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，需要改进的图像引导。目前，手术是“盲目”进行的，对于需要切除的组织（如癌症）、需要避免切除的组织（如神经）或在手术过程中无意中缺血的健康组织（如夹紧）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，该系统利用外源性荧光团和不可见的近红外光来帮助指导手术。该成像系统采用连续波（CW）激发和简单反射光学，目前已进入临床试验阶段。虽然可能在许多类型的手术中发现实用性，但目前的成像系统仅产生定性信息，并且无法定量地重建活组织的吸收（即¿A）和散射（即¿S）特性以及荧光团量子产率（QY）。这些信息将立即产生临床影响，因为它将首次允许对组织氧合进行无创、基于图像的评估，并将通过减少自身荧光大大提高近红外荧光团的灵敏度。在本应用中，我们建议使用空间调制近红外光（SMNL）来产生基本实时的¿A，¿S'和QY的定量成像。我们的合作伙伴，加州大学欧文分校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（www.bli.uci.edu/lammp）激光微束和医疗计划（LAMMP）的一部分。最近在初步研究中显示的结果表明，SMNL现在可以在不需要激光激励源的情况下优化用于大手术场。当结合本研究中提出的新型led光源，以及PI实验室心脏和呼吸门控技术的最新进展时，SMNL应该能够为外科医生提供直接测量¿a，¿S'和QY，从而改善几乎所有图像引导的手术干预。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”，快速优化新型临床成像系统的性能。具体目标集中在那些SMNL采集参数和人类手术所需的性能指标的数学建模；一种基于led的新型光源的工程设计，该光源能够在直径15厘米的视场上投射多波长、高通量的图案光；以及利用大型动物手术模型对实时成像技术进行优化。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二期期间有效地转化为临床。7. 人类外科手术，尤其是肿瘤外科手术，需要改进图像引导。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，或者在手术过程中无意中受伤的健康组织，没有视觉线索。成功完成本应用程序的特定目标将确保一种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.