Wireless Amplified Nuclear MR Detector (WAND) for High-Spatial-Resolution MR Imaging of Internal Organs: Preclinical Demonstration in a Rodent Model

Abstract

Purpose:To assess the feasibility of imaging deep-lying internal organs at high spatial resolution by imaging kidney glomeruli in a rodent model with use of a newly developed, wireless amplified nuclear magnetic resonance (MR) detector. Materials and Methods:This study was approved by the Animal Care and Use Committee at the National Institutes of Health/National Institute of Neurologic Disorder and Stroke. As a preclinical demonstration of this new detection technology, five different millimeter-scale wireless amplified nuclear MR detectors configured as double frequency resonators were chronically implanted on the medial surface of the kidney in five Sprague-Dawley rats for MR imaging at 11.7 T. Among these rats, two were administered gadopentetate dimeglumine to visualize renal tubules on T1-weighted gradient-refocused echo (GRE) images, two were administered cationized ferritin to visualize glomeruli on T2*-weighted GRE images, and the remaining rat was administered both gadopentetate dimeglumine and cationized ferritin to visualize the interleaved pattern of renal tubules and glomeruli. The image intensity in each pixel was compared with the local tissue signal intensity average to identify regions of hyper-or hypointensity. Results:T1-weighted images with 70-mm in-plane resolution and 200-mm section thickness were obtained within 3.2 minutes to image renal tubules, and T2*-weighted images of the same resolution were obtained within 5.8 minutes to image the glomeruli. Hyperintensity from gadopentetate dimeglumine enabled visualization of renal tubules, and hypointensity from cationic ferritin enabled visualization of the glomeruli. Conclusion:High-spatial-resolution images have been obtained to observe kidney microstructures in vivo with a wireless amplified nuclear MR detector.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

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.…”

Live nephron imaging by MRI

“…To positively identify these bright regions as glomeruli, cationized ferritin was infused to detect individual glomeruli, as previously reported (16). Figure 2E1 shows the T 2 *-weighted image of the same region after administration of cationized ferritin.…”

“…In a previous study, Gd-DTPA was used in combination with the WAND to image rat kidneys at high resolution (16). Because Gd-DTPA could have strong T 2 * effects at increased concentrations, it was only used at 5 mol/kg body wt to avoid significant signal loss after water reabsorption in renal tubules.…”

“…This gain level is sufficient to maintain the local sensitivity of the WAND for a distance separation that is 10 times its own diameter. Compared with a local detector of similar dimension with direct cable connection, the WAND retains 70% sensitivity, which is much higher than the sensitivity achievable by an external coil or an internal detector with passive coupling (16).…”

“…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 (T 2 *) contrast introduced by cationized ferritin, and renal tubules enhanced by gadopentetate dimeglumine (Gd-DTPA) in longitudinal relaxation (T 1 ) weighted images (16). In this work, we extended the contrast available for kidney anatomy and function.…”