Modulated Imaging: A Wide-field Optical Imaging Platform for Clinical Research

描述（由申请人提供）：组织结构和功能的定量表征是医学影像学中最具挑战性的问题之一。视场、询问深度和分辨率是显著影响图像质量和信息内容的关键特性。为此，我们建议推进一种称为调制成像（MI）的新成像技术的发展，并评估其作为临床设备的可行性，该设备将提供可用于确定体内组织状态的客观参数。调制成像采用模式照明，以非侵入性地获得生物组织的地下图像。这种非接触式方法可以在宽视场范围内快速定量测定组织的光学特性。当与多光谱成像相结合时，可以使用多个波长的光学特性来定量确定与皮瓣健康相关的发色团的体内浓度，即氧和脱氧血红蛋白。此外，可以对不同空间频率的图像进行处理，以显示散射和吸收方面的地下特征。一旦针对特定应用进行了优化，MI就可以使用消费级电子产品（例如目前用于数码相机和DLP投影仪的电子产品）来执行。因此，考虑调制成像作为一种相对廉价的医疗设备的潜力是合理的。该提案的总体目标是开发一个强大的，用户友好的MI平台，能够在临床现场部署适当的定量成像。它将具有足够的时空分辨率来研究组织中几毫米深度的快速（即毫秒时间尺度）和局部（即数百m到mm）事件。这将使我们能够定量了解伤口愈合、皮肤病学、皮肤癌和重建手术等领域的疾病进展和治疗反应。为了实现这一目标，我们建议设计和制造一个基于调制成像（MI）的平台仪器，这是一项在最近的激光和医疗微束计划（LAMMP；一个NIH/NCRR生物医学技术资源中心）资助期间开发的技术。拟议的研究将遵循一个有系统的开发计划，包括以下步骤：1)设计和制造用于人体受试者测量的标准化调制成像平台，2)设计和开发用于临床使用的交钥匙软件接口，3)在实验室环境中验证MI设备的性能，4)在临床上部署MI设备进行实际测试和评估。利用现有的IRB批准的临床方案和正在进行的LAMMP相关研究，我们将对皮肤相关应用进行可行性研究，包括正常皮肤、葡萄酒斑、黑色素瘤和皮瓣手术。在成功完成本文概述的第一阶段研究后，我们打算进行第二阶段提案，其中将涉及多个设备的制造和部署。最终，我们的目的是有条不紊地发展调制成像作为商业上可行的医疗设备。公共卫生相关性：我们建议开发一个强大的成像平台，用于临床成像应用的表面下组织特性定量成像。该系统将实现调制成像（MI）技术，这是一种非接触式成像方法，由加州大学欧文分校贝克曼激光研究所的激光微束和医学项目中心开发。通过在手术或重症监护病房（ICU）中准确地了解组织的哪些区域是健康的，医生可以进行干预并更及时地进行手术，以避免永久性的组织损伤。其益处包括识别皮肤癌病变的边缘，减少不必要的伤口护理程序，如糖尿病和创伤患者的截肢，以及烧伤患者的皮肤移植。从经济上讲，调制成像设备将减少这些患者不必要的额外住院天数，从而降低医院成本。

DESCRIPTION (provided by applicant): Quantitative characterization of tissue structure and function is one of the most challenging problems in Medical Imaging. Field of view, depth of interrogation, and resolution are critical features that dramatically impact image quality and information content. To this end, we propose to advance the development of a new imaging technique known as Modulated Imaging (MI) and to assess the viability of this as a clinical device that will provide objective parameters that can be used to determine status of in-vivo tissue. Modulated Imaging employs patterned illumination to non-invasively obtain subsurface images of biological tissues. This non-contact approach enables rapid quantitative determination of the optical properties of tissues over a wide field-of-view. When combined with multi-spectral imaging, the optical properties at several wavelengths can be used to quantitatively determine the in-vivo concentrations of chromophores that are relevant to flap health, namely, oxy- and deoxy-hemoglobin. Furthermore, images at various spatial frequencies can be processed to visualize subsurface features in terms of scattering and absorption. Once optimized for a particular application, MI can be executed using consumer grade electronics such as those currently employed in digital cameras and DLP projectors. Hence, it is plausible to consider the potential for Modulated Imaging to be executed as a relatively inexpensive medical device. The broad goal of this proposal is to develop a robust, user-friendly MI platform capable of quantitative imaging appropriate for deployment at clinical sites. It will possess sufficient spatio-temporal resolution to study both fast (i.e., ms timescale) and localized (i.e., hundreds of m to mm) events at depths of several millimeters in tissues. This will enable quantitative insight into disease progression and therapeutic response in areas such as wound healing, dermatology, skin cancer and reconstructive surgery. To achieve this, we propose to design and fabricate a platform instrument based on Modulated Imaging (MI), a technology that has been developed over the course of the most recent Laser and Medical Microbeam Program (LAMMP; a NIH/NCRR Biomedical Technology Resource Center) funding period. The proposed research will following a methodical development plan including the following steps: 1) Design and fabrication of a standardized Modulated Imaging platform for human subject measurements, 2) Design and development of a turnkey software interface for clinical use, 3) Validation of the MI device performance in a laboratory setting and 4) Deployment of the MI device clinically for real-world testing and evaluation. Leveraging existing IRB approved clinical protocols and ongoing LAMMP- related studies, we will perform feasibility studies for skin-related applications, including normal skin, port-wine stain, melanoma, and skin flap surgeries. Upon successful completion of the Phase I research outlined herein, we intend to pursue a Phase II proposal that will involve fabrication and deployment of multiple devices. Ultimately, our intent is to methodically develop Modulated Imaging as a commercially viable medical device. PUBLIC HEALTH RELEVANCE: We propose to develop a robust imaging platform for quantitative imaging of subsurface tissue properties for clinical imaging applications. This system will implement Modulated Imaging (MI) technology, a non-contact imaging method developed under the Laser Microbeam and Medical Program center at the Beckman Laser Institute, UC Irvine. By accurately knowing what areas of tissue are healthy during surgery or in the Intensive Care Units (ICU), doctors may intervene and perform more timely procedures to avoid permanent tissue damage. Benefits include margin identification of skin cancer lesions, reducing unnecessary wound care procedures such as amputations in diabetic and trauma patients, and skin grafting in burn patients. Economically, the Modulated Imaging device will reduce hospital costs by eliminating unnecessary additional hospital days for these patients.