One in four adult Americans experiences a mental health disorder in a given year. About 2.4 million Americans live with schizophrenia. There are considerable and growing evidences suggesting schizophrenia may originate from early neurodevelopment involving abnormal neuronal circuits. However, schizophrenia still cannot be diagnosed until young adulthood at the earliest when the most rapid phase of neurodevelopment has already completed. The lack of earlier risk assessment has severely limited our understanding of the developmental trajectory of the disease thus preventing more effective intervention before symptom onset. This project will develop a novel non-invasive MRI technique that will provide the necessary sensitivity and resolution (10 micron) to detect potential developmental abnormalities associated with neuronal circuits. Our preliminary studies have demonstrated a markedly improved sensitivity and resolution compared to state-of- the-art MRI techniques. We will further develop this novel technique and determine its molecular basis of the improved sensitivity. We will test the technique on transgenic mouse models of schizophrenia and investigate its ability to detect abnormalities in neuronal circuits before symptoms occur. In particular, we will determine the relationship between the new image contrast and abnormalities of myelination and synapses associated with corticostriatal and corticohippocampal connectivity. The rationale of the research is that the proposed multidisciplinary imaging-genetics study would help us to better understand the genetic and developmental components of the disease, to detect circuit abnormalities before behavioral symptoms, and to eventually guide treatment strategies.

Public Health Relevance

This research will develop an in vivo MRI-based technique for assessing brain development. In addition to the study of normal brain development and schizophrenia, this technique could be relevant for applications to many brain disorders, including demyelination diseases and brain trauma. If our hypotheses are correct, this may save lives by providing earlier diagnosis of developmental brain disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH096979-02
Application #
8657111
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Freund, Michelle
Project Start
2013-05-03
Project End
2018-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
Wei, Hongjiang; Cao, Peng; Bischof, Antje et al. (2018) MRI gradient-echo phase contrast of the brain at ultra-short TE with off-resonance saturation. Neuroimage 175:1-11
Wei, Hongjiang; Lin, Huimin; Qin, Le et al. (2018) Quantitative susceptibility mapping of articular cartilage in patients with osteoarthritis at 3T. J Magn Reson Imaging :
Zhang, Yuyao; Wei, Hongjiang; Cronin, Matthew J et al. (2018) Longitudinal data for magnetic susceptibility of normative human brain development and aging over the lifespan. Data Brief 20:623-631
Zhang, Yuyao; Wei, Hongjiang; Sun, Yawen et al. (2018) Quantitative susceptibility mapping (QSM) as a means to monitor cerebral hematoma treatment. J Magn Reson Imaging 48:907-915
Zhang, Yuyao; Wei, Hongjiang; Cronin, Matthew J et al. (2018) Longitudinal atlas for normative human brain development and aging over the lifespan using quantitative susceptibility mapping. Neuroimage 171:176-189
Lin, Huimin; Wei, Hongjiang; He, Naying et al. (2018) Quantitative susceptibility mapping in combination with water-fat separation for simultaneous liver iron and fat fraction quantification. Eur Radiol 28:3494-3504
Dibb, Russell; Liu, Chunlei (2017) Joint eigenvector estimation from mutually anisotropic tensors improves susceptibility tensor imaging of the brain, kidney, and heart. Magn Reson Med 77:2331-2346
He, Naying; Huang, Pei; Ling, Huawei et al. (2017) Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease. NMR Biomed 30:
Wei, Hongjiang; Dibb, Russell; Decker, Kyle et al. (2017) Investigating magnetic susceptibility of human knee joint at 7 Tesla. Magn Reson Med 78:1933-1943
Li, Wei; Liu, Chunlei; Duong, Timothy Q et al. (2017) Susceptibility tensor imaging (STI) of the brain. NMR Biomed 30:

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