the Big Data problem in AD-OCT, and enable real-time feedback at the time of imaging. Aim 2 will quantitatively compare the performance of Gaussian-beam OCT (with and without HAO correction of tissue aberrations) vs. AD-OCT (with HAO correction of tissue aberrations). This will include measurements of the depth-dependent 3D point-spread-function, which will also fill an important knowledge gap in fundamental research on MS in OCT. Aim 3 will demonstrate AD-OCT beyond the current OCT multiple scattering limit in human skin and mouse brain in vivo (we will ‘unlock’ the 2-5 mm depth range). If successful, this proposal will demonstrate the deepest OCT imaging ever performed in human skin and mouse brain, and so is significant from the perspective of fundamental imaging science and the biomedical applications of OCT.

扩展成像深度是光学显微镜面临的重大挑战之一，并且有许多创造性的方法