Neural Interface Research
Laboratory





Primary Projects

We aim to investigate the safety and efficacy of the neural interface device, such as retinal prostheses, using experimental animal models. In our group, we develop a multi-disciplinary platform across engineering and biomedical sciences using in vivo electrophysiological recording, and molecular techniques combined with neural signal processing and computer vision. We also aim to study the dynamics of the brain following retinal degeneration. Overall, we hope to devise meaningful and novel strategies in biomedical health sector particularly in the visual science communities.


Research image 1

Electrophysiological Study of Visual Implants

Collaborator: Dr. Tianzhun Wu (SIAT/BME)
Collaborator: Dr. Weibao Qiu (SIAT/BME)
Collaborator: Dr. Guoxing Wang (SJTU/Microelectronics)

Devices to electrically stimulate the retina have shown great promises to elicit visual percepts to patients suffered from a rare genetic eye condition called Retinitis Pigmentosa (RP). The green light from regulatory bodies for the two retinal implant devices (the Argus II Retinal Prosthesis System, Second Sight Medical Products, Inc.; and the Alpha IMS, Retinal Implant AG) gives hope to those blinded by RP. Much progress has been made from benchtop to bedside,


but the development towards a high resolution retina implant is still in its infant stage. Optimal stimulation strategy and competent conditions for therapeutic efficacy still remain an open question. The present study has systematically investigated the effect of stimulus pulse width, stimulus intensity, stimulus frequency on primary visual cortical (V1) response patterns. For each set of stimulus parameters, the V1 responses thresholds were mapped in space with respect to the stimulating electrode position. After the single electrode stimulation experiments, paired-pulse stimulation was performed to assess the spatial interaction dependent on stimulus intensity. The study of these spatial interactions will provide essential knowledge for developing high-resolution retinal implants.

References

• S. Agadagba, X. Li, L. L. H. Chan, "Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice," Frontiers in Neuroscience, 14:572299 (2020).

• H. Xie, C. H. Shek, Y. Wang, L. L. H. Chan, "Effect of interphase gap duration and stimulus rate on threshold of visual cortical neurons in the rat," 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 1817-1820 (2019).

• Q. Jiang, G. Li, H. Zhao, W. Sheng, L. Yue, M. Su, S. Weng, L. L.-H. Chan, Q. Zhou, M. S. Humayun, W. Qiu, H. Zheng, "Temporal Neuromodulation of Retinal Ganglion Cells by Low-frequency Focused Ultrasound Stimulation," IEEE Transactions on Neural Systems & Rehabilitation Engineering, 26(5), 969-976 (2018).

• M. Gao, Y. Yu, H. Zhao, G. Li, H. Jiang, C. Wang, F. Cai, L. L.-H. Chan, B. Chiu, W. Qian, W. Qiu, H. Zheng, "Simulation study of an ultrasound retinal prosthesis with a novel contact-lens array for noninvasive retinal stimulation," IEEE Transactions on Neural Systems & Rehabilitation Engineering, 25(9), 1605-1611 (2017).

• X. Sui, Y. Huang, F. Feng, C. Huang, L. L. H. Chan, G. Wang, "3D Finite Element Modeling of Epi-retinal Stimulation - Impact of Prosthetic Electrode Size and Distance from the Retina.," The International Journal of Artificial Organs, 38(5), 277-287 (2015).

• L. L. H. Chan, E.-J. Lee, M. S. Humayun, J. D. Weiland, "Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina," Journal of Neurophysiology, 105(6), 2687-97 (2011).

• A. Ray, L. L. Chan, Gonzalez A., M. S. Humayun, J. D. Weiland, "Impedance as a method to sense proximity at the electrode-retina interface," IEEE Trans Neural Syst Rehabil Eng, 19(6), 696-9 (2011).

• L. H. Chan, A. Ray, B. B. Thomas, M. S. Humayun, J. D. Weiland, "In vivo study of response threshold in retinal degenerate model at different degenerate stages," 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 1781-1784 (2008).

• A. Ray, L. Chan, B. Thomas, J. D. Weiland, "Effects of prolonged stimulation at the electrode-retina interface," 28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 1285-1287 (2006).


Research image 2

Visual cortex reorganization under retinal degeneration

Collaborator: Dr. Ke Chen (UESTC/BME)

The role of the dynamic nature of the brain is critical in the success of treatments aimed at restoring visions at the retinal level, such as bioelectronic implants and stem-cell therapy. Development of such approaches aims at treating the major blinding diseases such as retinitis pigmentosa caused by degeneration of photoreceptors, resulting in loss of visual inputs and remodeling of central nervous system circuitry. The success of these treatments highly relies on the functionality of the surviving neurons along the entire visual pathway. Hence, not only the but the visual cortex also plays an important role to allow patients suffering from retinal disease to perceive the fine details of a visual scene.

However, changes in sensory input can, over a period of time, alter receptive field and cortical topography. We aim to study the cortical reorganization after retinal degeneration by recording visual driven and spontaneous activity in the visual cortex of an animal model with rhodopsin mutation resembling the RP in humans (S334ter). We measured the orientation tuning, spatial and temporal frequency tunings and the receptive field size for V1 neurons from S334ter-3 rats and Long-Evans rats. V1 neurons in the S334ter-3 rats showed weaker orientation selectivity, lower optimal spatial and temporal frequency values and a smaller receptive field size compared to the LE rats. These results suggest that the visual cognitive ability significantly changes during retinal degeneration.

References

• K. Chen, B. Hou, Y. Zhao, P. Yuan, D. Yao, L. L. H. Chan, "Residual contrast response in primary visual cortex of rats with inherited retinal degeneration," Vision Research, 177: 6-11 (2020).

• B. Hou, K. Chen, Y. Zhao, L. L. H. Chan, "Variation in Spontaneous Activity and Visual Evoked Response in Primary Visual Cortex of the S334ter-3 Rats," International Conference on Energy, Environment and Bioengineerin (ICEEB), 185: 03034 (2020).

• Y. Wang, K. Chen, L. L. H. Chan, "Responsive neural activities in the primary visual cortex of retina-degenerated rats," Neuroscience, 383, 84-97 (2018).

• Y. Wang, K. Chen, L. L. H. Chan, "Information transmission in the primary visual cortex of retinal degenerated rats," 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 3632-3635 (2017).

• K. Chen, Y. Wang, X. Liang, Y. Zhang, T, K. Ng, L. L. H. Chan, "Electrophysiology alterations in primary visual cortex neurons of retinal degeneration (S334ter-line-3) rats," Scientific Reports, 6, 26793 (2016).

• Y. Wang, K. Chen, P. Xu, T. K. Ng, L. L. H. Chan, "Spontaneous neural activity in the primary visual cortex of retinal degenerated rats," Neuroscience Letters, 623, 42-46 (2016).

• A. Ray, G. J. Sun, L. Chan, N. M. Grzywacz, J. Weiland, E.-J. Lee, " Morphological alterations in retinal neurons in the S334ter-line3 transgenic rat," Cell Tissue Research , 339(3), 481-491 (2010).


Research image 3

Biological-inspired Computer Vision

Collaborator: Prof. Hong Yan (CITYU/EE)
Collaborator: Prof. Yongjie Li (UESTC/BME)

This project aims to design effective object proposal approaches for target detection. Feature-fusion approach is also used to improve the detection performance. We have applied these image processing techniques in night-time vehicle detection and multi-class fruit classification. For nighttime vehicle detection, we first improve the image quality via a multi-scale retinex (MSR) based image enhancement or a bio-inspired image enhancement approach,


and then accurate regions of interest (ROIs) are extracted via combining vehicle light detection and Edgeboxes or object proposal generation based on Bayes saliency, finally multiple features are fused using average accuracy contribution or weights learnt using linear SVM. For multi-class fruit detection, we design an image-region selection approach to select a set of optimal features, then current object proposals are improved using image region similarity to extract ROIs, finally five features are combined using learnt weights for detecting five classes of fruit. Experimental results demonstrate that our proposed nighttime vehicle detection approaches and multi-class fruit detection approach can detect objects accurately and are more effective than some state-of-the-art methods.

References

• H. Kuang, L. L. H. Chan, C. Liu and H. Yan, ""Feature Selection Based on Tensor Decomposition and Object Proposal for Night-Time Multiclass Vehicle Detection," ", IEEE Transactions on Systems, Man, and Cybernetics: Systems, 49(1), 71-80 (2019).

• Y. Duan, H. Kuang, W. Qiu, L. L. H. Chan, H. Yan, "Cascade feature selection and coarse-to-fine mechanism for nighttime multiclass vehicle detection," Journal of Electronic Imaging, 27(3), 033042 (2018).

• H. Kuang, C. Liu, L. L. H. Chan, H. Yan, "Multi-class fruit detection based on image region selection and improved object proposals," Neurocomputing, 283, 241-255 (2018).

• H. Kuang, K.-F. Yang, Y.-J. Li, L. L. H. Chan, H. Yan, "Bayes saliency based object proposal generator nighttime traffic images," IEEE Transactions on Intelligent Transportation Systems, 19(3), 814-825 (2018).

• H. Kuang, X. Zhang, Y.-J. Li, L. L. H. Chan, H. Yan, "Nighttime vehicle detection based on bio-inspired image enhancement and weighted score-level feature fusion," IEEE Transactions on Intelligent Transportation Systems, 18(4), 927-936 (2017).

• H. Kuang, L. Chen, F. Gu, J. Chen, L. L. H. Chan, H. Yan, "Combining region of interest extraction and image enhancement for nighttime vehicle detection," IEEE Intelligent Systems, 31(3), 57-65 (2016).

• H. Kuang, L. L. H. Chan, C. Liu, H. Yan, "Fruit classification based on weighted score-level feature fusion," Journal of Electronic Imaging, 25(1), 013009 (2016).

• H. Kuang, L. L. H. Chan, H. Yan, "Multi-class fruit detection based on multiple color channels," International Conference on Wavelet Analysis and Pattern Recognition (2015).


Other Projects
Research image 4

Fabrication of nanostructure electrode for neural stimulation

Collaborator: Prof. Amine Bermak (HKUST/ECE)
Collaborator: Prof. Stella Pang (CITYU/EE)
Collaborator: Dr. Johnny Ho (CITYU/AP)

Long-lasting functional materials are the key to achieving effective neural implants. These neural interfaces modulate neural behavior by stimulating neurons using implanted electrodes. Among all neural prostheses, retinal implants have been among the few that have gained market approval in recent years. Thus, over the past years, the development of a high-resolution retinal implant has become a paramount goal among researchers, with various studies proposing novel electrodes with high charge injection capacity and three-dimensional structures.

Since the charge injection limit of traditional electrodes is low, much effort has been expended to modify the surface of neural electrodes with different coatings. However, the gradual delamination and degradation of such coatings make them difficult to use for long-term applications. In search of new electrode materials, a growing number of researchers have recognized the potential of nanotechnology for neural interfacing. In the past decade, emerging nanomaterials, such as nanostructured conducting polymers and carbon nanotubes, have been utilized to improve the efficacy and safety of neural electrodes. Graphene and silicon nanostructures are two other nanomaterials that hold promise as neural electrode materials. We aim to fabricate neural stimulating electrode using carbon nanotubes and graphene nanostructures. In vitro biocompatibility and stimulation efficacy of microelectrodes will be determined afterwards.

References

• L. U. Vinzons, L. Shu, S. P. Yip, C.-Y. Wong, L. L. H. Chan, J. C. Ho, "Unraveling the morphological evolution and etching kinetics of porous silicon nanowires during metal-assisted chemical etching," Nanoscale Research Letters, 12:385 (2017).

• J. Wang, H. Xie, T. Chung, L. L. H. Chan, S. W. Pang, "Neural probes with integrated temperature sensors for monitoring retina and brain implantation and stimulation," IEEE Transactions on Neural Systems and Rehabilitation Engineering, 25(9), 1663-1673 (2017).

• H. Xu, L. L. H. Chan, A. Bermak, "Novel structure of carbon nanotube micro electrode for high-resolution stimulation of neurons," 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 6170-6173 (2016).

• A. Khalifa, Z. Gao, A. Bermak, Y. Wang, L. L. H. Chan, "A Novel Method for the Fabrication of a High-Density Carbon Nanotube Microelectrode Array," Sensing and BioSensing Research, 5, 1-7 (2015).


Research image 5

Study of power transfer efficiency under coil misalignment in biomedical applications

Collaborator: Prof. Henry Chung (CITYU/EE)

It is sometimes unavoidable to use loosely coupled coils in applications, like biomedical devices, for transferring electric energy wirelessly. However, coil misalignment causes degradation of the power transfer efficiency. It is well known that the power transfer efficiency of classical parallel coils is primarily determined by the quality factors of the coils and the coupling coefficient between the coils,


and is maximized by choosing an optimal turns-ratio between the coils. Changing the number of turns of the coils cannot effectively overcome such misalignment effect. We aim to study a structure that comprises two orthogonally placed windings for lessening the variation of the coupling coefficient due to the coil misalignment. An experimental prototype has been built and evaluated on a test bed, which allows different degrees of lateral and angular misalignments. Results reveal that the proposed structure can effectively increase the minimum efficiency zone, allowing more lateral and angular misalignments. These investigations lay the foundation for future understanding more complex loosely coupled winding structures.

References

• J. P.-W. Chow, H. S.-H. Chung, L. L.-H. Chan, R. Shen, S. C. Tang, "Optimal Design and Experimental Assessment of a Wireless Power Transfer System for Home-Cage Monitoring," IEEE Transactions on Power Electronics, 34(10), 9779-9793 (2019).

• J. P. W. Chow, H. S. H. Chung, L. L. H. Chan, N. J. McDannold, S. C. Tang, "Design of wireless power transfer system for devices carried by a freely moving animal in cage," IEEE Energy Conversion Congress and Exposition (ECCE), 4398-4405 (2017).

• J. P. W. Chow, H. S. H. Chung, C. S. Cheng, A. Gungor, S. C. Tang, L. L. H. Chan, "Modeling and experimentation of loosely-coupled coils with transmitter having orthogonally-placed windings," IEEE Energy Conversion Congress and Exposition (ECCE), 4927-4934 (2015).

• J. P. W. Chow, N. Chen, H. S. H. Chung, L. L. H. Chan, "An investigation into the use of orthogonal winding in loosely coupled link for improving power transfer efficiency under coil misalignment," IEEE Transactions on Power Electronics, 30(10), 5632-5649 (2015).

• J. P. W. Chow, H. S. H. Chung, C. S. Cheng, A. Gungor, S.C. Tang, L. L. H. Chan, "Modeling and experimentation of misalignment-tolerable loosely-coupled coils with transmitter having orthogonal windings," IEEE Energy Conversion Congress and Exposition (ECCE), 4927-4934 (2015).

• J. P. W. Chow, N. Chen, H. S. H. Chung, L. L. H. Chan, "Modeling and experimentation of misalignment-tolerable loosely-coupled coil structure," IEEE Energy Conversion Congress and Exposition (ECCE), 5429-5436 (2014).

• J. P. W. Chow, N. Chen, H. S. H. Chung, L. L. H. Chan, "Misalignment tolerable coil structure for biomedical applications with wireless power transfer," 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 775-778 (2013).


On-going research projects
  • "Aperiodic Stimulation Patterns for Visual Implants"
    General Research Fund 2019/20, Hong Kong Research Grants Council, PI
  • "Pre-Clinical Studies of High Performance Flexible Micro Electrode Arrays for Artificial Retina"
    Guangdong - Hong Kong Technology Cooperation Funding Scheme 2018/19, Innovation and Technology Fund, PI
  • "Functional and Behavioral Changes Induced by Retinal Electrical Stimulation in Experimental Animal Models of Retinal Degeneration"
    General Research Fund 2018/19, Hong Kong Research Grants Council, PI

Completed research projects
  • "Flexible carbon nanotube microelectrode array for stimulation of retinal tissue"
    General Research Fund 2014/15, Hong Kong Research Grants Council, PI
  • "Visual cortex reorganization in animal model of retinal degeneration"
    General Research Fund 2013/14, Hong Kong Research Grants Council, PI
  • "Study of response to electrical stimulation in the development of high resolution retinal implant"
    Early Career Scheme 2012/13, Hong Kong Research Grants Council, PI