The objective of this research is to develop a quantitative MRI method for mapping iron deposits in cerebral microbleeds (CMB). There is significant scientific and clinical interest in studying CMB, which are focal lesions of hemosiderin deposits from red blood cells leaked out of small brain vessels. CMB have become an important concern for managing stroke patients, particularly for assessing the risk of devastating intracerebral hemorrhage (ICH) in patients under anticoagulation. Quantitative mapping of iron deposits in CMB can be very valuable for stratifying risk of anticoagulation therapy. Currently, dark regions in T2* weighted MRI have been used to identify the presence of iron by interpreting the observed signal loss caused by the intravoxel dephasing effect of local magnetic fields of iron deposits. This hypointensity depends on voxel size and orientation, may be confused with other signal voids, and does not allow accurate quantification of iron. We propose a novel quantitative susceptibility mapping (QSM) approach to generate quantitative mapping of iron deposits using MRI by making full use of both phase and magnitude information in the T2* gradient echo image data. The phase image, typically neglected in MRI, is used to generate a local magnetic field map for fitting with susceptibility via the Maxwell equation. The magnitude image is used to extract tissue structure information for matching with susceptibility interfaces via least discordance. This morphology enabled dipole inversion approach is feasible for quantitatively mapping iron compound concentrations, as demonstrated in our preliminary studies, therefore enabling standardized and quantitative evaluation of CBM. Our proposed research consists of the following specific aims for developing and applying brain iron mapping technology. 1) Optimize data acquisition for mapping fields of CMB in the whole brain. 2) Develop a robust reconstruction for QSM of CMB iron deposits. 3) Validate QSM of bleeds and microbleeds in the brain using histological correlation. 4) Apply QSM to measure CMB in warfarin-treated patients with and without ICH.

Public Health Relevance

This proposed research will develop a quantitative susceptibility mapping of iron deposits in cerebral microbleeds using noninvasive MRI for assessing the risk of intracerebral hemorrhage in patient treated with warfarin. There is an urgent need to standardize the MRI evaluation of cerebral microbleeds, a known risk for the devastating intracerebral hemorrhage in hypertensive patients. Currently MRI is the method of choice for the detection of cerebral microbleeds, but it is not quantitative. Successful development of this research would lead to a standardized evaluation of cerebral microbleeds and an accurate assessment of the risk of intracerebral hemorrhage for patients under warfarin treatment for their heart problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS072370-02
Application #
8251167
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Babcock, Debra J
Project Start
2011-04-15
Project End
2016-02-29
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$352,356
Indirect Cost
$141,319
Name
Weill Medical College of Cornell University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Wang, Yi; Liu, Tian (2015) Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker. Magn Reson Med 73:82-101
Wisnieff, Cynthia; Ramanan, Sriram; Olesik, John et al. (2015) Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron. Magn Reson Med 74:564-70
Pei, Mengchao; Nguyen, Thanh D; Thimmappa, Nanda D et al. (2015) Algorithm for fast monoexponential fitting based on Auto-Regression on Linear Operations (ARLO) of data. Magn Reson Med 73:843-50
Chen, Weiwei; Zhu, Wenzhen; Kovanlikaya, Iihami et al. (2014) Intracranial calcifications and hemorrhages: characterization with quantitative susceptibility mapping. Radiology 270:496-505
Wen, Yan; Zhou, Dong; Liu, Tian et al. (2014) An iterative spherical mean value method for background field removal in MRI. Magn Reson Med 72:1065-71
Zhou, Dong; Liu, Tian; Spincemaille, Pascal et al. (2014) Background field removal by solving the Laplacian boundary value problem. NMR Biomed 27:312-9
Liu, Tian; Eskreis-Winkler, Sarah; Schweitzer, Andrew D et al. (2013) Improved subthalamic nucleus depiction with quantitative susceptibility mapping. Radiology 269:216-23
Wisnieff, Cynthia; Liu, Tian; Spincemaille, Pascal et al. (2013) Magnetic susceptibility anisotropy: cylindrical symmetry from macroscopically ordered anisotropic molecules and accuracy of MRI measurements using few orientations. Neuroimage 70:363-76
Wang, Shuo; Lou, Min; Liu, Tian et al. (2013) Hematoma volume measurement in gradient echo MRI using quantitative susceptibility mapping. Stroke 44:2315-7
Liu, Tian; Xu, Weiyu; Spincemaille, Pascal et al. (2012) Accuracy of the morphology enabled dipole inversion (MEDI) algorithm for quantitative susceptibility mapping in MRI. IEEE Trans Med Imaging 31:816-24

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