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Molecular MR Imaging of Renal Fibrogenesis in Mice
Yin-Ching Chen1, Philip A Waghorn1,2, Ivy A Rosales3
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
Background:
In most CKDs, lysyl oxidase oxidation of collagen forms allysine side chains, which then form stable crosslinks. We hypothesized that MRI with the allysine-targeted probe Gd-oxyamine (OA) could be used to measure this process and noninvasively detect renal fibrosis.
Methods:
Two mouse models were used: hereditary nephritis in Col4a3-deficient mice (Alport model) and a glomerulonephritis model, nephrotoxic nephritis (NTN). MRI measured the difference in kidney relaxation rate, ΔR1, after intravenous Gd-OA administration. Renal tissue was collected for biochemical and histological analysis.
Results:
ΔR1 was increased in the renal cortex of NTN mice and in both the cortex and the medulla of Alport mice. Ex vivo tissue analyses showed increased collagen and Gd-OA levels in fibrotic renal tissues and a high correlation between tissue collagen and ΔR1.
Conclusions:
Magnetic resonance imaging using Gd-OA is potentially a valuable tool for detecting and staging renal fibrogenesis.
Insights
Magnetic resonance imaging using Gd-oxyamine (Gd-OA) can detect collagen crosslinks in chronic kidney disease (CKD). This novel MRI technique shows promise for noninvasively assessing renal fibrosis progression.
Area of Science:
- Biomedical Imaging
- Nephrology
- Biochemistry
Background:
- Chronic kidney diseases (CKDs) involve lysyl oxidase-mediated collagen crosslinking, forming stable structures.
- This process, leading to renal fibrosis, is a hallmark of CKD progression.
Purpose of the Study:
- To investigate the utility of MRI with an allysine-targeted contrast agent, Gd-oxyamine (Gd-OA), for detecting and quantifying renal fibrosis.
- To assess the correlation between MRI-derived measurements and biochemical markers of fibrosis.
Main Methods:
- Utilized two mouse models of kidney disease: Alport syndrome (hereditary nephritis) and nephrotoxic nephritis (NTN).
- Administered Gd-OA intravenously and measured the change in kidney relaxation rate (ΔR1) using MRI.
- Performed ex vivo biochemical and histological analyses of renal tissues to quantify collagen and Gd-OA levels.
Main Results:
- Increased ΔR1 was observed in the renal cortex of NTN mice and in both the cortex and medulla of Alport mice.
- Ex vivo analysis revealed elevated collagen and Gd-OA levels in fibrotic kidney tissues.
- A strong positive correlation was found between tissue collagen content and ΔR1 measurements.
Conclusions:
- MRI with Gd-OA is a promising noninvasive tool for detecting renal fibrogenesis.
- This technique has the potential to aid in the staging and monitoring of renal fibrosis in CKD.
