This renewal grant responds to BRG PAR-13-1371 for the development of noninvasive and nondestructive imaging methods for in vivo monitoring;novel diagnostic and medical devices;and new bioengineering ap- proaches to cardiovascular treatment. The grant targets atherosclerosis, which in advanced disease, is characterized by lesions with lipids, calcification, and fibrous caps whose rupture are a leading cause of stroke, heart attack and death. While typically diagnosed by X-ray catheterization, X-ray can't assess plaque contents, vulnerability to rupture, or early stage wall-thickening. Our goal is to develop a novel, safe, mini- mally-invasive, fast, high-resolution, cardiovascular imaging modality employing high-field intravascular (IV) magnetic resonance imaging (MRI), to assess and monitor disease, and provide targeted therapy delivery. In the expiring grant period we created novel dosimetry tools for testing the safety of internal devices dur- ing MRI. We showed theoretically and experimentally that the signal-to-noise ratio of internal detectors in- creased with MRI field strength-squared, at least up to 7 Tesla (T). This enabled 80?m IVMRI at 3T and 40- 50?m at 7T to visualize plaque morphology. We developed a new ?-imaging method, 'MRI endoscopy'that provides a stream of images intrinsically locked to the probe's viewpoint at up to 2 fr/s. Because IVMRI resolution at 40-50?m is now within a range that could identify plaques vulnerable to rupture, and because chemically-selective imaging of mobile lipids is also possible at higher MRI fields, the possibility of character- izing key attributes of vulnerable plaque-thin fibrous caps and mobile lipid contents by IVMRI, now exists. But technical issues remain: we need still faster IVMRI, and reduced sensitivity to motion. We need a method of chemically selective IVMRI. We don't know how IVMRI compares with other IV modalities-IV ul- trasound (IVUS) or optical coherence tomography (OCT). And if we see disease, can we intervene? This re- newal addresses all these key questions.
Aim 1 creates a high-speed real-time, motion-insensitive IVMRI capability using novel sparse sampling and frame-shifting methods.
Aim 2 develops high-field 40-50?m IV MRI and chemically-selective lipid imaging to characterize plaque caps and contents.
Aim 3 performs com- parative studies in vitro and in vivo of IVMRI, OCT, and IVUS.
Aim 4 creates an interventional platform for high-resolution IVMRI-targeting, demonstrated for angioplasty, and cellular and ultrasound ablation thera- pies. This project, supported by progress in the 1st grant and new preliminary work, can provide important new IV imaging and interventional tools to advance understanding and treatment of cardiovascular disease.

Public Health Relevance

The goal of this grant is to develop a novel, safe, minimally-invasive, fast, high-resolution, transluminal cardiovascular imaging modality employing intravascular (IV) magnetic resonance imaging (MRI), capable of detecting key chemical and structural factors affecting the vulnerability of atherosclerotic plaques to rupture with consequences that are often dire. It will place IVMRI in the context of other IV imaging modalities, and develop and demonstrate its use for providing precision targeted therapy delivery, pursuant to PAR-13-137.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
2R01EB007829-10
Application #
8749827
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Liu, Guoying
Project Start
2000-12-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Liu, Xiaoyang; Ellens, Nicholas; Williams, Emery et al. (2017) A Combined Intravascular MRI Endoscope and Intravascular Ultrasound (IVUS) Transducer for High-Resolution Image-Guided Ablation. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 25:1178
Wang, Guan; Zhang, Yi; Hegde, Shashank Sathyanarayana et al. (2017) High-resolution and accelerated multi-parametric mapping with automated characterization of vessel disease using intravascular MRI. J Cardiovasc Magn Reson 19:89
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2017) Chemical exchange saturation transfer (CEST) imaging with fast variably-accelerated sensitivity encoding (vSENSE). Magn Reson Med 77:2225-2238
Zhang, Yi; Heo, Hye-Young; Jiang, Shanshan et al. (2017) Fast, Reliable 3D Amide Proton Transfer Imaging of Brain Tumors at 3T with Variably-accelerated Sensitivity Encoding (vSENSE). Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 25:
Zhang, Yi; Liu, Xiaoyang; Zhou, Jinyuan et al. (2017) Ultrafast compartmental relaxation time mapping with linear algebraic modeling. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 25:0071
Zhang, Yi; Heo, Hye-Young; Jiang, Shanshan et al. (2016) Highly accelerated chemical exchange saturation transfer (CEST) measurements with linear algebraic modeling. Magn Reson Med 76:136-44
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2016) Fast Chemical Exchange Saturation Transfer (CEST) Imaging with Variably-accelerated Sensitivity Encoding (vSENSE). Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 24:1522
Wang, Guan; Zhang, Yi; Hegde, Shashank Sathyanarayana et al. (2016) Highly Accelerated, Intravascular T1, T2, and Proton Density Mapping with Linear Algebraic Modeling and Sensitivity Profile Correction at 3T. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 24:2829
Ertürk, M Arcan; Sathyanarayana Hegde, Shashank; Bottomley, Paul A (2016) Radiofrequency Ablation, MR Thermometry, and High-Spatial-Resolution MR Parametric Imaging with a Single, Minimally Invasive Device. Radiology 281:927-932
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2016) Highly-accelerated CEST Measurements in Three Dimensions with Linear Algebraic Modeling. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 24:1524

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