可提供光譜分析的細胞級解析度眼底鏡

Abstract

眼底鏡對眼科醫師而言，就像聽診器對外科醫師一樣重要。這兩個儀器有一個共通的特性：不必透過血淋淋的解剖就能得到極有價值的資訊。然而直到上世紀末，也就是在荷姆霍茲(Hermann von Helmholtz)發明它的兩百多年之後，隨著雷射掃描顯微術與適應性光學元件的蓬勃發展，此儀器的光學設計才有重大的演進。 近年來的適應性光學雷射掃描眼底鏡正是一個顯著的例子。它大體上繼承了共軛焦雷射掃描顯微術的架構，但因為應用上的所遭遇的問題，仍需要許多修改。主要的問題在於從眼底反射回來的光強度太弱，相較之下掃描系統中的透鏡所產生的表面反射會造成相對明亮的背景。在這篇論文裡，我們將發表一個僅由面鏡架構而成的適應性光學雷射掃描眼底鏡。當我們以球面鏡取代凸透鏡，可以有效解決表面反射的問題。但球面鏡架構並不是一個完美的解決方案，它會造成斜向入射像差。本文將分析球面鏡架構的斜向入射像差，並提出一個特殊的幾何設計來補償這種像差。只有面鏡的適應性光學雷射掃描眼底鏡有另一發展潛力：在寬頻的光源/光訊號上的應用。將寬頻雷射光源導入這個系統，可提供光譜解析度極高的影像資訊。 我們的眼底鏡的性能經過光學程式的模擬及最佳化之後，在整個掃描範圍之內，都能達到繞射極限的標準。文中將描述它的架構方式，並說明如何將系統的密實度、光路架設的可行性以及系統性能全部納入考慮。透過波前及光譜的測量，我們將展示在光波長550 nm至750 nm之間，這個系統達到繞射極限的能力。

The significance of an ophthalmoscope to an oculist is as that of a stethoscope to a cardiologist, because these instruments collect valuable information without things going into bloody anatomy. Nevertheless, after Hermann von Helmholtz invented his ophthalmoscope in 1851, there was no major improvement of its optical design until the booming era of laser scanning microscopy and adaptive optics in the late twentieth century. Though the adaptive optics scanning laser ophthalmoscope (AOSLO) inherits the concept of confocal laser scanning microscopy (CLSM), modifications should be done to suit its application. The main issue is that the extremely weak signal, due to the low reflectivity of the retina, would suffer from a relatively bright background scattered back from the surfaces of convex lenses of the scanning system. In this thesis, a spectro-ophthalmoscope with mirror-based scanning system and adaptive optics system is demonstrated, mainly to replace all the convex lenses with spherical mirrors. The disadvantage of mirror-based systems, the off-axis aberration, is illustrated and analyzed. We propose a specific geometrical design to compensate this aberration. With only mirrors in our spectro-ophthalmoscope, broadband capability can be achieved by choosing appropriate metallic coatings. Coupled with a broadband laser source the possibility of obtaining high-spectral-resolution information is provided. The performance of our spectro-ophthalmoscope is simulated and optimized using optical design software. Through the optimization the diffraction-limited performance is achieved within the entire scanning area. The physical construction of this system is presented, and the compactness, optics alignment and performance of the system are all taken into considerations. With wavefront measurements, we demonstrate the diffraction-limited performance of this system from 550-nm to 750-nm wavelength.