I am working on breaking the limitations of traditional biomedical imaging in tomography and microscopy applications, by inspiring from the optical and mathematical methodologies, depending on the interdisciplinary knowledges, integrating Photo-Electro-Mechanical instruments, and creating the leading imaging techniques and prototype systems.

By collaborating with Prof. Ming Jiang and other excellent colleagues in different departments of Peking University, my most significant research works and contributions are in the following aspects.

[Multi-modality Tomography]

Since 2009, I have developed an X-ray computed tomography(XCT) system based on a commercial digital radiography(DR) system. By implementing automatic scanning mechanism, performing geometric alignment and calibration, manipulating devices in programmed GUI and fabricating physical phantoms, the complete projection data have been acquired and reconstructed to validate our XCT algorithm under the two-circles-plus-one-line trajectory, which is applied to the limited space scanning XCT. This work has been applied for Chinese Invention Patent and published in Physics in Medicine and Biology:

• Heng Mao, Jiansheng Yang, Yanbin Lu, Yuanzheng Si, Yu Zhou, John W. Emerson, Tie Zhou, Ming Jiang, A Multimodality in vivo Tomographic Imaging System, Invention, No.201010299375.4, licensing date Jun 13, 2012.

• Yanbin Lu, Jiansheng Yang, John W Emerson, Heng Mao, Tie Zhou, Yuanzheng Si, Ming Jiang, Cone-beam reconstruction for the two-circles-plus-one-line trajectory, Physics in Medicine and Biology 57(9): 2689 - 2707, 2012. Download

Meantime, I have proposed a generalized hybrid algorithm for Bioluminescence tomography (BLT) based on graph cuts and gradient-based algorithms. In this hybrid algorithm, the graph cuts algorithm is adopted to estimate a reliable source support without prior knowledge, which gets rid of the support assumption required in other reported BLT algorithms and remarkably enhances the stability of reconstruction. This work has been published in Biomedical Optics Express:

• Shengkun Shi, Heng Mao*, A generalized hybrid algorithm for bioluminescence tomography, Biomedical Optics Express 4(5): 709-724, 2013. Download

In the last two years, funded by the Sino-German Center and working with collaborators, we are working on multi-modality joint reconstruction theory and algorithm for XCT, DOT(Diffuse Optical Tomography) and BLT. In this project, I have already implemented a proof-of-principle DOT system which could quantitatively measure the power, position and direction of NIR narrow beam on surface of phantom. That would be the crucial factor for multi-modality joint reconstruction in eliminating the unknown differences between physical system and diffusion model approximated from the radiative transfer equation (RTE). Please refer to my other pages for more details.

Key words: X-ray Computed Tomography, Bioluminescence tomography, Diffuse Optical Tomography, Multi-modality Imaging, Multi-modality joint Reconstruction.

Collaborators: Alfred K. Louis, Saarland University; Peter Maaß, University of Bremen; Ming Jiang, Peking University;Xiaoqun Zhang, Shanghai Jiao Tong University.

[Large FOV Gigapixel Photography]

Since 2014, I have been building an alternative gigapixel camera prototype in outer-path chip mosaic, which covers the Full Frame FOV (15.6×10.5 degree, 36×24mm) within almost 0.2 Gigapixel and up to 24Hz video output. Comparing with the gigapixel camera in inner-path chip mosaic, our prototype has such advantages in compactness, low complexity, simplicity in optical design and flexibility for specific applications, by integrating all bare CMOS chips on four PCB boards to get rid of bulky chip packagings, employing four high quality commercial lenses for simplifying the outer-path mosaic optical system, and executing online computational imaging for real-time image mosaic within single pixel accuracy. This new concept gigapixel camera would has great potentials in Remote Sensing and On-line Surveillance. This work has been applied for Chinese Invention Patent:

• Huizhu Jia, Heng Mao, Xiange Wen, Rui Chen, Xiaodong Xie, Wen Gao, A Large FOV Gigapixel Remote Camera and Imaging Method, Invention, No.201610773148.8, Application Date 08/30/2016.

In the computational imaging, basing on parameters calibration and model estimation, the vignetting distribution and relative positioning errors of each chip, including rotation errors, tip/tilt errors, scaling errors, and displacement errors, are updated frame by frame so that 8-axis translation stages could compensate the non-negligible chip displacements and post-processing could correct the residual errors and complete the on-line 2D image mosaic. Please refer to my other pages for the parameters calibration and on-line computation.

Key words: Large FOV, Gigapixel Camera, Multi-axis Alignment and Calibration, Computational Imaging.

Collaborators: Wen Gao, Xiaodong Xie, Huizhu Jia, and Xiange Wen, NELVT, EECS, PKU

[in vivo Tracking Microscopy]

Since 2012, funded by the National Natural Science Foundation of China(NSFC), I have been a Principal Investigator and fully developing a high spatio-temporal resolution real-time tracking fluorescent Microscope for the interested neural circuits of freely moving Caenorhabditis elegans. Other than reported worm tracking microscopies in the world, I dedicate to track a real freely moving C. elegans on the agar substrate without any constraints, even a coverslip. Due to the high requirements in sub-pixel position accuracy, more than 10Hz closed loop and less than 2 microns depth of field(DOF), this becomes a very challenging motion tracking problem.

For the worm ROI tracking calculation, I have modified a high efficient worm centerline localization algorithm based on distance metric and skeletonization. In addition, another optimization based centerline localization algorithm has been proposed and validated in practice. This work has been published in SCIENTIA SINICA: Mathematica:

• Heng Mao, Xuancheng Li, Haiwen Li, Louis Tao, Tie Zhou*, Active Contour Model based centerline tracking algorithm for freely moving Caenorhabditis elegans, SCIENTIA SINICA: Mathematica, 46(7), 2016.

For the worm ROI tracking control, I have presented a hierarchical control and tracking strategy based on 2-axis piezo stage. This strategy consists of the basic level for single motion step and high level for motion tracking loops. In the basic level, a closed-loop model for motion response of each piezo axis has been characterized, and a look-up table of optimized PID parameters in different axes, different positions and different steps has been established for real-time control. In the upper level, variable metric based tracking loop has been given to enhance the execution efficiency and adaptivity. The experiment results have demonstrated less than one pixel (~5μm) tracking errors existed in each tracking loop except the motion increment. This work has been submitted to Biomedical Optics Express:

• Haiwen Li, Liang Shan, Shuxiang Dong, Louis Tao, Heng Mao*, Real-time Motion Tracking of Freely Moving Caenorhabditis elegans via 2-axis Piezo-stage, 2016. Download

For the worm calcium imaging, by adopting a two-axis galvo scanner and multiplexing method, the frame rate of calcium imaging would be raised to 400Hz. Moreover, by introducing the Adaptive Optics technique to correct low-order aberrations through the entire optical system, the effective spatial resolution of our microscope could achieve to less than 500nm under the 20X 0.7NA objective without immersion and coverglass. This systematic innovation has been applied for Chinese Invention Patent:

• Heng Mao, Louis Tao, Han Qiao, Xuancheng Li, Ming Jiang, A Real-time Tracking System for Neural Circuit of Caenorhabditis elegans, Invention, No.201410117593.X, Licensing Date 08/31/2016.
• Heng Mao, Louis Tao, Ming Jiang, A Neural Circuit in vivo Imaging System, Invention, No.201310255101.9, Licensing Date 03/16/2016.

High resolution worm tracking videos both in behavior and neuronal calcium indication have been simultaneously recorded. Depending on this desired microscope, we are turning into the biological researches about C. elegans behavior and neural activities in different sensory mechanisms. Please refer to my other pages for more details.

Key words: Caenorhabditis elegans, ROI Tracking, Pan-Neuronal Calcium Imaging, Neural Circuit Modeling.

Collaborators: Louis Tao and Dong Liu, SLS, PKU

[2-photon Lightsheet Microscopy]

In order to improve the two-photon three-axis digitally scanning light-sheet microscope (2P3A-DSLM) to image into the dense, deep, and scattering biological specimen, I proposed to attempt dual-layer adaptive optics (AO) wavefront sensing (WFS) and compensation (WFC) technique to correct space-variant point spread functions over wide FOV. This systematic innovation has been applied for Chinese Invention Patent:

• Heng Mao, Louis Tao, Ming Jiang, Liangyi Chen, Haiwen Li, Jie An, Weijian Zong, A High Spatio-temporal Resolution Light Sheet Fluorescence Microscope and Imaging Method, Invention, No.201510683873.1, Application Date 10/20/2015.

Recently, we are working on the system implementation and WFS algorithm.

Key words: 3D Volumetric Imaging, Deep Tissue Imaging, Adaptive Optics, High Spatio-temporal Resolution

Collaborators: Liangyi Chen, IMM, PKU

1. Haiwen Li, Fan Feng, Muyue Zhai, Jiazhi Zhang, Jingyuan Jiang, Yifan Su, Liangyi Chen, Shangbang Gao*, Louis Tao*, Heng Mao*, Fast whole-body motor neuron calcium imaging of freely moving Caenorhabditis elegans without coverslip pressed, Cytometry Part A, 99(11):1143-1157, 2021.
2. Yanquan Mo, Fan Feng, Heng Mao, Junchao Fan* and Liangyi Chen*, Structured illumination microscopy artefacts caused by illumination scattering, Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences, 2021, 379(2199):20200153.
3. Zhe Zhang, Dongzhou Gou, Fan Feng, Ruyi Zheng, Ke Du, Hongrun Yang, Guangyi Zhang, Huitao Zhang, Louis Tao, Liangyi Chen*, Heng Mao*, 3D Hessian deconvolution of thick light-sheet z-stacks for high-contrast and high-SNR volumetric imaging, Photonics Research, 2020, 8(6):1011.
4. Dashan Dong, Xiaoshuai Huang, Liuju Li, Heng Mao, Yanquan Mo, Guangyi Zhang, Zhe Zhang, Jiayu Shen, Wei Liu, Zeming Wu, Guanghui Liu, Yanmei Liu, Hong Yang, Qihuang Gong, Kebin Shi*, Liangyi Chen*. Super-resolution fluorescence-assisted diffraction computational tomography reveals the three-dimensional landscape of the cellular organelle interactome, Light: Science & Applications , 9(1):1-15, 2020.
5. Heng Mao*, Jie He, Jiazhi Zhang, Yuanchao Bai, Muyue Zhai, Haiwen Li, Xiange Wen, Rui Chen, Huizhu Jia, Louis Tao, and Ming Jiang, High Cost-efficient and Computational Gigapixel Video Camera Based on Commercial Lenses and CMOS Chips, Applied Optics, 57(29), 2018.
6. Muyue Zhai, Haiwen Li, Jiazhi Zhang, Louis Tao, Shanshan Wang*, Heng Mao*, Temporal multiplexing of the scientific grade camera for hyper-frame-rate imaging, Optics Express, 26(16), 2018.
7. Xiaoshuai Huang, Junchao Fan, Liuju Li, Haosen Liu, Runlong Wu, Yi Wu, Lisi Wei, Heng Mao, Amit Lal, Peng Xi, Liqiang Tang, Yunfeng Zhang, Yanmei Liu,Shan Tan*, Liangyi Chen*, Fast, long-term super-resolution imaging with Hessian structured illumination microscopy, Nature Biotechnology, 4115, 2018.
8. Mengdi Zhao, Jie An, Haiwen Li, Jiazhi Zhang, Shang-Tong Li, Xue-Mei Li, Meng-Qiu Dong, Heng Mao*, Louis Tao*, Segmentation and classification of two-channel C. elegans nucleus-labeled fluorescence images, BMC Bioinformatics, 18:412, 2017.
9. Caihua Zhang, Zhiwei Zhao, Liangyi Chen, Zhaoliang Cao*, Heng Mao*, Application of adaptive optics in biological fluorescent microscopy, SCIENTIA SINICA: Physica, Mechanica & Astronomica, 47(1), 2017.
10. Heng Mao, Louis Tao, Liangyi Chen, Application and development of Adaptive Optics to three-dimensional in vivo deep tissue fluorescent microscopy, Infrared and Laser Engineering, 45(6), 2016.
11. Heng Mao, Xuancheng Li, Haiwen Li, Louis Tao, Tie Zhou*, Active Contour Model based centerline tracking algorithm for freely moving Caenorhabditis elegans, SCIENTIA SINICA: Mathematica, 46(7), 2016.
12. Shengkun Shi, Heng Mao*, A generalized hybrid algorithm for bioluminescence tomography, Biomedical Optics Express 4(5): 709-724, 2013.
13. Yanbin Lu, Jiansheng Yang, John W Emerson, Heng Mao, Tie Zhou, Yuanzheng Si, Ming Jiang,Cone-beam reconstruction for the two-circles-plus-one-line trajectory, Physics in Medicine and Biology 57(9): 2689 - 2707, 2012.
14. Yuanzheng Si, Heng Mao, Bin Zhang, and Ming Jiang, Diffusive reflectance for the free-space light propagation theory, Applied Physics Letters 96, 013702, 2010.
15. Heng Mao, and Dazun Zhao, Alternative Phase-Diverse Phase Retrieval algorithm based on Levenberg-Marquardt nonlinear optimization, Optics Express 17(6), 4540-4552, 2009.
16. Heng Mao, Xiao Wang, and Dazun Zhao, Application of Phase-Diverse Phase Retrieval to wavefront sensing in non-connected complicated pupil optics, Chinese Optics Letters 5(7) , 397-399, 2007.
17. Heng Mao, Xiao Wang, Dazun Zhao, Phase Retrieval Algorithm and Experimental Validation of Complicated Pupil Wavefront, Acta Optica Sinica 29(3), 575-581, 2009.
18. Heng Mao, Dazun Zhao, Xinqi Hu, Methods for Increasing the Wavefront Detection SNR Based on Extended-Beacon, Transactions of Beijing Institute of Technology 26(5), 2006.

1. Di He, Jie He, Heng Mao, Phantom Preparation and Optical Property Determination, Oral Presentation, International Conference on Sensing and Imaging(ICSI), Chengdu, 2017.
2. Jiazhi Zhang, Jie He, Haiwen Li, Yuanchao Bai, Huizhu Jia, Louis Tao, Heng Mao, Computational Calibration and Correction for Gigapixel Imaging System, Oral Presentation, International Conference on Sensing and Imaging(ICSI), Chengdu, 2017.
3. Muyue Zhai, Xiaoshuai Huang, Heng Mao, Shanshan Wang, Qiudong Zhu, Using Electrically Tunable Lens to Improve Axial Resolution and Imaging Field in Light Sheet Fluorescence Microscope, Oral Presentation, International Conference on Sensing and Imaging(ICSI), Chengdu, 2017.
4. Haiwen Li, Liang Shan, Shuxiang Dong, Louis Tao, Heng Mao, Adaptive PID control of two-axis piezo-stage for real-time tracking freely moving Caenorhabditis elegans, Oral Presentation, International Conference on Sensing and Imaging(ICSI), Taiyuan, 2016.
5. Mengdi Zhao, Jie An, Haiwen Li, Shangtong Li, Mengqiu Dong, Heng Mao, Louis Tao, Segmentation and classification of the Caenorhabditis elegans nucleus-labeled images from spinning disk confocal microscope, Oral Presentation, International Conference on Sensing and Imaging(ICSI), Taiyuan, 2016.
6. Jie An, Dashan Dong, Kebin Shi, Liangyi Chen, Louis Tao, Heng Mao, 3D refraction index reconstruction algorithm on optical diffraction tomography microscope, Oral Presentation, International Conference on Sensing and Imaging(ICSI), Taiyuan, 2016.
7. Yanbin Lu, Heng Mao, Jiansheng Yang and Ming Jiang, Calibration methods for an x-ray cone-beam CT system, Oral Presentation, 13th International Congress of Stereology, Beijing, 2011.
8. Heng Mao, Xiao Wang, and Dazun Zhao, Phase Retrieval based wavefront sensing experimental implementation and wavefront sensing accuracy calibration, Oral Presentation, SPIE 7283, Chengdu, 2009.
9. Heng Mao, Xiao Wang, and Dazun Zhao, Modified wavefront sensing and correction methodology for active segment mirror of large space telescope, Oral Presentation, OSA’s 92nd Annual Meeting, OSA Technical Digest, Rochester, 2008.
10. Heng Mao, Xiao Wang, and Dazun Zhao, Hybrid Phase-Diverse Phase Retrieval algorithm in wavefront sensing for segmented optics, Oral Presentation, SPIE 6624, Beijing, 2007.

1. Heng Mao, Guangyi Zhang, Liangyi Chen, Compound reconstruction and its acceleration method of light-field microscopy, Invention, No.201911227287.0, Licensing Date 06/23/2020.
2. Huitao Zhang, Yining Zhu, Peng Zhang, Heng Mao, A distributed and cascading Micro-CT System, Invention, No.201810833310.X, Application Date 07/26/2018.
3. Heng Mao, Louis Tao, Muyue Zhai, Jiazhi Zhang, Liang Shan, Haiwen Li, An exposure control method for the TDI camera under the non-uniform velocity scanning, Invention, No.201810634090.8, Application Date 06/20/2018.
4. Heng Mao, Louis Tao, Muyue Zhai, Jiazhi Zhang, Liang Shan, Haiwen Li, A High-speed, High-content Morphological Testing System for in-vivo Small-size Specimen, Invention, No.201810397730.8, Application Date 04/28/2018.
5. Heng Mao, Louis Tao, Muyue Zhai, Jiazhi Zhang, Liang Shan, Haiwen Li, A High-speed, High-content Morphological Testing System for in-vivo Small-size Specimen, Utility Model, No.201820626896.8, Licensing Date 12/04/2018.
6. Heng Mao, Louis Tao, Jiazhi Zhang, Muyue Zhai, Liang Shan, Haiwen Li, A Separating and Distributed Object-side Scanning System, Invention, No.201810383832.4, Licensing Date 07/04/2019.
7. Yining Zhu, Heng Mao, Muyue Zhai, Huitao Zhang, Yong Wei, Peng Fu, A Super-resolution Micro-CT System and Imaging Method, Invention, No.201711009477.6, Application Date 10/25/2017.
8. Heng Mao, High-throughput, High-content, Parallel Imaging and Screening System for Cell Microarray, Invention, No.201710366402.7, Licensing Date 05/07/2019.
9. Heng Mao, Shuang Wen, Ming Jiang, An Electron Microscope based Tomography System and Imaging Method, Invention, No.201611207099.8, Licensing Date 03/19/2019.
10. Huizhu Jia, Heng Mao, Xiange Wen, Rui Chen, Xiaodong Xie, Wen Gao, A Large FOV Gigapixel Remote Camera and Imaging Method, Invention, No.201610773148.8, Licensing Date 02/21/2019.
11. Heng Mao, Louis Tao, Ming Jiang, Liangyi Chen, Haiwen Li, Jie An, Weijian Zong, A High Spatio-temporal Resolution Light Sheet Fluorescence Microscope and Imaging Method, Invention, No.201510683873.1, Licensing Date 12/04/2017.
12. Heng Mao, Louis Tao, Han Qiao, Xuancheng Li, Ming Jiang, A Real-time Tracking System for Neural Circuit of Caenorhabditis elegans, Invention, No.201410117593.X, Licensing Date 10/12/2016.
13. Heng Mao, Louis Tao, Ming Jiang, A Neural Circuit in vivo Imaging System, Invention, No.201310255101.9, Licensing Date 03/16/2016.
14. Heng Mao, Louis Tao, Ming Jiang, A Neural Circuit in vivo Imaging System, Utility Model, No.201320368802.9, Licensing Date 11/27/2013.
15. Heng Mao, Jiansheng Yang, Yanbin Lu, Yuanzheng Si, Yu Zhou, John W Emerson, Tie Zhou, Ming Jiang, A Multimodality in vivo Tomographic Imaging System, Invention, No.201010299375.4, Licensing Date 06/13/2012.
16. Dazun Zhao, Xiao Wang, Heng Mao, Xin Wang, Xinqi Hu, Qiudong Zhu, Xin Yu, An Aberration Sensing System for Surface Errors of Primary Mirror in the Space Telescope, Invention, No.200810057446.2, Licensing Date 11/25/2009.

1. Heng Mao, Louis Tao, 2016SR173013, 2D Real-time Tracking System for Neural Circuit of Caenorhabditis elegans, Peking University, V1.0, Licensing Date 07/08/2016.
2. Heng Mao, Louis Tao, 2016SR347917, Multi-Source, Multi-camera and Multi-axis Control and High Speed Synchronized Imaging System, Peking University, Multi-SOCAS, V1.0, Licensing Date 12/01/2016.