The organization of 2,3-iron-naphthalocyanine molecules on substrate as revealed by scanning tunneling microscopy

Surface morphology of thin molecular layer of 2,3-Iron-naphthalocyanine (2,3 FeNPc) was studied by scanning tunneling microscopy (STM) at the ambient conditions. Organic layer with thickness of 40 nm was vapour phase deposited on amorphous carbon substrate. The STM images have revealed the pecularities of surface molecular organization from large range (hundreds of nm) down to atomic scale. Arrays of locally ordered linear stuctures have been distinguished as the main morphological features of the examined surface. At several places the well-ordered STM patterns have been distinguished at the atomic scale. They can be described as stacks of periodicity approximatelly 0.4 nm in a row and 1.5 nm between stacks. These results can be explained by arrangement of 2,3-FeNPh molecules in stacks with a main plane being perpendicular to the substrate surface

Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction

Detailing the relation between renal T(2)* and renal tissue pO2 using an integrated approach of parametric magnetic resonance imaging and invasive physiological measurements

OBJECTIVES: This study was designed to detail the relation between renal T2* and renal tissue pO2 using an integrated approach that combines parametric magnetic resonance imaging (MRI) and quantitative physiological measurements (MR-PHYSIOL. MATERIALS AND METHODS: Experiments were performed in 21 male Wistar rats. In vivo modulation of renal hemodynamics and oxygenation was achieved by brief periods of aortic occlusion, hypoxia, and hyperoxia. Renal perfusion pressure (RPP), renal blood flow (RBF), local cortical and medullary tissue pO2, and blood flux were simultaneously recorded together with T2*, T2 mapping, and magnetic resonance-based kidney size measurements (MR-PHYSIOL). Magnetic resonance imaging was carried out on a 9.4-T small-animal magnetic resonance system. Relative changes in the invasive quantitative parameters were correlated with relative changes in the parameters derived from MRI using Spearman analysis and Pearson analysis. RESULTS: Changes in T2* qualitatively reflected tissue pO2 changes induced by the interventions. T2* versus pO2 Spearman rank correlations were significant for all interventions, yet quantitative translation of T2*/pO2 correlations obtained for one intervention to another intervention proved not appropriate. The closest T2*/pO2 correlation was found for hypoxia and recovery. The interlayer comparison revealed closest T2*/pO2 correlations for the outer medulla and showed that extrapolation of results obtained for one renal layer to other renal layers must be made with due caution. For T2* to RBF relation, significant Spearman correlations were deduced for all renal layers and for all interventions. T2*/RBF correlations for the cortex and outer medulla were even superior to those between T2* and tissue pO2. The closest T2*/RBF correlation occurred during hypoxia and recovery. Close correlations were observed between T2* and kidney size during hypoxia and recovery and for occlusion and recovery. In both cases, kidney size correlated well with renal vascular conductance, as did renal vascular conductance with T2*. Our findings indicate that changes in T2* qualitatively mirror changes in renal tissue pO2 but are also associated with confounding factors including vascular volume fraction and tubular volume fraction. CONCLUSIONS: Our results demonstrate that MR-PHYSIOL is instrumental to detail the link between renal tissue pO2 and T2* in vivo. Unravelling the link between regional renal T2* and tissue pO2, including the role of the T2* confounding parameters vascular and tubular volume fraction and oxy-hemoglobin dissociation curve, requires further research. These explorations are essential before the quantitative capabilities of parametric MRI can be translated from experimental research to improved clinical understanding of hemodynamics/oxygenation in kidney disorders

Detailing renal hemodynamics and oxygenation in rats by a combined near-infrared spectroscopy and invasive probe approach

We hypothesize that combining quantitative near-infrared spectroscopy (NIRS) with established invasive techniques will enable advanced insights into renal hemodynamics and oxygenation in small animal models. We developed a NIRS technique to monitor absolute values of oxygenated and deoxygenated hemoglobin and of oxygen saturation of hemoglobin within the renal cortex of rats. This NIRS technique was combined with invasive methods to simultaneously record renal tissue oxygen tension and perfusion. The results of test procedures including occlusions of the aorta or the renal vein, hyperoxia, hypoxia, and hypercapnia demonstrated that the combined approach, by providing different but complementary information, enables a more comprehensive characterization of renal hemodynamics and oxygenation

Experimental MRI monitoring of renal blood volume fraction variations en route to renal magnetic resonance oximetry

Diagnosis of early-stage acute kidney injury (AKI) will benefit from a timely identification of local tissue hypoxia. Renal tissue hypoxia is an early feature in AKI pathophysiology, and renal oxygenation is increasingly being assessed through T(2)*-weighted magnetic resonance imaging (MRI). However, changes in renal blood volume fraction (BVf) confound renal T(2)*. The aim of this study was to assess the feasibility of intravascular contrast-enhanced MRI for monitoring renal BVf during physiological interventions that are concomitant with variations in BVf and to explore the possibility of correcting renal T(2)* for BVf variations. A dose-dependent study of the contrast agent ferumoxytol was performed in rats. BVf was monitored throughout short-term occlusion of the renal vein, which is known to markedly change renal blood partial pressure of O(2) and BVf. BVf calculated from MRI measurements was used to estimate oxygen saturation of hemoglobin (SO(2)). BVf and SO(2) were benchmarked against cortical data derived from near-infrared spectroscopy. As estimated from magnetic resonance parametric maps of T(2) and T(2)*, BVf was shown to increase, whereas SO(2) was shown to decline during venous occlusion (VO). This observation could be quantitatively reproduced in test-retest scenarios. Changes in BVf and SO(2) were in good agreement with data obtained from near-infrared spectroscopy. Our findings provide motivation to advance multiparametric MRI for studying AKIs, with the ultimate goal of translating MRI-based renal BVf mapping into clinical practice en route noninvasive renal magnetic resonance oximetry as a method of assessing AKI and progression to chronic damage

Subsegmentation of the Kidney in Experimental MR Images Using Morphology-Based Regions-of-Interest or Multiple-Layer Concentric Objects.

Functional renal MRI promises access to a wide range of physiologically relevant parameters such as blood oxygenation, perfusion, tissue microstructure, pH, and sodium concentration. For quantitative comparison of results, representative values must be extracted from the parametric maps obtained with these different MRI techniques. To improve reproducibility of results this should be done based on regions-of-interest (ROIs) that are clearly and objectively defined.Semiautomated subsegmentation of the kidney in magnetic resonance images represents a simple but very valuable approach for the quantitative analysis of imaging parameters in multiple ROIs that are associated with specific anatomic locations. Thereby, it facilitates comparing MR parameters between different kidney regions, as well as tracking changes over time.Here we provide detailed step-by-step instructions for two recently developed subsegmentation techniques that are suitable for kidneys of small rodents: i) the placement of ROIs in cortex, outer and the inner medulla based on typical kidney morphology and ii) the division of the kidney into concentrically oriented layers.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers

Monitoring kidney size to interpret MRI-based assessment of renal oxygenation in acute pathophysiological scenarios

AIM: Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T(2) and T(2) * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here we used dynamic MRI to monitor KS for physiological interpretation of T(2) * and T(2) changes in acute pathophysiological scenarios. METHODS: KS was determined from T(2) *,T(2) mapping in rats. Six interventions which acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions which change the blood and/or tubular volume. A biophysical model was used to estimate changes in O(2) saturation of haemoglobin from changes in T(2) * and KS. RESULTS: Upon aortic occlusion KS decreased; this correlated with a decrease in T(2) *,T (2). Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T(2) *,T(2). Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T(2)*,T(2). Hypoxaemia induced mild reductions in KS and T(2) *,T . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T(2) *,T(2) followed by a decrease. Furosemide caused T(2) *,T(2) elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T(2) *. CONCLUSION: Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T(2) *,T(2) . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies

Monitoring renal hemodynamics and oxygenation by invasive probes: experimental protocol

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe methods to study control of renal hemodynamics and tissue oxygenation by means of invasive probes in anesthetized rats. Step-by-step protocols are provided for two setups, one for experiments in laboratories for integrative physiology and the other for experiments within small-animal magnetic resonance scanners.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by a separate chapter describing the basic concepts of quantitatively assessing renal perfusion and oxygenation with invasive probes