bluuebunny/crossref_metadata_2025 huggingface dataset:
The calibration of experimental self‐developing Gafchromic® HXR film for the measurement of radiation dose in computed tomography
Authors: Gorny K. R. , Leitzen S. L. , Bruesewitz M. R. , Kofler J. M. , Hangiandreou N. J. , McCollough C. H.
Published: April 2005

A prototype, self‐developing Gafchromic® HXR film has sensitivity an order of magnitude larger than that of the commercially available Gafchromic XR film used in interventional radiological applications. The higher sensitivity of the HXR film allows the possibility of acquisition of high‐resolution calibrated dose profiles within the diagnostic range of exposure levels, below . We employed a commercially available, optical flatbed scanner for digitization of the film and image analysis software to determine the response of the HXR films to ionizing radiation. Spatial uniformity and temporal repeatability of the flatbed scanner were determined and used in optimization of the digitization protocol. The HXR film postexposure density growth and sensitivity to ambient light were determined using multiple scans of two simultaneously exposed sheets, one stored in light‐tight conditions and the other continuously illuminated with white light. A calibrated step wedge of the HXR film was obtained by simultaneous irradiation of a portion of a film strip and a calibrated ionization chamber using a radiographic x‐ray tube with beam characteristics matched to a typical CT scanner ( Al HVL, ). Repeated digitization of the calibration film was used to determine the precision of the film response measurements. The precision, as measured by the standard deviation of multiple measurements, was better than 1% over the full dynamic range of film response. This precision was measured using exposures ranging from . This exposure range is highly relevant to x‐ray computed tomography. Preliminary radiation dose profiles demonstrate the utility of this technique.
Patient self‐attenuation and technologist dose in positron emission tomography
Authors: Zeff Benjamin W. , Yester Michael V.
Published: April 2005

Positron emission tomography (PET), with 511‐keV radiation and long patient‐uptake times, presents unique radiation safety concerns. This two‐part study considers aspects of PET radiation safety as they relate to PET suite design, dose to the public, and technologist occupational dose. In the first part of the study, the self‐attenuation of radiation by patients’ bodies was quantified. The radiation exposure was measured at three positions from 64 patients injected with fluorine‐18 fluorodeoxyglucose (FDG) during the uptake period. Compared with an in vitro control used as a point source, a significant decrease in exposure ( at 1 m) was observed due to nonuniform distribution of FDG and attenuation within the patients. The attenuation data are consistent with results from simulations [M. E. Phelps, “Comments and Perspectives,” J. Nucl. Med. 45, 1601 (2004)] that treat the body as a uniform, water‐filled cylinder. As distance is often the principal source of protection for 511‐keV radiation, the considerable self‐attenuation may allow for more compact PET suites. However, despite high patient self‐attenuation, shielding, and standard precautionary measures, PET technologist occupational doses can remain quite high . The second part of this study tracked the daily dose received by PET technologists. Close technologist‐patient interaction both during and following FDG administration, as much as , contribute to the high doses and point to the need for a more innovative approach to radiation protection for PET technologists.
Method for a detailed measurement of image intensity nonuniformity in magnetic resonance imaging
Authors: Wang Deming , Doddrell David M.
Published: April 2005

In magnetic resonance imaging (MRI), the MR signal intensity can vary spatially and this spatial variation is usually referred to as MR intensity nonuniformity. Although the main source of intensity nonuniformity arises from inhomogeneity of the coil acting as a receiver and/or transmitter, geometric distortion also alters the MR signal intensity. It is useful on some occasions to have these two different sources be separately measured and analyzed. In this paper, we present a practical method for a detailed measurement of the MR intensity nonuniformity. This method is based on the same three‐dimensional geometric phantom that was recently developed for a complete measurement of the geometric distortion in MR systems. In this paper, the contribution to the intensity nonuniformity from the geometric distortion can be estimated and thus, it provides a mechanism for estimation of the intensity nonuniformity that reflects solely the spatial characteristics arising from . Additionally, a comprehensive scheme for characterization of the intensity nonuniformity based on the new measurement method is proposed. To demonstrate the method, the intensity nonuniformity in a 1.5 T Sonata MR system was measured and is used to illustrate the main features of the method.
Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI
Authors: Choe Regine , Corlu Alper , Lee Kijoon , Durduran Turgut , Konecky Soren D. , Grosicka‐Koptyra Monika , Arridge Simon R. , Czerniecki Brian J. , Fraker Douglas L. , DeMichele Angela , Chance Britton , Rosen Mark A. , Yodh Arjun G.
Published: April 2005

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three‐dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.
Four‐dimensional computed tomography: Image formation and clinical protocol
Authors: Rietzel Eike , Pan Tinsu , Chen George T. Y.
Published: April 2005

Respiratory motion can introduce significant errors in radiotherapy. Conventional CT scans as commonly used for treatment planning can include severe motion artifacts that result from interplay effects between the advancing scan plane and object motion. To explicitly include organ/target motion in treatment planning and delivery, time‐resolved CT data acquisition (4D Computed Tomography) is needed. 4DCT can be accomplished by oversampled CT data acquisition at each slice. During several CT tube rotations projection data are collected in axial cine mode for the duration of the patient's respiratory cycle (plus the time needed for a full CT gantry rotation). Multiple images are then reconstructed per slice that are evenly distributed over the acquisition time. Each of these images represents a different anatomical state during a respiratory cycle. After data acquisition at one couch position is completed, x rays are turned off and the couch advances to begin data acquisition again until full coverage of the scan length has been obtained. Concurrent to CT data acquisition the patient's abdominal surface motion is recorded in precise temporal correlation. To obtain CT volumes at different respiratory states, reconstructed images are sorted into different spatio‐temporally coherent volumes based on respiratory phase as obtained from the patient's surface motion. During binning, phase tolerances are chosen to obtain complete volumetric information since images at different couch positions are reconstructed at different respiratory phases. We describe 4DCT image formation and associated experiments that characterize the properties of 4DCT. Residual motion artifacts remain due to partial projection effects. Temporal coherence within resorted 4DCT volumes is dominated by the number of reconstructed images per slice. The more images are reconstructed, the smaller phase tolerances can be for retrospective sorting. From phantom studies a precision of about for quasiregular motion and typical respiratory periods could be concluded. A protocol for 4DCT scanning was evaluated and clinically implemented at the MGH. Patient data are presented to elucidate how additional patient specific parameters can impact 4DCT imaging.
Quantitation of the reconstruction quality of a four‐dimensional computed tomography process for lung cancer patients
Authors: Lu Wei , Parikh Parag J. , El Naqa Issam M. , Nystrom Michelle M. , Hubenschmidt James P. , Wahab Sasha H. , Mutic Sasa , Singh Anurag K. , Christensen Gary E. , Bradley Jeffrey D. , Low Daniel A.
Published: April 2005

We have developed a four‐dimensional computed tomography (4D CT) technique for mapping breathing motion in radiotherapy treatment planning. A multislice CT scanner (slices) operated in ciné mode was used to acquire 12 contiguous slices in each couch position for 15 consecutive scans (rotation,between scans) while the patient underwent simultaneous quantitative spirometry measurements to provide a sorting metric. The spirometry‐sorted scans were used to reconstruct a 4D data set. A critical factor for 4D CT is quantifying the reconstructed data set quality which we measure by correlating the metric used relative to internal‐object motion. For this study, the internal air content within the lung was used as a surrogate for internal motion measurements. Thresholding and image morphological operations were applied to delineate the air‐containing tissues (lungs, trachea) from each CT slice. The Hounsfield values were converted to the internal air content. The relationship between the air content and spirometer‐measured tidal volumewas found to be quite linear throughout the lungs and was used to estimate the overall accuracy and precision of tidal volume‐sorted 4D CT. Inspection of the CT‐scan air content as a function of tidal volume showed excellent correlations (typically) throughout the lung volume. Because of the discovered linear relationship, the ratio of internal air content to tidal volume was indicative of the fraction of air change in each couch position. Theoretically, due to air density differences within the lung and in room, the sum of these ratios would equal 1.11. For 12 patients, the mean value was, indicating the high quality of spirometry‐based image sorting. The residual of a first‐order fit betweenandwas used to estimate the process precision. For all patients, the precision was better than 8%, with a mean value of. This quantitative analysis highlights the value of using spirometry as the metric in sorting CT scans. The 4D reconstruction provides the CT data required to measure the three‐dimensional trajectory of tumor and lung tissue during free breathing.
Monte Carlo simulation of a protontherapy platform devoted to ocular melanoma
Authors: Hérault J. , Iborra N. , Serrano B. , Chauvel P.
Published: April 2005

Patients with ocular melanoma have been treated since June 1991 at the medical cyclotron of the Centre Antoine Lacassagne (CAL). Positions and sizes of the ocular nozzle elements were initially defined based on experimental work, taking as a pattern functional existing facilities. Nowadays Monte Carlo (MC) calculation offers a tool to refine this geometry by adjusting size and place of beam modeling devices. Moreover, the MC tool is a useful way to calculate the dose and to evaluate the impact of secondary particles in the field of radiotherapy or radiation protection. Both LINAC and cyclotron producing x rays, electrons, protons, and neutrons are available in CAL, which suggests choosing MCNPX for its particle versatility. As a first step, the existing installation was input in MCNPX to check its aptitude to reproduce experimentally measured depth‐dose profile, lateral profile, output‐factor (OF), and absolute dose. The geometry was defined precisely and described from the last achromatic bending magnet of our proton beam line to the position of treated eyes. Relative comparisons of percentage depth‐dose and lateral profiles, performed between measured data and simulations, show an agreement of the order of 2% in dose and in range accuracy. These comparisons, carried out with and without beam‐modifying device, yield results compatible to the required precision in ocular melanoma treatments, as long as adequate choices are made on MCNPX input decks for physics card. Absolute dose and OF issued from calculations and measurements were also compared. Results obtained for these two kinds of data, carried out in the simplified situation of an unmodulated beam, indicate that MC calculation could effectively complement measurements. These encouraging results are a large source of motivation to promote further studies, first in a new design of the ocular nozzle, and second in the analysis of the influence of beam‐modifying devices attached to the final patient collimator, such as wedge or compensators, on dose values.
Investigation of using a power function as a cost function in inverse planning optimization
Authors: Xia Ping , Yu Naichang , Xing Lei , Sun Xuepeng , Verhey Lynn J.
Published: April 2005

The purpose of this paper is to investigate the use of a power function as a cost function in inverse planning optimization. The cost function for each structure is implemented as an exponential power function of the deviation between the resultant dose and prescribed or constrained dose. The total cost function for all structures is a summation of the cost function of every structure. When the exponents of all terms in the cost function are set to 2, the cost function becomes a classical quadratic cost function. An independent optimization module was developed and interfaced with a research treatment planning system from the University of North Carolina for dose calculation and display of results. Three clinical cases were tested for this study with various exponents set for tumor targets and sensitive structures. Treatment plans with these exponent settings were compared, using dose volume histograms. The results of our study demonstrated that using an exponent higher than 2 in the cost function for the target achieved better dose homogeneity than using an exponent of 2. An exponent higher than 2 for serial sensitive structures can effectively reduce the maximum dose. Varying the exponent from 2 to 4 resulted in the most effective changes in dose volume histograms while the change from 4 to 8 is less drastic, indicating a situation of saturation. In conclusion, using a power function with exponent greater than 2 as a cost function can effectively achieve homogeneous dose inside the target and/or minimize maximum dose to the critical structures.
Determination of maximum leaf velocity and acceleration of a dynamic multileaf collimator: Implications for 4D radiotherapy
Authors: Wijesooriya K. , Bartee C. , Siebers J. V. , Vedam S. S. , Keall P. J.
Published: April 2005

The dynamic multileaf collimator (MLC) can be used for four‐dimensional (4D), or tumor tracking radiotherapy. However, the leaf velocity and acceleration limitations become a crucial factor as the MLC leaves need to respond in near real time to the incoming respiration signal. The aims of this paper are to measure maximum leaf velocity, acceleration, and deceleration to obtain the mechanical response times for the MLC, and determine whether the MLC is suitable for 4D radiotherapy. MLC leaf sequence files, requiring the leaves to reach maximum acceleration and velocity during motion, were written. The leaf positions were recorded every , from which the maximum leaf velocity, acceleration, and deceleration were derived. The dependence on the velocity and acceleration of the following variables were studied: leaf banks, inner and outer leaves, MLC‐MLC variations, gravity, friction, and the stability of measurements over time. Measurement results show that the two leaf banks of a MLC behave similarly, while the inner and outer leaves have significantly different maximum leaf velocities. The MLC‐MLC variations and the dependence of gravity on maximum leaf velocity are statistically significant. The average maximum leaf velocity at the isocenter plane of the MLC ranged from 3.3 to . The acceleration and deceleration at the isocenter plane of the MLC ranged from 50 to and 46 to , respectively. Interleaf friction had a negligible effect on the results, and the MLC parameters remained stable with time. Equations of motion were derived to determine the ability of the MLC response to fluoroscopy‐measured diaphragm motion. Given the present MLC mechanical characteristics, 4D radiotherapy is feasible for up to 97% of respiratory motion. For the largest respiratory motion velocities observed, beam delivery should be temporarily stopped (beam hold).
Measuring blood flow velocities based on three image processing techniques
Authors: Zeng Yan‐Jun , Zhang Jian‐Hua , Shen Bing , Diao Yue , Xu Xiao‐Hu , Xu Hong
Published: April 2005

The classification of microcirculation can be based on the size of the capillary and the velocity of the blood flow. For each type of microcirculation, the ad hoc method is required to measure the blood flow velocity. In this paper, the correlation method is used to measure blood flow velocity in the small‐size capillary. The large‐size capillaries are classified into three types based on the blood velocities, say low‐speed, high‐speed, and unstable one. The template‐matching algorithm, the Fast Fourier Transform algorithm and a high‐speed video camera measurement are used to measure the blood velocities corresponding to those three types of large‐size capillary. It was shown by several experiments that fairly good results for different types of capillary may be obtained by using the proposed three image processing algorithms.
Enlarged longitudinal dose profiles in cone‐beam CT and the need for modified dosimetry
Authors: Mori Shinichiro , Endo Masahiro , Nishizawa Kanae , Tsunoo Takanori , Aoyama Takahiko , Fujiwara Hideaki , Murase Kenya
Published: April 2005

In order to examine phantom length necessary to assess radiation dose delivered to patients in cone‐beam CT with an enlarged beamwidth, we measured dose profiles in cylindrical phantoms of sufficient length using a prototype 256‐slice CT‐scanner developed at our institute. Dose profiles parallel to the rotation axis were measured at the central and peripheral positions in PMMA (polymethylmethacrylate) phantoms of 160 or diameter and length. For practical application, we joined unit cylinders ( long) together to provide phantoms of length. Dose profiles were measured with a pin photodiode sensor having a sensitive region of approximately and thickness. Beamwidths of the scanner were varied from 20 to . Dose profile integrals (DPI) were calculated using the measured dose profiles for various beamwidths and integration ranges. For the body phantom (‐diam phantom), 76% of the DPI was represented for a beamwidth and 60% was represented for a beamwidth if dose profiles were integrated over a range, while more than 90% of the DPI was represented for beamwidths between 20 and if integration was carried out over a range. The phantom length and integration range for dosimetry of cone‐beam CT needed to be more than to represent more than 90% of the DPI for the body phantom with the beamwidth of more than . Although we reached this conclusion using the prototype 256‐slice CT‐scanner, it may be applied to other multislice CT‐scanners as well.
Respiratory motion estimation from slowly rotating x‐ray projections: Theory and simulation
Authors: Zeng Rongping , Fessler Jeffrey A. , Balter James M.
Published: April 2005

Understanding the movement of tumors caused by respiratory motion is very important for conformal radiatherapy. However, respiratory motion is very difficult to study by conventional x‐ray CT imaging since object motion causes inconsistent projection views, leading to artifacts in reconstructed images. We propose to estimate the parameters of a nonrigid, free breathing motion model from a set of projection views of the thorax that are acquired using a slowly rotating cone‐beam CT scanner. This approach involves deforming a motion‐free reference thorax volume according to the estimated parameters and comparing its projections to the corresponding measured projection views. The parameters are optimized by minimizing a regularized squared error cost function. Simulation results with a fan‐beam geometry show good agreement between the estimated motion and the true motion, which supports the potential of this approach for estimating four‐dimensional (three‐dimensional spatial + temporal) respiratory motion.
A least‐squares error minimization approach in the determination of ferric ion diffusion coefficient of Fricke‐infused dosimeter gels
Authors: Tseng Y. J. , Huang Sung‐Cheng , Chu W. C.
Published: April 2005

A least‐squares error minimization approach was adopted to assess ferric ion diffusion coefficient of Fricke‐agarose gels. Ferric ion diffusion process was modeled as a Gaussian‐shaped degradation kernel operating on an initial concentration distribution. Diffusion coefficient was iteratively determined by minimizing the error function defined as the difference between the theoretically calculated and the experimentally measured dose distributions. A rapid MR image‐based differential gel dosimetry technique that time resolves the evolution of the ferric ion diffusion process minimizes smearing of the dose distribution. Our results showed that for a Fricke‐agarose gel contained 1 mM ammonium ferrous sulfate, 1% agarose, 1 mM sodium chloride, and 50 mM sulfuric acid, its ferric ion diffusion coefficient is at room temperature. This value falls within the range previously reported under varying gelling ingredients and concentrations. This method allows a quick, nondestructive evaluation of the ferric ion diffusion coefficient that can be used in conjunction with the in situ gel dosimetry experiment to provide a practical diffusion characterization of the dosimeter gel.
Radiological properties of normoxic polymer gel dosimeters
Authors: Venning A. J. , Nitschke K. N. , Keall P. J. , Baldock C.
Published: April 2005

The radiological properties of the normoxic polymer gel dosimeters MAGIC, MAGAS, and MAGAT [methacrylic and ascorbic acid in gelatin initiated by copper; methacrylic acid gelatine gel with ascorbic acid; and methacrylic acid gelatine and tetrakis (hydroxymethyl) phosphonium chloride, respectively] have been investigated. The radiological water equivalence was determined by comparing the polymer gel macroscopic photon and electron interaction cross sections over the energy range from 10 keV to 20 MeV and by Monte Carlo modeling of depth doses. Normoxic polymer gel dosimeters have a high gelatine and monomer concentration and therefore mass densityup to 3.8% higher than water. This results in differences between the cross‐section ratios of the normoxic polymer gels and water of up to 3% for the attenuation, energy absorption, and collision stopping power coefficient ratios through the Compton dominant energy range. The mass cross‐section ratios were within 2% of water except for the mass attenuation and energy absorption coefficients ratios, which showed differences with water of up to 6% for energies less than 100 keV. Monte Carlo modeling was undertaken for the polymer gel dosimeters to model the electron and photon transport resulting from a 6 MV photon beam. The absolute percentage differences between gel and water were within 1% and the relative percentage differences were within 3.5%. The results show that the MAGAT gel formulation is the most radiological water equivalent of the normoxic polymer gel dosimeters investigated due to its lower mass density measurement compared with MAGAS and MAGIC gels.
Photon‐beam subsource sensitivity to the initial electron‐beam parameters
Authors: Fix Michael K. , Keall Paul J. , Siebers Jeffrey V.
Published: April 2005

One limitation to the widespread implementation of Monte Carlo (MC) patient dose‐calculation algorithms for radiotherapy is the lack of a general and accurate source model of the accelerator radiation source. Our aim in this work is to investigate the sensitivity of the photon‐beam subsource distributions in a MC source model (with target, primary collimator, and flattening filter photon subsources and an electron subsource) for 6‐ and 18‐MV photon beams when the energy and radial distributions of initial electrons striking a linac target change. For this purpose, phase‐space data (PSD) was calculated for various mean electron energies striking the target, various normally distributed electron energy spread, and various normally distributed electron radial intensity distributions. All PSD was analyzed in terms of energy, fluence, and energy fluence distributions, which were compared between the different parameter sets. The energy spread was found to have a negligible influence on the subsource distributions. The mean energy and radial intensity significantly changed the target subsource distribution shapes and intensities. For the primary collimator and flattening filter subsources, the distribution shapes of the fluence and energy fluence changed little for different mean electron energies striking the target, however, their relative intensity compared with the target subsource change, which can be accounted for by a scaling factor. This study indicates that adjustments to MC source models can likely be limited to adjusting the target subsource in conjunction with scaling the relative intensity and energy spectrum of the primary collimator, flattening filter, and electron subsources when the energy and radial distributions of the initial electron‐beam change.
Study on computer‐aided diagnosis of hepatic MR imaging and mammography
Authors: Zhang Xuejun
Published: April 2005

It is well known that the liver is an organ easily attacked by diseases. The purpose of this study is to develop a computer‐aided diagnosis (CAD) scheme for helping radiologists to differentiate hepatic diseases more efficiently. Our software named LIVERANN integrated the magnetic resonance (MR) imaging findings with different pulse sequences to classify the five categories of hepatic diseases by using the artificial neural network (ANN) method. The intensity and homogeneity within the region of interest (ROI) delineated by a radiologist were automatically calculated to obtain numerical data by the program for input signals to the ANN. Outputs were the five pathological categories of hepatic diseases (hepatic cyst, hepatocellular carcinoma, dysplasia in cirrhosis, cavernous hemangioma, and metastasis). The experiment demonstrated a testing accuracy of 93% from 80 patients. In order to differentiate the cirrhosis from normal liver, the volume ratio of left to whole (LTW) was proposed to quantify the degree of cirrhosis by three‐dimensional (3D) volume analysis. The liver region was firstly extracted from computed tomography (CT) or MR slices based on edge detection algorithms, and then separated into left lobe and right lobe by the hepatic umbilical fissure. The volume ratio of these two parts showed that the LTW ratio in the liver was significantly improved in the differentiation performance, with in cirrhosis versus the normal liver . In addition, the application of the ANN method for detecting clustered microcalcifications in masses on mammograms was described here as well. A new structural ANN, so‐called a shift‐invariant artificial neural network (SIANN), was integrated with our triple‐ring filter (TRF) method in our CAD system. As the result, the sensitivity of detecting clusters was improved from 90% by our previous TRF method to 95% by using both SIANN and TRF.
A comparison of two data analyses from two observer performance studies using Jackknife ROC and JAFROC
Authors: Zheng Bin , Chakraborty Dev P. , Rockette Howard E. , Maitz Glenn S. , Gur David
Published: April 2005

The authors compared two methodological approaches, Jackknife ROC and JAFROC, in analyzing data ascertained during FROC (free‐response receiver operating characteristics) type studies. Observer rating data obtained from two observer performance studies were analyzed. During the first study, seven radiologists interpreted 120 mammography examinations depicting 57 masses under five different conditions with and without the results of computer‐aided detection (CAD). In the second study, eight radiologists interpreted 110 examinations depicting 51 masses under six different display conditions with and without CAD results. Readers rated the detection task in a FROC type response. Jackknife ROC (using the software of LABMRMC with the highest rating per case) and JAFROC were used to compute differences, if any, in summary performance levels among all reading modes in each study as well as for all paired data sets. The results of the different analytical approaches are compared. The overall results for all modes were significantly different for the first study and not significant for the second study using either analytical approach. In the first study, the performance levels represented by three paired data sets were significantly different when computed using LABMRMC and four pairs were significantly different using JAFROC. In eight of ten pairs, JAFROC produced lower values than LABMRMC. In the second study, LABMRMC showed no significant differences for any paired data sets and JAFROC showed a significant difference for one pair. In 15 of 16 pairs, values computed by JAFROC were lower than those computed by LABMRMC.
The effect of ambient pressure on well chamber response: Monte Carlo calculated results for the HDR 1000 Plus
Authors: Bohm Tim D. , Griffin Sheridan L. , DeLuca Paul M. , DeWerd Larry A.
Published: April 2005

The determination of the air kerma strength of a brachytherapy seed is necessary for effective treatment planning. Well ionization chambers are used on site at therapy clinics to determine the air kerma strength of seeds. In this work, the response of the Standard Imaging HDR 1000 Plus well chamber to ambient pressure is examined using Monte Carlo calculations. The experimental work examining the response of this chamber as well as other chambers is presented in a companion paper. The Monte Carlo results show that for low‐energy photon sources, the application of the standard temperature pressure correction factor produces an over‐response at the reduced air densities/pressures corresponding to high elevations. With photon sources of 20 to 40 keV, the normalized corrected chamber response is as much as 10% to 20% over unity for air densities/pressures corresponding to an elevation of 3048 m (10000 ft) above sea level. At air densities corresponding to an elevation of 1524 m (5000 ft), the normalized ‐corrected chamber response is 5% to 10% over unity for these photon sources. With higher‐energy photon sources , the normalized corrected chamber response is near unity. For low‐energy sources of 0.25 to 0.50 MeV, the normalized ‐corrected chamber response is as much as 4% to 12% over unity for air densities/pressures corresponding to an elevation of 3048 m (10000 ft) above sea level. Higher‐energy sources have a normalized corrected chamber response near unity. Comparing calculated and measured chamber responses for common ‐ and ‐based brachytherapy seeds show agreement to within 2.7% and 1.9%, respectively. Comparing MCNP calculated chamber responses with EGSnrc calculated chamber responses show agreement to within 3.1% at photon energies of 20 to 40 keV. We conclude that Monte Carlo transport calculations accurately model the response of this well chamber. Further, applying the standard correction factor for this well chamber is insufficient in accounting for the change in chamber response with air pressure for low‐energy photon and low‐energy sources.
Density resolution of proton computed tomography
Authors: Schulte Reinhard W. , Bashkirov Vladimir , Loss Klock Márgio C. , Li Tianfang , Wroe Andrew J. , Evseev Ivan , Williams David C. , Satogata Todd
Published: April 2005

Conformal proton radiation therapy requires accurate prediction of the Bragg peak position. Protons may be more suitable than conventional x rays for this task since the relative electron density distribution can be measured directly with proton computed tomography (CT). However, proton CT has its own limitations, which need to be carefully studied before this technique can be introduced into routine clinical practice. In this work, we have used analytical relationships as well as the Monte Carlo simulation tool GEANT4 to study the principal resolution limits of proton CT. The noise level observed in proton CT images of a cylindrical water phantom with embedded tissue‐equivalent density inhomogeneities, which were generated based on GEANT4 simulations, compared well with predictions based on Tschalar's theory of energy loss straggling. The relationship between phantom thickness, initial energy, and the relative electron density resolution was systematically investigated to estimate the proton dose needed to obtain a given density resolution. We show that a reasonable density resolution can be achieved with a relatively small dose, which is comparable to or even lower than that of x‐ray CT.
Molecular Detection of
Mycobacterium bovis
and
Mycobacterium bovis
BCG (Pasteur) in Soil
Authors: Young Jamie S. , Gormley Eamonn , Wellington Elizabeth M. H.
Published: April 2005

PCR primers specific for the
Mycobacterium tuberculosis
complex were used to detect the presence of
Mycobacterium bovis
BCG (Pasteur) in soil microcosms and
Mycobacterium bovis
in environmental samples taken from a farm in Ireland with a history of bovine tuberculosis.
M. bovis
genes were detected in soil at 4 and 21 months after possible contamination. Gene levels were found in the range of 1 × 10
3
to 3.6 × 10
3
gene copies g of soil
−1
, depending on the sampling area. Areas around badger setts had the highest levels of detectable genes and were shown to have the highest levels of gene persistence.
M. bovis
-specific 16S rRNA sequences were detected, providing evidence of the presence of viable cells in Irish soils. Studies of DNA turnover in soil microcosms proved that dead cells of
M. bovis
BCG did not persist beyond 10 days. Further microcosm experiments revealed that
M
. bovis BCG survival was optimal at 37°C with moist soil (−20 kPa; 30% [vol/wt]). This study provides clear evidence that
M. bovis
can persist in the farm environment outside of its hosts and that climatic factors influence survival rates.
Simplified Fluorescent Multiplex PCR Method for Evaluation of the T-Cell Receptor Vβ-Chain Repertoire
Authors: Fernandes Sanjit , Chavan Surendra , Chitnis Vivek , Kohn Nina , Pahwa Savita
Published: April 2005

Rationale: evaluation of the T-cell receptor (TCR) Vβ-chain repertoire by PCR-based CDR3 length analysis allows fine resolution of the usage of the TCR Vβ repertoire and is a sensitive tool to monitor changes in the T-cell compartment. A multiplex PCR method employing 24 labeled upstream Vβ primers instead of the conventionally labeled downstream Cβ primer is described. Method: RNA was isolated from purified CD4 and CD8 T-cell subsets from umbilical cord blood and clinical samples using TRI reagent followed by reverse transcription using a Cβ primer and an Omniscript RT kit. The 24 Vβ primers were multiplexed based on compatibility and product sizes into seven reactions. cDNA was amplified using 24 Vβ primers (labeled with tetrachloro-6-cardoxyfluorescein, 6-carboxyfluorescein, and hexachloro-6-carboxyfluorescein), an unlabeled Cβ primer, and Taqgold polymerase. The fluorescent PCR products were resolved on an automated DNA sequencer and analyzed using the Genotyper 2.1 software. Results: Vβ spectratypes of excellent resolution were obtained with RNA amounts of 250 ng using the labeled Vβ primers. The resolution was superior to that obtained with the labeled Cβ primer assay. Also the numbers of PCRs were reduced to 7 from the 12 required in the Cβ labeling method, and the sample processing time was reduced by half. Conclusion: The method described for T-cell receptor Vβ-chain repertoire analysis eliminates tedious dilutions and results in superior resolution with small amounts of RNA. The fast throughput makes this method suitable for automation and offers the feasibility to perform TCR Vβ repertoire analyses in clinical trials.
Korean Red Ginseng Slows Depletion of CD4 T Cells in Human Immunodeficiency Virus Type 1-Infected Patients
Authors: Sung Heungsup , Kang Sang-Moo , Lee Moo-Song , Kim Tai Gyu , Cho Young-Keol
Published: April 2005

We have previously showed that long-term intake of Korean red ginseng (KRG) delayed disease progression in human immunodeficiency virus type 1 (HIV-1)-infected patients. In the present study, to investigate whether this slow progression was affected by KRG intake alone or in combination with HLA factor, we analyzed clinical data in 68 HIV-1-infected patients who lived for more than 5 years without antiretroviral therapy. The average KRG intake over 111.9 ± 31.3 months was 4,082 ± 3,928 g, and annual decrease in CD4 T cells was 35.0 ± 28.7/μl. Data analysis showed that there are significant inverse correlations between the HLA prognostic score (0.29 ± 1.19) and annual decrease in CD4 T cells (r= −0.347;P< 0.01) as well as between the amount of KRG intake and annual decrease in CD4 T cells (r= −0.379;P< 0.01). In addition, KRG intake significantly slowed the decrease in CD4 T cells even when influence of HLA class I was statistically eliminated (repeated-measure analysis of variance;P< 0.05). We also observed significant correlation between KRG intake and a decrease in serum-soluble CD8 antigen level (r= 0.62;P< 0.001). In conclusion, these data show that KRG intake independently and significantly affected the slow depletion of CD4 T cells irrespective of HLA class I.
Assessment by Flow Cytometry of Cytokine Production in Malnourished Children
Authors: Rodríguez Leonor , González Cristina , Flores Luis , Jiménez-Zamudio Luis , Graniel Jaime , Ortiz Rocío
Published: April 2005

Malnutrition in children is associated with an increased risk of infection and death. Multiple abnormalities in the immune response, including cytokine production, in protein energy-malnourished children have been described and could account for the increased severity and frequency of infections. In this study, we used flow cytometry to investigate the effects of malnutrition on the production of cytokines (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-4, and IL-10) in CD4+and CD8+cells and the activation capability (as indicated by CD69+and CD25+cells). CD4+and CD8+cells from malnourished children showed increased production of IL-4 and IL-10 cytokines and decreased production of IL-2 and IFN-γ cytokines compared to that in cells from well-nourished, uninfected and well-nourished, infected children. In addition, malnourished children showed impaired activation capability, since the fluorescence intensity of CD69+and CD25+cells was lower than that in cells from well-nourished, uninfected and well-nourished, infected children. These results indicate that malnutrition alters the capacity of CD4+and CD8+cells to produce IL-2, IFN-γ, IL-4, and IL-10 in response to stimulus. We concluded that both cytokine production and activation capacity were impaired in malnourished children. This functional impairment may be involved in the failure to develop a specific immune response and the predisposition to infection in these children.
Reference Values of CD4 T Lymphocytes in Human Immunodeficiency Virus-Negative Adult Nigerians
Authors: Aina Olumuyiwa , Dadik Jelpe , Charurat Manhattan , Amangaman Patience , Gurumdi Silas , Mang Edwina , Guyit Ruth , Lar Ndam , Datong Pam , Daniyam Comfort , Kanki Phyllis , Abimiku Alash'le
Published: April 2005

A cross-sectional study that involved secondary analysis of data collected from 681 pregnant women and 183 miners (94 men and 89 women; ratio of men to women, 1:0.95) in Jos, Nigeria, was carried out to determine the reference ranges for CD4
+
-cell counts in healthy HIV-negative adult Nigerians. The main results of interest were CD4
+
-cell counts and odds ratios (ORs) of low CD4
+
-cell counts, defined as below 350 cells per μl. CD4
+
-cell counts were similar in men and nonpregnant women, with a mean (standard deviation) of 828 (203) cells per μl, but pregnant women had a lower value of 771 (250) cells per μl. None of the factors assessed was related to the odds of having a low CD4
+
-cell count among men and nonpregnant women, but age, age of marriage, and alcohol usage were significant predictors in pregnant women. Compared to pregnant women less than 20 years old, older women had significantly lower odds of a low CD4
+
-cell count (ORs were 0.06 for women aged 20 to 29 years and 0.22 for those aged 30 to 39 years). When compared with those pregnant women who were married before 20 years of age, those who married at 20 to 29 years and 30 to 39 years had odds ratios of 6.41 and 9.40, respectively. Previous alcohol use was also associated with low CD4
+
-cell counts (OR, 5.15). The 95% confidence interval for CD4
+
-cell counts in healthy adult Nigerians is 547 to 1,327 cells per μl, and this is the first time this has been determined.
Rapid Competitive Enzyme-Linked Immunosorbent Assay for Detection of Antibodies to Peste des Petits Ruminants Virus
Authors: Choi Kang-Seuk , Nah Jin-Ju , Ko Young-Joon , Kang Shien-Young , Jo Nam-In
Published: April 2005

Peste des petits ruminants (PPR) is a contagious viral disease of small ruminants that is of economic importance in Africa, the Middle East, and Asia. We developed a rapid competitive enzyme-linked immunosorbent assay (rapid c-ELISA) for the diagnosis and surveillance of PPR. This assay detects PPR virus (PPRV) antibodies in serum samples by quantifying the amount of monoclonal antibody (MAb) P-3H12 after 30 min of incubation of a serum-MAb conjugate mixture on plates coated with a PPRV recombinant nucleocapsid protein (rPPRV-N). We tested 249 PPRV-positive serum samples and 733 PPRV-negative serum samples from field ruminants. The threshold of percent inhibition (PI) was determined to be <50 on the basis of the mean PI plus 3 standard deviations for sera from PPRV-negative ruminants. The relative specificity and sensitivity of the rapid c-ELISA were 98.5% (722 of 733 serum samples) and 93.4% (234 of 249 serum samples), respectively. The rapid c-ELISA sensitively detected PPRV antibodies in hyperimmune sera (virus neutralization test [VNT] titer, >512), even at dilutions ≥512 in normal goat serum, and as early as 6 to 13 days postinfection from 12 goats, each of which was infected with one of the four PPRV lineages. Hyperimmune sera from animals experimentally vaccinated with rinderpest virus gave positive results by the rapid c-ELISA when the rinderpest virus VNT titers were >512, although the rapid c-ELISA titers were very low (2 to 16). However, the rapid c-ELISA was negative when the rinderpest virus VNT titer was ≤128. The rapid c-ELISA developed in the present work provides a short turnaround time and could be a useful tool for the diagnosis of PPR and screening for PPRV in the field.
Comparing Genomes of
Helicobacter pylori
Strains from the High-Altitude Desert of Ladakh, India
Authors: Kauser Farhana , Hussain M. Abid , Ahmed Irshad , Ahmad Naheed , Habeeb Aejaz , Khan Aleem A. , Ahmed Niyaz
Published: April 2005

The genomic diversity of
Helicobacter pylori
from the vast Indian subcontinent is largely unknown. We compared the genomes of 10
H. pylori
strains from Ladakh, North India. Molecular analysis was carried out to identify rearrangements within and outside the
cag
pathogenicity island (
cag
PAI) and DNA sequence divergence in candidate genes. Analyses of virulence genes (such as the
cag
PAI as a whole,
cagA
,
vacA
,
iceA
,
oipA
,
babB
, and the plasticity cluster) revealed that
H. pylori
strains from Ladakh are genetically distinct and possibly less virulent than the isolates from East Asian countries, such as China and Japan. Phylogenetic analyses based on the
cagA
-
glr
motifs, enterobacterial repetitive intergenic consensus patterns, repetitive extragenic palindromic signatures, the
glmM
gene mutations, and several genomic markers representing fluorescent amplified fragment length polymorphisms revealed that Ladakhi strains share features of the Indo-European, as well as the East Asian, gene pools. However, the contribution of genetic features from the Indo-European gene pool was more prominent.
Clonal Spread of a Vancomycin-Resistant
Enterococcus faecium
Strain among Bloodstream-Infecting Isolates in Italy
Authors: Stampone Lucia , Del Grosso Maria , Boccia Delia , Pantosti Annalisa
Published: April 2005

Recent data indicated that the rate of vancomycin resistance in bloodstream-infecting enterococcal isolates in Italy is one of the highest in Europe. The aims of this study were to characterize bloodstream-infecting vancomycin-resistant enterococci (VRE) obtained from various Italian hospitals and to establish whether the isolates were clonally related. During the years 2001 to 2003, a total of 39 VRE isolates were obtained from 19 hospital laboratories in various areas of Italy. Species identification and resistance genotypes of the isolates were obtained by multiplex PCR. Further characterization included antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA, detection of virulence genes (
esp
and
hyl
), and multilocus sequence typing (MLST) of selected isolates. VRE were identified as 31
Enterococcus faecium
(VREfm) isolates and 8
E. faecalis
isolates. All but one isolate carried the
vanA
gene; one VREfm isolate carried the
vanB
gene. Analysis of the PFGE profiles showed that 28 VREfm isolates shared a similar electrophoretic profile, designed type 1, and were clonally related. All type 1 isolates were resistant to ampicillin, streptomycin, gentamicin, and rifampin and were positive for the
esp
gene. MLST identified an allelic profile (ST78) comprising
purK
allele 1, belonging to the C1 clonal lineage, characteristic of human infection and hospital outbreak isolates. The
vanB
-carrying VREfm isolate, of PFGE type 2, was shown to be a single-locus variant of ST78. Our data indicate that the recent increase in the number of bloodstream infections caused by VRE in Italy is due to the spread of a hospital-adapted, multidrug-resistant VREfm clone belonging to an internationally disseminated lineage.