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Biomedical subjects

Yu Zou

Publications and source records attributed to Yu Zou.

At least 19 recordsLinked to original sources

Validation of an HPLC method for the simultaneous determination of DZ5 and its active metabolite in dog plasma and its pharmacokinetics.

A validated HPLC method is described for the simultaneous determination of daidzein 7,4'-di-succinic acid mon-ester-O-ethoxy (DZ5) and its active metabolite daidzein 7,4'-dioxy-ethoxy (DZ4) in dog plasma. DZ5 and DZ4 were determined by reversed-phase HPLC (column: Hypersil C18 5 microm silica, 200 mm x 4.6 mm i.d.; eluent: 400 ml water, 500 microl 85% phosphoric acid, 600 ml methanol) and photometric detection (250 nm), with Kaempferol as the internal standard. The calibration curve was linear over the range 0.1-50.0 microg/ml in dog plasma. The average extraction recoveries were 84.6% (DZ5), 82.7% (DZ4) and the within-day and between-day precisions were less than 10.93%. The assay was applied to the analysis of samples from a pharmacokinetic study. Following the oral administration and intravenous administration of DZ5, DZ5 was eliminated rapidly from the plasma and DZ4 was found in plasma. The absolute bioavailability of total DZ5 and DZ4 was 41.5%. The method was demonstrated to be feasible for pharmacokinetic studies of DZ5 in dogs.

Animals↗

Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis.

The most common reason for heart failure in young adults is dilated cardiomyopathy often resulting from myocarditis. Clinical studies and animal models provide evidence that an autoimmune response against heart myosin is the underlying reason for the disease. IL-12 has been suggested to play a key role in development of experimental autoimmune myocarditis (EAM), as IL-12p40 and IL-12Rbeta1 knockouts are protected from disease. In this study, we have compared IL-12p40-/- mice, IL-12p35-/- mice and mice treated with a neutralizing IL-23 antibody in EAM and found that in fact IL-23, not IL-12, is responsible for inflammatory heart disease. However, these cytokines appear to have redundant activity for priming and expansion of autoreactive CD4 T cells, as specific T cell proliferation was only defective in the absence of both cytokines. IL-23 has been suggested to promote a pathogenic IL-17-producing T cell population. We targeted IL-17 by capitalizing on an active vaccination approach that effectively breaks B cell tolerance. Neutralization of IL-17 reduced myocarditis and heart autoantibody responses, suggesting that IL-17 is the critical effector cytokine responsible for EAM. Thus, targeting of IL-23 and IL-17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy.

Animals↗

Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis.

Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases.

Animals↗

Region of interest reconstruction from truncated data in circular cone-beam CT.

The circular scanning trajectory is one of the most widely adopted data-acquisition configurations in computed tomography (CT). The Feldkamp, Davis, Kress (FDK) algorithm and its various modifications have been developed for reconstructing approximately three-dimensional images from circular cone-beam data. When data contain transverse truncations, however, these algorithms may reconstruct images with significant truncation artifacts. It is of practical significance to develop algorithms that can reconstruct region-of-interest (ROI) images from truncated circular cone-beam data that are free of truncation artifacts and that have an accuracy comparable to that obtained from nontruncated cone-beam data. In this work, we have investigated and developed a backprojection-filtration (BPF)-based algorithm for ROI-image reconstruction from circular cone-beam data containing transverse truncations. Furthermore, we have developed a weighted BPF algorithm to exploit "redundant" information in data for improving image quality. In an effort to validate and evaluate the proposed BPF algorithms for circular cone-beam CT, we have performed numerical studies by using both computer-simulation data and experimental data acquired with a radiotherapy cone-beam CT system. Quantitative results in these studies demonstrate that the proposed BPF algorithms for circular cone-beam CT can reconstruct ROI images free of truncation artifacts.

Algorithms↗

Chord-based image reconstruction in cone-beam CT with a curved detector.

Modern computed tomography (CT) scanners use cone-beam configurations for increasing volume coverage, improving x-ray-tube utilization, and yielding isotropic spatial resolution. Recently, there have been significant developments in theory and algorithms for exact image reconstruction from cone-beam projections. In particular, algorithms have been proposed for image reconstruction on chords; and advantages over the existing algorithms offered by the chord-based algorithms include the high flexibility of exact image reconstruction for general scanning trajectories and the capability of exact reconstruction of images within a region of interest from truncated data. These chord-based algorithms have been developed only for flat-panel detectors. Many cone-beam CT scanners employ curved detectors for important practical considerations. Therefore, in this work, we have derived chord-based algorithms for a curved detector so that they can be applied to reconstructing images directly from data acquired by use of a CT scanner with a curved detector. We have also conducted preliminary numerical studies to demonstrate and evaluate the reconstruction properties of the derived chord-based algorithms for curved detectors.

Algorithms↗

Equation-free dynamic renormalization: self-similarity in multidimensional particle system dynamics.

We present an equation-free dynamic renormalization approach to the computational study of coarse-grained, self-similar dynamic behavior in multidimensional particle systems. The approach is aimed at problems for which evolution equations for coarse-scale observables (e.g., particle density) are not explicitly available. Our illustrative example involves Brownian particles in a 2D Couette flow; marginal and conditional inverse cumulative distribution functions (ICDFs) constitute the macroscopic observables of the evolving particle distributions.

Journal Article↗

Minimum data image reconstruction algorithms with shift-invariant filtering for helical, cone-beam CT.

We derive accurate and efficient reconstruction algorithms for helical, cone-beam CT that employ shift-invariant filtering. Specifically, a new backprojection-filtration algorithm is developed, and a minimum data filtered-backprojection algorithm is derived. These reconstruction algorithms with shift-invariant filtering can accept data with transverse truncation, and hence allow for minimum data image reconstruction.

Algorithms↗

Evidence for dramatic acceleration of a C-H bond ionization rate in thiamin diphosphate enzymes by the protein environment.

The hypothesis that thiamin diphosphate-dependent enzymes achieve a significant fraction of their catalytic rate acceleration by providing a protein environment that helps to stabilize unstable zwitterionic/dipolar intermediates (including the enamine/C2alpha-carbanion present on all such enzymes) was tested experimentally using the intermediate C2alpha-hydroxyethylthiamin diphosphate (HEThDP) with the Escherichia coli pyruvate dehydrogenase complex and its E1 subunit (PDHc-E1). Using pre-steady-state and steady-state methods, it was shown that HEThDP is a substrate for this enzyme after ionization of the C2alpha-H bond. An experiment was then carried out to measure the PDHc-E1 catalyzed pre-steady-state rate constant for the D --> H exchange from the C2alpha position of HEThDP-d(4), as an indicator of the formation of the enamine. Importantly, the enzyme accelerates the rate of ionization of this bond by a factor of 10(7), corresponding to a 10 kcal/mol stabilization of the enamine intermediate by the enzyme. This finding is likely a general feature of thiamin diphosphate enzymes.

Acetylation↗

Image reconstruction in regions-of-interest from truncated projections in a reduced fan-beam scan.

In a reduced fan-beam scan, the scanned angular range is smaller than that in a short scan (i.e., a half-scan). In this work, we have developed a new algorithm, which is referred to as the backprojection-filtration (BPF) algorithm, for exact image reconstruction within ROIs from reduced-scan data containing truncations. Explicit conditions on data acquisition have also been derived for exact image reconstruction within an ROI. We have performed a preliminary quantitative study whose results demonstrated and verified the proposed fan-beam BPF algorithm and the derived conditions on data acquisition. The proposed BPF algorithm can have significant implications for clinical and animal CT imaging, therapy imaging, electron paramagnetic resonance imaging and other tomographic imaging because it allows for reconstruction from truncated data and for a potentially drastic reduction of radiation dose and/or of imaging time.

Algorithms↗

Half-time image reconstruction in thermoacoustic tomography.

Thermoacoustic tomography (TAT) is an emerging imaging technique with great potential for a wide range of biomedical imaging applications. In this paper, we propose and investigate reconstruction approaches for TAT that are based on the half-time reflectivity tomography paradigm. We reveal that half-time reconstruction approaches permit for the explicit control of statistically complementary information that can result in the optimal reduction of image variances. We also show that half-time reconstruction approaches can mitigate image artifacts due to heterogeneous acoustic properties of an object. Reconstructed images and numerical results produced from simulated and experimental TAT measurement data are employed to demonstrate these effects.

Acoustics↗

Feasibility of half-data image reconstruction in 3-D reflectivity tomography with a spherical aperture.

Reflectivity tomography is an imaging technique that seeks to reconstruct certain acoustic properties of a weakly scattering object. Besides being applicable to pure ultrasound imaging techniques, the reconstruction theory of reflectivity tomography is also pertinent to hybrid imaging techniques such as thermoacoustic tomography. In this work, assuming spherical scanning apertures, redundancies in the three-dimensional (3-D) reflectivity tomography data function are identified and formulated mathematically. These data redundancies are used to demonstrate that knowledge of the measured data function over half of its domain uniquely specifies the 3-D object function. This indicates that, in principle, exact image reconstruction can be performed using a "half-scan" data function, which corresponds to temporally untruncated measurements acquired on a hemi-spherical aperture, or using a "half-time" data function, which corresponds to temporally truncated measurements acquired on the entire spherical aperture. Both of these minimal scanning configurations have important biological imaging applications. An iterative reconstruction method is utilized for reconstruction of a simulated 3-D object from noiseless and noisy half-scan and half-time data functions.

Algorithms↗

Image reconstruction in peripheral and central regions-of-interest and data redundancy.

Algorithms have been developed for image reconstruction within a region-of-interest (ROI) from fan-beam data less than that required for reconstructing the entire image. However, these algorithms do not admit truncated data. In this work, we investigate exact ROI-image reconstruction from fan-beam data containing truncations by use of the so-called fan-beam backprojection-filtration (BPF) algorithm. We also generalize the fan-beam BPF algorithm to exploit redundant information inherent in the truncated fan-beam data. Because the parallel-beam scan can be interpreted as a special case of the fan-beam scan, based upon the fan-beam BPF algorithm, we derive a parallel-beam BPF algorithm for exactly reconstructing ROI images from truncated parallel-beam data. Furthermore, we investigate image reconstruction within two types of distinctive ROIs, which are referred to as the peripheral and central ROIs, respectively, from fan-beam data containing truncations and discuss their potential clinical applications. The results can readily be generalized to reconstructing 3D ROI images from data acquired in circular and helical cone-beam scan. They can also be extended to address ROI-image-reconstruction problems in parallel-, fan-, and cone-beam scans with general trajectories. The work not only has significant implications for clinical and animal-imaging applications of CT, but also may find applications in other imaging modalities.

Algorithms↗

PI-line-based image reconstruction in helical cone-beam computed tomography with a variable pitch.

Current applications of helical cone-beam computed tomography (CT) involve primarily a constant pitch where the translating speed of the table and the rotation speed of the source-detector remain constant. However, situations do exist where it may be more desirable to use a helical scan with a variable translating speed of the table, leading a variable pitch. One of such applications could arise in helical cone-beam CT fluoroscopy for the determination of vascular structures through real-time imaging of contrast bolus arrival. Most of the existing reconstruction algorithms have been developed only for helical cone-beam CT with constant pitch, including the backprojection-filtration (BPF) and filtered-backprojection (FBP) algorithms that we proposed previously. It is possible to generalize some of these algorithms to reconstruct images exactly for helical cone-beam CT with a variable pitch. In this work, we generalize our BPF and FBP algorithms to reconstruct images directly from data acquired in helical cone-beam CT with a variable pitch. We have also performed a preliminary numerical study to demonstrate and verify the generalization of the two algorithms. The results of the study confirm that our generalized BPF and FBP algorithms can yield exact reconstruction in helical cone-beam CT with a variable pitch. It should be pointed out that our generalized BPF algorithm is the only algorithm that is capable of reconstructing exactly region-of-interest image from data containing transverse truncations.

Algorithms↗

Reconstruction of 3D regions-of-interest from data in reduced helical cone-beam scans.

The sufficiency conditions are derived for exact image reconstruction of a 3D ROI from projections acquired with a reduced helical scan over an angular range considerably smaller than that required by image reconstruction in, e.g., the conventional long object problem, for which the scanned angular range is often more than 2pi. ROI reconstruction is investigated by a recently developed filtered-backprojection algorithm that can make use of data acquired with a reduced helical scan. Preliminary numerical studies demonstrate and validate the ROI reconstruction. This work may have significant practical implications because a reduced scan in CT often translates to reduced motion artifacts and reduced radiation dose delivered to the subject.

Algorithms↗

Theory and algorithms for image reconstruction on chords and within regions of interest.

We introduce a formula for image reconstruction on a chord of a general source trajectory. We subsequently develop three algorithms for exact image reconstruction on a chord from data acquired with the general trajectory. Interestingly, two of the developed algorithms can accommodate data containing transverse truncations. The widely used helical trajectory and other trajectories discussed in literature can be interpreted as special cases of the general trajectory, and the developed theory and algorithms are thus directly applicable to reconstructing images exactly from data acquired with these trajectories. For instance, chords on a helical trajectory are equivalent to the n-PI-line segments. In this situation, the proposed algorithms become the algorithms that we proposed previously for image reconstruction on PI-line segments. We have performed preliminary numerical studies, which include the study on image reconstruction on chords of two-circle trajectory, which is nonsmooth, and on n-PI lines of a helical trajectory, which is smooth. Quantitative results of these studies verify and demonstrate the proposed theory and algorithms.

Algorithms↗

An extended data function and its generalized backprojection for image reconstruction in helical cone-beam CT.

We have recently proposed a general formula (i.e., equations (9) to (11) in Zou and Pan (2004a Phys. Med. Biol. 49 941-59)) for image reconstruction from helical cone-beam data. On the basis of the formula, we have also developed two reconstruction algorithms, which are referred to as the backprojection filtration (BPF) algorithm (Zou and Pan 2004a) and the filtered backprojection (FBP) algorithm (Zou and Pan 2004b Phys. Med. Biol. 49 2717-31), respectively. The two algorithms have been implemented and evaluated in numerical studies. In this note, however, we point out that the data function previously used for proving the general formula in Zou and Pan (2004a) is incomplete and that, instead, an extended data function and its generalized backprojection, which are described in this note, should be used to complete the proof of the general formula. On the other hand, we also demonstrate in this note that the additional term in the extended data function has no effect on the previously developed BPF and FBP algorithms. The results can also be extended to general, smooth trajectories.

Algorithms↗

A unified analysis of FBP-based algorithms in helical cone-beam and circular cone- and fan-beam scans.

A circular scanning trajectory is and will likely remain a popular choice of trajectory in computed tomography (CT) imaging because it is easy to implement and control. Filtered-backprojection (FBP)-based algorithms have been developed previously for approximate and exact reconstruction of the entire image or a region of interest within the image in circular cone-beam and fan-beam cases. Recently, we have developed a 3D FBP-based algorithm for image reconstruction on PI-line segments in a helical cone-beam scan. In this work, we demonstrated that the 3D FBP-based algorithm indeed provided a rather general formulation for image reconstruction from divergent projections (such as cone-beam and fan-beam projections). On the basis of this formulation we derived new approximate or exact algorithms for image reconstruction in circular cone-beam or fan-beam scans, which can be interpreted as special cases of the helical scan. Existing algorithms corresponding to the derived algorithms were identified. We also performed a preliminary numerical study to verify our theoretical results in each of the cases. The results in the work can readily be generalized to other non-circular trajectories.

Algorithms↗

Image reconstruction on PI-lines by use of filtered backprojection in helical cone-beam CT.

Recently, we have derived a general formula for image reconstruction from helical cone-beam projections. Based upon this formula, we have also developed an exact algorithm for image reconstruction on PI-line segments from minimum data within the Tam-Danielsson window. This previous algorithm can be referred to as a backprojection-filtration algorithm because it reconstructs an image by first backprojection of the data derivatives and then filtration of the backprojections on PI-line segments. In this work, we propose an alternative algorithm, which reconstructs an image by first filtering the modified data along the cone-beam projections of the PI-lines onto the detector plane and then backprojecting the filtered data onto PI-line segments. Therefore, we refer to this alternative algorithm as the filtered-backprojection algorithm. A preliminary computer-simulation study was performed for validating and demonstrating this new algorithm. Furthermore, we derive a practically useful expression to accurately compute the derivative of the data function for image reconstruction. The proposed filtered-backprojection algorithm can reconstruct the image within any selected ROI inside the helix and thus can handle naturally the long object problem and the super-short scan problem. It can also be generalized to reconstruct images from data acquired with other scanning configurations such as the helical scan with a varying pitch.

Algorithms↗