Next generation deep tissue quantitative optical imaging

项目摘要 近20年的临床研究表明，基于频率的近红外光学成像 域扩散光谱（FD-DOS）可以是一个强大的工具，研究，诊断， 人类疾病的个性化治疗。用于神经成像时（即功能性近红外成像） 与标准连续波相比，FD-DOS可以提供更大的成像深度 (CW)fNIRS因此到达更深的皮质层并提供与浅表层的更好区分。在 FD-DOS可有效预测个体对新辅助化疗的反应， 在重症监护、运动生理学、乳腺癌、 诊断和其他应用。尽管有这些令人信服的临床数据，FD-DOS还没有被翻译成 任何适应症的标准临床应用。原因有两方面。首先，漫射光学成像方法，作为一种 总体而言，仍然受到低空间分辨率和信噪比的影响。此外， 可以从FD-DOS提供的高级定量和更深的灵敏度中受益，但FD-DOS不愿意采用 该方法因为其缺乏用于高密度、高分辨率成像的可缩放性并且过于复杂， 缓慢，难以使用。本项目将通过创建一个基于反射的FD-DOS来消除这些障碍 用于定量深层组织光谱和断层扫描的成像平台，具有前所未有的可扩展性， 精确度和速度，使精确度和空间分辨率大幅提高。这将是 通过开发和评估可扩展的多频FD硬件和软件， 它以高精度在100个空间密度对组织进行采样。目前的方法是不够的，因为 数据采集太慢，所需的硬件（例如光学设备/光纤和电子设备）太大， 繁重的、标准的数据处理和3D重建算法不能合理地处理这些大的 数据集。该项目介绍了多波长光源和灵敏探测器的创新，多波长， 频率FD调制和解调，高空间密度组织采样方法，FD相控阵 组织的结构化询问和2D/3D图像重建。提高性能将是 通过乳腺成像和定量fNIRS的人体验证研究证实。结果也将 显著提高了可穿戴传感能力，并改善了其他光学模态的量化， 如光声成像。没有其他医学成像技术可以提供定量的深层组织， 实时测量内源和外源分子以及组织散射参数， 紧凑、可扩展的平台。总之，这些进展将迎来下一代定量组织 光谱学，导致改善诊断和个性化护理，特别是在神经病学，乳腺癌， 肿瘤学和个人健康 1

PROJECT SUMMARY Nearly 20 years of clinical research has shown that near-infrared optical imaging based upon frequency domain diffuse optical spectroscopy (FD-DOS) can be a powerful tool for the study, diagnosis, and personalized treatment of human disease. When used for neuroimaging (i.e. functional near-infrared spectroscopy, fNIRS), FD-DOS can provide a greater imaging depth compared to standard continuous-wave (CW) fNIRS thus reaching deeper cortical layers and providing better distinction from superficial layers. In breast cancer, FD-DOS is effective for predicting individual response to neoadjuvant chemotherapy and similar strong evidence supporting FD-DOS has been collected in critical care, exercise physiology, breast cancer diagnosis, and other applications. Despite this convincing clinical data, FD-DOS has not yet been translated to standard clinical use for any indication. The reasons are two-fold. First, diffuse optical imaging methods, as a whole, still suffer from low spatial resolution and signal-to-noise ratio. Furthermore, clinical applications that can benefit from the advanced quantitation and deeper sensitivity afforded by FD-DOS are reluctant to adopt the method because it lacks scalability for high density, high resolution imaging and is prohibitively complex, slow, and difficult to use. This project will remove these barriers by creating a reflectance-based FD-DOS imaging platform for quantitative deep tissue spectroscopy and tomography with unprecedented scalability, precision, and speed that enables dramatic improvements in accuracy and spatial resolution. This will be enabled by the development and evaluation of massively-scalable multi-frequency FD hardware and software that samples tissue at ultrahigh spatial densities with high precision. Current methods are insufficient because data acquisition is too slow, the hardware needed (e.g. optical devices/fibers and electronics) is too bulky and heavy, and standard data processing and 3D reconstruction algorithms cannot reasonably handle these large datasets. This project introduces innovations in multi-wavelength optical sources and sensitive detectors, multi- frequency FD modulation and demodulation, high spatial density tissue sampling methods, FD phased-array structured interrogation of tissue, and 2D/3D image reconstruction. Improved performance will be demonstrated through human validation studies of breast imaging and quantitative fNIRS. The results will also significantly advance wearable sensing capabilities and improve quantification in other optical modalities such as photoacoustic imaging. No other medical imaging technology can provide quantitative, deep tissue, and real-time measurements of both endogenous and exogenous molecules and tissue scattering parameters in a compact, scalable platform. Together, these advances will usher in a next generation of quantitative tissue optical spectroscopy that lead to improved diagnostics and individualized care, especially in neurology, breast oncology, and personal health. 1