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

描述（由申请人提供）：人类手术，尤其是肿瘤手术，需要改进的图像引导。目前，外科手术是“盲目地”进行的，没有需要移除的组织的视觉提示（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缺血的健康组织（例如，夹持）。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NIR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器件，目前正在进入临床试验。虽然可能在许多类型的外科手术中找到实用性，但是本成像系统仅产生定性信息，并且不能定量地重建吸收（即，A）和散射（即，活组织的性质和荧光团量子产率（QY）。这样的信息将具有直接的临床影响，因为它将首次允许对组织氧合进行非侵入性的基于图像的评估，并且将通过减少自发荧光而大大提高NIR荧光团的灵敏度。在该应用中，我们提出使用空间调制的近红外光（SMNL）来基本上实时地产生<$A、<$S '和QY的定量成像。我们的合作者，位于欧文市的加州大学贝克曼激光研究所的Tromberg小组，率先将这项技术用于定量、深度分辨光谱成像，作为贝克曼激光研究所激光微束和医疗计划（LAMMP）的一部分（www.bli.uci.edu/lammp）。初步研究中显示的最新结果表明，SMNL现在可以优化用于大手术野，而无需激光激发源。当与本研究中提出的基于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相结合时，SMNL应该能够为外科医生提供<$A、<$S '和QY的直接测量，从而改善几乎所有的图像引导手术干预。该项目的第一阶段利用了两个成像组的互补专业知识，并使用“协作反馈”来快速优化新型临床成像系统的性能。具体目标侧重于人体手术所需的SMNL采集参数和性能指标的数学建模;能够在15 cm直径FoV上投射多波长、高通量率图案化光的新型LED光源的工程设计;以及使用大型动物手术模型优化实时成像技术。成功完成特定目标和目标将确保在项目第二阶段将这种用于图像引导介入的新技术有效地转化为临床。7.人类手术，特别是肿瘤手术，需要改进的图像引导。目前，外科手术是“盲目地”进行的，没有针对需要被移除的组织、需要被避开的组织或在手术期间无意中受伤的健康组织的视觉提示。成功完成本申请中的特定目标将确保用于图像引导手术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.