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 #
5R01NS072370-05
Application #
8811480
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Babcock, Debra J
Project Start
2011-04-15
Project End
2016-02-29
Budget Start
2015-03-01
Budget End
2016-02-29
Support Year
5
Fiscal Year
2015
Total Cost
$361,594
Indirect Cost
$144,857
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
Liu, Zhe; Spincemaille, Pascal; Yao, Yihao et al. (2018) MEDI+0: Morphology enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference for quantitative susceptibility mapping. Magn Reson Med 79:2795-2803
Wen, Yan; Nguyen, Thanh D; Liu, Zhe et al. (2018) Cardiac quantitative susceptibility mapping (QSM) for heart chamber oxygenation. Magn Reson Med 79:1545-1552
Jafari, Ramin; Chhabra, Shalini; Prince, Martin R et al. (2018) Vastly accelerated linear least-squares fitting with numerical optimization for dual-input delay-compensated quantitative liver perfusion mapping. Magn Reson Med 79:2415-2421
Wang, Yi; Spincemaille, Pascal; Liu, Zhe et al. (2017) Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care. J Magn Reson Imaging 46:951-971
Eskreis-Winkler, Sarah; Zhou, Dong; Liu, Tian et al. (2017) On the influence of zero-padding on the nonlinear operations in Quantitative Susceptibility Mapping. Magn Reson Imaging 35:154-159
Kee, Youngwook; Liu, Zhe; Zhou, Liangdong et al. (2017) Quantitative Susceptibility Mapping (QSM) Algorithms: Mathematical Rationale and Computational Implementations. IEEE Trans Biomed Eng 64:2531-2545
Zhou, Dong; Cho, Junghun; Zhang, Jingwei et al. (2017) Susceptibility underestimation in a high-susceptibility phantom: Dependence on imaging resolution, magnitude contrast, and other parameters. Magn Reson Med 78:1080-1086
Liu, Zhe; Kee, Youngwook; Zhou, Dong et al. (2017) Preconditioned total field inversion (TFI) method for quantitative susceptibility mapping. Magn Reson Med 78:303-315
Liu, Wei; Soderlund, Karl; Senseney, Justin S et al. (2016) Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury. Radiology 278:536-45
Wisnieff, Cynthia; Liu, Tian; Wang, Yi et al. (2016) The influence of molecular order and microstructure on the R2* and the magnetic susceptibility tensor. Magn Reson Imaging 34:682-9

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