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Weiguo Lu

Publications and source records attributed to Weiguo Lu.

13 recordsLinked to original sources

Accurate convolution/superposition for multi-resolution dose calculation using cumulative tabulated kernels.

Convolution/superposition (C/S) is regarded as the standard dose calculation method in most modern radiotherapy treatment planning systems. Different implementations of C/S could result in significantly different dose distributions. This paper addresses two major implementation issues associated with collapsed cone C/S: one is how to utilize the tabulated kernels instead of analytical parametrizations and the other is how to deal with voxel size effects. Three methods that utilize the tabulated kernels are presented in this paper. These methods differ in the effective kernels used: the differential kernel (DK), the cumulative kernel (CK) or the cumulative-cumulative kernel (CCK). They result in slightly different computation times but significantly different voxel size effects. Both simulated and real multi-resolution dose calculations are presented. For simulation tests, we use arbitrary kernels and various voxel sizes with a homogeneous phantom, and assume forward energy transportation only. Simulations with voxel size up to 1 cm show that the CCK algorithm has errors within 0.1% of the maximum gold standard dose. Real dose calculations use a heterogeneous slab phantom, both the 'broad' (5 x 5 cm2) and the 'narrow' (1.2 x 1.2 cm2) tomotherapy beams. Various voxel sizes (0.5 mm, 1 mm, 2 mm, 4 mm and 8 mm) are used for dose calculations. The results show that all three algorithms have negligible difference (0.1%) for the dose calculation in the fine resolution (0.5 mm voxels). But differences become significant when the voxel size increases. As for the DK or CK algorithm in the broad (narrow) beam dose calculation, the dose differences between the 0.5 mm voxels and the voxels up to 8 mm (4 mm) are around 10% (7%) of the maximum dose. As for the broad (narrow) beam dose calculation using the CCK algorithm, the dose differences between the 0.5 mm voxels and the voxels up to 8 mm (4 mm) are around 1% of the maximum dose. Among all three methods, the CCK algorithm is demonstrated to be the most accurate one for multi-resolution dose calculations.

Algorithms↗

PTEN promoter methylation and protein expression in normal early placentas and hydatidiform moles.

OBJECTIVE: To investigate the relationship between PTEN promoter methylation and protein expression, and the possible involvement of the PTEN gene in development of gestational trophoblasts and the pathogenesis of hydatidiform moles. METHODS: DNA was extracted from choria of normal early placentas, partial hydatidiform moles, complete hydatidiform moles, and invasive moles, and overdigested by methylation-sensitive endonuclease HpaII. The PTEN promoter was amplificated by polymerase chain reaction. PTEN protein expression was detected by immunohistochemistry. RESULTS: In partial and complete hydatidiform moles, the PTEN promoter methylation rate was significantly higher than in early placentas (72%, 59.4%, 14.3%; P = .000, .002, respectively), and the PTEN protein expression rate was significantly lower than in early placentas (9.1%, 4.5%, 90.5%; P = .000, .000, respectively). However, partial hydatidiform moles, complete hydatidiform moles, and invasive moles were not significant different in terms of PTEN promoter methylation and protein expression. CONCLUSIONS: These findings suggest that the regulation of PTEN expression may play an important role in the development of the early gestational trophoblast and in the pathogenesis of hydatidiform mole, but not in its malignant transformation.

DNA Methylation↗

Motion-encoded dose calculation through fluence/sinogram modification.

Conventional radiotherapy treatment planning systems rely on a static computed tomography (CT) image for planning and evaluation. Intra/inter-fraction patient motions may result in significant differences between the planned and the delivered dose. In this paper, we develop a method to incorporate the knowledge of intra/inter-fraction patient motion directly into the dose calculation. By decomposing the motion into a parallel (to beam direction) component and perpendicular (to beam direction) component, we show that the motion effects can be accounted for by simply modifying the fluence distribution (sinogram). After such modification, dose calculation is the same as those based on a static planning image. This method is superior to the "dose-convolution" method because it is not based on "shift invariant" assumption. Therefore, it deals with material heterogeneity and surface curvature very well. We test our method using extensive simulations, which include four phantoms, four motion patterns, and three plan beams. We compare our method with the "dose-convolution" and the "stochastic simulation" methods (gold standard). As for the homogeneous flat surface phantom, our method has similar accuracy as the "dose-convolution" method. As for all other phantoms, our method outperforms the "dose-convolution." The maximum motion encoded dose calculation error using our method is within 4% of the gold standard. It is shown that a treatment planning system that is based on "motion-encoded dose calculation" can incorporate random and systematic motion errors in a very simple fashion. Under this approximation, in principle, a planning target volume definition is not required, since it already accounts for the intra/inter-fraction motion variations and it automatically optimizes the cumulative dose rather than the single fraction dose.

Algorithms↗

Mismatch repair gene promoter methylation and expression in hydatidiform moles.

METHODS: In this study, to investigate the significance of mismatch repair genes (MMR) promoter methylation and expression in the pathogenesis and malignant transformation of hydatidiform moles, we assayed promoter methylation and protein expression of the MMR genes hMLH1 and hMSH2 in gestational trophoblastic diseases (GTDs). DNA was extracted from normal placentas, partial hydatidiform moles, complete hydatidiform moles, and invasive moles, over-digested by methylation-sensitive endonuclease Hpa II, and then the promoters were amplificated by polymerase chain reaction. The protein expression was detected by immunohistochemistry. RESULTS: In the normal placentas, neither hMLH1 nor hMSH2 promoter methylation was detected. Expression of hMLH1 and hMSH2 in cytotrophoblasts was strongly positive. In partial hydatidiform moles and complete hydatidiform moles, hMLH1 and hMSH2 promoter methylation rates were significantly higher than that of normal placentas (P = 0.000), and the protein expression in cytotrophoblasts was significantly lower (P = 0.000). In the invasive moles, hMLH1 and hMSH2 promoter methylation was not significantly different compared with the partial hydatidiform moles and complete hydatidiform moles (P > 0.05). Expression of hMLH1 in the invasive moles (54.5%, 6 out of 11) was not significantly different compared with the partial hydatidiform moles and complete hydatidiform moles (P > 0.05). But hMSH2 expression in the invasive moles (36.5%, 4 out of 11) was weaker than that in complete hydatidiform moles (P = 0.044). Promoter methylation and less expression of hMSH2 were correlated in complete hydatidiform moles (P = 0.001) and invasive moles (P = 0.039). CONCLUSIONS: These results indicated that strong expression of hMLH1 and hMSH2 in the cytotrophoblasts of normal placentas may maintain genome stability. Promoter methylation and down-regulation of the expression of hMLH1 and hMSH2 are probably involved in the pathogenesis of hydatidiform moles.

Adaptor Proteins, Signal Transducing↗

Fast free-form deformable registration via calculus of variations.

In this paper, we present a fully automatic, fast and accurate deformable registration technique. This technique deals with free-form deformation. It minimizes an energy functional that combines both similarity and smoothness measures. By using calculus of variations, the minimization problem was represented as a set of nonlinear elliptic partial differential equations (PDEs). A Gauss-Seidel finite difference scheme is used to iteratively solve the PDE. The registration is refined by a multi-resolution approach. The whole process is fully automatic. It takes less than 3 min to register two three-dimensional (3D) image sets of size 256 x 256 x 61 using a single 933 MHz personal computer. Extensive experiments are presented. These experiments include simulations, phantom studies and clinical image studies. Experimental results show that our model and algorithm are suited for registration of temporal images of a deformable body. The registration of inspiration and expiration phases of the lung images shows that the method is able to deal with large deformations. When applied to the daily CT images of a prostate patient, the results show that registration based on iterative refinement of displacement field is appropriate to describe the local deformations in the prostate and the rectum. Similarity measures improved significantly after the registration. The target application of this paper is for radiotherapy treatment planning and evaluation that incorporates internal organ deformation throughout the course of radiation therapy. The registration method could also be equally applied in diagnostic radiology.

Algorithms↗

VEGF, VEGFRs expressions and activated STATs in ovarian epithelial carcinoma.

OBJECTIVE: To investigate the expressions of vascular endothelial growth factor (VEGF), VEGFRs and activation of signal transducers and activators of transcription (STATs) in ovarian epithelial carcinoma and the relationships among them. METHODS: The tissue samples of 42 primary ovarian epithelial carcinoma, 29 benign ovarian tumor and 11 normal ovarian tissue were used to determine the expression of VEGF, VEGFR1, VEGFR2, P-STAT1, P-STAT3, P-STAT5 and P-STAT6 proteins by immunohistochemical staining. RESULTS: VEGF in ovarian carcinomas was significantly higher than that in benign and normal ovarian tissues. VEGFRs expression was in agreement with VEGF expression. In tumor cells and endothelial cells of ovarian carcinomas, expressions of P-STAT3 and P-STAT5 were significantly higher than those in benign and normal ovarian tissues. In endothelial cells, the expression of VEGFR1 and P-STAT5 closely correlated with each other, as well as VEGFR2 and P-STAT3. However, in ovarian carcinoma cells, expressions of VEGF, VEGFR1 and VEGFR2 were significantly correlated with P-STAT3 and P-STAT5, but not with P-STAT1 and P-STAT6. CONCLUSIONS: There exist overexpressions of VEGF, VEGFRs, and STAT3, STAT5 activation. Furthermore, these results indicate that VEGF secreted by ovarian carcinoma cells may activate STAT pathway via VEGFRs in ovarian carcinoma themselves.

Adult↗

Fast treatment plan modification with an over-relaxed Cimmino algorithm.

A method to quickly modify a treatment plan in adaptive radiotherapy was proposed and studied. The method is based on a Cimmino-type algorithm in linear programming. The fast convergence speed is achieved by over-relaxing the algorithm relaxation parameter from its sufficient convergence range of (0, 2) to (0, infinity). The algorithm parameters are selected so that the over-relaxed Cimmino (ORC) algorithm can effectively approximate an unconstrained re-optimization process in adaptive radiotherapy. To demonstrate the effectiveness and flexibility of the proposed method in adaptive radiotherapy, two scenarios with different organ motion/deformation of one nasopharyngeal case were presented with comparisons made between this method and the re-optimization method. In both scenarios, the ORC algorithm modified treatment plans have dose distributions that are similar to those given by the re-optimized treatment plans. It takes us using the ORC algorithm to finish a treatment plan modification at least three times faster than the re-optimization procedure compared.

Algorithms↗

Treatment plan optimization incorporating respiratory motion.

Similar to conventional conformal radiotherapy, during lung tomotherapy, a motion margin has to be set for respiratory motion. Consequently, large volume of normal tissue is irradiated by intensive radiation. To solve this problem, we have developed a new motion mitigation method by incorporating target motion into treatment optimization. In this method, the delivery-breathing correlation is determined prior to treatment plan optimization. Beamlets are calculated by using the CT images at the corresponding breathing phases from a dynamic (four-dimensional) image sequence. With the displacement vector fields at different breathing phases, a set of deformed beamlets is obtained by mapping the dose to the primary phase. Optimization incorporating motion is then performed by using the deformed beamlets obtained by dose mapping. During treatment delivery, the same breathing-delivery correlation can be reproduced by instructing the patient to breathe following a visually displayed guiding cycle. This method was tested using a computer-simulated deformable phantom and a real lung case. Results show that treatment optimization incorporating motion achieved similar high dose conformality on a mobile target compared with static delivery. The residual motion effects due to imperfect breathing tracking were also analyzed.

Biophysical Phenomena↗

Image guidance for precise conformal radiotherapy.

PURPOSE: To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS: Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS: Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS: Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

Animals↗

[Development of intraperitoneally transplantated human ovarian carcinoma model with immune reconstruction in severe combined immunodeficient mice].

OBJECTIVE: To develop an intraperitoneally transplanted human ovarian carcinoma model in humanized severe combined immunodeficient (SCID) mice. METHODS: Twelve CB17SCID mice were randomly divided into 4 groups: group A intraperineally injected with phosphate-buffered saline, group B injected with human ovarian carcinoma cells SKOV3, group C injected with human peripheral blood lymphocyte (PBL) for immune reconstruction, and group D injected with PBL and SKOV3 cells. The behaviors of mice, tumor growth and morphology, human IgG in peripheral blood, cancer antigen 125 (CA125) immunohistochemical staining, tumor infiltrating lymphocyte (TIL), and status of graft versus host disease (GVHD) were detected. RESULTS: The survival period was > 28 days in all groups. The ratio of successful tumor transplantation was 3/3 in groups B and D. The tumor was widespread in peritoneal cavity, mainly in diaphragm, liver, and mesentery, with bloody ascites. The number and size of tumor were less in the humanized group. CA125 expression was positive in primary transplanted tumor cells and SKOV3 cells. IgG was detected in humanized groups (C and D). The level of human IgG was significantly higher in group D than in group C (P < 0.05). TIL infiltration was remarkable in group injected with PBL and SKOV3 cells and failed to be found in group injected with SKOV3 cells. No GVHD was found in all groups. CONCLUSION: An intraperitoneal transplanted human ovarian carcinoma model has been established in humanized SCID mice that simulates the biological behavior of human ovarian carcinoma disseminating intraperitoneally in patients with immune function and may function as an ideal animal model for preclinical research of ovarian carcinoma treatment.

Animals↗

Tomographic motion detection and correction directly in sinogram space.

Patient motion, especially respiratory motion, results in various artefacts such as blurring and streaks in tomographic images. The interplay of the movement of the beam aperture and variations of organ anatomy during delivery can create 'hot' and 'cold' spots throughout the field in intensity-modulated radiation therapy (IMRT). Detection and correction of patient motion is extremely important in tomographic imaging and IMRT. Tomographic projection data (sinogram) encode not only the patient anatomy information, but also the intra-scanning motion information. In this paper, we developed an algorithm to detect and correct the in-plane respiratory motion directly in sinogram space. The respiratory motion is modelled as time-varying scaling along the x and y directions. Its effects on the sinogram are discussed. Based on the traces of some nodal points in the sinogram, the intra-scanning motion is determined. The motion correction is also implemented in sinogram space. The motion-corrected sinogram is used for reconstruction by the filtered back-projection (FBP) method. Computer simulations validate the motion detection and correction algorithm. The reconstructed images from the motion-corrected sinogram eliminate the majority of the artefacts. The method could be applied to projection data used in CT and ECT, as well as in tomotherapy delivery modification and dose reconstruction.

Computer Simulation↗

[Histological classification in 10 288 cases of ovarian malignant tumors in China].

OBJECTIVE: The histological types of ovarian tumors were investigated and analyzed in China in order to compare with those in other countries, which will benefit to the prevention and treatment of ovarian carcinoma. METHODS: The pathological data from 42 197 cases of ovarian tumors in ten years during 1980 to 1989 were registered according to the WHO classification for ovarian tumors. Some unsure cases pathologically in the previous diagnosis should be reconfirmed according to the WHO classification. RESULTS: Forty-two thousand one hundred and ninety seven cases of ovarian tumors were selected from all tumors in 21 provinces and 3 major regional cities in China. There were 10 288 (24.4%) malignant tumors in all cases. They were composed by 5 650 (54.9%) cases of epithelial tumors, 1 871 (18.2%) cases of germ cell tumors, 873 (8.5%) cases of sex cord tumors, 1 003 (9.7%) cases of secondary tumors, and 891 (8.7%) cases of other tumors. The malignant tumors constituent ratios were 52.8% and 47.2% respectively in the north and south of the Yangtze River. The histological types of ovarian tumors were about the same ratios, but the malignant tumors were different in Chinese 6 major administrative region and also in the region both north and south of the Yangtze River. The ratio of borderline epithelial ovarian tumors to epithelial carcinoma was 1.0:5.9. Borderline serous cystadenocarcinoma appeared to be similar to borderline mucinous cystadenocarcinoma in frequency. Serous cystadenocarcinoma was found to be the most frequent one in malignant epithelial tumors. CONCLUSIONS: Compared with reports abroad, the different types of malignant ovarian tumors in China represent a different distributive pattern. The malignant epithelial ovarian tumors were lower than that in other countries, while the malignant germ cell tumors and sex cord stromal tumors were 6 and 3 times higher than those abroad, the main metastasizing tumors come from gastroenteric carcinoma.

China↗

[Antiangiogenesis of ginsenoside Rg3 in severe combined immunodeficient mice with human ovarian carcinoma].

OBJECTIVE: To investigate the antiangiogenesis of ginsenoside Rg3 in severe combined immunodeficient (SCID) mice with human ovarian carcinoma by detecting vascular endothelial growth factor (VEGF) mRNA, VEGF protein level and microvascular density (MVD). METHODS: The SCID mice with human ovarian carcinoma SKOV3 cells were treated with Rg3 (300 microgram 400 microl(-1) mouse(-1)), mice with phosphate buffered solution (PBS) and without Rg3 and PBS were used as control. Tumor volume, metastasis, ascites, VEGF mRNA, VEGF protein and MVD were detected. The level of VEGF mRNA in tumor tissue was determined by relative quantative reverse transcription polymerase chain reaction. VEGF protein level in sera and ascitic fluids were determined by enzyme-linked immunosorbent assay. MVD was calculated by immunohistochemistry (anti-CD34). RESULTS: (1) No ascites was formed and the size of metastasis decreased in SKOV3/Rg3 group. (2) Expression of VEGF mRNA level in SKOV3/Rg3 group (119 +/- 16) was lower significantly than those of the control groups (254 +/- 4, 273 +/- 44, respectively, P < 0.05). (3) Serum VEGF level in SKOV3/Rg3 group [(14.6 +/- 0.7) pg/ml] was lower significantly than those of SKOV3 group and SKOV3/PBS group [(18.5 +/- 2.1) and (20.5 +/- 1.7) pg/ml, respectively, P < 0.05]. (4) MVD in tumor tissues of SKOV3/Rg3 group (43 +/- 7) was lower than that of each control group (65 +/- 12, 73 +/- 10, respectively, P < 0.05). CONCLUSION: Ginsenoside Rg3 can block angiogenesis and inhibit tumor growth and metastasis by down regulating the expression of VEGF mRNA and protein and reducing microvascular density.

Angiogenesis Inhibitors↗