This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Use the Center for In Vivo Microscopy's 7T system to develop and test iMQC pulse sequences for use on a GE scanner. The research addresses fundamental limitations of MRI and MR spectroscopy (MRS) in vivo, enhancing their utility and enabling new clinical and preclinical applications. MRI and MRS have become very powerful clinical modalities, and applications continue to evolve. However, sensitivity is relatively low, so in most MRI studies, the signal arises mostly from water, and contrast arises primarily from parameters, which often only have indirect clinical relevance or correlation with metabolism and cell biochemistry. Most contrast agents have limited specificity, and usually need to be present in high concentration to affect the signal. Localized detection of other molecules (MRS) is hampered by low concentrations, by competition with the strong water peak, and (in many organs) by local susceptibility variations that broaden resonances and thus reduce selectivity. The research proposed here addresses these fundamental limitations using intermolecular multiple- quantum coherences (iMQCs), both by themselves and with long-lived hyperpolarized reagents. iMQCs correspond to simultaneous spin flips on separated molecules in solution (the separation is typically hundreds of microns). In the previous grant period, we developed methods that significantly strengthen iMQC signals, applications such as temperature imaging where iMQCs have clear advantages, novel contrast agents that amplify the signal from small lung metastases, and approaches that dramatically increase the lifetimes of specific hyperpolarized reagents. Just since October 2008, this work includes two published Science papers and a submitted PNAS paper. This renewal includes specific aims, which exploit these developments, with a focus on targeted clinical applications and localized spectroscopy. The common theme of these applications is high precision spectroscopy, enabled by the intrinsic ability of appropriate iMQC sequences to compensate for susceptibility variations and inhomogeneous broadening. This compensation can be achieved without throwing away chemical shift differences, and the intermolecular coherences can connect molecules which are not in immediate proximity. In organs or tissues with substantial heterogeneity (such as the breast) the line width reductions are dramatic.
The specific aims exploit these characteristics to enable two clinically promising research directions (absolute temperature imaging in hyperthermic therapy and brown adipose tissue detection), to improve proton MRS in fatty tissue, and to enhance the utility of carbon hyperpolarized reagents by detecting sharp lines from water-carbon iMQCs. This work ranges from phantom studies to our participation in an ongoing human clinical trial, and includes innovative pulse sequence development as well as applications of existing sequences.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR005959-22
Application #
8363196
Study Section
Special Emphasis Panel (ZRG1-SBIB-P (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
22
Fiscal Year
2011
Total Cost
$12,272
Indirect Cost
Name
Duke University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Tang, Xinyan; Jing, Liufang; Richardson, William J et al. (2016) Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration. J Orthop Res 34:1316-26
Hodgkinson, Conrad P; Bareja, Akshay; Gomez, José A et al. (2016) Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology. Circ Res 118:95-107
Schmeckpeper, Jeffrey; Verma, Amanda; Yin, Lucy et al. (2015) Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. J Mol Cell Cardiol 85:215-25
Roos, Justus E; McAdams, Holman P; Kaushik, S Sivaram et al. (2015) Hyperpolarized Gas MR Imaging: Technique and Applications. Magn Reson Imaging Clin N Am 23:217-29
He, Mu; Robertson, Scott H; Kaushik, S Sivaram et al. (2015) Dose and pulse sequence considerations for hyperpolarized (129)Xe ventilation MRI. Magn Reson Imaging 33:877-85
Huang, Jing; Guo, Jian; Beigi, Farideh et al. (2014) HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection. J Mol Cell Cardiol 66:157-64
Huang, Lingling; Walter, Vonn; Hayes, D Neil et al. (2014) Hedgehog-GLI signaling inhibition suppresses tumor growth in squamous lung cancer. Clin Cancer Res 20:1566-75
Yuan, Ying; Gilmore, John H; Geng, Xiujuan et al. (2014) FMEM: functional mixed effects modeling for the analysis of longitudinal white matter Tract data. Neuroimage 84:753-64
He, Mu; Kaushik, S Sivaram; Robertson, Scott H et al. (2014) Extending semiautomatic ventilation defect analysis for hyperpolarized (129)Xe ventilation MRI. Acad Radiol 21:1530-41
Liu, Chunlei; Li, Wei (2013) Imaging neural architecture of the brain based on its multipole magnetic response. Neuroimage 67:193-202

Showing the most recent 10 out of 239 publications