Next generation deep tissue quantitative optical imaging

项目总结 近20年的临床研究表明，基于频率的近红外光学成像 区域漫反射光谱分析(FD-DOS)是一种强有力的研究、诊断和分析工具。 个性化治疗人类疾病。用于神经成像时(即功能性近红外 FNIRS)，与标准连续波相比，FD-DOS可以提供更大的成像深度 (CW)fNIR，从而到达更深的皮质层，并提供与浅层更好的区分。在……里面 对于乳腺癌，FD-DOS可有效地预测个体对新辅助化疗及类似治疗的反应 在重症监护、运动生理学、乳腺癌等领域收集了支持FD-DOS的有力证据 诊断和其他应用程序。尽管有这些令人信服的临床数据，FD-DOS尚未被翻译成 任何适应症的标准临床用法。原因有两个。第一，漫反射光学成像方法，作为 总体来说，仍然存在空间分辨率和信噪比较低的问题。此外，临床应用 可以受益于FD-DOS提供的高级量化和更高的敏感度，但不愿采用 该方法因为其缺乏用于高密度、高分辨率成像的可扩展性并且极其复杂， 速度慢，很难使用。该项目将通过创建基于反射比的FD-DOS来消除这些障碍 具有前所未有的可扩展性的定量深层组织光谱和断层成像成像平台， 精度和速度，使精确度和空间分辨率得以显著提高。这将是 通过开发和评估可大规模扩展的多频率FD硬件和软件实现 以超高空间密度对组织进行高精度采样。目前的方法是不够的，因为 数据采集太慢，所需的硬件(如光学设备/光纤和电子设备)太笨重， 繁重的、标准的数据处理和3D重建算法无法合理地处理这些庞大的 数据集。该项目介绍了多波长光源和灵敏探测器的创新，多波长光源和多波长探测器 频率FD调制解调、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。改进的性能将是 通过乳房成像和定量fNIR的人体验证研究证实了这一点。结果也将是 显著提升可穿戴式传感功能，并改进其他光学模式的量化，例如 作为光声成像。没有其他医学成像技术可以提供定量的、深层的组织和 内源性和外源性分子和组织散射参数的实时测量 紧凑、可扩展的平台。总之，这些进展将带来下一代定量组织 光学光谱学，导致改善诊断和个性化护理，特别是在神经学、乳房 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