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Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents

Award Number: R01HL148788
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/24/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents - PROJECT SUMMARY Ischemic heart disease (IHD) is the leading cause of death in the United States. It emanates from narrowing of coronary arteries (CAD) and/or development of microvascular dysfunction culminating in myocardial ischemia – a condition where the oxygen demand of the myocardium is far in excess of the available supply. IHD accounts for more than 1 in 3 deaths and >1 million hospitalizations each year in the US. The extent and severity of myocardial ischemia has been shown to provide incremental prognostic value over standard clinical variables across the spectrum of presentation of patients with IHD. Long-established (SPECT or PET) and more recently established (e.g., first pass-perfusion MRI) methods are routinely used to gather this information. In spite of their capabilities, these methods have key limitations – they expose the patients to either ionizing radiation or exogenous contrast agents, which carry risks to the patients. This is particularly a critical problem in at least half a million patients with end-stage renal disease (ESRD) in the US. In ESRD patients, annual ischemia testing is needed since the risk of cardiovascular mortality is > 10-fold greater than in the general population. Hence there is an unmet and growing need for safe and reliable assessment of myocardial ischemia in all patients, and is most pressing in ESRD patients, whose prevalence in the US is on the rise. Blood-Oxygen-Level-Dependent (BOLD) Cardiac MRI (CMR) is a potential alternative to standard clinical methods since it is free of ionizing radiation and exogenous contrast media. It also has the capability to provide physiological insight into the disease based on measurements of impaired oxygen supply, and not from surrogate metrics (wall motion, ECG changes, or contrast kinetics). Over the past two decades, the technical capabilities of BOLD CMR have led to clinical testing. However, limitations in reliability (sensitivity, specificity and accuracy) remain a major impediment for widespread clinical use of BOLD CMR. To overcome the reliability limitations of BOLD CMR, in a previous R01 funding (2013 to 2017), we hypothesized that repeat stimulations of the heart, analogous to brain activation studies using BOLD MRI (brain fMRI), could improve the reliability of BOLD CMR. Subsequently, we went onto demonstrate that (i) a targeted change in arterial partial pressure of CO2 (PaCO2) can be a potent non-invasive vasoactive stimulus; and a (ii) high-resolution, whole heart BOLD CMR at 3T with repeat PaCO2 stimulation of the heart, when combined with a statistical framework, can reliably detect BOLD signal changes in large, healthy, animals. To successfully translate the promising impact of this BOLD CMR approach into the clinical arena, further advances and validation will be required. This proposal aims to continue the successful advancement of this BOLD CMR approach towards clinical feasibility so that it can enable a truly noninvasive and cost-effective ischemia testing that is free of ionizing radiation, exogenous contrast agents, intravenous pharmacological agents or even needles. Thus, this proposal is a critical step towards advancing the care of a large segment of IHD patients in the US.


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 = $671,018 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cardiovascular Diseases Research	003	4	8/9/2023	NON-COMPETING CONTINUATION	$671,018
2023	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cardiovascular Diseases Research	002	3	12/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$971,284
2023	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	001	2	12/22/2022	NON-COMPETING CONTINUATION	-$800,362
2023	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	12/22/2022	NEW	-$170,922
														Subtotal = $671,018

Issue Date FY: 2022 ( Subtotal = $716,960 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cardiovascular Diseases Research	001	3	8/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$716,960
2022	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	2	8/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $716,960

Issue Date FY: 2021 ( Subtotal = $800,362 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	2	6/11/2021	NON-COMPETING CONTINUATION	$800,362
														Subtotal = $800,362

Issue Date FY: 2020 ( Subtotal = $815,926 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	6/24/2020	NEW	$815,926
														Subtotal = $815,926

Grand Total All Awards = $3,004,266

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Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents

Award Number: R01HL148788

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/24/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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