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Biomedical subjects

M R Sontag

Publications and source records attributed to M R Sontag.

At least 19 recordsLinked to original sources

Determination of differential scatter-air ratios (dSAR) for three-dimensional scatter integration.

Scatter dose may be calculated by summing the scatter contribution from individual volume elements. These contributions may be represented by differential scatter-air ratios (dSAR). Determination of dSAR from measured data is only approximately correct for second and higher orders of scatter and yields values often limited to one significant figure. Monte Carlo calculation, on the other hand, is time intensive, requires some knowledge of the beam's x-ray spectrum, and mastering the complexities of a program such as EGS4. Total scatter dose at a point may be determined by measuring depth dose or tissue-air ratios and partitioning the dose into its primary and scatter components. Scatter may be represented by scatter-air ratios, which can be characterized by the sum of first, second, and higher orders of scatter. The first scatter dose may be computed exactly by summing the first scatter contribution from individual elements, determined from the first principle. Separation of dSAR into primary attenuation and depth-independent terms allows the latter to be precomputed once for a given energy and stored in tabular form. Second scatter may be treated in a similar manner. The higher orders of scatter are computed by subtracting the sum of calculated first and second scatter doses from the total scatter dose. Elements close to and approximately 1 cm above the point of calculation contribute most heavily to the first scatter dose. Compared to the first scatter dose, the second scatter dose contribution is lower, particularly for elements close to the point of calculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Clinical use of a concomitant boost technique using a gypsum compensator.

PURPOSE: To develop a clinical procedure to treat field within a field (concomitant boost) portals with a single compensated field. METHODS AND MATERIALS: An ordinary manual cerrobend block former was used to produce styrofoam molds from simulator film data. A special gypsum compound was poured into the molds. The compensator block is independently mounted to the treatment machine via a custom-made compensator holder. RESULTS: Measurements confirm that the inhomogeneous dose distribution has been reliably delivered via this technique. The accuracy of placement of the high dose region is sufficient for clinical use. CONCLUSION: The procedure enables the concomitant boost effect to be easily implemented in the clinic without increasing clinical setup time.

Calcium Sulfate

Synaptonemal complex aberrations in the pseudoautosomal region of X, Y chromosomes in irradiated hamsters.

The effects of X-radiation, bleomycin and amsacrine (m-AMSA) on the meiotic chromosomes of male Armenian hamsters were determined by electron microscopic analysis of synaptonemal complex (SC) damage. Pachytene stage cells were analyzed 5 or 6 days following their treatment at putative preleptotene-leptotene stages of meiosis. Of the multiple types of SC aberrations observed to be significantly increased over control levels, lateral element breakage and synaptic anomalies were most prevalent. The focus of these studies was on the sex chromosomes which, in the Armenian hamster, reveal an unusually well-defined pseudoautosomal region. In the XY pair, radiation and chemical treatments caused certain forms of structural and synaptic anomalies which appeared to be preferentially localized to telomeric and/or crossover regions. The nature of these specific aberrations, involving breakage, bridge formation and asynapsis, is not well understood; however, their distributions are suggestive of possible relationships with sites and processes of crossing over.

Amsacrine

Techniques of experimental animal radiotherapy.

Animal research is a crucial component of the generation of new knowledge in human and veterinary medicine. Total body irradiation, whole brain irradiation, total lymphoid irradiation, and local field irradiation of experimental animals are powerful tools for immunology, oncology, studies of normal tissue radiation tolerance, and medical physics. Animal radiotherapy requires specialized techniques. Because of necessarily smaller field sizes, beam localization must be particularly precise. Care must be taken to obtain optimum and accurate dose distribution. This requires consultation with a medical physicist. Optimum dose distribution may be obtained, depending upon the circumstance, by use of either a single beam or two parallel opposed beams with or without bolus. To ensure a proper dose to the animal target volume, care must be paid to the selection of beam energy and the use of radiation attenuators. Beams may be shaped by custom-made lead alloy blocks. Radiation dose rate may be modified by changing the linear accelerator output or the distance from the beam source to the animal, or by attenuating the beam. Reliable targeting of animals requires, for fields other than total body irradiation, anesthesia-utilizing agents such as ether, ketamine, and pentobarbital. The objective of this report is to review the techniques of experimental animal radiotherapy.

Anesthesia

Interspecies cytogenetic comparisons: studies with X-radiation and bleomycin sulfate.

A series of in vitro experiments were conducted to determine if there are innate differences in the sensitivity of peripheral blood lymphocytes (PBLs) from different mammalian species to clastogens. Mouse, rat, and human whole blood samples were exposed to either 0, 0.38, 0.75, 1.5, or 3.0 Gy x-radiation or 0, 5, 10, 20, 40, or 80 micrograms/ml bleomycin for 4 hr. Bromodeoxyuridine-containing cultures were initiated and the PBLs stimulated to divide with phytohemagglutinin. All cultures were harvested following a 3-hr colcemid treatment. Slides were made and differentially stained, and first-division metaphases were scored for chromosome aberrations. In the x-radiation studies human PBLs were significantly more sensitive than mouse PBLs which were in turn more sensitive than rat PBLs as measured by either the total percent aberrant cells or the number of dicentrics. Data from all three species could be fitted to a linear-quadratic model. Results with bleomycin suggest that the mouse and human PBLs are equally sensitive to the clastogenic effects of bleomycin. Both appeared to be more sensitive than the rat PBLs, but the variation between experiments was such that the results among species were not significantly different. These results indicate that there may be inherent differences in sensitivity among PBLs of mammalian species; however, more studies are needed to determine if the differences presented here hold for other agents.

Animals

The radiation dose-response relationship in a human glioma xenograft and an evaluation of the influence of glutathione depletion by buthionine sulfoximine.

We have used an extensively characterized human glioma cell line in an athymic mouse model to evaluate new therapeutic approaches for human supratentorial high grade gliomas. The tumor, D-54MG, is a subline of a human anaplastic glioma. Eight days after homozygous nu/nu BALB/c athymic mice received intracranial (IC) injections of a tumor homogenate, the whole brain was irradiated with either single fractions of 4, 8, 9, and 12 Gy or twice daily fractions, separated by least 6 hr, of 2.28 Gy x 2 or 7.53 Gy x 2. To evaluate whether or not glutathione depletion influenced animal survival, animals at each dose level received either intraperitoneal (IP) buthionine sulfoximine (BSO) alone or I.P. BSO plus BSO in the drinking water. There was a stepwise prolongation of animal survival with increasing doses of external beam radiation. Mean survival in 9 of the 10 control groups (8-12 animals per group) ranged from 14.1 to 18.8 days. Mean survival ranged from 15.3 to 22.5 days at 4 Gy, 25 to 30 days at 8 Gy, 22.3 to 29.7 days at 9 Gy, and 32.9 to 33.6 days at 12 Gy single dose irradiation. At 2.28 Gy x 2 split dose irradiation mean survival was 29.3 days, for 7.53 Gy x 2 mean survival was over 47 days. The data for single fraction irradiation fit a linear regression line (r = 0.908) of mean animal survival = (1.22 [dose in Gy] + 16.7) days. Tumor GSH levels were decreased with all BSO dosing regimens tested. The most aggressive regimen (I.P. BSO+oral BSO for 5 days), reduced tumor GSH to 6.2% of control. Increased survival in irradiated glutathione depleted mice versus mice receiving radiation alone was not seen.

Animals

Interinstitutional experience in verification of external photon dose calculations.

Under the auspices of NCI contracts, four institutions have collaborated to assess the accuracy of the pixel-based dose calculation methods they employ for external photon treatment planning. The approach relied on comparing calculations using each group's algorithm with measurements in phantoms of increasing complexity. The first set of measurements consisted of ionization chamber measurements in water phantoms in normally incident square fields, an elongated field, a wedged field, a blocked field, and an obliquely incident beam. The second group of measurements was carried out using thermoluminescent dosimeters in phantoms designed to investigate the effects of surface curvature, high density heterogeneities, and low density heterogeneities. The final study tested the entire treatment planning system, including CT data conversion, in an anthropomorphic phantom. Overall, good agreement between calculation and measurements was found for all algorithms. Regions in which discrepancies were observed are pointed out, areas for algorithm improvement are identified and the clinical import of algorithm accuracy is discussed.

Humans

Three-dimensional photon treatment planning of the intact breast.

Three-dimensional treatment planning for the intact breast was performed on two patients who had undergone CT scanning. A total of 38 treatment plans were evaluated. Multiple plans were evaluated for each patient including plans with and without inhomogeneity corrections, plans using varying photon energies of 60Co, 4 MV, 6 MV, 10 MV, and 15 MV, and three-dimensionally unconstrained plans. Increased hot spots were appreciated in the central axis plane when lung inhomogeneity corrections were used. Additional hot spots were appreciated in off-axis planes towards the cephalad and caudad aspects of the target volume because of lung inhomogeneity corrections and changes in the breast contour. The use of 60Co was associated with an increase in the magnitude and volume of hot spots, whereas the use of higher energy photons such as 10 MV and 15 MV was associated with an unacceptable target coverage at shallow depths. Therefore, for the two patients studied, the use of a medium energy photon beam (such as from a 6 MV linear accelerator) appeared to be the energy of choice for treatment of the intact breast. The three-dimensionally unconstrained plans were able to improve slightly upon the standard plans, particularly with relationship of dose to normal tissue structures. Areas for future research were identified, including the use of tissue compensators.

Adult

Induction of micronuclei by X-radiation in human, mouse and rat peripheral blood lymphocytes.

We compared the radiosensitivity of human, rat and mouse peripheral blood lymphocytes (PBLs) by analyzing micronuclei (MN) in cytochalasin B-induced binucleated (BN) cells. For each species and dose 4-ml aliquots of whole blood were X-irradiated to obtain doses of 38, 75, 150 or 300 cGy. Controls were sham-irradiated. After exposure to X-rays, mononuclear leukocytes were isolated using density gradients and cultured in RPMI 1640 medium containing phytohemagglutinin to stimulate mitogenesis. At 21 h cytochalasin B was added to produce BN PBLs, and all cultures were harvested at 52 h post-initiation using a cytocentrifuge. Significant dose-dependent increases in the percentage of micronucleated cells and the number of MN per BN cell were observed in all three species. The linear-quadratic regression curves for the total percentage of micronucleated cells for the three species were similar; however, the curve for the mouse PBLs had a larger quadratic component than either of the curves for the rat or human PBLs. Although the correlation between the percentage of cells with MN and those with chromosome aberrations was high (r2 greater than 0.95), the mouse and rat PBLs were over twice as efficient as human PBLs in forming MN from presumed acentric fragments. These data indicate that the induction of MN in BN cells following ionizing radiation is similar in human, rat and mouse PBLs, but care must be taken in using the MN results to predict frequencies of cells with chromosomal aberrations.

Adult

Stage-specific damage to synaptonemal complexes and metaphase chromosomes induced by X rays in male mouse germ cells.

Synaptonemal complexes reveal mutagen-induced effects in germ cell meiotic chromosomes. This study was aimed at characterizing relationships between damage to synaptonemal complexes and metaphase I chromosomes following radiation exposure at various stages of spermatogenesis. Male mice were irradiated with doses of 0, 2, or 4 Gy, and spermatocytes were harvested at times consistent with earlier exposures as spermatogonial stem cells, preleptotene cells (premeiotic DNA synthesis), or meiotic prophase cells. After stem-cell exposure, twice as many rearrangements were observed in synaptonemal complexes as in metaphase I chromosomes. Irradiation during premeiotic DNA synthesis resulted in dose-related increases in synaptonemal complex breakage and rearrangements (including novel forms) and in metaphase chromosomal aberrations. Following prophase exposure, various types and levels of damage to synaptonemal complexes and metaphase chromosomes were observed. Irradiation of zygotene cells led to high frequencies of chromosome multivalents in metaphase I without a correspondingly high level of damage in preceding prophase synaptonemal complexes. Thus irradiation of premeiotic and meiotic cells results in variable relationships between damage to synaptonemal complexes and metaphase chromosomes. Interpretations of these relationships are based upon what is known about both radiation clastogenesis and the structural/temporal relationships between synaptonemal complexes at prophase and chromosomes at metaphase I of meiosis.

Animals

Practice of 3-dimensional treatment planning at the Fox Chase Cancer Center, University of Pennsylvania.

The use of 3-dimensional (3-D) dose distributions and dose-volume histograms in radiation therapy treatment planning is illustrated on a patient with a head and neck tumor. The patient was immobilized in a rectangular tissue compensation bolus box. The treatment was planned with a 14 MeV D-T derived fast neutron therapy beam. The isodose distributions and the dose-volume histograms at multiple adjacent levels are used to evaluate the adequacy of coverage of target volumes and the doses to the normal tissues. Such dose-volume histograms are useful and practical in summarizing the dose distribution throughout the irradiated volume, assessing the degree of uniformity of the dose distribution within the target volume, quantifying the amount of normal tissue irradiated, and evaluating rival treatment plans for both particle and nonparticle beams.

Fast Neutrons

Rapid three-dimensional treatment planning: I. Ray-tracing approach to primary component dose calculations.

Algorithms for fully three-dimensional divergent-beam radiotherapy treatment planning have been developed to achieve very high sampling of dose in heterogeneous (inhomogeneous density) tissue throughout an arbitrarily oriented patient volume, in clinically acceptable times of calculation. Dose is calculated at points along numerous rays which sample each beam. To display the dose distribution, the calculated dose values for each beam are interpolated onto rectilinear grids of (arbitrary) parallel planes, scaled for beam weight and finally merged with the weighted dose contributions of other beams. In this paper we describe and demonstrate the algorithm for the primary component of the three-dimensional photon dose distribution delivered to a patient.

Clinical Trials as Topic

A clinically operational method for three-dimensional dose calculations.

Three-dimensional dose calculations can now be performed for both photon and neutron beam therapy in reasonable times on a minicomputer. The method described is a scatter-air ratio-tissue-air ratio (SAR-TAR) model which, for any beam, finds the correct depth at each point in a patient even when the beam passes obliquely through more than one transverse section of the patient. Scatter dose is determined by performing a Clarkson integration over both angle and radial distance, with the correct depth of the beam calculated at both accumulation and scatter points. Doses are computed and displayed over a 0.33 cm sampling grid superimposed on each transverse CT slice used in treatment planning. Dose-volume histograms are made for the entire patient volume and for internal organs and target volumes outlined by the physician. The clinical efficacy of the method in therapy planning is demonstrated and a comparison is made between this method and single section two-dimensional methods.

Breast Neoplasms

Clinical application of a CT based treatment planning system.

An AECL (TP-11) treatment planning system has been modified to allow multiple CT scans to be used directly for dosage calculation and display. This CT/TP-11 system has incorporated the "equivalent tissue-air ratio method" to make corrections for the effects of tissue heterogeneity and the three-dimensional nature of patient shape. In test situations, using an anatomical phantom, an accuracy of ca. 2% has been attained. An investigation has also been made to assess the importance of the reproducibility of patient position and its effect on the validity of such dosage calcualtions. When representing an advance in sophistication of existing facilities, this system has also been designed with practically in mind.

Humans

The equivalent tissue-air ratio method for making absorbed dose calculations in a heterogeneous medium.

The CT scanner makes three-dimensional anatomical information available for treatment planning, the calculational algorithm being the limiting factor in dose calculations. A method has been developed, called the "effective tissue-air ratio method," that uses all the information but reduces it to manageable proportions. The accuracy is satisfactory for a wide range of photon beam energies and clinical applications. It has been implemented in such a way that the CT scan can be used directly without the intermediate step of manually obtaining structures from either a viewing screen or a hard copy of the CT image.

Air

Implications of computed tomography for inhomogeneity corrections in photon beam dose calculations.

Patient inhomogeneity information is investigated for use in radiotherapy planning. Absorbed doses measured in a phantom are compared to doses calculated for photon beams using various treatment planning inhomogeneity correction methods. Delineation of inhomogeneities with a spatial resolution of 5 mm and with an electron density accuracy of 2% in usually sufficient to allow doses to be calculated with a mean accuracy of better than 2% for 60Co and 3% for 25-MV x rays if the authors' Equivalent Tissue-Air Ratio Method is used.

Cobalt Radioisotopes

Dose measurements in the build-up region for cobalt-60 therapy units.

The dose in the build-up region for four different Cobalt-60 therapy units was measured. It was found that, for large collimator openings and relatively short SSDs, a new dose peak occurs at a depth very much smaller than 0.5 cm. The dose at this peak is a function of collimator openings and SSDs and, in some extreme case, could be 15% or more higher than the dose at the conventional peak dose of 0.5 cm. The new dose peak is probably due to electrons produced in the source capsule and the part of the collimator close to the source; it can be almost eliminated by a filter placed just below the collimator.

Cobalt Radioisotopes