Retinal Hemodynamic Imaging with Tracking Doppler Flowmetry

描述（由申请人提供）：物理科学公司（PSI）提议将新的和现有的视网膜成像技术结合起来，以产生强大的新的无染料、功能性的眼血流成像能力。我们之前展示了一种名为跟踪多普勒血流法（TDF）的新技术，用于获取视网膜的宽视场，高动态范围多普勒频率分辨图。通过这种方式，对于患有诸如年龄相关性黄斑变性等疾病的眼睛，或者响应影响神经元或代谢活动的因素（光刺激、运动或药物），可以使用新的分形、颜色编码和均衡技术显示和量化血流信息。TDF的长共焦范围门是有益的，由于包含了多个散射事件，散射接收角大，在长相互作用范围内对输入光束角的灵敏度低，提供了高的流动灵敏度和对比度，并且不利于流动的轴向定位。相反，光学多普勒断层扫描具有窄相干范围门，提供高轴向流判别，但仅对轴向速度分量在窄接受角内的单散射敏感。在该计划中，我们将开发两种方法来改善TDF的轴向识别：立体操作和利用傅里叶域光学相干层析成像原理与扫描源杂交。先进的数据处理算法也将被实现。改进后的系统将在人类志愿者身上进行测试，以1)演示可量化和可重复的深度分辨视网膜多普勒血流图；2)测量与视觉刺激诱发的神经血管耦合机制相关的血流变化；3)通过与心脏周期同步，实现跨一系列血管大小和流速的详细脉动流相肖像。这项工作将为临床医生和研究人员研究视网膜功能、眼病的机制和治疗提供有价值的诊断工具。本研究与公众健康的相关性：视网膜是人体血管化程度最高的组织之一，也是最容易因血流不足而受损的组织。许多眼部退行性和血管生成性疾病，如年龄相关性黄斑变性和糖尿病性视网膜病变，都有血流动力学后果或原因，尽管许多机制仍然未知或不清楚。更好的诊断工具的发展将导致对血管血流和毛细血管灌注对视网膜疾病的发生和发展的贡献的更多理解，以及对视觉信号转导，高阶大脑处理和调节以及高级治疗相互作用和药物作用的研究。

DESCRIPTION (provided by applicant): Physical Sciences Inc. (PSI) proposes to combine new and existing retinal imaging technologies to yield powerful new dye-free, functional imaging capabilities to ocular blood flow. We have previously demonstrated a new technique called tracking Doppler flowmetry (TDF) for the acquisition of wide-field, high dynamic range Doppler frequency-resolved maps of the retina. In this manner, blood flow information can be displayed and quantified with novel binning, color encoding, and equalization techniques for eyes with diseases such as age-related macular degeneration, or in response to factors affecting neuronal or metabolic activity (light stimulation, exercise, or pharmaceutical agent). The long confocal range gate of TDF is at once beneficial, providing high flow sensitivity and contrast due to inclusion of multiple-scattering events, large scattering receive angle, and low sensitivity to input beam angle within a long interaction range, and detrimental in terms of axial localization of flow. Optical Doppler tomography, conversely, has a narrow coherence range gate that provides high axial flow discrimination but is sensitive only to single-scattering with axial velocity components in a narrow acceptance angle. In the proposed program, we will develop 2 methods for improved axially discrimination with TDF: stereoscopic operation and hybridization with swept sources using the principles of Fourier domain optical coherence tomography. Advanced data processing algorithms will also be implemented. The improved system will be tested in human volunteers to 1) demonstrate quantifiable and reproducible depth-resolved retinal Doppler blood flow mapping; 2) measure blood flow changes in relation to visual stimulus-evoked neuro-vascular coupling mechanisms; and 3) enable detailed pulsatile flow phase portraits across a range of vessel sizes and flow velocity by synchronization to the cardiac cycle. This work will provide a valuable diagnostic tool to clinicians and researchers for the study of retinal function and the mechanisms and treatment of eye disease. Relevance of this research to public health: The retina is 1 of the most highly vascularized tissues in the body and is also most susceptible to damage from deficits in blood flow. Many degenerative and angiogenerative diseases of the eye, such as age-related macular degeneration and diabetic retinopathy, have either hemodynamic consequences or causes, though many of the mechanisms remain unknown or obscure. Development of better diagnostic tools will lead to increased understanding of the contribution of vascular blood flow and capillary perfusion to the inception and progression of retinal diseases, and also to research on visual signal transduction, higher order brain processing and modulation, and the study of advanced therapeutic interactions and pharmaceutical effects.