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Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis

Award Number: R01DK125783
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY: The overarching goal of our research is to improve the management and health of an estimated 1 million Americans suffering from end-stage liver disease (cirrhosis) through non-invasive MRI-based blood flow measurements. In cirrhosis, increased resistance to blood flow leads to formation of collateral vessels that shunt blood away from the liver. Many forms of collaterals can develop, but gastroesophageal varices (GEV) are the most important to monitor - GEV are fragile submucosal vessels that can rupture without warning and cause fatal internal bleeding. Once bleeding starts, mortality is extraordinarily high: 1/3 of patients who bleed will die. Current clinical guidelines recommend esophagogastroduodenoscopy (EGD) surveillance every 1-3 years, to facilitate prophylactic treatment and avoid life-threatening bleeding. Unfortunately. EDG is invasive, expensive, and requires sedation. Importantly, most patients undergoing EGD do not have treatable varices, and compliance with surveillance is very poor. For these reasons, the AASLD has identified the development of non-invasive markers that predict the presence of high-risk varices as a major unmet need in the management of cirrhosis. We aim to address this need through development of non-invasive MRI-based markers of portal blood flow that leverage the primary biological mechanism for development and rupture of GEV: reversed flow from the portal circulation into GEV via the left gastric vein. Currently available markers include catheter-based hepatic venous pressure gradient measurements, and emerging non-invasive markers such as platelet-to-spleen ratio, and liver and spleen stiffness (using ultrasound or MRI). Unfortunately, these markers only provide a global assessment of liver disease, and do not have the specificity necessary to identify high-risk GEV. The investigative team at UW are pioneers in radial 4D flow MRI for comprehensive hemodynamic characterization of blood flow in the liver. Our pilot data demonstrates that radial 4D flow MRI can accurately identify high-risk GEV, by quantifying reversed flow in the LGV, with high sensitivity and specificity. We propose to translate advanced 4D flow MRI to address this unmet clinical need by overcoming remaining technical challenges, performing preclinical validation and optimization, and determining its diagnostic performance. Aim 1: Technical development of velocity-optimized, accelerated 4D flow MRI, to quantify flow in the portal circulation, in < 3 minutes. Aim 2: Rigorous validation of the proposed method in anatomically correct 3D-printed flow phantoms. Aim 3: Determine the diagnostic performance of the proposed method in cirrhotic adults undergoing EGD, to assess diagnostic accuracy and test-retest repeatability. Aim 4: evaluate the effects and added value of a meal challenge to assess for high-risk GEV. If successful, the proposed strategy would transform the management of cirrhosis, through: 1) prompt triage of patients to therapeutic EGD 2) reduction of unnecessary EGD procedures, and 3) increased compliance of GEV surveillance through access to a non-invasive method, ultimately improving the care and long-term survival of patients with cirrhosis.


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: 2024 ( Subtotal = $557,551 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	5/10/2024	NON-COMPETING CONTINUATION	$34,846
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/4/2024	NON-COMPETING CONTINUATION	$522,705
														Subtotal = $557,551

Issue Date FY: 2023 ( Subtotal = $617,697 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	1/9/2023	NON-COMPETING CONTINUATION	$61,768
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/2/2022	NON-COMPETING CONTINUATION	$555,929
														Subtotal = $617,697

Issue Date FY: 2022 ( Subtotal = $533,499 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/9/2021	NON-COMPETING CONTINUATION	$480,148
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	3/30/2022	NON-COMPETING CONTINUATION	$53,351
														Subtotal = $533,499

Issue Date FY: 2021 ( Subtotal = $521,185 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	4/7/2021	NEW	$0
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/19/2021	NEW	$521,185
														Subtotal = $521,185

Grand Total All Awards = $2,229,932

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Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis

Award Number: R01DK125783

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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