bluuebunny/crossref_metadata_2025 huggingface dataset:
TU‐C‐12A‐08: Thermally‐Stabilized Isotropic Diffusion Phantom for Multisite Assessment of Apparent Diffusion Coefficient Reproducibilty
Authors: Boss M , Chenevert T , Waterton J , Morris D , Ragheb H , Jackson A , deSouza N , Collins D , van Beers B , Garteiser P , Doblas S , Persigehl T , Hedderich D , Martin A , Mukherjee P , Keenan K , Russek S , Jackson E , Zahlmann G
Published: July 2014

Purpose:

To construct an appropriate phantom for quality control use in diffusion‐weighted imaging (DWI), to establish ground truth for measurement of apparent diffusion coefficient (ADC) and to characterize measurement linearity across a relevant physiological range of ADC.

Methods:

Aqueous solutions containing the polymer polyvinylpyrrolidone (PVP) were mixed at concentrations of 0, 10, 20, 30, 40 and 50% by mass PVP. These solutions were placed in 20 mL vials, arranged in concentric inner and outer circles, with a central water vial, and were fixed in a spherical phantom with a diameter of 194 mm, designed to fit into commercially‐available MRI head coils. Two prototype phantoms were constructed, and underwent inter‐site comparison in the US and EU. The phantoms were filled with an ice‐water bath to ensure stable temperature; 0 °C temperature was verified by use of a thermocouple before and after scans. The phantoms were scanned using b‐values of 0, 500 and 900 s/mm2 at several sites, using coronal and/or axial orientations and scan planes.

Results:

ADC values ranged from 0.12 to 1.12 × 10‐3 mm2/s, and exhibited a high degree of reproducibility across different scanners and imaging sites (coefficient of variations (CoV) ranged from 1.1 to 2.2% for 0 to 40% PVP, with 50% PVP at 11.3%). Little difference in ADCs was seen between inner and outer ring vials of the same PVP concentration (average CoV< 5% across vials, 10.3% for 50% PVP).

Conclusion:

The range of ADCs covers a relevant physiological range, most notably in brain white matter. The ADCs of water vials were in excellent agreement with literature values of the diffusion coefficient of water at 0 °C (1.1 × 10‐3 mm2/s). The phantom provides a much needed quality control tool for DWI, and provides ground truth with the diffusion coefficient of water at 0 °C.
TU‐D‐BRD‐01: Image Guided SBRT II: Challenges ' Pitfalls
Authors: Chang Z , Yin F , Cho J
Published: July 2014

Stereotactic body radiation therapy (SBRT) has been effective treatment for the management of various diseases, which often delivers high radiation dose in a single or a few fractions. SBRT therefore demands precise treatment delivery to the tumor while sparing adjacent healthy tissue. Recent developments in image guidance enable target localization with increased accuracy. With such improvements in localization, image‐guided SBRT has been widely adopted into clinical practice. In SBRT, high radiation dose is generally delivered with small fields. Therefore, it is crucial to accurately measure dosimetric data for the small fields during commissioning. In addition, image‐guided SBRT demands accurate image localization to ensure safety and quality of patient care. Lately, the reports of AAPM TG 142 and TG 104 have been published and added recommendations for imaging devices that are integrated with the linear accelerator for SBRT. Furthermore, various challenges and potential pitfalls lie in the clinical implementation of image‐guided SBRT. In this lecture, these challenges and pitfalls of image‐guided SBRT will be illustrated and discussed from dosimetric, technical and clinical perspectives.Being a promising technique, image‐guided SBRT has shown great potentials, and will lead to more accurate and safer SBRT treatments.

Learning Objectives:

To understand dosimetric challenges and pitfalls for IGRT application in SBRT.

To understand major clinical challenges and pitfalls for IGRT application in SBRT.

To understand major technical challenges and pitfalls for IGRT application in SBRT.
TU‐D‐9A‐01: TG176: Dosimetric Effects of Couch Tops and Immobilization Devices
Authors: Olch A
Published: July 2014

The dosimetric impact from devices external to the patient is a complex combination of increased skin dose, reduced tumor dose, and altered dose distribution. Although small monitor unit or dose corrections are routinely made for blocking trays, ion chamber correction factors, or tissue inhomogeneities, the dose perturbation of the treatment couch top or immobilization devices are often overlooked. These devices also increase surface dose, an effect which is also often ignored or underestimated. These concerns have grown recently due to the increased use of monolithic carbon fiber couch tops which are optimal for imaging for patient position verification but cause attenuation and increased surface dose compared to the ‘tennis racket’ style couch top they often replace. Also, arc delivery techniques have replaced stationary gantry techniques which cause a greater fraction of the dose to be delivered from posterior angles. A host of immobilization devices are available and used to increase patient positioning reproducibility, and these also have attenuation and skin dose implications which are often ignored. This report of Task Group 176 serves to present a survey of published data that illustrates the magnitude of the dosimetric effects of a wide range of devices external to the patient. The report also provides methods for modeling couch tops in treatment planning systems so the physicist can accurately compute the dosimetric effects for indexed patient treatments. Both photon and proton beams are considered. A discussion on avoidance of high density structures during beam planning is also provided. An important aspect of this report are the recommendations we make to clinical physicists, treatment planning system vendors, and device vendors on how to make measurements of skin dose and attenuation, how to report these values, and for the vendors, an appeal is made to work together to provide accurate couch top models in planning systems.

Learning Objectives:

What are the dosimetric effects of couch tops

What are the dosimetric effects of immobilization devices

How can one model couch tops in the treatment planning system

How can one measure attenuation and surface dose changes due to external devices
TU‐F‐BRE‐07: In Vivo Neutron Detection in Patients Undergoing Stereotactic Ablative Radiotherapy (SABR) for Primary Kidney Cancer Using 6Li and 7Li Enriched TLD Pairs
Authors: Lonski P , Franich R , Siva S , Keehan S , Taylor M , Kron T
Published: July 2014

Purpose:

Stereotactic ablative radiotherapy (SABR) for primary kidney cancer often involves the use of high‐energy photons combined with a large number of monitor units. While important for risk assessment, the additional neutron dose to untargeted healthy tissue is not accounted for in treatment planning. This work aims to detect out‐of‐field neutrons in vivo for patients undergoing SABR with high‐energy (>10 MV) photons and provides preliminary estimates of neutron effective dose.

Methods:

3 variations of high‐sensitivity LiF:Mg,Cu,P thermoluminescent dosimeter (TLD) material, each with varying 6Li / 7Li concentrations, were used in custom‐made Perspex holders for in vivo measurements. The variation in cross section for thermal neutrons between Li isotopes was exploited to distinguish neutron from photon signal. Measurements were made out‐of‐field for 7 patients, each undergoing 3D‐conformal SABR treatment for primary kidney cancer on a Varian 21iX linear accelerator.

Results:

In vivo measurements show increased signal for the 6Li enriched material for patients treated with 18 MV photons. Measurements on one SABR patient treated using only 6 MV showed no difference between the 3 TLD materials. The out‐of‐field photon signal decreased exponentially with distance from the treatment field. The neutron signal, taken as the difference between 6Li enriched and 7Li enriched TLD response, remains almost constant up to 50 cm from the beam central axis. Estimates of neutron effective dose from preliminary TLD calibration suggest between 10 and 30 mSv per 1000 MU delivered at 18 MV for the 7 patients.

Conclusion:

TLD was proven to be a useful tool for the purpose of in vivo neutron detection at out‐of‐field locations. Further work is required to understand the relationship between TL signal and neutron dose. Dose estimates based on preliminary TLD calibration in a neutron beam suggest the additional neutron dose was <30 mSv per 1000 MU at 18 MV.
TU‐F‐BRE‐08: Significant Variations in Measured Small Cone Output Factor for FFF Beams
Authors: Sudhyadhom A , Ma L , Kirby N
Published: July 2014

Purpose:

To evaluate the measurement accuracy of several dosimeters for small cone output factors in two SRS/SBRT dedicated systems with Flattening Filter Free (FFF) beams: a Varian TrueBeam STx (TB) and an Accuray CyberKnife VSI (CK). Output factors (OFs) were measured for both machines and for CK, compared against a Monte Carlo model.

Methods:

Dose measurements were taken using three different FFF beams (TB 6XFFF, TB 10XFFF, and CK 6XFFF). Three commonly used types of dosimeters were examined in this work: a micro‐ion chamber (Exradin A16), two shielded diodes (PTW TN60008 and PTW TN60017), and radiochromic film (Gafchromic EBT2). Measured OFs from these dosimeters were compared with each other and OFs measured with an Exradin W1 scintillator. Monte Carlo determined correction factors for the CK beam for the micro‐ion chamber and diodes were applied to the respective OF measurements and compared against scintillator measured OFs corrected for volume averaging.

Results:

OFs measured for the smallest fields using the micro‐ion chamber, diodes, scintillator, and film varied substantially (with up to a 16% difference between dosimeters). Micro‐ion chamber and film OF measurements were up to 9% and 10%, respectively, lower than scintillator measurements for the smallest fields. OF measurements by diode were up to 6% greater than scintillator measurements for the smallest fields. With correction factors, the micro‐ion chamber and diode measured OFs showed good agreement with scintillator measured OFs for the CK 6XFFF beam (within 3% and 1.5%, respectively).

Conclusion:

Uncorrected small field OFs vary significantly with dosimeter. The accuracy of scintillator measurements for small field OFs may be greater than the other dosimeters studied in this work (when uncorrected). Measurements involving EBT2 film may Result in lower accuracy for smaller fields (less than 10mm). Care should be taken in the choice of the dosimeter used for small field OF measurements.
TU‐F‐BRE‐09: Towards the Establishment of Dosimetric References in Small Fields Using the New Concept of Dose‐Area Product
Authors: Dufreneix S , Bordy J , Delaunay F , Delaunay F , Daures J , Gouriou J , Le Roy M , Ostrowsky A , Rapp B , Sommier L
Published: July 2014

Purpose:

To establish dosimetric references of absorbed dose in water in radiation fields smaller than 2 cm used in radiotherapy thanks to a new methodology based on the use of dosimeters larger than the field size.

Methods:

A new graphite calorimeter was constructed with a large sensitive volume (diameter of the core: 30 mm). This primary dosimeter was fully characterized and compared to previous LNE‐LNHB graphite calorimeters in a 60Co large field. A specially designed graphite parallel‐plate ionization chamber with a 30 mm collecting electrode was also assembled and tested. Measurements were then conducted in two 6 MV small circular fields of 2 cm and 1 cm diameter respectively, using the new concept of dose‐area product instead of punctual dose commonly used in radiotherapy.

Results:

The dose rate established in a large 60Co field with the new calorimeter is in agreement within 0.4% with previous calorimeters. The ionization chamber shows good characteristics except for a 0.06% drift per hour in water. The ratio of calorimetric against ionometric measurements in the 2 cm diameter field is 1.1% higher than the one in the 1 cm diameter field (with respectively 0.30% and 1.03% type A uncertainty for each field).

Conclusion:

Results presented here highlight the possibility of measuring dose‐area products in small fields with a graphite calorimeter and a parallel‐plate ionization chamber. Measurements in a 0.75 cm diameter field are already underway to confirm the trend observed in the 2 cm and 1 cm diameter fields. The last step to establish precise dosimetric references in small fields is to calculate correction factors thanks to Monte Carlo simulations.
TU‐F‐BRF‐05: Level Set Based Segmentation with a Dynamic Shape Prior
Authors: Liu W , Ruan D
Published: July 2014

Purpose:

To perform accurate segmentation on low‐SNR MR images subject to motion artifacts and signal voids.

Methods:

We have developed a novel level set based segmentation method that incorporates a dynamic shape prior. In contrast to conventional shape prior models that are either based on a single template or statistical models, we modeled the shape prior as sparse linear combinations of templates in a shape library. The proposed method was applied to segment real‐time kidney geometry from an abdominal MR series acquired under respiration and compared with the Chan‐Vese approach. Synthetic occlusions were further introduced to assess performance robustness. We compared the segmentation results with the ground truth contours and evaluated the segmentation accuracy based on the Dice similarity coefficient.

Results:

The proposed method successfully segmented all kidneys in the testing series. The corresponding shape priors were reasonably reconstructed from a small number of shape templates in the library, as expected. On testing dataset without occlusion, the proposed method achieved mean DSC of 0.97, which was more accurate than the Chan‐Vese approach with a DSC of 0.93. When tested on dataset with synthetic occlusions, the proposed method made robust inference on the occlusion sites and achieved mean DSC of 0.95, compared to 0.76 from the Chan‐Vese method, demonstrating the advantage of incorporating the proposed shape prior.

Conclusion:

We have developed a novel level set based segmentation method with a novel regularization to incorporate a dynamic shape prior. The shape prior is dynamically updated during the segmentation process as a sparse linear combination of templates from a shape library. Preliminary results have demonstrated the ability of the proposed method in improving segmentation accuracy, especially when noises and/or signal voids are present. Future work will consider dynamically update and evolve the shape library to encode shape priors as segmentations are being performed.
TU‐F‐BRF‐09: Feasibility Study of Spatial and Temporal Fractionation Using a Table‐Top Image‐Guided MRT System
Authors: Zhang L , Inscoe C , Yuan H , Burk L , Ger R , Chtcheprov P , Lu J , Chang S , Zhou O
Published: July 2014

Purpose:

Microbeam radiation therapy is a promising experimental radiotherapy method for cancer treatment. Synchrotron studies have shown that MRT can preferentially ablate tumors while mostly preserving the surrounding normal tissues. Our purpose is to develop a compact microbeam irradiator that can be accessible for laboratory research on MRT's therapeutic mechanism, with the ultimate goal of translating this technique for clinical applications. Utilizing a carbon nanotube field emission X‐ray source array, our lab has developed a first of its kind table‐top microbeam irradiator. The purpose of this study is to investigate the possibility of increasing the total dose to the tumor region using spatial and temporal fractionation.

Methods:

MRI and CT scans were acquired and registered to locate both the target region and the landmark in the treatment coordinate space. A crossbeam treatment configuration was planned to achieve the desired dosage and tumor coverage. One array of 300 μm‐thick microbeams was delivered to the target on the first day. Another array, perpendicular to the first one, was delivered the next day targeting the same region. The feasibility of this image‐guided MRT procedure was evaluated using a phantom. Gafchromic EBT2 film was employed to characterize the targeting accuracy and the delivered tumor dose.

Results:

The preliminary phantom study showed that a cross‐pattern of microbeam arrays was successfully delivered with sub‐millimeter targeting accuracy. The delivered dose in the target region was doubled. The fraction of tumor volume that received the peak dose was increased.

Conclusion:

Temporal fractionation of crosspatterned microbeams can be delivered to the same target region. The feasibility of this procedure was investigated with a phantom study. Once implemented, this procedure has the potential of increasing the tumor control effect of MRT and of achieving better normal tissue recovery.
TU‐F‐17A‐01: BEST IN PHYSICS (JOINT IMAGING‐THERAPY) – An Automatic Toolkit for Efficient and Robust Analysis of 4D Respiratory Motion
Authors: Wei J , Yuan A , Li G
Published: July 2014

Purpose:

To provide an automatic image analysis toolkit to process thoracic 4‐dimensional computed tomography (4DCT) and extract patient‐specific motion information to facilitate investigational or clinical use of 4DCT.

Methods:

We developed an automatic toolkit in MATLAB to overcome the extra workload from the time dimension in 4DCT. This toolkit employs image/signal processing, computer vision, and machine learning methods to visualize, segment, register, and characterize lung 4DCT automatically or interactively. A fully‐automated 3D lung segmentation algorithm was designed and 4D lung segmentation was achieved in batch mode. Voxel counting was used to calculate volume variations of the torso, lung and its air component, and local volume changes at the diaphragm and chest wall to characterize breathing pattern. Segmented lung volumes in 12 patients are compared with those from a treatment planning system (TPS). Voxel conversion was introduced from CT# to other physical parameters, such as gravity‐induced pressure, to create a secondary 4D image. A demon algorithm was applied in deformable image registration and motion trajectories were extracted automatically. Calculated motion parameters were plotted with various templates. Machine learning algorithms, such as Naive Bayes and random forests, were implemented to study respiratory motion. This toolkit is complementary to and will be integrated with the Computational Environment for Radiotherapy Research (CERR).

Results:

The automatic 4D image/data processing toolkit provides a platform for analysis of 4D images and datasets. It processes 4D data automatically in batch mode and provides interactive visual verification for manual adjustments. The discrepancy in lung volume calculation between this and the TPS is <±2% and the time saving is by 1–2 orders of magnitude.

Conclusion:

A framework of 4D toolkit has been developed to analyze thoracic 4DCT automatically or interactively, facilitating both investigational and clinical use. More software tools are under development for automatic analysis of other 4D imaging modalities.

This research is in part supported by NIH (U54CA137788/132378) and City Seed FY13(Grant No. 93348‐14 01). AY would like to thank MSKCC summer medical student research program supported by National Cancer Institute and hosted by Department of Medical Physics at MSKCC.
TU‐F‐17A‐06: Motion Stability and Dosimetric Impact of Spirometer‐Based DIBH‐RT of Left‐Sided Breast Cancer
Authors: McKenzie E , Yang W , Burnison M , Mirhadi A , Hakimian B , Stephen S , Robert R , Yue Y , Sandler H , Fraass B
Published: July 2014

Purpose:

Patients undergoing radiotherapy (RT) for left‐sided breast cancer have increased risk of coronary artery disease. Deep Inhalation Breath Hold assisted RT (DIBH‐RT) is shown to increase the geometric separation of the target area and heart, reducing cardiac radiation dose. The purposes of this study are to use Cine MV portal images to determine the stability of spirometer‐guided DIBH‐RT and examine the dosimetric cardiopulmonary impact of this technique.

Methods:

Twenty consecutive patients with left‐sided breast cancer were recruited to the IRB‐approved study. Free‐breathing (FB) and DIBH‐CT's were acquired at simulation. Rigid registration of the FB‐CT and DIBH‐CT was performed using primarily breast tissue. Treatment plans were created for each FB‐CT and DIBH‐CT using identical paired tangent fields with field‐in‐field or electronic compensation techniques. Dosimetric evaluation included mean and maximum (Dmax) doses for the left anterior descending artery (LAD), mean heart dose, and left lung V20. Cine MV portal images were acquired for medial and lateral fields during treatment. Analysis of Cine images involved chest wall segmentation using an algorithm developed in‐house. Intra‐ and inter‐fractional chest wall motion were determined through affine registration to the first frame of each Cine.

Results:

Dose to each cardiac structure evaluated was significantly (p<0.001) reduced with the DIBH plans. Mean heart dose decreased from 2.9(0.9–6.6) to 1.6(0.6–5.3) Gy; mean LAD dose from 16.6(3–43.6) to 7.4(1.7–32.7) Gy; and LAD Dmax from 35.4 (6.1–53) to 18.4(2.5–51.2) Gy. No statistically significant reduction was found for the left lung V20. Average AP and SI median chest wall motion (intrafractional) was 0.1 (SD=0.9) and 0.5 (SD=1.1) mm, respectively. Average AP inter‐fractional chest wall motion was 2.0 (SD=1.4) mm.

Conclusion:

Spirometer‐based DIBH treatments of the left breast are reproducible both inter‐ and intra‐fractionally, and provide a statistically and potentially clinically useful dosimetric advantage to cardiac structures.
WE‐D‐9A‐04: Improving Multi‐Modality Image Registration Using Edge‐Based Transformations
Authors: Wang Y , Tyagi N , Veeraraghavan H , Deasy J
Published: July 2014

Purpose:

Multi‐modality deformable image registration (DIR) for head & neck (HN) radiotherapy is difficult, particularly when matching computed tomography (CT) scans with magnetic resonance imaging (MRI) scans. We hypothesized that the ‘shared information’ between images of different modalities was to be found in some form of edge‐based transformation, and that novel edge‐based DIR methods might outperform standard DIR methods.

Methods:

We propose a novel method that combines gray‐scale edge‐based morphology and mutual information (MI) in two stages. In the first step, we applied a modification of a previously published mathematical morphology method as an efficient gray scale edge estimator, with denoising function. The results were fed into a MI‐based solver (plastimatch). The method was tested on 5 HN patients with pretreatment CT and MR datasets and associated follow‐up weekly MR scans. The followup MRs showed significant regression in tumor and normal structure volumes as compared to the pretreatment MRs. The MR images used in this study were obtained using fast spin echo based T2w images with a 1 mm isotropic resolution and FOV matching the CT scan.

Results:

In all cases, the novel edge‐based registration method provided better registration quality than MI‐based DIR using the original CT and MRI images. For example, the mismatch in carotid arteries was reduced from 3–5 mm to within 2 mm. The novel edge‐based method with different registration regulation parameters did not show any distorted deformations as compared to the non‐realistic deformations resulting from MI on the original images. Processing time was 1.3 to 2 times shorter (edge vs. non‐edge). In general, we observed quality improvement and significant calculation time reduction with the new method.

Conclusion:

Transforming images to an ‘edge‐space,’ if designed appropriately, greatly increases the speed and accuracy of DIR.
WE‐D‐9A‐07: SRGB Displays: A Good Choice for Medical Color Images?
Authors: Avanaki A , Espig K , Xthona A , Kimpe T
Published: July 2014

Purpose:

As of today there is no agreed standard for visualization of color information on medical displays. Today most medical color display systems use sRGB standard gamut. This paper studies whether sRGB displays are fit for visualization of medical color images. Special attention is paid to variability between display systems and perceptual linearity of display color behavior.

Methods:

Four new sRGB displays (Samsung 850 Series, NEC P241W‐BK, HP ZR24W, Dell U2413) were purchased and characterized with a Minolta CS‐100A. For each display the color gamut was compared to sRGB standard gamut. In addition chroma of the neutral grey curve was measured (shift of color point when driving neutral grey from black to white). Finally perceptual linearity of color behavior was calculated. Perceptually linear color behavior is important to guarantee consistent appearance and visibility of subtle differences in color tints.

Results:

Measurements show significant variation in color gamut, despite the fact that all displays were new and claim correspondence to sRGB gamut. The expectation is that these differences will only become larger when displays age. For grey tracking the measurements reveal major differences between the display systems, especially for the darker levels. A DICOM GSDF compliance check, as expected, shows that sRGB gamut for neutral grey tones does not map onto DICOM GSDF. This is not to be neglected since still a significant number of greyscale images are being visualized on color medical displays. By making use of deltaE2000 as metric, perceptual linearity of the color behavior of the displays was quantified, showing a lack of perceptual linearity in color and significant variation in display behavior.

Conclusion:

sRGB displays still suffer from significant variability in color gamut and grey tracking, and a lack of perceptual linear color behavior. Extending GSDF towards color (CSDF) may be a good step towards a solution.

Authors are employees of Barco
WE‐E‐BRE‐05: Ensemble of Graphical Models for Predicting Radiation Pneumontis Risk
Authors: Lee S , Ybarra N , Jeyaseelan K , Faria S , Kopek N , El Naqa I
Published: July 2014

Purpose:

We propose a prior knowledge‐based approach to construct an interaction graph of biological and dosimetric radiation pneumontis (RP) covariates for the purpose of developing a RP risk classifier.

Methods:

We recruited 59 NSCLC patients who received curative radiotherapy with minimum 6 month follow‐up. 16 RP events was observed (CTCAE grade ≥2). Blood serum was collected from every patient before (pre‐RT) and during RT (mid‐RT). From each sample the concentration of the following five candidate biomarkers were taken as covariates: alpha‐2‐macroglobulin (α2M), angiotensin converting enzyme (ACE), transforming growth factor β (TGF‐β), interleukin‐6 (IL‐6), and osteopontin (OPN). Dose‐volumetric parameters were also included as covariates. The number of biological and dosimetric covariates was reduced by a variable selection scheme implemented by L1‐regularized logistic regression (LASSO). Posterior probability distribution of interaction graphs between the selected variables was estimated from the data under the literature‐based prior knowledge to weight more heavily the graphs that contain the expected associations. A graph ensemble was formed by averaging the most probable graphs weighted by their posterior, creating a Bayesian Network (BN)‐based RP risk classifier.

Results:

The LASSO selected the following 7 RP covariates: (1) pre‐RT concentration level of α2M, (2) α2M level mid‐ RT/pre‐RT, (3) pre‐RT IL6 level, (4) IL6 level mid‐RT/pre‐RT, (5) ACE mid‐RT/pre‐RT, (6) PTV volume, and (7) mean lung dose (MLD). The ensemble BN model achieved the maximum sensitivity/specificity of 81%/84% and outperformed univariate dosimetric predictors as shown by larger AUC values (0.78∼0.81) compared with MLD (0.61), V20 (0.65) and V30 (0.70). The ensembles obtained by incorporating the prior knowledge improved classification performance for the ensemble size 5∼50.

Conclusion:

We demonstrated a probabilistic ensemble method to detect robust associations between RP covariates and its potential to improve RP prediction accuracy. Our Bayesian approach to incorporate prior knowledge can enhance efficiency in searching of such associations from data.

The authors acknowledge partial support by: 1) CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290) and 2) The Terry Fox Foundation Strategic Training Initiative for Excellence in Radiation Research for the 21st Century (EIRR21)
WE‐E‐BRE‐06: High‐Dose Microbeam Radiation Induces Different Responses in Tumor Microenvironment Compared to Conventional Seamless Radiation in Window Chamber Tumor Models
Authors: Chang S , Fontanella A , Boss M , Zhang J , Hadsell M , Schroeder T , Berman K , Palmer G , Dewhirst M
Published: July 2014

Purpose:

Microbeam radiation therapy and GRID therapy are different forms of Spatially‐Fractioned Radiation Therapy (SFRT) that is fundamentally different from the conventional seamless and temporally fractionated radiation therapy. SFRT is characterized by a ultra‐high dose (10s –100s Gy) dose single treatment with drastic inhomogeneity pattern of given spatial frequencies. Preclinical and limited clinical studies have shown that the SFRT treatments may offer significant improvements in reducing treatment toxicity, especially for those patients who have not benefited from the state‐of‐the‐art radiation therapy approaches. This preliminary study aims to elucidate the underlying working mechanisms of SFRT, which currently remains poorly understood.

Methods:

A genetically engineered 4T1 murine mammary carcinoma cell line and nude mice skin fold window chamber were used. A nanotechnology‐based 160kV x‐ray irradiator delivered 50Gy (entrance dose) single treatments of microbeam or seamless radiation. Animals were in 3 groups: mock, seamless radiation, and 300μm microbeam radiation. The windows were imaged using a hyperspectral system to capture total hemoglobin/saturation, GFP fluorescence emission, RFP fluorescence emission, and vessel density at 9 time points up to 7 days post radiation.

Results:

We found unique physiologic changes in different tumor/normal tissue regions and differential effects between seamless and microbeam treatments. They include 1) compared to microbeam and mock radiation seamless radiation damaged more microvasculature in tumor‐surrounding normal tissue, 2) a pronounced angiogenic effect was observed with vascular proliferation in the microbeam irradiated portion of the tumor days post treatment (no such effect observed in seamless and mock groups), and 3) a notable change in tumor vascular orientation was observed where vessels initially oriented parallel to the beam length were replaced by vessels running perpendicular to the irradiation portion of the tumor.

Conclusion:

Our preliminary study indicated that microbeam radiation modified tumor microenvironment in ways significantly different than of the conventional seamless radiation.
WE‐E‐BRE‐11: New Method to Simulate DNA Damage Using Ionization Cross‐Sections and a Geometrical Nucleosome Model
Authors: Pater P , Seuntjens J , El Naqa I
Published: July 2014

Purpose:

To obtain probability distributions of various DNA damage types as a function of the incident electron kinetic energy.

Methods:

Using Geant4‐DNA electron ionization cross‐sections, we calculated path length distributions for electrons of energies between 10 eV and 1 MeV, defined as the length between two subsequent interactions. These path lengths were then convolved with probability distributions for the creation of same‐strand damage, opposite‐strand damage, clustered damage, isolated damage, and same DNA strand target damage. These probability distributions of DNA damage were obtained by a Monte Carlo routine calculating probabilities of interaction in DNA targets inside a nucleosome geometrical model. Results represent the probability of a secondary electron, initially created inside a DNA strand target, of undergoing its next interaction: (1) in the opposite strand (DSB), (2) in the same strand (SSB+), (3) in either the opposite or same‐strand (clustered), (4) in the same DNA target (multiple‐hit) or (5) more than 10 base pairs away (isolated).

Results:

Electrons with kinetic energy between 50 and 250 eV have a maximal probability of creating DSB, SSB+, clustered damage and multiple‐hits in the same target The probabilities for these damage patterns have values of 2.5%, 4.3%, 6.7% and 5.4%, respectively. Isolated damage is most probable between 700 eV to 900 eV with a probability of 0.2%.

Conclusion:

We obtained DNA damage probability distributions as a function of electron incident energy. We showed that electrons with kinetic energies between 50 and 250 eV have the highest probability of producing complex forms of DNA damage (DSB, SSB+). We also showed that a double ionization within the same DNA target is the most frequent outcome occurring 5% of the time. It is expected that electron slowing down spectra can be convolved with our formalism to calculate source specific DNA damage patterns.

Research grants from governments of Canada and Quebec. PP acknowledges partial support by the CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290)
WE‐E‐17A‐01: Characterization of An Imaging‐Based Model of Tumor Angiogenesis
Authors: Adhikarla V , Jeraj R
Published: July 2014

Purpose:

Understanding the transient dynamics of tumor oxygenation is important when evaluating tumor‐vasculature response to anti‐angiogenic therapies. An imaging‐based tumor‐vasculature model was used to elucidate factors that affect these dynamics.

Methods:

Tumor growth depends on its doubling time (Td). Hypoxia increases pro‐angiogenic factor (VEGF) concentration which is modeled to reduce vessel perfusion, attributing to its effect of increasing vascular permeability. Perfused vessel recruitment depends on the existing perfused vasculature, VEGF concentration and maximum VEGF concentration (VEGFmax) for vessel dysfunction. A convolution‐based algorithm couples the tumor to the normal tissue vessel density (VD‐nt). The parameters are benchmarked to published pre‐clinical data and a sensitivity study evaluating the changes in the peak and time to peak tumor oxygenation characterizes them. The model is used to simulate changes in hypoxia and proliferation PET imaging data obtained using [Cu‐ 61]Cu‐ATSM and [F‐18]FLT respectively.

Results:

Td and VD‐nt were found to be the most influential on peak tumor pO2 while VEGFmax was marginally influential. A +20 % change in Td, VD‐nt and VEGFmax resulted in +50%, +25% and +5% increase in peak pO2. In contrast, Td was the most influential on the time to peak oxygenation with VD‐nt and VEGFmax playing marginal roles. A +20% change in Td, VD‐nt and VEGFmax increased the time to peak pO2 by +50%, +5% and +0%. A −20% change in the above parameters resulted in comparable decreases in the peak and time to peak pO2. Model application to the PET data was able to demonstrate the voxel‐specific changes in hypoxia of the imaged tumor.

Conclusion:

Tumor‐specific doubling time and vessel density are important parameters to be considered when evaluating hypoxia transients. While the current model simulates the oxygen dynamics of an untreated tumor, incorporation of therapeutic effects can make the model a potent tool for analyzing anti‐angiogenic therapies.
WE‐E‐17A‐04: CT Based Radiomics Data Predicts for Nodal Involvement and Overall Survival in NSCLC
Authors: Coroller T , Grossman P , Rios E , Mak R , Aerts H
Published: July 2014

Purpose:

Recent advances in medical imaging technologies provide opportunities to quantify the tumor phenotype throughout the course of treatment non‐invasively. The emerging field of Radiomics addresses this by converting medical images into minable data using a large number of quantitative imaging algorithms. The ability of radiomics to predict clinical outcomes such as survival or nodal involvement, can provide valuable complementary information. This study aims to evaluate the predictability of CT based radiomics features for node stages and survival time.in non‐small cell lung cancer (NSCLC) patients.

Method:

We included 118 patients with NSCLC in our analysis. Seventy‐four quantitative radiomic features describing the tumor phenotype based on intensity, shape, and texture, were extracted from planning CT scans. Association of the radiomics features with node involvement (Yes/No) was assessed using the area under the curve (AUC) of the receiver operating characteristics (ROC). Association with overall survival was assessed using the C‐Index (CI).

Results:

We found 30 radiomic features that were significantly (FDR corrected) associated with nodal involvement (range AUC=0.73‐0.60). Seventeen features were significantly associated survival (range CI=0.56‐0.62). Gray Level Non‐Uniformity, describing intra‐tumor heterogeneity, was the best predictor for both nodal stage (AUC=0.73) and survival time (CI=0.62). It is noteworthy that tumor volume is only the 8th best predictor for both nodal stage (AUC=0.71) and survival (CI =0.61).

Conclusion:

Radiomics analysis was able to predict node stage and survival time by looking at complex image features. Although tumor volume has been routinely used to predict outcome, this study shows that radiomic features capturing detailed information of the tumor phenotype can provide better prediction for clinical relevant factors such as nodal involvement and survival.
WE‐E‐18A‐03: How Accurately Can the Peak Skin Dose in Fluoroscopy Be Determined Using Indirect Dose Metrics?
Authors: Jones A , Pasciak A
Published: July 2014

Purpose:

Skin dosimetry is important for fluoroscopically‐guided interventions, as peak skin doses (PSD) that Result in skin reactions can be reached during these procedures. The purpose of this study was to assess the accuracy of different indirect dose estimates and to determine if PSD can be calculated within ±50% for embolization procedures.

Methods:

PSD were measured directly using radiochromic film for 41 consecutive embolization procedures. Indirect dose metrics from procedures were collected, including reference air kerma (RAK). Four different estimates of PSD were calculated and compared along with RAK to the measured PSD. The indirect estimates included a standard method, use of detailed information from the RDSR, and two simplified calculation methods. Indirect dosimetry was compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the indirect estimates were examined.

Results:

PSD calculated with the standard calculation method were within ±50% for all 41 procedures. This was also true for a simplified method using a single source‐to‐patient distance (SPD) for all calculations. RAK was within ±50% for all but one procedure. Cases for which RAK or calculated PSD exhibited large differences from the measured PSD were analyzed, and two causative factors were identified: ‘extreme’ SPD and large contributions to RAK from rotational angiography or runs acquired at large gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD.

Conclusions:

Using indirect dose metrics, PSD can be determined within ±50% for embolization procedures, and usually to within ±35%. RAK can be used without modification to set notification limits and substantial radiation dose levels. These results can be extended to similar procedures, including vascular and interventional oncology. Film dosimetry is likely an unnecessary effort for these types of procedures.
WE‐G‐12A‐01: High Intensity Focused Ultrasound Surgery and Therapy
Authors: Farahani K , O' Neill B
Published: July 2014

More and more emphasis is being made on alternatives to invasive surgery and the use of ionizing radiation to treat various diseases including cancer. Novel screening, diagnosis, treatment and monitoring of response to treatment are also hot areas of research and new clinical technologies. Ultrasound(US) has gained traction in all of the aforementioned areas of focus. Especially with recent advances in the use of ultrasound to noninvasively treat various diseases/organ systems. This session will focus on covering MR‐guided focused ultrasound and the state of the art clinical applications, and the second speaker will survey the more cutting edge technologies e.g. Focused Ultrasound (FUS) mediated drug delivery, principles of cavitation and US guided FUS.

Learning Objectives:

Fundamental physics and physical limitations of US interaction with tissue and nanoparticles

The alteration of tissue transport using focused ultrasound

US control of nanoparticle drug carriers for targeted release

The basic principles of MRI‐guided focused ultrasound (MRgFUS) surgery and therapy

the current state of the art clinical applications of MRgFUS

requirements for quality assurance and treatment planning
TH‐A‐19A‐06: Site‐Specific Comparison of Analytical and Monte Carlo Based Dose Calculations
Authors: Schuemann J , Dowdell S , Grassberger C , Paganetti H
Published: July 2014

Purpose:

To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy.

Methods:

Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head & neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50) were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two‐dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80‐ R20), were analyzed.

Results:

We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site‐specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations.

Conclusion:

Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we recommend treatment plan verification using Monte Carlo simulations for patients with complex geometries.
TH‐A‐19A‐12: A GPU‐Accelerated and Monte Carlo‐Based Intensity Modulated Proton Therapy Optimization System
Authors: Ma J , Wan Chan Tseung H , Beltran C
Published: July 2014

Purpose:

To develop a clinically applicable intensity modulated proton therapy (IMPT) optimization system that utilizes more accurate Monte Carlo (MC) dose calculation, rather than analytical dose calculation.

Methods:

A very fast in‐house graphics processing unit (GPU) based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified gradient based optimization method was used to achieve the desired dose volume histograms (DVH). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve the spatial resolution. The optimizations were computed on a multi‐GPU framework to mitigate the memory limitation issues for the large dose influence maps that

Result from maintaining the intrinsic CT resolution and large number of proton spots. The dose effects were studied particularly in cases with heterogeneous materials in comparison with the commercial treatment planning system (TPS). Results:

For a relatively large and complex three‐field bi‐lateral head and neck case (i.e. >100K spots with a target volume of ∼1000 cc and multiple surrounding critical structures), the optimization together with the initial MC dose influence map calculation can be done in a clinically viable time frame (i.e. less than 15 minutes) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The DVHs of the MC TPS plan compare favorably with those of a commercial treatment planning system.

Conclusion:

A GPU accelerated and MC‐based IMPT optimization system was developed. The dose calculation and plan optimization can be performed in less than 15 minutes on a hardware system costing less than 45,000 dollars. The fast calculation and optimization makes the system easily expandable to robust and multi‐criteria optimization.

This work was funded in part by a grant from Varian Medical Systems, Inc.
TH‐A‐BRF‐05: MRI of Individual Lymph Nodes to Guide Regional Breast Radiotherapy
Authors: van Heijst T , van Asselen B , Lagendijk J , van den Bongard D , Philippens M
Published: July 2014

Purpose:

In regional radiotherapy (RT) for breast‐cancer patients, direct visualization of individual lymph nodes (LNs) may reduce target volumes and Result in lower toxicity (i.e. reduced radiation pneumonitis, arm edema, arm morbidity), relative to standard CT‐based delineations. To this end, newly designed magnetic resonance imaging (MRI) sequences were optimized and assessed qualitatively and quantitatively.

Methods:

In ten healthy female volunteers, a scanning protocol was developed and optimized. Coronal images were acquired in supine RT position positioned on a wedge board on a 1.5 T Ingenia (Philips) wide‐bore MRI. In four volunteers the optimized MRI protocol was applied, including a 3‐dimensional (3D) T1‐weighted (T1w) fast‐field‐echo (FFE). T2w sequences, including 3D FFE, 3D and 2D fast spin echo (FSE), and diffusion‐weighted single‐shot echo‐planar imaging (DWI) were also performed. Several fatsuppression techniques were used. Qualitative evaluation parameters included LN contrast, motion susceptibility, visibility of anatomical structures, and fat suppression. The number of visible axillary and supraclavicular LNs was also determined.

Results:

T1 FFE, insensitive to motion, lacked contrast of LNs, which often blended in with soft tissue and blood. T2 FFE showed high contrast, but some LNs were obscured due to motion. Both 2D and 3D FSE were motion‐insensitive having high contrast, although some blood remained visible. 2D FSE showed more anatomical details, while in 3D FSE, some blurring occurred. DWI showed high LN contrast, but suffered from geometric distortions and low resolution. Fat suppression by mDixon was the most reliable in regions with magnetic‐field inhomogeneities. The FSE sequences showed the highest sensitivity for LN detection.

Conclusion:

MRI of regional LNs was achieved in volunteers. The FSE techniques were robust and the most sensitive. Our optimized MRI sequences can facilitate direct delineation of individual LNs. This can Result in smaller target volumes and reduced toxicity in regional RT compared to standard CT planning.