Systemic Administration of Polyelectrolyte Microcapsules: Where Do They Accumulate and When? In Vivo and Ex Vivo Study

Multilayer capsules of 4 microns in size made of biodegradable polymers and iron oxide magnetite nanoparticles have been injected intravenously into rats. The time-dependent microcapsule distribution in organs was investigated in vivo by magnetic resonance imaging (MRI) and ex vivo by histological examination (HE), atomic absorption spectroscopy (AAS) and electron spin resonance (ESR), as these methods provide information at different stages of microcapsule degradation. The following organs were collected: Kidney, liver, lung, and spleen through 15 min, 1 h, 4 h, 24 h, 14 days, and 30 days after intravenous injections (IVIs) of microcapsules in a saline buffer at a dosage of 2.5 × 109 capsule per kg. The IVI of microcapsules resulted in reversible morphological changes in most of the examined inner organs (kidney, heart, liver, and spleen). The capsules lost their integrity due to degradation over 24 h, and some traces of iron oxide nanoparticles were seen at 7 days in spleen and liver structure. The morphological structure of the tissues was completely restored one month after IVI of microcapsules. Comprehensive analysis of the biodistribution and degradation of entire capsules and magnetite nanoparticles as their components gave us grounds to recommend these composite microcapsules as useful and safe tools for drug delivery applications.

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Dynamics of the Tracheal Airway and Its Influences on Respiratory Airflows: An Exemplar Study

Journal of Biomechanical Engineering ◽

10.1115/1.4043723 ◽

2019 ◽

Vol 141 (11) ◽

Cited By ~ 1

Author(s):

Bora Sul ◽

Talissa Altes ◽

Kai Ruppert ◽

Kun Qing ◽

Daniel S. Hariprasad ◽

...

Keyword(s):

Morphological Changes ◽

Minute Ventilation ◽

Correlation Coefficients ◽

Dynamic Imaging ◽

Imaging Data ◽

Cross Sectional ◽

Mild Conditions ◽

Large Airways ◽

Magnetic Resonance Imaging Mri

Respiration is a dynamic process accompanied by morphological changes in the airways. Although deformation of large airways is expected to exacerbate pulmonary disease symptoms by obstructing airflow during increased minute ventilation, its quantitative effects on airflow characteristics remain unclear. Here, we used in vivo dynamic imaging and examined the effects of tracheal deformation on airflow characteristics under different conditions based on imaging data from a single healthy volunteer. First, we measured tracheal deformation profiles of a healthy lung using magnetic resonance imaging (MRI) during forced exhalation, which we simulated to characterize the subject-specific airflow patterns. Subsequently, for both inhalation and exhalation, we compared the airflows when the modeled deformation in tracheal cross-sectional area was 0% (rigid), 33% (mild), 50% (moderate), or 75% (severe). We quantified differences in airflow patterns between deformable and rigid airways by computing the correlation coefficients (R) and the root-mean-square of differences (Drms) between their velocity contours. For both inhalation and exhalation, airflow patterns were similar in all branches between the rigid and mild conditions (R > 0.9; Drms < 32%). However, airflow characteristics in the moderate and severe conditions differed markedly from those in the rigid and mild conditions in all lung branches, particularly for inhalation (moderate: R > 0.1, Drms < 76%; severe: R > 0.2, Drms < 96%). Our exemplar study supports the use of a rigid airway assumption to compute flows for mild deformation. For moderate or severe deformation, however, dynamic contraction should be considered, especially during inhalation, to accurately predict airflow and elucidate the underlying pulmonary pathology.

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The emerging role of MRI in quantitative renal glomerular morphology

AJP Renal Physiology ◽

10.1152/ajprenal.00714.2012 ◽

2013 ◽

Vol 304 (10) ◽

pp. F1252-F1257 ◽

Cited By ~ 36

Author(s):

K. M. Bennett ◽

John F. Bertram ◽

Scott C. Beeman ◽

Norbert Gretz

Keyword(s):

Ex Vivo ◽

Kidney Volume ◽

Minimal Sample ◽

Kidney Morphology ◽

Glomerular Size ◽

Magnetic Resonance Imaging Mri ◽

Primary Advantage ◽

Glomerular Morphology

Techniques to measure morphological parameters, such as glomerular (and thereby nephron) number, glomerular size, and kidney volume, have been vital to understanding factors contributing to chronic kidney disease (CKD). These techniques have also been important to understanding the associations between CKD and other systemic and cardiovascular diseases and have led to the identification of developmental risk factors for these pathologies. However, existing techniques in quantitative kidney morphology are resource- and time-consuming and are destructive to the organ. This review discusses the emerging generation of techniques to study kidney morphology quantitatively using magnetic resonance imaging (MRI) using the intravenous injection of the superparamagnetic nanoparticle cationic ferritin, which binds to the glomerular basement membrane. A primary advantage of MRI over previously established techniques is the ability to quantify morphology in the intact organ with minimal sample preparation. We highlight areas of research where MRI-based morphological measurements will be helpful in animal models and possibly diagnostic clinical nephrology, discuss technical challenges in light of the progress in MRI techniques to date, and identify novel measurements that may be possible using MRI, both ex vivo and in vivo.

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Age-dependent visualization of neural progenitor cells within the rostral migratory stream via MRI and endogenously labeled micron-sized iron oxide particles

10.1101/429787 ◽

2018 ◽

Cited By ~ 2

Author(s):

Dorela D. Shuboni-Mulligan ◽

Shatadru Chakravarty ◽

Christiane L. Mallett ◽

Alexander M. Wolf ◽

Stacey Forton ◽

...

Keyword(s):

Iron Oxide ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Ex Vivo ◽

Neural Progenitor ◽

Rostral Migratory Stream ◽

Iron Oxide Particles ◽

The Impact ◽

Migratory Stream

AbstractThe subventricular zone (SVZ) is one of the primary sources for rodent neural progenitor cells (NPC), however, aging greatly impacts the substructure of the region and rate of new cell birth. To determine if age impacts the rate of in vivo migration within animals, we examined the rostral migratory stream (RMS) of animals across 12 days using an established MRI technique. To visualize NPCs, we injected micron sized particles of iron oxide (MPIO) into the lateral ventricle to endogenously label cells within the SVZ, which then appeared as hypo-intensive spots within MR images. Our in vivo MRI data showed that the rate of migration was significantly different between all ages examined, with decreases in the distance traveled as age progressed. The total number of iron oxide labeled cells within the olfactory bulb on day 12, decrease significantly when compared across ages in ex vivo high-resolution scans. We also, for the first time, demonstrated the endogenous labeling of cells within the dentate gyrus (DG) of hippocampus. Here too, there was a significant decrease in the number of labeled cells within the structure across age. Histology of the NPCs verified the decrease in labeling of cells with doublecortin (DCX) as age progressed for both regions. The dramatic reduction of labeling in NPCs within the SVZ and DG observed with MRI, demonstrates the importance of understanding the impact of age on the relationship of NPC and disease.

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Abstract 474: Early Events in Dissecting Aneurysms Induced by Angiotensin-II Infusion: The Geometry-Driven Aspect of a Multifaceted Problem

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.474 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Lydia Aslanidou ◽

Bram Trachet ◽

Mauro Ferraro ◽

Alessandra Piersigilli ◽

Rodrigo Fraga-Silva ◽

...

Keyword(s):

Finite Element ◽

Angiotensin Ii ◽

Ex Vivo ◽

Apoptotic Cell ◽

Morphological Changes ◽

Aortic Tissue ◽

Isotropic Resolution ◽

Circumferential Distribution ◽

Dissecting Aneurysms

While research on dissecting aneurysms in Angiotensin-II infused mice spans more than a decade, the temporal sequence of initial events still remains unclear. Recent findings in our group suggested that focal medial tears at the vicinity of suprarenal side branches are the primary event in disease formation. In this study we used a combined experimental-computational approach to investigate the hypothesis that initial events of dissecting AAAs originate at branching sites along the aorta. Male apolipoprotein-deficient mice were infused with Angiotensin-II (n=11) and saline 0.9% (n=6) for 3 days and scanned with contrast-enhanced microCT prior to sacrifice. One animal presented an in-vivo rupture during the microCT scan, and was rescanned after 2.5 hours to observe real-time morphological changes. In all other animals, the excised aortic tissue was imaged with Phase Contrast X-Ray Tomographic Microscopy (PCXTM) at 6.5um isotropic resolution. An automatic morphing code was developed to map the ex-vivo geometry onto the in vivo geometry, and a finite element simulation yielded a stress distribution that represents an estimation of the wall tension, not only due to the pressurization, but also due to the local stretch field. We found that the nanoparticulate microCT contrast agent had infiltrated the aortic wall in 11/11 Ang-II infused animals, while no infiltration was observed in 6/6 control mice. The infiltration affected at least one pair of intercostal arteries in 11/11 mice, and in 9/11 mice the coeliac region was also affected. Image-guided histology allowed us to determine the circumferential distribution of microlesions at branching sites, including disruption of elastin fibers, apoptotic cell appearance, subintimal leukocyte infiltration and intramural hematomas. In the animal whose aorta had ruptured during the in vivo scan, the initial hematoma had originated around 3 pairs of intercostal arteries and quickly propagated afterwards. Mouse-specific finite element simulations revealed a co-location of computed peak stresses at the vessel wall and histologically identified vascular damage. We conclude that the aortic geometry, and side branches in particular, play a pivotal role in the onset of dissecting AAA.

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Sensitive detection of extremely small iron oxide nanoparticles in living mice using MP2RAGE with advanced image co-registration

Scientific Reports ◽

10.1038/s41598-020-80181-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joong H. Kim ◽

Stephen Dodd ◽

Frank Q. Ye ◽

Andrew K. Knutsen ◽

Duong Nguyen ◽

...

Keyword(s):

Iron Oxide ◽

Contrast Agents ◽

Iron Oxide Nanoparticles ◽

Mouse Brain ◽

Oxide Nanoparticles ◽

Non Invasive ◽

T1 Map ◽

Magnetic Resonance Imaging Mri ◽

Molecular Contrast

AbstractMagnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared—RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm3 voxel at 9.4 T. Test–retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.

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Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue

Magnetic Resonance Insights ◽

10.4137/mri.s23557 ◽

2015 ◽

Vol 8s1 ◽

pp. MRI.S23557 ◽

Cited By ~ 11

Author(s):

Daniel J. Korchinski ◽

May Taha ◽

Runze Yang ◽

Nabeela Nathoo ◽

Jeff F. Dunn

Keyword(s):

Iron Oxide ◽

Contrast Agents ◽

Cell Tracking ◽

Ex Vivo ◽

Cerebral Aneurysms ◽

Cell Types ◽

Mri Contrast Agent ◽

Mri Contrast ◽

Different Cell Types

Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation.

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Subcortical Atlas of the Rhesus Macaque (SARM) for Magnetic Resonance Imaging

10.1101/2020.09.16.300053 ◽

2020 ◽

Author(s):

Renée Hartig ◽

Daniel Glen ◽

Benjamin Jung ◽

Nikos K. Logothetis ◽

George Paxinos ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Rhesus Macaque ◽

Ex Vivo ◽

Brain Structures ◽

List Type ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Mri ◽

Dorsal Lateral Geniculate

AbstractDigitized neuroanatomical atlases are crucial for localizing brain structures and analyzing functional networks identified by magnetic resonance imaging (MRI). To aid in MRI data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. The structural scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (RMBSC4; Paxinos et al., in preparation). The SARM features six parcellation levels, arranged hierarchically from fine regions-of-interest (ROIs) to broader composite regions, suited for fMRI studies. As a test, we ran a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques and found significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MR data processing software, such as AFNI, where the atlas can be embedded into the software alongside cortical macaque atlases.HighlightsWe present the Subcortical Atlas of the Rhesus Macaque (SARM).SARM provides a neuroanatomical reference frame for neuroimaging analysis.The entire subcortex is mapped, including the thalamus, basal ganglia, and brainstem.ROIs are grouped hierarchically, making SARM useful at multiple spatial resolutions.SARM is in the NMT v2 template space and complements the CHARM atlas for the cortex.

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In-vivo histology of iron and myelin in the brain using magnetic susceptibility source separation in MRI

10.1101/2020.11.07.363796 ◽

2020 ◽

Author(s):

Hyeong-Geol Shin ◽

Jingu Lee ◽

Young Hyun Yun ◽

Seong Ho Yoo ◽

Jinhee Jang ◽

...

Keyword(s):

Magnetic Susceptibility ◽

Ex Vivo ◽

Biophysical Model ◽

Normal Brain ◽

Brain Functions ◽

Magnetic Resonance Imaging Mri ◽

The Individual ◽

Multiple Sclerosis Patients ◽

The Brain

ABSTRACTObtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in a few neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of iron and myelin to MRI signals via their difference in magnetic susceptibility (i.e., paramagnetic iron vs. diamagnetic myelin). Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of iron and myelin. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen (e.g., co-localization of iron and myelin in Gennari line), healthy volunteers (e.g., myelin-lacking and iron-rich pulvinar), and multiple sclerosis patients (e.g., demyelinated iron-rim lesion). This new in-vivo histology technology, taking less than 20 min, may serve as a practical tool for exploring the microstructural information of the brain.

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Modeling Tumor Cellularity in Newly Diagnosed GBMs using MR Imaging and Spectroscopy

10.54294/d9fe89 ◽

2010 ◽

Author(s):

Alexandra Constantin ◽

Sarah Nelson ◽

Ruzena Bajcsy

Keyword(s):

Expectation Maximization ◽

Ex Vivo ◽

Resonance Imaging ◽

Tissue Samples ◽

Imaging And Spectroscopy ◽

Magnetic Resonance Imaging Mri ◽

Definition Of ◽

Quantitative Definition ◽

The Relationship

In this paper, we analyze the relationship between parameters of brain tumors obtained through in vivo magnetic resonance imaging (MRI), in vivo magneticnresonance spectroscopy (MRS), and ex vivo immunohistochemistry (IHC). The goal of our project is to provide a quantitative definition of tumor cellularity based on the in vivo parameters. Biopsy samples obtained from previously untreated patients with a diagnosis of GBM are used to find the link between imaging parameters at the specific biopsy locations and IHC parameters from the corresponding tissue samples. A functional tree (FT) model of tumor cellularity is learned from the in vivo parameters and the remaining histological parameters. The tumor cellularity model is then tested on examples which contain only in vivo parameters, by first estimating the remaining IHC parameters by applying the Expectation Maximization (EM) algorithm, and then using the complete parameter vector for classification.

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IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis

Journal of Experimental Medicine ◽

10.1084/jem.20092265 ◽

2010 ◽

Vol 207 (6) ◽

pp. 1307-1319 ◽

Cited By ~ 40

Author(s):

Rahul Mittal ◽

Ignacio Gonzalez-Gomez ◽

Ashok Panigrahy ◽

Kerstin Goth ◽

Richard Bonnet ◽

...

Keyword(s):

Escherichia Coli ◽

Ex Vivo ◽

Morphological Changes ◽

Neonatal Meningitis ◽

Prostaglandin E ◽

Antibody Treatment ◽

Antibiotic Resistant ◽

E Coli ◽

Escherichia Coli K1

Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10−/− mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis.

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