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和许多创造性方法的巨大挑战之一 正在开发中，以减轻“光学散射”现象的有害影响并启用 在散射介质中更深的光学成像。在密集组织中传播的光经历散射事件 争夺传播光波前的相位，从而破坏所需的建设性干扰 将光聚焦/空间定位到衍射限制的焦点斑点。因此，显微镜分辨率是 通常仅在所谓的“单碎片”（SS）或“弹道”光制方面可用。 OCT是领导者之一 深度显微镜领域的模态，最大成像深度通常在散射组织中为1-2 mm。 但是，与其他光学成像相比，OCT在某些方面取得了令人难以置信的成功导致动力较低 领域开发新方法来解决多个散射（MS）的问题。这也很棒 机会 - 通过建立已经深刻的成像功能，OCT有机会再次成为 在推动光学显微镜的成像深度极限的研究的最前沿。我们提出了一个综合的 结合（1）长波长10月（1700 nm窗口，较低散射系数支撑）的方法 更深的成像），（2）偶联成像配置中的光谱域OCT（SD-OCT）以增强 相对于标准成像配置，（3）硬件的深度OCT信号相对于2-3个数量级 自适应光学元件（HAO）纠正组织诱导的像差，从而提高了弹道信号的深处 组织，（4）用于抑制MS的异差多样性OCT（AD-OCT）。我们最近开发的ad-oct 方法结合了基于纤维的OCT系统的优势和高度前景的原则 单个散射（CASS）方法的相干积累。 CASS方法一致地积累了SS 多个照明角度（全场成像几何形状中的平面波照明），而相干性 积累了通过以不同的已知像差态照明样品并利用样品产生的SS 计算自适应光学器件（CAO）规避通常与这些相关的分辨率罚款 畸变。 AIM 1将开发一种克服异常多样性饱和极限的方法，实施高 基于GPU的加速处理以解决AD-OCT中的大数据问题，并在 成像的时间。 AIM 2将定量比较高斯梁OCT的性能（有和没有） HAO校正组织畸变）与AD-OCT（组织畸变的HAO校正）。这将包括 深度依赖性3D点传播功能的测量，这也将填补重要的知识差距 在10月对MS的基本研究中。 AIM 3将展示超出当前OCT倍数的AD-OCT 人体皮肤和小鼠大脑的散射极限（我们将“解锁” 2-5 mm的深度范围）。如果成功， 该提案将证明在人类皮肤和小鼠大脑中执行的最深的OCT成像，以及 因此，从基本成像科学和OCT的生物医学应用的角度来看，这是重要的。