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Biomedical subjects

R L Maughan

Publications and source records attributed to R L Maughan.

At least 55 records · Page 3Linked to original sources

Shielding and radiation safety around a superconducting cyclotron neutron therapy facility.

Prior to routine operation of the neutron therapy unit a radiation survey was performed in order to confirm the shielding design and to assure the safety of the personnel involved in the operation of the unit. The shielding requirements were calculated in accordance with NCRP Report No. 51. The contributions of the neutron and gamma dose equivalents have been measured separately outside the treatment room. The exposure outside the shield is negligible. In general, the measured values were lower than those derived from the shielding calculations. The highest total dose equivalents were registered at locations corresponding to the highest calculated values.

Cyclotrons↗

A direct measurement of strontium-89 activity in bone metastases.

The total absorbed dose after systemic administration of 89Sr has been determined by measuring directly its activity in bone metastases. Autoradiography was performed on sections of bones obtained from patients treated with 89Sr to study the pattern of deposition. Discs of 5 and 8 mm diameter were cut from metastatic sites and normal bone. The beta-ray activity was determined with a scintillation counter, which was calibrated using similar bovine cancellous bone discs, onto which a known activity of 89Sr was transferred by pipette. From the activity measured, the initial activity (at the time of 89Sr administration) was calculated. The absorbed dose was estimated using the methodology described in NCRP Report No. 58. The estimated initial activity of 89Sr in the bone metastases varied from 2.3 to 240 MBq kg-1, with a mean value of 31 +/- 27 MBq kg-1. The total absorbed dose ranged from 1.3 to 64 Gy, with a mean of 18 +/- 16 Gy. The average total dose to normal bone sites was 1.1 +/- 0.4 Gy. The metastases to normal bone dose ratio in individual samples varied from 8 +/- 4 to 40 +/- 25. These estimates are in agreement with those obtained previously by indirect methods.

Autoradiography↗

Calculations of x-ray and neutron transmission through multirod arrays.

Multirod arrays can be used to produce irregularly shaped irradiation fields for use in external beam photon and neutron radiation therapy. Two prototype multirod collimators have been built for use with high energy photon beams. A practical multirod collimator is in routine use with the fast neutron beam at a superconducting cyclotron based neutron therapy facility. A simple computer program has been written for calculating the transmission of photon and neutron beams through multirod arrays. The results of calculations for both close packed and spaced rod arrays are presented, and compared with available photon and neutron transmission data. The transmission through a regularly packed array exhibits a pattern of maxima and minima which occur with a spacing corresponding to the rod radius. The program predicts the positions and magnitudes of the transmission peaks. The rod diameter and spacing, the source size, and the position of the multirod collimator and the measurement plane relative to the source, all effect the exact nature of the measured transmission pattern. The transmission of 15-MV photons through close packed and spaced rod arrays was calculated using the program and compared with measurements made in a close packed tungsten rod array and with a prototype multirod collimator. Calculations for the transmission of a p(42)-Be neutron beam through a close packed tungsten rod array were compared with previously published data. Good agreement between calculations and measured data was obtained in all cases. The program was used to design a practical multirod collimator for a d(50)- Be fast neutron beam.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclotrons↗

Radiological properties of a prototype multi-rod collimator for producing irregular fields in photon radiation therapy.

A prototype multi-rod collimator for producing irregular fields in photon radiation therapy has been designed and built. The mechanical details of the design and operation of the multi-rod collimator are discussed. Beam profiles for an approximately 10 x 10 cm2 field have been measured at various depths in phantom, and compared with profiles obtained using the secondary collimator jaws alone and with cast metal blocks. The ability of the collimator to produce irregular fields is demonstrated with reference to some commonly encountered therapy fields and the ability to produce central blocks and island blocks is discussed. Isodose curves for selected irregular fields are presented.

Models, Structural↗

Physical characteristics of a clinical d(48.5)+Be neutron therapy beam produced by a superconducting cyclotron.

The Harper Hospital and Wayne State University fast neutron therapy facility is the only one in the world to use a compact superconducting cyclotron and multirod collimator. Neutrons are produced by the interaction of the 48.5-MeV deuteron beam with a thick internal beryllium target and the compact accelerator is gantry mounted to allow full 360 degrees rotation of the neutron beam about the therapy couch. The deuteron beam strikes the beryllium target at a glancing angle. A flattening filter is used to flatten the asymmetric neutron beam which results from this geometry. Details of the flattening filter design and construction are discussed. The physical characteristics of the resulting neutron therapy beam were measured. The central axis depth-dose values are approximately equivalent to those of a 4-MV photon beam. The dose buildup curve reaches its maximum value at a depth of 9 mm in a water phantom and the surface dose is approximately 42%. The beam penumbra produced by the multirod collimator has been measured in terms of the distance between the 20% and 80% isodose lines. The penumbra width for a 10 x 10-cm2 field at a depth of 10 cm in a water phantom is 1.65 +/- 0.1 cm, and is comparable to that achieved with other high-energy neutron beams. The long-term stability of the dose monitoring system has been measured and found to be satisfactory. The physical characteristics of the neutron beam are comparable with those of other modern fast neutron therapy facilities.

Beryllium↗

A superconducting cyclotron for neutron radiation therapy.

The physical and clinical specifications of a neutron therapy facility utilizing a superconducting cyclotron are presented. The cyclotron and its support system are described. Details of the operation of the cyclotron in a hospital environment are given; the requirements of the helium liquifier and cryogenic system are described together with a summary of its mode of operation. The simplicity of the cyclotron control system is discussed. The physical characteristics of the neutron beam are described. The central axis percent depth dose curve is equivalent to that of a 4 MV x-ray beam. The depth of maximum dose occurs at approximately 9 mm depth and the surface dose is between 40% and 45%. The multirod collimator allows for the production of irregularly shaped fields of size up to 26.5 x 30 cm, without excessive exposure to operating personnel.

Cyclotrons↗

Synergy of radiation therapy and immunotherapy in murine renal cell carcinoma.

The treatment of metastatic renal cell carcinoma with immunotherapy has resulted in objective anti-tumor responses in 15-30% of patients. To enhance the therapeutic effects of immunotherapy, it is becoming evident that this approach should be combined with other treatment modalities. In this study, a spontaneously metastasizing murine renal adenocarcinoma (Renca), transplanted under the renal capsule, was treated with either radiation therapy, immunotherapy or a combination of both. In order to distinguish between the local and systemic effects of radiation therapy, total body irradiation was compared to irradiation of the tumor-bearing kidney only, or irradiation of the whole mouse with the tumor-bearing kidney shielded. Immunotherapy was administered with interleukin-2 (IL-2) alone or with IL-2 and lymphokine activated killer (LAK) cells. Combined radiation and immunotherapy induced a better anti-tumor response than either modality alone. The best response was obtained by local tumor irradiation and IL-2 therapy and resulted in a significant reduction in primary tumor size, elimination of lung metastases and a significant increase in survival.

Animals↗

Transmission measurements in multi-rod arrays: a design study for a multi-rod collimator.

The results of transmission measurements for neutrons, cobalt-60 gamma-rays, and 10 and 15 MV photons made with close-packed arrays of tungsten rods are presented. These results indicate that tungsten rod arrays of reasonable thickness can provide for primary or secondary collimation of all these radiation beams. Development work on a collimation system utilizing the multi-rod concept which is capable of producing irregularly shaped fields and suitable for use in photon or neutron radiation therapy is described.

Humans↗

An animal model of pulmonary radiation fibrosis with biochemical, physiologic, immunologic, and morphologic observations.

An animal model of pulmonary radiation fibrosis was established, using male CBA/j mice. Both lungs of each mouse in one group (DL) were irradiated with two doses of 8.5 Gy each, separated by 30 days. A control group (CG) was sham-irradiated. There was a small but significant difference (P less than 0.03) in average breathing rate between DL and CG 27 weeks after the second irradiation which increased until the 34th week followed by a plateau. The accumulated hydroxyproline content of the irradiated mouse lung was 40% greater (P less than 0.02) than that of the sham-irradiated lung at 42 weeks and thereafter. Anticollagen antibodies assayed 52 weeks after irradiation by enzyme-linked immunosorbent assay were elevated by 49% in sera from the irradiated mice compared to sera from sham-irradiated mice. Mortality during the 52-week period following the second irradiation was low (13%) for both groups. Histological comparison of irradiated and control mouse lungs fixed under uniform inflation pressure indicated no significant differences. The model has unique features including an increase in collagen deposition, no acute changes attributable to radiation, a small but statistically significant abnormality in pulmonary function, an immunologic response to collagen, and low mortality.

Animals↗

The use of 'top-up' experiments to investigate the effect of very small doses per fraction in mouse skin.

The partial tolerance type of 'top-up' experiment has been investigated to determine the resolution of this approach for studying the damage to mouse skin from very small doses of X-rays and neutrons. The effect of 20 fractions, each as small as 0.10 Gy of X-rays or of 0.05 Gy of neutrons, can be detected if 3 MeV neutrons are used as the 'top-up' reference radiation. This capability results from the almost linear underlying dose-response curve and highly reproducible dose-effect relationship for the low energy neutrons. The data fit the linear quadratic model of dose fractionation for X-rays down to fractional doses of 0.75 Gy, but at lower doses there is a trend towards an increase in the skin radiosensitivity. Modelling shows that this might be consistent with a sub-population of the cells showing an exceptional radiosensitivity, and a replenishment of this subpopulation occurring in the 8 h between small dose fractions. More experiments are needed at very low doses in order to confirm this hypothesis for skin and for other tissues.

Animals↗

Microdosimetric investigation of a fast neutron radiobiology facility utilising the d(4)-9Be reaction.

For fast neutron therapy and radiobiology beams, knowledge of the primary neutron spectrum is the most fundamental requirement for the definition of radiation quality. However, microdosimetric measurements in the form of single-event spectra not only complement the primary neutron spectrum as a statement of radiation quality but also provide a sensitive method of detecting changes in the radiation field in situations where it is no longer possible to have precise knowledge of the primary neutron spectrum, for example after collimator changes and in positions where the radiation field consists of a large scattered component. For the various collimator arrangements employed at the Gray Laboratory facility small perturbations of the radiation field are observed which can be related to a softening of the primary neutron spectrum with increasing field size of the collimator. Gamma fraction determinations are in very good agreement with measurements employing the dual chamber technique and also show small changes with collimator field size giving rise to gamma components ranging from 0.09 to 0.12, the higher values being measured for the larger field sizes. Quality changes represented by the shape of the measured event-size spectra and the derived microdosimetric parameters were greatest for off axis and phantom measurements. With increasing depth in water, yD was found to decrease from 47.3 keV micron-1 at 5 cm to 35.6 keV micron-1 at 15 cm depth, and the gamma fraction was found to increase from 0.23 to 0.40. Although there is no generally accepted and agreed method of relating microdosimetric information to biological effectiveness, the dual radiation theory in its original form (Kellerer and Rossi 1972) has been shown to be a very useful model for the assessment of the biological effectiveness of fast neutrons (Kellerer et al 1976). The microdosimetric parameter which is used in the dual radiation model is the dose mean specific energy corrected for saturation zeta* which, for a 2 micron simulated diameter, is related to the dose mean lineal energy corrected for saturation y* by zeta* = y* keV micron-1 X 0.51 X 10(-2) Gy. Values of y* determined for each of the collimator arrangements used at the Gray Laboratory show a spread of some 6% (table 1) and, as the dose fraction between lineal energies 5 and 150 keV micron-1 (the recoil proton component) do not alter by more than 3%, radiobiological experiments performed with different collimator arrangements would show no observable differences.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Repair in mouse lung for up to 20 fractions of X rays or neutrons.

Local irradiation of the mouse thorax followed by the measurement of lung damage up to 17 months after irradiation has been carried out with up to 20 fractions of 3 MeV neutrons or of 240 kV X rays. Doses per fraction down to 0.28 and 1.5 Gy respectively were used. Repair capacity and RBE values were assessed by measuring breathing rate and lethality at monthly intervals up to 17 months. Only a small sparing of neutron damage was found. Sparing with X rays continued to increase as the size of each fraction was decreased, and was the main influence on the RBE values. The single-dose RBE was approximately 1.8, increasing to approximately 5 at the lowest dose per fraction measured. Dose-response curves derived for each fraction were well fitted by the formula alpha d + beta d2 where the repair parameter alpha/beta has values of 2-4 Gy after X irradiation. A slight fall of alpha/beta with time after X irradiation was observed, from about 4 Gy for pneumonitis to about 2 Gy for late fibrosis. This was significant for lethality but not for the increase of breathing rate. With neutrons the value of alpha was much higher than with X rays and a trend of increasing value of alpha at later times after irradiation was seen. Use of the linear quadratic dose-response formula predicts a continuing increase in the sparing of X-ray damage in lung as doses per fraction are decreased below those used here, and a limiting low-dose RBE of about 7.

Animals↗

Effects of radiomodifiers on high and low LET responses in vivo.

The radioprotector WR-2721 and the radiosensitizer misonidazole have been studied for their influence on the response of mouse skin and tumours when irradiated with either single or fractionated doses of 240 kV X-rays or 3 MeV neutrons. The modification of radiosensitivity to neutrons was significantly less than that for X-rays, both for tumours and skin. When the two drugs were given in combination before single neutron doses, competitive interaction was observed.

Animals↗

The interaction between X-rays and 3 MeV neutrons in the skin of the mouse foot.

Mouse feet were irradiated with mixtures of 3 MeV neutrons and 140 kVp X-rays given simultaneously or within 24 hours of each other. The effects of different treatments were contrasted by comparing the doses required to give equal skin reactions. Irradiation was given as 1, 2, 4 or 8 equal fractions, in order to assess r.b.e. and the shapes of the underlying dose-response curves for mixed beams over a wide range of dose per fraction. All dose-effect curves were well fitted by a linear-quadratic (alpha, beta) model. For X-rays and neutrons given simultaneously, the linear coefficient (alpha) decreased by a factor of 4.80 while the quadratic coefficient (beta) increased by a factor of only 1.44 when the proton contamination in the beam increased from 11 to 100 per cent, with alpha/beta changing from 95.0 to 13.8. The data from simultaneous X-ray and neutron irradiation were consistent with full interaction of those effects from the two radiations which give rise to the total quadratic component of effect. When the two radiations are separated by up to 24 h, this interaction decreases but does not entirely disappear.

Animals↗

Neutron RBEs for mouse skin at low doses per fraction.

The effect of low doses of 240 kVp X rays or of 3 MeV neutrons has been investigated using skin reactions on mouse feet as the biological system. Eight or nine repeated small doses of radiation were used, followed by graded "top-up" doses to bring the reactions into a detectable range. By comparing dose-response curves, the RBE has been determined for neutron doses per fraction ranging from 0.25-1.0 Gy. The data are consistent with a limiting RBE of between 7 and 10 at very low doses. A review of other published RBE values for low doses per fraction shows a wide range of RBEs . Very few studies show a plateau value for the RBE. These findings are more consistent with dose-response data that fit a linear-quadratic model than with a multitarget single-hit model.

Animals↗

Is there a loss of repair capacity in mouse lungs with increasing numbers of dose fractions?

The capability of mouse lung to repair sublethal damage after up to 10 fractions of X rays was assessed by an in situ breathing rate assay and lethality. The whole thorax of mice was irradiated "daily" with 4, 7 or 10 fractions of 2.75 or 3.0 Gy of X rays followed at 24 hours by graded "test" doses of X rays or neutrons. Repair capability was measured by determining the difference in test dose between 4 and 7 fractions or 7 and 10 fractions at a given isoeffect. Damage was assessed monthly up to 76 weeks after irradiation, during pneumonitis and chronic fibrosis. The data from both assays for the pneumonitis phase suggested that there may be some loss of repair between 7 and 10 fractions, although it was not large enough in only 10 fractions to be clearly demonstrated. In contrast, there was no suggestion of loss of repair for late damage after up to 10 fractions of X rays using either assay.

Animals↗