Image mapped spectroscopy for snapshot 3-D biomedical imaging

描述（由申请人提供）：高分辨率的组织微观结构体内成像可以潜在地改善许多疾病的诊断和管理。一些旨在实现高分辨率体内显微镜的技术正在实验室和临床前研究中开发，包括共聚焦显微镜、光学相干断层扫描和多光子显微镜。为了在临床上有用，这些技术都旨在全面成像整个组织的三维体积；然而，没有一个可以在一次采集事件中捕获完整的3d图像数据集。所有这些都需要对样品进行聚焦照明光束的机械扫描，或者对照明波长进行扫描，这会减慢数据采集速度，限制灵敏度，增加系统成本和复杂性，并通过运动伪影的存在降低图像质量。在这里，我们首次提出了一种无需在任何空间维度或波长上进行扫描就能实现高分辨率快照三维光学成像的方法。这种方法，我们称之为图像映射光学相干断层扫描（IM-OCT），由于三种技术的出现而成为可能，其中两种技术是我们直接参与的：(1)通过图像映射光谱的高光谱成像，(2)傅里叶域OCT，(3)高灵敏度，高速CCD和CMOS阵列探测器的可用性。我们的长期假设是，这种方法将显著提高临床医生对组织微观结构进行原位评估的能力。在这个R21项目中，我们的目标是进行技术开发和初步测试，以建立IM-OCT在生物组织中的成像能力。在目标1中，我们将设计，组装和测试原型快照IM-OCT系统。这将包括一个关键组件的内部制造-一个包含多个角度反射面的图像映射镜。在目标2中，我们将全面测试和评估IM-OCT的光学和成像性能。我们将使用我们的精密微加工设备来生产3d测试对象，以表征我们成像平台的光学性能。然后，测试和评估过程将继续通过一系列日益复杂的生物成像实验，从体外组织模拟研究到体外人体组织标本的初步研究。

DESCRIPTION (provided by applicant): High-resolution in vivo imaging of tissue microstructure can potentially improve the diagnosis and management of many diseases. Several techniques aimed at enabling high-resolution in vivo microscopy are under development in laboratory and pre-clinical studies, including confocal microscopy, optical coherence tomography, and multiphoton microscopy. To be clinically useful, these techniques all aim to comprehensively image an entire 3-dimensional volume of tissue; however, none can capture a full 3-D image dataset in a single acquisition event. All require either mechanical scanning of a focused illumination beam across the sample, or scanning of the illumination wavelength, which slows data acquisition, limits sensitivity, increases system cost and complexity, and reduces image quality through the presence of motion artifacts. Here, we propose a method that for the first time will enable high-resolution snapshot 3-D optical imaging, without the requirement for scanning in any spatial dimension or wavelength. The method, which we term Image Mapped Optical Coherence Tomography (IM-OCT) has become possible by the emergence of three enabling technologies, two of which we have been directly involved with: (1) Hyperspectral imaging by image- mapping spectrometry, (2) Fourier-domain OCT, and (3) the availability of high-sensitivity, high-speed CCD and CMOS array detectors. Our long-term hypothesis is that this approach will significantly advance clinicians' ability to perform in situ evaluation of tissue microstructure. Within this R21 project, we aim to carry out the technical development and preliminary testing to establish the capabilities of IM-OCT imaging in biological tissues. In Aim 1, we will design, assemble, and test a prototype snapshot IM-OCT system. This will include in-house fabrication of a key component - an image mapping mirror comprising multiple angled reflected facets. In Aim 2, we will thoroughly test and evaluate the optical and imaging performance of IM-OCT. We will use our precision microfabrication facilities to produce 3-D test objects, to characterize the optical performance of our imaging platform. The test and evaluation process will then continue through a series of increasingly complex biological imaging experiments, from in vitro tissue phantom studies, to a pilot study with ex vivo human tissue specimens. PUBLIC HEALTH RELEVANCE: High-resolution, instantaneous imaging of tissue microstructure has the potential to aid clinicians in diagnosis and management of many conditions, including cancer, cardiovascular, and retinal diseases. Here, we propose a method that for the first time will provide high-resolution 3-D images of tissue, by acquiring full volumetric image data in a single camera frame capture. We anticipate that this capability will improve the yield of biopsy collection in screening situations, and provide diagnostic information at locations where tissue could not otherwise be removed.