Label-free imaging of hemoglobin degradation and hemosiderin formation in brain tissues with femtosecond pump-probe microscopy
Lili Zhang1‡, Xiang Zou2‡, Bohan Zhang1, Liyuan Cui3, Jiayi Zhang3, Ying Mao2, Liang Chen2 Corresponding address, Minbiao Ji1 Corresponding address
Theranostics 2018; 8(15):4129-4140. doi:10.7150/thno.26946
1. State Key Laboratory of Surface Physics and Department of Physics, Collaborative Innovation Center of Genetics and Development, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China
2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
3. State Key Laboratory of Medical Neurobiology, Institute of Bain Science, Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Abstract
The degradation of hemoglobin in brain tissues results in the deposition of hemosiderin, which is a major form of iron-storage protein and closely related to neurological disorders such as epilepsy. Optical detection of hemosiderin is vitally important
yet challenging for the understanding of disease mechanisms, as well as improving surgical resection of brain lesions. Here, we provide the first label-free microscopy study of sensitive hemosiderin detection in both an animal model and human brain
tissues.
Methods: We applied spectrally and temporally resolved femtosecond pump-probe microscopy, including transient absorption (TA) and stimulated Raman scattering (SRS) techniques, to differentiate hemoglobin and hemosiderin in brain tissues. The label-free
imaging results were compared with Perls' staining to evaluate our method for hemosiderin detection.
Results: Significant differences between hemoglobin and hemosiderin transient spectra were discovered. While a strong ground-state bleaching feature of hemoglobin appears in the near-infrared region, hemosiderin demonstrates pure excited-state absorption
dynamics, which could be explained by our proposed kinetic model. Furthermore, simultaneous imaging of hemoglobin and hemosiderin can be rapidly achieved in both an intracerebral hemorrhage (ICH) rat model and human brain surgical specimens, with perfect
correlation with Perls' staining.
Conclusion: Our results suggest that rapid, label-free detection of hemosiderin in brain tissues could be realized by femtosecond pump-probe microscopy. Our method holds great potential in providing a new tool for intraoperative detection of hemosiderin
during brain surgeries.
Keywords: hemoglobin, hemosiderin, pump-probe microscopy, transient absorption, stimulated Raman scattering
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How to cite this article:
Zhang L, Zou X, Zhang B, Cui L, Zhang J, Mao Y, Chen L, Ji M. Label-free imaging of hemoglobin degradation and hemosiderin formation in brain tissues with femtosecond pump-probe microscopy. Theranostics 2018; 8(15):4129-4140. doi:10.7150/thno.26946.
Available from
http://www.thno.org/v08p4129.htm
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