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Biomedical subjects

P M DeLuca

Publications and source records attributed to P M DeLuca.

At least 19 recordsLinked to original sources

The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working group regarding quantities and units.

This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and definition of the involved quantities and units. The isoeffective dose, as introduced here for radiation therapy applications, is the dose that delivered under reference conditions would produce the same clinical effects as the actual treatment in a given system, all other conditions being identical. It is expressed in Gy. The reference treatment conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week. The isoeffective dose D(IsoE) is the product of the physical quantity absorbed dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor that takes into account all factors that could influence the clinical effects like dose per fraction, overall time, radiation quality (RQ), biological system and effects. The numerical value of W(IsoE) is selected by the radiation-oncology team for a given patient (or treatment protocol). It is part of the treatment prescription. Evaluation of the influence of RQ on W(IsoE) raises complex problems because of the clinically significant RBE variations with biological effect (late vs. early) and position in depth in the tissues which is a problem specific to ion-beam therapy. Comparison of the isoeffective dose with the equivalent dose frequently used in proton- and ion-beam therapy is discussed.

Heavy Ion Radiotherapy↗

Glancing-angle ion enhanced surface diffusion on gaAs(001) during molecular beam epitaxy.

We describe the effects of glancing incidence 3-4 keV Ar ion bombardment on homoepitaxial growth on vicinal GaAs(001). The average adatom lifetime on surface terraces, measured during growth using specular ion scattering, decreased monotonically with increasing ion current density. The results indicated that surface diffusivity was increased by the ions. The ion beam also suppressed growth oscillations and decreased the film surface roughness. This indicates a change from two-dimensional island nucleation to step-flow growth due to increased adatom surface diffusivity. A simple model, involving direct momentum transfer from ions to adatoms, is shown to be consistent with the measured enhanced diffusion.

Journal Article↗

Experimental kerma coefficients and dose distributions of C, N, O, Mg, Al, Si, Fe, Zr, A-150 plastic, Al203, AlN, SiO2 and ZrO2 for neutron energies up to 66 MeV.

Low-pressure proportional counters (LPPCs) with walls made from the elements C, Mg, Al, Si, Fe and Zr and from the chemical compounds A-150 plastic, AlN, Al2O3, SiO2 and ZrO2 were used to measure neutron fluence-to-kerma conversion coefficients at energies up to 66 MeV. The LPPCs served to measure the absorbed dose deposited in the gas of a cavity surrounded by the counter walls that could be converted to the absorbed dose to the wall on the basis of the Bragg-Gray cavity theory. Numerically the absorbed doses to the walls were almost equal to the corresponding kerma values of the wall materials. The neutron fluence was determined by various experimental methods based on the reference cross sections of the 1H(n, p) scattering and/or the 238U(n, f) reactions. The measurements were performed in monoenergetic neutron fields of energies of 5 MeV, 8 MeV, 15 MeV and 17 MeV and in polyenergetic neutron beams with prominent peaks of energies of 34 MeV, 44 MeV and 66 MeV. For the measurements in the polyenergetic neutron beams, significant corrections for the contributions of the non peak energy neutrons were applied. The fluence-to kerma conversion coefficients of N and O were determined using the difference technique applied with matched pairs of LPPCs made from a chemical compound and a pure element. This paper reports experimental fluence-to-kerma conversion coefficient values of eight elements and four compounds measured for seven neutron energies, and presents a comparison with data from previous measurements and theoretical predictions. The distributions of the absorbed dose as a function of the lineal energy were measured for monoenergetic neutrons or, for polyenergetic neutron fields, deduced by applying iterative unfolding procedures in order to subtract the contributions from non-peak energy neutrons. The dose distributions provide insight into the neutron interaction processes.

Aluminum↗

Longitudinal relaxation times of 129Xe in rat tissue homogenates at 9.4 T.

Longitudinal relaxation times of 129Xe were measured in homogenates of rat brain, kidney, liver, and lung at varying oxygenation levels as a means to assess the feasibility of magnetic resonance (MR) imaging of tissue using laser-polarized (LP) 129Xe as the signal source. The measured relaxation times ranged from 4.4 +/- 0.4 sec in deoxygenated lung homogenate to 22 +/- 2 sec in deoxygenated brain homogenate. When the LP gas is introduced to the subject via inhalation, these relaxation times are long enough to allow accumulation and subsequent MR imaging of LP 129Xe in tissues. Imaging of dissolved LP 129Xe will yield an intrinsic signal-to-noise ratio (SNR) that is approximately 3% of the proton intrinsic SNR. This relatively low intrinsic SNR is expected to be adequate for some tracer applications. T1 of 129Xe was found to depend on the oxygenation level of the tissue, and the effect of oxygenation is likely dependent on the amount of hemoglobin in the tissue homogenate.

Animals↗

Nuclear data for radiotherapy: presentation of a new ICRU report and IAEA initiatives.

An ICRU report entitled "Nuclear Data for Neutron and Proton Radiotherapy and for Radiation Protection" is in preparation. The present paper presents an overview of this report, along with examples of some of the results obtained for evaluated nuclear cross sections and kerma coefficients. These cross sections are evaluated using a combination of measured data and the GNASH nuclear model code for elements of importance for biological, dosimetric, beam modification and shielding purposes. In the case of hydrogen both R-matrix and phase-shift scattering theories are used. In the report neutron cross sections and kerma coefficients will be presented up to 150 MeV and proton cross sections up to 250 MeV. An IAEA Consultants' Meeting was also convened to examine the "Status of Nuclear Data needed for Radiation Therapy and Existing Data Development Activities in Member States". Recommendations were made regarding future endeavours.

Models, Theoretical↗

A consistent set of neutron kerma coefficients from thermal to 150 MeV for biologically important materials.

Neutron cross sections for nonelastic and elastic reactions on a range of elements have been evaluated for incident energies up to 150 MeV. These cross sections agree well with experimental cross section data for charged-particle production as well as neutron and photon production. Therefore they can be used to determine kerma coefficients for calculations of energy deposition by neutrons in matter. Methods used to evaluate the neutron cross sections above 20 MeV, using nuclear model calculations and experimental data, are described. Below 20 MeV, the evaluated cross sections from the ENDF/B-VI library are adopted. Comparisons are shown between the evaluated charged-particle production cross sections and measured data. Kerma coefficients are derived from the neutron cross sections, for major isotopes of H, C, N, O, Al, Si, P, Ca, Fe, Cu, W, Pb, and for ICRU-muscle, A-150 tissue-equivalent plastic, and other compounds important for treatment planning and dosimetry. Numerous comparisons are made between our kerma coefficients and experimental kerma coefficient data, to validate our results, and agreement is found to be good. An important quantity in neutron dosimetry is the kerma coefficient ratio of ICRU-muscle to A-150 plastic. When this ratio is calculated from our kerma coefficient data, and averaged over the neutron energy spectra for higher-energy clinical therapy beams [three p (68) + Be beams, and a d (48.5) + Be beam], a value of 0.94 +/- 0.03 is obtained. Kerma ratios for water to A-150 plastic, and carbon to oxygen, are also compared with measurements where available.

Biophysical Phenomena↗

Direct determination of kerma for a d(48.5) + Be therapy beam.

An experimental determination of the neutron kerma ratio between muscle tissue and A-150 plastic was performed at the newly commissioned d(48.5)+ Be therapy facility in Detroit. Low-pressure proportional counters with separate walls made from A-150 plastic, graphite, zirconium oxide and zirconium served to measure ionization yield spectra. The absorbed dose in the wall of each counter was determined and rendered the A-150 and carbon kerma directly, whilst that for oxygen was deduced from differences between the matched metal oxide and metal pair. This enabled the evaluation of an effective kerma ratio as a function of radiation field size and hydrogenous filtration. Although filtration was observed to harden the beam, the application of a single kerma ratio for the various irradiation conditions investigated was found to be appropriate. A neutron kerma ratio of 0.90+/-0.03 was assessed for the Detroit facility, which is lower at the 1sigma level than the 0.95 currently recommended in the dosimetry protocol for high-energy neutron beams.

Carbon↗

A double mirror W/C multilayer monochromator for radiation biology applications.

A double-mirror multilayer monochromator was developed for the purpose of irradiating live cell cultures at the Synchrotron Radiation Center, University of Wisconsin-Madison. The monochromator is designed for the soft x-ray region with photon energies between 270 and 2400 eV. Multilayer mirrors with 55 bilayers of W/C and a bilayer spacing of d = 3.0 nm are sputter deposited on Si substrates. By proper masking of the sputtering sources, variation in the bilayer spacing over the area of the mirror is minimized. The uniformity of the bilayer spacing was measured to be delta d/d < 1%, over the 75 mm x 25 mm area of the mirrors. The reflectivity was measured as a function of energy to determine the integrated reflectivity and evaluate the contribution of the specular reflection and higher orders to the monochromatic beam. The use of suitable filters with a Si(Li) detector allows determination of the spectral output of the monochromator. The output power of the monochromator between 270 and 2400 eV is measured. The resolution of the monochromator is delta lambda/lambda = 0.04. Applications of the monochromator to radiation biology are discussed.

Cells, Cultured↗

Synchroton-produced ultrasoft X rays: equivalent cell survival at the isoattenuating energies 273 eV and 860 eV.

In this paper we report on survival of Chinese hamster V79 and mouse C3H 10T1/2 cells after irradiation with synchrotron-produced 273 eV and 860 eV ultrasoft X rays. These two energies, which are available by multilayer monochromatization of the synchrotron output spectrum, exhibit equal attenuation within living cells. Such an isoattenuating energy pair allows the direct examination of how biological effectiveness varies with the energy of the ultrasoft X rays. In comparing survival results, we find similar biological effectiveness of these two energies for both the C3H 10T1/2 and the V79 cells. These results are not consistent with previous findings of increasing RBE with decreasing ultrasoft X-ray energies. In addition, after correcting for mean nuclear dose based on measurements of cell thickness obtained with confocal microscopy, we find no significant differences in survival between the two ultrasoft X-ray energies and 250 kVp X rays. These results suggest that RBE does not increase with decreasing energy of ultrasoft X rays between 860 eV and 273 eV. The possible impact of our results on past results for ultrasoft X rays is discussed.

Animals↗

A comparison of cytotoxicity after whole- or partial-cell irradiation with synchrotron-produced ultrasoft X rays.

We introduce a method which allows partial-volume irradiation of live cells using synchrotron-produced ultrasoft X rays and micro-fabricated irradiation masks. The masks were made by X-ray lithography at the University of Wisconsin Synchrotron Radiation Center, and they consist of 1.85-microm-wide stripes of gold 1.35 microm apart plated onto thin silicon nitride membranes. When placed adjacent to Mylar on which live cells are plated, these masks allow cells to be irradiated in a striped pattern with dimensions much smaller than the cell nuclei. Using 1340 eV synchrotron-produced X rays, we compare the survival of cells subjected to uniform irradiation and cells subjected to partial-volume irradiation. Our results show that, at equal mean dose to the nucleus (i.e. equal total energies deposited), survival is not statistically different for the two treatments over a wide range of doses. Thus imparting equal energies to smaller intranuclear volumes does not appear to enhance cell killing.

Animals↗

Response of thermoluminescent lithium fluoride (TLD-100) to photon beams of 275, 400, 500, 600, 730, 900, 1200, 1500, and 2500 eV.

LiF:Mg,Ti (TLD-100) extruded ribbons and cleaved crystals were exposed to monoenergetic photons of 275-2550 eV energy to determine their potential usefulness as radiation dosimeters for radiobiology experiments at these energies. The radiation source was synchrotron radiation from the 1 GeV electron storage ring, Aladdin. The authors report TLD response and glow curves for He- and air-annealed dosimeters. The undesirable effects of air annealing increase with decreasing photon penetration in the dosimeter. Under certain experimental conditions, UV radiation produced anomalous bleaching of high-temperature traps. The crystals and the chips presented a supralinear response, Supralinearity factors were determined to be of the order of 1.5 for crystals, and 1.7 for the chips. The authors' results indicate that TLDs are a reliable means to monitor the total energy deposited in irradiated cells and are now used routinely for radiobiology cell irradiations.

Biophysical Phenomena↗

Lung calcium-dependent phospholipid-binding proteins: structure and function.

Distinct peptide maps of two rabbit lung Ca2(+)-dependent phospholipid-binding proteins (PLBPs), 36,000 and 33,000, were generated by cyanogen bromide (CNBr) cleavage, trypsin or Staphylococcus aureus V8 proteinase digestion. The amino acid sequence of a CNBr-cleaved peptide of the 36,000 PLBP was aligned to the amino terminus of human lipocortin I with more than 77% identity, but had no identity with the known amino terminal sequence of other known annexins. Partial amino acid sequence of a 33,000 PLBP peptide demonstrated a close (56%) relationship to endonexin II, human placental anticoagulant protein, and porcine intestine protein II, but shared only 32% identity with lipocortin I, 30% with lipocortin II. Antiserum generated against purified 36,000 PLBP reacted strongly with the 33,000 PLBP, but did not react with any other rabbit lung cytosolic proteins. Both PLBPs inhibited the phospholipase A2 reaction when dioleoyl phosphatidylcholine and phosphatidylglycerol vesicles or monolayers were used as substrates. In the vesicle assay, the phospholipase A2 reaction was inhibited at lower substrate phospholipid concentrations but not at nearly saturating substrate concentrations. In the monolayer assay, the phospholipid-binding proteins did not inhibit phospholipase A2 at a low phospholipid surface concentration of 3.8.10(-3) molecules/A2, but they did at higher surface concentrations between 1.1 x 10(-2) and 3.8 x 10(-2) molecules/A2. The inhibition of phospholipase A2 by rabbit lung phospholipid-binding proteins is most likely due to the prevention of penetration by phospholipase A2 into the interface, a requirement for the enzyme to act on the substrate.

Amino Acid Sequence↗

The use of a multichannel scaling method to detect radioactive species in spread monolayers.

This study describes a simple and inexpensive method for monitoring radioactive species spread as monolayers at the air/water interface. The combination of a discriminator and multichannel scalar counter with a personal computer functions to unify all measurements, to simplify the operational process and data acquisition, and to provide a real-time display of the data. Its use is demonstrated by following the hydrolysis of L-alpha-[1-14C]dioleoyl phosphatidylcholine by the enzyme, phospholipase A2, isolated from the porcine pancreas.

Animals↗

An in vivo technique for the measurement of bone blood flow in animals.

A new technique to measure the in vivo clearance of 41Ar from the bone mineral matrix is demonstrated following fast neutron production of 41Ar in bone via the 44Ca(n, alpha) reaction at 14.1 MeV. At the end of irradiation, the 41Ar activity is assayed with a Ge(Li) detector where sequential gamma-ray spectra are taken. Following full-energy peak integration, background and dead time correction, the activity of 41Ar as a function of time is determined. Results indicated that the Ar washout from bone in rats using this technique was approximately 16 ml (100 ml min)-1 and in agreement with other measurement techniques. For sheep the bone perfusion in the tibia was approximately 1.9 +/- 0.2 ml (100 ml min)-1.

Animals↗

Neutron field measurements at the Aladdin Synchrotron Light Source.

The neutron field near the inflector of the 800-MeV electron storage ring was studied. Photon-induced neutrons are produced by 100-MeV electrons bombarding the inflector during injection into the synchrotron ring. Neutrons were measured with moderating detectors made of 15 X 15 X 20 cm Lucite blocks and Au activation foils. Detector response was established with a Pu-Be neutron source and a 25.4-cm polyethylene sphere and Au foil detector. The neutron yield was 0.97 +/- 0.14 X 10(12) kJ-1. For 1.38 W of electron pulse power, the dose equivalent rate 1 m aside and 1 m above the inflector was 4.35 +/- 0.47 mu Sv s-1 and 3.13 +/- 0.23 mu Sv s-1, respectively. A measured dose equivalent transmission curve for polyethylene yielded an attenuation coefficient of 15.7 m-1.

Electrons↗

Survival of parenchymal hepatocytes irradiated with 14.3 MeV neutrons.

The purpose of these experiments was to estimate the RBE of neutrons for parenchymal hepatocytes as a function of neutron dose and to determine the ability of liver cells to repair potentially lethal damage (PLD) after neutron exposure. Hepatocyte reproductive survival was used as the biological end point in these studies and hepatocyte survival was determined with an in vivo transplantation clonogenic assay system. The 14.3 MeV neutrons were generated by a D-T reaction at the University of Wisconsin's gas target neutron source. The average neutron dose rate was 20 cGy/min. The estimated survival data for neutron exposed hepatocytes were best described by a single hit-single target model (i.e., n = 1.0) with a D0 = 170 cGy. In contrast to the results obtained with 60Co, hepatocytes exposed to neutrons are unable to repair PLD. The RBE value, when the reproductive survival was estimated 30 min after radiation exposure, is independent of neutron dose and equal to 1.6 +/- 0.1. In contrast, when the reproductive survival was estimated 24 hrs after radiation exposure, the RBE was found to increase with decreasing neutron dose and equal 4.2 +/- 0.5 at 50 cGy.

Animals↗