bluuebunny/crossref_metadata_2025 huggingface dataset:
WE‐G‐BRA‐05: Post‐Radiation Normalized FDG‐PET versus Radiation Dose Correlates with Radiation Pneumonitis Symptoms and the Nitric Oxide Ratio
Authors: McCurdy M , Wazni M , Martinez J , Castillo R , Guerrero T
Published: November 2011

Purpose: To quantify the relationship between the post‐treatment [18F]‐2‐fluoro‐2‐deoxyglucose (18F‐FDG) positron emission tomography (PET) uptake and radiation dose received and correlate this relationship with prospectively scored pulmonary radiation toxicity. Methods: 34 patients treated for esophageal cancer with thoracic radiotherapy were evaluated prospectively at the MD Anderson Cancer Center. The treatment planning computed tomography (CT) imaging was registered with the restaging PET/CT. Using histogram analysis, the voxel average FDG‐PET uptake vs. radiation dose was obtained for each case and linear regression was performed. The slope of the linear regression was termed the pulmonary metabolic response rate (PMRR). Common Toxicity Criteria version 4 was used to score pneumonitis. Exhaled nitric oxide (eNO) was measured on the first and last days of radiation treatment. Receiver operating characteristic curves were used to determine the threshold PMRR, mean lung dose, volume of lung receiving 5, 10, 20 and 30 Gy and eNO ratio (End/beginning) that can best predict symptomatic patients. Results: 29 patients were evaluable. The median of the mean standard uptake value from lung that received 0–5 Gy was 0.51 (range, 0.34–1.24), 5–10 Gy was 0.71 (range, 0.39–1.32), 10–20 Gy was 0.78 (0.40–1.56), and > 20 Gy was 1.10 (range, 0.43–3.01). 25 patients had grade 0 or 1 pulmonary symptom score and 4 patients had grade 2 or higher (symptomatic) score. Both PMRR and the eNO ratio gave a significant area under the curve of 0.86 (p = 0.02) and 1 (p<0.001) respectively. Using a PMRR threshold of 0.0184 yielded a true positive rate of 0.75 and false positive rate of 0.125. Conclusions: In this prospective study, the PMRR predicted for development of radiation pneumonitis. This unique quantitative assessment of radiation pnuemonitis can be used for quality control to deliver higher doses of radiation safely.
WE‐G‐BRC‐06: Magnetic Resonance Imaging : Enhancing Concepts through Desktop Models and Supplementing Clinical Rotations with Video Presentations
Authors: Sinha U , Sinha S
Published: November 2011

Purpose: Magnetic Resonance Imaging is a challenging area of Medical Physics. Concepts presented in didactic lectures can be reinforced if hands‐on laboratory procedures can be simultaneously performed by students. This can be accomplished on a clinical scanner if access is unlimited. However, the constraints of scanner availability usually preclude students from experimenting with different procedures. Further, it is not feasible to allow students to experiment extensively with clinical systems since scanner performance cannot be compromised. Methods: To address the need for hands‐on training as well as the limited availability of MR scanners, we have integrated a desktop Earthˈs field MRI system to reinforce concepts in NMR and MRI and a video presentation of a comprehensive MR Quality Control procedure performed by a MR physicist. The desktop Earthˈs Field MRI system (TerraNova) allows students to learn NMR and MRI fundamentals. The video records a MR QC procedure and takes students through the different steps to perform the comprehensive QC exam for ABR. In addition, the video highlights procedural errors and simulates conditions that result in commonly encountered artifacts. The video and MR images are provided to students so that they can independently analyze the images. The sequence of presentation was as follows: didactic lecture (prior semester), desktop experiments, video of MRQC culminating with the actual clinical rotation. Results: A one hour lecture and 4 hour lab was developed with the desktop model and students successfully completed the lab in groups of two. Video and image analysis were completed individually by each student prior to the clinical lab rotation. Surveys conducted at each step confirmed the additional learning value of the desktop model and the video. Conclusions: In addition to enhancing the learning of MRI, the novel approach also resulted in an improved efficiency of the MR clinical rotation.

Funding Support: P1 16V090024, Department of Education, FIPSE.
WE‐G‐214‐03: Investigating the Repeatability of Quantitative PET Imaging of Heterogeneous Tumors
Authors: McCall K , Jallow N , Bowen S , Deveau M , Forrest L , Jeraj R
Published: November 2011

Purpose: High precision within quantitative imaging studies is required to define biological targets for dose painting, and to evaluate responses to therapy. However, within PET imaging systems there are position‐dependent systematic fluctuations in contrast‐recovery. The objective of this study was to determine the impact of patient set‐up on PET‐based quantification of heterogeneous tumors. Methods: Ten dogs with sinonasal tumors received six repeated [18F]FDG‐PET scans. Between each PET acquisition, known set‐up errors were produced by varying patient position in precisely controlled 1.0±0.5 mm steps. Image noise was investigated by retrospectively varying acquisition time of a stationary scan. Resulting changes in SUVmax and PET‐based target volumes were evaluated. Correlation between corresponding voxels of co‐registered images determined repeatability of spatial distributions. A theoretical upper limit of repeatability was estimated from simulated PET images using empirical models of position‐dependent contrast‐recovery. Results: From the simulated PET images, a theoretical upper limit of 0.90 was estimated for the repeatability of spatial distributions when set‐up errors are present. When only image noise was varied between [18F]FDG‐PET scans, repeatability of spatial distributions was measured at 0.95. However, set‐up errors lead to significant decreases (p < 0.01) in voxel correlations. Introducing set‐up errors between [18F]FDG‐PET acquisitions reduced the repeatability of spatial distributions to 0.80, and caused changes of 5% in SUVmax and 10% in volumes of PET‐based targets. Conclusions: Set‐up errors as small as a few millimeters (< 3mm) reduced the reproducibility of quantitative PET imaging of heterogeneous tumors. PET‐based quantitative values generally varied within 10%, but target volumes within some tumors changed by 30%. Errors during PET acquisition will lead to uncertainty in quantifying changes in tumor function, and to limited accuracy and precision of PET‐based biological target volumes. Therefore, tumor delineation must be independent of SUV thresholds and uncertainty margins are required for PET‐based response quantification.
WE‐G‐214‐04: MR Simulation Environment for MR‐Guided Radiation Therapy
Authors: Stanescu T , Wachowicz K , Jaffray D
Published: November 2011

Purpose: To develop and implement a comprehensive framework for simulating MR‐like images with associated distortions relevant to radiation therapy. The toolkit is designed to accurately determine image distortions and to be used to evaluate the performance of new MR‐guided radiation therapy methods. Methods: Techniques aimed to determine the 3D fields of both types of MR image distortions, i.e., system‐related and patient‐induced, were developed and extensively validated against experimental data (i.e., phantoms and patient data). MR‐like images relevant to RT planning and verification were synthetically generated by applying the distortion field information to CT data (free of spatial artifacts). Specifically, partial (e.g., contours) or full (i.e., images) CT data was warped to embed and exhibit the local distribution of MR geometrical artifacts. Depending on the site of interest (e.g., brain, prostate, spine) one or both types of distortions were implied. Three types of MR‐like image datasets were simulated: a) CT data warped to include the 3D system distortion field, b) CT data warped by applying the susceptibility distortion field, and c) CT data warped with both system and susceptibility distortion fields. Results: The simulation platform for generating MR‐like images was successfully implemented for a number of clinically relevant cases such as a) susceptibility‐induced artifacts in hemorrhagic brain metastases treated with radiosurgery, b) evaluation of artifacts due to metal implants, c) evaluation of PTV margins for prostate MR‐guided radiation therapy, and d) investigation of MR image susceptibility artifacts for patient verification. The metric of success of each project implementation was given by the clinical requirements. Conclusions: The proposed simulation framework can be used to stress test ideas regarding the suitability of certain MR imaging techniques for newly emerging MRIgRT techniques (in particular applied to MR‐linac systems).
WE‐G‐214‐07: Proton Beam Range Verification with PET: Comparison of O‐18, O‐16 and C‐12 Activation
Authors: Cho J , Mawlawi O , Gillin M , Titt U , Gonzalez‐Lepera C , Ibbott G
Published: November 2011

Purpose: Accurate estimation of the Bragg‐peak‐distal‐edge (BPDE) location is crucial in proton therapy dose delivery. Current range verification techniques includes PET imaging which takes advantage of the Beta+ emitters produced following proton interaction within the patient body. However, such interactions produce negligible PET signal at the BPDE due largely to the decrease in proton energy with depth, which reduces the efficiency of Beta+ emitter production. The objective of this study is to investigate the feasibility of overcoming this limitation by infusing 18O into the treatment volume through 18O(p,n)18F interaction while leveraging the longer 18F t1/2 and its lower interaction energy threshold. This study compares PET signals from irradiated 18O water with 16O water and heptane over different depths of BPDE to estimate the improvement 18O water brings about in BPDE estimation. Methods: Petri dishes containing 2 mm depth of 18O water, 16O water, or Heptane (C7H16) were stacked on a water‐equivalent plastic phantom of thickness chosen to position the samples in the distal 99% to 8% dose region of a proton beam. A dose of 10 Gy was delivered to the 100% dose point. The petri dishes were then positioned in FOV of a PET/CT scanner 20 min post irradiation and scanned for 15 min. Mean activities of all samples were obtained over different BPDE region and normalized to maximum of 18O water. MC activity simulation for the three sample materials was performed for comparison. Results: Mean activities for each sample are as follow for BPDE 99%∼87%, 87%∼65%, 65%∼20%, and 39%∼8% regions. 18O water — 100%, 19%, 5%, 2%; 16O water — 29%, 4%, and negligible; heptanes — 12% and negligible. MC simulation showed consistent results with measurements. Conclusions: Strong to reasonable activities from 18O water over all BPDE regions indicates the possibility of using 18O for reliable range verification.

Funding provided by the University of Texas MD Anderson Cancer Center.
WE‐G‐110‐05: Evaluation of Maximum Likelihood Ground Truth and Performance of Readers Stratified by Aggressiveness from the Lung Image Database Consortium (LIDC) Study
Authors: OˈDell W
Published: November 2011

Purpose: The Lung Image Database Consortium (LIDC) is an ongoing multi‐institutional study funded by the NIH to collect and evaluate volumetric image data of tumors of the lung. A primary objective of this study is to ascertain a definitive nodule‐detection ground‐truth for future training and testing of competing computer‐assisted detection algorithms. However, a great disparity exists among the (four) readersˈ interpretations preventing an objective determination of ground truth. The goal of the current work is to apply statistical methodologies to determine the maximum‐likelihood nodule‐detection ground truth for the LIDC data. Methods: Our method is motivated by the Simultaneous Truth and Performance Level Estimation approach by Warfield et al. and is a specific implementation of iterative, expectation‐maximization and maximum likelihood (EM‐ML) steps tailored for the nodule detection task. A key, necessary preliminary step is the ranking of readers, on a per patient basis, by the number of nodules detected; that is, their relative aggressiveness in detection. Results: Application of the EM‐ML iterative scheme resulted in a reasonable estimate of reader performance and ground‐truth that was obtained consistently for a variety of initial states. The converged ground truth conveniently matched identically the three out of four consensus from the LIDC readers, independent of stratification by aggressiveness. Conclusions: The application of statistical methods to the problem of nodule detection from multiple readers in the absence of a known ground‐truth has been implemented on the LIDC outcomes to produce a reasonable and objective determination of ground‐truth. This ground‐truth permits the assessment of the performance of the LIDC readers based on relative aggressiveness and enables the LIDC detection data to be used for future CAD evaluation.
WE‐G‐110‐07: Hybridmantis: A Novel Method for Faster Monte Carlo Simulation of X‐Ray Imaging Detectors
Authors: Sharma D , Badal A , Fang Y , Badano A
Published: November 2011

PURPOSE: We describe a novel hybrid approach for Monte Carlo simulations that maximizes utilization of CPUs and GPUs within modern workstations. We apply the method to the simulation of indirect radiation detectors using a modified version of the code mantis. METHODS: We modified penelope to output coordinates and energy deposited during x‐ray and electron interactions occurring within the scintillator which are then used as source for optical showers using detect2. The main program dynamically allocates optical transport showers to the GPU and CPU cores using the detect2 routines in mantis. In this paper, we describe a GPU implementation of the basic physics models in detect2 (we call this gpu‐ detect2) and a serial CPU version of the same code. The hybrid approach allows the main program to farm optical showers to computing cores as they become available. RESULTS: Our preliminary results suggest that a speedup factor of up to 26 between GPU and CPU versions of the new gpu‐ detect2 code, and up to three orders of magnitude compared to the optical transport routines in mantis can be achieved. Further validation is needed and additional optimizations are possible. CONCLUSION: The rationale of this novel method relies on three aspects, the last two being unique to this type of simulation. First, current workstations typically have computing power available both in CPU and GPU cores. Second, not all Monte Carlo simulation packages are easily ported into a GPU implementation. Lastly, optical transport has been shown to be the major computational bottleneck in the Monte Carlo modeling of indirect x‐ray imaging detectors. We introduce a hybrid approach for the Monte Carlo modeling of indirect x‐ray imaging devices that promises to significantly speed up simulations.
WE‐G‐211‐02: A Fast Aberration Correction Method for 3D Reconstruction with Confocal Microscopic Images
Authors: Zhang Y , Hu X , Wang P , Yang Y , Niu R , Sa Y , Yang C , Feng Y
Published: November 2011

Purpose: Accurate study of 3D cell morphology with confocal imaging method requires correction of the z‐axis aberration. A fast method with fluorospheres has been developed to achieve this goal. Methods: Fluorospheres with nominal diameter of 10um(+−2%) were used for this study. The z‐stack images were obtained using Zeiss‐410 CLSM system with the stepsize of 0.4 um in air along the z‐axis. Ideally, a sphere should be shown as a disk with diameter d in each image of the stack. But the measured data showed significant deviation in d vs z relation from the expected one due to the optical aberration by light refraction at various index‐mismatched interfaces. To correct this aberration, the following algorithm were developed and used to fit the measured data and obtain a rescaling factor for accurate 3D reconstruction along z‐axis. We define three parameters, 1. Covariance between theoretical and experimental data of the disk diameter arrays (Pcov), the maximum of which means the optimal match with the theoretical model; 2. Eccentricity of the largest disk which is in the middle layers and less influenced by the PSF (Pecc); 3. The mean eccentricity of all the stacks measured (Pmecc). These parameters were utilized and weighted with factors of a, b and c, respectively, in the objective function (F). F = a*Pcov + b*Pecc + c*Pmecc Results: 29 images were acquired for the fluorosphere as the measured image stack. After the data fitting and optimization, diameters in all images were corrected to obtain the rescaling factor (f=0.862), and the aberration was reduced significantly in the reconstructed 3D image of the fluorosphere. Conclusions: It is shown that the above method can significantly improve the quality of the reconstructed 3D image of the fluorosphere from the confocal images. Additional test results will be presented for evaluation of the methodˈs effectiveness.
WE‐G‐220‐02: Ultrasound Symposium: Computational Modeling of High‐Intensity Focused Ultrasound Mediated Drug Delivery
Authors: Haemmerich D , Dreher M , Gasselhuber A
Published: November 2011

Purpose: Low‐Temperature Sensitive Liposomes (LTSL) are drug delivery vehicles with that release the drug upon heating above ∼40 °C. The combination of LTSL with local heat generated by focused ultrasound may thus allow non‐invasively targeted drug delivery. The complex interplay between heat based cancer treatments like thermal ablation and chemotherapy requires computational models to identify the relationship between heat exposure and pharmacokinetics in order to optimize drug delivery. Methods: We developed mathematical models combining a model of tissue heating with a drug delivery model. Deposited HIFU energy (i.e. SAR) was calculated from phantom experiments, and used as input data for the model. Microvascular perfusion was modeled according to Pennesˈ Bioheat Equation, and was varied with temperature. A spatio‐temporal multi‐compartment pharmacokinetic model was created to describe the release of doxorubicin (DOX) from LTSL into the tumor plasma, subsequent transport into the interstitium, and finally uptake by the cells. Tissue was heated for varying times to target temperatures between 42 °C and 60 °C at the ultrasound focal spot, and spatio‐temporal drug concentration profiles were calculated. Results: At target temperatures in the hyperthermic range, maximum drug concentrations of ∼ 9 ug/g were observed in the central heating area, with very localized drug deposition. At ablative temperatures similar maximum drug concentrations were observed, with a ring‐like spatial concentration profile due to progressive shut‐down of perfusion at temperatures above 45 °C. Concentration increased approximately linearly with time during the examined time periods.Conclusion: HIFU mediated targeted drug delivery via LTSL locally keeps plasma concentration of bioavailable drug high during hyperthermic temperature exposure, allowing for localized cellular uptake at heated locations. Heating induced temperature changes in perfusion considerably affect drug delivery, particularly if cessation of perfusion is induced. Multi‐ physics mathematical models may allow for optimization of heat‐mediated targeted drug delivery from LTSL, as well as for treatment planning.

Educational objectives:

1. Learn basic components of a drug delivery model

2. Learn how computational models allow optimization of drug delivery

3. Learn importance of treatment planning in targeted drug delivery
TH‐A‐224‐03: Atlas Based Auto‐Segmentation Based on Deformable Image Registration
Authors: Dong L , Yang J , Zhang Y , Zhang L
Published: November 2011

Inverse planning based on intensity‐modulated radiation therapy (IMRT) requires the delineation of target volumes and normal critical organs. Anatomy segmentation becomes an important step in modern radiation therapy. Unfortunately, anatomy segmentation is traditionally done by a manual contouring process, which can be labor‐intensive and subject to inter‐observer variations. When many anatomical structures are to be contoured in 3D or 4D CT datasets, the manual contouring process can be a bottleneck for IMRT planning, especially in adaptive radiotherapy which involves multiple, sequential re‐planning. Recently, deformable image registration demonstrates its advantage for auto‐segmentation. The basic assumption is that patientˈs anatomy can be deformably mapped from a previously defined anatomy configuration — the atlas. This reference anatomy can be the same patient (in adaptive radiotherapy) or a different patient within the same class (or a patient with the same type of cancer). Deformable image registration provided a voxel‐by‐voxel transformation field, which can be used to map contours (or the labeled volumes) from the reference patient to the new image. Atlas‐based auto‐segmentation has a special advantage in image‐guided adaptive radiotherapy, because the original atlas contains both target volume and normal structures, and is already defined in the original treatment plan, making treatment adaptation a much simple process. In this presentation, we will discuss our clinical experience for using atlas‐based segmentation for intra‐object (the same patient) contour propagation and inter‐object (a different patient) auto‐ segmentation. Validation of auto‐segmentation is also an important step to be discussed.

Educational Objectives:

1. Describe deformable image registration for auto‐segmentation

2. Understand the achievable accuracy and validation methods for anatomy‐segmentation.

3. Illustrate applications of atlas‐based auto‐segmentation in radiation therapy
TH‐A‐214‐04: Impact of Body Size of Obese Patients on PET/CT Dose Estimates: Monte Carlo Calculations Using a Set of BMI‐Adjustable Phantoms
Authors: Ding A , Mille M , Caracappa P , Xu X
Published: November 2011

Purpose: To assess the effect of obese patientˈs body mass index (BMI) on organ doses from CT and PET exams. Methods: A set of 5 computational phantoms with different BMIs were created for PET and CT dose calculations using the Monte Carlo N‐Particle Extended (MCNPX) code. The phantoms represent patients having a BMI ranging from 23 (normal weight) to 44 (morbidly obese) with increasing amounts of subcutaneous and visceral fat. The external CT dose calculations assumed a whole‐body, diagnostic scan with a GE LightSpeed 16 scanner operating at a tube voltage of 120 kVp. The internal PET dose was based on S‐values for F‐18 and the ICRP‐106 FDG biokinetic model. Results: For the same tube current, ratios of the morbidly obese phantom CT organ doses compared to the normal weight phantom ranged from 0.46∼1 with an average of 0.7 because of shielding by the extra fat. This effect was greatest for deep organs in the abdomen (e.g. colon, lungs, stomach, liver, urinary bladder). For the same injected radioactivity, the average PET organ dose ratios were 0.95 and 0.65 for source organs (e.g. brain, heart, liver, urinary bladder) and organs in the remainder, respectively (e.g. colon, stomach, spleen, etc.). These PET dose differences are due primarily to the obese phantomˈs smaller remainder source S‐values which arise from the addition of the extra fat to the remainder compartment. Conclusions: After adjusting for the increased tube current and tube voltage, the results suggest that obese patients can receive higher absorbed dose to some organs, depending on the protocols. This work, as part of the VirtualDose software development, demonstrates the ability to improve the estimate of organ doses from PET and CT scans for obese patients and will be useful to on‐going efforts to optimize image quality and imaging doses.
TH‐A‐220‐02: Improving Localization of Lung Cancer Targets for Radiotherapy Using Semi‐Deformable Featurelet Registration
Authors: Robertson S , Weiss E , Badawi AM , Hugo GD
Published: November 2011

Purpose: To assess errors in online localization of deforming and regressing target structures, and to evaluate potential error reduction using rigid registration of individual featurelets distributed on the target surface. Methods: Fifteen patients with locally advanced non‐small‐cell lung cancer received weekly CT scans throughout treatment under active breathing control. The primary gross tumor volume (GTV) was contoured on each image by a physician, including two GTVs for one patient. To eliminate patient setup errors during image acquisition, secondary images were manually registered to the reference image using bony anatomy. Initial errors were computed as the distance between centroids of the GTV from reference and secondary images in this alignment. Six separate rigid registrations were then performed to align featurelets contained by the left, right, anterior, posterior, superior, and inferior subvolumes of the GTV, including a 1 cm margin. A final translation was computed by averaging the two registrations along each patient axis. Residual errors were defined as the remaining distance between centroids of the GTV from reference and secondary images in this final orientation. Improvements were gauged relative to bony alignment and to standard whole‐target registration. Results: The mean (standard deviation) of the absolute value of initial errors was 3.0 (2.7) mm, 3.8 (3.7) mm, and 3.6 (3.4) mm in the lateral, anterior‐posterior, and superior‐inferior directions, respectively. Whole‐target registration reduced corresponding errors to as low as 1.6 (1.5) mm, 1.8 (2.0) mm, and 2.4 (2.3) mm. Featurelet registration provided the lowest absolute mean residual errors of 1.5 (1.3) mm, 1.4 (1.2) mm, and 1.9 (1.6) mm. Conclusions: Featurelet registration demonstrated improved tumor centroid reproducibility compared to bony‐anatomy and whole‐target alignments. Future work includes automation and optimization of featurelet detection and subvolume definition.

Supported in part by NIH R01CA116249
TH‐A‐220‐03: On the Dosimetric Effect and Correction of Inverse Consistency and Transitivity Errors in Dose Accumulation
Authors: Hardcastle N , Bender E , Tome W
Published: November 2011

Purpose: To investigate the dosimetric effect of deformable image registration (DIR) inverse consistency and transitivity errors in dose accumulation and to propose a correction strategy to reduce the impact of these errors. Methods: Given three images, A, B and C, deformation maps are defined as third‐order transitive if the deformation A‐>B‐>C‐>A results in the image A. Four tomotherapy MVCT images from a head and neck treatment were selected representing the anatomical change over the duration of the treatment course. A research version of the Pinnacle RTPS (v9.1) was used for all planning, DIR and dose warping. A seven‐field IMRT plan was created delivering 69.3Gy, 60 & 56Gy to the high, intermediate and low‐dose PTVs respectively. This plan was copied to each of the other three images and the dose calculated on all images. All images were deformed to each other using the fast symmetric Demons algorithm. This algorithm is not inverse‐consistent or transitive error‐free. The dose from each image was warped to and accumulated on the fourth image to result in ‘D_AC1’. The dose from each image was then warped to and accumulated on the third image to result in ‘C_AC1’. ‘C_AC1’ was then warped to the fourth image to result in ‘DAC2’. The difference in between ‘D ACT’ and ‘D_AC2’ was measured. This dose accumulation process was then repeated after all deformation maps were made inverse consistent and then transitive. Results: Inverse consistency and transitivity errors lead to an observable difference between ‘D_AC1’ and ‘D_AC2’. The difference decreased with inverse‐consistent DVFs and decreased further with transitive DVFs. Conclusion: Inverse consistency and transitivity errors lead to discrepancies between doses warped to the same image via different pathways. These discrepancies can be significantly reduced by enforcing inverse consistency and transitivity between all DVFs used in dose accumulation.

N Hardcastle is funded by Philips Healthcare
TH‐A‐220‐11: Comparative Study of Tumor Volume Segmentation Techniques and Their Sensitivity to Imaging Parameters
Authors: Galavis P , Paliwal B , Jeraj R
Published: November 2011

Purpose: PET imaging with FDG has been proposed for accurate tumor delineation in radiotherapy. Different methods have been proposed to segment tumors using PET‐images. However, their sensitivity to imaging parameters variations is usually neglected. This work compares delineation techniques and investigates their sensitivity to imaging parameters. Methods: PET/CT scans of twenty patients were acquired in both 2D and 3D mode. Ten images per patient were created by varying parameters in the reconstruction algorithm within clinical settings. Tumor volumes within each image were segmented using the techniques of thresholding (40% of maximum standardized uptake value), gradient‐based (local‐maximum gradient), and region‐growing (nearest‐pixel within a fixed phantom‐based‐cutoff). Percent volume change was used to assess the tumor volume sensitivity to imaging parameters for each segmentation technique. Results: Tumor volumes were largest (29.2±46.2cm3) using gradient‐based and smallest (20.1±36.6cm3) for thresholding. Thresholding was least sensitive to varying imaging parameters while region growing presented the largest volume discrepancies. Across the ten combinations of acquisition/reconstruction parameters variations, the volume differences were 10%±9% (range [−45%,60%]), 18%±15% (range [−70%,75%]) and 24%±24% (range, [−80%, 140%]) for thresholding, gradient‐based and region‐growing respectively. Thresholding showed least sensitivity when iteration number and grid size were varied; however gradient‐based was least sensitive to post‐reconstruction‐filter variation. Conclusions: Phantom‐based analysis showed small volume difference between segmentation techniques. However, analysis of patient images showed large range of volume variations to imaging parameters, even with more sophisticated segmentation methods, such as gradient‐based and region‐growing. Sensitivity studies of segmentation algorithms against imaging parameters must precede acceptance and use in the clinical environment, especially if these techniques are used in multi‐centre clinical trials where inconsistency in tumor definition could have an effect on treatment outcomes.
TH‐C‐BRB‐01: Toward a thorough Evaluation of IMPT Plan Sensitivity to Uncertainties: Revisit the Worst‐Case Analysis with An Exhaustively Sampling Approach
Authors: Li Y , Liu W , Li X , Quan E , Zhang X
Published: November 2011

Purpose: Intensity‐modulated proton therapy (IMPT) has a great potential to further advance proton therapy. However, it is widely accepted that IMPT is very sensitive to uncertainties. The worst‐case analysis (WA) originally proposed by Lomax has been adopted in our institute to evaluate IMPT plan sensitivity to range and setup uncertainties. Here, we propose an evaluation method by exhaustively sampling uncertainties and apply it to validate WA. Methods: A series of perturbations to modify proton beam ranges and to shift the iso‐center in x‐, y‐ and z‐directions were sampled for 500 times to generate the probability distribution of plan qualities. The magnitude of a perturbation was assigned randomly following a normal distribution with specified standard deviations in each perturbation dimension. Perturbed dose was calculated for each sampling and compared to the WA dose. Dose‐volume‐histograms (DVH) were obtained for all perturbed doses. The distribution of DVHs and dose‐volume indices were examined. Prostate and head/neck cases were selected for demonstration. Results: In both cases, the DVHs of 500 perturbed doses spread over bands with various widths, and the DVH curves of WA lie within these bands and near the “worst” edges. for CTV, 97.6% in the prostate case and 97% in the head/neck case of the perturbed doses show a D95 value higher than the value given by WA. For normal tissues, at least 96.4% of the perturbed doses show lower dose‐volume indices (e.g. V70 of rectum and bladder) than the ones by WA. Conclusions: After exhaustively sampling the possible uncertainties, we verified that the worst‐case analysis may reasonably evaluate the IMPT plan sensitivity to setup and range uncertainties without considerably over‐ or under‐estimating it. The exhaustively sampling approach proposed here could offer a great outset toward comprehensively evaluating the IMPT plan sensitivity to a broader spectrum of planning and delivery uncertainties.
TH‐C‐BRB‐06: Comparison of Prompt Gamma and PET Imaging for Range Verification in Proton Therapy
Authors: Moteabbed M , Espana S , Paganetti H
Published: November 2011

Purpose: To compare the clinical adaptability of prompt gamma (PG) imaging and positron emission tomography (PET) as in‐vivo treatment verification tools in proton radiation therapy. Methods: In order to study the proton induced photon emission process in a patient during proton therapy, Monte Carlo simulations were performed using the GEANT4 toolkit. A thorough investigation of several different tumor sites such as head and neck, prostate, spine and abdomen, irradiated by passive scattered and pencil fields was performed. The calculated dose, PG rays and PET isotopes with decay times between 2 and 20 minutes were scored on the CT grid. The acquisition time delay and biological washout were implemented in the PET distribution post simulation. The correlation between dose and PG/PET was analyzed along lines parallel to the beam direction spaced about 2 mm apart from each other. Results: For all subjects, the PG method showed approximately 10 times higher gamma production rate than the PET method before, and 60 to 80 times higher production after including the washout and time corrections. This rate was directly proportional to the tissue density. For passive fields, the correlation between dose and PG/PET was strongly dependent on the location of the line profile within the field. This dependence can be related to the tissue heterogeneity and the position of the distal falloff within the patient. For pencil beams, the distances between both PG/PET and dose falloffs were consistent and therefore well correlated. This was mainly due to the smaller beam size and better‐defined distal falloffs. Conclusions: PG imaging was found more appropriate than PET for pencil beam scanning due to in‐situ capabilities and reduced limitations and uncertainties. However, current detector technology does not allow full utilization of this method, while PET range verification has already been studied clinically.
TH‐C‐BRC‐01: The Effects of Adaptive Gating on Treatment Accuracy and Delivery Time
Authors: Lewis J , Friesen S , Rottmann J , Nishioka S , Shirato H , Berbeco R , Hacker F
Published: November 2011

Purpose: To evaluate the effect of an adaptive gating system on treatment accuracy and delivery time as compared to gating based only on an external surrogate. Methods: Two studies were designed to simulate the process of treatment planning, patient setup, and treatment delivery for 1) external surrogate‐based; and 2) adaptive gating. External surrogate‐based gating used only chestwall motion to generate the respiratory gating signal, while adaptive gating updates the external/internal correlation periodically based on the location of implanted fiducial markers. Lung tumor trajectories with corresponding chestwall motions acquired from 8 patients with multiple days of radiation treatments. A total of 20,026 seconds of data from 163 treatment beams was used. The average target miss percentage is defined to be the percentage of beam‐on time that the target is thought to be within the gating window but is actually outside of it. The average duty cycle is defined as the beam‐on time divided by the sum of beam‐on and beam‐off time. Results: The average target miss percentage for adaptive gating was 17.6% (range: 8.0–23.6%) and 22.6% (range: 8.1–44.5%) without adaptation. The magnitude of the average miss was 1.7 mm (range: 0.6–4.8 mm) with adaptation and 1.8 mm (range: 0.6–4.3 mm) without adaptation. The average miss percentage for misses of over 5 mm was 0.6 % (range: 0.0–3.3%) for adaptive gating and 0.9 % (range: 0.0–3.7%) without adaptation, suggesting that additional planning margins of 5 mm would mitigate most gating errors with either method. The average duty cycle using adaptive gating was 33% (range: 23–39%), compared to 45% (range: 35–57%) without adaptation. Conclusion: We have shown that adaptive gating can improve the accuracy of gated treatments, at the cost of longer treatment times. However, both adaptive and non‐adaptive techniques perform well if an additional planning margin of 5 mm is used.
TH‐C‐BRC‐03: Comparison of 4D Dose Distribution Delivered with Two Different Tumor Tracking Strategies for Patients with Irregular Breathing: DRRT vs CDRT
Authors: Yang X , Han‐Oh S , Gui M , Niu Y , Yu C , Yi B
Published: November 2011

Purpose: Dose‐rate‐regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor and adapts to breathing irregularities during delivery using dose rate regulation. Constant‐dose‐rate tracking (CDRT) adjusts the MLC motion based on real‐time detection of tumor displacement. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods when dealing with breathing irregularities. Methods: Step‐and‐ shoot IMRT plans optimized at a reference phase were extended to the remaining phases to generate 10‐phased 4D‐IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM‐based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires pre‐programming of the MLC aperture sequence. Delivery of the 4D plans using DRRT and CDRT tracking approaches was simulated assuming the breathing period is either shorter or longer than the planning day. In DRRT, dose rate was regulated to speed‐up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT strategy, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in OAR dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing irregularities. Conclusions: In delivery of SAM‐ based 4D‐IMRT treatment plans considering tumor deformation as well as motion irregularities, the DRRT tracking method was found to be much more effective and more accurate than the CDRT strategy.

This research was supported in part by NIH grant 1R01CA133539‐01A2.
TH‐C‐214‐03: The Good the Bad and the Ugly about Using PET for Treatment Planning?”
Authors: Visvikis D
Published: November 2011

The use of PET data into the treatment planning process has been the focus of intense development over the past few years. The availability of multi‐ modality devices such as PET/CT has clearly intensified the interest on the use of PET information for treatment planning and associated research and development. The potential of such functional data includes the identification of tumour specific physiological processes and associated 3D functional volumes which in turn hold the potential of personalized treatment planning. However, there are numerous issues associated with the use of PET derived information in treatment planning, starting from the image acquisition protocols, the tracer or combination of tracers to be used, the fusion of PET and planning CT images, the accurate extraction of 3D functional volumes from the reconstructed PET images, and finally the different scenarios for the incorporation of the functional information in dose planning and delivery. This paper will review, primarily from a technological point of view, the current status of the integration of PET/CT data into the treatment process, discussing current successes and failures, as well as reflecting on the future. The use of PET data must be based upon a clear understanding of the interpretation and limitations of the functional signal. Subsequently consideration will be given to the requirements of PET/CT data acquisition and subsequent image processing accounting for technological limitations associated with current state of the art PET/CT devices. Approaches for the definition of functional/tumour volumes and the mechanisms available to measure and include physiological motion into the imaging process will be also reviewed. Finally the impact of these technological issues on current protocols for the implementation of functional data in the treatment planning process will be presented.

Learning objectives:

1. Understand the main incentives behind the use of PET in treatment planning.

2. Understand the issues associated with the use of PET information in treatment planning.

3. Understand the current status and potential future developments for the optimal integration of PET functional data in treatment planning
TH‐C‐301‐01: Accuracy and Utility of Diagnostic Ionization Dosimeters
Authors: Wagner L
Published: November 2011

Ionization chambers have been used in medicine for nearly a century. They are the standard instrument for measuring exposure and its related quantity, air kerma. In diagnostic medicine, there is a wide range of conditions under which air kerma must be measured. Air kerma rates important to diagnostic and image‐guided interventional radiology vary from less than 10 microgray per hour to many gray per minute. Energies range from less than 10 keV to 150 keV. Photon directivity can be nearly unidirectional, isotropic, or anisotropic. The manufacture of a variety of ionization chambers is necessary to meet the challenges of various tasks. This presentation will discuss the various forms of ionization chambers and their limitations and versatility for use in diagnostic medicine.

Learning objectives:

1. To understand limitations in the use of air‐kerma ionization meters

2. To be able to select the proper meter for a given task

3. To understand how different tasks place different challenges on the measurement of air kerma
TH‐C‐220‐03: Extraction of Radiosensitivity Coefficients from Multiparametric Molecular Imaging Data through Computational Tumor Modeling
Authors: Titz B , Jallow N , Jeraj R
Published: November 2011

Purpose: Patient‐specific differences in tumor radiosensitivity are generally disregarded in radiation therapy (RT), an approach that overlooks subgroups with different therapeutic responses. In this study, we extracted voxel‐based radiosensitivity coefficients from multiparametric molecular imaging data using a computational tumor growth and response model. Methods: Thirteen canine patients with sinonasal tumors underwent pre‐therapy PET/CT imaging of metabolic activity ([18F]FDG), proliferation ([18F]FLT), and hypoxia ([61Cu]Cu‐ATSM) using bite‐block immobilization. Following two RT fractions and two off‐treatment days, proliferative response was assessed via [18F]FLT‐PET/CT. Using a previously developed tumor simulation model, voxel‐based ‘effective’ linear radiosensitivity coefficients (alpha) were determined by simulating treatment response based upon pre‐therapy PET data and iteratively minimizing differences between simulated and imaged proliferative response. Resulting alpha values were investigated for inter‐ and intra‐patient heterogeneity, histology dependence, and spatial correlations with pre‐therapy PET data. Results: Alpha values in carcinomas (mean=0.061/Gy, SD=0.051/Gy) were higher than those found in sarcomas (mean=0.042/Gy, SD=0.024/Gy). Carcinomas were more heterogeneous in response (range=0.554/Gy) than sarcomas (range=0.110/Gy), which correlated with a more heterogeneous pre‐therapy uptake of all three PET imaging surrogate markers. Increased [61Cu]Cu‐ATSM uptake (SUV>4) alone indicated radioresistance, while simultaneous [18F]FLT uptake lowered effective alpha values. Using Akaikeˈs information criterion, five carcinomas were identified to exhibit bimodal or trimodal alpha distributions, while all sarcomas were found to be unimodal. Conclusion: Within this patient population, carcinomas were more radiosensitive and heterogeneous in alpha and PET tracer uptake. Extracted alpha values and their correlations with pre‐therapy PET data differed between tumor histologies. Results suggest that imaged hypoxia might not necessarily indicate increased levels of radioresistance as high proliferation potentially offsets this effect. After correlating early treatment response to late outcome, this model could be used to identify potential biological targets within tumors, stratify candidate dose painting patients, and to transform voxel‐ based information into biological treatment planning objectives.
TH‐C‐220‐04: Development and Characterization of a Prototype Compact Microbeam Radiation Therapy Device Based on Carbon Nanotube Field Emission X‐Ray Source Technology
Authors: Hadsell M , Zhang J , Cao G , Laganis P , Sprenger F , Schreiber E , Chang S , Lu J , Zhou O
Published: November 2011

Purpose: The use of spatially fractionated, ultra high flux arrays of microplanar X‐ray beams (MRT) has been shown by research groups at various synchrotron facilities to cause significant damage to radioresistant brain tumors while leaving normal tissue relatively unscathed. We wish to show that our development of a compact MRT device using carbon nanotube (CNT) field emission X‐ray technology has the capability to produce dose distributions in phantoms similar to that of synchrotron‐ generated microbeams while maintaining a reasonably high dose rate. Methods: CNT Cathodes were arranged in a linear array and electrostatically focused onto a reflection type tungsten target held at 160kV. A microbeam collimator assembly perpendicular to the anode plane was used to select a slice of the resulting wedge shaped radiation pattern. The collimated microplanar beam was projected onto a cylindrical phantom, slicing through it at 10 degrees. Two orthogonal dosimetric films were placed in the phantom to measure percentage depth dose and microbeam profile. Results: With initial limitations caused by an inadequate power supply, an instantaneous microbeam dose rate of 12Gy/min was achieved . This translates to continuous dose rate of 21 Gy/min at full power and maximum duty cycle. The microbeam profile showed a 350um FWHM with initial calibration and sub‐optimal system configuration. With further optimization, we expect to be able to achieve a smaller beam profile and double the dose rate. Conclusions: Based on the initial data, we strongly believe that we will be able to deliver high enough doses in microbeam distributions for preliminary biological studies with this first generation device. Finally, based on lessons learned during the construction of this first small‐scale MRT irradiator, we have already started designs of a first revision with which we hope to produce multiple thinner lines of radiation while maintaining a high enough dose rate for comparison studies.