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Biomedical subjects

He Wang

Publications and source records attributed to He Wang.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Inhibition of HPV16 E6 oncogene in cervical cancer by RNA interference].

OBJECTIVE: The efficiency of HPV16 E6 gene silenced by RNA interference in vitro and in vivo was assessed. METHODS: The specific siRNA of HPV16 E6 was designed and transfected into CaSki cells by liposome. Cell apoptotic rates and the changes in HPV16 E6 mRNA and protein before and after transfection were measured. Cervical cancer nude mice models were set up, siRNA was injected directly into subcutaneous tumor. The function of siRNA was evaluated by the changes in tumor volume, HPV16 E6 protein expression and apoptosis of tumor cells. RESULTS: In vitro research, the cell apoptotic rates were 7.7%, 11.8%, 37.4% and 12.6% respectively at 24 h, 48 h, 5th day and 9th day after transfection. The HPV16 E6 mRNA was reduced by 77%, 83%, 59% and 41% at 24 h, 48 h, 5th day and 9th day after transfection. The inhibition rates of E6 protein measured by Flow cytometry were 79.7%, 80.4%, 71.3% and 57.4% at 24 h, 48 h, 5th day and 9th day after transfection, which were confirmed by the results of Western blot. In vivo research, E6 siRNA administration groups had great power in inhibiting tumor growth, restraining E6 protein expression, increasing tumor necrosis and apoptosis. The result of repeated injections of siRNA was better than that of single injection. CONCLUSION: RNA interference with HPV16 E6 is specific and highly efficient in vitro and in vivo.

Animals↗
PubMed2006

[Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in adenomyosis].

OBJECTIVE: To investigate the expressions of matrix metalloproteinase -2, -3 (MMP-2,-3) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in internal uterine endometriosis tissue and endometrium from women with and without endometriosis throughout the menstrual cycle. METHODS: Immunohistochemical staining of tissues was performed to study the expressions and locations of MMP-2, MMP-3, TIMP-2 between women with and without endometriosis. The real-time PCR technique was applied to detected the mRNA expressions of MMP-2, MMP-3 and TIMP-2. RESULTS: We found that ectopic endometrium from patients with endometriosis expressed higher levels of MMP-2 and MMP-3 and lower levers of TIMP-2 than normal controls did (P < 0.05). MMP-2 and MMP-3 were detected strongly in both stromal and epithelial cells of ectopic endometrium from patients with endometriosis, when mostly detected in the epithelial cells in the control group. All eutopic and ectopic endometrium samples from women with and without endometriosis throughout the menstrual cycle showed similar expressions of MMP-2, MMP-3 and TIMP-2. Quantitative expressions of MMP-2 mRNA, MMP-3 mRNA and TIMP-2 mRNA were significantly lower in eutopic endometrium from controls compared with ectopic endometrium from patients with endometriosis (P < 0.05). Eutopic endometrium from controls in the proliferative phase showed significantly increased expressions of MMP-2 mRNA compared with that in the secretory phase (P < 0.05). CONCLUSION: The results suggest that ectopic endometrium with adenomyosis has more invasiveness and is prone to peritoneal implantation maybe to involved in the high expressions of MMP-2 and MMP-3 and the less expressions of TIMP-2 than endometrium from women without adenomyosis does.

Adult↗
PubMed2006

[Detection of physical status of human papillomavirus 16 in cervical cancer tissue and SiHa cell line by multiplex real-time polymerase chain reaction].

BACKGROUND & OBJECTIVE: The integration of high-risk human papillomavirus (HPV) into host cell genome is one of the major contributing factors to cervical malignant transformation. The detection of HPV integration is helpful for understanding its role in cervical carcinogenesis and tumor progression. However, there is no ideal detection method of HPV physical status for clinical use. The study was to explore an ideal method of detecting the physical status of HPV-16. METHODS: Setting HPV-16 plasmid as standard, multiplex real-time polymerase chain reaction (PCR) using 2 different fluorescent report radicals was used to quantify the copy numbers of E2 and E6 genes for analysis of the physical status of HPV-16 according to E2/E6. Multiplex real-time PCR test and Southern blot results of cervical cancer cell line SiHa and 27 specimens of HPV-16-positive cervical squamous cell carcinoma were compared. RESULTS: There was a linear relationship between the threshold cycle values and the copy numbers of E2 and E6 in both standard curves, with the correlation coefficients of 1.00 and the amplification efficiencies of above 95%. The 95% reference range of plasmid E2/E6 ratio, in which the amount of E2 DNA was equal to that of E6 DNA, was 0.81-1.29. The cut-off value of E2/E6, which was used to distinguish the pure episomal form from a mixed form of episomal and integrated HPV-16, was 0.81 in the multiplex real-time PCR test. HPV-16 was observed to be integrated into the host genome of SiHa cells by multiplex real-time PCR and Southern blot. The coincidence rate of multiplex real-time PCR and Southern blot was 81.5% (22/27) in the cervical squamous cell cancer tissues (kappa=0.844, P<0.001). CONCLUSION: Multiplex real-time PCR test is a rapid, sensitive and reliable method for detecting the physical status of HPV-16 DNA, and is convenient to be applied in paraffin-embedded tissue and small preneoplastic or early neoplastic cervical lesions, even in cervical scrapes which contain a small amount of DNA.

Adult↗
PubMed2006

[Functional expression of adenylyl cyclase and phosphodiesterase in ejaculated human spermatozoa].

OBJECTIVE: To compare the differences of expressions of adenylyl cyclase (AC) and phosphodiesterase (PDE) in ejaculated spermatozoa between healthy volunteers and the patients with asthenospermia. METHODS: Ejaculated spermatozoa were collected from healthy volunteers and the patients with asthenospermia. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of AC and PDE subtypes in human spermatozoa. The concentrations of cAMP and cGMP in the samples were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with healthy volunteers, expression of sAC mRNA and concentration of cAMP were significantly decreased in the patients with asthenospermia (P < 0.01) , while the expression of PDE4C mRNA was significantly increased at the same time (P <0.01). There were no marked differences in the expression of ACIII mRNA and concentration of cGMP between the two groups. CONCLUSION: The sAC down-regulation and PDE4C up-regulation are possible reasons for asthenospermia.

Adenylyl Cyclases↗
PubMed2006

[Biologic activity of bispecific single chain antibody against human gamma-seminoprotein and CD3 molecule].

AIM: To construct a recombinant vector which expresses bispecific single chain antibody (BsscFv) against human gamma-seminoprotein and CD3 molecule and evaluate its biologic activity. METHODS: The BsscFv gene was constructed by the splicing overlap extensive (SOE) PCR and then a flexible peptide linker was inserted between anti-human gamma-seminoprotein single chain Fv gene and anti-CD3 single chain Fv gene. The fusion gene was subcloned into the pSectag2-B plasmid and was expressed in HeLa cell lines. After being analyzed by SDS-PAGE and Western blot, the expressed product was purified through a Ni(2+)-NTA superflow affinity chromatography column. Flow cytometry (FCM) was used to detect the binding activity of BsscFv to CD3(+) cell line Jurkat cells and prostate carcinoma cells LNCaP. In vitro killing effect on target cells (LNCaP) mediated by BsscFv was determined by chromium(51)-release test. The effect of CTLs mediated by BsscFv on inhibiting tumor growth was observed by utilizing nude mice bearing prostate cancer cells. RESULTS: DNA sequencing indicated that BsscFv gene consisted of 1,500 bp, encoding 500 amino acids. SDS-PAGE and Western blot analysis showed that the expressed product with relative molecular mass of 61,000 existed in culture supernatant of Hela cells. Flow cytometry analysis demonstrated that the binding rate of BsscFv to LNCaP cells and Jurkat cells was 54.1% and 53.7%, respectively. In vitro, BsscFv mediated cytotoxicity of CTLs to LNCaP cells as confirmed by chromium(51)-release assay. In prostate cancer nude mouse model, BsscFv inhibited tumor's growth as compared with control group. CONCLUSION: The BsscFv against human gamma-seminoprotein and CD3 molecule possesses certain biologic activity, and in vitro and in vivo it can mediate cytotoxicity of CTLs to prostate cancer cells.

Animals↗
PubMed2006

[Reversal of multi-drug resistance in ovarian cancer cell by RNA interference].

OBJECTIVE: To investigate the effects of small interference RNA (siRNA) on the inhibition of MDR1 mRNA and P-gp expression of ovarian cancer cells with high expression of MDR1 gene, and reversal of drug resistance. METHODS: siRNA was synthesized and transfected into human ovarian cancer cell line OVCAR8/TR by liposome. The expression of MDR1 mRNA at different times after transfection was measured by real time RT-PCR and the P-gp expression was detected by flow cytometry. Adenosine triphosphate (ATP)-bioluminence assay was applied to check the drug sensitivity to four different chemotherapeutic agents before and after transfection. RESULTS: The suppression rates of MDR1 mRNA were 26.42%, 84.00%, 78.43%, 45.85% and 0 respectively at 24, 48, 72, 96 and 120 hours after transfection. The P-gp suppression rates were 16.71%, 49.64%, 85.23%, 65.98%, 9.44% respectively at 24, 48, 72, 96 and 120 hours after transfection. The maximal suppression rates of MDR1 mRNA and P-gp occurred at 48 and 72 hours after transfection respectively. ATP-bioluminence assay showed that OVCAR8/TR cells were sensitive to fluorouracil, resistant to cisplatin, doxorubicin (adriamycin) and paclitaxel (taxol). After siRNA treatment, OVCAR8/TR cells were sensitive to paclitaxel and doxorubicin, but the resistance to cisplatin could not be reversed. CONCLUSIONS: RNA interference (RNAi) presents in human ovarian cancer cells. siRNA can effectively inhibit the expression of mRNA and P-gp of the multidrug resistance gene MDR1, and can reverse the drug resistance to chemotherapeutic agents which are transferred by P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

[Penetrability and therapeutic effect of vancomycin to the prostates of rats with bacterial prostatitis (BP) or BPH-BP].

OBJECTIVE: To explore the penetrability and therapeutic effect of vancomycin to the prostates of rats with bacterial prostatitis (BP) or benign prostate hyperplasia (BPH)-BP. METHODS: The experimental rats with BP or BPH-BP were injected with vancomycin through the tail vein. The prostate tissues and sera were isolated respectively from the rats at 10 min to approximately 24 h after treatment and the antibiotic activities of the samples were detected by serial dilution test and agar diffusion test. The rats with BP or BPH-BP were treated with vancomycin by intravenous injection daily for 5 days. The prostates were collected the second day after injection and bacteria were isolated and determined. One to five weeks after treatment, the prostates of the animals were isolated and pathologic tests were done. RESULTS: No bacteria could be isolated from the prostates of the normal rats, but positive isolation was achieved from the prostates of the infected animals 28th day after infection. In the first 4 days after treatment, a decrease of bacteria could be detected in the prostate samples of the rats treated with BP or BPH-BP. After 5th day, no bacteria could be detected from 91.7% prostates of the treated groups. Obvious antibiotic activity in both sera and prostates could be detected 10 to approximately 150 min after the antibiotic injection. Antibiotic activity of the prostate tissues could be lower or higher than or equal to that of the sera in the same period. Pathologic tests detected obvious exudation and leukocyte invasion in the prostate tissues of the BP rats and gland proliferation in the BPH rats. Vancomycin treatment and the consequent reduction of bacteria obviously alleviated the inflammatory pathological changes in the prostates of the BP rats. CONCLUSION: Vancomycin given intravenously has more penetrability to the prostates of either BP or BPH-BP rats. The antibiotic concentration in the prostate tissues may be equal to or higher than that of the sera, so that the susceptive bacteria in the prostates will be killed and the alleviation of the inflammation and repair of the tissues accelerated effectively.

Animals↗
PubMed2006

[Effects of different acupuncture intensities on the therapeutic effect and the gastric electric activity in the patient of diabetic gastroparesis].

OBJECTIVE: To observe clinical therapeutic effect of different acupuncture intensities on diabetic gastroparesis and to search for the best acupuncture intensity for treatment of diabetic gastroparesis. METHODS: Eighty cases were randomly divided into 4 groups, strong, moderate, weak acupuncture intensity groups and an oral hypoglycemic drug group, 20 cases in each group. Two weeks of treatment constituted one course. RESULTS: The total effective rates were 85.0%, 95.0%, 85.0% in the acupuncture groups, respectivelly, with significant difference as compared with 65.0% of the control group (P<0.05). The moderate intensity acupuncture group had the best clinical therapeutic effect. The principal frequency and amplitude of the stomach electrogastrogram in the gastric antrum and the stomach body significantly improved in the acupuncture groups, which was better than those in the control group (P<0.05). CONCLUSION: Acupuncture has significant therapeutic effect on diabetic gastroparesis, and there is a dose-effect relation between different intensities of acupuncture and curative effects,which are correlated with the regulation of the gastric electric parameters.

Acupuncture Therapy↗
PubMed2006

[Analysis and research of the proteins for the wild type and the rough type of Salmonella typhi by 2D-PAGE].

To find out the protein properties of the wild type and the rough type of Salmonella typhi (S. typhi); to probe the genetic mechanism of the rough variation of S. typhi. The proteins were separated from the wild type and the rough type of S. typhi, and then the samples were processed by 2D-PAGE and stained by Coomassie Brilliant R-250. The properties and relationship of the protein patterns were analyzed by the software Imagemaster 6.0. By the 2D-PAGE, the similar protein patterns with 78% Sd (similar data) would be found between the wild type and the rough type of S. typhi. The distribution of most protein spots was in the range of pH 3.0 - 6.4 where the molecular weight of protein was smaller than 30kDa. According to the characters of differential proteins, there is not only the polysaccharide side chain of the O antigen but also some proteins that could be lost or changed in the rough strain of S. typhi. Most proteins in it would be the same as those in the parental bacteria so that the characteristic protein pattern of Salmonella can be found by 2D-PAGE. This property is useful for analysis and identification of the homologue between variations and their parental bacteria.

Bacterial Proteins↗
PubMed2005

Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression.

Tumor-derived glucose-regulated protein 94 (GRP94/gp96) has shown great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the efficacy of immunotherapy is often not ideal when used alone. In this study, we explored the therapeutic efficacy of a combined GRP94/gp96-based genetic immunotherapy and radiation therapy strategy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model. An adenovirus encoding a modified, secretable form of GRP94 gene (AdsGRP94) was constructed and evaluated in various antitumor experiments. Lethally irradiated, virus-infected cells were used as vaccines. Adenoviral vectors were also injected directly into tumors in conjunction with tumor irradiation. Vaccination with lethally irradiated, AdsGRP94-infected 4T1 cells completely prevented subsequent tumor growth from challenge inoculations of as many as 10(7) cells per mouse. In established tumor models, vaccinations alone had minimal effect on local and metastatic tumor growth. However, when vaccination was combined with radiation therapy and i.t. AdsGRP94 injections, local tumor growth and pulmonary metastasis were markedly inhibited. In some cases, complete tumor regression was observed. In these cases, the mice were resistant to subsequent tumor challenge and remain tumor free up to 10 months after initial therapy. Our results indicate that combined AdsGRP94-based immunotherapy and radiation therapy may be a potentially effective strategy for cancer treatment.

Adenoviridae↗
PubMed2005

Reversible membrane association of dinitrogenase reductase activating glycohydrolase in the regulation of nitrogenase activity in Rhodospirillum rubrum; dependence on GlnJ and AmtB1.

In the photosynthetic bacterium Rhodospirillum rubrum nitrogenase activity is regulated by reversible ADP-ribosylation of dinitrogenase reductase in response to external so called "switch-off" effectors. Activation of the modified, inactive form is catalyzed by dinitrogenase reductase activating glycohydrolase (DRAG) which removes the ADP-ribose moiety. This study addresses the signal transduction between external effectors and DRAG. R. rubrum, wild-type and P(II) mutant strains, were studied with respect to DRAG localization. We conclude that GlnJ clearly has an effect on the association of DRAG to the membrane in agreement with the effect on regulation of nitrogenase activity. Furthermore, we have generated a R. rubrum mutant lacking the putative ammonium transporter AmtB1 which was shown not to respond to "switch-off" effectors; no loss of nitrogenase activity and no ADP-ribosylation. Interestingly, DRAG was mainly localized to the cytosol in this mutant. Overall the results support our model in which association to the membrane is part of the mechanism regulating DRAG activity.

Bacterial Proteins↗
PubMed2005

Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A.

A G-protein coupled receptor to niacin (nicotinic acid) was identified recently but the physiological/pharmacological role of the receptor remains poorly defined. We present our studies to demonstrate that HM74A, but not HM74, binds niacin at high affinities and effectively mediates Gi signaling events in human embryonic kidney HEK293 cells as well as in 3T3L1 adipocytes expressing HM74A. Furthermore, HM74A, but not HM74, expressed in differentiated 3T3L1 adipocytes effectively mediated inhibition of lipolysis by niacin. Our results provided direct evidence indicating that HM74A, but not HM74, was sufficient to mediate anti-lipolytic effect of niacin in adipose tissue.

3T3-L1 Cells↗
PubMed2005

Cloning and functional characterization of the rabbit C-C chemokine receptor 2.

BACKGROUND: CC-family chemokine receptor 2 (CCR2) is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model. RESULTS: Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled 125I-mouse JE (murine MCP-1) with a calculated Kd of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1alpha or MIP-1beta. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of 125I-mouse JE (IC50 = 2.3 nM) to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis. CONCLUSION: In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1.

Amino Acid Sequence↗
PubMed2005

Validation of an accelerated 'demons' algorithm for deformable image registration in radiation therapy.

A greyscale-based fully automatic deformable image registration algorithm, originally known as the 'demons' algorithm, was implemented for CT image-guided radiotherapy. We accelerated the algorithm by introducing an 'active force' along with an adaptive force strength adjustment during the iterative process. These improvements led to a 40% speed improvement over the original algorithm and a high tolerance of large organ deformations. We used three methods to evaluate the accuracy of the algorithm. First, we created a set of mathematical transformations for a series of patient's CT images. This provides a 'ground truth' solution for quantitatively validating the deformable image registration algorithm. Second, we used a physically deformable pelvic phantom, which can measure deformed objects under different conditions. The results of these two tests allowed us to quantify the accuracy of the deformable registration. Validation results showed that more than 96% of the voxels were within 2 mm of their intended shifts for a prostate and a head-and-neck patient case. The mean errors and standard deviations were 0.5 mm+/-1.5 mm and 0.2 mm+/-0.6 mm, respectively. Using the deformable pelvis phantom, the result showed a tracking accuracy of better than 1.5 mm for 23 seeds implanted in a phantom prostate that was deformed by inflation of a rectal balloon. Third, physician-drawn contours outlining the tumour volumes and certain anatomical structures in the original CT images were deformed along with the CT images acquired during subsequent treatments or during a different respiratory phase for a lung cancer case. Visual inspection of the positions and shapes of these deformed contours agreed well with human judgment. Together, these results suggest that the accelerated demons algorithm has significant potential for delineating and tracking doses in targets and critical structures during CT-guided radiotherapy.

Algorithms↗
PubMed2005

An automatic CT-guided adaptive radiation therapy technique by online modification of multileaf collimator leaf positions for prostate cancer.

PURPOSE: To propose and evaluate online adaptive radiation therapy (ART) using in-room computed tomography (CT) imaging that detects changes in the target position and shape of the prostate and seminal vesicles (SVs) and then automatically modifies the multileaf collimator (MLC) leaf pairs in a slice-by-slice fashion. METHODS AND MATERIALS: For intensity-modulated radiation therapy (IMRT) using a coplanar beam arrangement, each MLC leaf pair projects onto a specific anatomic slice. The proposed strategy assumes that shape deformation is a function of only the superior-inferior (SI) position. That is, there is no shape change within a CT slice, but each slice can be displaced in the anteroposterior (AP) or right-left (RL) direction relative to adjacent slices. First, global shifts (in SI, AP, and RL directions) were calculated by three-dimensional (3D) registration of the bulk of the prostate in the treatment planning CT images with the daily CT images taken immediately before treatment. Local shifts in the AP direction were then found using slice-by-slice registration, in which the CT slices were individually registered. The translational shift within a slice could then be projected to a translational shift in the position of the corresponding MLC leaf pair for each treatment segment for each gantry angle. Global shifts in the SI direction were accounted for by moving the open portal superiorly or inferiorly by an integral number of leaf pairs. The proposed slice-by-slice registration technique was tested by using daily CT images from 46 CT image sets (23 each from 2 patients) taken before the standard delivery of IMRT for prostate cancer. A dosimetric evaluation was carried out by using an 8-field IMRT plan. RESULTS: The shifts and shape change of the prostate and SVs could be separated into 3D global shifts in the RL, AP, and SI directions, plus local shifts in the AP direction, which were different for each CT slice. The MLC leaf positions were successfully modified to compensate for these global shifts and local shape variations. The ART method improved geometric coverage of the prostate and SVs compared with the couch-shift method, particularly for the superior part of the prostate and all the SVs, for which the interfraction shape change was the largest. The dosimetric comparison showed that the ART method covered the target better and reduced the rectal dose more than a simple couch-translation method. CONCLUSIONS: ART corrected for interfraction changes in the position and shape of the prostate and SVs and gave dose distributions that were considerably closer to the planned dose distributions than could be achieved with simple alignment strategies that neglect shape change. The ART proposed in this investigation requires neither contouring of the daily CT images nor extensive calculations; therefore, it may prove to be an effective and clinically practical solution to the problem of interfraction shape changes.

Algorithms↗
PubMed2005

Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes.

PURPOSE: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. METHODS AND MATERIALS: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye-view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose-volume histograms and dose-volume and dose-response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today's image, and (c) from a new full-fledged IMRT plan designed based on today's image. RESULTS: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye-view are a good approximation of full-fledged replanning compared with other alternatives. CONCLUSIONS: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.

Algorithms↗
PubMed2005

Implementation and validation of a three-dimensional deformable registration algorithm for targeted prostate cancer radiotherapy.

PURPOSE: Daily prostate deformation hinders accurate calculation of dose, especially to intraprostatic targets. We implemented a three-dimensional deformable registration algorithm to aid dose tracking for targeted prostate radiotherapy. METHODS AND MATERIALS: The algorithm registers two computed tomography (CT) scans by iteratively minimizing their differences in image intensity. For validation, we measured the accuracy in registering (a) a pelvic CT set to its mathematically deformed counterpart, (b) CT scans of a deformable pelvic phantom with and without an endorectal balloon inflated, to simulate intraprostatic targets, 23 CT-opaque seeds were embedded in the prostate, and (c) two pelvic CT scans of a patient obtained on 2 separate days. RESULTS: The mean (SD) error in registering the pelvic CT set to its transformed set was 0.5 mm (1.5), with correlation coefficient improvement from 0.626 to 0.991. Using the deformable pelvic phantom, the correlation coefficient improved from 0.543 to 0.816 after registration. The mean (SD) error in tracking the intraprostatic seeds was 0.8 mm (0.5). The correlation coefficient improved from 0.610 to 0.944 after registration of the two patient CT sets. CONCLUSION: The algorithm had an accuracy of about 1 mm. It could be used for optimizing dose calculation and delivery for prostate radiotherapy.

Algorithms↗