Brainsmatics - Deciphering genetically defined cell types and connectome with brain-wide positioning system
Huazhong University of Science and Technology
Wuhan National Laboratory for Optoelectronics
Deciphering the fine morphology and precisely positioning the neurons and neural circuits are crucial to enhance our understanding of brain function and diseases. Traditionally, we have to map brain images to coarse axial-sampling planar reference atlases to orient neural structures, which might fail to orient neural projections at single-cell resolution due to position errors resulting from individual differences at the cellular level. In last one and half decade, my lab developed a Micro-Optical Sectioning Tomography (MOST) and several types of fluorescence MOST (fMOST), which is a novel combination of the microscopic optical imaging and the physical sectioning to obtain the tomographic information of a whole brain with sub-micron voxel resolution. In the first part of my talk, I will introduce the principles of Brain-wide Positioning Systems (BPS) which refers to MOST/fMOST serial techniques. In the second part of my talk, I will demonstrate how to brain-widely position the labelled neurons and neuronal networks, including whole-brain samples preparing, whole-brain optical imaging as well as massive brain-image processing and analyzing. The unique features of BPS include 1) robust absorption/fluorescence imaging, 2) multi-color imaging, 3) submicron voxel resolution for a single cm-size whole mouse brain, 4) automatic in sectioning, imaging and data acquisition, 5) no registration needed for 3-D imaging, 6) extensible for 3-D large scale imaging, potentially to 10´10´10 cm3. Based on BPS, we have acquired the first 3D structure atlas of whole mouse brain at single-neuron resolution; achieved tracing axonal pathways in the mouse brain without interruption for the first time; firstly dissected neural structures with anatomical annotation at single-neuron resolution; revealed the mechanism of fluorescent signal change in resin-embedded sample; realized the automatic tracing and reconstruction of neuronal populations with dense dendrites. We propose a new term: BRAINSMATICS, which refers to the integrated, systematic approach of measuring, analyzing, managing and displaying brain spatial data with unprecedented single-neuron resolution. The serial BPS have the advantages of high resolution, high throughput and long-time stability. With the brain-spatial information of neuron types, neural circuits, vascular networks and 3D fine brain atlas, we believe that brainsmatics makes it possible to better decipher genetically defined cell types and connectome.
Dr. Qingming Luo is the Vice-President of Huazhong University of Science and Technology (HUST) and Director of Wuhan National Laboratory for Optoelectronics. He is an elected Fellow of The American Institute for Medical and Biological Engineering (AIMBE), The International Society for Optics and Photonics (SPIE), The Institution of Engineering and Technology (IET), The Optical Society (OSA) and Chinese Optical Society (COS).
He is the founder of HUST-Suzhou Institute for Brainsmatics. His research interests focus primarily on multi-scale optical bioimaging and cross-level information integration. Since 1996, he has been devoted to new techniques and novel applications in life sciences, including laser speckle imaging (LSI) and combination with optical intrinsic signal imaging (ISI), small animal imaging of fluorescence diffusion optical tomography (fDOT) coregistered with micro-CT, micro-optical sectioning tomography (MOST), and functional near infrared (NIR) imaging. He is currently leading the project Visible Brain-wide Networks at single-neuron resolution and the Chief Scientist of National Major Scientific Instruments & Equipment’s Development Project “Instrument Development and Application Demonstration of the Micro-Optical Sectioning Tomography System”. He created “the most detailed three-dimensional map of all the connections between the neurons in a complete mouse brain” and “demonstrated the first long-range tracing of individual axons in the mouse brain”.
Dr. Luo holds 80 patents and has co-authored more than 200 papers in peer-reviewed journal, including Science, Nature Cell Biology, Nature Communications, PNAS, Optics Letters, Optics Express and Journal of Biomedical Optics. He won the Cheung Kong Professorship of Ministry of Education of China in 1999, the National Science Fund for Distinguished Young Scholars in 2000, the second-place prize in State Natural Sciences Award in 2010, China’s Top Ten Major Scientific Progress, and the second-place prize in State Technological Invention Award in 2014.