3D segmentation and registration of macular SD-OCT for application in MS

描述（由申请人提供）：至少55%的多发性硬化症（MS）患者视力受损，可能是疾病发作的最初表现。光谱域光学相干断层扫描（SD-OCT）能够对视网膜进行体内高分辨率研究，并且越来越多地用作神经退行性疾病的生物标志物。SD-OCT提供了视网膜神经纤维层、神经节细胞层和整体视网膜变薄的表型测量，表明MS中的轴突和神经元视网膜病变。有诱人的证据表明，MS中的视网膜深层也受到影响，这是特别令人感兴趣的，因为这些神经元从未髓鞘化。因此，SD-OCT测量已被证明可用于开发关于MS病理生理学的新科学理论。这些测量也可能用于疾病的早期检测、疾病严重程度分期、评估疾病进展和确定个体MS患者的治疗效果。虽然先进的自动化算法分割和测量的关键视网膜功能正在出现在研究实验室和商业仪器，仍然有几个关键的技术限制，充分利用这种三维成像技术。首先，视网膜分割方法目前不提供亚体素精度，它们对于黄斑水肿的存在也不鲁棒。第二，虽然视网膜的三维比较在标准眼科检查中是常规的，但是所使用的黄斑配准方法并没有将刚性和可变形成分分离以在归一化空间中进行详细的群体比较。第三，视网膜厚度通常是沿沿着直线向外计算的，而不对相对姿态进行补偿。总之，这些缺陷阻碍了3D纵向和横截面科学研究，并限制了对特定受试者疾病进展的监测。拟议的研究将：1）开发对水肿鲁棒的黄斑的亚体素视网膜层分割方法; 2）开发刚性和可变形配准方法，其将允许在归一化空间中分析SD-OCT体积; 3）开发固有视网膜厚度测量技术和平均黄斑图谱空间;和4）在标准化空间中对正常受试者和MS患者进行横截面和纵向研究，以测试以下假设： MS和ii）在MS中的视网膜深层中观察到纵向萎缩。我们还将探讨在MS受试者中区域性黄斑水肿是否先于内核层变薄。这些研究还将包括功能/结构回归，使用完整的黄斑体积，纵向评估，视力功能评分。图像处理和回归算法将在开源Java Image Science Toolkit（JIST）框架内开发，并作为开源软件发布。

DESCRIPTION (provided by applicant): Vision is compromised in at least 55% of multiple sclerosis (MS) patients and may represent the very first manifestation of disease onset. Spectral domain optical coherence tomography (SD-OCT) enables in-vivo, high-resolution studies of the retina, and is increasingly being used as a biomarker in neurodegenerative diseases. SD-OCT has provided phenotypical measurements of the retinal nerve fiber layer, ganglion cell layer, and overall retinal thinning, indicating both axonal and neuronal retinal pathology in MS. There is tantalizing evidence that deeper retinal layers are also affected in MS, which is of particular interest since these neurons are never myelinated. Thus, SD-OCT measurements have proven useful in the development of new scientific theories about the pathophysiology of MS. These measurements are also potentially useful in early detection of disease, staging disease severity, assessing disease progression, and determining therapeutic efficacy for individual MS patients. Although advanced automated algorithms for segmentation and measurement of key retinal features are emerging in both research labs and commercial instruments, there remain several key technical limitations to full exploitation of this three-dimensional imaging technique. First, retinal segmentation methods do not presently provide subvoxel precision nor are they robust to the presence of macular edema. Second, although three-dimensional comparisons of retinas are routine in standard ophthalmologic exams, the macular registration methods that are used do not separate the rigid and deformable components for detailed population comparisons in a normalized space. Third, retinal thicknesses are generally computed extrinsically along straight lines without compensation for relative pose. Together, these deficiencies hamper 3D longitudinal and cross-sectional scientific studies and limit monitoring disease progression in specific subjects. The proposed research will: 1) Develop a subvoxel retinal layer segmentation method for the macula that is robust to edema; 2) Develop both rigid and deformable registration methods that will permit analysis of SD-OCT volumes in a normalized space; 3) Develop intrinsic retinal thickness measurement techniques and an average macular atlas space; and 4) Carry out both cross-sectional and longitudinal studies of normal subjects and MS patients in a normalized space to test the hypotheses that i) deeper retinal layers are involved in MS and ii) longitudinal atrophy is observed in deeper retinal layers in MS. We will also explore whether regional macular edema precedes thinning in the inner nuclear layer in MS subjects. These studies will also include function/structure regression using the full macular volume, longitudinally assessed, against visual acuity functional scores. Image processing and regression algorithms will be developed within the open-source Java Image Science Toolkit (JIST) framework and released as open source software.