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PubMed2002

Experimental tools for track structure investigations: new approaches for dosimetry and microdosimetry.

In recent years, several new methods have been developed for track structure investigations. They use macroscopic gas volumes to transfer the results to microscopic dimensions and are based on either the cluster counting principle or on optical methods for full track analysis. The first type of method allows cluster size distributions in nanometre dimensions to be measured. The second type reveals the full topology of the ionisation pattern of tracks or track segments within a volume of a few micrometres with a spatial resolution down to 5 nm. The basic principles of these instruments and their main features are summarised and a selection of results obtained to date are shown.

Cluster Analysis↗

PubMed2004

Effect of medium on chromatin damage in bystander mammalian cells.

In the present study, we examined the potential contribution of irradiated medium to the bystander effect using custom-made double-Mylar stainless steel rings. Exponentially growing human-hamster hybrid (A(L)) cells were plated on either one or both sides of double-Mylar dishes 2-4 days before irradiation. One side (with or without cells) was irradiated with alpha particles using the track segment mode of a 4 MeV Van de Graaff accelerator at the Radiological Research Accelerator Facility of Columbia University. Since alpha particles can traverse only a very limited distance (around 23 microm in water), cells plated on the other side of a medium-filled Mylar dish will not be irradiated by the alpha particles. The results of the cytogenetic assay of unirradiated target cells that were attached to the top Mylar layer indicate that the number of chromatid-type aberrations was higher when there was a bottom layer of cells in the medium-filled chambers than with just medium alone. Furthermore, when the medium was transferred from these cell-irradiated dishes to fresh A(L) cell cultures, chromatid-type aberrations were produced in the unirradiated fresh cells. In contrast, medium irradiated in the absence of cells had no effect on chromatid aberrations. These results suggest that certain unidentified modulating factors secreted from the irradiated cells on the bottom Mylar layer into the medium induce chromatin damage in the unirradiated bystander cells.

Animals↗

PubMed2000

Development of ammonium tartrate as an ESR dosimeter material for clinical purposes.

The crystalline substance ammonium tartrate is investigated with respect to its suitability as a clinical dosimetry material. The properties investigated are: the radical stability for absorbed doses relevant for clinical use, the improvement in sensitivity when the crystals are deuterated and the linear electron transfer (LET)-dependence. After photon irradiation to an absorbed dose of 20 Gy, the signal increases rapidly during the first 6 h. After this period, the changes are more moderate and can be corrected for. The signal-to-noise ratio of irradiated ammonium tartrate is twice the corresponding value of alanine. By deuterating the crystals, the sensitivity can be further improved by a factor of 1.4. As expected, the signal decreases with increasing LET of the radiation, but no changes in the spectrum shape was observed.

Deuterium↗

PubMed2003

Pseudostenosis of the internal carotid artery in 3D time-of-flight MR angiography: effects of a magnetization transfer contrast pulse and metallic material.

Pseudostenosis or pseudoocclusion of the internal carotid artery in 3D time-of-flight MR angiography has been reported to be caused by susceptibility artifacts due to the presence of a metallic foreign body in the subject's neck. We experimentally demonstrate that the use of a non-slice-selective magnetization transfer contrast (MTC) pulse increases the degree of pseudostenosis, whereas slice-selective MTC does not. Selective MR angiography demonstrating this phenomenon was also performed. We then report a case that exhibited this phenomenon. We conclude that the magnetic field inhomogeneity induced by metallic material causes the non-slice-selective MTC pulse to act as a local presaturation pulse. Selective MR angiography using this phenomenon can be applied on varieties of MR scanners from different vendors.

Adult↗

PubMed1997

A model for image formation and image quality prediction in diagnostic radiology.

A computer program modelling the formation of radiological images and predicting values of physical quantities that determine diagnostic image quality has been developed. The quantities are the modulation transfer function (MTF), the noise power spectrum (NPS), and the detective quantum efficiency (DQE) associated with signal to noise ratio (SNR). The program is based on mathematical models that describe the effects of x-ray interactions with the imaged object and the image detector as well as phenomena concerning the optical signal propagation within the detector. All data on x-ray effects necessary for computer calculations were derived from published work whereas optical data were determined in our laboratory using experimental techniques. Model predictions were compared with direct quality measurements performed after image formation, on the image itself.

Computer Simulation↗

PubMed2006

Effective cross sections for production of single-strand breaks in plasmid DNA by 0.1 to 4.7 eV electrons.

We determined effective cross sections for production of single-strand breaks (SSBs) in plasmid DNA [pGEM 3Zf(-)] by electrons of 10 eV and energies between 0.1 and 4.7 eV. After purification and lyophilization on a chemically clean tantalum foil, dry plasmid DNA samples were transferred into a high-vacuum chamber and bombarded by a monoenergetic electron beam. The amount of the circular relaxed DNA in the samples was separated from undamaged molecules and quantified using agarose gel electrophoresis. The effective cross sections were derived from the slope of the yield as a function of exposure and had values in the range of 10(-15)- 10(-14) cm2, giving an effective cross section of the order of 10(-18) cm2 per nucleotide. Their strong variation with incident electron energy and the resonant enhancement at 1 eV suggest that considerable damage is inflicted by very low-energy electrons to DNA, and it indicates the important role of pi* shape resonances in the bond-breaking process. Furthermore, the fact that the energy threshold for SSB production is practically zero implies that the sensitivity of DNA to electron impact is universal and is not limited to any particular energy range.

Computer Simulation↗

PubMed2003

MRI feedback temperature control for focused ultrasound surgery.

A temperature feedback controller routine using a physical model for temperature evolution was developed for use with focused ultrasound surgery. The algorithm for the controller was a multi-input, single-output linear quadratic regulator (LQR) derived from Pennes' bioheat transfer equation. The controller was tested with simulated temperature data that had the same characteristics as those obtained with magnetic resonance imaging (MRI). The output of the controller was the appropriate power level to be used by the transducer. Tissue parameters estimated prior to the simulated treatments were used to determine the controller parameters. The controller performance was simulated in three dimensions with varying system parameters, and sufficient temperature tracking was achieved. The worst-case overshoot was 7 degrees C and the steady-state error was 5 degrees C. The simulated behaviour of the controller suggests satisfactory performance and that the controller may be useful in controlling the power output during MRI-monitored ultrasound surgery.

Computer Simulation↗

PubMed1996

Perfusion corrections for ultrasonic heating in nonperfused media.

The linear bio-heat transfer equation proposed by Pennes is widely used to predict temperature rise in perfused media. In this article, a mathematical relationship between the predicted temperature increase under perfused and nonperfused conditions is derived based on an analysis of the Pennes equation. The perfused temperature at time t and position r, Tperf(r,t) can be calculated from the unperfused temperature history Tunperf(r,t) and the time constant for perfusion, tau: [formula: see text] When the full nonperfused temperature history is not available, a simpler approximate method of estimating the perfused temperature is also suggested, requiring only a knowledge of the time constant for perfusion. Results are given showing the effects of perfusion after different exposure times for a range of beamwidths and perfusion time constants.

Algorithms↗

PubMed2006

The role of hydration in the distribution of free radical trapping in directly ionized DNA.

The purpose of this study was to elucidate the role of hydration (Gamma) in the distribution of free radical trapping in directly ionized DNA. Solid-state films of pUC18 (2686 bp) plasmids were hydrated to Gamma in the range 2.5 < or = Gamma < or = 22.5 mol water/mol nucleotide. Free radical yields, G(Sigmafr), measured by EPR at 4 K are seen to increase from 0.28 +/- 0.01 micromol/J at Gamma = 2.5 to 0.63 +/- 0.01 micromol/J at Gamma= 22.5, respectively. Based on a semi-empirical model of the free radical trapping events that follow the initial ionizations of the DNA components, we conclude that two-thirds of the holes formed on the inner solvation shell (Gamma < 10) transfer to the sugar-phosphate backbone. Likewise, of the holes produced by direct ionization of the sugar-phosphate, about one-third are trapped by deprotonation as neutral sugar-phosphate radical species, while the remaining two-thirds are found to transfer to the bases. This analysis provides the best measure to date for the probability of hole transfer (approximately 67%) into the base stack. It can thus be predicted that the distribution of holes formed in fully hydrated DNA at 4 K will be 78% on the bases and 22% on the sugar-phosphate. Adding the radicals due to electron attachment (confined to the pyrimidine bases), the distribution of all trapped radicals will be 89% on the bases and 11% on the sugar-phosphate backbone. This prediction is supported by partitioning results obtained from the high dose-response curves fitted to the two-component model. These results not only add to our understanding of how the holes redistribute after ionization but are also central to predicting the yield and location of strand breaks in DNA exposed to the direct effects of ionizing radiation.

Computer Simulation↗

PubMed2005

Temperature rises in the crystalline lens from focal irradiation.

Many types of ophthalmic instruments produce a concentrated focal irradiance in the lens. Instruments that illuminate large areas of the retina-known as "Maxwellian-view," are but one example, and there are concerns about the potential hazards associated with this optical system. The transfer of the heat generated in the human eye in Maxwellian-view illumination or similar focal-beam situations was simulated using a mathematical model to determine the temperature elevations induced in the human eye. The maximum temperature rise in the lens region was examined to quantitatively assess the potential thermal hazard to the lens. It was shown that Maxwellian-view illumination or similar focal-beam situations can cause thermal injury to the lens under certain conditions, and that this hazard is greater for incident wavelengths of about 320-420 nm than for longer wavelengths. The risk of thermal injury increases as exposure duration increases, and the risk tends to increase as the beam waist diameter or Maxwellian-view angle decreases.

Body Temperature↗

PubMed1976

Influence of heavy ions on the transforming activity of DNA.

Changes in functional activity following treatment of DNA with heavy ions were analysed by transformation assay. Biological response to exposure to charged particles, 10B, 12C, and 22Ne, was evaluated by the extent of inactivation of ability of DNA to transfer the genetic marker of tryptophane independence. The possibility of protecting the biological activity of DNA was studied using a conventional protector, cysteamine hydrochloride, or the preparation cytriphos, synthesized at the Institute of Radiobiology and Radiation Hygiene, Sofia. Dried samples of donor DNA isolated from a Bacillus subtilis prototroph strain were exposed to doses of 50 krad to 1 Mrad. For the three types of charged particles used, dose response of the inactivation process was defined by an exponential function. Comparison of response curves for the three types of radiation showed the effect to be dependent on LET, being highest for 10B and lowest for 22Ne. In all three cases, addition of a protective substance failed to produce any change in the biological effect observed.

Bacillus subtilis↗

PubMed2004

Exciton exciton annihilation dynamics in chromophore complexes. II. Intensity dependent transient absorption of the LH2 antenna system.

Using the multiexciton density matrix theory of excitation energy transfer in chromophore complexes developed in a foregoing paper [J. Chem. Phys. 118, 746 (2003)], the computation of ultrafast transient absorption spectra is presented. Beside static disorder and standard mechanisms of excitation energy dissipation the theory incorporates exciton exciton annihilation (EEA) processes. To elucidate signatures of EEA in intensity dependent transient absorption data the approach is applied to the B850 ring of the LH2 found in rhodobacter sphaeroides. As main indications for two-exciton population and resulting EEA we found (i) a weakening of the dominant single-exciton bleaching structure in the transient absorption, and (ii) an intermediate suppression of long-wavelength and short-wavelength shoulders around the bleaching structure. The suppression is caused by stimulated emission from the two-exciton to the one-exciton state and the return of the shoulders follows from a depletion of two-exciton population according to EEA. The EEA-signature survives as a short-wavelength shoulder in the transient absorption if orientational and energetic disorder are taken into account. Therefore, the observation of the EEA-signatures should be possible when doing frequency resolved transient absorption experiments with a sufficiently strongly varying pump-pulse intensity.

Absorption↗

PubMed2002

Alpha-particle-induced increases in the radioresistance of normal human bystander cells.

Numerous investigators have reported that direct exposure of cells to a low dose of ionizing radiation can induce a condition of enhanced radioresistance, i.e. a "radioadaptive" response. In this report, we investigated the hypothesis that a radioadaptive bystander effect may be induced in unirradiated cells by a transmissible factor(s) present in the supernatants of cells exposed to a low dose of alpha particles. Normal human lung fibroblasts (HFL-1) were irradiated with 1 cGy of alpha particles and their supernatants were transferred to unirradiated HFL-1 cells as a bystander cell model. Compared to directly irradiated cells that were not treated with supernatants from HFL-1 cells exposed to low-dose radiation, such treatment resulted in increased clonogenic survival after subsequent exposure to 10 and 19 cGy of alpha particles. Increases in protein levels of AP-endonuclease, a redox and DNA base excision repair protein, were found in the bystander cells, but not in directly irradiated cells. Supernatants from alpha-particle-irradiated cells were also found to increase the clonogenicity of unirradiated cells. These results, in conjunction with our earlier findings that supernatants from cells exposed to a low dose of alpha particles contain growth-promoting activity, suggest that this new bystander effect may be related to an increase in DNA repair and cell growth/cell cycle regulation.

Adaptation, Physiological↗

PubMed2006

Bystander-mediated genomic instability after high LET radiation in murine primary haemopoietic stem cells.

Communication between irradiated and unirradiated (bystander) cells can result in responses in unirradiated cells that are similar to responses in their irradiated counterparts. The purpose of the current experiment was to test the hypothesis that bystander responses will be similarly induced in primary murine stem cells under different cell culture conditions. The experimental systems used here, co-culture and media transfer, are similar in that they both restrict communication between irradiated and bystander cells to media borne factors, but are distinct in that with the media transfer technique, cells can only communicate after irradiation, and with co-culture, cells can communication before, during and after irradiation. In this set of parallel experiments, cell type, biological endpoint, and radiation quality and dose, were kept constant. In both experimental systems, clonogenic survival was significantly decreased in all groups, whether irradiated or bystander, suggesting a substantial contribution of bystander effects (BE) to cell killing. Genomic instability (GI) was induced under all radiation and bystander conditions in both experiments, including a situation where unirradiated cells were incubated with media that had been conditioned for 24h with irradiated cells. The appearance of delayed aberrations (genomic instability) 10-13 population doublings after irradiation was similar to the level of initial chromosomal damage, suggesting that the bystander factor is able to induce chromosomal alterations soon after irradiation. Whether these early alterations are related to those observed at later timepoints remains unknown. These results suggest that genomic instability may be significantly induced in a bystander cell population whether or not cells communicate during irradiation.

Animals↗

PubMed2006

Mechanism of the 15N(p,alpha)12C reaction at Ep=9.09-43.7 MeV.

The spectroscopic-factor amplitudes for the triton-cluster transfer are used in distorted wave born approximation (DWBA) analyses for the first six (12)C states, up to E(x)=17.76 MeV, in the reaction (15)N(p,alpha) for E(p)=9.09-43.7 MeV. Agreements are obtained for most (12)C states between the theoretically predicted spectroscopic factors (S) and both of experimental and theoretical forward integrated cross-section values (at E(p) approximately 43.7 MeV) and their sequence states with the same nuclear parameters. The theoretical spectroscopic factors failed to predict the transition strengths for the two (12)C states at 7.6542 and 17.76 MeV, while the DWBA predictions failed to reproduce the strengths of the three (12)C states at 7.6542, 14.083 and 17.76 MeV. This is probably, in the first case, due to the inclusion of other direct mechanisms and (or) to the multi-step processes in their mechanism, while for the second case, it is may be due to either the angular momentum mismatching effect or the choice of the optical parameters. The agreement between theoretical and experimental data for the first six investigated (12)C states indicate the success of the Cohen-Kurath wave-functions itself and their accuracy. They also indicate the success of the model of calculations of spectroscopic factors.

Carbon↗

PubMed2003

Bystander responses induced by low LET radiation.

Radiation-induced bystander responses are observed when cells respond to their neighbours being irradiated. Considerable evidence is now available regarding the importance of these responses in cell and tissue models. Most studies have utilized two approaches where either a media-transferable factor has been assessed or cells have been exposed to low fluences of charged particles, where only a few percent are exposed. The development of microbeams has allowed nontargeted responses such as bystander effects to be more carefully analysed. As well as charged particle microbeams, X-ray microprobes have been developed, and several groups are also developing electron microbeams. Using the Gray Cancer Institute soft X-ray microprobe, it has been possible to follow the response of individual cells to targeted low doses of carbon-characteristic soft X-rays. Studies in human fibroblasts have shown evidence of a significant radiation quality-dependent bystander effect, measured as chromosomal damage in the form of micronuclei which is radiation quality dependent. Other studies show that even under conditions when only a single cell is targeted with soft X-rays, significant bystander-mediated cell killing is observed. The observation of bystander responses with low LET radiation suggests that these may be important in understanding radiation risk from background levels of radiation, where cells observe only single electron track traversals. Also, the indirect evidence for these responses in vivo indicates that they may have a role to play in current radiotherapy approaches and future novel strategies involving modulating nontargeted responses.

Animals↗

PubMed2003

Comparisons of phosphorothioate with phosphate transfer reactions for a monoester, diester, and triester: isotope effect studies.

Phosphorothioate esters are sometimes used as surrogates for phosphate ester substrates in studies of enzymatic phosphoryl transfer reactions. To gain better understanding of the comparative inherent chemistry of the two types of esters, we have measured equilibrium and kinetic isotope effects for several phosphorothioate esters of p-nitrophenol (pNPPT) and compared the results with data from phosphate esters. The primary (18)O isotope effect at the phenolic group ((18)k(bridge)), the secondary nitrogen-15 isotope effect ((15)k) in the nitro group, and (for the monoester and diester) the secondary oxygen-18 isotope effect ((18)k(nonbridge)) in the phosphoryl oxygens were measured. The equilibrium isotope effect (EIE) (18)k(nonbridge) for the deprotonation of the monoanion of pNPPT is 1.015 +/- 0.002, very similar to values previously reported for phosphate monoesters. The EIEs for complexation of Zn(2+) and Cd(2+) with the dianion pNPPT(2-) were both unity. The mechanism of the aqueous hydrolysis of the monoanion and dianion of pNPPT, the diester ethyl pNPPT, and the triester dimethyl pNPPT was probed using heavy atom kinetic isotope effects. The results were compared with the data reported for analogous phosphate monoester, diester, and triester reactions. The results suggest that leaving group bond fission in the transition state of reactions of the monoester pNPPT is more advanced than for its phosphate counterpart pNPP, while alkaline hydrolysis of the phosphorothioate diester and triester exhibits somewhat less advanced bond fission than that of their phosphate ester counterparts.

Hydrolysis↗

PubMed2005

Absorbed fractions for alpha-particles in tissues of trabecular bone: considerations of marrow cellularity within the ICRP reference male.

UNLABELLED: Alpha-particles are of current interest in radionuclide therapy due to their short range and high rates of energy transfer to target tissues. Published values of alpha-particle absorbed fraction phi in the skeletal tissues, as needed for patient-specific dosimetry under the MIRD schema, do not generally account for its variation with particle energy or skeletal site. Furthermore, variations in alpha-particle absorbed fraction with marrow cellularity have yet to be fully considered. METHODS: In this study, a 3-dimensional (3D) chord-based radiation transport model (or 3D-CBIST) is presented, which combines (a) chord-based techniques for tracking alpha-particles across bone trabeculae, endosteum, and marrow cavities and (b) a spatial model of the marrow tissues that explicitly considers the presence of marrow adipocytes. Chord-length distributions are taken from a 44-y male subject (ICRP [International Commission on Radiological Protection] Reference Male) and are identical to those used currently for clinical dose estimates for beta-particle emitters. RESULTS: Values of phi(active marrow<--active marrow) given by the 3D-CBIST model are shown to be considerably lower than phi = 1.0 assumed under the ICRP Publication 30 and 2003 Eckerman bone models. For example, values of absorbed fraction for the self-dose to active bone marrow in the ribs, cervical vertebra, and parietal bone are 0.81, 0.80, and 0.55 for 6-MeV alpha-particles and are 0.74, 0.72, and 0.43 for 9-MeV alpha-particles, where each is evaluated at ICRP reference cellularities in the 3D-CBIST model (72%, 72%, and 42%, respectively, at age 25 y). CONCLUSION: Improvements in patient-specific dosimetry of skeletal tissues require explicit consideration of not only changes in target mass with variable patient marrow cellularity (i.e., active marrow) but also corresponding changes in values of the absorbed fraction. The data given in this study provide a more-firm basis for application of the MIRD schema to patient-specific dosimetry for newly developing therapies using alpha-particle emitters.

Adult↗