Publications by authors named "Angelica Perez-Andujar"

14 Publications

  • Page 1 of 1

Optimizing beam models for dosimetric accuracy over a wide range of treatments.

Phys Med 2019 Feb 24;58:47-53. Epub 2019 Jan 24.

Department of Radiation Oncology, University of California San Francisco, 1600 Divisadero Street, Suite H1031, San Francisco, CA 94115, United States.

This work presents a systematic approach for testing a dose calculation algorithm over a variety of conditions designed to span the possible range of clinical treatment plans. Using this method, a TrueBeam STx machine with high definition multi-leaf collimators (MLCs) was commissioned in the RayStation treatment planning system (TPS). The initial model parameters values were determined by comparing TPS calculations with standard measured depth dose and profile curves. The MLC leaf offset calibration was determined by comparing measured and calculated field edges utilizing a wide range of MLC retracted and over-travel positions. The radial fluence was adjusted using profiles through both the center and corners of the largest field size, and through measurements of small fields that were located at highly off-axis positions. The flattening filter source was adjusted to improve the TPS agreement for the output of MLC-defined fields with much larger jaw openings. The MLC leaf transmission and leaf end parameters were adjusted to optimize the TPS agreement for highly modulated intensity-modulated radiotherapy (IMRT) plans. The final model was validated for simple open fields, multiple field configurations, the TG 119 C-shape target test, and a battery of clinical IMRT and volumetric-modulated arc therapy (VMAT) plans. The commissioning process detected potential dosimetric errors of over 10% and resulted in a final model that provided in general 3% dosimetric accuracy. This study demonstrates the importance of using a variety of conditions to adjust a beam model and provides an effective framework for achieving high dosimetric accuracy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmp.2019.01.011DOI Listing
February 2019

Commissioning and Evaluation of an Electronic Portal Imaging Device-Based In-Vivo Dosimetry Software.

Cureus 2018 Feb 2;10(2):e2139. Epub 2018 Feb 2.

Radiation Oncology, University of California San Francisco.

This study reports on our experience with the in-vivo dose verification software, EPIgray® (DOSIsoft, Cachan, France). After the initial commissioning process, clinical experiments on phantom treatments were evaluated to assess the level of accuracy of the electronic portal imaging device (EPID) based in-vivo dose verification. EPIgray was commissioned based on the company's instructions. This involved ion chamber measurements and portal imaging of solid water blocks of various thicknesses between 5 and 35 cm. Field sizes varied between 2 x 2 cm and 20 x 20 cm. The determined conversion factors were adjusted through an additional iterative process using treatment planning system calculations. Subsequently, evaluation was performed using treatment plans of single and opposed beams, as well as intensity modulated radiotherapy (IMRT) plans, based on recommendations from the task group report TG-119 to test for dose reconstruction accuracy. All tests were performed using blocks of solid water slabs as a phantom. For single square fields, the dose at isocenter was reconstructed within 3% accuracy in EPIgray compared to the treatment planning system dose. Similarly, the relative deviation of the total dose was accurately reconstructed within 3% for all IMRT plans with points placed inside a high-dose region near the isocenter. Predictions became less accurate than < 5% when the evaluation point was outside the treatment target. Dose at points 5 cm or more away from the isocenter or within an avoidance structure was reconstructed less reliably. EPIgray formalism accuracy is adequate for an efficient error detection system with verifications performed in high-dose volumes. It provides immediate intra-fractional feedback on the delivery of treatment plans without affecting the treatment beam. Besides the EPID, no additional hardware is required. The software evaluates local point dose measurements to verify treatment plan delivery and patient positioning within 5% accuracy, depending on the placement of evaluation points.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.2139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880591PMC
February 2018

Puerto Rico: After María.

Int J Radiat Oncol Biol Phys 2018 03;100(4):834-835

Department of Radiation Physics, University of California, San Francisco, San Francisco, California. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2017.12.267DOI Listing
March 2018

Characterization of the effect of a new commercial transmission detector on radiation therapy beams.

Pract Radiat Oncol 2017 Nov - Dec;7(6):e559-e567. Epub 2017 Apr 9.

Department of Radiation Oncology, University of California San Francisco, San Francisco, California. Electronic address:

Purpose: To evaluate the influence of a new commercial transmission detector on radiation therapy beams.

Methods And Materials: A transmission detector designed for online treatment monitoring was characterized on a TrueBeam STx linear accelerator with 6-MV, 6-flattening filter free, 10-MV, and 10-flattening filter free beams. Measurements of percentage depth doses, in-plane and cross-plane off-axis profiles at different depths, transmission factors, and skin dose were acquired with 3 × 3, 5 × 5, 10 × 10, 20 × 20, and 40 × 40 cm field sizes at 100 cm and 80 cm source-to-surface distance (SSD). A CC04 chamber was used for all profile and transmission factor measurements. Skin dose was assessed at 100, 90, and 80 cm SSD using a variety of detectors (Roos and Markus parallel-plate chambers and optically stimulated luminescent dosimeters [OSLDs]). Skin dose was also assessed for various patient sample plans with OSLDs.

Results: The percentage depth doses showed small differences between the unperturbed and perturbed beams for 100 cm SSD (≤4 mm depth of maximum dose difference, <1.2% average profile difference) for all field sizes. At 80 cm SSD, the differences were larger (≤8 mm depth of maximum dose difference, <3% average profile difference). The differences were larger for the flattened beams and larger field sizes. The off-axis profiles showed similar trends. Field penumbras looked similar with and without the transmission detector. Comparisons in the profile central 80% showed a maximum average (maximum) profile difference between all field sizes of 1.0% (2.6%) and 1.4% (6.3%) for 100 and 80 cm SSD, respectively. The average measured skin dose increase at 100 cm (80 cm) SSD for a 10 × 10 cm field size was <4% (<35%) for all energies. For a 40 × 40 cm field size, this increased to <31% (≤63%). For the sample patient plans, the average skin dose difference was 0.53% (range, -6.6% to 10.4%).

Conclusions: The transmission detector has minimal effect on clinically relevant radiation therapy beams for intensity modulated radiation therapy and volumetric arc therapy (field sizes 10 × 10 cm and less). For larger field sizes, some perturbations are observable that would need to be assessed for clinical impact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prro.2017.04.001DOI Listing
July 2018

Dosimetric characterization of hypofractionated Gamma Knife radiosurgery of large or complex brain tumors versus linear accelerator-based treatments.

J Neurosurg 2016 12;125(Suppl 1):97-103

Departments of 1 Radiation Oncology and.

OBJECTIVE Noninvasive Gamma Knife (GK) platforms, such as the relocatable frame and on-board imaging, have enabled hypofractionated GK radiosurgery of large or complex brain lesions. This study aimed to characterize the dosimetric quality of such treatments against linear accelerator-based delivery systems that include the CyberKnife (CK) and volumetric modulated arc therapy (VMAT). METHODS Ten patients treated with VMAT at the authors' institution for large brain tumors (> 3 cm in maximum diameter) were selected for the study. The median prescription dose was 25 Gy (range 20-30 Gy) in 5 fractions. The median planning target volume (PTV) was 9.57 cm (range 1.94-24.81 cm). Treatment planning was performed using Eclipse External Beam Planning V11 for VMAT on the Varian TrueBeam system, Multiplan V4.5 for the CyberKnife VSI System, and Leksell GammaPlan V10.2 for the Gamma Knife Perfexion system. The percentage of the PTV receiving at least the prescription dose was normalized to be identical across all platforms for individual cases. The prescription isodose value for the PTV, conformity index, Paddick gradient index, mean and maximum doses for organs at risk, and normal brain dose at variable isodose volumes ranging from the 5-Gy isodose volume (V5) to the 15-Gy isodose volume (V15) were compared for all of the cases. RESULTS The mean Paddick gradient index was 2.6 ± 0.2, 3.2 ± 0.5, and 4.3 ± 1.0 for GK, CK, and VMAT, respectively (p < 0.002). The mean V15 was 7.5 ± 3.7 cm (range 1.53-13.29 cm), 9.8 ± 5.5 cm (range 2.07-18.45 cm), and 16.1 ± 10.6 cm (range 3.58-36.53 cm) for GK, CK, and VMAT, respectively (p ≤ 0.03, paired 2-tailed t-tests). However, the average conformity index was 1.18, 1.12, and 1.21 for GK, CK, and VMAT, respectively (p > 0.06). The average prescription isodose values were 52% (range 47%-69%), 60% (range 46%-68%), and 88% (range 70%-94%) for GK, CK, and VMAT, respectively, thus producing significant variations in dose hot spots among the 3 platforms. Furthermore, the mean V5 values for GK and CK were similar (p > 0.79) at 71.9 ± 36.2 cm and 73.3 ± 31.8 cm, respectively, both of which were statistically lower (p < 0.01) than the mean V5 value of 124.6 ± 67.1 cm for VMAT. CONCLUSIONS Significantly better near-target normal brain sparing was noted for hypofractionated GK radiosurgery versus linear accelerator-based treatments. Such a result supports the use of a large number of isocenters or confocal beams for the benefit of normal tissue sparing in hypofractionated brain radiosurgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2016.7.GKS16881DOI Listing
December 2016

Estimating the probability of underdosing microscopic brain metastases with hippocampal-sparing whole-brain radiation.

Radiother Oncol 2016 08 9;120(2):248-52. Epub 2016 Jul 9.

Department of Radiation Oncology, University of California, San Francisco, United States.

Purpose/objectives: Whole-brain radiation for brain metastases can result in cognitive side effects. Hippocampal-sparing techniques have been developed to decrease morbidity, but they carry the risk of underdosing lesions near the hippocampus due to the unavoidable dose gradient from the hippocampal surface to the prescription isodose surface. This study examines the impact of variable levels of hippocampal sparing on the underdosing of potential brain metastases.

Materials/methods: Helical intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were developed for hippocampal-sparing whole-brain treatment. For all plans, 30Gy was prescribed in 10 fractions to result in mean hippocampal doses of 6-12Gy. From a series of expanded shells, we determined the distance from the hippocampus at which the parenchyma would receive less than specified doses. Then, using published data, a mathematical model was constructed to predict the incident probability of potential brain metastases receiving different doses for different levels of hippocampal sparing.

Results: Whole-brain radiation plans were able to spare the hippocampi to mean doses of 7-12Gy under our planning constraints; more stringent constraints compromised brain coverage. The dose gradients were ∼4% per mm, regardless of the hippocampal constraint, and they decreased sharply by a factor of almost 4 at approximately 15mm from the hippocampi. A mathematical model was constructed and combined the plan information with published data on the distribution of brain metastases, to determine the percentage of potential brain metastases receiving specified doses, as a function of technique and level of hippocampal sparing.

Conclusions: Our results describe the characteristics of an array of hippocampal-sparing whole-brain radiation dose distributions. These can be used as a decision-making guideline for weighing the benefit of decreased dose to the hippocampi against the cost of decreased dose to potential brain metastases when deciding on a hippocampal-sparing whole-brain irradiation treatment approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2016.05.030DOI Listing
August 2016

Assessment of image quality and dose calculation accuracy on kV CBCT, MV CBCT, and MV CT images for urgent palliative radiotherapy treatments.

J Appl Clin Med Phys 2016 03 8;17(2):279-290. Epub 2016 Mar 8.

University of California San Francisco.

A clinical workflow was developed for urgent palliative radiotherapy treatments that integrates patient simulation, planning, quality assurance, and treatment in one 30-minute session. This has been successfully tested and implemented clinically on a linac with MV CBCT capabilities. To make this approach available to all clin-ics equipped with common imaging systems, dose calculation accuracy based on treatment sites was assessed for other imaging units. We evaluated the feasibility of palliative treatment planning using on-board imaging with respect to image quality and technical challenges. The purpose was to test multiple systems using their commercial setup, disregarding any additional in-house development. kV CT, kV CBCT, MV CBCT, and MV CT images of water and anthropomorphic phantoms were acquired on five different imaging units (Philips MX8000 CT Scanner, and Varian TrueBeam, Elekta VersaHD, Siemens Artiste, and Accuray Tomotherapy linacs). Image quality (noise, contrast, uniformity, spatial resolution) was evaluated and compared across all machines. Using individual image value to density calibrations, dose calculation accuracies for simple treatment plans were assessed for the same phantom images. Finally, image artifacts on clinical patient images were evaluated and compared among the machines. Image contrast to visualize bony anatomy was sufficient on all machines. Despite a high noise level and low contrast, MV CT images provided the most accurate treatment plans relative to kV CT-based planning. Spatial resolution was poorest for MV CBCT, but did not limit the visualization of small anatomical structures. A comparison of treatment plans showed that monitor units calculated based on a prescription point were within 5% difference relative to kV CT-based plans for all machines and all studied treatment sites (brain, neck, and pelvis). Local dose differences > 5% were found near the phantom edges. The gamma index for 3%/3 mm criteria was ≥ 95% in most cases. Best dose calculation results were obtained when the treatment isocenter was near the image isocenter for all machines. A large field of view and immediate image export to the treatment planning system were essential for a smooth workflow and were not provided on all devices. Based on this phantom study, image quality of the studied kV CBCT, MV CBCT, and MV CT on-board imaging devices was sufficient for treatment planning in all tested cases. Treatment plans provided dose calculation accuracies within an acceptable range for simple, urgently planned palliative treatments. However, dose calculation accuracy was compromised towards the edges of an image. Feasibility for clinical implementation should be assessed separately and may be complicated by machine specific features. Image artifacts in patient images and the effect on dose calculation accuracy should be assessed in a separate, machine-specific study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1120/jacmp.v17i2.6040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874969PMC
March 2016

Inter-Institutional Comparison of Personalized Risk Assessments for Second Malignant Neoplasms for a 13-Year-Old Girl Receiving Proton versus Photon Craniospinal Irradiation.

Cancers (Basel) 2015 Mar 10;7(1):407-26. Epub 2015 Mar 10.

Medical Physics Program, Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Tower Dr., Baton Rouge, LA 70803, USA.

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient's body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers7010407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381265PMC
March 2015

Quality assurance of stereotactic alignment and patient positioning mechanical accuracy for robotized Gamma Knife radiosurgery.

Phys Med Biol 2014 Dec 10;59(23):N221-6. Epub 2014 Nov 10.

The automatic patient positioning system and its alignment is critical and specified to be less than 0.35 mm for a radiosurgical treatment with the latest robotized Gamma Knife Perfexion (GKPFX). In this study, we developed a quantitative QA procedure to verify the accuracy and robustness of such a system. In particular, we applied the test to a unit that has performed >1000 procedures at our institution. For the test, a radiochromic film was first placed inside a spherical film phantom and then irradiated with a sequence of linearly placed shots of equal collimator size (e.g. 4 mm) via the Leksell Gamma Knife Perfexion system (PFX). The shots were positioned with either equal or unequal gaps of approximately 8 mm both at center and off-center positions of the patient positioning system. Two independent methods of localizing the irradiation shot center coordinates were employed to measure the gap spacing between adjacent shots. The measured distance was then compared with the initial preset values for the test. On average, the positioning uncertainty for the PFX delivery system was found to be 0.03 ± 0.2 mm (2σ). No significant difference in the positioning uncertainty was noted among measurements in the x-, y- and z-axis orientations. In conclusion, a simple, fast, and quantitative test was developed and demonstrated for routine QA of the submillimeter PFX patient positioning system. This test also enables independent verification of any patient-specific shot positioning for a critical treatment such as a tumor in the brainstem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/0031-9155/59/23/N221DOI Listing
December 2014

Monte Carlo and analytical model predictions of leakage neutron exposures from passively scattered proton therapy.

Med Phys 2013 Dec;40(12):121714

Department of Radiation Physics, Unit 1202, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.

Purpose: Stray neutron radiation is of concern after radiation therapy, especially in children, because of the high risk it might carry for secondary cancers. Several previous studies predicted the stray neutron exposure from proton therapy, mostly using Monte Carlo simulations. Promising attempts to develop analytical models have also been reported, but these were limited to only a few proton beam energies. The purpose of this study was to develop an analytical model to predict leakage neutron equivalent dose from passively scattered proton beams in the 100-250-MeV interval.

Methods: To develop and validate the analytical model, the authors used values of equivalent dose per therapeutic absorbed dose (H∕D) predicted with Monte Carlo simulations. The authors also characterized the behavior of the mean neutron radiation-weighting factor, wR, as a function of depth in a water phantom and distance from the beam central axis.

Results: The simulated and analytical predictions agreed well. On average, the percentage difference between the analytical model and the Monte Carlo simulations was 10% for the energies and positions studied. The authors found that wR was highest at the shallowest depth and decreased with depth until around 10 cm, where it started to increase slowly with depth. This was consistent among all energies.

Conclusion: Simple analytical methods are promising alternatives to complex and slow Monte Carlo simulations to predict H∕D values. The authors' results also provide improved understanding of the behavior of wR which strongly depends on depth, but is nearly independent of lateral distance from the beam central axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1118/1.4829512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843753PMC
December 2013

Management of vestibular schwannoma: focus on vertigo.

CNS Oncol 2013 Jan;2(1):99-104

Department of Radiation Oncology, University of California at San Francisco, 505 Parnassus Avenue, Room L-08 (Box 0226), San Francisco, CA 94143-0226, USA.

This article reviews published literature on vertigo and a 'sense of imbalance' affecting patients who are treated with radiosurgery (RS) for vestibular schwannoma. This is a relatively understudied complaint, along with tinnitus, in this patient population, despite its significant impact on quality of life. It is also a symptom that is most inconsistently impacted by either RS or surgery. This article aims to highlight the importance of this symptom in patients managed for vestibular schwannoma primarily with RS to encourage a more systematic study of vertigo as an outcome measure and to help elucidate its potential etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/cns.12.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169458PMC
January 2013

Microdosimetric measurements for neutron-absorbed dose determination during proton therapy.

Radiat Prot Dosimetry 2012 Aug 14;151(2):365-73. Epub 2012 Feb 14.

Department of Medical Physics, University of Wisconsin, 1005 Wisconsin Institutes for Medical Research 1111 Highland Ave., Madison, WI 53705, USA.

This work presents microdosimetric measurements performed at the Midwest Proton Radiotherapy Institute in Bloomington, Indiana, USA. The measurements were done simulating clinical setups with a water phantom and for a variety of stopping targets. The water phantom was irradiated by a proton spread out Bragg peak (SOBP) and by a proton pencil beam. Stopping target measurements were performed only for the pencil beam. The targets used were made of polyethylene, brass and lead. The objective of this work was to determine the neutron-absorbed dose for a passive and active proton therapy delivery, and for the interactions of the proton beam with materials typically in the beam line of a proton therapy treatment nozzle. Neutron doses were found to be higher at 45° and 90° from the beam direction for the SOBP configuration by a factor of 1.1 and 1.3, respectively, compared with the pencil beam. Meanwhile, the pencil beam configuration produced neutron-absorbed doses 2.2 times higher at 0° than the SOBP. For stopping targets, lead was found to dominate the neutron-absorbed dose for most angles due to a large production of low-energy neutrons emitted isotropically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rpd/ncs002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422515PMC
August 2012

An analytic model of neutron ambient dose equivalent and equivalent dose for proton radiotherapy.

Phys Med Biol 2010 Dec 12;55(23):6975-85. Epub 2010 Nov 12.

Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.

Stray neutrons generated in passively scattered proton therapy are of concern because they increase the risk that a patient will develop a second cancer. Several investigations characterized stray neutrons in proton therapy using experimental measurements and Monte Carlo simulations, but capabilities of analytical methods to predict neutron exposures are less well developed. The goal of this study was to develop a new analytical model to calculate neutron ambient dose equivalent in air and equivalent dose in phantom based on Monte Carlo modeling of a passively scattered proton therapy unit. The accuracy of the new analytical model is superior to a previous analytical model and comparable to the accuracy of typical Monte Carlo simulations and measurements. Predictions from the new analytical model agreed reasonably well with corresponding values predicted by a Monte Carlo code using an anthropomorphic phantom.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/0031-9155/55/23/S01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001300PMC
December 2010

Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system.

Phys Med Biol 2009 Feb 16;54(4):993-1008. Epub 2009 Jan 16.

University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705-2221, USA.

In this work the neutron production in a passive beam delivery system was investigated. Secondary particles including neutrons are created as the proton beam interacts with beam shaping devices in the treatment head. Stray neutron exposure to the whole body may increase the risk that the patient develops a radiogenic cancer years or decades after radiotherapy. We simulated a passive proton beam delivery system with double scattering technology to determine the neutron production and energy distribution at 200 MeV proton energy. Specifically, we studied the neutron absorbed dose per therapeutic absorbed dose, the neutron absorbed dose per source particle and the neutron energy spectrum at various locations around the nozzle. We also investigated the neutron production along the nozzle's central axis. The absorbed doses and neutron spectra were simulated with the MCNPX Monte Carlo code. The simulations revealed that the range modulation wheel (RMW) is the most intense neutron source of any of the beam spreading devices within the nozzle. This finding suggests that it may be helpful to refine the design of the RMW assembly, e.g., by adding local shielding, to suppress neutron-induced damage to components in the nozzle and to reduce the shielding thickness of the treatment vault. The simulations also revealed that the neutron dose to the patient is predominated by neutrons produced in the field defining collimator assembly, located just upstream of the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/0031-9155/54/4/012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136452PMC
February 2009