In silico optimization of radioluminescence microscopy

Wang, Qian; Sengupta, Debanti; Kim, Tae Jin; Pratx, Guillem

doi:10.1002/jbio.201700138

Cited by 5 publications

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A variety of factors including scintillator film composition and thickness as well as pixel binning, microscope magnification, and the electron-multiplication gain would impact further advances in spatial resolution. We have discussed the optimization of these factors using computer simulation in a separate manuscript 20 . While radioluminescence microscopy has thus far been used for single cell visualization, additional applications are possible as the technique is refined.…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy

Sengupta

Kim

Almasi

et al. 2018

Analyst

Self Cite

View full text Add to dashboard Cite

Radioluminescence microscopy is an emerging modality that can be used to image radionuclide probes with micron-scale resolution. This technique is particularly useful as a way to probe the metabolic behavior of single cells and to screen and characterize radiopharmaceuticals, but the quality of the images is critically dependent on the scintillator material used to image the cells. In this paper, we detail the development of a microscopy dish made of a thin-film scintillating material, Lu2O3:Eu, that could be used as the blueprint for a future consumable product. After developing a simple quality control method based on long-lived alpha and beta sources, we characterize the radioluminescence properties of various thin-film scintillator samples. We find consistent performance for most samples, but also identify a few samples that do not meet the specifications, thus stressing the need for routine quality control prior to biological experiments. In addition, we test and quantify the transparency of the material, and demonstrate that transparency correlates with thickness. Finally, we evaluate the biocompatibility of the material and show that the microscopy dish can produce radioluminescent images of live single cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy

Sengupta

Kim

Almasi

et al. 2018

Analyst

Self Cite

View full text Add to dashboard Cite

show abstract

“…Experimental results were also compared by simulating the radioluminescence process using a Monte Carlo software package (Geant4). Similar to our previous work [ 18 , 19 ], a single 18 F point source with 1 Bq of radioactivity was generated in virtual space to represent a single radiolabeled cell. An optical model was implemented by convoluting the simulated scintillation tracks with the 3D point-spread function of the microscope’s objective, then applying pixel noise characteristic of the EMCCD camera.…”

Section: Methodsmentioning

confidence: 99%

Single-cell radioluminescence microscopy with two-fold higher sensitivity using dual scintillator configuration

et al. 2020

Self Cite

View full text Add to dashboard Cite

Radioluminescence microscopy (RLM) is an imaging technique that allows quantitative analysis of clinical radiolabeled drugs and probes in single cells. However, the modality suffers from slow data acquisition (15–30 minutes), thus critically affecting experiments with short-lived radioactive drugs. To overcome this issue, we suggest an approach that significantly accelerates data collection. Instead of using a single scintillator to image the decay of radioactive molecules, we sandwiched the radiolabeled cells between two scintillators. As proof of concept, we imaged cells labeled with [ 18 F]FDG, a radioactive glucose popularly used in oncology to image tumors. Results show that the double scintillator configuration increases the microscope sensitivity by two-fold, thus reducing the image acquisition time by half to achieve the same result as the single scintillator approach. The experimental results were also compared with Geant4 Monte Carlo simulation to confirm the two-fold increase in sensitivity with only minor degradation in spatial resolution. Overall, these findings suggest that the double scintillator configuration can be used to perform time-sensitive studies such as cell pharmacokinetics or cell uptake of short-lived radiotracers.

show abstract

“…Experimental results were also compared by simulating the radioluminescence process using a Monte Carlo software package (Geant4), as described in our previous work [18,19]. A single 18 F point source with 1 Bq of radioactivity was generated in virtual space to represent a single radiolabeled cell.…”

Section: Methodsmentioning

confidence: 99%

Single-cell radioluminescence microscopy with two-fold higher sensitivity using dual scintillator configuration

Kim

Wang²,

Shelor³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

11Radioluminescence microscopy (RLM) is an imaging technique that allows quantitative analysis 12 of clinical radiolabeled drugs and probes in single cells. However, the modality suffers from slow 13 data acquisition (10 -15 minutes), thus critically affecting experiments with short-lived 14 radioactive drugs. To overcome this issue, we suggest an approach that significantly accelerates 15 data collection. Instead of using a single scintillator to image the decay of radioactive molecules, 16 we sandwiched the radiolabeled cells between two scintillators. As proof of concept, we imaged 17 cells labeled with [ 18 F]FDG, a radioactive glucose popularly used in oncology to image tumors. 18Results show that the double scintillator configuration increases the microscope sensitivity by two-19 fold, thus reducing the image acquisition time by half to achieve the same result as the single 20 scintillator approach. The experimental results were also compared with Geant4 Monte Carlo 21 simulation to confirm the two-fold increase in sensitivity with only minor degradation in spatial 2 22 resolution. Overall, these findings suggest that the double scintillator configuration can be used to 23 perform time-sensitive studies such as cell pharmacokinetics or cell uptake of short-lived 24 radiotracers. 25 26 157 Cell ROI are shown in Fig 3b for single and double scintillator configurations. As expected, 158 [ 18 F]FDG uptake demonstrated a heterogeneous behavior, with some cells taking up the radiotracer 159 3 -4 times more than other cells. Furthermore, the measured average cell uptake was increased by 160 two-fold when the second scintillator was added. The average uptake values were 407 ± 156 161 counts/cell for the double scintillator configuration and 200 ± 90 counts/cell for the single 162 scintillator case. Linear regression (dotted red line) of the two datasets found a linear relationship 163 between the two datasets, y = 1.59 x + 87.86 (r 2 > 0.83). 9 164 165 Fig 3. Graphs representing single vs. double scintillator results. Scatter plot of decay counts 166 detected in 90 μm ROI (N = 66) for (a) background devoid of cells and (b) areas containing single 167 cells. The solid blue line and dotted red lines represent the linear regression fit. 168 169 Spatial Resolution 170The spatial resolution of the single and dual scintillator cases was quantitatively assessed by 171 drawing a line profile across two radioactive cells (Fig 4a). The profile was normalized according 172 to the maximum count values for both configurations (Fig 4b). Results clearly show two peaks 173 separated by a valley, which correspond to two cells with [ 18 F]FDG uptake along the line profile. 174Furthermore, no qualitative discrepancies in peak, valley, and background values can be observed 175 between the two configurations. This simple comparison suggests that the sensitivity of RLM can 176 be increased without significant degradation in spatial resolution. 177 178 Fig 4. Radioactive decay profile of two closely positioned cells. (a) A profile is ...

show abstract

In silico optimization of radioluminescence microscopy

Cited by 5 publications

References 24 publications

Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy

Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy

Single-cell radioluminescence microscopy with two-fold higher sensitivity using dual scintillator configuration

Single-cell radioluminescence microscopy with two-fold higher sensitivity using dual scintillator configuration

Contact Info

Product

Resources

About