Renal hypoxia plays a key role in the pathophysiology of several diseases and has been implicated in acute kidney injury and in the initiation and progression of chronic kidney disease. The ability to non-invasively assess renal hypoxia can be an important tool for assessing a subject's renal health early and initiating targeted treatment that can slow disease progression, reduce complications of the decreased glomerular filtration rate and improve quality of life. MRI sequences based on the blood oxygen level-dependent (BOLD) contrast mechanism have been used for following changes in renal oxygenation. However, recent studies have shown that these measurements are sensitive to other confounding factors in addition to oxygenation. There still exists a need for a reliable, quantitative and non-invasive measure of renal oxygenation. In this proposal, we will investigate the use of R2' as a BOLD MRI parameter and validate it against independent measures of blood and tissue oxygen by invasive phosphorimetry. Furthermore, we will explore alternative methods for analyzing BOLD MRI parametric maps to minimize subjectivity and hence allow for comparing data across laboratories. Our overall hypothesis is that methods that can directly probe renal oxygenation, without influences from confounding factors, along with an objective analysis of the parametric maps, will provide for widespread utility of these measurements both in pre-clinical and clinical settings.

Public Health Relevance

Healthy kidney function is highly dependent on sufficient levels of oxygen delivery, with regions actually operating at severely reduced oxygen levels which can be further decreased by disease. This spatial variation makes imaging an ideal candidate for oxygen assessment. The goal of this project is to develop and validate a quantitative method for estimating kidney oxygenation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31HL123360-01A1
Application #
8838321
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Welniak, Lisbeth A
Project Start
2015-02-01
Project End
2018-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Li, Lu-Ping; Thacker, Jon; Li, Wei et al. (2018) Consistency of Multiple Renal Functional MRI Measurements Over 18 Months. J Magn Reson Imaging 48:514-521
Prasad, Pottumarthi V; Li, Wei; Raj, Dominic S et al. (2018) Multicenter Study Evaluating Intrarenal Oxygenation and Fibrosis Using Magnetic Resonance Imaging in Individuals With Advanced CKD. Kidney Int Rep 3:1467-1472
Li, Lu-Ping; Tan, Huan; Thacker, Jon M et al. (2017) Evaluation of Renal Blood Flow in Chronic Kidney Disease Using Arterial Spin Labeling Perfusion Magnetic Resonance Imaging. Kidney Int Rep 2:36-43
Thacker, Jon; Zhang, Jeff L; Franklin, Tammy et al. (2017) BOLD quantified renal pO2 is sensitive to pharmacological challenges in rats. Magn Reson Med 78:297-302
Prasad, Pottumarthi V; Thacker, Jon; Li, Lu-Ping et al. (2015) Multi-Parametric Evaluation of Chronic Kidney Disease by MRI: A Preliminary Cross-Sectional Study. PLoS One 10:e0139661
Thacker, Jon M; Li, Lu-Ping; Li, Wei et al. (2015) Renal Blood Oxygenation Level-Dependent Magnetic Resonance Imaging: A Sensitive and Objective Analysis. Invest Radiol 50:821-7