bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 hypoxia2. To learn about differences between various PET hypoxia tracers3. 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 with1. Principles of Inverse Geometry CT (IGCT)2. Advantages of IGCT3. Challenges and disadvantages of IGCT4. 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‐220‐06: 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‐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 killing2. To understand the effects of radiation quality and oxygen concentration on cell killing in proton and carbon ion radiotherapy
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‐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</sup> or the input‐variable‐squared‐prediction‐error) based on surrogate measurements alone exceeded 70,th</sup> 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.