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Biomedical subjects

J M Galvin

Publications and source records attributed to J M Galvin.

At least 19 recordsLinked to original sources

A comparison of multileaf-collimator and alloy-block field shaping.

PURPOSE: The purpose of this report was to compare the dose distribution at a field edge defined with divergent alloy blocks to the distribution obtained with a multileaf collimator (MLC). The comparison is made for simple block replacement situations. METHODS AND MATERIALS: A tertiary multileaf collimator mounted on a linear accelerator operating at 6 MV was compared to divergent alloy blocks positioned at the level of the blocking tray. The leaves of the MLC were positioned to give maximum stepping (leaf displacement equals leaf width), and the blocking produced the same field shape. Three different treatment plans were compared: single field, opposed fields, and a four-field "box." Dose distributions were determined using radiographic film scanned with a laser densitometer with a 0.45-mm spot size. One experiment was repeated using radiochromic film with reduced energy dependence. Dose distributions were examined on the isocenter plane, and on planes displaced by 1.0 and 2.5 cm. The effect of daily setup variations was also studied by comparing a single fraction treatment with a fractionated treatment consisting of 15 fields slightly displaced relative to each other. The magnitude of these displacements was determined using available literature on treatment reproducibility. RESULTS: For a single field plan, maximum stepping of an MLC-defined edge produces an obvious undulating dose pattern compared to an alloy block edge. At the isocenter plane, this pattern is unchanged when parallel opposed fields are used. However, blurring occurs for both MLC and block edges when planes displaced from the isocenter are examined. The gradient for the block edge is 8%/mm for opposed fields and a plane 2.5 cm from the isocenter, compared to 15%/mm for the isocenter plane. Adding two additional fields does not change the dose pattern in the isocenter plane, but does reduce the gradient across the steepest portion of the penumbra to 8%/mm, and shifts the isodose line with the most pronounced stepping to higher values (from 50 to 80%). Introducing daily setup variations results in a reduction of the sharp dose gradient along the sides of a single field, and around the periphery of the beam at the isocenter plane of opposed fields. Smaller changes are found for edges already blurred by other factors. Radiochromic film was generally noisier than radiographic film, but comparison of the two films did not show a significant difference, indicating that the energy dependence of the radiographic film was not a problem. CONCLUSIONS: The obvious dose stepping seen on a portal image of a single field with MLC shaping is shown to be partially erased by the addition of other fields, and for planes away from the isocenter. However, the effects of daily setup variations must be included to more effectively blur dose stepping along the external envelope of a single field or near the isocenter plane of opposed fields. This result conflicts with attempts to improve immobilization.

Particle Accelerators

Warping CT scans from nontreatment to treatment position.

This paper describes a cost-effective technique that optimally utilizes all available diagnostic studies for three-dimensional treatment planning. A simulator unit modified to produce cross-sectional images (simulator-CT unit) is used to create a reference data set with the patient in the treatment position. Registration software (qsh) brings other diagnostic studies into agreement with this reference data set. Two cases are presented as examples of the use of this technique. Registration of abdominal scans from the same patient demonstrates the warping of a nontreatment position study to the treatment position. The second case is based on paired data sets through the head, in which the diagnostic study was obtained by using a gantry tilt to follow the base of the skull and to avoid sections passing through the teeth. The registration software provides a method for combining diagnostic studies into a single "master" data set. The success of the transformation depends on the operator's ability to identify corresponding anatomic landmarks for different data sets and on the magnitude of the variation in the patient's position from one procedure to the next. Limitations in image quality and the number of cross-sections obtainable from a simulator-CT unit can be partially overcome by using the described technique. Thus, the information contained in nontreatment position diagnostic tests can be used accurately for treatment planning at limited cost.

Anatomy, Cross-Sectional

Field edge smoothing for multileaf collimators.

PURPOSE: To smooth the scalloped dose pattern that occurs for stepped leaves at a treatment field edge defined by a multileaf collimator. METHODS AND MATERIALS: Fields with centers shifted slightly in space were superimposed to blur the staggered dose distribution at the field edge. Film dosimetry was used to monitor changes. The dose distribution for a single field position was compared to the distribution for one and three shifts. Three depths were examined and divergent alloy blocks were included in the comparison. RESULTS: The structure that appears at an edge for a single field when leaves are staggered was nearly eliminated when the field was shifted three times to give a total of four different positions. However, shifting the field one time so that two fields were superimposed gave an intermediate result with only slight improvement in the undulating dose distribution. For the four superimposed fields, the 50% isodose pattern converged to a smoothed line running along the center of the original undulating pattern. The 80 and 20% isodoses did not converge to the center of their scalloped patterns. Instead, these isodose lines were spread leaving a larger penumbra width than a divergent alloy block. CONCLUSIONS: Shifting and adding fields is an effective method for smoothing the staggered dose distribution that results when the leaves of a multileaf collimator are stepped to form an irregular field pattern. However, the width of the penumbra for the combined fields is wider than the penumbra for a cerrobend block.

Radiotherapy

The use of digitally reconstructed radiographs for three-dimensional treatment planning and CT-simulation.

PURPOSE: Recent interest in computed tomography-simulation (CT-simulation) suggests the possibility of a shift to digital images for field verification. This article examines the quality of Digitally Reconstructed Radiographs (DRRs) to determine if they can reasonably be substituted for conventional simulator films, and suggests techniques to improve these images. METHODS AND MATERIALS: Special developmental software and computer hardware allowed extremely rapid reformatting of CT data to produce images geometrically equivalent to treatment unit portal films. The technique uses a trilinear interpolation algorithm and gives a 512 x 512 DRR for any arbitrary beam direction. Resolution in line pairs/cm (lp/cm) for both simulator radiographs and DRRs was measured with a special test phantom. Patient data was reformatted to illustrate methods for improving the quality of the DRR. RESULTS: The equipment used for this study reformats 50 512 x 512 CT scans in 8 s. The resolution for a DRR is limited by the voxel size of the CT scans. For typical voxel dimensions, the resolution was found to be 7 lp/cm transverse and 1.0 lp/cm longitudinal compared to 21.0 lp/cm for a simulator radiograph. Patient movement during the scan procedure further degrades the DRR. The reduced quality of this image makes it more difficult to discern structures, and it may not always be possible to perform essential tasks such as counting vertebral bodies. However, viewing the treatment field superimposed on a DRR displayed with a step function to include only bone aided in the identification of relevant landmarks. Switching between soft tissue, bone, or air windows takes less than 10 s on the equipment used for this study, and the use of different display techniques improved the viewer's ability to evaluate field positioning. CONCLUSIONS: A DRR cannot match the spatial resolution of a radiograph taken with a short exposure and small focal spot, but the ability to change the display mode for the DRR increases the usefulness of these images. Fast reformatting is particularly important when evaluation of field position requires the comparison of each portal image to a series of DRRs.

Humans

Evolution of drug resistance in CCRF-CEM human leukemia cells selected by intermittent methotrexate exposure.

A clinically relevant mechanism of acquired methotrexate (MTX) resistance is decreased MTX polyglutamate (MTXGn) synthesis (McCloskey et al. J. Biol. Chem. 266:6181, 1991) secondary to deficient folylpolyglutamate synthetase (FPGS) activity. Earlier studies showed that this mechanism resulted after intermittent MTX treatment, but did not define its evolution in populations or its clonal frequency of occurrence and heterogeneity. We thus studied evolution of resistance in CCRF-CEM human leukemia cell populations and clones after repeated treatment with 30 microM MTX for 24 h. In populations, MTX resistance was detectable after 1 treatment and increased in degree as total cycles increased to 7. Defective MTXGn synthesis in populations was the only resistance mechanism detected, and FPGS activity in extracts decreased with treatment cycle. After 1 treatment, defective MTXGn synthesis was the major (27/48 clones) form of resistance; 18 clones were sensitive, while 1 clone with a DHFR-related change, no clones with decreased MTX uptake, and 2 complex phenotypes were observed. Sporadic clones with DHFR-mediated resistance appeared up to cycle 4, but defective MTXGn synthesis remained the major resistance mechanism. The degree of clonal resistance tended to increase with treatment cycle, but 1 clone in cycle 2 was similar to the clones from cycle 7. No change in FPGS gene copy number or restriction pattern, or FPGS mRNA level or size (2.3 Kb) was detected in populations. Decreased FPGS activity must result from decreased translation, increased protein turnover, or a point mutation affecting catalysis.

Antimetabolites, Antineoplastic

Combining multileaf fields to modulate fluence distributions.

PURPOSE: A method for modulating beam fluence from a linear accelerator is discussed. The beam modulation is accomplished remotely using a multileaf collimator and does not require entering the treatment room. METHODS AND MATERIALS: The multileaf collimator is used to define a series of field shapes that are superimposed at a fixed gantry angle to produce any desired fluence pattern. A heuristic technique for deriving the field shapes and corresponding monitor unit settings is described. The technique has been tested on randomly generated fluence distributions and on distributions with a limited number of peaks and valleys. The second type of distribution more closely simulates fluence patterns obtained with dose optimization software. Estimates of the time required to use this approach to treat a four-field plan are given and compared to the technique of placing a physical compensator in each beam. RESULTS: It has been demonstrated that complex fluence patterns within a 15 x 15 cm2 field can be achieved with less than 20 fields. Estimates show that this technique is faster than entering the treatment room to change physical compensators. Some limitations of the method are discussed. CONCLUSION: Optimized distributions that conform the dose to irregularly shaped target volumes that wrap around critical structures are possible using superimposed multileaf fields. A method for defining the field shapes is presented.

Humans

A new technique for positioning tangential fields.

PURPOSE: A technique that eliminates the use of a mechanical "breast-bridge" for positioning tangential fields for treatment of the intact breast or chest wall has been developed. METHODS AND MATERIALS: Treatment set-up parameters are determined using measuring capabilities (gantry angles and source-skin distances) available on a standard simulator unit. A programmable scientific calculator is used to determine field geometry from polar coordinates for various points on the patient's skin. The calculator program determines the field size, a depth and lateral shift from a skin reference point to the isocenter for the tangential fields, and the gantry angles. The program provides additional information which facilitates the simulation process: First, the coordinates of the isocenter for the tangential fields are expressed relative to couch coordinates for an initial arbitrary isocenter so that the "auto go to" capability available on some simulators can be used. Second, the coordinates of the medial and lateral entry points can be edited when the first set of tangents are not accepted. This part of the program allows quick and efficient adjustment of the fields to obtain adequate treatment volume coverage and a minimum of irradiated lung or heart. RESULTS: Simulation of more than 300 patients has shown the technique to be a practical and efficient method for positioning tangential fields for breast or chest wall irradiation. CONCLUSION: The technique described here takes full advantage of the capabilities of the new generation of computer controlled simulators, and offers an alternative to previous methods employing a mechanical "breast-bridge."

Breast Neoplasms

Positional stability of sources during low-dose-rate brachytherapy for cervical carcinoma.

PURPOSE: A presumed advantage of high dose rate gynecologic applicators is the fixed relationship maintained between applicator and anatomic structures during the brief exposure. However, it has never been demonstrated that movement of applicators during low dose rate procedures is significant. Therefore, we assessed the magnitude of changes in positioning and attendant alterations in dosimetry which occur during LDR applications. METHODS AND MATERIALS: Fifteen consecutive cervix cancer patients who were treated with combined external beam and brachytherapy (Fletcher-Suit-Delclos applicator), agreed to have orthogonal pelvic radiographs prior to after-loading and following removal of Cesium-137 sources. RESULTS: The median duration of the insertion was 56.5 hours. The average shift was 3.0 mm. Detailed analysis of source movement showed the following changes in median dose (external plus implant): point A, 1.4%; point B, 1.7%; point P, 0.9%; bladder point, 1.9%; rectal point, 2.6%. CONCLUSION: The geometric relationships between the intracavitary gynecologic applicator and the target tissue as well as the critical structures can be adequately maintained throughout the course of a low dose rate implant. Source movement does not result in significant dose changes in terms of decreased cure rates or added complications. Thus, while rationale for high dose rate applicators continues to be proposed, maintenance of a fixed geometric relationship should not be an impetus for the selection of high dose rate intracavitary applicators when treating cervical tumors.

Adult

Initiation of multi-leaf collimator conformal radiation therapy.

Clinical studies have been initiated in conformal radiotherapy using a computer controlled multi-leaf collimator. Quantitative dosimetry and treatment planning studies comparing field shaping by lead alloy blocks and the multi-leaf collimator demonstrate the clinical acceptability of the multi-leaf collimator. Sixteen patients with tumors in multiple sites have received some part of their treatments with both blocking systems. Studies of dosimetry and field shaping show that the multi-leaf collimator produces clinically acceptable blocking for most field shapes and disease sites. The 80-20% penumbra was characterized for a wide range of shaped beams. For straight edges perpendicular to the leaf travel, the penumbra of measured dose distributions from the multi-leaf collimator is equal to conventional divergent blocking. When the multi-leaf collimator leaves approach a contour at an angle, the penumbra increases. At forty-five degrees, the maximum angle of approach, the penumbra is approximately 4 mm wider than that for divergent blocks. Three-dimensional treatment planning demonstrates that equivalent dose distributions can be obtained from the two field shaping systems. The multi-leaf collimator can be used effectively and efficiently to treat a variety of disease sites. Its optimal utility may be in treating complex fields--five or more shaped coplanar or non-coplanar beams. It is well suited for conformal therapy applications.

Humans

Characterization of a multi-leaf collimator system.

Commissioning measurements for a multi-leaf collimator installed on a dual energy accelerator with 6 and 15 MV photons are described. Detailed dosimetric characterization of the multi-leaf collimator is a requirement for modeling the collimator with treatment planning software. Measurements include a determination of the penumbra width, leaf transmission, between-leaf leakage, and localization of the leaf ends and sides. Standard radiographic film was used for the penumbra measurements, and separate experiments using radiochromic film and thermoluminescent dosimeters were performed to verify that distortions of the dose distribution at an edge due to changing energy sensitivity of silver bromide film are negligible. Films were analyzed with a scanning laser densitometer with a 210 micron spot. Little change in the penumbra edge distribution was noted for different positions of a leaf in the field. Experiments localizing the physical end of the leaves showed less than 1 mm deviation from the 50% decrement line. This small difference is attributed to the shaped end on the leaves. One side of a single leaf corresponded to the 50% decrement line, but the opposite face was aligned with a lower value. This difference is due to the tongue and groove used to decrease between-leaf leakage. For both energies, approximately 2% of photons incident on the multi-leaf collimator are transmitted and an additional 0.5% leakage occurs between the leaves. Alignment of the leaves to form a straight edge results in a penumbra profile which compares favorably with the standard technique of using alloy blocks. When the edge is stepped, the isodose lines follow the leaf pattern and the boundary is poorly defined compared to divergent blocks.

Equipment Design

Reproductive performance in relation to uterine and embryonic traits during early gestation in Meishan, large white and crossbred sows.

Previous studies have shown that females of the Chinese Meishan breed and of their F1 cross with European Large White pigs are very prolific, producing about four more piglets per litter than control Large White females. The main cause of this prolificacy is enhanced prenatal survival for a given ovulation rate in Meishan and F1 females and this is controlled by genes of the mother, not those of the conceptus. The objectives of this study were to determine whether genotypic differences in embryo survival were apparent in the period immediately after attachment and to compare embryonic and uterine development at this time. Sows in their third parity (20 Large White, 14 Meishan, 25 Large White x Meishan F1 and 25 Meishan x Large White F1) were killed 20-22 days after mating and their reproductive tracts recovered for further study. There were significant differences between the purebred sows, and crossbred sows were approximately intermediate for the number of corpora lutea (20.7 +/- 0.9, 27.8 +/- 1.1, 22.4 +/- 0.8 and 23.3 +/- 0.8 for the four genotypes, respectively), the number of embryos (15.2 +/- 0.9, 23.4 +/- 1.1, 17.2 +/- 0.8 and 18.8 +/- 0.8, respectively) and the proportionate embryo survival (0.74 +/- 0.04, 0.84 +/- 0.04, 0.78 +/- 0.03 and 0.82 +/- 0.03, respectively). There was a negative association within genotype between embryo survival and the number of corpora lutea. Adjusting for the genotypic difference in the number of corpora lutea increased the genotypic differences in embryo survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Improved methods for determination of variability in patient positioning for radiation therapy using simulation and serial portal film measurements.

Variability in patient positioning was determined by analyzing simulation and portal film measurements for 318 portals in 51 patients treated with external beam radiotherapy to the head and neck. Several indicators of error in patient positioning were examined: random error, a measure of the deviation of all portal films from the average portal film position, systematic error, a measure of the difference between the average portal film and the simulation film, and total uncertainty, a measure of the overall deviation, including both random and systematic uncertainties. The median differences noted were 0.4 cm, 0.6 cm, and 0.7 cm, for Random Error, Systematic Error, and Total Uncertainty, respectively. The treatment fields analyzed in this study show a substantial treatment-to-treatment and simulation-to-treatment variability in patient positioning. The methods described provide an improved means for the systematic analysis of variability in patient positioning.

Head and Neck Neoplasms

Evaluation of multileaf collimator design for a photon beam.

Various aspects of multileaf collimator (MLC) design are examined relative to clinical requirements. The characteristics studied included: (a) irregular field edge definition or "effective" penumbra, (b) optimum field coverage for the multileaf portion of the field, and (c) leaf velocity. A film dosimetry technique was developed to measure the rapid 2-dimensional change in dose at an edge defined by a multileaf collimator with the segments staggered. The method applies a correction factor which allows for the changing ratio of scattered to primary photons at the field edge so that the energy dependence of the film is corrected. Stepped lead alloy blocks were irradiated with 6 MV photons to obtain films simulating a double-focused multileaf collimator, and the results were compared to films of fields shaped with standard divergent blocks. The effect of the shape of the leaf face (the end of the leaf) on penumbra was also studied. Proper shaping of the leaf ends may eliminate the need to exactly match beam divergence so that the mechanical of the collimator system is simplified. Leaves having several different end shapes and moving horizontally to intercept a vertical beam were compared to the divergent design where a straight face moves along an arc. The measurements showed that the "effective" penumbra (measured as the distance from the 80 to 20% isodose lines) for the multileaf collimator is a function of the angle between the direction of leaf motion and the edge defined by the leaves. In addition, all leaf end shapes showed some increase in penumbra compared to standard divergent blocking and also had increasing penumbra width as they moved over or back from the field center line. A total of 459 treatment fields and six disease sites were examined to determine the percentage of fields potentially shaped by multileaf segments of specified length. This study showed 93% of the fields had lengths of 30 cm or less and 99% had widths of 25 cm or less. A study conducted to determine the required leaf velocity to shape various target volume configurations during complete rotation (at 1 RPM) showed that a leaf speed of at least 1.5 cm/sec at isocenter is needed for dynamic conformal treatment.

Equipment Design

Contouring structures for 3-dimensional treatment planning.

Three-dimensional (3-D) treatment planning is a labor-intensive process with contouring of the target volume and critical normal tissues being a significant time-consuming component. The use of 3-D treatment planning on a routine basis may be limited by the time required to complete treatment plans. Despite the need to increase the efficiency of the process, there is little literature addressing the speed and accuracy of contouring systems. In an attempt to initiate systematic analysis of the contouring process, data sets consisting of 10 CT images each were developed on two patients with esophageal carcinoma. Nine different operators manually contoured structures (target volume, spinal canal, lungs) on the data sets using four different contouring systems present in our department. These included both commercially available systems and those developed by the authors. There was a wide variation in the hardware and software characteristics of these systems. The time required to contour the CT data sets was recorded and analyzed. The contouring accuracy was assessed by comparison with a standard template derived from the CT data set for each image. The contouring time was found to be dependent on the system design, previous contouring experience, and the type of drawing instrument (lightpen vs mouse). The mean contouring time ranged from 26 minutes per patient for the fastest system to 41 minutes for the slowest. Potential clinically significant errors in contouring were rare for the spinal canal and lungs but present at a greater rate for the target volume (30.3%). The implications of this finding are discussed.

Adenocarcinoma

Steroid regulation of the synthesis and secretion of retinol-binding protein by the uterus of the pig.

The endometrium of the pig secretes retinol-binding protein (RBP) under the influence of progesterone (P4). The objective of this study was to determine how conceptus-derived estrogen might modulate this production of RBP around days 11-13 of pregnancy when conceptuses elongate from spheres to long thread-like forms. Concentrations of retinol and RBP were low (35 +/- 7 ng/ml) in uterine flushings obtained on days 10-12 of the estrous cycle or from pregnant gilts in which conceptuses had not elongated. Concentrations of retinol and RBP increased 7- to 8-fold (P less than 0.01) in flushings where filamentous conceptuses were present. Size exclusion and ion exchange chromatography demonstrated that virtually all retinol assayed in uterine flushings was associated with RBP. Northern blot analysis with a cDNA representing uterine RBP revealed a single endometrial mRNA 1.1 kilobases in length. Expression of RBP mRNA in uterine endometrium was measured in ovariectomized prepubertal gilts after the administration of steroids according to the following regimens: I, corn oil (days 0-16; n = 10); II, estradiol benzoate (EB; days 13-14; n = 11); III, EB (days 1-2; n = 12); IV, EB (days 1-2) plus P4 (days 3-16; n = 12); and V, EB (days 1-2) plus P4 (days 3-16) plus EB (days 13-14; n = 12). EB (200 micrograms) and P4 (100 mg) were administered twice daily. Treatment IV was designed to stimulate the estrous cycle, and treatment V simulated early pregnancy. All gilts were hysterectomized on day 16, and total uterine mRNA (3 micrograms) was analyzed by Northern blotting. No RBP mRNA was detected in groups I, II, or III. In group IV, 5 of 12 gilts had detectable RBP mRNA, as measured by densitometric scanning (OD = 0.35 +/- 0.14). RNA isolated from all gilts in group V (12 of 12) gave a strong hybridization signal (OD = 1.58 +/- 0.22) for RBP. Finally, RBP mRNA was examined in the uterine endometrium of mature gilts on day 13 of the estrous cycle (n = 4), day 13 of pseudopregnancy (2.5 mg EB given on days 11-12; n = 4), or day 13 of pregnancy after conceptuses had elongated (n = 4). RBP mRNA was present in all groups, but was enhanced approximately 12-fold (P less than 0.01) in pregnant and pseudopregnant gilts compared to that in control gilts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals