Kai-Hsiang Chuang received his PhD on biomedical engineering from the National Taiwan University, Taipei, Taiwan (2001). He then worked as an associated MRI scientist in the Department of Radiology, Veterans General Hospital, Kaohsiung, Taiwan (2002-2003). He joined Dr. Alan P. Koretsky’s laboratory at the National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland, USA in 2003. In this period, he focused on contrast agents for molecular imaging of neuronal activity, connectivity and metabolism in small animals. He moved to Singapore in 2008 as the head of the MRI group in the Singapore Bioimaging Consortium, A*STAR, where he established the first preclinical imaging facility in Singapore and worked closely with academic and pharmaceutical partners on the development and application of functional, molecular and multimodality imaging in mouse models of neurodegeneration, cancer, metabolic diseases for understanding pathophysiology and drug development. As a joint faculty at the Clinical Imaging Research Centre and adjunct associate professor at the Department of Physiology, National University of Singapore, he also led several clinical researches on pain, epilepsy, stroke and dementia using perfusion and connectivity imaging. He will arrive at the Queensland Brain Institute (QBI) in September 2015 as an Associate Professor.
The goal of the lab is to understand the neural endophenotype of diseases using functional and molecular imaging. Magnetic resonance imaging (MRI) is an excellent tool for in vivo imaging of brain structure, function and metabolism. Together with molecular information by positron emission tomography (PET) and optical imaging, they could be biomarkers for tracking pathophysiological progression of diseases in vivo. These imaging biomarkers will be validated in rodent (especially transgenic mouse) models of brain disorders and translated to human to facilitate the understanding of mechanism, early detection, better prognosis and treatment development.
Especially, growing evidence indicates that many neurodegenerative and psychiatric disorders show deficit/atrophy in certain brain regions and fiber tracts unique to that disorder. These brain regions form a network pattern that suggests the disease-specific connectome may underlie the disease progression and implicate the mechanism. Therefore, a main focus of the lab is to determine and understand the functional connectome of diseases using non-invasive structural, functional and molecular imaging. We will examine genetic mutation dependent change of the connectome and its relationship with neurotransmission, electrophysiology, behaviour and other disease phenotypes.
Currently, three major projects are:
1) Neural basis of resting-state fMRI and its application in mouse models.
Resting-state fMRI is a new way for mapping the intrinsic neural networks based on spontaneous neural synchrony (functional connectivity). However the neural basis of the fMRI signal oscillation is still unknown and hence hinders the interpretation of the results. We will apply pharmacological and optogenetic manipulations to understand the neural mechanisms, especially the neurotransmission basis, of the resting-state functional connectivity imaging and validate with electrophysiology. The techniques will be applied in various mouse models of brain disorders to track the functional connectome of diseases.
2) Develop methods for imaging neural activity, connectivity and transmission.
We will advance imaging techniques for quantitative measure of specific neuronal activity, connectivity, transmission and metabolism. These include: Arterial Spin Labeling (ASL) for imaging cerebral blood flow (CBF), spectroscopic imaging for brain metabolites/neurotransmitters, Chemical Exchange Saturation Transfer (CEST) for molecular imaging, quantitative susceptibility mapping (QSM) for demyelination and iron deposition, Manganese Enhanced MRI (MEMRI) for Ca2+ dependent neuronal activity and connectivity, and functional PET for neurotransmission.
3) Connectomic biomarkers for early detection of neurodegenerative diseases.
As disease-specific connectome may underlie the progression of neurodegenerative diseases, connectome imaging may provide early biomarkers for diagnosis. We will integrate multimodality biomarkers from MRI, MRS, PET and optical imaging on an atlas and associate that with genetic defects or gene expression to build comprehensive mapping of the structural, functional and molecular connectome. This would allow us to identify better biomarkers for early detection of neurodegenerative diseases.
- Associate Professor Darryl Eyles
- Professor Jürgen Götz
- Professor Tianzi Jiang
- Dr Fatima Nasrallah
- Professor Linda J. Richards
- Professor Pankaj Sah
FA Nasrallah, LY Yeow, B Biswal, KH Chuang. “Dependence of BOLD signal fluctuation on arterial blood pCO2 and pO2: implication for resting-state functional connectivity.” NeuroImage, 117:29-39, 2015.
R Rajendran, JM Liang, S Choo, B Henry, KH Chuang. “Quantitative Tumor Perfusion in Mouse Xenograft Model using Arterial Spin Labeling MRI: Optimization and Implication.” NMR Biomed, 2015 in press.
FA Nasrallah, A Low, SK Lew, K Chen, KH Chuang. “Pharmacological insight into neurotransmission origins of resting-state functional connectivity: α2 adrenergic agonist vs antagonist.” Neuroimage, 103:364-373, 2014.
FA Nasrallah, HC Tay, KH Chuang. “Detection of functional connectivity in the resting mouse brain.” NeuroImage, 86:417–424, 2014.
FA Nasrallah, SK Lew, A Low, KH Chuang. “Neural correlate of resting-state functional connectivity under α2 adrenergic agonist, medetomidine.” NeuroImage, 84:27-34, 2014.
J Zhong, A Rifkin-Graboi, AT Ta, KL Yap, KH Chuang, MJ Meaney, A Qiu. “Functional Networks in Parallel with Cortical Development Associate with Executive Functions in Children.” Cereb Cortex, 24:1937-47, 2014.
FA Nasrallah, G Pagès, PW Kuchel, X Golay, KH Chuang. “Imaging brain deoxyglucose uptake and metabolism by glucoCEST MRI.” J Cereb Blood Flow Metab, 33:1270-8, 2013.
R Rajendran, SK Lew, CX Yong, J Tan, DJJ Wang, KH Chuang. “Quantitative mouse renal perfusion using arterial spin labeling.” NMR Biomed, 26:1225-32, 2013.
J Sundaram, C Poore, NH Sulaimee, T Pareek, ABMA Asad, R Rajkumar, GS Dawe, KH Chuang, H Pant, S Kesavapany. “Specific Inhibition of p25/Cdk5 Activity by the Cdk5 Inhibitory Peptide Reduces Neurodegeneration in vivo.” J Neurosci, 33:334-43, 201
ESG Choo, E Peng, R Rajendran, P Chandrasekharan, CT Yang, J Ding, KH Chuang, JM Xue. “Superparamagnetic Nanostructures for Off-Resonance Magnetic Resonance Spectroscopic Imaging.” Adv Funct Mater, 23: 496–505, 2013.
P Chandrasekharan, CX Yong, Z Poh, T He, Z He, S Liu, EG Robins, KH Chuang, CT Yang. “Gadolinium Chelate with DO3A Conjugated 2-(Diphenylphosphoryl)- ethyldiphenylphosphonium Cation as Potential Tumor-Selective MRI Contrast Agent.” Biomaterials, 33:9225-31, 2012.
CT Yang, KH Chuang. “Gd(III) Chelates for MRI Contrast Agents: from High Relaxivity to Smart, from Blood-Pool to Blood-Brain Barrier Permeable.” Med Chem Commun, 3:552-565, 2012.
FA Nasrallah, ELQ Lee, KH Chuang. “Optimization of flow-sensitive alternating inversion recovery (FAIR) for perfusion fMRI of rodent brain.” NMR Biomed, 25:1209-16, 2012.
FA Nasrallah, J Tan, KH Chuang. “Pharmacological modulation of functional connectivity: α2 adrenergic receptor agonist alters synchrony but not neural activation.” NeuroImage, 60:436-446, 2012.
N Chou, J Wu, J Bai, A Qiu, KH Chuang. “Robust automatic rodent brain extraction using 3D Pulse-coupled Neural Networks (PCNN).” IEEE Trans Imag Proc 20:2554-64, 2011.
JC Weng, KH Chuang, A Goloshevsky, SJ Dodd, K Sharer. “Mapping plasticity in the forepaw digit barrel subfield of rat brains using functional MRI.” NeuroImage 54:1122-29, 2011.
KH Chuang, L Belluscio, AP Koretsky. “In Vivo Detection of Individual Glomeruli in the Rodent Olfactory Bulb Using Manganese Enhanced MRI.” Neuroimage 49:1350-6, 2010.
G Pelled, DA Bergstrom, PL Tierney, R Conroy, KH Chuang, D Yu, DA Leopold, JR Walters, AP Koretsky. “Ipsilateral cortical fMRI responses after peripheral nerve damage in rats reflect increased interneuron activity.” Proc Natl Acad Sci USA 106:14114-9, 2009.
KH Chuang, JH Lee, AC Silva, L Belluscio, AP Koretsky. “Manganese Enhanced MRI Reveals Active Olfactory Circuitry in Response to Odorant Stimuli.” Neuroimage 44:363-72, 2009.
KH Chuang, P van Geldren, J Bodurka, VN Ikonomidou, AP Koretsky, JH Duyn, SL Talagala. “Mapping Resting-state Functional Connectivity by Perfusion MRI.” Neuroimage 40:1595-1605, 2008.
F Hyodo, KH Chuang, A Goloshevsky, AP Koretsky, MC Krishna. “Brain Redox Imaging using Blood-Brain Barrier-Permeable Nitroxide MRI Contrast Agent.” J Cereb Blood Flow Metab 28:1165-74, 2008.
KH Chuang, AP Koretsky. “Improved Neuronal Tract Tracing using Manganese Enhanced MRI with Fast T1 Mapping.” Magn Reson Med 55:604-11, 2006.