Biomedical subjects

Ed X Wu

Publications and source records attributed to Ed X Wu.

15 recordsLinked to original sources

PubMed2006

beta(2)-Adrenergic stimulation attenuates left ventricular remodeling, decreases apoptosis, and improves calcium homeostasis in a rodent model of ischemic cardiomyopathy.

The benefit of the beta(2)-adrenergic agonist, clenbuterol, in left ventricular assist device patients with dilated cardiomyopathy has been reported, but its effect on ischemic heart failure (HF) is unknown. We investigated whether clenbuterol improves left ventricular remodeling, myocardial apoptosis and has synergy with a beta(1) antagonist, metoprolol, in a model of ischemic HF. Rats were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF + clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left anterior descending artery (LAD) artery ligation and confirmed by decreased left ventricular fractional shortening, decreased maximum left ventricular dP/dt (dP/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP) compared with sham rats (p < 0.01). After 9 weeks of oral therapy, echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume relationship (EDPVR) measurements were obtained. Immunohistochemistry was performed for myocardial apoptosis and DNA damage markers. Levels of calcium-handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF rats (p < 0.05). The metoprolol-treated group had a lower LVEDP and higher dP/dt(max) versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had decreased myocardial apoptosis and DNA damage markers and increased DNA repair markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-, metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However, as a combination therapy, there were no synergistic effects of clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR, apoptosis, and calcium homeostasis but does not have synergy with metoprolol in our model of ischemic HF.

Adrenergic beta-Agonists↗

PubMed2006

Combo acquisitions: balancing scan time reduction and image quality.

Recently a new technique for the combined acquisition of multicontrast images, termed "combo acquisition," was introduced. In combo acquisitions, the three concepts of 1) variable acquisition parameters, 2) k-space data sharing, and 3) multicontrast imaging are systematically integrated to reduce MRI scan time and improve data utilization in a clinical setting. In this study, two-contrast and three-contrast spin-echo (SE) and turbo spin-echo (TSE) combo acquisition protocols that were designed and optimized in simulation experiments were implemented on a 1.5 T clinical scanner. Phantom and human brain data from volunteers and patients were acquired. Scan time reductions of 25-52% were achieved compared to standard acquisitions, largely confirming the simulation results. We evaluated the resulting images by quantitatively analyzing the preservation of contrast and the signal-to-noise ratio (SNR). In addition, data sets for 10 clinical cases obtained with TSE combo and corresponding standard acquisitions were graded by two experienced neuroradiologists in terms of the level of artifacts and image quality for comparison. Only minor image degradation with the combo scans was observed, indicating an inherent trade-off between scan time reduction and image quality. The specific aspects of combo acquisitions with respect to motion, flow, and k-space data weighting are discussed.

Algorithms↗

PubMed2005

Rapid in vivo Taxotere quantitative chemosensitivity response by 4.23 Tesla sodium MRI and histo-immunostaining features in N-Methyl-N-Nitrosourea induced breast tumors in rats.

BACKGROUND: Sodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere. AIM: To evaluate the association of in vivo intracellular sodium magnetic resonance image intensities with immuno-biomarkers and histopathological features to monitor the early tumor response to Taxotere chemotherapy in Methyl-Nitroso-Urea induced rat xenograft breast tumors. METHODS AND MATERIALS: Methyl-Nitroso-Urea (MNU) induced rat xenograft breast tumors were imaged for sodium MRI and compared with tumor histology, immunostaining after 24 hours chemotherapy. RESULTS: Sodium MRI signal intensities represented sodium concentrations. Excised tumor histological sections showed different in vitro histological end points i.e. single strand DNA content of cell nuclei during cell cycle (G1/S-G2/M), distinct S or M histograms (Feulgen labeling to nuclear DNA content by CAS 200), mitotic figures and apoptosis at different locations of breast tumors. Necrosis and cystic fluid appeared gray on intracellular (IC) sodium images while apoptosis rich regions appeared brighter on IC sodium images. After 24 hours Taxotere-treated tumors showed lower 'IC/EC ratio' of viable cells (65-76%) with higher mitotic index; apoptotic tumor cells at high risk due to cytotoxicity (>70% with high apoptotic index); reduced proliferation index (270 vs 120 per high power field) associated with enhanced IC sodium in vivo MR image intensities and decreased tumor size (3%; p < 0.001; n = 16) than that of pre-treated tumors. IC-Na MR signal intensities possibly indicated Taxotere chemosensitivity response in vivo associated with apoptosis and different pre-malignant features within 24 hours of exposure of cancer cells to anti-neoplastic Taxotere drug. CONCLUSION: Sodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features.

Journal Article↗

PubMed2004

Regional cerebral blood volume reduction in transgenic mutant APP (V717F, K670N/M671L) mice.

Recent advance in nuclear magnetic resonance (NMR) microimaging has enabled in vivo cerebral blood volume (CBV) mapping with high spatial resolution. Using an intravascular susceptibility contrast agent and T(2)-weighted magnetic resonance imaging (MRI) on a 9.4T NMR microimager, the regional CBV was measured in mice as the transverse relaxation increase induced by the contrast agent. CBV maps in an Alzheimer's disease mouse model at resting state were obtained and examined. Four-month-old male transgenic mutant APP (V717F, K670N/M671L) mice (N = 10) and littermate wild-type controls (N = 12) were used. Regional analysis of the multi-slice CBV maps revealed statistically significant CBV reductions among the APP mice in cerebral cortex (-9.29%, P = 0.0002), hippocampus (-4.22%, P = 0.02), and thalamus (-5.21%, P = 0.03), indicating an early change of microvasculature in these selected regions. No significant difference was found in olfactory bulb, pons, midbrain, superior colliculus, medulla, and cerebellum.

Animals↗

PubMed2004

Late measures of brain injury after neonatal hypoxia-ischemia in mice.

BACKGROUND AND PURPOSE: This work was undertaken to determine to what degree long-term neurofunctional outcome of neonatal hypoxic-ischemic (HI) brain injury in mice correlates with anatomical extent of cerebral damage assessed by magnetic resonance imaging (MRI) and histopathology. METHODS: On postnatal day 7, mice were subjected to HI. At 7 to 9 weeks after HI neurofunctional outcome was assessed by water-maze, rota-rod, and open-field test performance, followed by cerebral MRI and histopathology evaluation. RESULTS: At 10 weeks after HI, MRI revealed ipsilateral brain atrophy alone or with porencephalic cyst formation and contralateral ventriculomegaly. Adult HI-affected mice, especially those that developed a porencephalic cyst, demonstrated significant neurofunctional deficit compared with age-matched naïve mice. HI-affected mice with ipsilateral cerebral atrophy but without porencephaly demonstrated no or an intermediate level of neurofunctional deficit. Neurobehavioral assessment of mice subjected to HI insult revealed a strong correlation between degree of brain injury and functional neurohandicap. CONCLUSIONS: This is the first study to demonstrate that long-term neurofunctional outcome in mice after a neonatal HI correlates tightly with anatomical pattern/extent of cerebral damage, defined by MRI and histopathology.

Animals↗

PubMed2004

Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium.

Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes. Therefore, the concept of stimulating myocyte mitotic divisions has dramatic implications for cardiomyocyte regeneration and hence, cardiovascular disease. Previous reports describing manipulation of cell cycle proteins have not shown induction of cardiomyocyte mitosis after birth. We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an increase in cardiomyocyte mitosis, noted in transgenic hearts at all time points examined, particularly during postnatal development. Several stages of mitosis were observed within cardiomyocytes and correlated with the nuclear localization of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These results reveal a previously unrecognized critical role for cyclin A2 in mediating cardiomyocyte mitosis, a role that may significantly impact upon clinical treatment of damaged myocardium.

Animals↗

PubMed2004

Mapping cyclic change of regional myocardial blood volume using steady-state susceptibility effect of iron oxide nanoparticles.

PURPOSE: To demonstrate an in vivo magnetic resonance imaging (MRI) technique that maps the cyclic change of regional myocardial blood volume (MBV) during the cardiac cycle. MATERIALS AND METHODS: The method is based on the dominant T(2)* shortening effect of iron oxide nanoparticle-induced magnetic susceptibility perturbation in myocardium in the steady state. The technique was demonstrated in vivo with normal mouse hearts at 9.4 T. The regional MBV maps in left ventricular myocardium were computed from the steady-state pre- and post-monocrystalline iron oxide nanoparticle (MION) gradient echo (GE) cine images. Cyclic changes of MBV in normal mice were analyzed quantitatively in different transmural and angular locations. RESULTS: High-resolution MBV maps at various cardiac points were obtained. The study showed a general regional MBV decrease from end-diastole (ED) to end-systole (ES). Percentage reductions were 18.2 +/- 6.6%, P < 0.03 in the lateral wall and 24.7 +/- 3.1%, P < 0.0002 in the interventricular septum. The heterogeneous characteristics of MBV transmural distribution were also reported. CONCLUSION: The steady-state susceptibility effect of intravascular superparamagnetic contrast agent (CA) can be used to map the cyclic change of regional MBV. This imaging approach is relatively simple and may provide a new perspective for functional assessment of the microvasculature in myocardium.

Animals↗

PubMed2004

In vivo study of microbubbles as an MR susceptibility contrast agent.

The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison, was studied with rat liver imaging at 7 T. Optison suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (deltaR2*) of 29.1 +/- 1.6 s(-1) (N = 2) and 61.5 +/- 12.9 s(-1) (N = 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro deltaR2* measurements of Optison suspension at different concentrations are also reported.

Albumins↗

PubMed2004

High-resolution MR imaging of mouse brain microvasculature using the relaxation rate shift index Q.

Magnetic resonance imaging (MRI) is a powerful method for in vivo quantification of tissue properties. It has been previously proposed that the index Q identical with Delta R2/(Delta R2*)2/3, where Delta R2 and Delta R2* are the spin echo and gradient echo relaxation rate shifts caused by the injection of an intravascular contrast agent, may be useful for characterizing microvasculature. In particular, Q is expected to correlate well with the density of microvessels. This study presents high-resolution in vivo Q-maps of normal mouse brain obtained with a superparamagnetic iron oxide contrast agent at a field of level of 9.4 T. Normative Q values are derived for several regions of interest and significant interregional variations are observed. Microvessel densities estimated from the Q-maps are found to be in reasonable accord with histologically determined values. A possible application of Q-maps is the assessment of angiogenic activity in tumors.

Animals↗

PubMed2004

Applications of ultrasmall superparamagnetic iron oxide contrast agents in the MR study of animal models.

Ultrasmall superparamagnetic iron oxide nanoparticles have been widely used during the past decade as MR intravascular contrast agents in the study of animal models. Such agents enhance both T1 and T2/T2* relaxation, although for animal studies it is the later type of enhancement that is most commonly exploited. Their strong microscopic intravascular susceptibility effect enables the local blood volume distribution to be mapped in various organs. High spatial resolution and sensitivity can be achieved, because the long half-life of these agents in blood, combined with anesthetization, permits steady-state measurements over extended periods. This capability has been utilized to study the cerebrovascular blood volume distributions and their changes in normal, activated, pathologic and pharmacologically or genetically modified states, particularly in rodent animal models. It has also been applied to study blood volume changes in other tissues, such as the myocardium. The relaxation rate shifts Delta R2 and Delta R2* induced by iron oxide agents may differ depending on certain morphological characteristics of the microvascular network, and sensitive Delta R2 and Delta R2* mapping can potentially provide, in addition to blood volume, measurement of other important microvascular parameters such as blood vessel density and size. This work aims to review the applications of ultrasmall superparamagnetic iron oxide contrast agents in MR animal studies, with an emphasis on the investigation of microvascular parameters.

Animals↗

PubMed2003

High-resolution in vivo CBV mapping with MRI in wild-type mice.

NMR microimaging has the potential to elucidate cerebrovascular abnormalities in mouse models. In this study, the relative regional cerebral blood volume (CBV) map is presented for C57BL6/J wild-type mice. The CBV mapping was based on changes in the steady-state NMR transverse relaxation rate (DeltaR(2)) associated with the presence of a superparamagnetic intravascular contrast agent (MION) with a long blood halflife. The experiments were performed at 9.4 T at a voxel size of 100 microm x 100 microm x 600 microm. Fine details, such as the hippocampal and olfactory bulb area, were visualized in the CBV map. The relative regional CBV values of various brain regions were measured. The DeltaR(2) dosage dependency and MION tissue clearance in mouse are also reported.

Animals↗

PubMed2003

Left ventricular systolic performance in failing heart improved acutely by left ventricular reshaping.

OBJECTIVE: If the geometric distortion during dilated heart failure could be corrected, the tension on the myocytes would be decreased, thereby leading to an improvement in left ventricular systolic function. We tested the effects of the CardioClasp (CardioClasp Inc, Pine Brook, NJ), a left ventricular reshaping device, on the failing heart, and our empirical data were compared with computationally derived data. METHODS: Heart failure was induced by 4-week rapid cardiac pacing. At the terminal experiment, an isolated failing heart preparation (isovolumic contraction, n = 5) or an intact failing heart in vivo (n = 7) was used. The effects of the reshaping device on left ventricular performance were assessed by the slopes (Ees) of the left ventricular end-systolic pressure-volume relations, hemodynamics, and echocardiograph before and after placing the CardioClasp on the heart. The change in Ees as the result of left ventricular reshaping was also estimated from computed theoretical analysis and compared with empirical data. RESULTS: There was a significant change in left ventricular dimension after placing the CardioClasp on the heart. In isolated heart preparation, Ees significantly increased from 1.40 +/- 0.44 mm Hg/mL to 2.42 +/- 0.63 mm Hg/mL after placing the device on the heart but returned to the baseline level (1.46 +/- 0.27 mm Hg) after removing it. Left ventricular developed pressure and left ventricular fractional area shortening were significantly increased as the result of left ventricular reshaping. Ees derived from computed theoretical analysis was highly correlated with confirming empirical data. CONCLUSIONS: The CardioClasp can reshape the left ventricle and improve left ventricular systolic performance in failing hearts.

Animals↗

PubMed2003

Combined MR data acquisition of multicontrast images using variable acquisition parameters and K-space data sharing.

A new technique to reduce clinical magnetic resonance imaging (MRI) scan time by varying acquisition parameters and sharing k-space data between images, is proposed. To improve data utilization, acquisition of multiple images of different contrast is combined into a single scan, with variable acquisition parameters including repetition time (TR), echo time (TE), and echo train length (ETL). This approach is thus referred to as a "combo acquisition." As a proof of concept, simulations of MRI experiments using spin echo (SE) and fast SE (FSE) sequences were performed based on Bloch equations. Predicted scan time reductions of 25%-50% were achieved for 2-contrast and 3-contrast combo acquisitions. Artifacts caused by nonuniform k-space data weighting were suppressed through semi-empirical optimization of parameter variation schemes and the phase encoding order. Optimization was assessed by minimizing three quantitative criteria: energy of the "residue point spread function (PSF)," energy of "residue profiles" across sharp tissue boundaries, and energy of "residue images." In addition, results were further evaluated by quantitatively analyzing the preservation of contrast, the PSF, and the signal-to-noise ratio. Finally, conspicuity of lesions was investigated for combo acquisitions in comparison with standard scans. Implications and challenges for the practical use of combo acquisitions are discussed.

Algorithms↗

PubMed2002

MRI cardiac tagging using a sinc-modulated RF pulse train.

A method of spatial modulation of magnetization using the RF pulse train is described for improved cardiac tagging. The method is based on a sinc-modulated RF pulse train in the presence of constant gradient. Such an RF pulse train yields a rectangular profile of saturated magnetization, and the bandwidth of the sinc envelope controls the width of the saturation tag. Compared to DANTE and SPAMM tagging techniques, this method offers sharper-edged tags and the ability to change the ratio of tag width to tag separation. The approach was implemented on a 9.4 T vertical bore NMR system and demonstrated with both phantom and in vivo mouse heart studies.

Animals↗

PubMed2002

High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats.

Magnetic resonance imaging (MRI) has the ability to discriminate between various soft tissues in vivo. Whole body, specific organ, total adipose tissue (TAT), intra-abdominal adipose tissue (IAAT), and skeletal muscle (SM) weights determined by MRI were compared with weights determined by dissection and chemical analysis in two studies with male Sprague-Dawley rats. A 4.2-T MRI machine acquired high-resolution, in vivo, longitudinal whole body images of rats as they developed obesity or aged. Weights of the whole body and specific tissues were determined using computer image analysis software, including semiautomatic segmentation algorithms for volume calculations. High correlations were found for body weight (r = 0.98), TAT (r = 0.99), and IAAT (r = 0.98) between MRI and dissection and chemical analyses. MRI estimated the weight of the brain, kidneys, and spleen with high accuracy (r > 0.9), but overestimated IAAT, SM, and liver volumes. No differences were detected in organ weights using MRI and dissection measurements. Longitudinal MRI measurements made during the development of obesity and aging accurately represented changes in organ and tissue mass.

Aging↗