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Biomedical subjects

G T Chen

Publications and source records attributed to G T Chen.

At least 19 recordsLinked to original sources
PubMed1992

The use of beam's eye view volumetrics in the selection of non-coplanar radiation portals.

In 3-dimensional treatment planning, beam's eye view (BEV) is used as an interactive tool to define portal entry angles that exclude critical structures while fully encompassing the target volume. With beam's eye view volumetrics (BEV volumetrics), the volume of intersected normal tissues is also calculated and is used as a quantitative tool to choose portal orientations that minimize normal tissue volumes irradiated. The axial beam entry angle and a polar angle (relative to the patient longitudinal axis) are specified to define the central axis orientation. Using BEV volumetrics, we have studied the quantities of normal tissues irradiated when treating tumors in the abdomen, thorax, and pelvis. The reduction of normal tissue irradiated is a strong function of site and patient-specific tumor size and location. Volumetrics combined with BEV is found to be useful in treatment planning because it (a) provides quantitative information needed in rationally choosing portal entry angles, (b) provides a near interactive speed approach to understanding the relative merits of different multiple field plans, and (c) compliments the information provided by the more time-consuming generation of dose volume histograms.

Humans↗
PubMed1992

Beam's eye view volumetrics: an aid in rapid treatment plan development and evaluation.

A well-designed treatment plan fully irradiates the target to the prescribed dose while minimizing radiation to adjacent critical structures. Beam's eye view is an important component of treatment planning systems because it provides the operator with tools needed to achieve this goal. Through interactive manipulation of displays, the planner uses beam's eye view to adequately cover the target volume while geometrically avoiding certain critical, normal structures. A factor not considered in current beam's eye view programs is the fractional volume of each structure irradiated given a specified beam direction. We have incorporated a rapid volume calculation capability in our beam's eye view program, and have applied it to provide a quantitative aid to treatment planning development and evaluation. Treatment planning of lung tumors has been studied using this tool. Volumes of lung and spinal cord treated as a function of portal angle may be calculated much more rapidly than dose volume histograms and yet provide quantitative indices which follow the trends of dose volume histograms as a function of field angle. Plots of normal tissue volume irradiated as a function of field angle identify the optimal angle to minimize irradiated volume of a structure at a glance. For multiple field plans, a bitmap approach identifies areas treated by various combinations of beams. Volumetrics combined with beam's eye view are useful in treatment planning because they (a) provide quantitative information needed in choosing and optimizing portal entry angle (b) provide an interactive approach to understanding the relative merits of different multiple field plans and (c) complement the information provided by the more time consuming generation of dose volume histograms. The clinical application of this tool in treatment planning is presented.

Computer Graphics↗
PubMed1992

Quantitation of treatment volumes from CT and MRI in high-grade gliomas: implications for radiotherapy.

Long-term survival of patients with high-grade gliomas remains extremely poor. The main reason for such an outcome is local failure, or recurrence, after surgery and/or radiotherapy. Higher doses of radiation may result in decreased local failure rates provided that the location (and extent) of gross tumor and microscopic disease can be defined accurately. The abnormalities appearing in images from diagnostic modalities, such as CT and MRI, are being used as a starting point and as a guide for the clinical definition of tumor and its extensions. However, some recent studies on two-dimensional specimens, correlating histopathological findings to CT and MRI images, showed that the resulting definition of tumor cell extensions was unsatisfactory, different, and in need of ample margins. We carried out a retrospective analysis to compare the target volumes that would have been defined by CT, T2-weighted MRI, and T1-weighted postgadolinium MRI images of the same individual and to explore the implications of the resulting volume definitions for radiotherapy. The results of our limited study, based on the margins used, indicate that the CT-defined target volume is consistently larger than that from either of the two MRI modalities and suggest that noncoplanar approaches for its treatment and other local approaches for tumor boost should be considered. We conclude that until more definitive histopathological guidelines correlated to image features have been formulated and agreed upon, one should try to make full use of all available diagnostic information in order to minimize the possibility of geographical miss of target extensions.

Adult↗
PubMed1992

Overproduction of a selenocysteine-containing polypeptide in Escherichia coli: the fdhF gene product.

The fdhF gene of Escherichia coli codes for the selenocysteine-including protein subunit of formate dehydrogenase H. The protein subunit consists of 715 amino acid residues containing a single selenocysteine residue at position 140 which is encoded by a UGA codon. The decoding of this opal termination codon occurs under anaerobic growth conditions by means of a specific tRNA, i.e. the selC gene product. The ability of E. coli cells to overproduce a selenopolypeptide was examined using the fdhF gene as a model system. Surprisingly, E. coli was able to synthesize the fdhF gene product at the level of approximately 12% of the total cellular protein. This was achieved by cloning fdhF in a multicopy plasmid together with a synthetic selC gene under the Ipp promoter. FdhF production was absolutely dependent upon the addition of selenium to the culture medium and was almost completely blocked in the presence of oxygen. The product was specifically labelled with 75Se, proving that it consisted of a selenoprotein. The product was purified to homogeneity and shown to exhibit the catalytic properties characteristic of formate dehydrogenase H.

Bacterial Proteins↗
PubMed1992

Beam's eye view--based radiation therapy: description of methods.

Improving three-dimensional target definitions and dose delivery may improve local control rates in radiation therapy. Computed tomography (CT)-based treatment planning is one step toward achieving this goal, but further progress is possible with beam's eye view (BEV)-based planning. Initially, CT is performed with the patient in the treatment position, and data are transferred to a computerized treatment planning system. Target volumes and vital structures are outlined on CT sections and digitized, and a treatment plan is produced. BEV display is used to calculate the angles needed for oblique fields that would avoid irradiation of vital structures. A BEV printout is obtained along with simulation radiographs. The radiograph is overlaid on the printout, all identified structures are matched, and the target volumes are transferred from the printout to the radiograph. BEV-based planning can improve three-dimensional coverage of a tumor, irradiation techniques, and the therapeutic ratio by decreasing the irradiation of normal tissue. The extra time required for BEV planning is acceptable, but further studies of long-term outcomes and cost-benefit analyses are needed.

Humans↗
PubMed1991

Beams eye view-based photon radiotherapy I.

Geographic miss, dosimetric miss (underdosing), and proximity of the tumor to sensitive normal tissues are some of the causes of inadequate radiation dose delivery; this is one of many causes of failure after radiotherapy. In the past decade, computerized tomography (CT)-based treatment planning has helped to overcome some of these problems. Beam's eye view (BEV)-based radiotherapy planning is an improvement over CT-based treatment planning that may further increase the therapeutic ratio. Since January 1988, we have treated 198 patients with BEV-based photon radiotherapy. About 40% of our patients treated with radical radiotherapy undergo BEV-based treatment, and about 70% of patients who undergo planning CT in the treatment position receive BEV-based radiotherapy. Our findings are as follows: (a) routine use of BEV-based RT (BEVRT) is possible in a busy radiation oncology department; (b) BEVRT improves geometric coverage of tumors; (c) BEVRT is extremely useful in the design of oblique portals; (d) time commitments for various members of the RT treatment-planning team are reasonable; (e) BEVRT helps individualize RT technique; (f) preliminary data suggest decreased acute toxicity with the use of BEVRT for prostate cancer patients. Whether these advantages will help to improve the outcome (i.e., improve local control and survival) and/or decrease the long-term toxicity is not yet known.

Breast Neoplasms↗
PubMed1991

Optimization of radical radiotherapy with beam's eye view techniques for non-small cell lung cancer.

The presence of vital and sensitive organs such as the spinal cord, heart, and lungs makes curative radiotherapy of non-small cell lung cancer difficult to implement and necessitates use of oblique portals. Defining the target volumes in oblique portals is very difficult. We now show, for non-small cell lung cancer, how beam's eye view-based radiotherapy can be used for accurate delineation of treatment volumes and for avoidance of real or dosimetric geographic misses. Furthermore, the beam's eye view-based method enables one to project accurately a 2-dimensional image of 3-dimensional disease extension, especially in oblique fields, thus facilitating the design of accurate customized blocking and avoiding inadvertent blocking of the tumor or unnecessary irradiation of normal tissues. Beam's eye view volumetric analysis is helpful for devising a customized treatment plan for each patient. Such customization may minimize local failure, which is one cause of poor results of radiotherapy in this site. Beam's eye view-based radiotherapy has the potential of improving local control and hence may improve the survival of patients with non-small-cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

An anterior appositional electron field technique with a hanging lens block in orbital radiotherapy: a dosimetric study.

A technique for orbital radiotherapy is presented consisting of an anterior, appositional electron beam with a hanging lens block. The beam was modified by introducing two 1.6 mm thick plastic spoilers, at about 3 cm and 15 cm from the lens, to boost in-scattering of electrons under the block. The 9 mm diameter, 2 cm long stainless steel cylindrical block was suspended 0.5-1.0 cm above the eye. We performed film, TLD (Thermo Luminescent Dosimetry), and diode dosimetry to determine the dose fill-in behind the lens. The introduction of the spoilers dramatically changed the dose distribution. The maximum dose under the block increased from 66% to 85% of the open field dose. Moreover, the dose to the posterior surface of the globe directly underneath the block, at a depth of 3 cm, increased from 48% to 76% of maximum dose, while the dose to the lens was still below 20%. This is a simple and easily reproducible treatment and is an improvement on a previously described technique. The dose distribution is adequate for cases where the target volume surrounds and is posterior to the globe.

Electrons↗
PubMed1991

Region of interest issues: the relationship between structure and function in the brain.

The comparison of data sets from individual subjects between imaging modalities is necessary in order to evaluate the normal physiologic responses of the brain or the pathophysiological changes that accompany disease states. Similarly, it is critical to compare data between individuals both within and across imaging modalities. In a collaborative project with a number of university groups, we have developed a system that allows for the within-subject alignment and registration of three-dimensional data sets obtained from different modalities for the same individuals. These data make use of proposed criteria for the optimal solution to positron emission tomography image acquisition and analysis originally established through a series of international workshops. The analysis takes into account errors induced by image acquisition, registration, and alignment with regard to scaling, translation, and rotation. Using the principles of morphometrics and homologous landmarks, the between-subject warping of individual brain anatomy to match that of other individuals, groups or an idealized model can be obtained. Resultant information can provide averaged between-subject data for populations of normal individuals or patients with specific neurologic disorders. Such a system, provides the means by which to compare objectively quantitative data between individuals in a highly automated fashion.

Brain↗
PubMed1991

Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain.

A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy.

Alzheimer Disease↗
PubMed1990

Modeling of dose to tumor and normal tissue from intraperitoneal radioimmunotherapy with alpha and beta emitters.

Dose distributions for normal and tumor tissues from intraperitoneally administered radiolabeled antibodies have been calculated for 90-Yttrium (90Y), 131-Iodine (131I), and 211-Astatine (211At). The dose calculations use data on the activity of intraperitoneal fluid administered, the percent injected dose/gm uptake by tumor, biological half life, and a model for diffusion of antibody/radionuclide complex into peritoneal tissues. Calculations are performed for planar and hemispherical tumor shapes, ranging in size to establish the influence of geometry on dose distribution. Calculations for tumor geometry obtained from biopsies are also performed. When the activity is concentrated on or near the tumor surface, the maximum dose to a planar tumor for a 20 mci administration of 90Y is approximately 60 Gy, and falls rapidly to 50% of this value within 1 mm. However, for a hemispherical tumor, the dose is a maximum of 26 Gy, with an average of approximately 20 Gy. The surface dose from 131I (130 mci) is 240 Gy, and diminishes to 20 Gy in .05 cm in the planar case, whereas a hemispherical tumor receives a dose of 90 Gy over a large fraction of the volume, with the distal portions receiving 40 Gy. The surface dose for an administration of 70 mci of 211 At is 450 Gy and decreases to 50% of this value in 30 microns. Both surface geometry and tumor size are important determinants in the heterogeneity of tumor dose, as are the dose administered, antibody uptake, biodistribution, and residence time factors. These initial studies suggest that the size of disease which may be effectively treated is much less than the range of the particle emitted by radiolabeled antibodies. Furthermore, therapy is ultimately limited by the degree to which the antibody/radionuclide complex can diffuse and permeate the tumor.

Antibodies, Monoclonal↗
PubMed1990

Beam's eye view based prostate treatment planning: is it useful?

Prostate cancer is a common malignancy often treated with radiation therapy. Treatment optimization may improve local control while reducing acute and long-term complications. We routinely obtained CT scans on prostate cancer patients in treatment position after simulation. We analyzed the impact and implications of using our 3-D Beam's Eye View (BEV) capability on field definition and blocking for 12 consecutive patients. Conclusions include: (a) it is necessary to use multiple bony landmarks to align BEV images with simulator films; (b) it is difficult to enter volumes precisely, that is, the exact inferior extent of prostate; (c) Beam's Eye View-based plans show more individual variability in field size and position than are allowed for by recommendations in the literature; and (d) in this small series we found no significant correlation between prostate volume and clinical staging. In addition, computerized Beam's Eye View capability enables us to do normal tissue dosimetry. We have used Dose Volume Histograms (DVH) to study the impact of Beam's Eye View on optimization of dose to the bladder and rectum while adequately treating the prostate, with or without the seminal vesicles. Dose Volume Histograms using Beam's Eye View are compared with Dose Volume Histograms using target volumes from the literature. The results will be discussed, as well as the relative advantages of using Beam's Eye View for prostate cancer on a routine basis.

Evaluation Studies as Topic↗
PubMed1990

Image correlation in oncology.

Image correlation techniques can provide objective spatial registration between multimodality data sets acquired during the planning and follow-up phases of radiation therapy. Correlation of pre-CT/MRI with follow-up CT/MRI and 3D dose matrices may provide insights into normal tissue tolerance. Correlation of SPECT and planar scintigraphs with anatomical maps derived from CT/MRI may be useful in the precise localization of disease and in the evaluation of new modalities, such as radiolabeled monoclonal antibodies, in the diagnosis and treatment of cancer. Correlation of PET and MRI may lead to a more precise understanding of structure-function relationships of the brain. The development and refinement of multimodality image-correlation techniques is a logical step in the evolving role of imaging in radiation therapy.

Brain Neoplasms↗
PubMed1989

Charged particle radiotherapy for lesions encircling the brain stem or spinal cord.

Since 1981, a specialized technique has been under development at the University of California Lawrence Berkeley Laboratory for charged particle irradiation of tumors partially or completely encircling the brain stem or spinal cord. By dividing the target volume into two or more portions and using a combination of beams, a reasonably homogeneous irradiation of the target volume can be obtained which protects critical CNS structures from over-irradiation. This technique requires knowledge of the physical and biological effects of charged particles, precise, reproducible patient immobilization, careful treatment planning based upon Metrizamide contrast CT and/or MRI scanning, compensation for tissue inhomogeneities, and accurate, verifiable radiation delivery. Uncertainties in the dose distribution must be taken into account when prescribing treatment. We have used this technique in 47 patients with a variety of tumors abutting the brain stem and spinal cord, including chordoma, chondrosarcoma, meningioma, osteosarcoma and metastatic tumors. The results have shown a significant local control rate (62%) and the incidence of serious complications has been acceptable (13%). The median follow-up is 20 months with a range of 6-90 months. We conclude that charged particles can be safely and effectively used to irradiate lesions encircling the brain stem or spinal cord to doses higher than can be achieved with low-LET irradiation.

Brain Neoplasms↗
PubMed1989

Computer assisted treatment planning for 125I ophthalmic plaque radiotherapy.

This paper describes a computer program for planning the treatment of ocular tumors with 125I plaques. The program permits the input of the tumor configuration into a model eye and facilitates the viewing of the relative geometry of the tumor and various eye structures in different perspectives. Custom-designed 125I plaques can be localized onto the globe, and dose distributions can be calculated and superimposed on the eye structures in any plane or on the inner eye surface. The program allows efficient evaluation of the plaque design in terms of radiation dose distribution relative to the tumor and critical structures.

Brachytherapy↗
PubMed1989

Specific high frequency rearrangements induced by MNNG in SV40-infected human keratinocytes.

In order to study carcinogen-induced changes in integrated viral sequences clonal sublines of SV40-transformed human keratinocytes were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at sublethal concentrations ranging up to 10 micrograms/ml for a period of 15 min and then examined by Southern blot hybridization using full-length SV40 DNA as a probe. Of the clonal sublines tested, one (AG34) was found to exhibit certain consistent, dose-dependent changes at 4 days post-treatment: (i) loss of at least two EcoRI fragments of approximately 4.4 and 3 kb, with the concomitant appearance of two bands migrating between 1.8 and 2.3 kb; and (ii) loss of a 1.5-kb fragment and the appearance of 2, 3.8 and 5 kb fragments in KpnI digests. Minor variable changes in restriction patterns were seen at 24 h post-treatment but consistent and pronounced effects were observed only at 4 days post-treatment. The altered restriction fragment patterns indicate that MNNG caused highly specific rearrangements in some subset of the DNA sequences associated with the integrated SV40 sequences in human epithelial cells. This differs from what has been found for SV40 sequences in other cell lines where amplification has been reported. These results suggest that (i) the site of SV40 integration may determine the response of integrated SV40 segments after carcinogen treatment, and (ii) carcinogen treatment can result in the induction of a common genetic event throughout the entire population of exposed cells. Genomic libraries created in a lambda phage vector have been used to isolate BamHI fragments containing SV40 sequences. Isolates have been found which exhibit EcoRI and KpnI restriction patterns consistent with the polymorphisms displayed in Southern blots.

Cell Division↗
PubMed1989

The brain: integrated three-dimensional display of MR and PET images.

Three patients with intractable epilepsy, two with brain tumors, and one with encephalitis were imaged with magnetic resonance (MR) and positron emission tomography (PET). MR data were used to construct a three-dimensional (3D) computer model of the brain surface depicting the precentral (movement), postcentral (sensation), left inferior frontal (speech), and left superior temporal (hearing) gyri. PET-derived measurements of average surface metabolism were encoded as colors and mapped onto the 3D model by means of a retrospective technique for registering the two scans. The integrated 3D model depicted the location of PET-detected metabolic abnormalities with respect to the gyral anatomy visualized with MR. In each case, the predicted relationships were confirmed intraoperatively by means of inspection of the brain and electroencephalography. Multimodality 3D displays are likely to be particularly valuable for interpreting PET studies of epileptic patients and others with normal MR anatomy.

Brain↗