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Biomedical subjects

M F Moyers

Publications and source records attributed to M F Moyers.

At least 19 recordsLinked to original sources
PubMed2004

In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric correlates.

Standard methods for risk assessments resulting from human exposures to mixed radiation fields in Space consisting of different particle types and energies rely upon quality factors. These are generally defined as a function of linear energy transfer (LET) and are assumed to be proportional to the risk. In this approach, it is further assumed that the risks for single exposures from each of the radiation types add linearly. Although risks of cancer from acute exposures to photon radiations have been measured in humans, quality factors for protons and ions of heavier atomic mass are generally inferred from animal and/or cellular data. Because only a small amount of data exists for such particles, this group has been examining tumourigenesis initiated by energetic protons and iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon iron ions or both protons and iron ions. The results suggest that the risk of mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56Fe ions and 250 MeV protons is less than additive. These data in conjunction with earlier results further suggest that risk assessments in terms of only mean LETs of the primary cosmic rays may be insufficient to accurately evaluate the relative risks of each type of particle in a radiation field of mixed radiation qualities.

Animals↗
PubMed2003

Range, range modulation, and field radius requirements for proton therapy of prostate cancer.

The Loma Linda University Proton Treatment Facility has treated over 5,000 patients for prostate cancer. Other institutions may find information regarding field size and range requirements for this population of patients useful for designing new proton beamlines. The maximum range, range modulation, and maximum field radius for 240 fields of prostate patients undergoing treatment were sampled and analyzed. Most fields required a range less than 290 mm of water, a modulation width less than or equal to 120 mm, and a radius less than 75 mm.

Humans↗
PubMed2001

Methodologies and tools for proton beam design for lung tumors.

PURPOSE: Proton beams can potentially increase the dose delivered to lung tumors without increasing the dose to critical normal tissues because protons can be stopped before encountering the normal tissues. This potential can only be realized if tissue motion and planning uncertainties are correctly included during planning. This study evaluated several planning strategies to determine which method best provides adequate tumor coverage, minimal normal tissue irradiation, and simplicity of use. METHODS AND MATERIALS: Proton beam treatment plans were generated using one or more of three different planning strategies. These strategies included designing apertures and boluses to the PTV, apertures to the PTV and boluses to the CTV, and aperture and bolus to the CTV. RESULTS: The planning target volume as specified in ICRU Report 50 can be used only to design the lateral margins of beams, because the distal and proximal margins resulting from CT number uncertainty, beam range uncertainty, tissue motions, and setup uncertainties, are different than the lateral margins resulting from these same factors. The best strategy for target coverage with the planning tools available overirradiated some normal tissues unnecessarily. The available tools also made the planning of lung tumors difficult. CONCLUSIONS: This study demonstrated that inclusion of target motion and setup uncertainties into a plan should be performed in the beam design step instead of creating new targets. New computerized treatment planning system tools suggested by this study will ease planning, facilitate abandonment of the PTV concept, improve conformance of the dose distribution to the target, and improve conformal avoidance of critical normal tissues.

Algorithms↗
PubMed2001

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation. I. Initial characterization of DNA damage, micronucleus formation, apoptosis, cell survival, and cell cycle phase redistribution.

The RBE of protons has been assumed to be equivalent to that of photons. The objective of this study was to determine whether radiation-induced DNA and chromosome damage, apoptosis, cell killing and cell cycling in organized epithelial cells was influenced by radiation quality. Thyroid-stimulating hormone-dependent Fischer rat thyroid cells, established as follicles, were exposed to gamma rays or proton beams delivered acutely over a range of physical doses. Gamma-irradiated cells were able to repair DNA damage relatively rapidly so that by 1 h postirradiation they had approximately 20% fewer exposed 3' ends than their counterparts that had been irradiated with proton beams. The persistence of free ends of DNA in the samples irradiated with the proton beam implies that either more initial breaks or a quantitatively different type of damage had occurred. These results were further supported by an increased frequency of chromosomal damage as measured by the presence of micronuclei. Proton-beam irradiation induced micronuclei at a rate of 2.4% per gray, which at 12 Gy translated to 40% more micronuclei than in comparable gamma-irradiated cultures. The higher rate of micronucleus formation and the presence of larger micronuclei in proton-irradiated cells was further evidence that a qualitatively more severe class of damage had been induced than was induced by gamma rays. Differences in the type of damage produced were detected in the apoptosis assay, wherein a significant lag in the induction of apoptosis occurred after gamma irradiation that did not occur with protons. The more immediate expression of apoptotic cells in the cultures irradiated with the proton beam suggests that the damage inflicted was more severe. Alternatively, the cell cycle checkpoint mechanisms required for recovery from such damage might not have been invoked. Differences based on radiation quality were also evident in the alpha components of cell survival curves (0.05 Gy(-1) for gamma rays, 0.12 Gy(-1) for protons), which suggests that the higher level of survival of gamma-irradiated cells could be attributed to the persistence of nonlethally irradiated thyrocytes and/or the capacity to repair damage more effectively than cells exposed to equal physical doses of protons. The final assessment in this study was radiation-induced cell cycle phase redistribution. Gamma rays and protons produced a similar dose-dependent redistribution toward a predominantly G(2)-phase population. From our cumulative results, it seems likely that a majority of the proton-irradiated cells would not continue to divide. In conclusion, these findings suggest that there are quantitative and qualitative differences in the biological effects of proton beams and gamma rays. These differences could be due to structured energy deposition from the tracks of primary protons and the associated high-LET secondary particles produced in the targets. The results suggest that a simple dose-equivalent approach to dosimetry may be inadequate to compare the biological responses of cells to photons and protons.

Animals↗
PubMed2000

Studies of physiology and the morphology of the cat LGN following proton irradiation.

PURPOSE: We have examined the effects of proton irradiation on the histologic and receptive field properties of thalamic relay cells in the cat visual system. The cat lateral geniculate nucleus (LGN) is a large structure with well-defined anatomical boundaries, and well-described afferent, efferent, and receptive field properties. METHODS AND MATERIALS: A 1.0-mm proton microbeam was used on the cat LGN to determine short-term (3 months) and long-term (9 months) receptive field effects of irradiation on LGN relay cells. The doses used were 16-, 40-, and 60-gray (Gy). RESULTS: Following irradiation, abnormalities in receptive field organization were found in 40- and 60-Gy short-term animals, and in all of the long-term animals. The abnormalities included "silent" areas of the LGN where a visual response could not be evoked and other regions that had unusually large or small compound receptive fields. Histologic analysis failed to identify cellular necrosis or vascular damage in the irradiated LGN, but revealed a disruption in retinal afferents to areas of the LGN. CONCLUSIONS: These results indicate that microbeam proton irradiation can disrupt cellular function in the absence of obvious cellular necrosis. Moreover, the area and extent of this disruption increased with time, having larger affect with longer post-irradiation periods.

Animals↗
PubMed2000

Determination of the air w-value in proton beams using ionization chambers with gas flow capability.

The purpose of this work was to determine the w-value of air for protons using the paired gas method. Several plastic- and magnesium-walled chambers were used with air, synthetic air, nitrogen, and argon flowing gases. Using argon as a reference gas, the w-value of air was measured and ranged from 32.7 to 34.5 J/C for protons with energies encountered in radiotherapy. Using nitrogen as a reference gas, the w-value of air ranged from 35.2 to 35.4 J/C over the same range of proton energies. The w-value was found, at a given energy, to be independent of the ion chamber used. The uncertainty in these measurements was estimated at 5.2% at the 2sigma level. This uncertainty was dominated by the 4.4% uncertainty in the w-value of the reference gas.

Air↗
PubMed2000

Acute effects of whole-body proton irradiation on the immune system of the mouse.

The acute effects of proton whole-body irradiation on the distribution and function of leukocyte populations in the spleen and blood were examined and compared to the effects of photons derived from a (60)Co gamma-ray source. Adult female C57BL/6 mice were exposed to a single dose (3 Gy at 0.4 Gy/min) of protons at spread-out Bragg peak (SOBP), protons at the distal entry (E) region, or gamma rays and killed humanely at six different times thereafter. Specific differences were noted in the results, thereby suggesting that the kinetics of the response may be variable. However, the lack of significant differences in most assays at most times suggests that the RBE for both entry and peak regions of the Bragg curve was essentially 1.0 under the conditions of this study. The greatest immunodepression was observed at 4 days postexposure. Flow cytometry and mitogenic stimulation analyses of the spleen and peripheral blood demonstrated that lymphocyte populations differ in radiosensitivity, with B (CD19(+)) cells being most sensitive, T (CD3(+)) cells being moderately sensitive, and natural killer (NK1.1(+)) cells being most resistant. B lymphocytes showed the most rapid recovery. Comparison of the T-lymphocyte subsets showed that CD4(+) T helper/inducer cells were more radiosensitive than the CD8(+) T cytotoxic/suppressor cells. These findings should have an impact on future studies designed to maximize protection of normal tissue during and after proton-radiation exposure.

Animals↗
PubMed1999

Dosimetry techniques for narrow proton beam radiosurgery.

Characterization of narrow beams used in proton stereotactic radiosurgery (PSRS) requires special efforts, since the use of finite size detectors can lead to distortion of the measured dose distributions. Central axis depth doses, lateral profiles and field size dependence factors are the most important beam characteristics to be determined prior to dosimetry calculations and beam modelling for PSRS. In this paper we report recommendations for practical dosimetry techniques which were developed from a comparison of beam characteristics determined with a variety of radiation detectors for 126 and 155 MeV narrow proton beams shaped with 2-30 mm circular brass collimators. These detectors included small-volume ionization chambers, a diamond detector, an Hi-p Si diode, TLD cubes, radiographic and radiochromic films. We found that both types of film are suitable for profile measurements in narrow beams. Good agreement between depth dose distributions measured with ionization chambers, diamond and diode detectors was demonstrated in beams with diameters of 20-30 mm. The diode detector can be used in smaller beams, down to 5 mm diameter. For beams with diameters less than 5 mm, reliable depth dose data may be obtained only with radiochromic film. The tested ionization chambers are appropriate for calibration of beams with diameters of 20-30 mm. TLD cubes and diamond detectors are useful to determine relative dose in beams with diameters of 10-20 mm. Field size factors for smaller beams should be obtained with diode and radiochromic film. We conclude that dosimetry characterization of proton beams down to several millimetres in diameter can be performed using the described procedures.

Calibration↗
PubMed1999

Treatment of macular degeneration with proton beams.

Subfoveal neovascular membranes (SNVMs) are a leading cause of severe visual loss in the elderly in the United States. Previously, the only treatment that could halt progression of this disease was laser photocoagulation, which was, however, accompanied by immediate reduction in visual acuity. A single narrow proton beam was used to irradiate 45 patients to either 8 or 14 Cobalt Gray Equivalent. The alignment technique and dosimetry of these treatments are described. The proton beam direction, range, and modulation were planned with the assistance of an eye-specific planning program. A single anterior beam was used, with patients looking nasally toward a blinking fixation light at an angle of 30 degrees. Patients were aligned using a light field projected through a slit collimator. Patients' positions were monitored during treatment with a short-focal-length camera. Depth dose in a flat phantom was measured with a small-diameter parallel plate ionization chamber. Lateral profiles were measured at several depths with silver halide film. Each treatment session lasted 15 min, of which 1 min consisted of beam delivery. The proton beam stopped in the orbital cavity, delivering no primary proton dose to the brain. Dose to the center of the lens of the involved eye was less than 0.5% of the dose delivered to the macula. Treatments of SNVMs with proton beams require only a short visit to the hospital, little immobilization effort, and a minimal amount of treatment room and beam time. Compared to previous treatment trials using x-ray beams, the dose to nonocular tissues is reduced significantly.

Dose-Response Relationship, Radiation↗
PubMed1996

Phase I/II study of proton beam irradiation for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: treatment techniques and preliminary results.

PURPOSE: Age-related macular degeneration is the prevalent etiology of subfoveal choroidal neovascularization (CNV). The only effective treatment is laser photocoagulation, which is associated with decreased visual acuity following treatment in most patients. This study assessed both the response of subfoveal CNV to proton beam irradiation and treatment-related morbidity. We evaluated preliminary results in patients treated with an initial dose of 8 Cobalt Gray Equivalents (CGE) using a relative biological effectiveness (RBE) of 1.1. METHODS AND MATERIALS: Twenty-one patients with subfoveal CNV received proton irradiation to the central macula with a single fraction of 8 CGE; 19 were eligible for evaluation. Treatment-related morbidity was based on Radiation Therapy Oncology Group (RTOG) criteria; response was evaluated by Macular Photocoagulation Study (MPS) guidelines. Fluorescein angiography was performed; visual acuity, contrast sensitivity, and reading speed were measured at study entry and at 3-month intervals after treatment. Follow-up ranged from 6 to 15 months. RESULTS: No measurable treatment-related morbidity was seen during or after treatment. Of 19 patients evaluated at 6 months, fluorescein angiography demonstrated treatment response in 10 (53%); 14 (74%) patients had improved or stable visual acuity. With a mean follow-up of 11.6 months, 11 (58%) patients have demonstrated improved or stable visual acuity. CONCLUSION: A macular dose of 8 CGE yielded no measurable treatment morbidity in patients studied. Fluorescein angiography demonstrated that regressed or stabilized lesions were associated with improved visual acuity as compared with MPS results. In the next phase, a dose of 14 CGE in a single fraction will be used to further define the optimal dose fractionation schedule.

Aged↗
PubMed1995

Deduction of the air w value in a therapeutic proton beam.

Utilization of air-filled ionization chambers with 60Co-based reference calibrations in proton dosimetry requires application of water to air stopping power ratios and the mean energy required to produce an ion pair (W or w). Accepted uncertainties in current w values for protons leads to a dosimetric uncertainty of 4 per cent when ionization chambers are employed to measure absorbed dose. For this reason, proton dosimetry protocols recommend the use of calorimetry as the absorbed dose standard. We used calorimetry in conjunction with an ionization chamber with 60Co reference calibrations to deduce the proton w value in the entrance region of a 250 MeV proton beam: 34.2 +/- 0.5 eV. Application of this w value, with its 1.5 per cent uncertainty, allows determination of dose in therapeutic proton beams, with uncertainties comparable to photon and electron values.

Air↗
PubMed1995

Effects of proton irradiation on radiolabeled monoclonal antibody uptake in human colon tumor xenografts.

A major limitation of radiolabeled monoclonal antibodies (MAbs) for cancer imaging and therapy is their low accumulation within solid tumors. We, and others, have previously shown that pretreatment of a tumor mass with gamma radiation can increase the level of radiolabeled MAb at the tumor site. Unlike that of conventional radiation, the dose distribution of protons allows for increasing the dose to the cancer volume while reducing the normal tissue dose. The Proton Radiation Therapy Facility at LLUMC treats patients and conducts research. In this study, we sought to determine if preirradiation with proton beam can enhance the localization of radiolabeled MAb within xenotransplanted human colon tumors. T380 colon tumors, implanted s.c. into athymic mice, were subjected to proton irradiation (10 Gy, single dose) when mean tumor volume was 125-135 mm3/group. 111In-ZCE025, a murine MAb directed against carcinoembryonic antigen, was injected i.p. 2 h later, and biodistribution studies were performed 38 h thereafter. Animals irradiated with 60Co and given either 111In-ZCE025 or 111In-MOPC21, an irrelevant MAb, served as controls. The mean percentage of injected radioactivity localized within tumors was highest in the group treated with protons + 111In-ZCE025 when expressed on a per gram basis (%ID/g = 19.3). Somewhat unexpectedly, higher radioactivity was also noted in the normal tissues of these animals compared to other groups. The mean %ID/g tumor values for those given 60Co + 111In-ZCE025 or the antibody alone were 12.5 and 9.0. Our data show that preirradiation of solid tumors increases the localization of tumor-specific radiolabeled MAb at the tumor site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Relative biological effectiveness and microdosimetry of a mixed energy field of protons up to 200 MeV.

We have studied radiation effects utilizing the new 250 MeV Synchrotron at Loma Linda University Medical Center. In this paper we present the data collected for the survival of Chinese hamster lung (V79) cells, that were irradiated with a beam of mixed energy protons up to 200 MeV. The RBE for protons, when compared to 60Co gamma rays, ranged from a low of 1.2 at the high energy portion of the field to 1.3+ at the low energy portion of the field. These results are consistent with the measured lineal energy (microdosimetric) spectra.

Animals↗
PubMed1992

Dosimetric evaluation of a two-dimensional, arc electron, pencil-beam algorithm in water and PMMA.

The accuracy of dose calculations from a pencil-beam algorithm developed specifically for arc electron beam therapy was evaluated at 10 and 15 MeV. Mid-arc depth-doses were measured for 0 degrees and 90 degrees arcs using 12 and 15 cm radius cylindrical water phantoms. Calculated depth-doses for the 90 degrees arced beams in the build-up region were as much as 3% less than measured values; the maximum dose was similar in magnitude but at a greater depth; and the therapeutic depth, R80, was 2-4 mm deeper. Calculated values of output (dose per monitor unit) at the depth of the maximum calculated dose were compared with measured values; for arcs ranging from 0-90 degrees, 12 and 15 cm radius water phantoms, and collimator widths of 4, 5 and 6 cm, results showed differences as great as 7%. Isodose countours for a 90 degrees arc were also measured in a 15 cm radius PMMA phantom. At the depth of maximum dose the algorithm predicted doses in the penumbral regions, both with and without collimation, which agreed within a few per cent of measured values. The largest discrepancies were 5%, which occurred in the penumbral portion of the depth-dose fall-off region. Differences between measurement and calculation are not believed to be clinically significant and are believed to be primarily due to the fact that the algorithm models neither large-angle scattering nor the effects of range straggling on the pencil-beam dose distribution.

Algorithms↗
PubMedDate not supplied

Neutron insensitive depolymerization of polyacrylamide for californium-252 photon dosimetry.

A photon dosimeter based on degradation of polyacrylamide (PAA) in dilute aqueous solution has been found to be insensitive to neutrons from Cf-252, independent of photon energy from 34 keVeff to 1.33 MeV, and useful over a dose range of 1 to 100 Gy. Because this dilute polymer solution is virtually 100% water, it is nearly tissue equivalent for photon absorption as well as neutron scatter and attenuation. Radiation response was determined by measuring decreases in viscosity three days after irradiation. The measured response is dose rate independent from 10 to over 300 Gy/h but increases rapidly at lower dose rates. Long-term, radiation-induced viscosity changes were also observed. The many advantages of this tissue equivalent system for photon/neutron dosimetry suggest the need for further studies of the observed over-response at low dose rates.

Acrylic Resins↗
PubMedDate not supplied

Dosimetric evaluation in heterogeneous tissue of anterior electron beam irradiation for treatment of retinoblastoma.

A dosimetric study of anterior electron beam irradiation for treatment of retinoblastoma was performed to evaluate the influence of tissue heterogeneities on the dose distribution within the eye and the accuracy of the dose calculated by a pencil beam algorithm. Film measurements were made in a variety of polystyrene phantoms and in a removable polystyrene eye incorporated into a tissue substitute phantom constructed from a human skull. Measurements in polystyrene phantoms were used to demonstrate the algorithm's ability to predict the effect of a lens block placed in the beam, as well as the eye's irregular surface shape. The eye phantom was used to measure dose distributions within the eye in both the sagittal and transverse planes in order to test the algorithm's ability to predict the dose distribution when bony heterogeneities are present. Results show (1) that previous treatment planning conclusions based on flat, uniform phantoms for central-axis depth dose are adequate; (2) that a three-dimensional heterogeneity correction is required for accurate dose calculations; and (3) that if only a two-dimensional heterogeneity correction is used in calculating the dose, it is more accurate for the sagittal than the transverse plane.

Electrons↗
PubMedDate not supplied

Determination of the neutron and photon spectra of a clinical fast neutron beam.

A simple technique to determine the neutron and photon spectra of a clinical fast neutron beam is described. This technique involves making narrow beam attenuation measurements with a pair of ionization chambers and an iterative fitting program to analyze the data. A method is also described for determining the first-guess neutron spectrum for input into the iterative program. The results of the analysis yield spectra suitable for use in dose calculation algorithms and dosimetry protocols. Presented here is the first-known published photon spectrum from a clinical machine.

Humans↗