Quantum dots enhanced Cerenkov luminescence imaging

Quantum dots enhanced Cerenkov luminescence imaging 1 2 equal first-author 1 2 equal 1 2 corresp Corresponding author, tangxiaobin@nuaa.edu.cn Corresponding author, tangxiaobin@nuaa.edu.cn tangxiaobin@nuaa.edu.cn 1 2 1 2 3 3 Department of Nuclear Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China Department of Nuclear Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Nanjing 210016, China Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Nanjing 210016, China Affiliated Hospital of Nanjing University of TCM, Nanjing 210016, China Affiliated Hospital of Nanjing University of TCM, Nanjing 210016, China Cerenkov luminescence imaging (CLI) has been widely investigated for biological imaging. However, the luminescence generated from Cerenkov Effect is relatively weak and has poor penetration ability in biological tissues. These limitations consequently hindered the clinical translation of CLI. In this study, we proposed an in-vitro experimental study for the demonstration of quantum dots (QDs) configurations affected by the improvement of the signal intensity of CLI. Results revealed that the optimal concentrations were 0.1 mg/mL and 0.25 mg/mL for the studied CdSe/ZnS QDs with fluorescence emission peaks of 580 nm and 660 nm, respectively. The detected optical signal intensity with long-wavelength emission QDs were stronger than those with short-wavelength emission QDs. This study illustrates an experiment to study the effects of concentrations and fluorescence emission peaks of QDs on an enhanced optical signal for the external detection of CLI. Cerenkov luminescence imaging Quantum dots Optical signal Wavelength shift 1 INTRODUCTION 1 Cerenkov luminescence imaging (CLI) is a promising technique for advanced biology imaging in the medical field [ 1 1 - 5 5 1-5 ]. The application of CLI has been extended to determine tumor location [ 6 6 , 7 7 ], monitor radionuclide uptake [ 8 8 , 9 9 ], and guide tumor resection surgery [ 10 10 , 11 11 ]. According to Frank and Tamm’s theory, the wavelength of Cerenkov luminescence (CL) is mostly distributed in the ultraviolet and blue range, which can only penetrate a few millimeters of biological tissues owing to high attenuation coefficients, thereby limiting the application of CLI. To overcome these limitations, several studies have been performed to explore novel technologies that can efficiently detect the signal, e.g., the CL endoscopy system [ 12 12 - 14 14 12-14 ]. Another potential solution is to shift the peak wavelength of CL to near-infrared or infrared ranges that have smaller attenuation coefficients. Cerenkov energy transfer (CRET) has demonstrated that CL can serve as an excitation source to excite various fluorescent particles, such as quantum dots (QDs) [ 15 15 , 16 16 ], gold nanoparticles [ 17 17 , 18 18 ], fluorophores [ 19 19 ], and lanthanides [ 20 20 , 21 21 ], where the fluorescent particles can act as fluorescence emitters of red-shifted emissions. Near-infrared or infrared light has lesser attenuation and absorption by biological tissues than ultraviolet or blue light [ 22 22 ]. Among various fluorescent particles, QDs were proposed to be combined with radioisotopes to construct CRET systems because QDs have superior optical properties, such as large Stokes shift, tunable fluorescence emission, high photostability, and high quantum yield [ 23 23 - 25 25 23-25 ]. However, whether high concentrations of QDs coupled with radioisotopes enhance optical signals for external detection still remains unclear. Appropriate fluorescence wavelength emissions of QDs can be selected for better optical signal enhancements considering the various penetrating abilities and quantum efficiencies of different photonic wavelengths of the external optical detector. In this study, two types of core/shell QDs (i.e CdSe/ZnS and CdTe/CdS) were selected to evaluate the effects of the concentration and fluorescence emission peaks of QDs on optical signal enhancement for external detection. 2 EXPERIMENTS SECTION 1 CdSe/ZnS and CdTe/CdS core/shell QDs were obtained from Xingzi New Material Technology Development Co. Ltd. (Shanghai, China). The fluorescence emission peaks were 580 nm and 660 nm for CdSe/ZnS QDs, and 580 nm and 620 nm for the CdTe/CdS QDs. Experiments were performed on an in-house developed optical imaging platform (see Fig. 1a Fig. 1a ), which was mainly composed by an EMCCD camera inside a black box to minimize the distortion of background light. The distance between the lens of the EMCCD and the transparent vials was 35 cm. The Na131I/QD mixed solution and the Na131I solution were imaged on the top of the sample. All o images were acquired with a 4 × 4 binning and a 5 min exposure time. The areas of the regions of interest were drawn over the optical sources of the images, and the average number of photons was calculated with Andor Solis that was used to provide the quantification information from the optical images. To evaluate the enhancement effect of QDs on optical signals for the Na 131 I solution, QDs with different fluorescence emission peaks (1 mL) were prepared in transparent vials with various concentrations (i.e 0.05, 0.1, 0.25, 0.5, 0.75, and 1 mg/mL) as shown in Fig. 1b Fig. 1b . The control group was prepared with zero QDs. Thereafter, 30 and 60 μCi Na 131 I (0.5 mL) solutions were added to each transparent vial respectively. To study the enhancement effect of QDs on the transmission ability in muscle tissues, a soft tissue of a pig was put on top of the vials. Fig. 2 Fig. 2 shows the experimental setup that was illustrated through the optical image of the muscle tissue covering the transparent vials. Different concentrations of CdTe/CdS QDs with 60 μCi of Na 131 I were placed in the transparent vials at 620 nm. The enhancement effect on the optical signal was related to the concentration of QDs for the same Na 131 I radioactivity. 3 Results and discussion 1 Fig. 3 Fig. 3 shows the optical images of different concentrations of CdTe/CdS QDs added with Na 131 I (60 μCi) solution at 620 nm. The signal intensity increases as the concentration of the QDs increases up to 0.75 mg/mL, and decreases as the concentration of the QDs further increases. The two types of QDs showed similar patterns. Figs. 4a and 4b Figs. 4a and 4b show the total number of photons at fluorescence emission peaks of 580 nm and 660 nm for the CdSe/ZnS QDs added with Na 131 I solution (30 and 60 μCi), and for CdTe/CdS QDs, respectively. This phenomenon may be due to the concentration quenching effect [ 26 26 ] that occurs when the concentration of QDs is excessively high while the excitation intensity remains unchanged [ 27 27 ]. Alternatively, the self-absorption of the solution is another factor that decreases the photons. Different kinds and emission peaks of QDs have different optimal concentrations to enhance the signal intensity of the Na 131 I solution. The optimal concentrations of CdSe/ZnS at fluorescence emission peaks of 580 nm and 660 nm were 0.1 mg/mL and 0.25 mg/mL, respectively. By comparison, the optimal concentrations of CdTe/CdS at fluorescence emission peaks of 580 nm and 620 nm were 0.1 and 0.75 mg/mL, respectively. Moreover, the number of photons in all mixed solutions was greater than that of the pure Na 131 I solution exposed to the same radioactivity level, suggesting that QDs successfully converted CL into red-shifted photons, which has higher penetration ability in tissues. Fig. 5 Fig. 5 shows the imaging of photons that are transmitted through the soft-tissue. Figs. 6a and 6b Figs. 6a and 6b show the results for CdTe/CdS QDs added with 60 μCi of Na 131 I solution. Under these conditions, the number of photons decreases as the thickness of the muscle tissue increases; however, it was always greater than that of the pure Na 131 I solution with the same radioactivity level. These results indicated that the QDs successfully converted CL into red-shifted photons that could enhance the penetration ability of photons in tissues. The spatial distribution of the tissue optical properties is indeed heterogeneous considering the whole sample; however, in our experiment, we attempt to determine a relatively uniform area for experiment that intentionally avoids the effect from the sample heterogeneity. Fig. 7 Fig. 7 shows the total number of photons at optimal concentrations of CdTe/CdS QDs added with 60 μCi of Na 131 I solution and covered with muscle tissues of different thicknesses. For the same type of QDs, the attenuation of the number of photons at the fluorescence emission peaks of short-wavelength emission QDs was more severe than that of long-wavelength emission QDs. Therefore, the fluorescence emission peaks of the long-wavelength emission QDs were more suitable for the enhancement of optical signal intensity for external detection than those of the short-wavelength emission QDs. This result is consistent with the previous studies on the in-vitro animal studies and optical properties of biological tissues, which generally show lower absorption efficiencies for longer-wavelength emission QDs [ 15 15 , 28 28 , 29 29 ]. To further explore the underlying mechanisms, the percentage of Cherenkov light that is being converted to longer wavelength photons could be explored through spectroscopic studies. 4 CONCLUSION 1 In this study, we experimentally observed the enhancement effect of CdSe/ZnS and CdTe/CdS QDs on optical signals that may be detected by an external optical detector (e.g. EMCCD) for CLI. The results indicated that QDs could effectively enhance the optical signal that could be detected by an external EMCCD, and different types and emission peaks of QDs have different patterns (e.g. various optimal concentrations) on the enhancement of the signal intensity of CL for external detection. 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Sci . 24 , 605 - 615 ( 2009 ). doi: 10.1007/s10103-008-0625-4 http://doi.org/10.1007/s10103-008-0625-4 Enhancement of light propagation depth in skin: cross-validation of mathematical modeling methods 10.1007/s41365-019-0599-x This work was supported in part by the Natural Science Foundation of Jiangsu Province (No. BK20180415), the National Natural Science Foundation of China (No. 11805100), the Fundamental Research Funds for the Central Universities (No. NS2018041), and the National Key Research and Development Program (Nos. 2016YFE0103600 and 2017YFC0107700). 2018-09-04 2018-12-22 2019-01-03 2019-04-09 2019-05-01 2021-04-10 © China Science Publishing & Media Ltd. (Science Press), Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, ChineseNuclear Society and Springer Nature Singapore Pte Ltd. 2019 This is a post-peer-review, pre-copyedit version of an article published in Nuclear Science and Techniques. The final authenticated version is available online at: http://dx.doi.org/10.1007/s41365-019-0599-x http://dx.doi.org/10.1007/s41365-019-0599-x . 2019 Nuclear Science and Techniques 05 30