B.S., Optoelectronics Engineering, Huazhong University of Science and Technology, Wuhan, China
Ph.D., Biomedical Engineering, University of Minnesota, Minneapolis, MN
I develop advanced optical imaging tools for brain imaging and apply them to understand brain structure and function. A brief introduction of previous projects:
a) Reconstructing white matter and vasculature network using label-free optical imaging
As the development of new methods that quickly discern brain structures and neural pathways becomes a pressing need, I work actively on optical techniques for visualizing and mapping the brain with intrinsic optical contrasts using PS-OCT at micrometer resolution. PS-OCT requires no histological staining or labeling, because the imaging contrasts originate from intrinsic optical properties of scattering and birefringence of fiber tracts. I developed serial PS-OCT to reconstruct white matter and vasculature connectivity of the brain (Liu et al., Neuroimage, 2021; Li, Liu and Akkin, Neurophotonics, 2019; Liu et al., Neurophotonics, 2017). The use of serial PS-OCT based on blockface imaging is a valuable tool to map the intricate fiber architecture and the white matter organization in the human brain. One advantage of serial PS-OCT is that it does not suffer from the nonlinear distortions plaguing slice-based histological techniques that demand a complex registration framework to correct. I also applied this methodology to quantify the white matter atrophy in a spinocerebellar ataxia type 1 mouse model at micrometer resolution for the first time (Liu et al., Neurobiol. Dis., 2018). I am currently further developing this approach to further understand the myelin degradation associated with vascular dysfunction in cerebral amyloid anigiopathy and Alzheimer's Disease Related Dementias.
b) Laminar difference in neurovascular coupling by multiphoton microscopy
The precise neuronal functional micro-architecture in the primary visual cortex (V1) of cats offers an ideal model system to examine laminar differences in stimulus selectivity across imaging modalities to further understand neurovascular coupling. However, the functional architecture of neurons and vessels in the deep cortical layers is unknown due to the lack of technology. I developed and optimized the performance of the state-of-the-art three-photon microscopy to image deeper into the brain (Farinella et al., Neurophotonics, 2021). Due to the lack of saucerful labeling of genetically encoded calcium indicators in layer 4 neurons, I also developed a bulk-loading approach in deeper cortical layers with synthetic calcium indicators (Liu et al., Sci. Rep., 2020). I further applied this technological development to understand the neurovascular coupling in cat V1. While comparing with fMRI, we examined arterial dilation and blood velocity responses to identical visual stimuli by using multiphoton imaging at the single-vessel resolution, which provided a measure of the hemodynamic signals of the highest spatial resolution (Cho et al., Neuroimage, 2022). Both fMRI and optical imaging revealed a laminar response pattern in which orientation selectivity in cortical layer 4 was significantly lower compared to layer 2/3. These new results are of paramount importance to the general community of neurobiology researchers relying on functional imaging tools to study the brain, and are particularly relevant for the rapidly increasing number of efforts attempting to use fMRI to study layer-specific brain function. The results are also of scientific interest for the general neuroscience community because very few studies have thus far examined how the sharpness of orientation tuning is distributed across cortical layers. I am currently continuing my research on the neovascular coupling of deep cortical layers in mice.
c) Cell migration in glioblastoma
Glioblastoma (GBM) remains one of the deadliest cancers. I have been working on various aspects of cell migration in GBM using optical imaging. Using a multimodal imaging approach (PS-OCT and confocal fluorescence microscopy) on human U251 glioma cell migration into mouse brain slices ex vivo, I studied the biophysical routes of glioma cell migration and found little correlation between white-matter-tract alignment and glioma cell migration, suggesting effective anti-invasive strategies will need to simultaneously limit parallel routes of both perivascular and televascular invasion through both gray and white matter (Liu et al., Biophy. J. 2019). Another signature of glioblastoma that might have clinical indication is the distinct molecular subtypes revealed by transcriptomic analyses. In another study, we showed the cell mechanics, invasiveness, and immune response differences in human and mouse GBM subtypes (Shamsan et al., under review). We showed while mesenchymal tumors are typically more invasive than proneural tumors, proneural tumors are associated with lower survival rates due to exclusion of immune cells and a "cold" immunological state by applying optical imaging, mathematical modeling, and transcriptional analysis. The data allowed for further understanding of the differences between GBM subtypes, particularly the migratory features of proneural vs. mesenchymal subtype, which can be used to strategize therapeutic approach in a personalized manner.