Search PubMed⌕ Search

Biomedical subjects

G T Chen

Publications and source records attributed to G T Chen.

At least 37 records · Page 2Linked to original sources

A three-dimensional algorithm for optimizing beam weights and wedge filters.

An essential step towards optimizing and automating radiation therapy treatment planning is to develop an effective algorithm to find the optimal beam weights and wedge filters for a given set of beam directions and modalities. This problem is solved by introducing a variable transformation based on the universal and omni wedge principles. Instead of directly optimizing an objective function with respect to wedge angles and orientations, each field is first decomposed into a superposition of an open field and two orthogonal wedged fields. This transforms the problem of finding J beam weights, wedge angles, and orientations to that of optimizing a system with 3J beam weights (J open beams and 2J nominal wedged beams), where J is the total number of incident beam directions. An iterative algorithm based on a method originally developed for image reconstruction is used to find the 3J beam weights. The technique is applied to a few clinical cases. Treatment plans are improved compared to those obtained through the conventional manual trial and error planning process. In addition, planning time and effort are greatly reduced.

Algorithms↗

17Beta-estradiol potentiates the stimulatory effects of progesterone on cadherin-11 expression in cultured human endometrial stromal cells.

Cadherin-11 (cad-11) is a novel member of the cadherin gene superfamily of calcium-dependent cell adhesion molecules. To date, the factors capable of regulating this cell adhesion molecule remain poorly characterized. We have recently determined that cad-11 expression in the human endometrium is tightly regulated during the menstrual cycle. The spatiotemporal expression of cad-11 in the stromal cells of the human endometrium during the menstrual cycle suggests that gonadal steroids regulate the expression of this endometrial cell adhesion molecule. In view of these observations, we have examined the ability of progestins, estrogens, and androgens, alone or in combination, to regulate cad-11 expression in isolated human endometrial stromal cells using Northern and Western blot analyses. In these studies, we have determined that progesterone, but not 17beta-estradiol or dihydrotestosterone, is capable of regulating cad-11 messenger RNA and protein expression levels in isolated endometrial stromal cells. In addition, 17beta-estradiol, but not dihydrotestosterone, was capable of potentiating the stimulatory effects of progesterone in a dose-dependent manner. Taken together, these observations suggest that both 17beta-estradiol and progesterone are required for maximal cad-11 expression in human endometrial stromal cells in vitro.

Blotting, Northern↗

Progesterone regulates beta-catenin mRNA levels in human endometrial stromal cells in vitro.

Cadherin-catenin complexes mediate cell-cell interactions and may play a central role in intracellular signaling. To date, the factors capable of coordinately regulating cadherin and catenin expression levels within a mammalian cell remain poorly characterized. We have recently determined that progesterone is a key regulator of cadherin-11 mRNA and protein expression levels in cultured human endometrial stromal cells. As a first step in determining whether gonadal steroids are also capable of regulating stromal catenin expression, we have examined the ability of progestins, estrogens, and androgens to regulate beta-catenin mRNA levels in these endometrial cell cultures. Here we report that progesterone, but not 17beta-estradiol or dihydrotestosterone, increased beta-catenin mRNA levels in cultured human endometrial stromal cells. The stimulatory effect of progesterone on the levels of the stromal beta-catenin mRNA transcript could not be potentiated by 17beta-estradiol. These studies not only demonstrate that gonadal steroids are capable of regulating beta-catenin mRNA levels in human endometrial stromal cells, but may also give us useful insight into the cellular mechanisms by which gonadal steroids regulate the cyclic remodeling processes that occur in the human endometrium during each menstrual cycle.

Adult↗

Regulated expression of cadherin-11 in human extravillous cytotrophoblasts undergoing aggregation and fusion in response to transforming growth factor beta 1.

Transforming growth factor beta 1 is believed to be a key regulator of extravillous cytotrophoblast invasion during the first trimester of pregnancy. In addition, this growth factor has been shown to regulate cellular differentiation and fusion in cultured extravillous cytotrophoblasts. To date, the cellular mechanisms by which transforming growth factor beta 1 promotes these developmental processes remain poorly understood. Recent studies indicate that the expression of the novel cadherin subtype, known as cadherin-11, is associated with the terminal differentiation and fusion of villous cytotrophoblasts isolated from the human term placenta and human myoblasts in vitro. In this study, cadherin-11 mRNA and protein expression were examined in primary cultures of human extravillous cytotrophoblasts cultured in the presence of increasing concentrations of transforming growth factor beta 1 using northern and western blot analysis, respectively. Transforming growth factor beta 1 was shown to increase cadherin-11 mRNA and protein expression in these cultured extravillous cytotrophoblasts in a dose-dependent manner. Cadherin-11 was further localized to the large cellular aggregates and multinucleated cells that formed in response to increasing concentrations of transforming growth factor beta 1 using immunocytochemistry. Collectively, these observations suggest that the morphogenetic effects of transforming growth factor beta 1 on cultured extravillous cytotrophoblasts are mediated, at least in part, by an increase in cadherin-11 expression. This study not only adds to the understanding of the cellular mechanisms by which transforming growth factor beta 1 promotes trophoblast differentiation and fusion but provides useful insight into the cell biology of the cadherins.

Analysis of Variance↗

Performance of a video-image-subtraction-based patient positioning system.

PURPOSE: We have developed and tested an interactive video system that utilizes image subtraction techniques to enable high precision patient repositioning using surface features. We report quantitative measurements of system performance characteristics. METHODS AND MATERIALS: Video images can provide a high precision, low cost measure of patient position. Image subtraction techniques enable one to incorporate detailed information contained in the image of a carefully verified reference position into real-time images. We have developed a system using video cameras providing orthogonal images of the treatment setup. The images are acquired, processed and viewed using an inexpensive frame grabber and a PC. The subtraction images provide the interactive guidance needed to quickly and accurately place a patient in the same position for each treatment session. We describe the design and implementation of our system, and its quantitative performance, using images both to measure changes in position, and to achieve accurate setup reproducibility. RESULTS: Under clinical conditions (60 cm field of view, 3.6 m object distance), the position of static, high contrast objects could be measured with a resolution of 0.04 mm (rms) in each of two dimensions. The two-dimensional position could be reproduced using the real-time image display with a resolution of 0.15 mm (rms). Two-dimensional measurement resolution of the head of a patient undergoing treatment for head and neck cancer was 0.1 mm (rms), using a lateral view, measuring the variation in position of the nose and the ear over the course of a single radiation treatment. Three-dimensional repositioning accuracy of the head of a healthy volunteer using orthogonal camera views was less than 0.7 mm (systematic error) with an rms variation of 1.2 mm. Setup adjustments based on the video images were typically performed within a few minutes. The higher precision achieved using the system to measure objects than to reposition them suggests that the variability in repositioning is dominated by the ability of the therapist to make small, controlled changes in the position of the patient. CONCLUSION: Using affordable, off-the-shelf technology, we have developed a patient positioning system that achieves repositioning accuracy normally associated with fractionated stereotactic systems. The technique provides real-time guidance and can be used to easily and quickly correct patient setup before every treatment, thus significantly reducing overall random positioning error. This improved positioning capability provides the precision required to realize the potential gains of conformal radiotherapy.

Computer Terminals↗

Functional imaging in treatment planning of brain lesions.

PURPOSE: Explore the use of functional imaging data in radiation treatment planning of brain lesions. METHODS AND MATERIALS: Compare the treatment-planning process with and without the use of functional brain imaging for clinical cases where functional studies using either single photon emission computed tomography or magnetic resonance imaging are available. RESULTS: A method to register functional image data with planning image studies is needed for functional treatment planning. Functional volumes are not simply connected regions. One activation study may produce many isolated functional areas. After finding the functional volumes and registering the functional information with the planning imaging data, the tools used for conventional three-dimensional treatment planning are sufficient for functional treatment planning. However, the planning system must provide dose-volume histograms for volumes of interest that consist of isolated pieces. Treatment plans that spare functional brain while providing identical target coverage can be constructed for lesions situated near the functional volume. However, the dose to other areas of the brain may be increased. CONCLUSIONS: Functional imaging will make determination of dose response of eloquent areas of the brain possible when combined with volumetric dose information and neuropsychological evaluation prior to and after radiation therapy. Realizing the full potential of functional imaging studies will require improved delineation of activated volumes and determination of the uncertainties in functional volume delineation. Optimization of treatment plans by minimizing dose to volumes activated during functional imaging studies should be used cautiously, because the dose to "silent," but possibly eloquent, brain may be increased.

Brain↗

Functional dose-volume histograms for functionally heterogeneous normal organs.

Functional dose-volume histograms are proposed as an extension of the conventional dose-volume histograms, for quantitative assessment of three-dimensional radiation dose coverage of functionally heterogeneous normal organs. Examples are given to illustrate possible applications of this approach to the treatment of a brain tumour or a lung tumour, in which cases the distribution of the normal organ function can be obtained from functional dose-volume modalities. It is shown that a significant difference exists between the functional dose-volume histograms and the conventional dose-volume histograms when the normal organ function is non-uniformly distributed within the organ. Utilization of functional dose-volume histograms as the input for the calculation of normal tissue complication probabilities is discussed for different normal tissue structures.

Humans↗

Analysis of the dose-surface histogram and dose-wall histogram for the rectum and bladder.

Dose distribution throughout a hollow organ is represented by either a dose-surface histogram (DSH) or a dose-wall histogram (DWH). A spherical shell model for the bladder and a cylindrical shell model for the rectum were introduced for quantifying the difference between the DWH and DSH. The difference was given by subtraction of the percent volume of the wall from the percent area of the surface for any specific dose level. Taking the dose-grid size and contour-delineation uncertainties into account, the DSH and DWH calculation errors were estimated by simplified formulas. The DSHs and DWHs for the rectum and bladder in patients undergoing four-field-prostate treatment and gynecological intracavitary brachytherapy were computed with a refined numerical algorithm. Results of the analytic models and the numerical calculations demonstrated that the difference between the DWH and DSH was small (about 5%) for a fully filled bladder or rectum but large (about 10%) for an empty rectum or a contracted bladder. The error of DSH was about 3%, which is smaller than that of DWH.

Humans↗

Optimization of relative weights and wedge angles in treatment planning.

An efficient technique to optimize beam weights and wedge angles in radiotherapy treatment planning has been developed. Based on the fact that a wedged field can be regarded as a superposition of an open field and a nominal wedged field, this approach reduces the problem of finding J beam weights and the corresponding wedge angles to optimizing a linear system with 2J unknowns (weights of J open beams and J nominal wedged beams), where J is the total number of incident beam directions. Two iterative algorithms similar to the iterative-least-square technique in image reconstruction are used to optimize the system. Application of the algorithms to two specific examples shows that this technique can reduce treatment planning time and effort, and promises to create a better solution for an arbitrarily complex treatment plan.

Algorithms↗

Volumetric visualization of anatomy for treatment planning.

PURPOSE: Delineation of volumes of interest for three-dimensional (3D) treatment planning is usually performed by contouring on two-dimensional sections. We explore the usage of segmentation-free volumetric rendering of the three-dimensional image data set for tumor and normal tissue visualization. METHODS AND MATERIALS: Standard treatment planning computed tomography (CT) studies, with typically 5 to 10 mm slice thickness, and spiral CT studies with 3 mm slice thickness were used. The data were visualized using locally developed volume-rendering software. Similar to the method of Drebin et al., CT voxels are automatically assigned an opacity and other visual properties (e.g., color) based on a probabilistic classification into tissue types. Using volumetric compositing, a projection into the opacity-weighted volume is produced. Depth cueing, perspective, and gradient-based shading are incorporated to achieve realistic images. Unlike surface-rendered displays, no hand segmentation is required to produce detailed renditions of skin, muscle, or bony anatomy. By suitable manipulation of the opacity map, tissue classes can be made transparent, revealing muscle, vessels, or bone, for example. Manually supervised tissue masking allows irrelevant tissues overlying tumors or other structures of interest to be removed. RESULTS: Very high-quality renditions are produced in from 5 s to 1 min on midrange computer workstations. In the pelvis, an anteroposterior (AP) volume rendered view from a typical planning CT scan clearly shows the skin and bony anatomy. A muscle opacity map permits clear visualization of the superficial thigh muscles, femoral veins, and arteries. Lymph nodes are seen in the femoral triangle. When overlying muscle and bone are cut away, the prostate, seminal vessels, bladder, and rectum are seen in 3D perspective. Similar results are obtained for thorax and for head and neck scans. CONCLUSION: Volumetric visualization of anatomy is useful in treatment planning, because 3D views can be generated without the need for segmentation. When relationships among anatomical structures, rather than geometric models of them, are important, volume rendering presents advantages. The presented algorithm is readily adaptable to distributed parallel implementation on a network of heterogeneous workstations.

Anatomy, Cross-Sectional↗

A comparison of four patient immobilization devices in the treatment of prostate cancer patients with three dimensional conformal radiotherapy.

PURPOSE: To determine the variability of patient positioning during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer treated with no immobilization or one of four immunobilization devices, and to determine the effects of patient body habitus and pelvic circumference on patient movement with each individual inmobilization technique. METHODS AND MATERIALS: To see whether our immobilization techniques have improved day-to-day patient movement, a retrospective analysis was carried out. A total of 62 patients treated at one facility on a single machine with 3D-CRT via a four-field box technique (anterior-posterior and opposed laterals) in the supine position with either no immobilization or one of four immobilization devices. Five groups of patients were compared: (a) group 1-no immobilization; (b) group 2-alpha cradle from the waist to upper thigh; (c) group 3-alpha cradle from waist to below the knees; (d) group 4-styrofoam leg immobilizer (below knees); and (e) group 5-aquaplast cast encompassing the entire abdomen and pelvis to midthigh with alpha cradle immobilization to their lower legs and feet. Prior to starting radiotherapy, portal films of all four treatment fields were obtained 1 day before treatment. Subsequently, portal films were then obtained at least once a week. Portal films were compared with the simulation films and appropriate changes were made and verified on the next day prior to treatment. A deviation of greater than 0.5 cm or greater was considered to be clincally significant in our analysis. We studied the difference among the types of immobilization and no immobilization by looking at the frequency of movements (overall, and on each of the three axes) that a patient had during the course of his treatment. Using a logistic regression model, the probability of overall and individual directional movement for each group was obtained. In addition, the effects of patient body habitus and pelvic circumference on movement were analyzed. RESULTS: The maximum deviation was 2 cm and the median deviation was 1.2 cm. For each patient, the probability of movement ranged from 0 to 76%, with a mean of 39%. There was no significant difference seen in overall movement with any of the immobilzation devices compared to no immobilization, but there was less vertical (9 vs. 18%; p = 0.03) and AP (6 vs. 15%; p = 0.14) movement with the aquaplast than any other group. However, when examining the lateral direction, the aquaplast had significantly more movement (32 vs. 9%; p < 0.001). When accounting for body habitus and pelvic circumference, no immobilization device was effective in reducing movement in obese patients or in patients with pelvic circumference greater than 105 cm. The aquaplast group had a significantly increased amount of lateral movement with obesity (42 vs. 23%; p < 0.05), and with pelvic circumference >105 cm (33 vs. 29%; p < 0.05). CONCLUSIONS: There was no significant reduction in overall patient movement noted with any of the immobilization devices compared to no immobilization. The aquaplast group had reduced vertical and AP movement of greater than 0.5 cm. There was significantly more lateral movement with aquaplast appreciated in obese patients or patients with pelvic circumferences greater than 105 cm. The aquaplast immobilization appears to be useful in reducing movement in two very clinicaly important dimensions (AP and vertical). Despite our findings, other immobilization may still be useful especially in the treatment of nonobese patients. It is clear that the optimal immobilization technique and patient positioning are yet to be determined.

Body Constitution↗

Iterative methods for inverse treatment planning.

Iterative algorithms used in imaging science are generalized to study inverse treatment planning in radiotherapy. These algorithms consist of iteratively changing trial incident fluence functions which eventually yield a dose distribution consistent with the prescribed distribution. Application of the algorithms is presented for test cases of a circular phantom with cylindrically symmetric dose distributions. A comparison of the iterative beam profiles with previous analytic solutions shows excellent agreement, indicating that iterative techniques are promising to create sophisticated treatment plans. The relationship between the algorithms and several existing inverse treatment planning methods is discussed.

Algorithms↗

A new source localization algorithm with no requirement of one-to-one source correspondence between biplane radiographs.

Conventional source localization algorithms require a one-to-one source correspondence between films. This requirement makes source localization cumbersome and error prone because multiple sources must be carefully digitized and some sources can be obscured or missed. A new source localization algorithm is described in this paper. The algorithm fits a ribbon or needle image on film to a linear-quadratic equation, then analytically determines the 3-D ribbon locus by its image on the other projection, and finally localizes the sources in the ribbon by tracing along the ribbon image. Only three points per ribbon per film are required, and corresponding points need not be identified on the other film. Phantom experiments and tests on clinical cases demonstrate that the source localization algorithm can increase the efficiency by a factor of up to 5, improve accuracy to about 1 mm, and reconstruct obscured or shifted sources without decreased accuracy and efficiency. The simplicity and minimal entry of data make this technique desirable for clinical use.

Algorithms↗

Implications of 3-dimensional target shape and motion in aperture design.

To determine the shape of a radiation beam aperture a margin is typically applied to the clinical target volume (CTV) to yield the planning target volume (PTV), and the aperture is then determined from the projection of the PTV onto the aperture plane. This margin accounts for setup variability and organ motion originating from respiration or other physiologic processes. The use of either a uniform margin, or alternatively one which takes into account only the expected magnitude and direction of target motion, fails to account for the three-dimensional nature of the target; such a method neglects the volumetric effect of target shape on the fractional target volume irradiated when the target shifts partially out of the aperture. A mathematical framework is developed to analyze and illustrate the consequences of irradiating an irregular target shape in the presence of target motion. The effect of target shape on volume coverage is demonstrated for selected cases involving conventional BEV aperture design techniques. The volumetric implications of target shape are considered from two complementary points of view. The first involves transformation into a "displacement space," which isolates the volumetric effect of the shape of the target allowing it to be studied independently of the probability distribution of target motion. The second point of view combines the effects of the 3D target shape and the probability distribution of motion in a manner independent of beam direction to yield a 3D "target distribution." The two points of view represent distinct starting points for computation of the expected value of fractional target volume coverage in the presence of target motion. In certain cases it may be beneficial to (1) employ "target distributions" for the target and normal tissues in place of the conventional static PTV and, (2) include the aperture shape, on equal footing with parameters such as beam weights and energies, into a quantitative optimization process explicitly accounting for uncertainties in the position of the target volume and critical structures.

Equipment Design↗

Localization of the prostatic apex for radiotherapy planning: a comparison of two techniques.

Autopsy and pathology studies have shown that the caudal portion of the prostate gland harbors tumour in 64-75% of specimens examined. Accurate localization of the prostatic apex may be important in improving local control with external beam radiation therapy. We compared the location of the apex obtained with CT based treatment planning versus localization using retrograde urethrography in 32 consecutive patients. The prostatic apex, localized by CT and retrograde urethrography, was compared relative to the ischial tuberosities and the symphysis pubis. Discordance between the location of the prostatic apex as defined on CT scan and retrograde urethrography was found in 50% of patients evaluated. There was 31% discordance between the location of the prostatic apex as defined on CT and retrograde urethrography when data were analysed with the location of the prostatic apex 1 cm above the narrowing on urethrography, a definition others have suggested. The urethrogram defined prostatic apex, as compared with the CT definition, necessitated the treatment of more of the surrounding normal tissues in 31% of our cases, with four-field techniques. Comparison of dose-volume histograms of the bladder, rectum and penis irradiated for target volumes defined by CT versus retrograde urethrography showed that more penis was irradiated in some patients with the urethrogram defined prostatic apex; irradiation of the base of the penis could be relatively avoided by using a six-field treatment plan instead of the standard four-field box. There is discordance between the CT and urethrogram defined prostatic apex. Dose-volume histogram information suggests that differences in apex localization can significantly affect doses to normal adjacent prostatic tissues. Combining CT localization with the urethrogram localization of the prostatic apex optimizes radiotherapy planning and dose delivery.

Humans↗

Photodynamic treatment of subcutaneous tumors in mice with photofrin II and Argon ion laser.

OBJECTIVE: To investigate the combined effects of photofrin (Pf) II and laser irradiation on mice bearing subcutaneous tumors. METHOD: Ehrlish ascites tumor cells (1 x 10(7)) were implanted subcutaneously into the breast area of ICR mice. The tumors, when grew up to 0.55 +/- 0.15cm3, was administered of laser irradiation (514.5nm, 112.5mW/cm2 for 11.12 min with a total energy 75j/cm2) after intraperitoneal injection of Pf II (5, 7.5, 10 and 15mg/kg body weight) once a day for three successive days. RESULTS: The mortality rate (MR120) in the tumor control was 93.7% and the mean survival time (MST120) was 46.6 days. The best therapeutic effect (50% mortality rate, 53.8% tumor control rate and mean survival time 86 days) was observed in the group treated with 7.5mg of Pf II per kg of body weight and total irradiation energy of 75J/cm2 (112.5mW/cm2 for 11.12 min) with 514.5nm argon ion laser light. CONCLUSIONS: The effect on the survival rate of tumor cells and synthetic rates of DNA, RNA and protein were obviously inhibited, as the dose of pf II and laser irradiation increased.

Animals↗