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

Several factors can lead to acute kidney injury, but damage following ischemia and reperfusion injuries is the main risk factor and usually develops 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 for the 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 acute kidney injury. 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 with 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.

MRI-CEST assessment of tumour perfusion using X-ray iodinated agents: comparison with a conventional Gd-based agent.

OBJECTIVES: X-ray iodinated contrast media have been shown to generate contrast in MR images when used with the chemical exchange saturation transfer (CEST) approach. The aim of this study is to compare contrast enhancement (CE) capabilities and perfusion estimates between radiographic molecules and a Gd-based contrast agent in two tumour murine models with different vascularization patterns. METHODS: MRI-CEST and MRI-CE T1w images were acquired in murine TS/A and 4 T1 breast tumours upon sequential i.v. injection of iodinated contrast media (iodixanol, iohexol, and iopamidol) and of gadoteridol. The signal enhancements observed in the two acquisition modalities were evaluated using Pearson's correlation, and the correspondence in the spatial distribution was assessed by a voxelwise comparison. RESULTS: A significant, positive correlation was observed between iodinated contrast media and gadoteridol for tumour contrast enhancement and perfusion values for both tumour models (r = 0.51-0.62). High spatial correlations were observed in perfusion maps between iodinated molecules and gadoteridol (r = 0.68-0.86). Tumour parametric maps derived by iodinated contrast media and gadoteridol showed high spatial similarities. CONCLUSIONS: A good to strong spatial correlation between tumour perfusion parameters derived from MRI-CEST and MRI-CE modalities indicates that the two procedures provide similar information. KEY POINTS: • Gd-based agents are the standard of reference for contrast-enhanced MRI. • Iodinated contrast media provides MRI-CEST contrast enhancement in animal tumour models. • Contrast enhancements were positively correlated between iodinated agents and gadoteridol. • Tumour perfusion map showed similar spatial distribution between iodinated agents and gadoteridol. • MRI-CEST with iodinated agents provide similar information to gadoteridol.

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents.

OBJECTIVES: The aim of this study was to evaluate 4 nonionic x-ray iodinated contrast agents (CAs), commonly used in radiographic procedures, as novel chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) agents by assessing their in vitro exchange properties and preliminary in vivo use as tumor enhancing agents. MATERIALS AND METHODS: The CEST properties, as function of pH (range, 5.5-7.9) and of radio frequency conditions (irradiation field strength range of 1-9 µT and time of 1-9 seconds), have been determined at 7 T and 310 K for 4 x-ray CAs commonly used in clinical settings, namely, iomeprol, iohexol, ioversol, and iodixanol. Their in vivo properties have been investigated upon intravenous injection in a murine HER2+ breast tumor model (n = 4 mice for each CA) using both computed tomography (CT) and MRI modalities. RESULTS: The prototropic exchange rates measured for the 4 investigated iodinated molecules showed strong pH dependence with base catalyzed exchange rate that was faster for monomeric compounds (20-4000 Hz in the pH range of 5.5-7.9). Computed tomography quantification showed marked (up to 2 mg I/mL concentration) and prolonged accumulation (up to 30 minutes postinjection) inside tumor regions. Among the 4 agents we tested, iohexol and ioversol display good CEST contrast properties at 7 T, and in vivo results confirmed strong and prolonged contrast enhancement of the tumors, with elevated extravasation fractions (74%-91%). A strong and significant correlation was found between CT and CEST-MRI tumor-enhanced images (R = 0.70, P < 0.01). CONCLUSIONS: The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information.