Sensitivity improved Cerenkov luminescence endoscopy using optimal system parameters

The challenges of clinical translation of optical imaging, including the limited availability of clinically used imaging probes and the restricted penetration depth of light propagation in tissues can be avoided using Cerenkov luminescence endoscopy (CLE). However, the clinical applications of CLE are limited due to the low signal level of Cerenkov luminescence and the large transmission loss caused by the endoscope, which results in a relatively low detection sensitivity of current CLE. The aim of this study was to enhance the detection sensitivity of the CLE system and thus improve the system for clinical application in the detection of gastrointestinal diseases.

Four optical fiber endoscopes were customized with different system parameters, including monofilament (MF) diameter of imaging fiber bundles, fiber material, probe coating, etc. The endoscopes were connected to the detector via a specifically designed straight connection device to form the CLE system. The β-2-[¹⁸F]-Fluoro-2-deoxy-D-glucose (¹⁸F-FDG) solution and the radionuclide of Gallium-68 (⁶⁸Ga) were used to evaluate the performance of the CLE system. The images of the ¹⁸F-FDG solution acquired by the CLE were used to optimize imaging parameters of the system. By using the endoscope with optimized parameters, including the MF diameter of imaging fiber bundles, fiber materials, etc., the resolution and sensitivity of the assembled CLE system were measured by imaging the radionuclide of ⁶⁸Ga.

The results of ¹⁸F-FDG experiments showed that larger MF diameter led to higher collection efficiency. The fiber material and probe coating with high transmission ratios in the range of 400-900 nm also increased signal collection and transmission efficiency. The results of ⁶⁸Ga evaluations showed that a minimum radioactive activity of radionuclides as low as 0.03 µCi was detected in vitro within 5 minutes, while that of 0.68 µCi can be detected within 1 minute. In vivo experiments also demonstrated that the developed CLE system achieved a high sensitivity at a submicrocurie level; that is, 0.44 µCi within 5 minutes, and 0.83 µCi within 1 minute. The weaker in vivo sensitivity was due to the attenuation of the signal by the mouse tissue skin and the autofluorescence interference produced by biological tissues.

By optimizing the structural parameters of fiber endoscope and imaging parameters for data acquisition, we developed a CLE system with a sensitivity at submicrocurie level. These results support the possibility that this technology can clinically detect early tumors within 1 minute.