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Biomedical subjects

E Grusell

Publications and source records attributed to E Grusell.

36 records · Page 2Linked to original sources
PubMed1994

Dose enhancement in fast neutron tumour therapy due to neutron captures in 10B.

High energy neutrons, applied in fast neutron tumour therapy, lose energy when passing through tissue and are at the end of their trajectories captured in nitrogen, hydrogen or other normally occurring elements. If the tissue contains 10B, which has a very high cross section for capture of thermal neutrons, then disintegration products of this process, helium and lithium ions, give a dose enhancement which, if the boron is targeted to tumour cells, may be beneficial. The dose enhancement was in the present study calculated as a function of the 10B concentration in the cells and as a function of different thermal neutron fluencies. If the tumour cells contained 10 or 100 microns 10B/g the average dose enhancement was about 20 or 200 mGy respectively. This was obtained with the thermal neutron fluency 2.0 x 10(10) n/cm2. The relative biological effectiveness of the neutron capture process is unknown but assuming the factor 2, these doses correspond to 0.04 or 0.4 CGE (cobolt-60 gray equivalent) respectively, which could directly be compared to the 2-3 Gy of low-LET radiation that is daily applied in conventional radiotherapy. However, if thermal or epithermal neutron fields are directly applied to the patients a hundred times higher thermal neutron fluency can be used. This gives, in the cases with 10 or 100 micrograms 10B/g, about a hundred times higher average doses so that 2-20 Gy, corresponding to about 4-40 CGE, can be given to the patients. Thus, a successful targeting with high amounts of 10B in the tumour cells gives a significant dose enhancement when applied in fast neutron therapy but it is then more reasonable to treat the patient directly with thermal or epithermal neutrons since the average dose enhancement in the latter case is about a hundred times higher and curable doses might be obtained by the tumour specific capture processes alone.

Boron Neutron Capture Therapy↗
PubMed1993

Relative biological effectiveness of intermediate energy protons. Comparisons with 60Co gamma-radiation using two cell lines.

Range modulated proton beams are used for radiotherapy of malignant tumours at several accelerator laboratories with the aim of introducing proton therapy as a clinical hospital-based therapy modality. Due to the finite range and the sharpness of the dose gradients, the dose to well defined target volumes can be raised without excessive irradiation of non-target tissue. The prescribed proton doses are determined in part on the basis of the relative biological effectiveness (RBE) of the particular radiation quality. In this study, RBE values were determined for a proton beam with a maximal range of 33 mm, which corresponds to an energy of approximately 67 MeV. The range modulated depth-dose distribution, with a 20 mm extended Bragg peak, was mainly designed for high precision treatment of small targets such as uveal melanomas. The tested cell lines, LS-174T and V79-379A, were chosen because of their suitability for clonogenic assays. The cells were irradiated with single doses in the range 2-10 Gy at different depths in the extended peak region of the range modulated proton beam. RBE values were determined by comparing the doses needed to obtain the same reduction in colony formation (0.5, 0.1 and 0.01) as with the reference 60Co gamma source. The mean RBE value was 1.22 with a standard deviation of 0.08. The variations depended on both cell type and on the survival levels considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cellular differentiation: a theory based on simulation with computer graphics.

Rules are outlined in order to construct graphically a computer model that deals with cell growth, multiplication and differentiation. The process starts with a multicoloured stem cell and the end product will be differentiated cells represented by different colours. Various biological processes and neoplastic transformation can also be simulated. Based on the idea that the model corresponds to real events, predictions are made about the possible results of future experiments.

Animals↗
PubMed1993

A facility for biomedical experiments with thermal neutrons.

The Studsvik thermal-neutron facility was originally designed for neutron capture radiography (NCR) at high thermal-neutron fluence and low fast-neutron contamination. It has now been modified to permit irradiation of living cells and animals without the need for stopping and restarting the R2-0 reactor. Previous calculations of the thermal-neutron intensity at the NCR position were performed using the two-dimensional diffusion theory code DIXY. In this report the Monte Carlo program MCNP 3B is used to calculate the neutron fluence at the radiography position, and neutron and photon fluences at the positions of the cell specimens. The normalized neutron fluences from the calculations agree well with measured values and show that the contamination with high-energy neutrons is low. The agreement between measured and calculated photon doses was reasonable. The thermal-neutron fluence rate is (2.3 +/- 0.1) x 10(9) cm-2 s-1 at 100 kW at the NCR position and (0.96 +/- 0.03 x 10(9) cm-2 s-1 at 100 kW at the front plate of the loading tube. The photon dose is about (1.6 +/- 0.2) x 10(-12) Gy per neutron. Survival curves of V79 cells grown as monolayers and irradiated in the thermal neutron beam, with and without boron, are presented.

Animals↗
PubMed1993

Quantitative neutron capture radiography for boron in biological specimens.

Track-etch detectors made of cellulose nitrate (LR 115, Kodak Pathé) and polycarbonate (CR 39, Pershore Mouldings Ltd) were compared regarding sensitivity and background when used as detectors for boron determination in biological samples. Measurements were made on two kinds of sample, cryosectioned biological tissue, and liquid samples deposited directly on the detector surface as microdroplets. The CR 39 films were pretreated or washed before irradiation. When cryosectioned tissue was used, measurements were made with and without the inclusion of Mylar foils between the samples and the detectors. Foil thicknesses used were 2 microns in the case of LR 115 and 2, 4, and 6 microns in the case of CR 39. All samples were irradiated with a thermal-neutron fluence of 5 x 10(12) neutrons cm-2 at the thermal-neutron facility in Studsvik, Sweden. The use of a Mylar foil generally suppressed the background tracks relative to the tracks from the 10B disintegration. No difference in resolution between CR 39 and LR 115 was observed. Pretreatment of the CR 39 resulted in an improved sensitivity of detection but the detector became saturated at 0.25 parts per million of 10B. The background was found to be lower in the pretreated detector.

Blood↗
PubMed1992

Accumulation of 10B in the central degenerative areas of human glioma and colon carcinoma spheroids after sulfhydryl boron hydride administration.

Sulfhydryl boron hydride (BSH) (10B enriched) is presently used for boron neutron capture therapy of malignant gliomas. BSH must be close to the target cells to be effective in the inactivation of cell proliferation because of the short range of the reaction products (5-9 microns). Clinical experience indicates that BSH is taken up in gliomas but it is not known to which structures it binds at the cellular level. In vitro tests on monolayer cultured cells have indicated that BSH does not bind, or only shows very weak binding, to single isolated cells. It is possible that BSH accumulates in tumor regions due to the special conditions in poorly vascularized tumor tissue, such as low pO2, low extracellular pH, metabolic gradients, and degenerative changes. To test this we incubated three types of multicellular tumor spheroids with BSH for different times and analyzed both penetration and binding. The spatial distribution of 10B in sections of the spheroids was analyzed by neutron capture autoradiography. We found extensive accumulation of 10B in the central regions of both glioma and colon carcinoma spheroids. The accumulation closely followed the pattern of the degenerative changes which were characterized by massive necrosis in the central regions of the colon carcinoma spheroids and by a continuously increasing frequency of pyknotic nuclei as a function of depth in the glioma spheroids. The accumulation of 10B in the prostatic carcinoma spheroids was much lower. The penetration assay, based on freeze-drying and vapor fixation, showed that BSH penetrated easily since 10B equilibrated within 5-15 min in the studied spheroids. Thus, the low accumulation in the prostatic carcinoma spheroids was not due to penetration difficulties. The results of the present study on cellular spheroids and the results from previous studies on transplanted tumors support the observation that BSH penetrates easily into the degenerative tumor areas and that 10B, for some tumor types, might accumulate in these regions as a result of the BSH administration.

Autoradiography↗
PubMed1991

Backscatter radiation at tissue-titanium interfaces. Analyses of biological effects from 60Co and protons.

It has been claimed that implanted metals can cause backscatter radiation in radiation therapy with a dose enhancement at the bone-metal and tissue-metal interfaces on the beam entrance side. Theoretical calculations and experimental measurements with ionization chambers have indicated that such effects might be significant. Titanium implants are increasingly used in oral and maxillo-facial surgery for reconstruction purposes. A more detailed knowledge of backscatter-induced effects is therefore desired when head and neck cancers in patients with implants are treated with radiotherapy. We have made comparisons of cell survival after irradiation of two types of cultured cells grown directly on titanium metal and on plastic control supports. The cell cultures were irradiated with either 60Co photons or range modulated protons. No significant differences in the colony-forming capacity were found between the irradiated cells grown on titanium and those grown on plastic control supports. This was the case for both radiation types and the results were also observed to be dose-independent. The only observed phenomena were that the two cell-lines differed in radiosensitivity and that protons gave higher biological effects than gamma radiation. The results show that there were no significant changes in cell survival at the interface between the tissue equivalent medium and titanium support indicating that a dose increase induced by backscatter radiation, which possibly could demolish the osseointegration or induce osteoradionecrosis, are minimal when high energy photons or range modulated protons are applied.

Animals↗
PubMed1991

The narrow proton beam therapy unit at the the Svedberg Laboratory in Uppsala.

The synchrocyclotron at the The Svedberg Laboratory (TSL) in Uppsala is now reconstructed and can presently operate with fixed frequency and proton energies up to 100 MeV. A first treatment room with a narrow proton beam unit for therapy of eye tumours is now in operation. Therapy of eye melanomas started in April, 1989 and during 1989 and 1990, 19 patients were treated with 72 MeV protons. The narrow beam unit provides a fixed horizontal beam and the patient is treated in a seated position. The present paper describes mainly the technical aspects of the unit which so far has been used only for eye melanomas. In the future, modifications of the unit will allow therapy of intracranial targets when higher proton energies are available. In its final form, the proton therapy facility at TSL will harbour a second treatment unit. Here a rotating gantry for 200 MeV protons will provide a broad beam, which will enable treatment of tumours located anywhere in the body.

Eye Neoplasms↗
PubMed1990

The possible use of a spallation neutron source for neutron capture therapy with epithermal neutrons.

Spallation is induced in a heavy material by 72-MeV protons. The resulting neutrons can be characterized by an evaporation spectrum with a peak energy of less than 2 MeV. The neutrons are moderated in two steps: first in iron and then in carbon. Results from neutron fluence measurements in a perspex phantom placed close to the moderator are presented. Monte Carlo calculations of neutron fluence in a water phantom are also presented under some chosen configurations of spallation source and moderator. The calculations and measurements are in good agreement and show that, for proton currents of less than 0.5 mA, useful thermal-neutron fluences are attainable in the depth of the brain. However, the dose contribution from the unavoidable gamma background component has not been included in the present investigation.

Boron↗
PubMed1989

The production by 72 MeV protons of keV neutrons for 10B neutron capture therapy.

Fast neutrons, produced in a spallation process by 72 MeV protons hitting heavy nuclei, can be moderated down to keV energies, suitable for 10B capture therapy. Measurements of neutron flux from copper and lead targets, after moderation by water and hydrocarbons, have been performed, together with measurements of the fast neutron and gamma-backgrounds. The comparisons with Monte Carlo calculations show good agreement. As neutron fluences up to 10(12) to 10(13)n/cm2 can be produced within a few hours in about 0.5 m target distance the technique seems to be suitable for clinical experiments.

Boron↗
PubMed1987

General specifications for silicon semiconductors for use in radiation dosimetry.

Silicon semiconductor detectors used in radiation dosimetry have different properties, just as e.g. ionisation chambers, affecting the interaction of radiation with matter in the vicinity of the sensitive volume of the detector, e.g. wall materials, and also the collection of the charges liberated in the detector by the radiation. The charge collection depends on impurities, lattice imperfections and other properties of the semiconductor crystal. In this paper the relevant parameters of a silicon semiconductor detector intended for dosimetry are reviewed. The influence of doping material, doping level, various effects of radiation damage, mechanical construction, detector size, statistical noise and connection to the electrometer is discussed.

Humans↗
PubMed1984

Radiation damage induced dose rate non-linearity in an n-type silicon detector.

Depth dose measurements in continuous cobalt radiation and pulsed roentgen rays were performed with nonirradiated and preirradiated detectors made of n-type silicon. A change in the relative signal at 15 cm depth of 5 to 10 per cent was found in pulsed roentgen ray fields when the detector was radiation damaged. Further experiments showed that the preirradiated detector had a superlinear dose response characteristic at high dose rates. A theoretic model was worked out and the non-linearity is explained by the properties of the recombination centers created during the preirradiation. The recombination centers are also responsible for the sensitivity drop after irradiation. At low dose rates in continuous radiation the non-linearity effect is not observed, which is in accordance with the theory. The theory in conjunction with our and other experimental results suggests that a p-silicon detector will remain linear also after heavy preirradiation.

Cobalt Radioisotopes↗
PubMed1984

Variance measurements with two semiconductor dose detectors.

Variance measurements were performed with pairs of semiconductor detectors of different ionization volumes in continuous and pulsed radiation fields. By a statistical analysis the relative variance of the detector was separated from that of the accelerator. The relative variance of the detector signal was shown to be correlated to the detector volume and to the dose per pulse. From the measurements the number of events per pulse within the detector volume was estimated and the number of pulses needed to have a reading with a given precision was estimated.

Cobalt Radioisotopes↗
PubMedDate not supplied

Patient dose measurements in photon fields by means of silicon semiconductor detectors.

Semiconductor detectors based on p-type silicon and designed for in vivo measurement of entrance dose at the reference point from photon radiation fields, are described. To estimate the absorbed dose at the reference point from measurements with a thin detector, field-size dependent correction factors must be applied to the reading, as the shape of the dose buildup curve varies with field size. To decrease or avoid field-size dependent correction factors, the detector can be covered with a buildup cap. The presence of such a detector will cause perturbation of the radiation field. Therefore, the design of a detector, irrespective of its type, intended for patient dosimetry involves a compromise between minimizing the radiation field perturbation and minimizing field-size dependent correction factors. Detectors with three different buildup caps were designed to cover the energy range from cobalt-60 to 16-MV x rays. The three different detector types were investigated with respect to their signal dependence on field size, field perturbation, and directional dependence. A summary of radiation damage effects on sensitivity, and of sensitivity variation with temperature is also presented.

Humans↗
PubMedDate not supplied

Selective shielding of a p-Si detector for quality independence.

p-silicon semiconductor detectors were partially shielded with lead filters of various geometries with the purpose to minimize the quality dependence in assessments of depth dose distributions in large fields of cobalt radiation. It is shown that a lead shielding of the detector, with the front side excluded, reduced the signal error from about 3 to less than one per cent of the maximum signal as compared with an ionization chamber. Shielding was also done by encapsulating the detector in a mixture of wolfram powder and epoxy resin, with similar results. The signal received at the surface was not affected by this filter geometry. The directional dependence was investigated and was far from uniform for the wolfram-shielded detector. This will however not cause any practical problems when the detector is oriented towards the radiation source.

Cobalt Radioisotopes↗
PubMedDate not supplied

Silicon diodes as detectors for backscatter radiation in photon fields.

We investigated the use of unencapsulated silicon semiconductor detectors for backscatter radiation detection. The results were compared with Monte Carlo (MC) calculations modelling the experimental set-up. A special diode was manufactured, which was designed so that it allowed the positioning of different materials in close contact with the detector surface. Polymethylmethacrylate (PMMA), Pb, Ti and Fe (stainless steel) were used as backscatter materials. The diode signal was measured by integrating the current when irradiating the diode with an equal photon fluence obtained from a medical Co-60 source. When compared to the signal with PMMA as backscatter material the increase in signal was 21%, 27% and 73% for Ti, Fe and Pb, respectively. This is in reasonable agreement with the MC calculations, when taking the effective measurement depth in the Si diode detector into account.

Cobalt Radioisotopes↗
PubMedDate not supplied

Cell type dependent effectiveness of tumour cell inactivation by radiation with increased ionisation density.

Radiation with increased ionization density, LET, will in the near future be applied in targeted radiotherapy and has already, to some degree, been applied in external radiotherapy with accelerated ions. There are indications from the literature that different types of cells are sensitized differently when the LET is increased. Radiation with three different ionisation densities was applied in the present study; 0.8 keV/microns photons from a reference 60Co source, 6 keV/microns helium ions from the entrance region of a monoenergetic helium ion beam and 25 keV/microns from a range modulated helium beam. Three types of cultured cells were analysed: human colon carcinoma LS-174T, human glioma U-343MG and hamster embryonic lung V79-379A. There were interesting differences between the cell types; the LS-174T cells showed strong sensitization already at an LET of 6 keV/microns and there was nearly no difference between the shape of the survival curves after irradiation with 6 or 25 keV/microns. The V79-379A cells were less sensitive to the 6 keV/microns radiation quality and the survival curve was, in this case, very similar to the reference 60Co survival curve. However, the V79-379A cells were sensitized when exposed to the 25 keV/microns helium ions. The U-343MG cells were intermediate in the sense that the 6 keV/microns curve fell in between the 60Co and the 25 keV/microns curves. These variations indicate that different types of cells react differently to changes in LET and that this is probably of special interest for intermediate LET radiation. Some cells might be easily sensitized by intermediate LET qualities while others might be more resistant and this is of importance for the future optimization of radiation treatment with both targeted agents and accelerated ions.

Alpha Particles↗