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Journal Article

Live nephron imaging by MRI


Yu,  X
Research Group Translational Neuroimaging and Neural Control, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Quian, C., Yu, X., Pothayee, N., Dodd, S., Bouraoud, N., Star, R., et al. (2014). Live nephron imaging by MRI. American Journal of Physiology - Renal Physiology, 307(10), F1162-F1168. doi:10.1152/ajprenal.00326.2014.

Cite as: http://hdl.handle.net/21.11116/0000-0000-FAFC-B
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 Mn2+ allowed the simultaneous detection of both glomeruli and renal tubules: Mn2+ was primarily reabsorbed by renal tubules, which would be distinguished from glomeruli due to higher enhancement in T1-weighted MRI. Dynamic studies of Mn2+ absorption confirmed the differential absorption affinity of glomeruli and renal tubules, potentially enabling the in vivo observation of nephron function. there has been considerable interest in observing individual nephrons and studying their function (6, 13, 14). Current techniques for nephron counting involve histology or acid maceration, thus are impractical for longitudinal preclinical studies or eventual clinical use. Micropuncture can study glomerular filtration of individual nephrons (7), but this destructive technique is applicable only to nephrons that are very close to the cortical surface. On the other hand, MRI is a nondestructive technique that has proven invaluable for structural and functional nephrology (4, 8, 9, 19–22). Contrast enhancement, based on the delivery of cationized ferritin, has enabled nondestructive observation of individual glomeruli (1, 2, 3, 5, 10). However, these high-resolution studies were mostly performed on ex vivo kidneys. In vivo observation of glomeruli is more challenging (5, 18), because it requires sensitive detection of remote signals emitted from deep inside the body. Whereas smaller MRI detectors placed close to the tissue of interest can improve local sensitivity, the need for cables to transfer the locally detected signals is cumbersome and introduces a risk of infection. Recently, a wireless amplified NMR detector (WAND) (15) was developed to actively amplify emitted signals from small, implantable MR detectors (11, 17). Such enhanced sensitivity enabled the in vivo observation of individual glomeruli using transverse dephasing (T2*) contrast introduced by cationized ferritin, and renal tubules enhanced by gadopentetate dimeglumine (Gd-DTPA) in longitudinal relaxation (T1) weighted images (16). In this work, we extended the contrast available for kidney anatomy and function. Glomeruli were observable in native kidney as hyperintense regions due to the high blood flow inside glomerulus arterioles. After MnCl2 was infused intravenously, the majority of Mn2+ accumulated in renal tubules and enhanced tubular signals to a greater extent, while glomeruli appeared as less enhanced regions compared with their surrounding tissues. Dynamic studies of MnCl2 absorption confirmed the differential affinity of glomeruli and renal tubules to Mn2+, paving way for in vivo studies of nephron function. The WAND technique can be used to noninvasively monitor nephron physiology in vivo and could potentially be used to study structure-function relationships and macromolecular filtration of individual nephrons. The ability to image glomeruli and renal tubules nondestructively may eventually enable the clinical use of the WAND as a chronic monitoring device for transplanted kidneys.