Abstract
The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally invasive renal pH imaging exams and test pH as a new diagnostic biomarker in animal models of kidney injury before clinical translation. Briefly, iodinated contrast agents approved by the US Food and Drug Administration (FDA) for computed tomography (CT) have demonstrated promise as novel chemical exchange saturation transfer (CEST) MRI agents for pH-sensitive imaging. The generalized ratiometric iopamidol CEST MRI analysis enables concentration-independent pH measurement, which simplifies in vivo renal pH mapping. This chapter describes quantitative CEST MRI analysis for preclinical renal pH mapping, and their application in rodents, including normal conditions and acute kidney injury.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure.
Highlights
Chemical exchange saturation transfer (CEST) Magnetic resonance imaging (MRI) provides a sensitive means to image microenvironment properties such as tissue pH, temperature, metabolites, and enzyme activities via dilute labile protons [1–12]
There has been an emerging library of iodinated-based CEST agents such as iopamidol, iobitridol, iopromide, and iodixanol, which have been approved by the U.S Food and Drug Administration (FDA) for computed tomography (CT) head and body imaging applications [39–47]
We describe variant ratiometric pH CEST MRI analysis techniques, image down-sampling expedited adaptive least-squares (IDEAL) fitting algorithm, smoothing splines interpolation algorithm and use of iodinated CEST agents for mapping renal pH in vivo [50, 70]
Summary
Chemical exchange saturation transfer (CEST) MRI provides a sensitive means to image microenvironment properties such as tissue pH, temperature, metabolites, and enzyme activities via dilute labile protons [1–12]. CEST detection which is specific to the administered agents [30– 34] This is because the labile proton exchange rate and chemical shifts can be designed/preselected to optimize these for exogenous CEST MRI contrast [35–38]. We describe variant ratiometric pH CEST MRI analysis techniques, image down-sampling expedited adaptive least-squares (IDEAL) fitting algorithm, smoothing splines interpolation algorithm and use of iodinated CEST agents for mapping renal pH in vivo [50, 70]. This analysis protocol chapter is complemented by two separate describing the basic concepts and experimental procedure, which are part of this book.
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