Retinal Hemodynamic Imaging with Tracking Doppler Flowmetry

描述(申请人提供)：物理科学公司(PSI)建议结合新的和现有的视网膜成像技术，以产生强大的新的无染料，功能成像能力的眼睛血液流动。我们之前已经演示了一种名为跟踪多普勒血流计(TDF)的新技术，用于获取大视野、高动态范围的多普勒频率分辨率视网膜图。以这种方式，血流信息可以用新的装箱、颜色编码和均衡技术来显示和量化，用于患有诸如年龄相关性黄斑变性的疾病的眼睛，或者响应于影响神经元或代谢活动的因素(光刺激、运动或药剂)。TDF的长共焦距门在长相互作用范围内具有很高的流动灵敏度和对比度，因为它包含多个散射事件、较大的散射接收角度和对输入光束角度的低灵敏度，而在流动的轴向局部化方面则是不利的。相反，光学多普勒层析成像有一个窄的相干范围门，它提供了高的轴向流动分辨率，但只对窄接受角内的轴向速度分量的单次散射敏感。在该方案中，我们将开发两种改进的TDF轴向分辨方法：立体操作和利用傅里叶域光相干层析成像原理的扫描源杂交。还将实施先进的数据处理算法。改进后的系统将在人体志愿者身上进行测试，以1)展示可量化和可重现的深度分辨率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有关的血流变化；3)通过与心脏周期同步，实现各种血管大小和血流速度的详细脉动流动相图。这项工作将为临床医生和研究人员提供一种有价值的诊断工具，用于研究视网膜功能以及眼部疾病的机制和治疗。这项研究与公共健康的相关性：视网膜是体内血管最丰富的组织之一，也最容易受到血液流动不足的损害。许多眼部退行性和血管生成疾病，如老年性黄斑变性和糖尿病视网膜病变，要么有血流动力学后果，要么有病因，尽管许多机制仍然不清楚或不清楚。开发更好的诊断工具将有助于加深对血管血流和毛细血管灌注在视网膜疾病发生和发展中的作用的了解，还将有助于研究视觉信号转导、更高阶脑处理和调制，以及高级治疗相互作用和药物效应的研究。

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.