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Novel MRI techniques for imaging cardiac fibrosis to improve clinical practice in patients with renal failure

Award Number: R01HL128592
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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¿ DESCRIPTION (provided by applicant): Cardiovascular disease affects millions of Americans, with heart failure as a common endpoint. The development of cardiac fibrosis occurs early in cardiovascular disease, promotes heart failure, and provides arrhythmogenic substrate leading to increased frequency of adverse cardiac events and higher mortality. Cardiac magnetic resonance imaging (CMR) is routinely used to measure changes in ventricular structure and function with balanced steady state free precession (bSSFP) imaging. With intravenously delivered gadolinium contrast agents, late gadolinium enhancement (LGE) CMR is the clinical standard for identifying focal fibrosis and quantifying fibrotic burden, and when combined with mapping of T1-relaxation times can quantify diffuse fibrosis through measurement of increased extracellular volume fraction (ECV). In individuals with chronic kidney disease a strong link exists between cardiac fibrosis and adverse cardiac events, however LGE is contraindicated due to the danger of nephrogenic systemic fibrosis. Emerging studies suggest that specific circulating hormones and peptides may be biomarkers of cardiac fibrosis and potential therapeutic targets in chronic kidney disease. However, the inability to measure fibrosis in such patients represents a major gap to the discovery of potential biomarkers, and leaves most studies measuring cardiac hypertrophy as an insensitive surrogate of fibrosis. This proposal seeks to develop a gadolinium free MRI method to measure fibrotic burden via reduced magnetization transfer (MT) in areas fibrotic tissue. This method, termed 2-point bSSFP, exploits an endogenous contrast mechanism in bSSFP imaging to identify fibrotic and edematous tissue. The proposed aims will validate 2-point bSSFP against standard of care LGE and measurement of diffuse fibrosis through ECV mapping. Finally, comparison of fibrotic burden (measured with 2-point bSSFP) to blood chemical workup in CKD patients will examine the correlation between fibrosis and potential biomarkes. The successful completion of these aims will enable rapid and gadolinium free imaging of cardiac fibrosis over the entire heart. Further, correlation of cardiac fibrosis with blood serum biomarkers in chronic kidney disease patients can help identify potential therapeutic targets to halt or reverse fibrosis, the efficacy f which can be serially monitored using 2-point bSSFP.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$97 )
2023	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Cardiovascular Diseases Research	000	5	11/10/2022	NON-COMPETING CONTINUATION	-$97
														Subtotal = -$97

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Cardiovascular Diseases Research	000	5	4/2/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $392,500 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Cardiovascular Diseases Research	000	5	4/29/2019	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2018 ( Subtotal = $880,226 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Cardiovascular Diseases Research	001	4	4/12/2018	NON-COMPETING CONTINUATION	$392,500
2018	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Cardiovascular Diseases Research	000	3	10/17/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$487,726
														Subtotal = $880,226

Issue Date FY: 2017 ( Subtotal = -$95,226 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Cardiovascular Diseases Research	003	3	4/4/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$392,500
2017	2016	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Cardiovascular Diseases Research	000	2	4/1/2017	NON-COMPETING CONTINUATION	$0
2017	2016	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Cardiovascular Diseases Research	002	2	4/4/2017	NON-COMPETING CONTINUATION	-$376,250
2017	2015	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Cardiovascular Diseases Research	001	1	4/4/2017	NEW	-$111,476
														Subtotal = -$95,226

Issue Date FY: 2016 ( Subtotal = $376,250 )
2016	2016	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Cardiovascular Diseases Research	000	2	4/30/2016	NON-COMPETING CONTINUATION	$376,250
														Subtotal = $376,250

Issue Date FY: 2015 ( Subtotal = $376,250 )
2015	2015	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Cardiovascular Diseases Research	000	1	7/27/2015	NEW	$376,250
														Subtotal = $376,250

Grand Total All Awards = $1,929,903

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Novel MRI techniques for imaging cardiac fibrosis to improve clinical practice in patients with renal failure

Award Number: R01HL128592

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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