bluuebunny/crossref_metadata_2025 huggingface dataset:
A dose‐gradient analysis tool for IMRT QA
Authors: Moran Jean M. , Radawski Jeffrey , Fraass Benedick A.
Published: February 2007

The use of intensity‐modulated radiation therapy (IMRT) has led to an increase in the number of complex fields that require measurement and comparison to calculated dose distributions in 2D. Current dose evaluation techniques, including isodose line comparisons, displays of the dose difference between calculated and measured distributions, and distance‐to‐agreement (DTA) comparisons, are useful for display of differences between two different dose distributions but are often of limited value for the assessment of the discrepancies in terms of significance and/or cause. In this paper, we present a new gradient compensation method for the evaluation of local dosimetric differences as a function of the dose gradient at each point in the dose distribution. To apply the method, the user specifies a distance parameter (typically 1 mm), which is the geometric tolerance the user is prepared to accept for the dose comparison. The expected geometric uncertainties in the comparison process can include finite calculation and measurement grids, small misalignments of measured and calculated results, and volume‐averaging effects in the measurement detector. Since these uncertainties can obscure the interpretation of any of the analysis tools described above, removing dose differences related to the tolerable geometric uncertainty helps the gradient compensation method highlight algorithm and delivery‐related differences. The remaining dose differences not explained by the geometric tolerance can then be evaluated graphically (dose difference display) or analytically (dose difference dose‐volume histograms) over the entire comparison region.

PACS number: 87.53.Xd
Interfractional anatomic variation in patients treated with respiration‐gated radiotherapy
Authors: Yorke Ellen , Rosenzweig Kenneth E. , Wagman Raquel , Mageras Gikas S.
Published: February 2007

As quality assurance for respiration‐gated treatments using the Varian RPM™ system, we monitor interfractional diaphragm variation throughout treatment using extra anterior‐posterior (AP) portal images. We measure the superior‐inferior (SI) distance between one or more bony landmarks and the ipsilateral diaphragm dome in each such radiograph and calculate its difference, D, from the corresponding distance in a planning CT scan digitally reconstructed radiograph (DRR). For each patient, the mean of D represents the systematic diaphragm displacement, and the standard deviation of D represents random diaphragm variations and is a measure of interfractional gating reproducibility. We present results for 31 sequential patients (21 lung, 10 liver tumors), each with at least 8 such portal images. For all patients, the gate included end‐exhale. The patient‐specific duty cycle ranged from 30% to 60%. All patients received customized audio prompting for simulation and treatment, and 14 patients also received visual prompting. Respiration‐synchronized fluoroscopic movies taken at a conventional simulator revealed patient‐specific diaphragm excursions from 1.0 cm to 5.0 cm and diaphragm excursion within the gate from 0.5 cm to 1.0 cm, demonstrating a significant reduction of intra‐fractional diaphragm (and by inference tumor) motion by respiratory gating. One standard deviation of the systematic displacement (the mean of D) was 0.63 cm and 0.48 cm for the lung and liver patient groups, respectively. The average SD of the random displacements (i.e., the average of the standard deviations of D) was and for the two groups, respectively. The similar magnitude of the systematic and random displacements suggests that both derive from a common distribution of interfractional variations. Combining visual with audio prompting did not significantly improve performance, as judged by D. Guided by these portal images, field changes were made during the course of treatment for 6 patients (1 lung, 5 liver).

PACS numbers: 87.53.‐j, 87.53.Oq
Validation of physics improvements for IMRT with a commercial treatment‐planning system
Authors: Cadman Patrick , McNutt Todd , Bzdusek Karl
Published: February 2007

A new Pinnacle 3D treatment‐planning system software release has recently become available (v7.4, Philips Radiation Oncology Systems, Milpitas, CA), which supports modeling of rounded multileaf collimator (MLC) leaf ends; it also includes a number of other software enhancements intended to improve the overall dose calculation accuracy. In this report, we provide a general discussion of the dose calculation algorithm and new beam‐modeling parameters. The accuracy of a diode dosimeter was established for measurement of MLC‐shaped beam profiles required by the new software version by comparison with film and ion chamber measurements in various regions of the field. The results suggest that a suitable diode or other small volume dosimeter with appropriate energy sensitivity should be used to obtain profiles for commissioning the planning system. Film should be used with caution, especially for larger field profile measurements. The dose calculation algorithm and modeling parameters chosen were validated through various test field measurements including a bar pattern, a strip pattern, and a clinical head and neck IMRT field. For the bar and strip patterns, the agreement between Pinnacle calculations and diode measurements was generally very good. These tests were helpful in establishing the new model parameter values, especially tongue‐and‐groove width, additional interleaf leakage, rounded leaf tip radius, and MLC transmission. For the clinical head and neck field, the comparison between Pinnacle and film measurements showed regions of approximately 2 cGy under‐ or overdose. However, the Pinnacle calculations agreed with diode measurements at all points to within 1 cGy or 1% of the maximum dose for the field (67 cGy). The greatest discrepancy between film and diode measurements for the clinical field (maximum of 2.8%) occurred in low‐dose regions in the central part of the field. The disagreement may be due to the overresponse of film to scattered radiation in the low‐dose regions, which have significant shielding by the MLCs.

PACS numbers: 87.53.Bn, 87.53.Dq
Book Review
Authors: Huda Amir
Published: February 2007

Primer on MR Imaging of the Abdomen and Pelvis, by Diego R. Martin, Michèle A. Brown, and Richard C. Semelka, John Wiley & Sons, Inc. 2005; ISBN 0‐471‐37340‐0; list price $59.95 (paperback)
Patient‐specific daily pretreatment setup protocol using electronic portal imaging for radiation therapy
Authors: Wittmer Michael H. , Pisansky Thomas M. , Kruse Jon J. , Herman Michael G.
Published: February 2007

The purpose of this study was to evaluate electronic portal imaging (EPI) as a means of identifying and correcting field displacement in patients with problematic external beam radiotherapy setups. Fourteen patients with problematic setups were identified for pretreatment daily EPI beam monitoring as part of a physician‐directed therapist intervention protocol. Pretreatment EPIs were used to realign fields as necessary to bring the setup within the physician‐prescribed tolerance level. For comparison, daily EPIs were available for 12 control patients who had no particular setup difficulties and for whom online beam realignment was not made. Anatomy‐matching software was used to measure setup variation along medial‐lateral, superior‐inferior, and anterior‐posterior axes. Online field realignment yielded a significant improvement when comparing initial and final setup variations. The mean standard deviation of setup displacement averaged over three axes was reduced from 6.4 mm to 3.1 mm after realignment. The final variation of protocol patients was comparable to that of control patients. In conclusion, EPI provided effective means to perform online beam realignment in a group of difficult‐to‐position patients. This procedure resulted in a reduction in setup displacement that was statistically significant, clinically relevant, and approached that of a more typical patient group.

PACS number: 87.53.Oq
New automated fluoroscopic systems for pediatric applications
Authors: Lu Zheng Feng , Nickoloff Edward L. , Ruzal‐Shapiro Carrie B. , So James C. , Dutta Ajoy K.
Published: February 2007

Pediatric patients are at higher risk to the adverse effects from exposure to ionizing radiation than adults. The smaller sizes of the anatomy and the reduced X‐ray attenuation of the tissues provide special challenges. The goal of this effort is to investigate strategies for pediatric fluoroscopy in order to minimize the radiation exposure to these individuals, while maintaining effective diagnostic image quality. Modern fluoroscopy systems are often entirely automated and computer controlled. In this paper, various selectable and automated modes are examined to determine the influence of the fluoroscopy parameters upon the patient radiation exposures and image quality. These parameters include variable X‐ray beam filters, automatic brightness control programs, starting kilovolt peak levels, fluoroscopic pulse rates, and other factors. Typical values of radiation exposure rates have been measured for a range of phantom thicknesses from 5 cm to 20 cm of acrylic. Other factors that have been assessed include spatial resolution, low‐contrast discrimination, and temporal resolution. The selection menu for various procedures is based upon the examination type, anatomical region, and patient size. For pediatric patients, the automated system can employ additional filtration, special automatic brightness control curves, pulsed fluoroscopy, and other features to reduce the patient radiation exposures without significantly compromising the image quality. The benefits gained from an optimal selection of automated programs and settings for fluoroscopy include ease of operation, better image quality, and lower patient radiation exposures.

PACS numbers: 87.59.‐e, 87.62.+n
AAPM Task Group 103 report on peer review in clinical radiation oncology physics
Authors: Halvorsen Per H. , Das Indra J. , Fraser Martin , Freedman D. Jay , Rice Robert E. , Ibbott Geoffrey S. , Parsai E. Ishmael , Robin T. Tydings , Thomadsen Bruce R.
Published: February 2007

This report provides guidelines for a peer review process between two clinical radiation oncology physicists. While the Task Group's work was primarily focused on ensuring timely and productive independent reviews for physicists in solo practice, these guidelines may also be appropriate for physicists in a group setting, particularly when dispersed over multiple separate clinic locations. To ensure that such reviews enable a collegial exchange of professional ideas and productive critique of the entire clinical physics program, the reviews should not be used as an employee evaluation instrument by the employer. Such use is neither intended nor supported by this Task Group. Detailed guidelines are presented on the minimum content of such reviews, as well as a recommended format for reporting the findings of a review. In consideration of the full schedules faced by most clinical physicists, the process outlined herein was designed to be completed in one working day.

PACS numbers: 87.53.Xd, 87.90.+y
Monte Carlo‐based lung cancer treatment planning incorporating PET‐defined target volumes
Authors: Chetty Indrin J. , Fernando Shaneli , Kessler Marc L. , Mcshan Daniel L. , Brooks Cassandra , Ten Haken Randall K. , (Spring) Kong Feng‐Ming
Published: February 2007

Despite the well‐known benefits of positron emission tomography (PET) imaging in lung cancer diagnosis and staging, the poor spatial resolution of PET has limited its use in radiotherapy planning. Methods used for segmenting tumor from normal tissue, such as threshold boundaries using a fraction of the standardized uptake value (SUV), are subject to uncertainties. The issue of respiratory motion in the thorax confounds the problem of accurate target definition. In this work, we evaluate how changing the PET‐defined target volume by varying the threshold value in the segmentation process impacts target and normal lung tissue doses. For each of eight lung cancer patients we retrospectively generated multiple PET‐target volumes; each target volume corresponds to those voxels with intensities above a given threshold level, defined by a percentage of the maximum voxel intensity. PET‐defined targets were compared to those from CT; CT targets comprise a composite volume generated from breath‐hold inhale and exhale datasets; the CT dataset therefore also includes the extents of tumor motion. Treatment plans using Monte Carlo dose calculation were generated for all targets; the dose uniformity was approximately within the internal target volume (ITV) (formed by a uniform 8‐mm expansion of the composite gross target volume (GTV)). In all cases differences were observed in the generalized equivalent uniform doses (gEUDs) to the targets and in the mean lung doses (MLDs) and normal tissue complication probabilities (NTCPs) to the normal lung tissues. The magnitudes of the dose differences were found to depend on the target volume, location, and amount of irradiated normal lung tissue, and in many instances were clinically meaningful (greater than a single 2 Gy fraction). For those patients studied, results indicate that accurate dosimetry using PET volumes is highly dependent on accurate target segmentation. Further study with correlation to clinical outcome will be helpful in determining how to apply these various PET and CT volumes in treatment planning, to potentially improve local tumor control and reduce normal tissue toxicities.

PACS number: 87.52.Tf
Evaluation of an automated seed loader for seed calibration in prostate brachytherapy
Authors: Wan Shuying , Joshi Chandra P. , Carnes Greg , Schreiner L. John
Published: February 2007

Automated seed loaders for permanent prostate implants are now commercially available. Besides improved radiation safety, these systems offer seed assay capability and ease of needle loading, making preplanned as well as intra‐operative implant procedures more time‐efficient. The Isoloader (Mentor Corp., CA) uses individual seeds (SL‐125 ProstaSeed) loaded in up to 199 chambers inside a shielded cartridge. The unit performs seed counting and calibration using a built‐in solid‐state detector. In order to evaluate the reproducibility and accuracy of the calibration process, two test cartridges were measured with the Isoloader itself and compared with a well‐type ionization chamber (HDR‐1000Plus, Standard Imaging).

The air kerma strength measurements for all seeds using the Isoloader had a standard deviation of about 2.7%. For the eight seeds assayed more intensively using both the Isoloader and well chamber, the standard deviations of the measurements for each seed were in the range of 0.8% to 2.8% and 0.6% to 1.3%, respectively. The variation in the Isoloader calibration is attributed to small detector solid angle and bead geometry within seed capsules (verified by radiographs). The reproducibility of the air kerma strength measured by the Isoloader was comparable to that from the well chamber and was clinically acceptable. Seed strength measured with the Isoloader was on average larger than that measured with the well chamber, indicating that the accuracy of the Isoloader was clinically acceptable.

PACS numbers: 87.53.Jw, 87.53.Xd, 87.56.Fc
Hepatic encephalopathy: A neurochemical, neuroanatomical, and neuropsychological study
Authors: Binesh Nader , Huda Amir , Thomas M. Albert , Wyckoff Nathaniel , Bugbee Mary , Han Steven , Rasgon Natalie , Davanzo Pablo , Sayre James , Guze Barry , Martin Paul , Fawzy Fawzy
Published: February 2007

Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternative and possibly more specific markers for HE. These methods were applied in conjunction with NP testing in order to determine their usefulness in the identification of HE and to understand the pathogenesis of HE more clearly. MR imaging and spectroscopy examinations, in addition to a battery of 15 NP tests, were administered to investigate 31 patients awaiting liver transplantation and 23 healthy controls. MR image intensities from the globus pallidus region were calculated and normalized to those of the thalamus. Absolute concentrations and ratios with respect to creatine (Cr) of several metabolites were computed from MR spectra. The MR data were correlated with the results of NP tests. The patients showed impairment in NP tests of attention and visuospatial and verbal fluency. In weighted MRI, the relative intensity of the globus pallidus with respect to that of the thalamus region was significantly elevated in patients and correlated (negatively) with three NP tests (Hooper, FAS, and Trails B). The absolute concentrations of myo‐inositol (mI) and choline (Ch) were significantly reduced in three brain regions. In addition, the absolute concentrations of glutamine (Gln) and combined glutamate and glutamine (Glx) were increased in all three locations, with Gln increase being significant in all areas while that of Glx only in the occipital white matter. In summary, this study partially confirms a hypothesized mechanism of HE pathogenesis, an increased synthesis of glutamine by brain glutamate in astrocytes due to excessive blood ammonia, followed by a compensatory loss of myo‐inositol to maintain astrocyte volume homeostasis. It also indicates that the hyperintensity observed in globus pallidus could be used as complementary to the NP test scores in evaluating the mental health of HE patients.

PACS number: 87.61.Pk
Performance optimization of the Varian aS500 EPID system
Authors: Berger Lucie , François Pascal , Gaboriaud Geneviève , Rosenwald Jean‐Claude
Published: February 2007

Today, electronic portal imaging devices (EPIDs) are widely used as a replacement to portal films for patient position verification, but the image quality is not always optimal. The general aim of this study was to optimize the acquisition parameters of an amorphous silicon EPID commercially available for clinical use in radiation therapy with the view to avoid saturation of the system. Special attention was paid to selection of the parameter corresponding to the number of rows acquired between accelerator pulses (NRP) for various beam energies and dose rates. The image acquisition system (IAS2) has been studied, and portal image acquisition was found to be strongly dependent on the accelerator pulse frequency. This frequency is set for each “energy — dose rate” combination of the linear accelerator. For all combinations, the image acquisition parameters were systematically changed to determine their influence on the performances of the Varian aS500 EPID system. New parameters such as the maximum number of rows (MNR) and the number of pulses per frame (NPF) were introduced to explain portal image acquisition theory. Theoretical and experimental values of MNR and NPF were compared, and they were in good agreement. Other results showed that NRP had a major influence on detector saturation and dose per image. A rule of thumb was established to determine the optimum NRP value to be used. This practical application was illustrated by a clinical example in which the saturation of the aSi EPID was avoided by NRP optimization. Moreover, an additional study showed that image quality was relatively insensitive to this parameter.

PACS numbers: 87.53.Oq; 87.59.Jq
Performance evaluation and quality assurance of Varian enhanced dynamic wedges
Authors: Alaei Parham , Higgins Patrick D.
Published: February 2007

Dynamic wedges have been used in clinical practice for many years. Obvious superiority of dynamic over physical wedges is accompanied by the increased overhead involved in verifying the accuracy and reliability of their use. Contrary to very limited QA required to ensure proper functioning of the physical wedges, dynamic wedges, like any other dynamic treatment, require a robust QA program. This work expands upon previous suggestions and describes a comprehensive QA program for Varian enhanced dynamic wedges (EDWs) and presents the results of an 18‐month evaluation of these wedges. The QA program includes daily, monthly, and yearly tests and individual treatment QA at the onset of use of the EDWs. The results of the 18‐month evaluation show reproducibility in the wedge factors of better than 1% and in dose profiles of better than 2% on a monthly basis. Daily output measurements are generally within 2% of expected values.

PACS numbers: 87.53.Xd, 87.56.Fc
Phase versus amplitude sorting of 4D‐CT data
Authors: Wink Nicole M. , Panknin Christoph , Solberg Timothy D.
Published: February 2007

Image quality of CT scans suffers when objects undergo motion. Respiratory motion causes artifacts, which prevents adequate visualization of anatomy. Four‐dimensional CT (4D‐CT) is a method in which image reconstruction of moving objects is retrospectively gated according to the recorded phase information of the monitored motion pattern. Although several groups have investigated the use of 4D‐CT in radiotherapy, little has been detailed with regard to the sorting method. We present a new retrospective gating technique with sorting based on the amplitude of the motion trace. This method is compared to previously developed methods that sort based on phase. A 16‐slice CT scanner (Sensation 16, Siemens Medical Solutions, Erlangen, Germany) was used to acquire images of two phantoms on a motion platform moving in two dimensions. The motion was monitored using a strain gauge inserted inside an adjustable belt. A 180° interpolation was used for reconstruction after gating. Significant improvement using the amplitude‐sorting technique was observed, particularly when testing nonperiodic motion functions.

PACS numbers: 87.59.Fm, 87.53.Kn, 87.57.Ce
Performance evaluation of an automated image registration algorithm using an integrated kilovoltage imaging and guidance system
Authors: Fox Timothy , Huntzinger Calvin , Johnstone Peter , Ogunleye Tomi , Elder Eric
Published: February 2007

Image‐guided radiation therapy delivery may be used to assess the position of the tumor and anatomical structures within the body as opposed to relying on external marks. The purpose of this manuscript is to evaluate the performance of the image registration software for automatically detecting and repositioning a 3D offset of a phantom using a kilovoltage onboard imaging system. Verification tests were performed on both a geometric rigid phantom and an anthropomorphic head phantom containing a humanoid skeleton to assess the precision and accuracy of the automated positioning system. From the translation only studies, the average deviation between the detected and known offset was less than 0.75 mm for each of the three principal directions, and the shifts did not show any directional sensitivity. The results are given as the measurement with standard deviation in parentheses. The combined translations and rotations had the greatest average deviation in the lateral, longitudinal, and vertical directions. For all dimensions, the magnitude of the deviation does not appear to be correlated with the magnitude of the actual translation introduced. The On‐Board Imager™ (OBI) system has been successfully integrated into a feasible online radiotherapy treatment guidance procedure. Evaluation of each patient's resulting automatch should be performed by therapists before each treatment session for adequate clinical oversight.

PACS numbers: 87.53.‐j, 87.53.Xd, 87.57.Gg
Accuracy of rapid radiographic film calibration for intensity‐modulated radiation therapy verification
Authors: Kulasekere Ravi , Moran Jean M. , Fraass Benedick A. , Roberson Peter L.
Published: February 2007

A single calibration film method was evaluated for use with intensity‐modulated radiation therapy film quality assurance measurements. The single‐film method has the potential advantages of exposure simplicity, less media consumption, and improved processor quality control. Potential disadvantages include cross contamination of film exposure, implementation effort to document delivered dose, and added complication of film response analysis. Film response differences were measured between standard and single‐film calibration methods. Additional measurements were performed to help trace causes for the observed discrepancies. Kodak X‐OmatV (XV) film was found to have greater response variability than extended dose range (EDR) film. We found it advisable for XV film to relate the film response calibration for the single‐film method to a user‐defined optimal calibration geometry. Using a single calibration film exposed at the time of experiment, the total uncertainty of film response was estimated to be (1%) for XV (EDR) film at 50 (100) cGy and higher, respectively.

PACS numbers: 87.53.‐j, 87.53.Dq
The dosimetric effect of inhomogeneity correction in dynamic conformal arc stereotactic body radiation therapy for lung tumors
Authors: Kavanagh Brian , Ding Meisong , Schefter Tracey , Stuhr Kelly , Newman Francis
Published: February 2007

For patients treated with lung stereotactic body radiation therapy (SBRT) using dynamic conformal arcs, the influence of inhomogeneity correction (IC) on normal tissue and tumor dosimetry was studied. For the same numbers of monitor units, the planning target volume equivalent uniform doses calculated without path‐length IC were lower than those calculated with IC (mean difference 18%, range 1% to 34%; ). Normal lung dose differences were of the same magnitude in the opposite direction. In reports of SBRT, it will be helpful to maintain clear communication about the type of IC used to avoid future uncertainties about true normal tissue tolerance and tumor dose‐response relationships.

PACS numbers: 87.50.Gi, 87.53.Bn, 87.53.Kn
Estimation of patient organ doses from CT examinations in Tanzania
Authors: Ngaile Justin E. , Msaki Peter K.
Published: February 2007

Although the use of CT in medical diagnosis delivers radiation doses to patients that are higher than those from other radiological procedures, lack of optimized protocols could be an additional source of increased dose in developing countries. The aims of this study are, first, to determine the magnitude of radiation doses received by selected radiosensitive organs of patients undergoing CT examinations and compare them with other studies, and second, to assess how CT scanning protocols in practice affect patient organ doses. In order to achieve these objectives, patient organ doses from five common CT examinations were obtained from eight hospitals in Tanzania. The patient organ doses were estimated using measurements of CT dose indexes (CTDI), exposure‐related parameters, and the ImPACT spreadsheet based on NRPB conversion factors. A large variation of mean organ doses among hospitals was observed for similar CT examinations. These variations largely originated from different CT scanning protocols used in different hospitals and scanner type. The mean organ doses in this study for the eye lens (for head), thyroid (for chest), breast (for chest), stomach (for abdomen), and ovary (for pelvis) were 63.9 mGy, 12.3 mGy, 26.1 mGy, 35.6 mGy, and 24.0 mGy, respectively. These values were mostly comparable to and slightly higher than the values of organ doses reported from the literature for the United Kingdom, Japan, Germany, Norway, and the Netherlands. It was concluded that patient organ doses could be substantially minimized through careful selection of scanning parameters based on clinical indications of study, patient size, and body region being examined. Additional dose reduction to superficial organs would require the use of shielding materials.

PACS numbers: 87.59 Fm; 87.66Jj; 87.52‐g
Evaluation of dosimetric effect of leaf position in a radiation field of an 80‐leaf multileaf collimator fitted to the LINAC head as a tertiary collimator
Authors: Kehwar Than S. , Bhardwaj Anup K. , Chakarvarti Shiv K.
Published: February 2007

This study evaluates changes in the dosimetric characteristics of a Varian Millennium 80‐leaf multileaf collimator (MLC) in a radiation field. In this study, dose rate, scatter factor, percentage depth dose, surface dose and dose in the buildup region, beam profile, flatness and symmetry, and penumbra width measurements were made for 6‐MV and 15‐MV photon beams. Analysis of widths between 50% dose levels of the beam profiles to reflect the field size at the level of profile measurement shows a significant difference between the fields defined by MLC and/or jaws and MLC (zero gap) and the fields defined by jaws only. The position of the MLC leaves in the radiation field also significantly affects scatter factors. A new relationship has, therefore, been established between the scatter factors and the position of the MLC, which will indeed be useful in the dose calculation for irregular fields. Penumbra widths increase with field size and were higher for fields defined by jaws and/or MLC than jaws and MLC (zero gap) by 1.5 mm to 4.2 mm and 3.8 mm to 5.0 mm, for 6‐MV, and 1.5 mm to 2.4 mm and 3.0 mm to 5.6 mm, for 15‐MV, at 20% to 80% and 10% to 90% levels, respectively. The surface dose and the dose in the buildup region were smaller for fields defined by jaws and MLC (zero gap) than the fields defined by jaws and/or MLC for both photon energies. No significant differences were found in percentage depth dose beyond , beam profiles above 80% dose level, and flatness and symmetry for both energies. The results of this study suggest that while one collects linear accelerator beam data with a MLC, the effects of the positions of the MLC leaves play an important role in dosimetric characteristics of 3D conformal radiation therapy as well as intensity‐modulated radiotherapy.

PACS number: 87.53.Dq
The Differential Agglutination Test as a Diagnostic Aid in Cases of Toxoplasmic Lymphadenitis
Authors: Montoya Jose G. , Berry Andrew , Rosso Fernando , Remington Jack S.
Published: February 2007

Lymphadenopathy (LN) is the most common clinical manifestation of acute acquired toxoplasma infection in humans. The diagnosis of toxoplasmic lymphadenitis (TL) is established by serological methods and/or lymph node biopsy. In the United States, the differential agglutination (of acetone [AC]-fixed versus that of formalin [HS]-fixed tachyzoites) test (AC/HS test) has primarily been used in assessments of pregnant women as a component of the toxoplasma serological profile to distinguish between recently acquired infections and infections acquired in the distant past. We studied the AC/HS test in patients with TL to define its usefulness in diagnosing individuals presenting with LN and to determine its kinetics after the onset of LN. One hundred nine consecutive patients (158 serum samples) diagnosed serologically and by lymph node biopsy as having TL were studied. Specific patterns in the AC/HS test were noted to be dependent on the time from the clinical onset of LN (COLN). Acute AC/HS patterns were observed for more than 75% of patients who according to their histories had developed their TL within 6 months after COLN. Acute patterns were not observed beyond the 12th month except for a single patient for whom an acute pattern (400/800) persisted to the 13th month after COLN. Equivocal patterns were observed up to 36 months after COLN. Nonacute patterns were observed only for serum samples drawn at least 13 months after COLN. A nonacute pattern in an individual at less than 12 months after COLN should suggest an etiology other than TL. In such cases, investigation for alternative causes, including malignancy, should be instigated.
Natural Mutations in the Receptor Binding Domain of Spike Glycoprotein Determine the Reactivity of Cross-Neutralization between Palm Civet Coronavirus and Severe Acute Respiratory Syndrome Coronavirus
Authors: Liu Li , Fang Qing , Deng Fei , Wang Hanzhong , Yi Christopher E. , Ba Lei , Yu Wenjie , Lin Richard D. , Li Taisheng , Hu Zhihong , Ho David D. , Zhang Linqi , Chen Zhiwei
Published: February 2007

The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.
Live Covisualization of Competing Adeno-Associated Virus and Herpes Simplex Virus Type 1 DNA Replication: Molecular Mechanisms of Interaction
Authors: Glauser Daniel L. , Strasser Regina , Laimbacher Andrea S. , Saydam Okay , Clément Nathalie , Linden R. Michael , Ackermann Mathias , Fraefel Cornel
Published: February 2007

We performed live cell visualization assays to directly assess the interaction between competing adeno-associated virus (AAV) and herpes simplex virus type 1 (HSV-1) DNA replication. Our studies reveal the formation of separate AAV and HSV-1 replication compartments and the inhibition of HSV-1 replication compartment formation in the presence of AAV. AAV Rep is recruited into AAV replication compartments but not into those of HSV-1, while the single-stranded DNA-binding protein HSV-1 ICP8 is recruited into both AAV and HSV-1 replication compartments, although with differential staining patterns. Slot blot analysis of coinfected cells revealed a dose-dependent inhibition of HSV-1 DNA replication by wild-type AAV but not by
rep
-negative recombinant AAV. Consistent with this, Western blot analysis indicated that wild-type AAV affects the levels of the HSV-1 immediate-early protein ICP4 and the early protein ICP8 only modestly but strongly inhibits the accumulation of the late proteins VP16 and gC. Furthermore, we demonstrate that the presence of Rep in the absence of AAV DNA replication is sufficient for the inhibition of HSV-1. In particular, Rep68/78 proteins severely inhibit the formation of mature HSV-1 replication compartments and lead to the accumulation of ICP8 at sites of cellular DNA synthesis, a phenomenon previously observed in the presence of viral polymerase inhibitors. Taken together, our results suggest that AAV and HSV-1 replicate in separate compartments and that AAV Rep inhibits HSV-1 at the level of DNA replication.
Deamination-Independent Inhibition of Hepatitis B Virus Reverse Transcription by APOBEC3G
Authors: Nguyen David H. , Gummuluru Suryaram , Hu Jianming
Published: February 2007

The APOBEC3 family of mammalian cytidine deaminases, including APOBEC3G (A3G), has been shown to function as innate antiviral factors against retroviruses and can also suppress the replication of the hepatitis B virus (HBV). The mechanism by which A3G inhibits HBV replication remains to be elucidated. In this study, we show that the inhibitory effect of APOBEC3 proteins on HBV replication was mainly at the DNA level, with only a minor effect on viral RNA packaging. The anti-HBV effect of A3G was independent of the DNA-editing function, and the mode of inhibition was not due to HBV DNA degradation. The editing-independent antiviral activity of A3G could target DNA-RNA hybrids as well as single-stranded DNA. Finally, we show that there was a preferential decrease in the accumulation of longer minus-strand DNA by A3G, compared to the shorter minus-strand DNA, and suggest that A3G exerts its inhibitory effect at very early stages during viral reverse transcription.
Major Subsets of Human Dendritic Cells Are Efficiently Transduced by Self-Complementary Adeno-Associated Virus Vectors 1 and 2
Authors: Veron Philippe , Allo Valérie , Rivière Christel , Bernard Jacky , Douar Anne-Marie , Masurier Carole
Published: February 2007

Dendritic cells (DC) are antigen-presenting cells pivotal for inducing immunity or tolerance. Gene transfer into DC is an important strategy for developing immunotherapeutic approaches against infectious pathogens and cancers. One of the vectors previously described for the transduction of human monocytes or DC is the recombinant adeno-associated virus (rAAV), with a genome conventionally packaged as a single-stranded (ss) molecule. Nevertheless, its use is limited by the poor and variable transduction efficiency of DC. In this study, AAV type 1 (AAV1) and AAV2 vectors, which expressed the enhanced green fluorescent protein and were packaged as ss or self-complementary (sc) duplex strands, were used to transduce different DC subsets generated ex vivo and the immunophenotypes, states of differentiation, and functions of the subsets were carefully examined. We show here for the first time that a single exposure of monocytes (Mo) or CD34+progenitors (CD34) to sc rAAV1 or sc rAAV2 leads to high transduction levels (5 to 59%) of differentiated Mo-DC, Mo-Langerhans cells (LC), CD34-LC, or CD34-plasmacytoid DC (pDC), with no impact on their phenotypes and functional maturation of these cells, compared to those of exposure to ss rAAV. Moreover, we show that all these DC subpopulations can also be efficiently transduced after commitment to their differentiation pathways. Furthermore, these DC subsets transduced with sc rAAV1 expressing a tumor antigen were potent activators of a CD8+-T-cell clone. Altogether, these results show the high potential of sc AAV1 and sc AAV2 vectors to transduce ex vivo conventional DC, LC, or pDC or to directly target them in vivo for the design of new DC-based immunotherapies.
Developmental Regulation of Human Cytomegalovirus Receptors in Cytotrophoblasts Correlates with Distinct Replication Sites in the Placenta
Authors: Maidji Ekaterina , Genbacev Olga , Chang Hsin-Ti , Pereira Lenore
Published: February 2007

Cytomegalovirus (CMV), the major viral cause of congenital disease, infects the uterus and developing placenta and spreads to the fetus throughout gestation. Virus replicates in invasive cytotrophoblasts in the decidua, and maternal immunoglobulin G (IgG)-CMV virion complexes, which are transcytosed by the neonatal Fc receptor across syncytiotrophoblasts, infect underlying cytotrophoblasts in chorionic villi. Immunity is central to protection of the placenta-fetal unit: infection can occur when IgG has a low neutralizing titer. Here we used immunohistochemical and function-blocking methods to correlate infection in the placenta with expression of potential CMV receptors in situ and in vitro. In placental villi, syncytiotrophoblasts express the virion receptor epidermal growth factor receptor (EGFR) but lack integrin coreceptors, and virion uptake occurs without replication. Focal infection can occur when transcytosed virions reach EGFR-expressing cytotrophoblasts that selectively initiate expression of αV integrin. In cell columns, proximal cytotrophoblasts lack receptors and distal cells express integrins α1β1 and αVβ3, enabling virion attachment. In the decidua, invasive cytotrophoblasts expressing coreceptors upregulate EGFR, thereby dramatically increasing susceptibility to infection. Our findings indicate that virion interactions with cytotrophoblasts expressing receptors in the placenta (i) change as the cells differentiate and (ii) correlate with spatially distinct sites of CMV replication in maternal and fetal compartments.
Mutational Evidence of Internal Fusion Loops in Herpes Simplex Virus Glycoprotein B
Authors: Hannah Brian P. , Heldwein Ekaterina E. , Bender Florent C. , Cohen Gary H. , Eisenberg Roselyn J.
Published: February 2007

Herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) is one of four glycoproteins necessary and sufficient for HSV cellular entry. Recently, the crystal structures of HSV-1 gB and vesicular stomatitis virus glycoprotein G were determined. Surprisingly, the two proteins share remarkable structural homology. Both proteins are homotrimeric and center about a long alpha-helix, features reminiscent of class I fusion proteins, such as influenza virus hemagglutinin or paramyxovirus F. However, these structures revealed that G has internal fusion loops, similar to the fusion loops of the class II fusion proteins, and that these loops are structurally conserved in gB. To examine whether these putative fusion loops are important for gB function, we mutated potential membrane-interacting (hydrophobic) residues to charged amino acids. Of most interest were mutant gB proteins that were expressed on the cell surface and were recognized by monoclonal antibodies against conformational epitopes but lacked the ability to function in cell-cell fusion assays. We find that three of the five hydrophobic amino acids targeted in these loops, tryptophan 174, tyrosine 179, and alanine 261, are integral in the function of gB. Our data suggest that they are part of an important functional domain. We hypothesize that two loops in domain 1 of HSV gB function as fusion loops. Our data are further evidence that gB is a viral fusogen and suggest clues as to how gB may function.
Resistance to Chronic Wasting Disease in Transgenic Mice Expressing a Naturally Occurring Allelic Variant of Deer Prion Protein
Authors: Meade-White Kimberly , Race Brent , Trifilo Matthew , Bossers Alex , Favara Cynthia , Lacasse Rachel , Miller Michael , Williams Elizabeth , Oldstone Michael , Race Richard , Chesebro Bruce
Published: February 2007

Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer or elk PrP in transgenic mice has induced susceptibility to chronic wasting disease (CWD), the prion disease of cervids. In the current experiments, transgenic mice expressing two naturally occurring allelic variants of deer PrP with either glycine (G) or serine (S) at residue 96 were found to differ in susceptibility to CWD infection. G96 mice were highly susceptible to infection, and disease appeared starting as early as 160 days postinfection. In contrast, S96 mice showed no evidence of disease or generation of disease-associated protease-resistant PrP (PrPres) over a 600-day period. At the time of clinical disease, G96 mice showed typical vacuolar pathology and deposition of PrPres in many brain regions, and in some individuals, extensive neuronal loss and apoptosis were noted in the hippocampus and cerebellum. Extraneural accumulation of PrPres was also noted in spleen and intestinal tissue of clinically ill G96 mice. These results demonstrate the importance of deer PrP polymorphisms in susceptibility to CWD infection. Furthermore, this deer PrP transgenic model is the first to demonstrate extraneural accumulation of PrPres in spleen and intestinal tissue and thus may prove useful in studies of CWD pathogenesis and transmission by oral or other natural routes of infection.
A New Crucial Protein Interaction Element That Targets the Adenovirus E4-ORF1 Oncoprotein to Membrane Vesicles
Authors: Chung Sang-Hyuk , Frese Kristopher K. , Weiss Robert S. , Prasad B. V. Venkataram , Javier Ronald T.
Published: February 2007

Human adenovirus type 9 exclusively elicits mammary tumors in experimental animals, and the primary oncogenic determinant of this virus is the
E4-ORF1
oncogene, as opposed to the well-known
E1A
and
E1B
oncogenes. The tumorigenic potential of E4-ORF1, as well as its ability to oncogenically stimulate phosphatidylinositol 3-kinase (PI3K), depends on a carboxyl-terminal PDZ domain-binding motif (PBM) that mediates interactions with several different membrane-associated cellular PDZ proteins, including MUPP1, PATJ, MAGI-1, ZO-2, and Dlg1. Nevertheless, because certain E4-ORF1 mutations that alter neither the sequence nor the function of the PBM abolish E4-ORF1-induced PI3K activation and cellular transformation, we reasoned that E4-ORF1 must possess an additional crucial protein element. In the present study, we identified seven E4-ORF1 amino acid residues that define this new element, designated domain 2, and showed that it mediates binding to a 70-kDa cellular phosphoprotein. We also discovered that domain 2 or the PBM independently promotes E4-ORF1 localization to cytoplasmic membrane vesicles and that this activity of domain 2 depends on E4-ORF1 trimerization. Consistent with the latter observation, molecular-modeling analyses predicted that E4-ORF1 trimerization brings together six out of seven domain 2 residues at each of the three subunit interfaces. These findings importantly demonstrate that PI3K activation and cellular transformation induced by E4-ORF1 require two separate protein interaction elements, domain 2 and the PBM, each of which targets E4-ORF1 to vesicle membranes in cells.
Thermo-chronology of the Barlet metamorphic basement unit: evidence for a Stephanian thermal event linked to Sb mineralization in the Haut Allier, France
Authors: van Hinsberg Vincent J. , Zinngrebe Enno , Wijs Hanno de , Vriend Simon P.
Published: February 2007

A thermo-chronological analysis of the Barlet basement unit (French Massif Central) reveals a four-stage history. Peak metamorphism (650 °C and 7 kbar) was followed by retrograde growth of albite blasts and development of the main foliation at 600 °C, and chloritization of the ferromagnesian minerals. The third stage is a marked reversal of cooling, with recrossing of the biotite isograd and local reappearance of garnet at 450 °C. This thermal event, inferred to result from hot fluid infiltration, is also recognized in the adjacent basin of Langeac, where it gives rise to anomalous coal grades (recording 200 °C at 1 km). A Stephanian age for this event correlates with a regional thermal event recognized throughout the Variscan, where it has been linked to delamination of the continental crust. This work represents the first instance in the Massif Central that recognizes this event in the shallow basement itself. Final cooling is accompanied by extensive fluid-induced sericitization, starting immediately after the peak of the thermal event and continuing to temperatures inferred for Sb–As ore deposition. This continuum leads us to conclude that reheating-related silicate reactions and ore deposition are caused by the same fluid and related to the wider regional Variscan thermal event.