Biomedical subjects

Zhong Zhong

Publications and source records attributed to Zhong Zhong.

At least 19 recordsLinked to original sources

PubMed2006

Interlaced x-ray microplanar beams: a radiosurgery approach with clinical potential.

Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25- to 90-microm thick and spaced 100-300 microm on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90-degree angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 x 3.4 x 3.4 mm(3) exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120- and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-microm dose falloff (80-20%) at the edge of the target, which is much less than the 2- to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.

Animals↗

PubMed2006

Computation of mass-density images from x-ray refraction-angle images.

In this paper, we investigate the possibility of computing quantitatively accurate images of mass density variations in soft tissue. This is a challenging task, because density variations in soft tissue, such as the breast, can be very subtle. Beginning from an image of refraction angle created by either diffraction-enhanced imaging (DEI) or multiple-image radiography (MIR), we estimate the mass-density image using a constrained least squares (CLS) method. The CLS algorithm yields accurate density estimates while effectively suppressing noise. Our method improves on an analytical method proposed by Hasnah et al (2005 Med. Phys. 32 549-52), which can produce significant artefacts when even a modest level of noise is present. We present a quantitative evaluation study to determine the accuracy with which mass density can be determined in the presence of noise. Based on computer simulations, we find that the mass-density estimation error can be as low as a few per cent for typical density variations found in the breast. Example images computed from less-noisy real data are also shown to illustrate the feasibility of the technique. We anticipate that density imaging may have application in assessment of water content of cartilage resulting from osteoarthritis, in evaluation of bone density, and in mammographic interpretation.

Absorptiometry, Photon↗

PubMed2006

Multiple-image radiography for human soft tissue.

Conventional radiography only provides a measure of the X-ray attenuation caused by an object; thus, it is insensitive to other inherent informative effects, such as refraction. Furthermore, conventional radiographs are degraded by X-ray scatter that can obscure important details of the object being imaged. The novel X-ray technology diffraction-enhanced imaging (DEI) has recently allowed the visualization of nearly scatter-free images displaying both attenuation and refraction properties. A new method termed multiple-image radiography (MIR) is a significant improvement over DEI, corrects errors in DEI, is more robust to noise and produces an additional image that is entirely new to medical imaging. This new image, which portrays ultra-small-angle X-ray scattering (USAXS) conveys the presence of microstructure in the object, thus differentiating homogeneous tissues from tissues that are irregular on a scale of micrometres. The aim of this study was to examine the use of MIR for evaluation of soft tissue, and in particular to conduct a preliminary investigation of the USAXS image, which has not previously been used in tissue imaging.

Arthrography↗

PubMed2006

A computed tomography implementation of multiple-image radiography.

Conventional x-ray computed tomography (CT) produces a single volumetric image that represents the spatially variant linear x-ray attenuation coefficient of an object. However, in many situations, differences in the x-ray attenuation properties of soft tissues are very small and difficult to measure in conventional x-ray imaging. In this work, we investigate an analyzer-based imaging method, called computed tomography multiple-image radiography (CT-MIR), which is a tomographic implementation of the recently proposed multiple-image radiography method. The CT-MIR method reconstructs concurrently three physical properties of the object. In addition to x-ray attenuation, CT-MIR produces volumetric images that represent the refraction and ultrasmall-angle scattering properties of the object. These three images can provide a rich description of the object's physical properties that are revealed by the probing x-ray beam. An imaging model for CT-MIR that is based on the x-ray transform of the object properties is established. The CT-MIR method is demonstrated by use of experimental data acquired at a synchroton radiation imaging beamline, and is compared to the pre-existing diffraction-enhanced imaging CT method. We also investigate the merit of an iterative reconstruction method for use with future clinical implementations of CT-MIR, which we anticipate would be photon limited.

Humans↗

PubMed2006

Diffraction-enhanced imaging of the rat spine.

INTRODUCTION: Diffraction-enhanced imaging (DEI) uses monochromatic synchrotron X-rays to image tissue. This technique has been shown to produce superior bony and soft tissue characterization when compared with conventional absorption radiography. Application of this imaging modality is under investigation, and this study represents the first DEI analysis of the vertebral column. METHODS: Four male Wistar rats were studied. Spine muscle blocks were imaged in 3 of the rats after thoracic laminectomy (n = 1), after lumbar laminectomy (n = 1), and in a control condition (n = 1). The fourth rat was imaged as a whole animal control. Conventional radiography and synchrotron-supported DEI at 40 keV were performed on all specimens. We compared images side by side, using a nonvalidated subjective assessment technique. RESULTS: DEI produced superior visualization of the vertebral anatomy, compared with conventional absorption radiography for all specimens. Greater bony and soft tissue detail was noted, with improved image contrast. In addition to imaging the anatomical structures, DEI showed the polyglactin suture material used for fascial closure in the 2 animals that underwent surgery. Artifact from air bubbles was present on DEI images but not on plain radiographs. CONCLUSIONS: This represents the first use of DEI, a novel imaging modality, to image the vertebral column. It provides excellent anatomic detail with superior contrast and visualization of both bone and soft tissue when compared with conventional radiography. Future applications of this investigational technique may include analysis of spinal fusion as well as degenerative and neoplastic conditions of the spine.

Animals↗

PubMed2005

A physical model of multiple-image radiography.

We recently proposed a phase-sensitive x-ray imaging method called multiple-image radiography (MIR), which is an improvement on the diffraction-enhanced imaging technique. MIR simultaneously produces three images, depicting separately the effects of absorption, refraction and ultra-small-angle scattering of x-rays, and all three MIR images are virtually immune to degradation caused by scattering at higher angles. Although good results have been obtained using MIR, no quantitative model of the imaging process has yet been developed. In this paper, we present a theoretical prediction of the MIR image values in terms of fundamental physical properties of the object being imaged. We use radiative transport theory to model the beam propagation, and we model the object as a stratified medium containing discrete scattering particles. An important finding of our analysis is that the image values in all three MIR images are line integrals of various object parameters, which is an essential property for computed tomography to be achieved with conventional reconstruction methods. Our analysis also shows that MIR truly separates the effects of absorption, refraction and ultra-small-angle scattering for the case considered. We validate our analytical model using real and simulated imaging data.

Algorithms↗

PubMed2005

Reliability of diffraction enhanced imaging for assessment of cartilage lesions, ex vivo.

OBJECTIVE: The assessment of articular cartilage integrity is of value for the detection of early degenerative joint disease in both the clinical and the research settings. It was the purpose of this study to determine the accuracy and reliability of identifying articular cartilage defects through Diffraction Enhanced Imaging (DEI), a high contrast radiographic imaging technique. DEI provides two new sources of image contrast to radiography: refraction and scatter rejection, besides the absorption of conventional radiography. DESIGN: Cadaveric tali were DEI imaged in the anterior-posterior position at the National Synchrotron Light Source. Two independent observers provided gross score evaluations (on a five point scale) of the trochlear surfaces. The DEI image of each trochlear surface was then graded (on a five point scale) by two additional independent observers who were blinded with regard to the gross evaluation of the articular surfaces. Inter-observer agreement for DEI grades was assessed with the weighted kappa statistic. Correlation of diffraction enhanced image score to the gross score was assessed with Spearman correlation coefficient. RESULTS: The defects of articular cartilage of talar trochleae could be visualized through DEI. The Spearman correlation of gross grades with DEI grades on the 165 talar regions for observers 1 and 2 were 0.91 and 0.91, respectively. The overall weighted kappa value for inter-observer agreement was 0.93, thus considered high agreement. CONCLUSIONS: DEI is accurate and reliable for detection of articular cartilage defects ex vivo. Even early stages of degeneration of cartilage can be visualized with this high contrast technique. Future studies will focus on the application of DEI to the identification of such lesions in vivo.

Aged↗

PubMed2005

Application of division arrest technology to cell-based HTS: comparison with frozen and fresh cells.

Cell-based functional assays are becoming popular in many HTS laboratories because of recent advances in detection and automation technologies. However, the supply of large amounts of live cells with consistent cellular response for day-to-day screening operations over several days/weeks is a tremendous challenge. The high cost of cell culture, labor-intensive nature of the work, and inherent variability in cellular responses from time to time tend to be prohibitive for extensive applications of cell-based assays in HTS. We therefore tested division-arrested cells that were prepared in a single batch and frozen at -80 degrees C before use in several cell-based assays and in a robotic screening campaign. Chinese hamster ovary cells expressing a Gq-coupled receptor were analyzed for the agonist-induced intracellular Ca2+ response measured on a fluorescent imaging plate reader. In this case, the division-arrested cells showed consistent agonist-induced intracellular Ca2+ concentration response as reflected by signal-to-basal ratio and EC50 even 48 h after cell plating. In comparison, the responses from untreated frozen cells and fresh cells declined significantly approximately 30 h after cell plating. In other cell-based assays tested (cyclic AMP assay, reporter gene beta-lactamase assay, and ion-channel assay), the division-arrested cells performed as well as frozen, or fresh cells. We thus conclude that the use of alternate strategies such as frozen cells or division-arrested cells may alleviate the need for several batches of cell plating each day during HTS while maintaining the desired robotic throughput and assay quality.

Animals↗

PubMed2005

Improving high-content-screening assay performance by using division-arrested cells.

As cell-based assays are used more commonly in robotic high-throughput compound screening, cells themselves have become critical reagents. Thus, it has become essential to produce cell reagents with high consistency and quality. We experimented with cells division-arrested with low-level mitomycin C treatment and demonstrate that they perform with better consistency than non-division-arrested counterparts in high-content screening imaging assays. We propose that for cell-based screening, it is possible to uncouple the cell production process from the screening process. Cells can be produced en masse, treated to become irreversibly division-arrested, and cryopreserved. These "ready-to-use" reagents can be thawed, plated, and used in screening with improved consistency and convenience.

Antibiotics, Antineoplastic↗

PubMed2005

Improving consistency of cell-based assays by using division-arrested cells.

In this article we describe the use of division-arrested cells for cell-based assays designed for high-throughput screening. Cells are the most critical and variable reagent for cell-based high-throughput screening. The robustness of robotic screening depends on the quality and consistency of cell reagents. We demonstrate that for most cell types commonly used for high-throughput screening, cells can be irreversibly division-arrested by mitomycin C treatment at doses that cause no apparent toxicity or obvious change to the cell signaling properties we measured. Our data also suggest that division-arrested cells perform favorably compared to regular growing cells in reporter and calcium flux assays, two platforms most commonly used in robotic screening. Division arrest technology effectively uncouples the process of cell production from robotic screening and brings the convenience of having quality-approved cell reagent on demand for cell-based high-throughput screening.

Animals↗

PubMed2005

High-pass-filtered diffraction microtomography by coherent hard x rays for cell imaging: theoretical and numerical studies of the imaging and reconstruction principles.

This paper presents theoretical and numerical studies of diffraction tomography using hard x rays, from the viewpoint of imaging and reconstruction methods for cell imaging. The proposed system employs a single-perfect-crystal analyzer in symmetric Laue-case transmission geometry to efficiently detect the higher spatial frequency components of an object's refractive-index distribution, and to effectively suppress interference between the unperturbated wave field and the wave field diffracted by the object. This system features acquisition of a single projection by a single exposure using a simple geometry and aggressive use of diffracted x rays. We present the physical description of the imaging method using the Fourier diffraction theorem derived from the Born approximation. First, we demonstrate that the reconstruction leads to the phase-retrieval problem. We then describe a reconstruction algorithm based on the classical Gerchberg-Saxton-Fienup algorithm. Finally, we show the efficacy of this system by computer simulation. Our simulation demonstrates that the imaging system delineates microstructure 3.5 microm in diameter in a phase object 400 microm in diameter.

Algorithms↗

PubMed2004

Improved image contrast of calcifications in breast tissue specimens using diffraction enhanced imaging.

The contrast of calcifications in images of breast tissue specimens using a synchrotron-based diffraction enhanced imaging (DEI) apparatus has been measured and is compared to the contrast in images acquired using a conventional synchrotron-based radiographic imaging modality. DEI is an imaging modality which derives image contrast from x-ray absorption, refraction and small-angle scatter-rejection (extinction), unlike conventional radiographic techniques, which can only derive contrast from absorption. DEI is accomplished by inserting an analyser crystal in the beam path between the sample and the detector. Two of the three breast tissue specimens contained calcifications associated with cancer, while a third contained benign calcifications. Results of the image analysis indicate that the DEI contrast of images taken with the analyser crystal tuned to the peak of its rocking curve, was as much as 19 times that of the conventional radiograph, with an average of 5.5 for all calcifications. This improved image contrast for even near-pixel-size calcifications suggests potential utility for DEI in breast imaging.

Breast Diseases↗

PubMed2003

Multiple-image radiography.

Conventional radiography produces a single image of an object by measuring the attenuation of an x-ray beam passing through it. When imaging weakly absorbing tissues, x-ray attenuation may be a suboptimal signature of disease-related information. In this paper we describe a new phase-sensitive imaging method, called multiple-image radiography (MIR), which is an improvement on a prior technique called diffraction-enhanced imaging (DEI). This paper elaborates on our initial presentation of the idea in Wernick et al (2002 Proc. Int. Symp. Biomed. Imaging pp 129-32). MIR simultaneously produces several images from a set of measurements made with a single x-ray beam. Specifically, MIR yields three images depicting separately the effects of refraction, ultra-small-angle scatter and attenuation by the object. All three images have good contrast, in part because they are virtually immune from degradation due to scatter at higher angles. MIR also yields a very comprehensive object description, consisting of the angular intensity spectrum of a transmitted x-ray beam at every image pixel, within a narrow angular range. Our experiments are based on data acquired using a synchrotron light source; however, in preparation for more practical implementations using conventional x-ray sources, we develop and evaluate algorithms designed for Poisson noise, which is characteristic of photon-limited imaging. The results suggest that MIR is capable of operating at low photon count levels, therefore the method shows promise for use with conventional x-ray sources. The results also show that, in addition to producing new types of object descriptions, MIR produces substantially more accurate images than its predecessor, DEI. MIR results are shown in the form of planar images of a phantom and a biological specimen. A preliminary demonstration of the use of MIR for computed tomography is also presented.

Absorptiometry, Photon↗

PubMed2003

Measurement of image contrast using diffraction enhanced imaging.

Refraction contrast of simple objects obtained using diffraction enhanced imaging (DEI) was studied and compared to conventional radiographic contrast. Lucite cylinders and nylon wires were imaged using monochromatic synchrotron radiation at the National Synchrotron Light Source (http://nslsweb. nsls.bnl.gov/nsls/Default.htm) at the Brookhaven National Laboratory. The DEI images were obtained by placing a silicon analyser crystal tuned to the [333] diffraction plane in the beam path between the sample and the detector. To compare the DEI images with conventional radiographic images requires a consistent definition of refraction and absorption contrast. Conventional definitions of contrast favour conventional radiography and DEI contrast is defined to emphasize the specific characteristics of DEI. The proposed definitions were then used to find the DEI gain (the ratio of the DEI contrast with respect to the conventional image contrast). The results presented here show that the DEI gain is consistently greater than 1, indicating that DEI provides more contrast information than conventional radiography.

Computer Simulation↗

PubMed2003

Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration.

Animals↗

PubMed2003

Radiography of soft tissue of the foot and ankle with diffraction enhanced imaging.

Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray imaging technique that could detect both bone and soft tissues seemed unrealistic. However, the introduction of diffraction enhanced X-ray imaging (DEI) which is capable of rendering images with absorption, refraction and scatter rejection qualities has allowed detection of specific soft tissues based on small differences in tissue densities. Here we show for the first time that DEI allows high contrast imaging of soft tissues, including ligaments, tendons and adipose tissue, of the human foot and ankle.

Adipose Tissue↗

PubMed2002

New pressure flow cell to monitor BaSO4 precipitation using synchrotron in situ angle-dispersive X-ray diffraction.

A flow cell has been commissioned to monitor in situ precipitation reactions under non-ambient conditions. The majority of high-pressure systems use anvils and presses to obtain high pressures around a small reaction area; however, this prototype is unique in that solutions may be examined as they flow through the cell under pressure. The cell is made of single-crystal silicon, which is capable of withstanding the high pressures created by liquid flow within the cell. With the capability of reaching pressures of up to 4 x 10(7) Pa, the cell is ideal for work on geological and oilfield systems. Here it is used to examine the formation of barium sulfate scale in situ under non-ambient conditions using angle-dispersive XRD on beamline X17b1 at the NSLS.

Journal Article↗

PubMed2002

Flavonol glycosides from Lysimachia capillipes.

Two new compounds, capilliposide I and capilliposide II, together with a known compound quercetin-3-O-(2,6-di-alpha-L-rhamnopyranosyl)-beta-D-galactopyranoside were isolated from the extracts of the whole herbs of Lysimachia capillipes. Their structures were established through their spectral data and chemical properties.

Chemistry Techniques, Analytical↗