Extreme Neurophotonics

Biomedical Photonics and Extreme Neurophotonics

Nano Bio-photonics Lab., led by Prof. Chi-Kuang Sun, College of Electrical Engineering and Computer Science, National Taiwan University, is dedicated to development of novel opto-electro-mechanical designs for the advancement of nonlinear optical microscopy (NLOM) technology. Our lab is equipped with multiple femtosecond lasers, and a single laser-based multi-wavelength excitation source for multicolor NLOM imaging. Our lab for the first time in Taiwan fully indigenously developed an industry leading NLOM technology with our proprietary opto-electro-mechanical designs together with a custom C++ written All in One software package, which for the first time enables a >1 mm-wide field of view with a <500 nm digital resolution, while utilizing a fast resonant-scanning. With our developed technology our lab is actively conducting several high impact studies, such as, but not limited to, rapid human brain tumor/cancer assessment, human- and/or animal-based Alzheimer disease (AD) assessment, animal-brain high-resolution 3D mapping, next generation rapid digital biopsy, etc. Apart from such core biological applications, our lab parallelly continues to develop various proprietary GPU-accelerated software algorithms, such as, but not limited to, rapid high-frequency noise suppression, rapid ultra-wide dynamic range compression, rapid optics-induced distortion correction,  rapid artifact-free digital image stitching operations, etc. Our lab has been continuously publishing important scientific journal papers, as well as filing international patents with our excellent research achievements.

Two-dimensional representation of a laser-scanning two-photon-excited Nav1.8-tdTomato positive mouse brain medulla tissue scanned with Nyquist-exceeding voxel size, being provided with color-coded depth information (Borah et al., 2021).

One critical application of our NLOM development is deep brain imaging. Neuronal microcircuits and structures are the primary mediators of the diverse functions of brain, involving movement to cognitive processes. Unraveling the neuronal circuitry and connectome will pave the way for new diagnostics and therapeutics for neuronal disorders. Neuronal connections, consisting of billions of neurons, transmit and receive electrochemical information via action potential, with millisecond kinetics. To decipher the neuronal activity and connections in the deep brain, 5 mm below the cortical surface, gradient refractive lens (GRIN) is currently incorporated into our NLOM system to be capable of scanning at 2000 frames per second to image the fast kinetics of voltage signaling. We are mapping the microcircuits and connectomics in Aromatic L-amino acid decarboxylase (AADC) deficiency mice as well as suprachiasmatic nucleus (SCN), the principal circadian clock of the brain, at hypothalamus. By visualizing the firing pattern of dopaminergic neurons in the substantia nigra compacta (SNc) and cellular plasticity, the repercussion of gene therapy in alleviating the AADC deficiency will be addressed. Furthermore, coupling of neurons in SCN will be mapped to understand how signal travels during circadian cycle.

Reference

B. Borah, J.-C. Lee, H.-H. Chi, Y.-T. Hsiao, C.-T. Yen, and C.-K. Sun, “Nyquist-exceeding High-voxel-rate Acquisition in Mesoscopic Multiphoton Microscopy for Full-field Sub-micron Resolution Resolvability,” iScience 24 (9), 103041 (2021).