Transverse relaxation in fixed tissue: Influence of temperature and resolution on image contrast in magnetic resonance microscopy.

To describe transverse relaxation of water in fixed tissue, we propose a model of transverse relaxation accelerated by diffusion and exchange (TRADE) that assumes exchange between free (visible) and bound (invisible) water, which relax by the dipole-dipole interaction, chemical exchange, and translation in the field gradient. Depending on the prevailing mechanism, transverse relaxation time (T ) of water in fixed tissue could increase (when dipole-dipole interaction prevails) or decrease with temperature (when diffusion in the field gradient prevails). Chemical exchange can make T even temperature independent.

Quantitative Magnetization Transfer Detects Renal Fibrosis in Murine Kidneys With Renal Artery Stenosis.

Background: Renal fibrosis is a common pathway in tubulointerstitial injury and a major determinant of renal insufficiency. Collagen deposition, a key feature of renal fibrosis, may serve as an imaging biomarker to differentiate scarred from healthy kidneys.

Purpose: To test the feasibility of using quantitative magnetization transfer (qMT), which assesses tissue macromolecule content, to measure renal fibrosis.

Influence of water based embedding media composition on the relaxation properties of fixed tissue.

Background: In MRI of formalin-fixed tissue one of the problems is the dependence of tissue relaxation properties on formalin composition and composition of embedding medium (EM) used for scanning. In this study, we investigated molecular mechanisms by which the EM composition affects T2 relaxation directly and T1 relaxation indirectly.

Objective: To identify principal components of formaldehyde based EM and the mechanism by which they affect relaxation properties of fixed tissue.

Measurement of murine kidney functional biomarkers using DCE-MRI: A multi-slice TRICKS technique and semi-automated image processing algorithm.

Purpose: To propose a rapid multi-slice T measurement method using time-resolved imaging of contrast kinetics (TRICKS) and a semi-automated image processing algorithm for comprehensive assessment murine kidney function using dynamic contrast-enhanced MRI (DCE-MRI).

Methods: A multi-slice TRICKS sampling scheme was implemented in an established rapid T measurement method. A semi-automated image-processing scheme employing basic image processing techniques and machine learning was developed to facilitate image analysis.

Three-dimensional NMR microscopy of zebrafish specimens.

While zebrafish embryos in the first five days after fertilization are clear and amenable to optical analysis, older juveniles and adults are not, due to pigmentation development and tissue growth. Thus other imaging methods are needed to image adult specimens. NMR is a versatile tool for studies of biological systems and has been successfully used for in vivo zebrafish microscopy.

Multiparametric MRI detects longitudinal evolution of folic acid-induced nephropathy in mice.

The rodent model of folic acid (FA)-induced acute kidney injury (AKI) provides a useful model for studying human AKI, but little is known about longitudinal changes in renal hemodynamics and evolution of renal fibrosis in vivo. In this work, we aimed to longitudinally assess renal structural and functional changes using multiparametric magnetic resonance imaging (MRI). Ten adult mice were injected with FA, after which a multiparametric MRI was used to measure kidney volume, hypoxia index R*, magnetization transfer ratio (MTR), perfusion, T, and glomerular filtration rate (GFR) at 2 wk posttreatment.

A rapid T mapping method for assessment of murine kidney viability using dynamic manganese-enhanced magnetic resonance imaging.

Purpose: Dynamic manganese-enhanced MRI (MEMRI) allows assessment of tissue viability by tracing manganese uptake. We aimed to develop a rapid T mapping method for dynamic MEMRI to facilitate assessments of murine kidney viability.

Methods: A multi-slice saturation recovery fast spin echo (MSRFSE) was developed, validated, and subsequently applied in dynamic MEMRI at 16.

Measurement of Murine Single-Kidney Glomerular Filtration Rate Using Dynamic Contrast-Enhanced MRI.

Purpose: To develop and validate a method for measuring murine single-kidney glomerular filtration rate (GFR) using dynamic contrast-enhanced MRI (DCE-MRI).

Methods: This prospective study was approved by the Institutional Animal Care and Use Committee. A fast longitudinal relaxation time (T ) measurement method was implemented to capture gadolinium dynamics (1 s/scan), and a modified two-compartment model was developed to quantify GFR as well as renal perfusion using 16.

Nocturia - Symptom or a Disease?

Waking at night to void is known as nocturia and it is a common condition experienced by both men and women with profound impact on patient's health, quality of life, and economic condition. It is often perceived as a symptom of an organic disease, but the pathophysiology of nocturia is now well-understood, and it is considered as a disease itself. It is classified based on four different pathophysiologic mechanisms (24-hour polyuria, nocturnal polyuria, reduced bladder capacity, and sleep disorders).

Evaluation of different egg quality traits and interpretation of their mode of inheritance in White Leghorns.

Aim: The experiment was carried out to evaluate different external and internal egg quality traits and to figure out their mode of inheritance from a set of hierarchically classified data.

Materials And Methods: The data collected from 548 progenies (1 egg from each progeny) of 282 dams mated to 47 sires (1 sire mated to 6 dams) of a White Leghorn flock were used in the present study. Phenotypic means and their standard errors were calculated for all the quality traits.

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring.

Several in vivo pre-clinical studies in Polycystic Kidney Disease (PKD) utilize orthologous rodent models to identify and study the genetic and molecular mechanisms responsible for the disease, and are very convenient for rapid drug screening and testing of promising therapies. A limiting factor in these studies is often the lack of efficient non-invasive methods for sequentially analyzing the anatomical and functional changes in the kidney. Magnetic resonance imaging (MRI) is the current gold standard imaging technique to follow autosomal dominant polycystic kidney disease (ADPKD) patients, providing excellent soft tissue contrast and anatomic detail and allowing Total Kidney Volume (TKV) measurements.

Utilizing magnetization transfer imaging to investigate tissue remodeling in a murine model of autosomal dominant polycystic kidney disease.

Purpose: Noninvasive imaging techniques that quantify renal tissue composition are needed to more accurately ascertain prognosis and monitor disease progression in polycystic kidney disease (PKD). Given the success of magnetization transfer (MT) imaging to characterize various tissue remodeling pathologies, it was tested on a murine model of autosomal dominant PKD.

Methods: C57Bl/6 Pkd1 R3277C mice at 9, 12, and 15 months were imaged with a 16.

MR microscopy of formalin fixed paraffin embedded histology specimens.

Purpose: Archived formalin-fixed paraffin-embedded (FFPE) tissue collections represent a valuable informational resource for numerous studies. However, there is no NMR signal from FFPE specimens at room temperature. To obtain MR images and enable comparison of magnetic resonance microscopy (MRM) and histology studies we propose to image FFPE tissue at elevated temperature.

Micro-computed tomography and nuclear magnetic resonance imaging for noninvasive, live-mouse cholangiography.

The cholangiopathies are a diverse group of biliary tract disorders, many of which lack effective treatment. Murine models are an important tool for studying their pathogenesis, but existing noninvasive methods for assessing biliary disease in vivo are not optimal. Here we report our experience with using micro-computed tomography (microCT) and nuclear magnetic resonance (MR) imaging to develop a technique for live-mouse cholangiography.

Preclinical (1)H-MRS neurochemical profiling in neurological and psychiatric disorders.

The ongoing development of animal models of neurological and psychiatric disorders in combination with the development of advanced nuclear magnetic resonance (NMR) techniques and instrumentation has led to increased use of in vivo proton NMR spectroscopy ((1)H-MRS) for neurochemical analyses. (1)H-MRS is one of only a few analytical methods that can assay in vivo and longitudinal neurochemical changes associated with neurological and psychiatric diseases, with the added advantage of being a technique that can be utilized in both preclinical and clinical studies. In this review, recent progress in the use of (1)H-MRS to investigate animal models of neurological and psychiatric disorders is summarized with examples from the literature and our own work.

Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1.

Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), we employed in vivo 16.

Acamprosate reduces ethanol drinking behaviors and alters the metabolite profile in mice lacking ENT1.

Acamprosate is clinically used to treat alcoholism. However, the precise molecular functionality of acamprosate in the central nervous system remains unclear, although it is known to antagonize glutamate action in the brain. Since elevated glutamate signaling, especially in the nucleus accumbens (NAc), is implicated in several aspects of alcoholism, we utilized mice lacking type 1 equilibrative nucleoside transporter (ENT1), which exhibit increased glutamate levels in the NAc as well as increased ethanol drinking behaviors.

Decoded calreticulin-deficient embryonic stem cell transcriptome resolves latent cardiophenotype.

Genomic perturbations that challenge normal signaling at the pluripotent stage may trigger unforeseen ontogenic aberrancies. Anticipatory systems biology identification of transcriptome landscapes that underlie latent phenotypes would offer molecular diagnosis before the onset of symptoms. The purpose of this study was to assess the impact of calreticulin-deficient embryonic stem cell transcriptomes on molecular functions and physiological systems.

Brainstem 1H nuclear magnetic resonance (NMR) spectroscopy: marker of demyelination and repair in spinal cord.

Measuring in vivo spinal cord injury and repair remains elusive. Using magnetic resonance spectroscopy (MRS) we examined brainstem N-acetyl-aspartate (NAA) as a surrogate for spinal cord injury in two mouse strains with different reparative phenotypes following virus-induced demyelination. Swiss Jim Lambert (SJL) and Friend Virus B (FVB) mice progressively demyelinate with axonal loss.

Rigid fixation of the spinal column improves scaffold alignment and prevents scoliosis in the transected rat spinal cord.

Study Design: A controlled study to evaluate a new technique for spinal rod fixation after spinal cord injury in rats. Alignment of implanted tissue-engineered scaffolds was assessed radiographically and by magnetic resonance imaging.

Objective: To evaluate the stability of implanted scaffolds and the extent of kyphoscoliotic deformities after spinal fixation.

Effect of hydrogel porosity on marrow stromal cell phenotypic expression.

This study describes investigation of porous photocrosslinked oligo[(polyethylene glycol) fumarate] (OPF) hydrogels as potential matrix for osteoblastic differentiation of marrow stromal cells (MSCs). The porosity and interconnectivity of porous hydrogels were assessed using magnetic resonance microscopy (MRM) as a noninvasive investigative tool that could image the water construct inside the hydrogels at a high-spatial resolution. MSCs were cultured onto the porous hydrogels and cell number was assessed using PicoGreen DNA assay.

Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme.

Despite the most aggressive medical and surgical treatments, glioblastoma multiforme remains incurable with a median survival of <1 year. We investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus (MV), derived from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA). CEA production as the virus replicates can serve as a marker of viral gene expression.