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: 10446063
• 负责人: Steven Graham Adie
• 金额: $ 37.8万
• 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/10446063
• 关键词: 3-Dimensional; Address; Algorithms; Attention; Ballistics; Big Data; Biological; Brain; Data Set; Development; Ensure; Event; Feedback; Fiber; Floor; Freedom; Gaussian model; 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; base; brain tissue; clinical application; data acquisition; deep field survey; experimental study; fundamental research; imaging capabilities; imaging science; in vivo; 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，也是许多创造性的方法 正在开发以减轻“光学散射”现象的有害影响，并使 散射介质中更深层次的光学成像。在致密组织中传播的光经历散射事件， 扰乱传播的光学波前的相位，从而扰乱所需的建设性干涉 将光聚焦/空间局部化到衍射有限的焦点。因此，微观分辨率是 通常只在所谓的“单次散射”(SS)或“弹道”光区可用。华侨城是领先的 在深度显微镜领域，最大成像深度通常为散射组织的1-2毫米。 然而，OCT令人难以置信的成功在某些方面导致了比其他光学成像更低的动机 开发解决多次散射(MS)问题的新方法。这也是一个很棒的 机遇-通过构建其已经深入的成像能力，OCT有机会再次成为 处于推动光学显微镜成像深度极限的研究前沿。我们提出了一种综合的 结合(1)长波长OCT(1700 nm窗口，低散射系数支持 更深成像)，(2)共轭成像配置中的光谱域OCT(SD-OCT)以增强 比标准成像配置深2-3个数量级的OCT信号，(3)硬件 自适应光学(HAO)，用于纠正组织诱导的像差，从而在深处增强弹道信号 组织，以及(4)用于抑制MS的不同像差OCT(AD-OCT)。 该方法结合了基于光纤的OCT系统的优势和极具前景的 相干累积单次散射(CASS)方法。CASS方法一致地从 多个照明角度(全场成像几何结构中的平面波照明)，而AD-OCT相干 通过用不同的已知像差状态照射样本并利用 计算自适应光学(CAO)，以规避通常与以下各项相关的分辨率损失 像差。目标1将开发一种克服像差-分集饱和限制的方法，实现高分辨率 加快基于GPU的处理速度，以解决AD-OCT中的大数据问题，并在 成像的时间。目标2将定量比较高斯光束OCT(有和没有)的性能 HAO组织像差矫正)与AD-OCT(具有组织像差HAO矫正)。这将包括 与深度相关的3D点扩展函数的测量，这也将填补一个重要的知识空白 在10月对MS的基础研究中。目标3将展示超过当前OCT倍数的AD-OCT 人体皮肤和小鼠脑内的散射限制(我们将‘解锁’2-5 mm深度范围)。如果成功， 这项提议将展示有史以来在人皮肤和小鼠大脑中进行的最深的OCT成像，以及 因此，从基础成像科学和OCT的生物医学应用的角度来看，OCT具有重要意义。