MRI-based techniques to measure whole-kidney nephron endowment MRI-based techniques to measure whole-kidney nephron endowment The broad, long-term goal of this work is to measure kidney nephron endowment in humans, in vivo. Each nephron contains a glomerulus, which functions as a high-pressure filter of blood macromolecules. Deficits in nephrons and glomeruli have been correlated with renal diseases such as diabetes, obesity, and hypertension. Nephron and glomerular deficits in animals and humans are correlated with primary renal pathologies and secondary vascular diseases. All previous studies of nephron deficits have used either acid maceration or sterological counting techniques. The imaging technique proposed here is nondestructive, and will be used to estimate the total number of individual glomeruli in the whole kidney. The proposed work will establish a real-time, in vivo glomerular counting technique in animal studies of renal and systemic diseases. We propose that contrastenhanced MRI, using novel MRI-detectable superparamagnetic nanoparticles targeted to the glomerular basement membrane, can be used to accurately count the total number of functioning glomeruli in the whole, intact kidney. This proposal is focused on establishing this technique in mice because there are multiple congenital mouse models relevant to human systemic and renal diseases. We will first develop the technique in vitro, based on our previous experience in rat models, and will further develop in vivo imaging techniques to assess renal uptake. In both in vivo and in vitro studies, we will assess the accuracy of the technique in the presence of systemic deficits in nephron endowment, and to study the toxicity of the nanoparticle contrast agents in detectable concentrations. This is the first example of a noninvasive in vivo imaging technique to precisely measure glomerular number and nephron endowment in the whole kidney. This work will lay the foundation for the use of MRI-detectable nanoparticles to study single nephron distribution and function in mouse models of renal disease. It therefore has a broad potential to impact our understanding of the development and treatment of renal and systemic disease.
|Effective start/end date||1/1/12 → 12/31/12|
- American Heart Association: Western States Affiliate: $70,000.00
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