Hyperspectral Imaging of the Normal and Age-related Macular Degeneration Fundus

描述(由申请人提供)：一个在眼科疾病、成像、视网膜病理和生物医学工程方面拥有世界级专业知识的团队将利用高光谱成像首次提供经组织病理学相关性验证的在体分子探测年龄相关性黄斑变性(AMD)。他们的系统是一种特别改装的眼底相机，利用尖端生物医学图像分析技术，将通过识别与AMD病变相关的各种发色团和荧光团的分布和光谱特征，为该领域带来革命性变化。玻璃斑疹是AMD的标志性病变，具有生物化学异质性，是了解这种疾病的关键。然而，即使是目前最高分辨率的技术也不能在体内确定它们的组成。高光谱成像数据现在可以通过一种新的快照高光谱设备在临床上获得，它提供了视网膜光谱活组织检查的愿景。这些数据被编码在一个四维的“超立方体”中，具有两个空间(x和y坐标)和两个频谱(幅度和波长)维度。这个复杂的数据立方体可以用先进的无监督数学工具来探索，这些工具在数据矩阵中搜索出主要的光谱特征。通过解剖玻璃斑疹和其他AMD病变的光谱反射和自体荧光(AF)特征，这项研究将实现这些病变的体内光谱分类。为了实现这一目标，研究团队计划获取AMD所有表型的高光谱、摄影、AF和红外扫描激光眼底镜(SLO)和光谱域光学相干断层扫描(SD-OCT)图像，并通过优化的矩阵分解协议对高光谱图像进行分析，以恢复主导光谱及其空间分布。通过添加适当的激发滤光片和屏障滤光片，还可以使用同一设备同时获取高光谱自动对焦图像。此外，基因分型供眼的高光谱成像将为玻璃体和其他与玻璃体光谱特征相关的AMD病变的成分提供组织病理学确认，以及强大的基因/表型相关性。长期目标：我们设想为AMD和眼科护理提供一个集成的成像系统，将这种技术范式的转变结合在一起。拥有这样一个活体分子探针系统将在研究中发挥重要作用。所获得的见解将对临床诊断和治疗具有重要价值。此外，这样的系统将通过对预期治疗药物的敏感和早期结果测试来加速转化研究，节省视力，从而为社会提供巨大的好处。 公共卫生相关性：在老年性黄斑变性(AMD)的研究中，使用特别改装的视网膜相机的高光谱成像将首次提供活体眼组织的分子探测，并通过对供体眼组织的检查进行验证。AMD病变的分布和生化性质的确定将独特地有助于了解AMD，这是我国的主要致盲原因。所获得的见解将在AMD患者的临床护理中具有很高的价值，并将导致挽救视力，给我们的社会带来巨大的好处。

DESCRIPTION (provided by applicant): A team with world-class expertise in ophthalmic disease, imaging, retinal pathology, and biomedical engineering will utilize hyperspectral imaging to provide, for the first time, in vivo molecular probing, validated with histopathologic correlation, of age-related macular degeneration (AMD). Their system, a specially modified fundus camera harnessed to cutting-edge biomedical image analysis techniques, will revolutionize the field by identifying the distribution and spectral signature of the various chromophores and fluorophores associated with AMD lesions. Drusen, the hallmark lesions of AMD, are biochemically heterogeneous and are key to understanding this disease. However, their composition cannot be determined in vivo with even the current highest resolution techniques. Hyperspectral imaging data, now uniquely clinically attainable with a new snapshot hyperspectral device, offers a vision of spectral biopsy of the retina. This data is encoded in a four-dimensional "hypercube," with two spatial (x and y coordinates) and two spectral (amplitude and wavelength) dimensions. This complex data cube can be explored with advanced unsupervised mathematical tools that search out the dominant spectral signatures in the data matrix. By dissecting the spectral reflectance and autofluorescence (AF) signatures from drusen and other AMD lesions, this research will achieve in vivo spectral classifications of these lesions. To accomplish this, the research team plans to acquire hyperspectral, photographic, AF and infrared scanning laser ophthalmoscope (SLO), and spectral domain optical coherence tomography (SD-OCT) images of all phenotypes of AMD, with analysis of the hyperspectral images by an optimized matrix factorization protocol to recover dominant spectra and their spatial distributions. Hyperspectral AF images will also be acquired simultaneously with the same device by adding appropriate excitation and barrier filters. Further, hyperspectral imaging of genotyped donor eyes will provide histopathologic confirmation of the components of drusen and other AMD lesions that correlate with the drusen spectral signatures, as well as robust genotype/phenotype correlations. Long-term goals: We envision an integrated imaging system for AMD and ophthalmologic care that incorporates this paradigm shift in technology. Having such a system of in vivo molecular probes will be instrumental in research. The insights so obtained will be of high value in clinical diagnosis and treatment. In addition, such a system will accelerate translational research with sensitive and early outcome testing of prospective therapeutic agents, saving sight and thereby providing enormous benefit to society. PUBLIC HEALTH RELEVANCE: Hyperspectral imaging with a specially modified retinal camera will provide, for the first time, molecular probing of living eye tissue, validated by examination of donor eye tissue, in the study of age-related macular degeneration (AMD). Identification of the distribution and biochemical nature of AMD lesions will be uniquely instrumental in understanding AMD, the leading cause of blindness in our country. Insights so obtained will be highly valuable in the clinical care of AMD patients and will result in saving sight, with enormous benefit to our society.