眼科 FLIM（FLIO）

Principles

眼科 FLIM

TCSPC FLIM系统非常灵敏，能够记录人眼眼底（背景）的终生图像。眼科 FLIM 系统将TCSPC FLIM与快速光束扫描和皮秒二极管激光激发相结合。海德堡工程公司 FLIO 系统的扫描仪在 x 方向上使用共振扫描，在 y 方向上使用振镜扫描。激光束通过扫描头的前透镜射入眼瞳。从眼球背景返回的荧光经扫描后投射到针孔中，分成两个波长通道，并由两个HPM-100-40 GaAsP 混合探测器进行检测。探测器发出的光子脉冲在两个并行的 SPC-150 TCSPC FLIM 模块中进行处理。在进行FLIM成像的同时，还以短时间间隔记录红外反射图像。这些图像用于补偿 FLIM 记录中的眼球运动。原理如下图所示。

眼部疾病的早期阶段往往伴随着眼底的新陈代谢变化。这反过来又会导致内源性荧光团的荧光衰减参数发生变化。眼科 FLIM 目前正处于临床试验阶段。研究结果表明，该技术能够在传统方法检测到眼疾之前就显示出眼疾的早期阶段，更重要的是，能够在眼疾对视网膜造成永久性损害之前就显示出来。

References

References for Ophthalmic FLIM

1. Karl M. Andersen, Lydia Sauer, Rebekah H. Gensure, Martin Hammer, Paul S. Bernstein, Characterization of Retinitis Pigmentosa Using Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO). TVST 7 No. 3 (2018)
2. Dysli, G. Quellec, M. Abegg, M. N. Menke, U. Wolf-Schnurrbusch, J. Kowal, J. Blatz, O. La Schiazza, A. B. Leichtle, S. Wolf, M. S. Zinkernagel, Quantitative Analysis of Fluorescence Lifetime Measurements of the Macula Using the Fluorescence Lifetime Imaging Ophthalmoscope in Healthy Subjects. IOVS 55, 2107-2113 (2014)
3. Dysli, M.Dysli, V. Enzmann, S. Wolf, M. S. Zinkernagel, Fluorescence Lifetime Imaging of the Ocular Fundus in Mice. IOVS 55, 7206-7215 (2014)
4. Dysli, S. Wolf, K. Hatz, M. S. Zinkernagel, Fluorescence Lifetime Imaging in Stargardt Disease: Potential Marker for Disease Progression. Invest Ophthalmol Vis Sci. 57, 832-841, (2016)
5. C. Dysli, S. Wolf, H.V. Tran, M.S. Zinkernagel, Autofluorescence lifetimes in patients with choroideremia identify photoreceptors in areas with retinal pigment epithelium atrophy. Invest Ophthalmol Vis Sci. 2016;57:6714–6721. DOI:10.1167/ iovs.16-20392
6. Dysli, C., Wolf, S., Berezin, M.Y., Sauer, L., Hammer, M., Zinkernagel, M.S., Fluorescence lifetime imaging ophthalmoscopy, Progress in Retinal and Eye Research (2017), doi: 10.1016/j.preteyeres.2017.06.005
7. J. B. Lincke, C Dysli, D Jaggi, R Fink, S. Wolf, M. S. Zinkernagel, The Influence of Cataract on Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO). Transl Vis Sci Technol 10(4), 33, 1-10 (2021)
8. Lydia Sauer, Rebekah H. Gensure, Karl M. Andersen, Lukas Kreilkamp, Gregory S. Hageman, Martin Hammer, Paul S. Bernstein, Patterns of Fundus Autofluorescence Lifetimes In Eyes of Individuals With Nonexudative Age-Related Macular Degeneration. IOVS 59 (2018)
9. Lydia Sauer, Rebekah H. Gensure, PhD,1 Martin Hammer, Paul S. Bernstein, Fluorescence Lifetime Imaging Ophthalmoscopy: A Novel Way to Assess Macular Telangiectasia Type 2. Ophthalmology Retina 2 (6), 587-598 (2018)
10. Lydia Sauer, Karl M. Andersen, Binxing Li, Rebekah H. Gensure, Martin Hammer, Paul S. Bernstein, Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) of Macular Pigment. Retina (2018)
11. Lydia Sauer, Dietrich Schweitzer, Lisa Ramm, Regine Augsten, Martin Hammer, Sven Peters, Impact of Macular Pigment on Fundus Autofluorescence Lifetimes. Retina 56, 4668–4679 (2015)
12. Schweitzer, S. Quick, S. Schenke, M. Klemm, S. Gehlert, M. Hammer, S. Jentsch, J. Fischer, Vergleich von Parametern der zeitaufgelösten Autofluoreszenz bei Gesunden und Patienten mit früher AMD. Der Ophthalmologe 8, 714-722 (2009)
13. Schweitzer, Quantifying fundus autofluorescence. In: N. Lois, J.V. Forrester, eds., Fundus autofluorescence. Wolters Kluwer, Lippincott Willams & Wilkins (2009)
14. Schweitzer, Metabolic Mapping. In: F.G. Holz, R.F. Spaide (eds), Medical retina, Essential in Opthalmology, Springer (2010)
15. Schweitzer, S. Quck, M. Klemm, M. Hammer, S. Jentsch, J. Dawczynski, Zeitaufgelöste Autofluoreszenz bei retinalen Gefäßverschlüssen. Der Ophthalmologe 12, 1145-1152 (2010)
16. Schweitzer, Autofluorescence diagnostics of ophthalmic diseases. In: V.V. Ghukasyan, A.H. Heikal, eds., Natural biomarkers for cellular metabolism. Biology, techniques, and applications. CRC Press, Taylor and Francis Group, Boca Raton, London, New York (2015)
17. Schweitzer, M. Hammer, Fluorescence Lifetime Imaging in Ophthalmology. In: W. Becker (ed.) Advanced time-correlated single photon counting applications. Springer, Berlin, Heidelberg, New York (2015)
18. Schweitzer, Ophthalmic applications of FLIM. In: L. Marcu. P.M.W. French, D.S. Elson, (eds.), Fluorecence lifetime spectroscopy and imaging. Principles and applications in biomedical diagnostics. CRC Press, Taylor & Francis Group, Boca Raton, London, New York (2015)
19. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, J. Dawczynski, Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy. J. Biomed. Opt. 20(6), 061106-1 to 13 (2015)

Products

Application Notes

• 抑制白内障患者 FLIO 图像中的晶状体荧光
• 荧光寿命成像眼底镜（FLIO）
• FLIO 数据采集与分析 – 通往成功之路
• Shifted-Component Model Improves FLIO Data Analysis