Development of a time-correlated single-photon counting (TCSPC) Raman spectrosensing platform for early diagnosis of neurodegeneration diseases

J. Wang, M.H. Greenlee, C. Yu
Iowa State University,
United States

Keywords: time-correlated single-photon counting, Raman spectrosensing, neurodegeneration diseases


Neurodegeneration diseases (Prion diseases, Alzheimer’s, Parkinson’s) are progressive disorders of the nervous system that are in general not curable, but early intervention can significantly improve their symptoms and patient welfare. Early signs of neurodegeneration may become detectable at the retina years before symptoms of the diseases emerge. In this study, a prototype of the time-resolved single-photon Raman imaging system was developed to interrogate mouse retinal tissue samples at very low laser exposure level. Samples were excited by 1.5-17 ns laser pulses. Raman photon emitted by the samples were then collected by a Time-Correlated Single Photon Counting – or TCSPC sampling system. TCSPC provides the detection times of individual photons and reconstructs the waveform. The overall instrument response time is ~30-40 ps, much less than the typical fluorescence lifetime of 1-10 ns for biological samples. Hence, fluorescence photons can be differentiated from Raman photons to increase the signal-to-noise ratio of Raman spectrometry by a factor of 1000. This is a uniquely-designed system that is tailored for imaging the retina, with power delivered at the retina being lowered to less than 0.1 mJ/cm2, significantly lower than the safety threshold. Retinal tissues from mice were investigated using this system, three types of mice were used, with a mutant showing signs of Parkinson’s development, a mutation control that has the same genotype with the mutant, but no signs of disease and an age control from normal mice at the same age without the disease-prone mutation. Results showed that diseased tissues can be differentiated from mutant and normal control at 78% and 80% accuracy. In a separate experiment, eyes from cattle with bovine spongiform encephalopathy (BSE)-prone mutations were investigated in comparison to that of healthy controls. It was shown that a 67.5% accuracy of differentiation was obtained for ganglion layer, and an 82.5% accuracy was obtained for plexiform layer. Overall, the TCSPC Raman spectrosensing technique has the potential to become a great tool for early diagnosis of neurodegeneration diseases.