In-line MRI-LINAC depth dose measurements using an in-house plastic scintillation dosimeter.

Plastic scintillation dosimeters (PSDs) have many properties that make them desirable for relative dosimetry with MRI-LINACs. An in-house PSD, Farmer ionisation chamber and Gafchromic EBT3 film were used to measure central axis percentage depth dose distributions (PDDs) at the Australian MRI-LINAC Mean errors were calculated between each detector's responses, where the in-house PSD was on average within 0.7% of the Farmer chamber and 1.4% of film, while the Farmer chamber and film were on average within 1.1% of each other. However, the PSD systematically over-estimated the dose as depth increased, approaching a maximum overestimation of the order of 3.5% for the smallest field size measured. This trend was statistically insignificant for all other field sizes measured; further investigation is required to determine the source of this effect. The calculated values of mean absolute error are comparable to the those of trusted dosimeters reported in the literature. These mean absolute errors, and the ubiquity of desirable dosimetric qualities inherent to PSDs suggest that PSDs in general are accurate for relative dosimetry with the MRI-LINAC. Further investigation is required into the source of the reported systematic trends dependent on field-size and depth of measurement.

Dosimetric Optimization and Commissioning of a High Field Inline MRI-Linac.

Purpose: Unique characteristics of MRI-linac systems and mutual interactions between their components pose specific challenges for their commissioning and quality assurance. The Australian MRI-linac is a prototype system which explores the inline orientation, with radiation beam parallel to the main magnetic field. The aim of this work was to commission the radiation-related aspects of this system for its application in clinical treatments. Methods: Physical alignment of the radiation beam to the magnetic field was fine-tuned and magnetic shielding of the radiation head was designed to achieve optimal beam characteristics. These steps were guided by investigative measurements of the beam properties. Subsequently, machine performance was benchmarked against the requirements of the IEC60976/77 standards. Finally, the geometric and dosimetric data was acquired, following the AAPM Task Group 106 recommendations, to characterize the beam for modeling in the treatment planning system and with Monte Carlo simulations. The magnetic field effects on the dose deposition and on the detector response have been taken into account and issues specific to the inline design have been highlighted. Results: Alignment of the radiation beam axis and the imaging isocentre within 2 mm tolerance was obtained. The system was commissioned at two source-to-isocentre distances (SIDs): 2.4 and 1.8 m. Reproducibility and proportionality of the dose monitoring system met IEC criteria at the larger SID but slightly exceeded it at the shorter SID. Profile symmetry remained under 103% for the fields up to ~34 × 34 and 21 × 21 cm2 at the larger and shorter SID, respectively. No penumbra asymmetry, characteristic for transverse systems, was observed. The electron focusing effect, which results in high entrance doses on central axis, was quantified and methods to minimize it have been investigated. Conclusion: Methods were developed and employed to investigate and quantify the dosimetric properties of an inline MRI-Linac system. The Australian MRI-linac system has been fine-tuned in terms of beam properties and commissioned, constituting a key step toward the application of inline MRI-linacs for patient treatments.

High resolution silicon array detector implementation in an inline MRI-linac.

PURPOSE: Dynamic dosimaging is a concept whereby a detector in motion is tracked with magnetic resonance imaging (MRI) to validate the amount and position of dose in a radiation therapy treatment on an MRI-linac. This work takes steps toward the realization of dynamic dosimaging with the novel high resolution silicon array detector: MagicPlate-512 (M512). The performance of the M512 was assessed in a 1.0 T inline MRI-linac, without simultaneous imaging and then during an imaging sequence, both during dosimetry. MR images were acquired to determine the effect of the detector and its components on image quality. METHODS: Beam profiles were measured using the M512 on the Australian MRI-Linac and a comparison made with Gafchromic EBT3 film to investigate any intrinsic magnetic field effects in the silicon. The M512 has 512 sensitive volumes, each 0.5 × 0.5 × 0.037 mm3 in dimension, organized in a two-dimensional array. Small field sizes up to 4.2 × 3.8 cm2 were investigated in both solid water and then solid lung phantoms. Beam profiles taken at 1.0 T were compared to 0 T conditions, and also to profiles taken during a gradient echo (GRE) imaging sequence. Differences in 80%-20% penumbral width and full width at half maximum (FWHM) were investigated. Localizer MR images were acquired of the detector adjacent to a water phantom. RESULTS: Good agreement was observed between the M512 and film, with average differences in penumbral width and FWHM of <1 mm in the absence of the imaging sequence. Concurrent imaging widened the penumbra by up to 1.2 mm due to RF noise affecting the detector; film profiles were unchanged. Magnetic resonance images were affected by noise, in particular, due to the large amount of aluminum present, as well as from the USB cable, which acted as an antenna. Unfortunately, due to these issues, suitable dynamic dose imaging was not achieved with the current M512/phantom configuration and the MRI-linac. However, progress was made toward achieving this goal for future work. CONCLUSIONS: The M512 silicon array detector successfully measured high-resolution beam profiles in agreement with Gafchromic film to within an average of <1 mm on the first MRI-linac in Australia. More effective noise reduction will be required for the achievement of dynamic dosimaging in the future.

Experimental characterization of magnetically focused electron contamination at the surface of a high-field inline MRI-linac.

PURPOSE: The fringe field of the Australian MRI-linac causes contaminant electrons to be focused along the central axis resulting in a high surface dose. This work aims to characterize this effect using Gafchromic film and high-resolution detectors, MOSkinTM and microDiamond. The secondary aim is to investigate the influence of the inline magnetic field on the relative dose response of these detectors. METHODS: The Australian MRI-linac has the unique feature that the linac is mounted on rails allowing for measurements to be performed at different magnetic field strengths while maintaining a constant source-to-surface distance (SSD). Percentage depth doses (PDD) were collected at SSD 1.82 m in a solid water phantom positioned in a low magnetic field region and then at isocenter of the MRI where the magnetic field is 1 T. Measurements for a range of field sizes were taken with the MOSkinTM , microDiamond, and Gafchromic® EBT3 film. The detectors' relative responses at 1 T were compared to the near 0 T PDD beyond the region of electron contamination, that is, 20 mm depth. The near surface measurements inside the MRI bore were compared among the different detectors. RESULTS: Skin dose in the MRI, as measured with the MOSkinTM , was 104.5% for 2.1 × 1.9 cm2 , 185.6% for 6.1 × 5.8 cm2 , 369.1% for 11.8 × 11.5 cm2 , and 711.1% for 23.5 × 23 cm2 . The detector measurements beyond the electron contamination region showed agreement between the relative response at 1 T and near 0 T. Film was in agreement with both detectors in this region further demonstrating their relative response is unaffected by the magnetic field. CONCLUSIONS: Experimental characterization of the high electron contamination at the surface was performed for a range of field sizes. The relative response of MOSkinTM and microDiamond detectors, beyond the electron contamination region, were confirmed to be unaffected by the 1-T inline magnetic field.

4D Monte Carlo dose calculations for pre-treatment quality assurance of VMAT SBRT: a phantom-based feasibility study.

Volumetric arc therapy (VMAT) for lung stereotactic body radiotherapy (SBRT) is challenging due to both breathing-induced motion and the dynamic components of the linear accelerator. In this study, a 4D Monte Carlo (4DMC) dose calculation method for VMAT SBRT is proposed and the feasibility of the method is evaluated. A rigidly-moving lung phantom was imaged using four dimensional computed tomography (4DCT). VMAT SBRT plans were generated on the average intensity projection dataset using the internal target volume (ITV) strategy (ITV-plan) and a single phase to simulate a dynamic treatment-couch tracking technique (TRACKING-plan). 4DMC simulations were performed and compared to 3D Monte Carlo (3DMC) and 3D- and 4D- calculations in the treatment planning system using the adaptive convolution (AC) algorithm. Dose metrics calculated for the ITV-plan showed an overestimation with 3D adaptive convolution (3DAC) for D[Formula: see text] (GTV) by 3.5% and by 2.0% for 3DMC, both compared to 4DMC. The TRACKING-plan D[Formula: see text] (GTV) calculated with the 3DAC method overestimated by 2.0% compared with 4DMC. Deviations between the calculation methods for D mean (Lung) and D[Formula: see text] (PTV) were minimal. For both plans, measurements were taken with EBT3 film inside the phantom tumour. EBT3 film profiles showed good agreement with 4DMC for the TRACKING-plan giving a gamma pass rate of 97.2% for 3%/3 mm global and for 3DAC compared with measured, 95.8%. Whereas for the ITV-plan, the 3D profiles varied from film in the ITV periphery region with a pass rates of 50% and 48.6% for 3DAC and 3DMC, respectively. 4DMC agreed more closely to measurements for this plan with a pass rate of 95.8%. We have proposed an accurate method to perform 4D dose calculations for pre-treatment quality assurance of VMAT SBRT. The method was compared to experimental measurements and for both plans, 4DMC dose agreed with measurements more closely than other evaluated dose calculation methods. This study has demonstrated the feasibility of this 4DMC method.

First measurements with a plastic scintillation dosimeter at the Australian MRI-LINAC.

MRI-LINACs combine MRI and LINAC technologies with the potential for image guided radiation therapy with optimal soft-tissue contrast. In this work, we present the advantages and limitations of plastic scintillation dosimeters (PSDs) for relative dosimetry with MRI-LINACs. PSDs possess many desirable qualities, including magnetic field insensitivity and irradiation angle independence, which are expected to make them suitable for dosimetry with MRI-LINACs. An in-house PSD was used to measure field size output factors as well as a percent depth dose distribution and the beam quality index TPR20/10 at a [Formula: see text] cm2 field size. Measurements were repeated with a Scanditronix/Wellhofer FC65-G ionisation chamber and PTW 60019 microDiamond detector for comparison. Relative differences were calculated between the three detectors, where the mean difference in dose was 1.2% between the PSD and ionisation chamber, 1.9% between the PSD and microDiamond detector and 1.3% between the microDiamond detector and the ionisation chamber. The closeness between the three mean differences in doses suggests that PSDs are feasible for relative dosimetry with MRI-LINACs.

A feasibility study for high-resolution silicon array detector performance in the magnetic field of a permanent magnet system.

PURPOSE: Magnetic field effects on dose distribution and detector functionality must be well understood. The detector utilized to investigate these magnetic field effects was the DUO silicon array detector; the performance of this high spatial resolution detector was assessed under these conditions. The results were compared to Gafchromic EBT3 film to highlight any intrinsic magnetic field effects in the silicon. The results were also compared to previously published MagicPlate-512 (M512) data. The DUO has an improved spatial resolution (200 µm) over the M512 (2 mm). METHODS: A permanent magnet named Magnetic Apparatus for RaDiation Oncology Studies (MARDOS) paired with a standard linear accelerator (linac) enables either transverse (1.2 T) or inline (0.95 T) orientations of the magnetic field with respect to the radiation beam. A 6 MV Varian 2100C Linac provided the radiation component for the measurements. The DUO detector has 505 sensitive volumes (each volume measuring 800 × 40 × 100 µm3 ) organized in two orthogonal, linear arrays. The DUO was embedded in a solid water phantom in the first set-up and then a solid lung phantom in the second set-up and placed between the magnet cones. Beam profiles were compared under the magnetic field conditions and 0 T. Small field sizes from 0.8 × 0.8 cm2 up to 2.3 × 2.3 cm2 were investigated. The size of the air gap above the sensitive volumes of the DUO was investigated in the transverse orientation to assess the anticipated magnetic field effects. Full width at half maximum (FWHM), 80-20% penumbral widths and maximum dose differences between detectors and between the presence/absence of a magnetic field were investigated. Symmetry was also assessed for investigation of profile skewness under the transverse field. RESULTS: The penumbral widths measured by the DUO detector demonstrated good agreement with film and the M512 to within an average of 0.5 mm (within uncertainty: ±1 mm). The static inline magnetic field had minimal effect on the profiles in solid water. As expected, the lower density of solid lung meant that this material was more susceptible to demonstrating magnetic field effects in the dose deposited. The greatest penumbral narrowing due to the inline field (0.7 mm) occurred in lung. Central axis dose increase was greatest in lung (maximum: 9%). The transverse field widened penumbra, most notably in the solid lung phantom, by a maximum of 2.3 mm. The largest asymmetry due to the transverse field (4.6%) was also in solid lung. When the air gap above the DUO was filled with bolus, the dose maximum measured by the DUO was within 1.4% of film. CONCLUSIONS: The DUO detector has been shown to be successful in accurately describing the dose changes for small field sizes to within a 200-µm resolution in an environment resembling that of an MRI-linac. The DUO measurements were in agreement with both film and the M512 measurements, and therefore the DUO was found to be an appropriate alternative to the M512, with improvement in terms of its higher spatial resolution. MARDOS provided a suitable environment for these preliminary tests before progressing to the MRI-linac.

Protein Ontology: a controlled structured network of protein entities.

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO's organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO's representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments.

Manipulating In-House Designed Drug Databases For The Prediction of pH-Dependent Aqueous Drug Solubility.

Chemical, pharmacokinetic, and pharmacodynamics properties are available in the package inserts of every Food and Drug Administration (FDA) approved prescription drug, including all available chemotherapy drugs. These inserts follow a specific format imposed by the FDA. Whether chemotherapy drugs are administered via the parenteral route or alimentary tract, a significant factor affecting their bioavailability, elimination and consequently the drug's effectiveness and potency, is its state of aqueous solubility. Water solubility has always lent itself poorly to the different predictive and experimental measures employed in the determination of a useful quantitative assessment. In this project, we first built a chemical structure based searchable database for 85 FDA approved chemotherapy drugs and then used Bio-Rad's KnowItAll® Informatics suite to focus on the drugs pH-dependent water solubility prediction. We compared the predicted values for water solubility to the available values reported in the drug inserts, testing the practical utility and the predictive ability of our model in reporting such a clinically relevant, underreported pharmacokinetic parameter. A relational cancer drug database (MySQL) was created to further facilitate analysis and/or prediction of a chemotherapy compound's missing pharmacokinetic properties.

The representation of protein complexes in the Protein Ontology (PRO).

BACKGROUND: Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. DESCRIPTION: We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. CONCLUSION: PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species.

The Protein Ontology: a structured representation of protein forms and complexes.

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontology Foundry.

A Database Developed with Information Extracted from Chemotherapy Drug Package Inserts to Enhance Future Prescriptions.

Package inserts of Food and Drug Administration (FDA) approved prescription drugs, including chemotherapy drugs, must follow a specific format imposed by the FDA. These inserts are created by unrelated pharmaceutical companies and as a result tend to be very different in the way the required information is reported. Chemical and pharmacokinetic properties including absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) are crucial elements to a prescribing information packet and are often missing from the reported data. This undergraduate research project analyzes the information packets of 85 randomly chosen chemically diverse chemotherapy drugs for four parameters important to patient care; viz, volume of distribution (VD), elimination half-life (t1/2), bioavailability, and water solubility. The prescribing information from the package inserts of each was analyzed in detail and pertinent information was consequently tabulated into a database using a commercial informatics platform. Then using a substructure search-tool, sixty-five chemotherapy drugs containing a carbonyl group in their chemical structure were selected and as hypothesized, it was found that many of these packets were significantly lacking in the reporting of the four parameters of interest. To further enhance this cataloged data, a freely available online database was consequently developed (http://annotation.dbi.udel.edu/CancerDB/) with the intention that the chemical, biological, and clinical community will now add some of the missing parameters.