The spatiotemporal coverage of an imaging technology plays a key role in the information that can be acquired about the dynamic interactions within 3D biological systems or tissues. High-throughput cellular-resolution imaging with large volumetric coverage is desirable for many biological studies. This can be beneficial for studying collective (emergent) behavior of cell populations in both engineered biological systems and in vivo models of diseases. In many biological tissues, imaging depth is limited by optical scattering to the superficial layers that are within 1-2 mm of the tissue surface. Extending imaging depth into scattering biological samples and tissues can be considered one of the ‘grand challenges’ of optical microscopy.
From an imaging science perspective, we seek out new ways to integrate computational image formation and hardware adaptive optics (AO), in order to split the ‘work’ of image formation between computation and optical hardware and do better than each method alone. We developed hybrid adaptive optics (hyAO) to enhance volumetric throughput of optical coherence microscopy (OCM) by addressing both the resolution and signal-collection penalties suffered at away-from-focus depths. We have also utilized hyAO to suppress the effects of multiple scattering and speckle via aberration-diverse OCT, which acquires multiple measurements of the sample with different known aberration states (applied with hardware AO); after computational adaptive optics (CAO) correction of the known aberrations, ballistic scattered signals at each voxel in the image coherently add up in phase, whereas the multiply-scattered signals get randomized by the different interactions that each aberrated illumination beam has with the scattering medium.
High-throughput volumetric OCM of NIH-3T3 fibroblast cell population in Matrigel. Computed OCM enables volumetric microscopy at a 2-μm isotropic resolution over a 1-mm³ volumetric field-of-view, allowing minute-scale cellular dynamics to be captured at 3-minute temporal sampling.
- Leartprapun N., Adie S.G., “Resolution-enhanced OCT and expanded framework of information capacity and resolution in coherent imaging”, arXiv:2104.02531, 2021.
- Wu, M., Small, D.M., Nishimura, N., Adie, S.G. “Computed optical coherence microscopy of mouse brain ex vivo,” J. Biomed. Opt., 24(11) 116002, 2019.
- Liu S., Mulligan J.A., and Adie S.G., “Volumetric optical coherence microscopy with a high space-bandwidth-time product enabled by hybrid adaptive optics”, Biomedical Optics Express, 9(7):3137-3152, 2018. * Selected as Editor’s Pick, which serves to “highlight articles with excellent scientific quality and are representative of the work taking place in a specific field”.
- Liu S., Lamont M.R.E., Mulligan J.A., and Adie S.G., “Aberration-diverse optical coherence tomography for suppression of multiple scattering and speckle”, Biomedical Optics Express, 9(10):4919-4935, 2018. *Selected as Feature of The Week on the website OCT News, 29 September 2018.