David C. Zhu
Michigan State University
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Featured researches published by David C. Zhu.
Bioconjugate Chemistry | 2010
Medha N. Kamat; Kheireddine El-Boubbou; David C. Zhu; Teri Lansdell; Xiaowei Lu; Wei Li; Xuefei Huang
Imaging and targeted delivery to macrophages are promising new approaches to study and treat a variety of inflammatory diseases such as atherosclerosis. In this manuscript, we have designed and synthesized iron oxide based magnetic nanoparticles bearing hyaluronic acid (HA) on the surface to target activated macrophages. The HA-coated nanoparticles were prepared through a co-precipitation procedure followed by postsynthetic functionalization with HA and fluorescein. The nanoparticles were characterized by transmission electron microscopy, thermogravimetric analysis, elemental analysis, dynamic light scattering, and high-resolution magic angle spinning NMR and were biocompatible with cells and colloidally stable in the presence of serum. The HA immobilized on the nanoparticles retained their specific biological recognition with the HA receptor CD44, which is present on activated macrophages in high-affinity forms. Cell uptake studies demonstrated significant uptake of HA nanoparticles by activated macrophage cell line THP-1, which enabled magnetic resonance imaging of THP-1 cells. The uptake of nanoparticles was found to be both HA and CD44 dependent. Interestingly, Prussian blue staining showed that the magnetite cores of the HA-coated nanoparticles were only transiently present inside the cells, thus reducing the potential concerns of nanotoxicity. Furthermore, fluorescein on the nanoparticle was found to be delivered to the cell nucleus. Therefore, with further development, these HA functionalized magnetic nanoparticles can potentially become a useful carrier system for molecular imaging and targeted drug delivery to activated macrophages.
Brain | 2013
Soo Eun Chang; David C. Zhu
Affecting 1% of the general population, stuttering impairs the normally effortless process of speech production, which requires precise coordination of sequential movement occurring among the articulatory, respiratory, and resonance systems, all within millisecond time scales. Those afflicted experience frequent disfluencies during ongoing speech, often leading to negative psychosocial consequences. The aetiology of stuttering remains unclear; compared to other neurodevelopmental disorders, few studies to date have examined the neural bases of childhood stuttering. Here we report, for the first time, results from functional (resting state functional magnetic resonance imaging) and structural connectivity analyses (probabilistic tractography) of multimodal neuroimaging data examining neural networks in children who stutter. We examined how synchronized brain activity occurring among brain areas associated with speech production, and white matter tracts that interconnect them, differ in young children who stutter (aged 3-9 years) compared with age-matched peers. Results showed that children who stutter have attenuated connectivity in neural networks that support timing of self-paced movement control. The results suggest that auditory-motor and basal ganglia-thalamocortical networks develop differently in stuttering children, which may in turn affect speech planning and execution processes needed to achieve fluent speech motor control. These results provide important initial evidence of neurological differences in the early phases of symptom onset in children who stutter.
Biomacromolecules | 2012
Mohammad H. El-Dakdouki; David C. Zhu; Kheireddine El-Boubbou; Medha N. Kamat; Jianjun Chen; Wei Li; Xuefei Huang
Currently, there is high interest in developing multifunctional theranostic platforms for cancer monitoring and chemotherapy. Herein, we report hyaluronan (HA)-coated superparamagnetic iron oxide nanoparticles (HA-SPION) as a promising system for targeted imaging and drug delivery. When incubated with cancer cells, HA-SPIONs were rapidly taken up and the internalization of HA-SPION by cancer cells was much higher than the NPs without HA coating. The high magnetic relaxivity of HA-SPION coupled with enhanced uptake enabled magnetic resonance imaging of cancer cells. Furthermore, doxorubicin (DOX) was attached onto the nanoparticles through an acid responsive linker. While HA-SPION was not toxic to cells, DOX-HA-SPION was much more potent than free DOX to kill not only drug-sensitive but also multi-drug-resistant cancer cells. This was attributed to differential uptake mechanisms and cellular distributions of free DOX and DOX-HA-SPION in cancer cells.
The Journal of Neuroscience | 2011
Taosheng Liu; Luke Hospadaruk; David C. Zhu; Justin L. Gardner
Human can flexibly attend to a variety of stimulus dimensions, including spatial location and various features such as color and direction of motion. Although the locus of spatial attention has been hypothesized to be represented by priority maps encoded in several dorsal frontal and parietal areas, it is unknown how the brain represents attended features. Here we examined the distribution and organization of neural signals related to deployment of feature-based attention. Subjects viewed a compound stimulus containing two superimposed motion directions (or colors) and were instructed to perform an attention-demanding task on one of the directions (or colors). We found elevated and sustained functional magnetic resonance imaging response for the attention task compared with a neutral condition, without reliable differences in overall response amplitude between attending to different features. However, using multivoxel pattern analysis, we were able to decode the attended feature in both early visual areas (primary visual cortex to human motion complex hMT+) and frontal and parietal areas (e.g., intraparietal sulcus areas IPS1–IPS4 and frontal eye fields) that are commonly associated with spatial attention. Furthermore, analysis of the classifier weight maps showed that attending to motion and color evoked different patterns of activity, suggesting that different neuronal subpopulations in these regions are recruited for attending to different feature dimensions. Thus, our finding suggests that, rather than a purely spatial representation of priority, frontal and parietal cortical areas also contain multiplexed signals related to the priority of different nonspatial features.
Journal of Cognitive Neuroscience | 2009
Christine L. Larson; Joel Aronoff; Issidoros Sarinopoulos; David C. Zhu
The urgent need to recognize danger quickly has been shown to rely on preferential processing in dedicated neural circuitry. In previous behavioral studies examining the pattern of the face when displaying anger, we found evidence that simple noncontextual geometric shapes containing downward-pointing V-shaped angles activate the perception of threat. We here report that the neural circuitry known to be mobilized by many realistic, contextual threatening displays is also triggered by the simplest form of this V-shaped movement pattern, a downward-pointing triangle. Specifically, we show that simple geometric forms containing only downward-pointing V-shapes elicit greater activation of the amygdala, subgenual anterior cingulate cortex, superior temporal gyrus, and fusiform gyrus, as well as extrastriate visual regions, than do presentations of the identical V-shape pointing upward. Thus, this simple V-shape is capable of activating neural networks instantiating detection of threat and negative affect, suggesting that recognition of potential danger may be based, in part, on very simple, context-free visual cues.
Brain | 2015
Soo Eun Chang; David C. Zhu; Ai Leen Choo; Mike Angstadt
The ability to express thoughts through fluent speech production is a most human faculty, one that is often taken for granted. Stuttering, which disrupts the smooth flow of speech, affects 5% of preschool-age children and 1% of the general population, and can lead to significant communication difficulties and negative psychosocial consequences throughout ones lifetime. Despite the fact that symptom onset typically occurs during early childhood, few studies have yet examined the possible neural bases of developmental stuttering during childhood. Here we present a diffusion tensor imaging study that examined white matter measures reflecting neuroanatomical connectivity (fractional anisotropy) in 77 children [40 controls (20 females), 37 who stutter (16 females)] between 3 and 10 years of age. We asked whether previously reported anomalous white matter measures in adults and older children who stutter that were found primarily in major left hemisphere tracts (e.g. superior longitudinal fasciculus) are also present in younger children who stutter. All children exhibited normal speech, language, and cognitive development as assessed through a battery of assessments. The two groups were matched in chronological age and socioeconomic status. Voxel-wise whole brain comparisons using tract-based spatial statistics and region of interest analyses of fractional anisotropy were conducted to examine white matter changes associated with stuttering status, age, sex, and stuttering severity. Children who stutter exhibited significantly reduced fractional anisotropy relative to controls in white matter tracts that interconnect auditory and motor structures, corpus callosum, and in tracts interconnecting cortical and subcortical areas. In contrast to control subjects, fractional anisotropy changes with age were either stagnant or showed dissociated development among major perisylvian brain areas in children who stutter. These results provide first glimpses into the neuroanatomical bases of early childhood stuttering, and possible white matter developmental changes that may lead to recovery versus persistent stuttering. The white matter changes point to possible structural connectivity deficits in children who stutter, in interrelated neural circuits that enable skilled movement control through efficient sensorimotor integration and timing of movements.
Magnetic Resonance Imaging | 2008
David C. Zhu; Marina S. Ferguson; J. Kevin DeMarco
An optimized 3D inversion recovery prepared fast spoiled gradient recalled sequence (IR FSPGR) on a 3-T scanner for carotid plaque imaging is described. It offers clear blood and fat signal suppression at the carotid artery bifurcation and highlights the regions of carotid plaque affected by hemorrhage at 3 T with high contrast and contrast-to-noise ratio compared with other sequences. It can potentially be used to replace the more traditional noncontrast T(1)-weighted 2D black-blood imaging for hemorrhage detection and offers additional benefits of high-resolution 3D volumetric visualization.
Journal of Neurotrauma | 2015
David C. Zhu; Tracey Covassin; Sally Nogle; Scarlett Doyle; Doozie Russell; Randolph Pearson; Jeffrey Monroe; Christine Liszewski; J. Kevin DeMarco; David I. Kaufman
Current diagnosis and monitoring of sports-related concussion rely on clinical signs and symptoms, and balance, vestibular, and neuropsychological examinations. Conventional brain imaging often does not reveal abnormalities. We sought to assess if the longitudinal change of functional and structural connectivity of the default-mode network (DMN) can serve as a potential biomarker. Eight concussed Division I collegiate football student-athletes in season (one participated twice) and 11 control subjects participated in this study. ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) was administered over the course of recovery. High-resolution three dimensional T1-weighted, T2*-weighted diffusion-tensor images and resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected from each subject within 24 h, 7±1 d and 30±1 d after concussion. Both network based and whole-brain based functional correlation analyses on DMN were performed. ImPACT findings demonstrated significant cognitive impairment across multiple categories and a significant increase of symptom severity on Day 1 following a concussion but full recovery by 6.0±2.4 d. While the structural connectivity within DMN and gross anatomy appeared unchanged, a significantly reduced functional connectivity within DMN from Day 1 to Day 7 was found in the concussed group in this small pilot study. This reduction was seen in eight of our nine concussion cases. Compared with the control group, there appears a general trend of increased DMN functional connectivity on Day 1, a significant drop on Day 7, and partial recovery on Day 30. The results of this pilot study suggest that the functional connectivity of DMN measured with longitudinal rs-fMRI can serve as a potential biomarker to monitor the dynamically changing brain function after sports-related concussion, even in patients who have shown clinical improvement.
American Journal of Neuroradiology | 2010
J.K. DeMarco; Hideki Ota; Hunter R. Underhill; David C. Zhu; Mathew J. Reeves; Michael J. Potchen; Arshad Majid; Alonso Collar; J.A. Talsma; S. Potru; Minako Oikawa; Li Dong; Xue-Qiao Zhao; Vasily L. Yarnykh; Chun Yuan
BACKGROUND AND PURPOSE: Recent research has suggested the importance of plaque composition to identify patients at risk for stroke. This study aims to identify specific plaque features on 3T carotid MR imaging and CE-MRA associated with recent carotid thromboembolic symptoms in patients with mild/moderate versus severe stenosis. MATERIALS AND METHODS: Ninety-seven consecutive patients (symptomatic, 13; asymptomatic, 84) with 50%–99% stenosis by sonography or CT angiography underwent carotid plaque imaging combined with MRA at 3T. The symptomatic carotid artery or the most stenotic asymptomatic carotid artery was chosen as the index vessel to be analyzed. Plaque features were compared by symptomatic status in patients with mild/moderate (30%–70%) versus severe (70%–99%) stenosis on MRA. RESULTS: Ninety (92.8%) patients had sufficient image quality for interpretation. In 50 patients with mild/moderate stenosis, there were significant associations between the presence of the following plaque characteristics and symptoms: thin/ruptured fibrous cap (100% versus 36%, P = .006) and lipid-rich necrotic core (100% versus 39%, P = .022), with marginal association with hemorrhage (86% versus 33%, P = .055). In 40 patients with severe stenosis, only the angiographic presence of ulceration (86% versus 36%, P = .039) was associated with symptoms. CONCLUSIONS: Several plaque components identified on 3T MR imaging are correlated with recent ipsilateral carotid thromboembolic symptoms. These preliminary results also suggest that associations between plaque characteristics and symptom history may vary by degree of stenosis. If confirmed in larger studies, carotid MR imaging may distinguish stable from unstable lesions, particularly in individuals with mild/moderate stenosis in whom the role of surgical intervention is currently unclear.
Journal of Magnetic Resonance Imaging | 2006
David C. Zhu; Michalis Xenos; Andreas A. Linninger; Richard D. Penn
To develop quantitative MRI techniques to measure, model, and visualize cerebrospinal fluid (CSF) hydrodynamics in normal subjects and hydrocephalic patients.