Physically-based in silico light sheet microscopy for visualizing fluorescent brain models

Abstract

BackgroundWe present a physically-based computational model of the light sheet fluorescence microscope (LSFM). Based on Monte Carlo ray tracing and geometric optics, our method simulates the operational aspects and image formation process of the LSFM. This simulated, in silico LSFM creates synthetic images of digital fluorescent specimens that can resemble those generated by a real LSFM, as opposed to established visualization methods producing visually-plausible images. We also propose an accurate fluorescence rendering model which takes into account the intrinsic characteristics of fluorescent dyes to simulate the light interaction with fluorescent biological specimen.ResultsWe demonstrate first results of our visualization pipeline to a simplified brain tissue model reconstructed from the somatosensory cortex of a young rat. The modeling aspects of the LSFM units are qualitatively analysed, and the results of the fluorescence model were quantitatively validated against the fluorescence brightness equation and characteristic emission spectra of different fluorescent dyes.AMS subject classificationModelling and simulation

Reconstruction and visualization of large-scale volumetric models of neocortical circuits for physically-plausible in silico optical studies

“…The resolution of the largest dimension of each volume is set to 8000 voxels. The area covered by the orange box in ( e ) represents the maximum volumetric extent that could be simulated in similar previous studies [ 28 , 29 ] …”

“…Note that we only voxelize a fraction of neurons to be able to visualize the volume, but in principle the volumes were created for all the neurons composing the circuit. Referring to previous studies [ 28 , 29 ], the scalability concerns addressed in this work has allowed the computational neuroscientists to extend the scale of their simulations from the size of the box colored in orange in Fig. 6 to an entire slice.…”

“…Building volumetric models of cortical tissue has been addressed in recent studies for the purpose of simulating microscopic experiments. Abdellah et al have presented two computational methods for modeling fluorescence imaging with low- [ 16 , 28 ] and highly-scattering tissue models [ 29 ]. The extent of their volumetric models was limited to tiny blocks of the cortical circuitry in the order of tens to hundreds of cubic micrometers.…”

Assessing the imaging performance of light sheet microscopies in highly scattering tissues

“…al. on the development of a computational workflow for in-silico analysis of LSM for brain models [42]. The simulated images of this study were used to generate plots of image contrast (SBR) as a function of optical length, which highlights the achievable imaging depth in tissue for each microscope geometry.…”

Highlights from the 5th Symposium on Biological Data Visualization: Part 1

“…Finally, three papers are included from the imaging field. Topics range from image generation, as discussed by Abdellah et al [ 7 ], to a method for parameter optimization in image processing by Pretorius et al [ 9 ] (e.g. for cell nuclei detection and colour deconvolution for histology), and all the way to graph-based exploration of histology images in the GRAPHIE system proposed by Ding et al [ 8 ].…”