Dual assessment of kidney perfusion and pH by exploiting a dynamic CEST‐MRI approach in an acute kidney ischemia–reperfusion injury murine model

Abstract

Several factors can lead to acute kidney injury (AKI), but damage following ischemia and reperfusion injuries are the main risk factors and usually develop into chronic disease. MRI has often been proposed as a method with which to assess renal function. It does so by measuring the renal perfusion of an injected Gd-based contrast agent. The use of pH-responsive agents as part of the CEST (Chemical Exchange Saturation Transfer)-MRI technique has recently shown that pH homeostasis is also an important indicator of kidney functionality.However, there is still a need for methods that can provide more than one type of information following the injection of a single contrast agent and therefore furnish the improved and multiparametric characterization of renal function.Herein, we propose, for the first time, dynamic CEST acquisition following iopamidol injection to quantify renal function by assessing both perfusion and pH homeostasis. The aim of this study is to assess renal functionality in a murine unilateral ischemia-reperfusion injury model at two time points (3 and 7 days) after AKI. The renal-perfusion estimates measured with iopamidol were compared with those obtained with a Gadolinium-based agent, via a Dynamic Contrast Enhanced (DCE)-MRI approach, to validate the proposed method.Compared to the contralateral kidneys, the clamped ones showed a significant decrease in renal perfusion, as measured using the DCE-MRI approach, which is consistent with reduced filtration capability. Dynamic CEST-MRI findings provided similar results, indicating that the clamped kidneys displayed significantly reduced renal filtration that persisted up to 7 days after the damage. In addition, CEST-MRI pH imaging showed that the clamped kidneys displayed significantly increased pH values, reflecting the disturbance to pH homeostasis.Our results demonstrate that a single CEST-MRI contrast agent can provide multiple types of information related to renal function and can discern healthy kidneys from pathological ones by combining perfusion measurements with renal pH mapping.

Basic principles and new advances in kidney imaging

“…55 Very recent developments include hyperpolarized-[1- 13 C]pyruvate imaging, allowing evaluation of metabolic status directly in ischemic kidneys 56 and MRI-CEST (chemical-exchange-saturation-transfer) pH-mapping to evaluate both acid-base homeostasis and renal filtration. 57 Viability. Dynamic manganese-enhanced MRI allows tracing of manganese uptake, reflecting cellular viability.…”

Clinical and experimental approaches for imaging of acute kidney injury

“…Using a db/db endothelial nitric oxide synthase knockout model, we evaluated the utility of CEST imaging in assessing the progression of diabetic nephropathy and identified CEST effects corresponding to relative glucose/glycogen levels [ 119 ]. Longo et al reported the use of CEST MRI with iopamidol for measuring temporary pH elevation in both kidneys in several AKI mouse models [ 120 , 121 ]. CEST MRI has also been applied in a lipopolysaccharide-induced septic AKI mouse model [ 122 ].…”

Hydrogen–Deuterium Exchange Desorption Electrospray Ionization Mass Spectrometry Visualizes an Acidic Tumor Microenvironment

“…The pH of the tumor microenvironment (TME) plays a vital role in cancer progression and malignancy. , Cancer cells undergo uncontrolled proliferation and survive in a more acidic microenvironment. The acidity is attributed to metabolic reprogramming through tuning the anaerobic glycolysis as the major pathway to generate energy accompanied by excessive lactic acid production .…”