Multiplexed molecular imaging in the second near infrared window
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The implement and multiplexing of the second near-infrared window (NIR-II) imaging was demonstrated. Multiplexing is a novel idea in medical imaging, which describes the paradigm of integrating various diagnostic and therapeutic methods around the information acquired by imaging for better medical practices. NIR-II imaging is the in vivo imaging method with the light in the wavelength range between 1050 nm and 1700 nm. The NIR-II imaging is superior to conventional imaging due to the lower scattering, deeper penetration, and negligible autofluorescence. In this thesis, the imaging system and fluorescent materials for NIR-II imaging, the implement of phantom and in vivo NIR-II imaging, as well as multiplexed NIR-II imaging with radiotherapy have been studied, and the NIR-II Cherenkov imaging based on Cu-64 has been explored. Two NIR-II imaging systems have been constructed to achieve high quality facile imaging, with the special optical design to boost the quantitative imaging ability. Three quantum dots with different emission peaks across the NIR-II region have been obtained, and synthetic protocols were provided. An online-monitoring system of the NIR-II fluorescence has been designed and constructed, to monitor the process of quantum dots synthesis real-time. NIR-II imaging have been conducted with the imaging system and the fluorescent quantum dots. The imaging results obtained with the commonly used Intralipid® liquid phantoms were analyzed with a quantitative pipeline, to evaluate the effect of various parameters in NIR-II imaging. Monte Carlo simulations were conducted to verify the findings. The NIR-II imaging was also applied on a tissue clearing technology called CLARITY, to obtain ex vivo images and further proved the imaging quality. Based on the previous results, two types of in vivo NIR-II fluorescence imaging studies have been implemented. The dynamic in situ perfusion imaging tracks the fluorophores injected to the blood vessels of the mouse at a high frame rate, and reveals the diffusion of the fluorescent nanoparticles in the blood stream. Tumor angiogenesis has been evaluated with this method. The real-time intestine imaging tracks the movement of the fluorophores inside the intestines of the mice and visualizes the intestine structure. The imaging experiments verified the superiority of the NIR-II imaging. To further exploit the value of the NIR-II imaging, it has been multiplexed with radiotherapy. Cherenkov emission is generated during the megavolt X-ray beams therapy. The NIR-II components of the Cherenkov emission is sufficient for in vivo imaging to reveal the radiation field. This Cherenkov emission could also excite the NIR-II-emitting quantum dots, and this multiplexed imaging method could be used to validate the delivery of the radiation dose. With the lead shield apparatus, the high-quality Cherenkov imaging and Cherenkov excited luminescence imaging results could be obtained with megavolt X-ray beams. An attempt was made to multiplex NIR-II imaging with positron emission tomography. A solid target electroplating technology was developed to enable the manufacture of Cu-64. With the nanoparticle probe labeled with Cu-64, effective tumor imaging was obtained. However, the NIR-II Cherenkov luminescence imaging and Cherenkov radiation energy transfer were not successful. This thesis has established the technical platform for NIR-II imaging, and conducted the multiplexed NIR-II imaging. There is a great significance in multiplexed NIR-II imaging which is worthy of exploration.