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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
- 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)
- 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)
- Dysli, M.Dysli, V. Enzmann, S. Wolf, M. S. Zinkernagel, Fluorescence Lifetime Imaging of the Ocular Fundus in Mice. IOVS 55, 7206-7215 (2014)
- 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)
- 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
- 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
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Schweitzer, Quantifying fundus autofluorescence. In: N. Lois, J.V. Forrester, eds., Fundus autofluorescence. Wolters Kluwer, Lippincott Willams & Wilkins (2009)
- Schweitzer, Metabolic Mapping. In: F.G. Holz, R.F. Spaide (eds), Medical retina, Essential in Opthalmology, Springer (2010)
- Schweitzer, S. Quck, M. Klemm, M. Hammer, S. Jentsch, J. Dawczynski, Zeitaufgelöste Autofluoreszenz bei retinalen Gefäßverschlüssen. Der Ophthalmologe 12, 1145-1152 (2010)
- 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)
- 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)
- 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)
- 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)