The Study Of Endoscopic Cerenkov Luminescence Imaging System And Signal Enhancement Method

As a molecular optical imaging modality with large number of available clinical radionuclide probes, Cerenkov Luminescence Imaging (CLI) attracts more and more attention since its proposed. However, the Cerenkov Luminescence (CL) is the second product during the decay of radionuclides, which is extremely weak and most of the luminescence is distributed in the spectrum of short wavelengths. Thus, tissue penetration depth of CL is insufficient for the detection of deeply seated targets because of high attenuation of light by biological tissue in ultraviolet of blue wavelength, which limits the extensive clinical translation of CLI.This dissertation mainly discusses the solution of detecting deeply seated targets. With the help of the widely used clinical endoscope, we firstly development an Endoscopic Cerenkov Luminescence Imaging (ECLI) system. Afterwards, based on the radioluminescence (RL) imaging phenomena, an enhancement strategy for CLI, as well as ECLI, was proposed, and applied to improve the detection sensitivity of the ECLI system. The main contributions of this dissertation could be summarized as follows:1. By integrating the clinically used endoscope with the Cerenkov luminescence imaging (CLI) technology, a new endoscopic Cerenkov luminescence imaging (ECLI) system was developed. The aim is to demonstrate the potential of translating CLI to clinical studies of gastrointestinal (GI) tract diseases. We systematically evaluated the feasibility and performance of the developed ECLI system with a series of in vitro and pseudotumor experiments. The ECLI system is comprised of an electron multiplying charge coupled device (EMCCD) camera coupled with a clinically used endoscope via an optical adapter. A 1951-USAF test board was used to measure the white-light lateral resolution, while a homemade test chart filled with 68Ga was employed to measure the CL lateral resolution. Both in vitro and pseudotumor experiments were conducted to obtain the sensitivity of the ECLI system. The results were validated with that of CLI using EMCCD only, and the relative attenuation ratio of the ECLI system was calculated. Results showed that The white-light lateral resolution of the ECLI system was 198 μm, and the luminescent lateral resolution was better than 1 mm. Sensitivity experiments showed a theoretical sensitivity of 0.186 KBq/μL (5.033 x 10-3 μCi/μL), and 1.218 KBq/μL (32.922 × 10-3 μCi/μL) for the in vitro and pseudotumor studies, respectively. The relative attenuation ratio of ECLI to CLI was about 96%. The luminescent lateral resolution of the ECLI system was comparable with that of positron emission tomography (PET). The pseudotumor study illustrated the feasibility and applicability of the ECLI system in living organisms, indicating the potential for translating the CLI technology to the clinic.2. Inspired by radioluminescence imaging (RLI) phenomena, an enhancement strategy for CL intensity was proposed. In this strategy, the radioluminescence (RL) material was bombarded by high-energy rays generated during the decay of radionuclides to emit RL. Thus, the hybrid luminescence consisted not only the CL but also the RL, resulting the enhancement of CL intensity. The RL material used in this proof-of-concept study was terbium doped Gd2O2S (Gd2O2S:Tb), and a series of in vitro and pseudotumor experiments were designed to evaluate the proposed enhancement strategy. Three conclusions were obtained:(1) Gd2O2S:Tb could be excited by high-energy rays generated during the decay of radionuclides to emit RL; (2) After using the Gd2O2S:Tb, the intensity and penetration capability of the CL was enhanced; (3) In vivo pseudotumor study further proved the huge potential of this enhancement strategy for improving the detection sensitivity of CLI/ECLI in living animal studies.3. Previous study showed a great attenuation for the ECLI system, resulting in relatively low detection sensitivity of radiotracers. In order to overcome this problem, the enhancement strategy proposed in this dissertation was used. The radionuclide, RL material, and the settings of EMCCD were the same with the dictation sensitivity evaluation experiment described in our previous study. The results showed that after using the Gd2O2S:Tb, the ECLI system gained a higher detection sensitivity with the improvement of 53.4-fold for in vitro and 50.1-fold for in vivo, respectively. It should be noted that the in vivo detection sensitivity was improved to 2.43 x 10-2 KBq/μL(6.56 x 10-4 μCi/uL),which guaranteed meeting the demands of the clinical diagnosis of gastrointestinal tract tumors.