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)
Type
Research Project (R01)
Project #
2R01EB007829-10
Application #
8749827
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Liu, Guoying
Project Start
Project End
Budget Start
Budget End
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
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2016) Chemical exchange saturation transfer (CEST) imaging with fast variably-accelerated sensitivity encoding (vSENSE). Magn Reson Med :
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
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
Erturk, M Arcan; Hegde, Shashank Sathyanarayana; Bottomley, Paul A (2015) A combined interventional high-resolution targeted ablation, thermometry and imaging probe. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 23:1645
Hegde, Shashank Sathyanarayana; Zhang, Yi; Bottomley, Paul A (2015) Acceleration and motion-correction techniques for high-resolution intravascular MRI. Magn Reson Med 74:452-61
Zhang, Yi; Lee, Dong-Hoon; Zhang, Kai et al. (2015) Multi-parametric MRI Assessment of Tumor Response to High-Intensity Focused Ultrasound in a Rat Glioma Model. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 2015:0036
Wang, Guan; Erturk, M Arcan; Hegde, Shashank Sathyanarayana et al. (2015) Automated classification of vessel disease based on high-resolution intravascular multi-parametric mapping MRI. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 2015:1659
Ertürk, M Arcan; El-Sharkawy, AbdEl-Monem M; Bottomley, Paul A (2015) Monitoring local heating around an interventional MRI antenna with RF radiometry. Med Phys 42:1411-23
Zhang, Yi; Zhou, Jinyuan; Bottomley, Paul A (2015) Minimizing lipid signal bleed in brain (1) H chemical shift imaging by post-acquisition grid shifting. Magn Reson Med 74:320-9
Wang, Guan; El-Sharkawy, AbdEl-Monem M; Bottomley, Paul A (2014) Minimum acquisition methods for simultaneously imaging T(1), T(2), and proton density with B(1) correction and no spin-echoes. J Magn Reson 242:243-55

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