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Biomedical subjects

L Xing

Publications and source records attributed to L Xing.

At least 19 recordsLinked to original sources
PubMed2005

Motion correction for improved target localization with on-board cone-beam computed tomography.

On-board imager (OBI) based cone-beam computed tomography (CBCT) has become available in radiotherapy clinics to accurately identify the target in the treatment position. However, due to the relatively slow gantry rotation (typically about 60 s for a full 360 degrees scan) in acquiring the CBCT projection data, the patient's respiratory motion causes serious problems such as blurring, doubling, streaking and distortion in the reconstructed images, which heavily degrade the image quality and the target localization. In this work, we present a motion compensation method for slow-rotating CBCT scans by incorporating into image reconstruction a patient-specific motion model, which is derived from previously obtained four-dimensional (4D) treatment planning CT images of the same patient via deformable registration. The registration of the 4D CT phases results in transformations representing a temporal sequence of three-dimensional (3D) deformation fields, or in other words, a 4D model of organ motion. The algorithm was developed heuristically in two-dimensional (2D) parallel-beam geometry and extended to 3D cone-beam geometry. By simulations with digital phantoms capable of translational motion and other complex motion, we demonstrated that the algorithm can reduce the motion artefacts locally, and restore the tumour size and shape, which may thereby improve the accuracy of target localization and patient positioning when CBCT is used as the treatment guidance.

Algorithms↗
PubMed2005

Tumor necrosis factor prevents alendronate-induced osteoclast apoptosis in vivo by stimulating Bcl-xL expression through Ets-2.

OBJECTIVE: To investigate why bisphosphonates are less effective at preventing focal bone loss in rheumatoid arthritis (RA) patients than in those with generalized osteoporosis, and the mechanisms involved. METHODS: The response of osteoclasts to alendronate (ALN) in tumor necrosis factor-transgenic (TNF-Tg) mice that develop erosive arthritis and in wild-type littermates was studied. TNF-Tg and wild-type mice were given ALN, and the osteoclast numbers in the inflamed joints and in the long bones were compared. The expression levels of Bcl-xL in the osteoclasts of TNF-Tg and wild-type mice were examined by immunostaining. The effect of overexpression of Bcl-xL and Ets-2 proteins on ALN-induced osteoclast apoptosis was determined using an in vitro osteoclast survival assay and retrovirus transfer approach. RESULTS: ALN reduced osteoclast numbers in the metaphyses by 97%, but by only 46% in the adjacent inflamed joints. Bcl-xL expression was markedly higher in osteoclasts in the joints than in those in the metaphyses of TNF-Tg mice. Bcl-xL or Ets-2 overexpression protected osteoclasts from ALN-induced apoptosis, and TNF stimulated Bcl-xL and Ets-2 expression in osteoclasts. Overexpression of Ets-2 increased Bcl-xL messenger RNA in osteoclasts, while a dominant-negative form of the Ets-2 blocked the protective effect of Bcl-xL or TNF on ALN-induced apoptosis. CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis.

Alendronate↗
PubMed2005

Radiation dose reduction in four-dimensional computed tomography.

Four-dimensional (4D) CT is useful in many clinical situations, where detailed abdominal and thoracic imaging is needed over the course of the respiratory cycle. However, it usually delivers a larger radiation dose than the standard three-dimensional (3D) CT, since multiple scans at each couch position are required in order to provide the temporal information. Our purpose in this work is to develop a method to perform 4D CT scans at relatively low current, hence reducing the radiation exposure of the patients. To deal with the increased statistical noise caused by the low current, we proposed a novel 4D penalized weighted least square (4D-PWLS) smoothing method, which can incorporate both spatial and phase information. The 4D images at different phases were registered to the same phase via a deformable model, thereby, a regularization term combining temporal and spatial neighbors can be designed for the 4D-PWLS objective function. The proposed method was tested with phantom experiments and a patient study, and superior noise suppression and resolution preservation were observed. A quantitative evaluation of the benefit of the proposed method to 4D radiotherapy and 4D PET/CT imaging are under investigation.

Biophysical Phenomena↗
PubMed2004

Mapping of the prostate in endorectal coil-based MRI/MRSI and CT: a deformable registration and validation study.

The endorectal coil is being increasingly used in magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) to obtain anatomic and metabolic images of the prostate with high signal-to-noise ratio (SNR). In practice, however, the use of endorectal probe inevitably distorts the prostate and other soft tissue organs, making the analysis and the use of the acquired image data in treatment planning difficult. The purpose of this work is to develop a deformable image registration algorithm to map the MRI/MRSI information obtained using an endorectal probe onto CT images and to verify the accuracy of the registration by phantom and patient studies. A mapping procedure involved using a thin plate spline (TPS) transformation was implemented to establish voxel-to-voxel correspondence between a reference image and a floating image with deformation. An elastic phantom with a number of implanted fiducial markers was designed for the validation of the quality of the registration. Radiographic images of the phantom were obtained before and after a series of intentionally introduced distortions. After mapping the distorted phantom to the original one, the displacements of the implanted markers were measured with respect to their ideal positions and the mean error was calculated. In patient studies, CT images of three prostate patients were acquired, followed by 3 Tesla (3 T) MR images with a rigid endorectal coil. Registration quality was estimated by the centroid position displacement and image coincidence index (CI). Phantom and patient studies show that TPS-based registration has achieved significantly higher accuracy than the previously reported method based on a rigid-body transformation and scaling. The technique should be useful to map the MR spectroscopic dataset acquired with ER probe onto the treatment planning CT dataset to guide radiotherapy planning.

Algorithms↗
PubMed2003

Independent dosimetric calculation with inclusion of head scatter and MLC transmission for IMRT.

Independent verification of the MU settings and dose calculation of IMRT treatment plans is an important step in the IMRT quality assurance (QA) procedure. At present, the verification is mainly based on experimental measurements, which are time consuming and labor intensive. Although a few simplified algorithms have recently been proposed for the independent dose (or MU) calculation, head scatter has not been precisely taken into account in all these investigations and the dose validation has mainly been limited to the central axis. In this work we developed an effective computer algorithm for IMRT MU and dose validation. The technique is superior to the currently available computer-based MU check systems in that (1) it takes full consideration of the head scatter and leaf transmission effects; and (2) it allows a precise dose calculation at an arbitrary spatial point instead of merely a point on the central axis. In the algorithm the dose at an arbitrary spatial point is expressed as a summation of the contributions of primary and scatter radiation from all beamlets. Each beamlet is modulated by a dynamic modulation factor (DMF), which is determined by the MLC leaf trajectories, the head scatter, the jaw positions, and the MLC leaf transmission. A three-source model was used to calculate the head scatter distribution for irregular segments shaped by MLC and the scatter dose contributions were computed using a modified Clarkson method. The system reads in MLC leaf sequence files (or RTP files) generated by the Corvus (NOMOS Corporation, Sewickley, PA) inverse planning system and then computes the doses at the desired points. The algorithm was applied to study the dose distributions of several testing intensity modulated fields and two multifield Corvus plans and the results were compared with Corvus plans and experimental measurements. The final dose calculations at most spatial points agreed with the experimental measurements to within 3% for both the specially designed testing fields and the clinical intensity modulated field. Furthermore, excellent agreement (mostly within +/- 3.0%) was also found between our independent calculation and the ion chamber measurements at both central axis and off-axis positions for the multifield Corvus IMRT plans. These results indicate that the approach is robust and valuable for routine clinical IMRT plan validation.

Algorithms↗
PubMed2002

Application of constrained least-squares techniques to IMRT treatment planning.

PURPOSE: The purpose of this work was to apply the method of constrained least-squares to inverse treatment planning and to explore its potential for providing a fast interactive planning environment for intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: The description of the dose inside a patient is a linear matrix transformation of beamlet weights. The constrained least-squares method adds additional matrix operators and produces beamlet weights by a direct linear transformation. These matrix operators contain a priori knowledge about the radiation distribution. The constrained least-squares technique was applied to obtain IMRT plans for prostate and paraspinal cancer patients and compared with the corresponding plans optimized using the CORVUS inverse planning system. RESULTS: It was demonstrated that a constrained least-squares technique is suitable for IMRT plan optimization with significantly increased computing speed. For the two cases we have tested, the constrained least-squares method was an order of magnitude faster than conventional iterative techniques because of the avoidance of the iterative calculations. We also found that the constrained least-squares method is capable of generating clinically acceptable treatment plans with less trial-and-error adjustments of system variables, and with improved target volume coverage as well as sensitive structure sparing in comparison with that obtained using CORVUS. CONCLUSIONS: The constrained least-squares method has the advantage that it does not require iterative calculation and thus significantly speeds up the therapeutic plan optimization process. Besides shedding important insight into the inverse planning problem, the technique has strong potential to provide a fast and interactive environment for IMRT treatment planning.

Algorithms↗
PubMed2002

Minimizing delivery time and monitor units in static IMRT by leaf-sequencing.

Intensity-modulated radiation therapy (IMRT) requires the determination of the appropriate multileaf collimator settings to deliver an intensity map. The purpose of this work was to attempt to reduce the number of segments required for IMRT delivery and the number of monitor units required to deliver an intensity map. An intensity map may be written as a matrix. Leaf sequencing was formulated as a problem of decomposing the matrix into a series of sub-matrices. Sets of random intensity matrices were created and the segmentations produced by applying different algorithms were compared. The number of segments, important if verification and record (VR) overhead is significant, and beam on times were examined. It is shown that reducing the value of the matrix entries by the maximum amount at each stage results in the smallest number of steps. Reducing the 2-norm (sum of the squares) of the matrix entries by the maximum amount at each step results in the smallest beam on time. Three new algorithms are introduced, two of which produce results that are superior to those generated by the algorithms of other researchers. The resulting methods can be expanded upon to include tongue and groove effects and leaf inter-digitization. With square random matrices of the order 15, the reduction in beam time and segmentation is up to 30-40%. Compared to previous algorithms, those presented here have demonstrated a reduction in the beam on time required to deliver an intensity map by 30-40%. Similarly, the number of segments needed to deliver an intensity map is also reduced.

Algorithms↗
PubMed2001

Pseudo beam's-eye-view as applied to beam orientation selection in intensity-modulated radiation therapy.

PURPOSE: To introduce the concept of pseudo beam's-eye-view (pBEV), to establish a framework for computer-assisted beam orientation selection in intensity-modulated radiation therapy (IMRT), and to evaluate the utility of the proposed technique. METHODS AND MATERIALS: To facilitate the selection of beam orientations for IMRT treatment planning, a scoring of beam direction was introduced. The score function was based on the maximum target dose deliverable by the beam without exceeding the tolerance doses of the critical structures. For the score function calculation, the beam portal at given gantry and couch angles was divided into a grid of beamlets. Each beamlet crossing the target was assigned the maximum intensity that could be used without exceeding the dose tolerances of the organs at risk (OARs) and normal tissue. Thereafter, a score was assigned to the beam according to the target dose delivered. The beams for the treatment were selected among those with the highest scores. In a sense, this technique is similar to the beam's-eye-view approach used in conventional radiation therapy, except that the evaluation by a human is replaced by a score function, and beam modulation is taken into account. RESULTS: The pBEV technique was tested on two clinical cases: a paraspinal treatment and a nasopharyngeal cancer with both coplanar and noncoplanar beam configurations. The plans generated under the guidance of pBEV for the paraspinal treatment offered superior target dose uniformity and reduced OAR doses. For the nasopharyngeal cancer case, it was also found that the pBEV-selected coplanar and noncoplanar beams significantly improved the target coverage without compromising the sparing of the OARs. CONCLUSIONS: The pBEV technique developed in this work provides a comprehensive tool for beam orientation selection in IMRT. It is especially valuable for complicated cases, where the target is surrounded by several sensitive structures and where it is difficult to select a set of good beam orientations. The pBEV technique has considerable potential for simplifying the IMRT treatment planning process and for maximizing the technical capacity of IMRT.

Humans↗
PubMed2001

Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development.

Runx (Cbfa/AML) transcription factors are critical for tissue-specific gene expression. A unique targeting signal in the C terminus directs Runx factors to discrete foci within the nucleus. Using Runx2/CBFA1/AML3 and its essential role in osteogenesis as a model, we investigated the fundamental importance of fidelity of subnuclear localization for tissue differentiating activity by deleting the intranuclear targeting signal via homologous recombination. Mice homozygous for the deletion (Runx2 Delta C) do not form bone due to maturational arrest of osteoblasts. Heterozygotes do not develop clavicles, but are otherwise normal. These phenotypes are indistinguishable from those of the homozygous and heterozygous null mutants, indicating that the intranuclear targeting signal is a critical determinant for function. The expressed truncated Runx2 Delta C protein enters the nucleus and retains normal DNA binding activity, but shows complete loss of intranuclear targeting. These results demonstrate that the multifunctional N-terminal region of the Runx2 protein is not sufficient for biological activity. We conclude that subnuclear localization of Runx factors in specific foci together with associated regulatory functions is essential for control of Runx-dependent genes involved in tissue differentiation during embryonic development.

Animals↗
PubMed2001

Role of beam orientation optimization in intensity-modulated radiation therapy.

PURPOSE: To investigate the role of beam orientation optimization in intensity-modulated radiation therapy (IMRT) and to examine the potential benefits of noncoplanar intensity-modulated beams. METHODS AND MATERIALS: A beam orientation optimization algorithm was implemented. For this purpose, system variables were divided into two groups: beam position (gantry and table angles) and beam profile (beamlet weights). Simulated annealing was used for beam orientation optimization and the simultaneous iterative inverse treatment planning algorithm (SIITP) for beam intensity profile optimization. Three clinical cases were studied: a localized prostate cancer, a nasopharyngeal cancer, and a paraspinal tumor. Nine fields were used for all treatments. For each case, 3 types of treatment plan optimization were performed: (1) beam intensity profiles were optimized for 9 equiangular spaced coplanar beams; (2) orientations and intensity profiles were optimized for 9 coplanar beams; (3) orientations and intensity profiles were optimized for 9 noncoplanar beams. RESULTS: For the localized prostate case, all 3 types of optimization described above resulted in dose distributions of a similar quality. For the nasopharynx case, optimized noncoplanar beams provided a significant gain in the gross tumor volume coverage. For the paraspinal case, orientation optimization using noncoplanar beams resulted in better kidney sparing and improved gross tumor volume coverage. CONCLUSION: The sensitivity of an IMRT treatment plan with respect to the selection of beam orientations varies from site to site. For some cases, the choice of beam orientations is important even when the number of beams is as large as 9. Noncoplanar beams provide an additional degree of freedom for IMRT treatment optimization and may allow for notable improvement in the quality of some complicated plans.

Algorithms↗
PubMed2001

Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival.

Mutant src(-/-) mice have osteopetrosis resulting from defective osteoclasts, the cells that resorb bone. However, signaling pathways involving Src family members in osteoclasts remain unclear. We demonstrate that expression of a truncated Src molecule, Src251, lacking the kinase domain, induces osteopetrosis in wild-type and src(+/-) mice and worsens osteopetrosis in src(-/-) mice by a novel mechanism, increased osteoclast apoptosis. Induction of apoptosis by Src251 requires a functional SH2, but not an SH3, domain and is associated with reduced AKT kinase activity. Expression of Src251 dramatically reduces osteoclast survival in response to RANKL/TRANCE/OPGL, providing evidence that Src family kinases are required in vivo for survival signaling pathways downstream from TNF family receptors.

Animals↗
PubMed2001

Adenovirus-mediated expression of pig alpha(1, 3) galactosyltransferase reconstructs Gal alpha(1, 3) gal epitope on the surface of human tumor cells.

Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.

Adenoviridae↗
PubMed2001

Linear algebraic methods applied to intensity modulated radiation therapy.

Methods of linear algebra are applied to the choice of beam weights for intensity modulated radiation therapy (IMRT). It is shown that the physical interpretation of the beam weights, target homogeneity and ratios of deposited energy can be given in terms of matrix equations and quadratic forms. The methodology of fitting using linear algebra as applied to IMRT is examined. Results are compared with IMRT plans that had been prepared using a commercially available IMRT treatment planning system and previously delivered to cancer patients.

Dose-Response Relationship, Radiation↗
PubMed2001

Optimization of the step-and-shoot leaf sequence for delivery of intensity modulated radiation therapy using a variable division scheme.

To deliver an intensity modulated radiation therapy (IMRT) plan by multileaf collimator (MLC) it is necessary to convert beam profiles, generated from the inverse treatment planning algorithm, into a series of instructions that the MLC control system can execute. An idealized IMRT beam profile can be regarded as a continuously varying two-dimensional function and is usually represented by an intensity map, i.e., a discretized description in space and in intensity of the beam profile. It is common to assume that the intensity map be defined over a regular grid with N steps and equal increments of intensity levels. In reality, this may not be the optimal representation of the beam profile and may introduce unnecessary discrepancies between the intensity pattern delivered and that ideally required. We have implemented an algorithm capable of minimizing the difference between the two patterns on a beam specific basis. In other words, it can produce optimized intensity maps, individually produced to suit the (continuous function) intensity profile they are intended to approximate. This enhancement in conformation is achieved by allowing variable step size and unconstrained intensity levels in the final leaf sequence.

Algorithms↗
PubMed2001

Computer-assisted selection of coplanar beam orientations in intensity-modulated radiation therapy.

In intensity-modulated radiation therapy (IMRT), the incident beam orientations are often determined by a trial and error search. The conventional beam's-eye view (BEV) tool becomes less helpful in IMRT because it is frequently required that beams go through organs at risk (OARs) in order to achieve a compromise between the dosimetric objectives of the planning target volume (PTV) and the OARs. In this paper, we report a beam's-eye view dosimetrics (BEVD) technique to assist in the selection of beam orientations in IMRT. In our method, each beam portal is divided into a grid of beamlets. A score function is introduced to measure the 'goodness' of each beamlet at a given gantry angle. The score is determined by the maximum PTV dose deliverable by the beamlet without exceeding the tolerance doses of the OARs and normal tissue located in the path of the beamlet. The overall score of the gantry angle is given by a sum of the scores of all beamlets. For a given patient. the score function is evaluated for each possible beam orientation. The directions with the highest scores are then selected as the candidates for beam placement. This procedure is similar to the BEV approach used in conventional radiation therapy, except that the evaluation by a human is replaced by a score function to take into account the intensity modulation. This technique allows one to select beam orientations without the excessive computing overhead of computer optimization of beam orientation. It also provides useful insight into the problem of selection of beam orientation and is especially valuable for complicated cases where the PTV is surrounded by several sensitive structures and where it is difficult to select a set of 'good' beam orientations. Several two-dimensional (2D) model cases were used to test the proposed technique. The plans obtained using the BEVD-selected beam orientations were compared with the plans obtained using equiangular spaced beams. For all the model cases investigated, the use of BEVD-selected beam orientations improved the dose distributions significantly. These examples indicate that the technique has considerable potential for simplifying the IMRT treatment planning process and allows for better utilization of the technical capacity of IMRT.

Humans↗
PubMed2001

Ability of transplanted cultured epithelium to respond to dermal papillae.

Cultured epithelium has been used successfully in the treatment of extensive burns. Regenerated epidermis, however, lacks such as hair follicles and sweat glands that are common in mammalian skin. We attempted to determine whether cultured epithelium could be induced to form hair follicles by dermal papillae, which are most important for the morphogenesis and growth of hair follicles. We cultivated adult rat sole keratinocytes, obtained the cultured epithelium, and prepared recombinants consisting of cultured epithelium and fresh dermal papillae with or without the sole dermis. These recombinants were then transplanted underneath the dermis of the dorsal skin of syngeneic rats or athymic mice. Histologic examination revealed that the transplanted cultured epithelium formed the follicular structures with sebaceous gland-like structure following induction of the dermal papillae, especially when supported by the dermis. We concluded that transplanted cultured epithelium of adult rat sole keratinocytes can respond to growth signals from adult dermal papillae.

Animals↗
PubMed2001

Multi-query sequence BLAST output examination with MuSeqBox.

SUMMARY: MuSeqBox is a program to parse BLAST output and store attributes of BLAST hits in tabular form. The user can apply a number of selection criteria to filter out hits with particular attributes. MuSeqBox provides a powerful annotation tool for large sets of query sequences that are simultaneously compared against a database with any of the standard stand-alone or network-client BLAST programs. We discuss such application to the problem of annotation and analysis of EST collections. AVAILABILITY: The program was written in standard C++ and is freely available to noncommercial users by request from the authors. The program is also available over the web at http://bioinformatics.iastate.edu/bioinformatics2go/mb/MuSeqBox.html.

Alternative Splicing↗