Nan-kuei Chen

Nan-kuei Chen

Associate Professor, Biomedical Engineering
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-0060

Research Interest

I am an MR physicist with extensive expertise in fast image acquisition methodology, pulse sequence design, and artifact correction for neuro MRI. In the past 18 years, I have developed novel approaches effectively addressing various types of challenging MRI artifacts, ranging from echo-planar imaging (EPI) geometric distortions, to susceptibility effect induced signal loss, to EPI Nyquist artifact, to motion-induced phase errors and aliasing artifacts in interleaved EPI based diffusion-weighted imaging. I am the original developer of multiplexed sensitivity encoded (MUSE) MRI, which can measure human brain connectivity in vivo at high spatial-resolution and accuracy, as shown in the publications listed below. More generally, my research involves the application of MR protocols in translational contexts. I have served as PI on NIH-funded R01, R21 and R03 grants, and have had extensive experience as a co-investigator on NIH-funded projects. The current focus of my research includes: * Development of high-throughput and motion-immune clinical MRI for imaging challenging patient populations * Imaging of neuronal connectivity networks for studies of neurological diseases * High-fidelity and multi-contrast MRI guided intervention * Characterization and correction of MRI artifacts * Signal processing and algorithm development * MRI studies of human development

Publications

Chou, Y. H., Sundman, M., Whitson, H. E., Gaur, P., Chu, M. L., Weingarten, C. P., Madden, D. J., Wang, L., Kirste, I., Joliot, M., Diaz, M. T., Li, Y. J., Song, A. W., & Chen, N. K. (2017). Maintenance and Representation of Mind Wandering during Resting-State fMRI. Scientific reports, 7, 40722.

Major advances in resting-state functional magnetic resonance imaging (fMRI) techniques in the last two decades have provided a tool to better understand the functional organization of the brain both in health and illness. Despite such developments, characterizing regulation and cerebral representation of mind wandering, which occurs unavoidably during resting-state fMRI scans and may induce variability of the acquired data, remains a work in progress. Here, we demonstrate that a decrease or decoupling in functional connectivity involving the caudate nucleus, insula, medial prefrontal cortex and other domain-specific regions was associated with more sustained mind wandering in particular thought domains during resting-state fMRI. Importantly, our findings suggest that temporal and between-subject variations in functional connectivity of above-mentioned regions might be linked with the continuity of mind wandering. Our study not only provides a preliminary framework for characterizing the maintenance and cerebral representation of different types of mind wandering, but also highlights the importance of taking mind wandering into consideration when studying brain organization with resting-state fMRI in the future.

Brass, S. D., Chen, N., Mulkern, R. V., & Bakshi, R. (2006). Magnetic resonance imaging of iron deposition in neurological disorders. Topics in magnetic resonance imaging : TMRI, 17(1), 31-40.

Deposition of iron in the brain is proposed to play a role in the pathophysiology of the normal aging process and neurodegenerative diseases. Whereas iron is required for normal neuronal metabolism, excessive levels can contribute to the formation of free radicals, leading to lipid peroxidation and neurotoxicity. Magnetic resonance imaging (MRI) is a powerful tool to detect excessive iron in the brain and longitudinally monitor changes in iron levels. Iron deposition is associated with a reduction in the T2 relaxation time, leading to hypointensity on spin-echo and gradient-echo T2-weighted images. The MRI changes associated with iron deposition have been observed both in normal aging and in various chronic neurological diseases, including multiple sclerosis, Alzheimer disease, and Parkinson disease. Magnetic resonance imaging metrics providing information about iron concentrations include R2, R2', and R2*. The purpose of this review is to discuss the role of iron and its detection by MRI in various neurological disorders. We will review the basic biochemical properties of iron and its influence on MRI signal. We will also summarize the sensitivity and specificity of MRI techniques in detecting iron. The MRI and pathological findings pertaining to brain iron will be reviewed with respect to normal aging and a variety of neurological disorders. Finally, the biochemistry and pathophysiology surrounding iron, oxidative stress, free radicals, and lipid peroxidation in the brain will be discussed, including therapeutic implications. The potential role of iron deposition and its assessment by MRI provides exciting potential applications to the diagnosis, longitudinal monitoring, and therapeutic development for disorders of the brain.

Chen, N., Avram, A. V., & Song, A. W. (2011). Two-dimensional phase cycled reconstruction for inherent correction of echo-planar imaging Nyquist artifacts. Magnetic resonance in medicine, 66(4), 1057-66.

The inconsistency of k-space trajectories results in Nyquist artifacts in echo-planar imaging (EPI). Traditional techniques often only correct for phase errors along the frequency-encoding direction (one-dimensional correction), which may leave significant residual artifacts, particularly for oblique-plane EPI or in the presence of cross-term eddy currents. As compared with one-dimensional correction, two-dimensional (2D) phase correction can be much more effective in suppressing Nyquist artifacts. However, most existing 2D correction methods require reference scans and may not be generally applicable to different imaging protocols. Furthermore, EPI reconstruction with these 2D phase correction methods is susceptible to error amplification due to subject motion. To address these limitations, we report an inherent and general 2D phase correction technique for EPI Nyquist removal. First, a series of images are generated from the original dataset, by cycling through different possible values of phase errors using a 2D reconstruction framework. Second, the image with the lowest artifact level is identified from images generated in the first step using criteria based on background energy in sorted and sigmoid-weighted signals. In this report, we demonstrate the effectiveness of our new method in removing Nyquist ghosts in single-shot, segmented and parallel EPI without acquiring additional reference scans and the subsequent error amplifications.

Chen, N., Oshio, K., & Panych, L. P. (2006). Application of k-space energy spectrum analysis to susceptibility field mapping and distortion correction in gradient-echo EPI. NeuroImage, 31(2), 609-22.

Echo-planar imaging (EPI) is widely used in functional MRI studies. It is well known that EPI quality is usually degraded by geometric distortions, when there exist susceptibility field inhomogeneities. EPI distortions may be corrected if the field maps are available. It is possible to estimate the susceptibility field gradients from the phase reconstruction of a single-TE EPI image, after a successful phase-unwrapping procedure. However, in regions affected by pronounced field gradients, the phase-unwrapping of a single-TE image may fail, and therefore the estimated field maps may be incorrect. It has been reported that the field inhomogeneity may be calculated more reliably from T2*-weighted images corresponding to multiple TEs. However, the multi-TE MRI field mapping increases the scan time. Furthermore, the measured field maps may be invalid if the subject's position changes during dynamic scans. To overcome the limitations in conventional field mapping approaches, a novel k-space energy spectrum analysis algorithm is developed, which quantifies the spatially dependent echo-shifting effect and the susceptibility field gradients directly from the k-space data of single-TE gradient-echo EPI. Using the k-space energy spectrum analysis, susceptibility field gradients can be reliably measured without phase-unwrapping, and EPI distortions can be corrected without extra field mapping scans or pulse sequence modification. The reported technique can be used to retrospectively improve the image quality of the previously acquired EPI and functional MRI data, provided that the complex-domain k-space data are still available.

Chu, M. L., Chang, H. C., Oshio, K., & Chen, N. K. (2018). A single-shot Tmapping protocol based on echo-split gradient-spin-echo acquisition and parametric multiplexed sensitivity encoding based on projection onto convex sets reconstruction. Magnetic resonance in medicine, 79(1), 383-393.

PURPOSE:To develop a high-speed T2 mapping protocol that is capable of accurately measuring T2 relaxation time constants from a single-shot acquisition.THEORY:A new echo-split single-shot gradient-spin-echo (GRASE) pulse sequence is developed to acquire multicontrast data while suppressing signals from most nonprimary echo pathways in Carr-Purcell-Meiboom-Gill (CPMG) echoes. Residual nonprimary pathway signals are taken into consideration when performing T2 mapping using a parametric multiplexed sensitivity encoding based on projection onto convex sets (parametric-POCSMUSE) reconstruction method that incorporates extended phase graph modeling of GRASE signals.METHODS:The single-shot echo-split GRASE-based T2 mapping procedure was evaluated in human studies at 3 Tesla. The acquired data were compared with reference data obtained with a more time-consuming interleaved spin-echo echo planar imaging protocol. T2 maps derived from conventional single-shot GRASE scans, in which nonprimary echo pathways were not appropriately addressed, were also evaluated.RESULTS:Using the developed single-shot T2 mapping protocol, quantitatively accurate T2 maps can be obtained with a short scan time (0.2 seconds per slice).CONCLUSION:Accurate T2 mapping with minimal signal contamination from CPMG high-order echo pathways can be achieved by the developed method that integrates single-shot echo-split GRASE acquisition and parametric-POCSMUSE reconstruction.