Live nephron imaging by MRI

Abstract

The local sensitivity of MRI can be improved with small MR detectors placed close to regions of interest. However, to maintain such sensitivity advantage, local detectors normally need to communicate with the external amplifier through cable connections, which prevent the use of local detectors as implantable devices. Recently, an integrated wireless amplifier was developed that can efficiently amplify and broadcast locally detected signals, so that the local sensitivity was enhanced without the need for cable connections. This integrated detector enabled the live imaging of individual glomeruli using negative contrast introduced by cationized ferritin, and the live imaging of renal tubules using positive contrast introduced by gadopentetate dimeglumine. Here, we utilized the high blood flow to image individual glomeruli as hyperintense regions without any contrast agent. These hyperintense regions were identified for pixels with signal intensities higher than the local average. Addition of Mn(2+) allowed the simultaneous detection of both glomeruli and renal tubules: Mn(2+) was primarily reabsorbed by renal tubules, which would be distinguished from glomeruli due to higher enhancement in T1-weighted MRI. Dynamic studies of Mn(2+) absorption confirmed the differential absorption affinity of glomeruli and renal tubules, potentially enabling the in vivo observation of nephron function.

Current MRI techniques for the assessment of renal disease

“…Although several technical challenges remain to make in vivo detection of CF practical, including the relaxivity of CF and differentiating background from blood, these studies clearly demonstrate the potential utility of MRI in assessing glomerular number, function, and pathology. In this context, it is noteworthy that Qian et al has recently shown that individual rat glomeruli can be identified as hyper intensive (high blood flow) regions by MRI in vivo , when MRI’s sensitivity is enhanced with an implantable Wireless Amplified NMR Detector (WAND)[61]. In this study, the authors also demonstrated that WAND enables the detection of CF-labeled glomeruli in vivo .…”

Biocompatibility of ferritin-based nanoparticles as targeted MRI contrast agents

“…CF has enabled visualization of the kidney GBM in rodents and humans using MRI (19,20,23), allowing the first whole-organ assessment of renal glomerular structure. CF accumulation, alone or with other agents, may also be used to measure renal function at the single-nephron level (24,25). MRI enhanced by CF (CFE-MRI) provides an opportunity to noninvasively monitor patients at risk for chronic kidney disease, determine risk for cardiovascular and kidney disease, improve transplant assessment, and determine the renal effects of new therapies.…”

Counting glomeruli and podocytes

“…A recent study by Qian et al [46] reported in vivo observation of rat glomeruli through signal amplification by a Wireless Amplified NMR Detector (WAND). Individual glomeruli were positively visualized by blood flow, and negatively visualized by ferritin and Mn 2+ .…”