Simultaneous Multiwavelength Imaging of Retinal Nerve Fiber Layer for Early Diagnosis of Glaucoma

青光眼是世界范围内导致失明的主要原因。早期诊断可以使早期医疗干预成为可能，以防止视网膜损伤造成不可逆转的视力丧失。为了评估青光眼的损害，临床上通常采用非接触式光学测量视网膜层厚度。然而，现有的光学测量技术还不够灵敏，无法评估青光眼视网膜损伤的早期迹象。最近的实验室研究表明，在视网膜明显厚度改变之前，视网膜的超微结构首先被破坏。随着疾病的发展，超微结构的损伤会导致不同波长的反射率下降。不幸的是，没有可用的光学设备可以实时评估视网膜的光谱反射率。该项目将设计和建造这样的成像设备。该项目的完成将带来一种新的非接触式光学方法，可以灵敏地检测早期青光眼损害。这项研究将通过青光眼大鼠模型发现视网膜光谱反射率变化与青光眼损害之间的关系。所获得的知识将对青光眼的早期诊断和相关医疗监测产生重大影响。这项拟议的研究将通过为研究生提供生物光子学、微电子机械系统和成像方面的多学科培训，并通过支持本科生的高级项目和暑期研究经验，使学术研究和教育受益。本项目的目标是设计、构建和探索一种新的眼底多波长成像模式，用于活体同时进行视网膜神经纤维层(RNFL)的多波长成像，并提供对RNFL反射光谱在体测量的透彻了解。这项工作建立在研究人员的体外实验基础上，这些实验得出的结论是：(1)在青光眼视网膜，RNFL的反射率在RNFL变薄之前降低，(2)RNFL的反射率下降在可见光波长发生得更早，在红外波长发生得更晚。该研究计划有三个具体目标：(1)设计、建造和探索一种新的眼底多波长成像设备；(2)通过比较同一RNFL在体内和体外在正常大鼠视网膜上的反射光谱来验证该眼底多波长成像设备的测量能力；以及(3)通过使用青光眼大鼠模型来研究青光眼视网膜损害的RNFL反射光谱。所获得的知识将对青光眼的早期诊断产生重大影响，这将防止由视网膜损伤导致的不可逆转的视力损失，以及相关的医疗监测。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Glaucoma is a leading cause of blindness worldwide. Early diagnosis can permit early medical intervention to prevent irreversible visual loss caused by damage to the retina. To assess the glaucoma damage, non-contact optical measurement of retina layer thickness is typically performed in clinical practice. The available optical measurement technique is, however, not sensitive enough to assess early signs of glaucomatous damage of the retina. Recent laboratory studies show that the ultrastructure of the retina is damaged first before apparent retina thickness change. The ultrastructure damage causes reflectance decreases at different wavelengths as disease progresses. Unfortunately, there is no available optical modality that can assess the retina spectral reflectance in real time. This project will design and construct such an imaging device. Completion of the project will lead to a new non-contact optical method that can sensitively detect early glaucoma damage. The study will find the relationship between retina spectral reflectance changes and glaucoma damage by using a rat model of glaucoma. The gained knowledge will have significant impact to the early diagnosis of glaucoma and related medical treatment monitoring. The proposed research will benefit academic research and education by providing graduate students with multidisciplinary training in biophotonics, microelectromechanical systems, and imaging, and by supporting undergraduate senior projects and summer research experiences. The goals of this project are to design, construct, and explore a novel fundus multiwavelength imaging modality for in vivo simultaneous multiwavelength imaging of the retinal nerve fiber layer (RNFL) and to provide a thorough understanding of in vivo measurement of the RNFL reflectance spectrum. The work builds on the investigators' in vitro experiments that concluded that (1) in the glaucomatous retinas RNFL reflectance decreases prior to thinning of the RNFL and (2) the decrease of RNFL reflectance occurs early at visible wavelength and later at infrared wavelength. The research plan is organized under three specific aims: (1) Design, construct, and explore a new fundus multiwavelength imaging device; (2) Validate measurement capability of the fundus multiwavelength imaging device by comparing the reflectance spectra of the same RNFL measured in vivo and in vitro in the normal rat retina; and (3) Study RNFL reflectance spectra in retinas with glaucoma damage by using a rat model of glaucoma. The gained knowledge will have significant impact on the early diagnosis of glaucoma, which will prevent irreversible visual loss caused by retinal damage, and related medical treatment monitoring.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.