bluuebunny/crossref_metadata_2025 huggingface dataset:
TU‐E‐BRB‐10: Investigation of the Water‐to‐Air Stopping Power Ratio for Carbon Ion Beam Dosimetry Based on Experimental Data and FLUKA Simulation
Authors: Sanchez‐Parcerisa D , Gemmel A , Parodi K , Jäkel O , Rietzel E
Published: November 2011

Purpose: Water‐to‐air stopping power ratio (Sw,air) is currently known with an uncertainty of 2% for carbon ion beams (IAEAˈs TRS‐398), and it is the main source of uncertainty in absolute dosimetry with air‐filled ionization chambers. We present here a more precise calculation of its value from measurements performed under controlled experimental conditions Methods: Sw,air is given in TRS‐398 as a particle fluence weighted average over all particles and energies, and it is derived from track‐lenght fluence of each particle in water and its mass stopping powers in water and air. All these quantities were calculated with the general‐purpose Monte Carlo code FLUKA. The input values to the code, including water and air mean ionization potentials of Iw = 75.9 ± 0.2 eV and Iair = 87 ± 3 eV, were chosen in accordance to experimental measurements of mono‐energetic carbon ion beams carried out at the Heidelberg Ion Therapy Center (HIT). The Sw,air was calculated for spread‐out Bragg Peaks (SOBPs) at different depths, and a possible dependence on the residual range was investigated. Results: For all the studied SOBPs, the uncertainty in the stopping power ratio could be reduced significantly by introducing a logarithmic dependence on the residual range. Moreover, using the fixed value of Sw,air =1.13 causes, on average, a dose underestimation of 0.1 % if used in the plateau area and of 0.4% if used n the peak (compared to Monte Carlo data), whereas using our Sw,air(z) model reduces this dose underestimation below 0.05% in all cases. Conclusions: The contribution presents a revised calculation of the water‐to‐air stopping power ratio using own experimental data that reduces significantly the uncertainty of the current reference value.

The research leading to these results has received funding from the European Communityˈs Seventh Framework Programme 2007–2013 under grant agreement n° 215840‐2 (PARTNER).
TU‐E‐BRC‐01: Volumetric 4D Computed Tomography with a 320‐Detector Row Scanner for Radiotherapy Simulation
Authors: Bracken J , Driscoll B , Jaffray D , Coolens C
Published: November 2011

Purpose: We propose to overcome the limitations of conventional helical 4D computed tomography (4DCT) using a volumetric 4DCT approach with a 320‐slice scanner. This scanner is able to acquire image volumes with 16 cm of superior‐inferior coverage with a single gantry rotation and no couch translation, preventing artifacts caused by retrospective image slice sorting. Image volume datasets over multiple breathing cycles can be acquired using this technique. Methods: A respiration motion phantom containing a cube and two sphere objects was scanned on a 320‐slice scanner using a volumetric approach and on a 16‐slice CT scanner using a helical scan technique. An irregular breathing pattern taken from a previous patient scan was programmed into the phantom. Volumes and centroid positions of these objects were segmented for volume and displacement measurements. A model was developed which predicted the number of samples of peak‐to‐peak displacement of a target that could be obtained with a conventional or volumetric scan technique. Results: Using a volumetric 4DCT scan technique to scan an irregular breathing pattern reduced the percent error in the measured volumes relative to the ground truth volumes of the cube and spheres by as much as 81%. No sorting artifacts or missing slices in these object volumes were present using the volumetric technique, unlike the conventional approach. The model predicted that the helical scan technique was limited to measuring 1–2 displacement samples. This limitation was not present with the volumetric scan technique, with which multiple samples of peak‐to‐peak displacement can be acquired. Conclusions: Volumetric 4DCT is a superior scan technique to the conventional helical approach, and its ability to acquire target volumes and displacements more accurately for irregular breathing patterns than the helical approach could help to improve internal target volume definitions for radiotherapy treatment planning.
TU‐E‐BRC‐03: Development of a Low Dose 4D‐CT Method to Study Lung Motion Using Nonlinear Registration
Authors: Pierce G , Wang A , Battista J , Lee T
Published: November 2011

Purpose: Develop a low dose 4D‐CT method and quantify the displacement uncertainties compared to regular dose scans. Methods: Two (2) landrace cross pigs were ventilated and scanned using a 64‐slice CT scanner (GE Healthcare, Discovery CT750HD). Each animal had a breath hold helical (BH) scan of its thorax performed at 200 mA and 100 kVp. An additional regular dose 4D‐CT scan (RD 4D‐CT) was performed, using the same scanning parameters, covering the same area as the BH scan and consisting of 8 respiratory phases. Simulated low dose 4D‐CT scans, at 10% and 1% of the original dose, were created through the addition of noise to the RD 4D‐CT scans (LD10 & LD1 4D‐CT). A nonlinear registration algorithm was employed to warp the BH volume to each of the of the RD & LD 4D‐CT phase volumes, producing three sets of warped 4D‐CT volumes (Warp(BH)‐RD, Warp(BH)‐LD10, Warp(BH)‐LD1). The average difference in voxel value (in HU) between the RD and each warped BH volume was calculated. Additionally, 6 vessel bifurcations were selected from the RD volumes and located in the warped BH volumes using rigid registration between corresponding segmented bifurcations. The average displacement of bifurcation location in the warped BH volumes compared to the RD volume was determined. Results: The average difference of voxel value from the RD volume was 3.9 4.5 HU and 3.7 4.4 HU for Warp(BH)‐RD, Warp(BH)‐LD10, Warp(BH)‐LD1 volumes respectively. The average displacement compared to the RD volumes of the 6 vessel bifurcations was 1.1 +/− 0.2 mm, 1.2 +/− 0.2 mm and 1.3 +/− 0.3 mm for the Warp(BH)‐RD, Warp(BH)‐LD10, Warp(BH)‐LD1 volumes respectively. Conclusions: We have developed a method to reduce the dose required for a 4D‐CT scan by approximately 90% and maintain an accuracy of 1.3 mm compared to 4D‐CT scans acquired at full dose.
TU‐E‐BRC‐04: High‐Statistics Breathing Motion‐Corrected Positron Emission Tomography by Deforming and Stacking Gated PET Images Using 4DCT‐Derived Motion Vectors
Authors: Lamb J , Santhanam A , Laforest R , Min Y , Dehdashti F , Robinson C , Bradley J , White B , Low D
Published: November 2011

Purpose: Positron emission tomography (PET) of lung tumors suffers due to breathing‐motion induced blurring. Gated PET ameliorates motion blurring, but the concomitant reduction in coincidence‐event statistics per gated image leads to increased image noise, decreasing the utility of the images. In this work we demonstrate a method of reducing motion‐induced blurring from PET images without decreasing coincidence‐event statistics. Methods: The method works by deforming and stacking gated PET images using lung tissue motion vectors derived from deformable image registration performed between the phases of respiratory‐correlated computed tomography (4DCT) images. A duration of 12 minutes of respiratory‐correlated FDG‐PET data in list‐mode format and two 4DCT scans were acquired from 3 patients with a total of 4 small (4–18cc) lung tumors. A motion‐corrected image was produced using the first 2 minutes of list‐mode data. The motion‐corrected image was compared to a high‐statistics gated end‐exhale PET image created from the remaining 10 minutes of PET list‐mode data, which was used as a gold‐standard approximating a truly motion‐free image. The images were also compared against an un‐gated PET image produced using the first two minutes of list‐mode data, to quantify the improvement provided by the motion‐correction process. Results: Tumor SUVmax was on average 44% higher for motion‐reduced images relative to un‐gated images, but still on average 14% lower than the gold‐standard high‐statistics gated images. Volumes of tumors segmented at 40% of SUVmax were on average 32% lower relative to un‐gated images, but still 22% higher than the high‐statistics gated images. Conclusions: A process for reducing motion blurring in PET images without increasing image noise was demonstrated. The motion‐corrected images are quantitatively and qualitatively improved relative to un‐gated images, however further improvement is needed in order to match the quality of high‐statistics gated images.
TU‐E‐BRC‐06: Rapid MRI for Personalized 4D Image‐Guided Lung Cancer Radiotherapy
Authors: Sawant A , Yuan Q , Khatri G , Joshi S
Published: November 2011

Purpose: Respiratory motion causes thoracic anatomy to change continuously in all four dimensions (4D = 3D+time). However, current image‐guidance tools (e.g., 4DCT) provide only a reconstituted, single‐cycle snapshot of motion, thereby ignoring complex cycle‐to‐cycle spatial and temporal effects. In this work, we investigate the use of rapid MRI as a truly 4D, non‐invasive monitoring tool for lung SBRT Methods: Under an IRB‐approved protocol, two lung cancer patients were imaged under free breathing conditions, without extrinsic contrast, on a 1.5T MRI scanner using a 4‐channel cardiac coil. A balanced SSFP sequence (TE/TR: 1.68/3.16 ms; FOV: 240×240 mm2; half‐Fourier acquisition; voxel: 2.4×3x5 mm3) was used to acquire 2D+t and 4D (8 slices, parallel acceleration=4) time series for 20s and 60s respectively. For each 2D+t series, the tumor centroid, the diaphragm and ∼15 points on the tumor boundary were manually contoured on one image frame. An optical fluid‐flow‐based deformable image registration algorithm was applied to the time series to map the motion trajectory of each point on each contour. A temporal smoothness constraint was imposed so as to avoid non‐physical registration. Results: Acquisition times of ∼0.15s/frame and ∼1.5s/volume were achieved for 2D+t and 4D acquisition, respectively. In each case, image quality was adequate to clearly delineate and monitor the motion of the tumor, the diaphragm and the cardiac wall. Both patients showed significant cycle‐to‐cycle variation in tumor position. One of the patients with a left mid‐lobe lesion showed significant tumor deformation and rotation (>4 degrees) due to the combined influence of cardiac and diaphragmatic motion. Conclusions: Rapid 2D+t and 4D MRI offers a highly attractive, non‐invasive tool for characterizing respiratory motion from a truly 4D perspective. Such image‐guidance will lay the groundwork for personalized motion management based on patient‐specific, long‐term monitoring, personalized 4D treatment planning and, if necessary, inter‐ and intra‐fraction treatment adaptations.
TU‐E‐BRC‐08: Investigation of Anatomical Surrogate for 4DCT Imaging
Authors: Cai J , Chang Z , OˈDaniel J , Yoo S , Jian Y , Ge H , Yin F
Published: November 2011

Purpose: Respiratory signal for 4DCT is typically extracted using an external respiratory positioning management device (RPM) which is often inconvenient and time consuming. The efficiency of 4DCT imaging could be substantially improved if anatomical body could be used as respiratory surrogate. The purpose of this study is to compare similarity of 4DCT sorted using respiratory signals extracted from anatomical surrogate (AS) to those extracted from RPM.Methods: 4DCT data of 31 cancer patients (15 male, 16 female, 67.0 mean age, 17 lung cancers, 14 abdominal cancers) were retrospectively analyzed. Respiratory signals/phases were derived from AS (body area of axial CT image) using pre‐sorted CT images and compared to those from RPM. The correlation coefficient (r) and absolute phase difference (|d|) between the two were calculated. Image quality of 4DCT reconstructed using the two methods (4DCTAS and 4DCTRPM) was scored (1 to 5, 1 is the best) for comparison. Results: The mean correlation coefficients were 0.92±0.05, 0.90±0.06, and 0.94±0.03, and mean absolute phase differences were 11.40±4.62%, 13.83±4.56%, and 8.45±2.56 for all patients, the lung cancer patients, and the abdominal cancer patients, respectively. The match between AS‐ and RPM‐derived phases was significantly better for the abdominal cancer patients than for the lung cancer patients (p‐value=0.04 and 0.001 for comparisons in r and |d| respectively. The phase difference was the greatest near the diaphragm in the lung cancer patients. No slice‐location dependency for phase difference was observed in the abdominal cancer patients. The 4DCTRPM slightly outperformed the 4DCTAS in image quality evaluation: mean scores were 2.5±0.6 and 3.1±0.8 (p‐value=0.02) respectively for the lung cancer patients, and were 2.6±0.7 and 2.8±0.9 (p‐value=0.59) respectively for the abdominal cancer patients. Conclusions: Anatomical surrogate for 4DCT sorting is comparable to RPM. Its performance is better for abdominal cancer patients than for lung cancer patients.
TU‐E‐BRC‐11: Clinical Impact of Dose Mapping Sensitivity to Deformable Image Registration Parameter Selection
Authors: Salguero F , Siebers J
Published: November 2011

Purpose: 4D dose mapping accuracy is limited by the accuracy of the displacement vector fields (DVF) generated by deformable image registration (DIR) algorithms. DIRs depend on user adjustable parameters whose election may result in different resulting DVFs. This work evaluates the clinical impact of DIR parameter selection on 4D accumulated doses. Methods: A 180 cGy/fraction PTV dose clinical treatment plan is generated, with dose calculated on each phase of a ten‐phase 4D lung CT image. Per‐ phase doses are mapped to a reference phase using DVFs from the demons DIR implemented in a research version of Pinnacle 9.1 for dose accumulation using a variety of settings for DIR user‐adjustable parameters. Dose‐volume histograms, TCP, and NTCP values are evaluated for each accumulated dose as are differences in accumulated dose values. Results: Cumulative dose values vary with the user adjustable parameters. The maximum dose difference is 62.5 cGy/fraction when the number of image filter histogram bins changes from 32 to 16 and 14.9 cGy/fraction when the number of level 4 iterations (where the image is downsampled to 1/8 of the original resolution) changes from 50 to 10. Dose variance tends to be in specific locations that accumulate most differences. These regions are suspect for dose accumulation errors. Despite the dose differences found, DVHs, TCP, and NTCP values varied little, indicating minimal clinical impact of DIR parameters. Conclusions: Accumulated dose variations due to DIR parameter selection occur in limited regions of an image. Such variation can be used to estimate the precision of 4D dose. Although minimal clinical impact is found for the case presented, additional study with more patients and different planning features are required prior to establishing global conclusions.

Supported by NIH‐P01CA116602 and Philips Medical Systems
TU‐E‐214‐01: Preclinical and Clinical Hypoxia Imaging: Current and Emerging Methods and Technology
Authors: Graves E
Published: November 2011

The absence of oxygen (hypoxia) is an important determinant of the malignant behavior of cancers and their response to radiation therapy. A variety of non‐invasive imaging techniques have been developed to study tissue oxygenation. The paramagnetism of oxygen molecules has been exploited for magnetic resonance imaging (MRI) of oxygen through the use of T1‐weighted and blood oxygen level‐dependent (BOLD) T2*‐weighted MRI. Electron paramagnetic resonance (EPR) as well as Overhauser‐ enhanced MR (OMR) methods have also been applied to image oxygen‐ sensitive spin probes in vivo. Positron emission tomography (PET) imaging of radioactively‐labeled compounds that selectively accumulate in hypoxic cells has also been rigorously developed, and a number of agents of this type are now being used clinically. As hypoxia and imaging biomarkers of hypoxia constitute an expanding area of cancer and radiation biology research, medical physicists must be aware of these advances in order to understand emerging literature, appreciate the significance of hypoxia in the practice of clinical oncology, and identify opportunities for further research. In this symposium, we will provide an overview of the field of preclinical and clinical hypoxia imaging, with an emphasis on MRI‐ and PET‐based methods that have been translated into clinical use. The course will focus on: the biological significance of hypoxia in cancer, a description of the basic underlying oxygen‐dependent contrast mechanisms, presentation of basic imaging protocols for each modality, an overview of the existing preclinical and clinical hypoxia imaging data, and identification of challenges and opportunities for research.

Learning objectives:

1. Enumerate existing techniques for hypoxia imaging and underlying contrast mechanisms.

2. Recognize major advantages/disadvantages of hypoxia imaging modalities.

3. Identify research opportunities in each hypoxia imaging domain.
TU‐E‐214‐02: Overhauser Oxygenation Imaging: Physics, Instrumentation and Pre‐Clinical Applications
Authors: Hristov D , Ahn K , Scott G
Published: November 2011

Tumor oxygenation and redox status are important determinants of the malignant behavior of cancers and their response to radiation therapy. Concentration of molecular oxygen is directly related to the generation of non‐restorable DNA damage. Tissue redox status indicates catalytic cellular activities to scavenge free radicals that initiate a chain of events for DNA damage by an ionizing radiation. Thus a non‐invasive system that obtains this information on relevant time scales with anatomical context could facilitate longitudinal studies of the multi‐faceted tumor environment.

Changes in the resonant properties of exogenous narrow‐line electron spin (free radical) probes in presence of oxygen can be sensed by electron paramagnetic resonance as well as Overhauser‐enhanced magnetic resonance (OMR). In OMR, the dipolar interaction between protons and the unpaired electron of the spin probe results in strong increase of the proton MR signal. The enhancement depends on several factors such as spin probe and oxygen concentration, longitudinal relaxation times, and the magnitude of the radiofrequency magnetic field that manipulates the electron spins. Specific imaging sequences decoupling these factors in spatially encoded manner can generate quantitative spatial maps not only of tumor oxygenation but also micro‐vascular parameters. Furthermore, these physiological maps can be natively fused with anatomical MR images generated with the same hardware in the same imaging session. This information can be acquired repeatedly for quantitative longitudinal imaging experiments to explore both oxygenation and redox status in small animals as prognostic factors for radiation therapy.

Learning objectives:

1. Understand the basic physics behind the Overhauser enhancement and enumerate the factors that determine its magnitude.

2. Recognize the main hardware components of an Overhauser oxygenation imager and understand the operating parameters of the imaging system in contrast to these of high‐field diagnostic MR scanner.

3. Understand a typical OMR imaging sequence and subsequent image analysis to derive oxygenation maps.

4. Understand typical OMRI applications in cancer‐related studies.
TU‐E‐214‐03: Preclinical and Clinical Hypoxia Imaging: Current and Emerging Methods and Technology
Authors: Jeraj R
Published: November 2011

The definition of tumor hypoxia is multifaceted, ranging from a simple physiological absence of molecular oxygen in tumor cells to a major factor associated with aggressive tumor phenotype; therefore, imaging of tumor hypoxia is equally poorly defined. Several compounds have been synthesized for PET hypoxia imaging studies: 18F‐fluoromisonidazole (FMISO), Cu‐diacetyl‐bis(N4‐methylthiosemicarbazone) (Cu‐ATSM), 2‐nitroimidazoles based markers such as 2‐(2‐nitroimidazol‐1[H]‐yl)‐N‐(3‐[F‐18]fluoropropyl) acetamide (EF1) and [2‐(2‐nitroimidazol‐1‐yl)‐N‐(3,3,3‐trifluoropropyl)‐acetamide], [2‐(2‐nitro‐1[H]‐imidazol‐1‐yl)‐N‐(2,2,3,3,3‐penta‐fluoropropyl)‐acetamide] (EF5), and most recently 1‐(5‐fluoro‐5‐deoxy‐alpha‐D‐arabinofuranosyl)‐2‐nitroimidazole (FAZA). All these compounds diffuse into normally oxygenated and hypoxic cells but are retained in substantially higher concentrations in hypoxic issues. Clinically most commonly used PET hypoxia tracers are FMISO and Cu‐ATSM. In this lecture, different PET hypoxia tracers will be reviewed, focusing on differences in their uptake mechanisms, which lead to differences in their clinical appearance. In addition, the most important clinical trials utilizing PET hypoxia imaging will be reviewed.

Learning objectives:

1. To learn about clinical PET imaging of hypoxia

2. To learn about differences between various PET hypoxia tracers

3. To learn about clinical trials utilizing PET hypoxia imaging
TU‐E‐110‐01: Inverse Geometry CT
Authors: Pelc N
Published: November 2011

Purpose: Computed tomographic imaging has made tremendous progress in recent decades but challenges remain, including dose efficiency and avoiding cone beam artifacts in rapid volumetric imaging. The goal of this research is to explore Inverse Geometry CT (IGCT) as a potential solution to these problems.Methods: Rather illuminating the entire object with a single source, IGCT uses a distributed array of sources, each illuminating a portion of the volume. Two approaches have been studied, one using a scanned anode source (SS‐IGCT) and another using an array of discrete sources each with its own electron emitter (MS‐IGCT). The sequential illumination of subvolumes allows a “virtual bowtie” wherein each source has its own optimized intensity as a function of angle. Results: Results show that distributed sources in the axial direction can readily control cone beam artifacts. A gantry‐based MS‐IGCT system has been built and initial images have been collected. Compared to a conventional system, the virtual bowtie concept can significantly reduce effective dose for the same image quality. A key challenge with IGCT is achieving high x‐ray statistics since only a fraction of the object is illuminating in any instant. Thus, the method is well suited to lower dose scanning. Conclusion: IGCT uses distributed x‐ray sources to ensure sufficient sampling and to sculpt the illuminating x‐ray field. Initial results are promising.

Research sponsored by GE Healthcare.

The learning objectives are to familiarize the audience with

1. Principles of Inverse Geometry CT (IGCT)

2. Advantages of IGCT

3. Challenges and disadvantages of IGCT

4. Progress in IGCT to‐date
TU‐E‐110‐04: Tetrahedron Beam Computed Tomography
Authors: Zhang T , Xu X , Kim J , Schulze D
Published: November 2011

Purpose: The image quality of cone beam CT (CBCT) is significantly inferior to that of diagnostic CT systems. The major problems of CBCT systems include excessive scatter, inferior detector performance, data truncation and approximate cone reconstruction. Its inferior image quality hinders the implementation of advanced IGRT treatment techniques, such as online and offline adaptive radiation treatment (ART). We are developing a novel tetrahedron beam computed tomography (TBCT) system which can significantly improve online image quality, thereby increasing the precision of radiation treatments.

Method: A multiple pixel x‐ray source may allow novel imaging systems with improved image quality, reduced x‐ray exposure and lower cost. With a single rotation, the volumes enclosed by a cone (pyramid) and tetrahedron are exactly the same. Hence a volumetric CT scan can also be achieved by rotating a tetrahedron, which is formed by a linear x‐ray source array and a linear detector array orthogonal to each other. In TBCT, scatter photons are mostly rejected thanks to the fan beam geometry. Image quality is further improved by the use of a high quality solid‐state CT detector. Approximate FDK cone reconstruction artifacts can be mitigated using iterative image reconstruction algorithms. Results: A TBCT benchtop system has been developed using a 75 pixel x‐ray tube and an in‐house developed CT detector array. An iterative image reconstruction algorithm has been developed. The system produced excellent CT images which are superior to that of commercial CBCT scanners and close to that of diagnostic CT scanners.

Conclusion: TBCT is able to produce image quality close to that of diagnostic CT scanners. Clinical implementation of TBCT in IGRT can improve the precision of radiation treatments. Due to its superior image quality and compact geometry, c‐arm TBCT can also possibly be used as low‐cost, mobile diagnostic CT scanners.
TU‐E‐220‐04: Quantitative Ultrasound Computed Tomography for Volumetric Breast Imaging
Authors: Andre M , Ojeda‐Fournier H , Olson L , Wiskin J , Borup D
Published: November 2011

The basic imaging paradigm of medical US has remained unchanged, namely image formation results from transmission‐reception of 180 degree backscatter assuming straight‐line propagation. Our group has developed Quantitative Ultrasound CT (USCT) that creates images of the breast from the full 3D scatter field including both transmitted and reflected signals. While modern US provides a two‐dimensional map of relative tissue “echogenicity,” USCT computes quantitative 3D maps of tissue acoustic properties including sound speed, attenuation, scatter density, etc., as approximations of components of the wave equation. The method corrects for refraction, absorption, multiple scattering and more. High resolution reflection tomography is performed in which the sound speed and attenuation maps are utilized for aberration correction to significantly improve image quality. Clinical measurements suggest that in breast tissue, benign lesions and cancerous lesions may be identified by these inherent acoustic. The scanner uses a multi‐frequency non‐linear 3D inverse‐ scattering algorithm and despite the historical computational complexity of the problem, our method is fast and practical. Conventional breast sonography is a notoriously difficult exam to perform; the quality is dependent on the skill of the operator as well as technical features of the scanner. In order to obtain the needed high resolution, the field of view in sonography is very small, which greatly complicates interpretation and localization of masses. USCT promises an automated whole‐breast scan providing a global view of the entire breast in 3D, facilitating comparison to prior exams in a reproducible geometry. Results of our trial with over 150 subjects with confirmed breast masses will be presented with detailed comparison to conventional sonography and MRI.

Learning Objectives:

1. Understand the principles of inverse‐scatter tomography.

2. Understand the unique data acquisition and processing applied in ultrasound computed tomography.

3. Understand the potential clinical advantages of quantitative whole breast ultrasound imaging.
TU‐E‐220‐05: Characterizing Breast Lesions and Their Environments with Ultrasound Tomography
Authors: Duric N
Published: November 2011

Purpose: The purpose of this presentation is to report on a clinical study investigating the use of ultrasound tomography for characterization of breast lesions and their environments.Methods: A series of clinical studies were carried out using a recently upgraded clinical prototype based on the principles of ultrasound tomography. The in‐vivo performance of the prototype was assessed by imaging patients at the Karmanos Cancer Instituteˈs Alexander J. Walt Comprehensive Breast Center. Patients were recruited on the basis of having suspicious masses on mammography and were subsequently imaged with the prototype. Reflection images were constructed using sum and delay type beamforming in post‐processing while sound speed and attenuation images were reconstructed using bent‐ray tomographic techniques. Masses were identified by biopsy and their locations inferred from conventional mammography and ultrasound exams to provide the ground truth against which the performance of the prototype was measured. Results: Our techniques successfully demonstrated tomographic imaging of breast architecture as well as masses as small as 4 mm in size. Detected masses included cancers, cysts, fibroadenomas and hamartomas while anatomical structures corresponding to fat, parenchyma and fibrous stroma were also revealed. Masses were characterized using a combination of qualitative reflection parameters and the quantitative acoustic parameters of sound speed and attenuation. Furthermore, visualization and characterization of the tumor environment was achieved by combining the three imaging parameters, leading to clear evidence of the interaction of cancer with its surroundings. Conclusions: These results indicate that operator‐independent whole‐breast imaging and the detection and characterization of cancerous breast masses and their environment are feasible using ultrasound tomography techniques. This approach has the potential to provide a low cost, non‐invasive, and non‐ionizing means of evaluating breast masses, leading to a better understanding of tumor development and possible improvements in lesion detection and identification compared to current breast imaging techniques.
TU‐E‐220‐06: Simulation and Tissue‐Mimicking Phantom Validation of Shear Strain Imaging for Mass Differentiation
Authors: Xu H , Varghese T , Madsen E L
Published: November 2011

Purpose: Axial and full‐shear strain imaging have been utilized to differentiate between benign breast masses that are loosely bound, from malignant masses that are firmly bound to the background normal tissue. We examine contributions of different mass properties such as modulus contrast, mass shape, and asymmetric location within the background tissue to the shear strain features. Methods: Both numerical and experimental tissue‐mimicking phantoms were utilized to evaluate the feasibility of axial and full‐shear strain imaging. Finite element analysis models a circular and elliptical inclusion in the center of a uniform background. Friction coefficient values at the inclusion/background interface is varied to simulate different bonding conditions. Experimental phantoms with ellipsoidal masses (both firmly and loosely attached) oriented at 00, 300, 600 and 900 and embedded into a uniformly elastic background are utilized to corroborate the numerical simulations. Shear strain images are estimated from the gradient of the local displacement vectors. Axial and full‐shear strain areas are normalized to the mass dimensions, applied deformation and strain contrast to quantify the shear strain features. Results: The normalized axial‐shear strain area (NASSA) and full‐shear strain area (NFSSA) features are both significantly larger for firmly bound masses when compared to loosely bound masses for both spherical and ellipsoidal shaped masses. Differentiation between loosely and firmly bound masses is improved for masses with larger modulus contrasts. Larger applied deformations may result in slippage of loosely bound masses. For asymmetric masses the best differentiation is obtained at orientations of 00 and 900 with respect to the direction of the applied deformation. Conclusions: Our numerical and phantom results demonstrate the feasibility of utilizing NASSA and NFSSA features to classify a mass as benign or malignant based on their bonding to the background tissue. This feature can be utilized in conjunction with stiffness contrast and size‐ratio features currently utilized in axial‐strain elastography.

This work is supported by Komen Foundation Grant BCTR0601153 and NIH Grants R01CA112192‐S103, 5R21CA140939‐02 and 5R21EB010098‐02.
TU‐E‐220‐07: Using Breast Density as an Indicator of Side Effects and Change Induced by Tamoxifen and Radiation Treatment for Ductal Carcinoma in Situ
Authors: Boyer S , Duric N
Published: November 2011

Purpose: Breast cancer kills more women in the United States than any other cancer except for lung cancer. Treatment is generally surgery followed by radiation therapy, chemotherapy and/or hormonal therapy. Many of these patients will have side effects to the treatment, including 80% of patients receiving radiation therapy, where 48% will have long term effects. The purpose of this paper is to identify if tracking breast density through treatment is possible, and if that breast density is indicative of side effects.Methods: Patient data were acquired from patients recruited into ongoing studies in accord with a Karmanos Cancer Institute and Wayne State University approved research protocol. Patients were selected if they exhibited a suspicious mass after mammography and/or follow‐up ultrasound. We tracked the patient volume‐averaged breast density throughout the course of treatment, starting on the first day of treatment. We recorded the volume‐averaged breast density of each breast generally once every week. To analyze this data, we plot the left and right volume‐averaged breast density to determine if and how the breast density is changing. We used excel to determine the slope (the change of volume‐averaged breast density in km/s vs. time in s) and the coefficient of determination (r2) for our data. Results: Our results show that the change in breast density over the course of radiation treatment, Tamoxifen treatment, and a combination of the two, is measureable. Conclusions: We can detect a small change in breast density, in‐vivo, on a weekly basis, throughout the course of treatment. The limitation to this study is the small number of patients, in this study only 5. Future studies are needed to determine the significance of our results. Currently, we believe that edema, and possibly fibrosis would be observable, which will be shown in future studies.
TU‐G‐BRA‐03: A Mechanism‐Based Approach to Predict Relative Biological Effectiveness and the Effects of Tumor Hypoxia in Charged Particle Radiotherapy
Authors: Carlson D
Published: November 2011

The potential biological advantages of charged particles, such as protons and carbon ions, have not yet been fully exploited in radiation oncology. With increasing particle stopping power, relative biological effectiveness (RBE) increases and the radioprotective effect of tumor hypoxia decreases. In this work, a mechanism‐based approach to quantify the effects of oxygen and radiation quality on double strand break (DSB) induction and cell killing is presented for clinically‐relevant proton and carbon ion beams. DSB yields are quantified as a function of stopping power and oxygen concentration using the Monte Carlo Damage Simulation (MCDS). Formulas derived from the Repair‐Misrepair‐Fixation (RMF) model are presented that link dose‐averaged linear‐quadratic (LQ) parameters to DSB induction and processing. Predicted trends in radiosensitivity parameters with stopping power and oxygen concentration are compared to published experimental data. The dependence of RBE estimates on dose, tissue radiosensitivity, and position within the spread out Bragg peak (SOBP) is shown. RBE‐weighted doses are calculated for representative SOBP and a range of oxygen concentrations. Alternate biological models are also briefly reviewed. The RMF model is shown to predict published survival data well up to an LET of ∼150–200 keV/micron for V79, HSG, and T1 cells irradiated with He‐3, C‐12, and Ne‐20 under normoxic and anoxic conditions. Clinically‐relevant RBE estimates are shown to increase as particle energy, dose, and tissue alpha/beta decrease. For normoxic chordoma tissue with (alpha/beta)x=2 Gy and a 5 cm SOBP with a nominal absorbed dose of 1 Gy, entrance RBE is ∼1.0 and ∼1.3 for proton and carbon ions, respectively. Proton RBE ranges from 1.03 to 1.34 from the proximal to distal edge. Under the same conditions, the RBE for carbon ions ranges from 1.8 to 5.4. For extreme levels of hypoxia, proton and carbon ion doses in the SOBP may need to be increased by factors as high as 2.9 and 1.6, respectively, to achieve a uniform biological effect. The proposed approach to calculate RBE for clinical beams of charged particles is advantageous because it is guided by well‐established physical and biological considerations. The use of biologically motivated models to estimate RBE and hypoxia effects for clinically relevant oxygen concentrations enhances our understanding of the potential for protons and carbon ions to overcome the radioprotective effect of tumor hypoxia. Large variations in predicted RBE across an SOBP may produce undesirable biological hot and cold spots. Biologically optimized treatment plans that correct for radiation quality and tissue oxygenation have the potential to substantially improve treatment outcomes.

Learning objectives:

1. To review the relationship between DSB induction and cell killing

2. To understand the effects of radiation quality and oxygen concentration on cell killing in proton and carbon ion radiotherapy
TU‐G‐BRB‐03: Respiratory Motion Effects on Lung Proton SBRT Treatment
Authors: Lin M , Tafo A Guemnie , Li J , Fourkal E , Ma C
Published: November 2011

Purpose: To investigate the dosimetric impact of the respiratory motion on lung SBRT treatment when proton beams are used. Methods: Ten patients with 4D‐CT scans treated by photon SBRT were recruited for this study. To be consistent with the clinical practice, the PTV density override was performed to account for the tumor movement. Intensity modulated proton therapy (IMPT) plans were generated using our MC based dose calculation and optimization system. To quantify the density variation caused by breathing, the average lung density of inhale, exhale and a middle phase was calculated accordingly for every patient. MC simulation was performed to investigate the effects of density variation and the heterogeneity on the SOBP under simple geometry first. The effects of lung density variation on patient dose calculation were investigated subsequently by recalculating the dose distributions of IMPT plans with a different lung density for every individual phase. To investigate the effect of density override, dose distributions of IMPT plans with and without PTV density override were compared. Results: The density variation (2.3%–120%,average 22%) and heterogeneity cause SOBP distal edge shift, distortion, and a higher exit dose, which consequently leads to underdosage inside the target and a higher dose to the lung/critical organ in the downstream. In reality, the PTV is composed of solid GTV and lung tissue rather than homogeneous tissue with the unity density set in PTV override. Therefore, in patient treatment, part of the proton beam penetrates deeper than expected. This can significantly increase the dose to the adjacent critical organ. Conclusion: The respiratory motion and density variation can significantly affect the critical organ dose and the target coverage, especially for a small tumor with large motion. To encompass the motion, treatment margin and density override should be carefully applied and respiratory gating is necessary for proton SBRT treatment.
TU‐G‐BRB‐08: 3D Proton Dose Distributions in an Anthropomorphic Lung Phantom, Comparing Monte Carlo, Film, and TLD Measurements
Authors: Perles L A , Ibbott G S , Blatnica A , Mirkovic D , Titt U , Gillin M , Mohan R
Published: November 2011

Purpose: Evaluate and determine the feasibility of using thoracic phantoms in the credentialing of proton therapy facilities, by using irradiations, treatment planning calculations and Monte Carlo simulations.Methods: The Radiological Physics Center (RPC, Houston, TX) has developed an anthropomorphic lung phantom to be used for credentialing of lung trials in proton therapy. The phantom has structures like heart, spinal cord, right and left lungs and a cylindrical target located in the middle of the left lung. EBT2 films were placed cutting the target on the axial, coronal and sagittal planes for relative dosimetry. The absolute dose was measured with LiF TLDs located in the center of the target. The proton stopping power ratio of each material used in the phantom as well the respective CT number was also evaluated for this work. Based on a CT image of the phantom we created a plan in ECLIPSE with two fields delivering 6 Gy RBE to the target. A customized table was used to translate the phantom CT numbers into stopping power ratio for the ECLIPSE plan. The treatment plan was also simulated in Monte Carlo using a customized version of MCNPX. The phantom was irradiated at University of Texas MD Anderson Proton Therapy Center, Houston, Texas. Profiles and the Gamma tool were used to compare the film measurements to ECLIPSE and MCNPX calculations. Results: The gamma agreement of the Monte Carlo and ECLIPSE calculations was above 85% in the GTV region for all planes. The profiles of the Monte Carlo showed a better agreement with film measurements than ECLIPSE calculations. We also identified LET dependence on film measurements. Conclusion: We concluded that this method can give accurate results for passive scattering proton beams for the GTV areas. We are conducting further studies to correct for the film LET response.

This project is supported in part by P01CA021239 from the National Cancer Institute.
TU‐G‐BRB‐09: The Effective Depth of Cylindrical Ionization Chambers in Water for Clinical Proton Beams
Authors: Bhullar A , Watchman C
Published: November 2011

Purpose: In this study, we have developed an explicit analytical model to compute the effective depth of cylindrical ionization chambers in water for clinical proton beams. We have compared our explicit analytical model with an existing series expansion model. We have calculated the shift of water equivalent depth for different cylindrical ionization chambers and have compared our results with the IAEA recommendations and series expansion model. Methods: We have developed a method to compute the elliptic integral in an explicit analytical form. Using this integral form, the shift of water equivalent depth has been computed by accounting for individual contributions of ionization chamber cavity, wall, central electrode and sleeve for proton energies ranging from 1.0 Kev to 1.0 Gev for thirty four commercially available ionization chambers. Results: The comparison of explicit analytical expression with series expansion reveals that integrations calculated by series expansion fail to converge when the ratio of radii of cylindrical ionization chambers is greater than 0.5. For all the ion chambers selected in this study, our results vary at maximum of 0.5 mm from the IAEA recommendations, whereas the maximum variation for the series expansion model is 1.5 mm. Conclusions: The findings of this study suggest that the developed analytical model is reliable for calculation of the effective depth in water. Further, verification of these results with Monte Carlo calculation may suggest the need for review of the standards for all commercial ionization chambers.
TU‐G‐BRC‐06: Patterns of Intra‐Fractional Motion and Uncertainties of Treatment Setup Reference Systems in Accelerated Partial Breast Irradiation of Right‐ and Left‐Sided Breast Cancer
Authors: Yue N , Goyal S , Braun K , Khan A , Haffty B
Published: November 2011

Purpose: This study investigated the patterns of intra‐fractional motion and accuracy of treatment setup strategies in 3D‐CRT APBI for right‐ and left‐sided breast cancer. Methods: 16 right and 17 left breast cancer patients were enrolled in an institutional APBI trial in which gold fiducial markers were strategically sutured to the surgical cavity walls. Daily pre‐ and post‐RT kV imaging were performed and were matched to DRRs based on bony anatomy and fiducial markers, respectively, to determine the intra‐fractional motion. The positioning differences of the laser‐tattoo and the bony anatomy based setups with respect to the marker based setup (benchmark) were determined to evaluate their accuracy. Student t test was employed to evaluate the differences between the right‐ and left‐sided breast treatments. Results: Statistical differences were found between the right‐ and left‐sided APBI treatments in vector directions of intra‐fractional motion and treatment setup reference systems, but not in their magnitudes. The directional difference was more pronounced in the lateral. It was found that the intra‐fractional motion and setup reference systems tended to deviate in the left direction for the right‐sided breast treatments and in the right direction for the left‐sided breast treatments. Average intra‐fractional motion magnitude was 4.3 vs 4.8 mm and was 2.7 vs 3.0 mm based on the marker and bony anatomy matching, respectively, for right and left breast treatments. The bony anatomy and laser‐tattoo based inter‐fractional setup errors were 6.4 vs 7.5 mm, and 9.5 vs 9.2 mm, respectively. Conclusions: It appears that the fiducial markers placed in the seroma cavity exhibits side dependent directional intra‐factional motion. Although bony anatomy based treatment setup improves the accuracy over laser‐tattoo, it is inadequate to rely on bony anatomy to assess intra‐fractional target motion in both magnitude and direction. These data further support that a seroma specific approach is the key to improve treatment accuracy.
TU‐G‐BRC‐08: Maintaining Tumor Targeting Accuracy in Gating and Tracking Systems for Respiration‐Induced Tumor Motion
Authors: Malinowski K , McAvoy T , George R , Dieterich S , DˈSouza W
Published: November 2011

Purpose: To maintain accuracy, respiratory surrogate‐based intra‐fraction tumor motion models must be updated periodically. The purpose of this study was to determine how best to time respiratory surrogate‐based tumor motion model updates by comparing a novel statistical process control (SPC) method, based on external measurements alone, to three direct measurement methods in clinical use.Methods: Position datasets recorded during 121 treatment fractions from 61 lung cancer patients were analyzed. Datasets included 26 Hz localizations of three surrogate markers affixed to the torso as well as tumor localizations from intermittent (approximately once per minute) stereoscopic radiographs. Partial‐least‐squares regression models of tumor position from marker motion were created from six concurrent tumor localizations. At each radiographic localization, model accuracy was assessed and model rebuilding with the six most recent tumor localizations was considered. Model updates were timed according to four methods: (1) never, (2) when an SPC metric (either Hotellingˈs T,2 or the input‐variable‐squared‐prediction‐error) based on surrogate measurements alone exceeded 70,th percentile confidence limits, (3) when model error >3mm, and (4) at each radiographic localization. Results: Radial tumor displacement prediction errors (mean +/− standard deviation) for the four schema described above were 2.4 +/− 1.2 mm, 1.9 +/− 0.9 mm, 1.9 +/− 0.9 mm, and 1.7 +/− 0.9 mm, respectively. The no‐update error was significantly larger than errors of the other methods, which did not differ significantly. Mean update counts were 0, 3.3, 9.2, and 18.5, respectively, over 20 minutes. SPC‐timed updates were 36% and 18% as frequent as error‐based and each‐localization updates. Conclusions: Tumor localization accuracy improved significantly with model updates. Despite comparable tumor localization accuracy amongst the update methods, there were significantly fewer SPC‐timed model updates than error‐timed updates. This study proves the feasibility of timing model updates through analysis of external measurements alone, without direct tumor localization.

This work was supported in part by grant # CA124766 from the NIH/NCI and by the Achievement Rewards for College Scientists (ARCS) scholarship.