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J Medin

Publications and source records attributed to J Medin.

17 recordsLinked to original sources

Ferrous sulphate gel dosimetry and MRI for proton beam dose measurements.

Ferrous sulphate gel dosimetry has the potential for measurement of absorbed dose distributions in proton therapy. The chemical properties of the gel are altered according to the radiation dose and these changes can be evaluated in three dimensions using MRI. The purpose of this work was to investigate the properties of a ferrous gel used with clinical proton beams. The gel was irradiated with both monoenergetic and range-modulated proton beams. It was then evaluated using MRI. The depth dose by means of the 1/T1 distribution was studied and compared with data from a plane-parallel plate ionization chamber. 1/T1 was shown to be proportional to the dose at a mean proton energy of approximately 90 MeV. The dose response was no different from that obtained using photon beams. However, on normalization at the entrance, the relative 1/T1 at the Bragg peak was 15-20% lower than the corresponding ionization chamber data for the monoenergetic proton beam. Better agreement was found for the modulated beam, but with significant differences close to the distal edge of the 1/T1 distribution. The change in sensitivity with depth was explained by means of a linear energy transfer dependence. This property was further studied using Monte Carlo methods.

Calibration

Fast 2D phantom dosimetry for scanning proton beams.

A quality control system especially designed for dosimetry in scanning proton beams has been designed and tested. The system consists of a scintillating screen (Gd2O2S:Tb), mounted at the beam-exit side of a phantom, and observed by a low noise CCD camera with a long integration time. The purpose of the instrument is to make a fast and accurate two-dimensional image of the dose distribution at the screen position in the phantom. The linearity of the signal with the dose, the noise in the signal, the influence of the ionization density on the signal, and the influence of the field size on the signal have been investigated. The spatial resolution is 1.3 mm (1 s.d.), which is sufficiently smaller than typical penumbras in dose distributions. The measured yield depends linearly on the dose and agrees within 5% with the calculations. In the images a signal to noise ration (signal/1 s.d.) of 10(2) has been found, which is in the same order of magnitude as expected from the calculations. At locations in the dose distribution possessing a strong contribution of high ionization densities (i.e., in the Bragg peak), we found some quenching of the light output, which can be described well by existing models if the beam characteristics are known. For clinically used beam characteristics such as a Spread Out Bragg peak, there is at most 8% deviation from the NACP ionization chamber measurements. The conclusion is that this instrument is a useful tool for quick and reliable quality control of proton beams. The long integration-time capabilities of the system make it worthwhile to investigate its applicability in scanning proton beams and other dynamic treatment modalities.

Brachytherapy

Monte Carlo calculated stopping-power ratios, water/air, for clinical proton dosimetry (50-250 MeV).

Calculations of stopping power ratios, water to air, for the determination of absorbed dose to water in clinical proton beams using ionization chamber measurements have been undertaken using the Monte Carlo method. A computer code to simulate the transport of protons in water (PETRA) has been used to calculate sw.air-data under different degrees of complexity, ranging from values based on primary protons only to data including secondary electrons and high-energy secondary protons produced in nonelastic nuclear collisions. All numerical data are based on ICRU 49 proton stopping powers. Calculations using primary protons have been compared to the simple continuous slowing-down approximation (c.s.d.a.) analytical technique used in proton dosimetry protocols, not finding significant differences that justify elaborate Monte Carlo simulations except beyond the mean range of the protons (the far side of the Bragg peak). The influence of nuclear nonelastic processes, through the detailed generation and transport of secondary protons, on the calculated stopping-power ratios has been found to be negligible. The effect of alpha particles has also been analysed, finding differences smaller than 0.1% from the results excluding them. Discrepancies of up to 0.6% in the plateau region have been found, however, when the production and transport of secondary electrons are taken into account. The large influence of nonelastic nuclear interactions on proton depth-dose distributions shows that the removal of primary protons from the incident beam decreases the peak-to-plateau ratio by a large factor, up to 40% at 250 MeV. It is therefore emphasized that nonelastic nuclear reactions should be included in Monte Carlo simulations of proton beam depth-dose distributions.

Air

Proton dosimetry intercomparison.

BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

Calibration

Phantom study of chest radiography with storage phosphor, selenium, and film-screen systems.

PURPOSE: Chest radiographs from 3 digital systems--2 based on luminescent phosphors and one on selenium--and a conventional film-screen system were evaluated and compared. MATERIAL AND METHODS: Computed radiography (CR) has for the past years been dominated by a single manufacturer, but now several systems have been marketed. Using a chest phantom and, as test objects, 2 simulated tumours for the lung and mediastinum, respectively, and one object simulating pulmonary lines, a total of 400 exposures were made, 100 on each system. The test objects were placed randomly with a ratio of presence/absence of each object of about 50. Six radiologists participated, 2 residents and 4 staff members. A receiver operating characteristics (ROC) analysis was performed with construction of curves, and the difference between the curves was estimated with a 2-tailed paired t-test. RESULTS AND CONCLUSION: The selenium-based system performed significantly better for pulmonary line detection than all the other systems, and better than one storage phosphor system for the lung "tumour" (p < 0.05), while one storage phosphor system was slightly better than the other in diagnosing all 3 test objects. The score for the film-screen system was only average.

Humans

Radiological videoconferencing in Sweden.

For the last four years there has been a videoconferencing link between the Karlskrona hospital and the university hospital of Lund. Because of a need to transmit angiographic films, its use has been gradually expanded to become an everyday routine, used for both elective and emergency examinations. During 1994 and 1995, 1121 cases were examined over the video link. Apart from 156 normal cases all were discussed with surgeons, most at 96 weekly conferences but approximately 50 at conferences taking place as soon as possible after the examination. Assuming that an average of three doctors attended the conferences before the video link was available, this amounts to a saving of 3 x 8 h in travelling time per videoconference. The average salary was 300 SKr/h and train tickets cost a further 400 SKr per person. The cost of the ISDN connection was approximately 1800 SKr/conference. The net gain was thus about 6500 SKr per videoconference, without taking into account the work that could be done with the doctors still in Karlskrona after the conference.

Angiography

Faraday cup dosimetry in a proton therapy beam without collimation.

A Faraday cup in a proton beam can give an accurate measurement of the number of protons collected by the cup. It is shown that the collection efficiency with a proper design can be close to unity. To be able to calibrate an ionization chamber from such a measurement, as is recommended in some dosimetry protocols, the energy spectrum of the proton beam must be accurately known. This is normally not the case when the lateral beam extension is defined by collimators. Therefore a method for relating an ionization chamber measurement in an uncollimated beam to the total number of protons in the beam has been developed and is described together with experimental results from calibrating an ionization chamber using this method in the therapeutic beam in Uppsala. This method is applicable to ionization chambers of any shape and the accuracy is estimated to be 1.6% (1 SD).

Biophysical Phenomena

Ionization chamber dosimetry of proton beams using cylindrical and plane parallel chambers. Nw versus Nk ion chamber calibrations.

Determinations of the absorbed dose in a 170 MeV proton beam have been performed using seven ionization chambers of different types: five cylindrical (two FWT IC-18 and three NE-2571, of which one was modified to have the central electrode made of graphite) and two plane parallel (NACP-02 and Roos FK-6). The ionization was converted into absorbed dose in the proton beam according to the generalization of the formalism provided by the IAEA Code of Practice (TRS 277), which enables the use of the same equations for all kinds of beam used in radiotherapy. The absorbed dose obtained with the two IC-18 chambers, a chamber type commonly used as a reference in proton beams, was up to 1.5% lower than that obtained with the Farmer NE-2571 chamber, which was used as the reference in this work when calibration factors in terms of NK were used. To investigate this difference, experimental ND factors for six chambers (the two IC-18 chambers, the NACP-02, the FK-6 and two of the NE-2571 chambers) were determined in a high-energy electron beam. The procedure commonly recommended for plane parallel ion chambers was used for all the chambers, using the same reference chamber, a Farmer NE-2571. In the 170 MeV proton beam all the ND factors yielded consistent absorbed dose determinations within the estimated experimental uncertainties. This finding calls into question the value of the product kattkm for the IC-18 chamber given by the IAEA Code of Practice used in this comparison, and points at possible chamber to chamber variations that theoretical kattkm factors cannot predict. The investigations enabled the determination of the Pwall(60Co) factor of the Roos FK-6 plane parallel chamber, yielding 1.003 +/- 0.5%, and a correction for the effect of the aluminium central electrode of NE-2571 chambers in proton beams, equal to 1.003 +/- 0.4%. Two of the chambers (the plane parallel FK-6 and the modified cylindrical NE-2571) were provided with calibration factors in terms of absorbed dose to water, Nw, at the quality of 60Co by the Primary Standard Dosimetry Laboratory in Germany (PTB). Using the Nw formalism excellent agreement was found with the determination based on the experimental ND, giving support to the implementation of the NW procedure in therapeutic proton beams.

Humans

Peroxisome proliferator-activated receptors and lipid metabolism.

PPARs are nuclear hormone receptors which, like the retinoid, thyroid hormone, vitamin D, and steroid hormone receptors, are ligand-activated transcription factors mediating the hormonal control of gene expression. Two lines of evidence indicate that PPARs have an important function in fatty acid metabolism. First, PPARs are activated by hypolipidemic drugs and physiological concentrations of fatty acids, and second, PPARs control the peroxisomal beta-oxidation pathway of fatty acids through transcriptional induction of the gene encoding the acyl-CoA oxidase (ACO), which is the rate-limiting enzyme of the pathway. Furthermore, the PPAR signaling pathway appears to converge with the 9-cis retinoic acid receptor (RXR) signaling pathway in the regulation of the ACO gene because heterodimerization between PPAR and RXR is essential for in vitro binding to the PPRE and because the strongest stimulation of this gene is observed when both receptors are exposed simultaneously to their activators. Thus, it appears that PPARs are involved in the 9-cis retinoic acid signaling pathway and that they play a pivotal role in the hormonal control of lipid metabolism.

Acyl-CoA Oxidase

Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers.

The nuclear hormone receptors called PPARs (peroxisome proliferator-activated receptors alpha, beta, and gamma) regulate the peroxisomal beta-oxidation of fatty acids by induction of the acyl-CoA oxidase gene that encodes the rate-limiting enzyme of the pathway. Gel retardation and cotransfection assays revealed that PPAR alpha heterodimerizes with retinoid X receptor beta (RXR beta; RXR is the receptor for 9-cis-retinoic acid) and that the two receptors cooperate for the activation of the acyl-CoA oxidase gene promoter. The strongest stimulation of this promoter was obtained when both receptors were exposed simultaneously to their cognate activators. Furthermore, we show that natural fatty acids, and especially polyunsaturated fatty acids, activate PPARs as potently as does the hypolipidemic drug Wy 14,643, the most effective activator known so far. Moreover, we discovered that the synthetic arachidonic acid analogue 5,8,11,14-eicosatetraynoic acid is 100 times more effective than Wy 14,643 in the activation of PPAR alpha. In conclusion, our data demonstrate a convergence of the PPAR and RXR signaling pathways in the regulation of the peroxisomal beta-oxidation of fatty acids by fatty acids and retinoids.

Animals

Mutational analysis of active site residues of human adenosine deaminase.

Adenosine deaminase was overexpressed in a baculovirus system. The pure recombinant and native enzymes were identical in size, Zn2+ content, and activity. Five amino acids, in proximity to the active site, were replaced by mutagenesis. The altered enzymes were purified to homogeneity and compared to wild-type adenosine deaminase with respect to zinc content, enzymatic activity, and kinetic parameters. All but one of the alterations produced significant activity perturbations. Replacement of Cys262 produced a protein that retained at least 30-40% of wild-type activity. In contrast, replacements of His17, His214, His238, and Glu217 resulted in dramatic losses of enzyme activity. None of these mutants exhibited large variations in Km. The proteins produced from alterations of amino acids implicated in metal coordination were slightly activated by inclusion of Zn2+ throughout purification. These experiments confirm that in the active enzyme Zn2+ plays a critical role in catalysis, that a histidine or glutamate residue plays a mechanistic role in the hydrolytic deamination step, and that cysteine is not involved in the catalytic mechanism of adenosine deaminase. These data support the roles for these amino acid residues suggested from the x-ray structure of murine adenosine deaminase (Wilson, D. K., Rudolf, F. B., and Quicho, F. A. (1991) Science 252, 1278-1284).

Adenosine Deaminase

Xenopus peroxisome proliferator activated receptors: genomic organization, response element recognition, heterodimer formation with retinoid X receptor and activation by fatty acids.

Peroxisome proliferator activated receptors are ligand activated transcription factors belonging to the nuclear hormone receptor superfamily. Three cDNAs encoding such receptors have been isolated from Xenopus laevis (xPPAR alpha, beta, and gamma). Furthermore, the gene coding for xPPAR beta has been cloned, thus being the first member of this subfamily whose genomic organization has been solved. Functionally, xPPAR alpha as well as its mouse and rat homologs are thought to play an important role in lipid metabolism due to their ability to activate transcription of a reporter gene through the promoter of the acyl-CoA oxidase (ACO) gene. ACO catalyzes the rate limiting step in the peroxisomal beta-oxidation of fatty acids. Activation is achieved by the binding of xPPAR alpha on a regulatory element (DR1) found in the promoter region of this gene, xPPAR beta and gamma are also able to recognize the same type of element and are, as PPAR alpha, able to form heterodimers with retinoid X receptor. All three xPPARs appear to be activated by synthetic peroxisome proliferators as well as by naturally occurring fatty acids, suggesting that a common mode of action exists for all the members of this subfamily of nuclear hormone receptors.

Acyl-CoA Oxidase

Constraints of the multiple-scattering theory of Molière in Monte Carlo simulations of the transport of charged particles.

The breakdown of Molière's multiple-scattering theory for short pathlengths occurring during Monte Carlo simulations with charged particles is demonstrated. It has been found that in certain conditions where the theory is assumed to be valid, significant distortions of the angular distribution occur that make the sampling of the polar angle questionable in numerous steps of Monte Carlo simulations. The limits of the theory have been investigated, both using a large number of terms in the Molière's series and using steps of Molière's theory where 1/B expansions are not involved. At B = 4.5 the commonly accepted 3-term series expansion yields differences up to +/- 6% compared with the evaluation of the complete Molière angular distribution, and up to 7 terms in the series are needed in order to achieve agreement within +/- 2%. One percent agreement requires B = 10. Numerical values of the full distribution are given in terms of Molière's parameters B and reduced angle theta. By using the general dependence of the distribution results are valid for both electron and proton Monte Carlo simulations in any material.

Biophysical Phenomena