Spatially Modulated Near-Infrared Light for Image-Guided Cancer Surgery

描述(由申请人提供)：人类外科，特别是肿瘤外科，需要改进的影像指导。目前，对于需要切除的组织(例如，癌症)、需要避免的组织(例如，神经)或在手术过程中无意中变得缺血的健康组织(例如，由于夹闭)，手术都是“盲目地”进行的，没有视觉提示。作为生物工程研究伙伴关系的一部分，PI的实验室开发了一种近红外(NIR)荧光成像系统，该系统利用外源荧光团和不可见的近红外光来帮助指导手术。该成像系统使用连续波(CW)激发和简单的反射光学，目前正在进入临床试验。虽然目前的成像系统有可能在许多类型的外科手术中找到用途，但它只产生定性信息，并且不能定量地重建活组织的吸收(即A)和散射(即S)性质以及荧光团量子产率(QY)。这些信息将立即产生临床影响，因为它将首次实现对组织氧合的非侵入性、基于图像的评估，并将通过减少自发荧光而极大地提高近红外荧光团的灵敏度。在这个应用中，我们建议使用空间调制的近红外光(SMNL)来产生基本上实时的A、S和QY的定量成像。我们的合作者，加州大学欧文分校贝克曼激光研究所的特伦伯格小组，作为贝克曼激光研究所激光微束和医学计划(LAMMP)的一部分，率先使用这项技术进行定量、深度分辨光谱成像(www.bli.uci.edu/lamp)。初步研究的最新结果表明，SMNL现在可以优化用于大范围的手术领域，而不需要激光激发源。结合本研究中提出的一种基于LED的新型光源，以及PI实验室在心脏和呼吸门控技术方面的最新进展，SMNL应该能够为外科医生提供A、S和QY的直接测量，从而改进几乎所有图像引导的外科干预。该项目的第一阶段利用两个成像小组的互补专业知识，并使用“协作反馈”来快速优化新型临床成像系统的性能。具体目标集中于对人类手术所需的SMNL采集参数和性能指标进行数学建模；设计一种新型的基于LED的光源，能够在直径15厘米的FOV上投射多波长、高通量率的图案光；以及使用大型动物外科模型优化实时成像技术。具体目标和里程碑的成功完成将确保这项用于图像引导干预的新技术在项目II阶段有效地转化到临床。7.项目叙事人类外科，特别是肿瘤外科，需要改进图像指导。目前，手术是“盲目”进行的，对于需要切除的组织、需要避免的组织或在手术过程中无意中受伤的健康组织，没有视觉提示。成功完成这一应用中的特定目标将确保一种用于图像引导外科干预的新型光学成像技术有效地转化为临床。

DESCRIPTION (provided by applicant): Human surgery, and especially oncologic surgery, is in need of improved image-guidance. Presently, surgery is performed "blindly," without visual cues for tissue that needs to be removed (e.g., cancer), tissue that needs to be avoided (e.g., nerves), or otherwise healthy tissue that is becoming inadvertently ischemic during the procedure (e.g., from clamping). As part of a Bioengineering Research Partnership, the PI's laboratory has developed a near-infrared (NIR) fluorescence imaging system that utilizes exogenous fluorophores and invisible NIR light to help guide surgery. The imaging system uses continuous wave (CW) excitation and simple reflectance optics, and is now entering clinical trials. Although likely to find utility in many types of surgery, the present imaging system produces only qualitative information, and is unable to reconstruct, quantitatively, the absorbing (i.e., ¿A) and scattering (i.e., ¿S') properties of living tissue, and fluorophore quantum yield (QY). Such information will have immediate clinical impact since it will, for the first time, permit non-invasive, image-based assessment of tissue oxygenation, and will greatly improve NIR fluorophore sensitivity by reducing autofluorescence. In this application, we propose the use of spatially-modulated NIR light (SMNL) to produce quantitative imaging of ¿A, ¿S', and QY in essentially real-time. Our collaborator, the Tromberg group at the Beckman Laser Institute of the University of California, Irvine, has pioneered the use of this technology for quantitative, depth-resolved spectroscopic imaging as part of the Laser Microbeam and Medical Program (LAMMP) at the Beckman Laser Institute (www.bli.uci.edu/lammp). Recent results shown in Preliminary Studies suggest that SMNL can now be optimized for use over a large surgical field without the need for a laser excitation source. When combined with a novel LED-based light source proposed in this study, and recent advances in cardiac and respiratory gating technology from the PI's laboratory, SMNL should be able to provide surgeons with direct measurement of ¿A, ¿S', and QY, and thus improve virtually all image-guided surgical interventions. Phase I of this project leverages the complementary expertise of two imaging groups, and uses "collaborative feedback," to rapidly optimize the performance of a novel clinical imaging system. The Specific Aims are focused on the mathematical modeling of those SMNL acquisition parameters and performance metrics required for human surgery; the engineering of a novel, LED-based light source capable of projecting multi-wavelength, high fluence rate patterned light over a 15 cm diameter FoV; and the optimization of the technology for real-time imaging using large animal surgical models. Successful completion of the Specific Aims and Milestones will ensure that this new technology for image-guided interventions is translated efficiently to the clinic during project Phase II. 7. PROJECT NARRATIVE Human surgery, and especially oncologic surgery, is in need of improved image-guidance. Presently, surgery is performed "blindly," without visual cues for tissue that needs to be removed, tissue that needs to be avoided, or otherwise healthy tissue that is becoming inadvertently injured during the procedure. Successful completion of the specific aims in this application will ensure that a novel optical imaging technology for image-guided surgical interventions is translated efficiently to the clinic.