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X Josette Chen

Publications and source records attributed to X Josette Chen.

10 recordsLinked to original sources
PubMed2006

Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis.

Dominant mutations in the T-box transcription factor gene TBX5 cause Holt-Oram syndrome (HOS), an inherited human disease characterized by upper limb malformations and congenital heart defects (CHDs) of variable severity. We hypothesize that minor alterations in the dosage of Tbx5 directly influences severity of CHDs. Using a mouse allelic series, we show a sensitive inverse correlation between Tbx5 dosage and abnormal cardiac morphogenesis and gene expression. The CHDs found in mice harbouring a hypomorphic allele of Tbx5 (Tbx5(lox/+) mice) are less pronounced than those found in Tbx5 haploinsufficient mice (Tbx5(del/+)), and homozygous hypomorphic (Tbx5(lox/lox)) embryos have noticeably more advanced cardiac development than Tbx5 null (Tbx5(del/del)) embryos. Examination of target gene expression across the allelic series uncovers very fine sensitivity across the range of Tbx5 dosages, in which some genes respond dramatically differently to only 15% differences in Tbx5 mRNA levels. This analysis was expanded to a genome-wide level, which uncovered a Tbx5 dosage-sensitive genetic program involving a network of cardiac transcription factors, developmentally important cell-cell signaling molecules, and ion channel proteins. These results indicate an exquisite sensitivity of the developing heart to Tbx5 dosage and provide significant insight into the transcriptional and cellular mechanisms that are disrupted in CHDs.

Alleles↗
PubMed2006

Mouse morphological phenotyping with magnetic resonance imaging.

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, with both MRI physicists and biologists starting to use MRI to identify mouse models of human disease. The purpose of this chapter is to provide details of the animal handling necessary for routine and robust in vivo imaging with particular emphasis on multiple-mouse imaging. In addition, techniques for perfusion-fixation for postmortem imaging of specimens and whole mice are given.

Animals↗
PubMed2005

Neuroanatomical differences between mouse strains as shown by high-resolution 3D MRI.

The search for new mouse models of human disease requires a sensitive metric to make three-dimensional (3D) anatomical comparisons in a rapid and quantifiable manner. This is especially true in the brain, where changes in complex shapes such as the hippocampus and ventricles are difficult to assess with 2D histology. Here, we report that the 3D neuroanatomy of three strains of mice (129S1/SvImJ, C57/Bl6, and CD1) is significantly different from one another. Using image co-registration, we 'morphed' together nine brains of each strain scanned by magnetic resonance imaging at (60 microm)3 resolution to synthesize an average image. We applied three methods of comparison. First, we used visual inspection and graphically examined the standard deviation of the variability in each strain. Second, we annotated 42 neural structures and compared their volumes across the strains. Third, we assessed significant local deviations in volume and displacement between the two inbred strains, independent of prior anatomical knowledge.

Algorithms↗
PubMed2005

Fast spin-echo for multiple mouse magnetic resonance phenotyping.

High-resolution magnetic resonance imaging is emerging as a powerful tool for phenotyping mice in biologic studies of genetic expression, development, and disease progression. In several applications, notably random mutagenesis trials, large cohorts of mice must be examined for abnormalities that may occur in any part of the body. In the aim of establishing a protocol for imaging multiple mice simultaneously in a standardized high-throughput fashion, this study investigates variations of a three-dimensional fast spin-echo sequence that implements driven equilibrium, modified refocusing, and partial excitation pulses. Sequence variations are compared by simulated and experimental measurements in phantoms and mice. Results indicate that when using a short repetition time (TR<or=T1) a sequence employing a partial excitation tip angle provides both improved signal and good T2 contrast compared with standard fast spin-echo imaging. This sequence is used to simultaneously acquire four live mouse head images at 100 microm isotropic resolution with a scan time under 3 h at 7 T.

Animals↗
PubMed2005

Magnetic resonance imaging for detection and analysis of mouse phenotypes.

With the enormous and growing number of experimental and genetic mouse models of human disease, there is a need for efficient means of characterizing abnormalities in mouse anatomy and physiology. Adaptation of magnetic resonance imaging (MRI) to the scale of the mouse promises to address this challenge and make major contributions to biomedical research by non-invasive assessment in the mouse. MRI is already emerging as an enabling technology providing informative and meaningful measures in a range of mouse models. In this review, recent progress in both in vivo and post mortem imaging is reported. Challenges unique to mouse MRI are also identified. In particular, the needs for high-throughput imaging and comparative anatomical analyses in large biological studies are described and current efforts at handling these issues are presented.

Animals↗
PubMed2004

Comprehensive transthoracic cardiac imaging in mice using ultrasound biomicroscopy with anatomical confirmation by magnetic resonance imaging.

High-frequency ultrasound biomicroscopy (UBM) has recently emerged as a high-resolution means of phenotyping genetically altered mice and has great potential to evaluate the cardiac morphology and hemodynamics of mouse mutants. However, there is no standard procedure of in vivo transthoracic cardiac imaging using UBM to comprehensively phenotype the adult mice. In this paper, the characteristic mouse thoracic anatomy is elucidated using magnetic resonance (MR) imaging on fixed mice. Besides the left parasternal and apical windows commonly used for transthoracic ultrasound cardiac imaging, a very useful right parasternal window is found. We present strategies for optimal visualization using UBM of key cardiac structures including: 1) the right atrial inflow channels such as the right superior vena cava; 2) the right ventricular inflow tract via the tricuspid orifice; 3) the right ventricular outflow tract to the main pulmonary artery; 4) the left atrial inflow channel, e.g., pulmonary vein; 5) the left ventricular inflow tract via the mitral orifice; 6) the left ventricular outflow tract to the ascending aorta; 7) the left coronary artery; and 8) the aortic arch and associated branches. Two-dimensional ultrasound images of these cardiac regions are correlated to similar sections in the three-dimensional MR data set to verify anatomical details of the in vivo UBM imaging. Dimensions of the left ventricle and ascending aorta are measured by M-mode. Flow velocities are recorded using Doppler at six representative intracardiac locations: right superior vena cava, tricuspid orifice, main pulmonary artery, pulmonary vein, mitral orifice, and ascending aorta. The methodologies and baseline measurements of inbred mice provide a useful guide for investigators applying the high-frequency ultrasound imaging to mouse cardiac phenotyping.

Animals↗
PubMed2004

Multiple mouse biological loading and monitoring system for MRI.

The use of mice to study models of human disease has resulted in a surge of interest in developing mouse MRI. The ability to take 3D, high-resolution images of live mice allows significant insight into anatomy and function. However, with imaging times on the order of hours, high throughput of specimens has been problematic. To facilitate high throughput, concurrent imaging of multiple mice has been developed; however, this poses further complexities regarding the ease and rapidity of loading several animals. In this study, custom-built equipment was developed to streamline the preparation process and to safely maintain seven mice during a multiple-mouse imaging session. Total preparation time for seven mice was approximately 24 min. ECG and temperature were monitored throughout the scan and maintained by regulating anesthetic and heating. Proof of principle was demonstrated in a 3-h imaging session of seven mice.

Animals↗
PubMed2004

Ultrasound-guided left-ventricular catheterization: a novel method of whole mouse perfusion for microimaging.

We describe a novel technique to perform whole-body perfusion fixation in mice with specific relevance to micro-imaging. With the guidance of high-frequency ultrasound imaging, we were able to perfuse fixative and contrast agents via a catheter inserted into the left ventricle, and therefore preserved the integrity of the chest and abdominal cavity. In this preliminary study, our success rate over 15 animals was 73%. We demonstrate applications of this technique for magnetic resonance imaging and micro-CT, but we expect that this method can be generally applied to whole-body perfusions of other small animals in which the intact body is necessary.

Animals↗
PubMed2002

MRI of the lungs using hyperpolarized noble gases.

The nuclear spin polarization of the noble gas isotopes (3)He and (129)Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments.

Animals↗