bluuebunny/crossref_metadata_2025 huggingface dataset:
SU‐HH‐AUD C‐08: Spatial Weighted Mutual Information for Image Registration in Image Guided Radiation Therapy
Authors: Park SB , Rhee FC , Monroe JI , Sohn JW
Published: July 2008

Purpose: To develop a robust registration algorithm for medical images, emphasizing the registration of plan images with cone beam computed tomography (CBCT) images for IGRT. Our Spatial Weighted Mutual Information (SWMI) technique assigns greater importance to user‐selected volume, allowing medically ‘important’ areas to dominate the registration process. Method and Materials: Mutual Information (MI) is the most popular measure of image registration due to its robustness and multi‐modal capability. However, MI does have difficulty where organ deformation is present. We reformulated the MI algorithm by incorporating an adaptable weight function to user selected spatial locations. Since MI is defined in probabilistic space, we proposed a spatial‐weighted joint probability, and composed a Spatial Weighted Mutual Information measure. Our image registration software and Graphical User Interface (GUI) was programmed in C++ to import DICOM images and DICOM‐RT information, and to perform image registration. For this study, we used Gaussian‐shaped spatial weights applied to a user‐defined volume. Our software allows a user to adjust the Gaussian parameters via the GUI. Convergence and robustness of our registration method was first tested with a head‐and‐neck plan and seven CBCT image sets. Then, a prostate plan with nine CBCT image sets was analyzed. Speed of convergence was tested by arbitrarily miss‐aligning two image sets ±15mm over 41 trials. We also applied our algorithm to fuse CT and MRI image sets. Results and Discussion: Image registration using our measure converges 10% faster than using Mutual Information. Our study showed image registration using a uniform weight over an entire volume lead to compromised target coverage. SWMI showed better alignment near target areas and neighboring critical organs even with organ deformation. Our method worked well in fusing MRI to CT images as well.

(This work is partly supported by Susan G. Komen Breast Foundation Grant: BTCR126506).
SU‐HH‐AUD C‐09: Bioanatomic MR Imaging for Characterization of Brain Tumor and Radiation Response in the Rat Brain
Authors: Atwood TF , Zhu J‐M , Bourland JD
Published: July 2008

Purpose: To examine the efficacy of bioanatomic magnetic resonance imaging (MRI) in brain tumor characterization, and the implications for radiation therapy (RT) treatment planning and assessment of treatment response. Method and Materials: Brain tumor models were created by implanting human high‐grade glioma cells into immunodeficient rats. Once the tumors reached a specified target size, animals underwent Gamma Knife™ Stereotactic Radiosurgery (GK SRS, 15–18 Gy to the 50 % isodose line). During tumor growth and after irradiation, animals underwent serial MR evaluation (dynamic susceptibility contrast, DSC‐MRI) to quantify changes in cerebral blood volume (CBV) throughout the brain regions containing the tumor. Upon completion of the experiment, CBV data were compared with conventional MR imaging data and histology to evaluate the usefulness of the additional biological information with respect to target volume delineation and response to irradiation. Results: A DSC‐MRI erfusion protocol was successfully developed to accurately quantify blood volume changes within the brain. During tumor progression, active areas of tumor growth showed increased CBV, while areas of developing necrosis demonstrated decreased CBV. Large intra‐tumor CBV heterogeneities were visible in the late stages of unirradiated tumors and within a week of those irradiated with GK SRS. In both cases CBV data provided biological information regarding tumor behavior, which was not elucidated by the corresponding anatomical images. Conclusion: This work illustrates the potential of bioanatomic MRI for improving brain tumor radiation therapy. Most current high‐grade glioma RT techniques focus solely on anatomical images, which often neglect biological information when determining target volumes. By incorporating DSC‐MRI into the therapy planning and response assessment procedures, changes in CBV could be used to better understand tumor behavior. This could eventually lead to a more accurate way to determine conformal target volumes, and a more sensitive method for monitoring the therapeutic response.
MO‐SAMS‐AUD B‐01: Stereotactic Body Radiation Therapy (SBRT) I: Clinical and Radiobiological Considerations
Authors: Kavanagh B , Chang E , Chang Eric Lin
Published: July 2008

Stereotactic Body Radiation Therapy (SBRT) has emerged as an important form of cancer therapy with broad application across a spectrum of tumor types in the primary and metastatic settings. The capability of safely administering a very high dose of therapeutic radiation to discrete extracranial tumor sites has raised new questions about the radiobiology of high dose per fraction treatment. Accumulating clinical experiences are yielding new insights into practical aspects of tumor and normal tissue responses to high dose per fraction treatment.

The current practice of SBRT has evolved to some extent from knowledge gained from principles learned from the practice of cranial stereotactic radiosurgery (SRS), and this presentation will begin with discussion of the use of SBRT for sites where the extracranial nervous system (spinal cord, cauda equina) is the major dose‐limiting structure. Some recent preclinical studies of spinal cord tolerance to high dose therapy will be presented, as well as the results of recent clinical trials involving spine SBRT from various centers. Next, the discussion will focus on other major extracranial sites where SBRT has been applied, with emphasis on SBRT for tumors in the liver and lung in particular, again with inclusion of theoretical and preclinical studies as well as reported clinical outcomes.

Educational Objectives:

1. Review and understand the major issues related to the use SBRT for tumors in the spine or paraspinous region, including key clinical observations.

2. Review and understand the common clinically observed normal tissue responses to SBRT and the inferences to be drawn regarding the practical radiobiology of high dose per fraction therapy.

3. Explore and highlight the major issues related to clinical application of SBRT for tumors in the lung and liver, including key clinical observations.
MO‐SAMS‐AUD B‐02: Stereotactic Body Radiation Therapy (SBRT) II: Physics and Dosimetry Considerations
Authors: Benedict S , Yenice K
Published: July 2008

SBRT of well defined extracranial targets in various anatomical locations demands special treatment planning considerations due to limitations of dose calculation algorithms in heterogeneous medium and small field dosimetry coupled with tumor/organ motion and multiple radiobiological constraints. Unlike conventional intracranial radiosurgery, SBRT treatment planning and delivery are confounded by reduced 3D physical space for beam placement due to possibility of treatment machine and patient collision as well as a multiplicity of surrounding serial and parallel architecture organs. Currently advanced treatment planning techniques with radiobiological considerations and precise image‐guided treatment delivery methods are practiced for SBRT delivery to a wide variety of tumor types.

The physics and dosimetry presentation will include an overview of the available technology for SBRT with an emphasis on image guidance, Quality Assurance, and clinical implementation of SBRT. The presentation will also include site specific treatment planning techniques with considerations to accuracy of dose calculation algorithms, radiobiological issues, and physics reporting strategies.

Educational Objectives:

1. Understand the issues related to the clinical implementation and technical aspects of SBRT techniques and technology and become familiar with the preliminary reporting of AAPM Task Group 101.

2. Understand the importance of QA procedures and guidelines and reporting requirements for SBRT.

3. Understand the practical aspects of SBRT treatment planning for paraspinal, lung, liver, and abdominal tumors and recognize the critical issues related to each site.

4. Understand the importance and limitations of dose calculation algorithms and heterogeneity correction methods for SBRT in various anatomical sites.
MO‐D‐AUD A‐01: Summarizing Our Knowledge of Normal Tissue Tolerances: The Progress and Future Directions of QUANTEC
Authors: Jackson A
Published: July 2008

AAPM and ASTRO are jointly funding an effort, called QUANTEC (QUAntitative Normal TissuE models in the Clinic), which aims to summarize our knowledge of dose volume dependencies of the normal tissue complications of external beam radiotherapy, and where possible, give quantitative guidance for clinical treatment planning and optimization. Following the initial QUANTEC meeting in Madison in October 2007, attended by approximately 75 physicists, MDs and bio‐statisticians, an upcoming special issue of the Red Journal is in preparation, which will include articles on complications in some 18 normal organs. For each of these organs, extensive literature reviews were undertaken, and clinically significant endpoints identified. Where possible, results were synthesized and compared, guided by the quality and levels of evidence of the studies. Criteria included prospective or retrospective nature, statistical power, presence and reliability of quantitative data on dose‐volume effects. Other clinical factors influencing complications were assessed, such as the influence of chemotherapy, fraction size and pre‐existing medical conditions. Special emphasis was placed on attempting to provide quantitative guidelines for clinical treatment planning. This talk will convey the mission, and give selected examples of the achievements of QUANTEC. It will outline the current state of our knowledge, and highlight areas where opportunities exist to improve our understanding.

Educational Objectives:

1. To understand the current state of knowledge of dose volume dependencies of complication probabilities.

2. To understand the criteria and methods used by QUANTEC in selecting and summarizing this knowledge.

3. To understand the shortcomings of the clinical data as it currently exists.

4. To understand the possible strategies for overcoming these shortcomings.
MO‐E‐342‐02: Quantitation in Nuclear Medicine
Authors: King M
Published: July 2008

The quantification of function and activity plays an important role clinically in nuclear medicine. Examples include the analysis of tracer kinetics to quantify dynamic function, the determination of the fraction of the cardiac blood pool ejected during contraction, the comparison of regional localization of uptake within the heart to that of a database to facilitate the recognition of perfusion defects in cardiac imaging, and the localization of F‐18 labeled FDG in potential lesions. Despite the present clinical utility of quantification a number of factors limit current methods. The successful addressing of these factors would expand the clinical utility of quantification and are the subject current and future investigations.

This lecture will provide an introduction to the application of quantification within nuclear medicine. It will point out some current deficiencies, and potential research directions aimed at over coming them.

Educational Objectives:

1. Understand the various types of quantification employed in nuclear medicine.

2. Recognize some of the limitations to robust application of quantification clinically.

3. Appreciate some of the proposed methods to overcome these limitations.
TU‐C‐350‐04: The Rationale and Realities of the CARE Bill
Authors: Vanek K
Published: July 2008

The Consistency, Accuracy, Responsibility, and Excellence in Medical Imaging and Radiation Therapy (CARE bill) was first introduced in the 106th Congress on September 26, 2000. Since that time, it has been introduced in all subsequent Congressional sessions including the current 110th Congress. The bills are now co‐sponsored by 122 US Representatives and 22 US Senators. The CARE bill directs the Secretary of Health and Human Services to establish education and credentialing standards for all persons performing medical imaging, planning, and delivering radiation therapy. Each individual State will be responsible for developing procedures to insure compliance with the federal regulations. The origin, history, and importance of the CARE bills will be discussed as well as AAPM's involvement with the Alliance in this legislative effort. Political realities that have been encountered during this process will be reviewed and suggested actions that members can take to help the CARE bill become law will be presented. Additional effort by the AAPM, the Alliance, and individual members after the CARE bill passage will be also be identified and discussed.

Educational Objectives:

1. Understand basic differences between certification, credentialing, registration, and licensure.

2. Understand the CARE bill and its importance to medical physicists.

3. Understand the current status of the CARE bill and actions that can be taken to help passage by Congress.

4. Understand the subsequent actions by members that will be required on a State government level.
TU‐C‐351‐08: Application of Principal Component Analysis for Marker‐Less Lung Tumor Tracking with Beam's‐Eye‐View EPID Images
Authors: Ionascu D , Park S‐J , Killoran JH , Allen AM , Berbeco RI
Published: July 2008

Purpose: Recent studies have shown the impact of beam's‐eye‐view (BEV) imaging during radiotherapy to monitor the tumor location. This information can be used for real‐time interventions, treatment setup and verification, adaptive radiotherapy and delivered dose calculation. Although the tumor‐lung tissue density contrast can be poor, we show that it can be sufficient for tracking without implanted markers. The pre‐treatment 4DCT information used to plan the treatment is employed to ascertain the tumor motion during the treatment. Method and Materials: Exit radiation is passively acquired during lung tumor radiotherapy by operating an EPID in cine mode. The cine‐EPID in‐treatment images and the pre‐treatment phase‐specific DRRs are registered and corrected for setup induced affine transformations. DRRs are made from each of the 10 phase bins from the 4DCT simulation scan. Principal Components Analysis is able to discriminate small differences between similar images by shifting the image space axes to cause significant differences. The multidimensional image space is generated using the collection of DRR and EPID images. Each image can be represented as a linear combination of the best principal components. Using the projection coefficients, a multidimensional distance between the images is computed to compare each in‐treatment image with the ten phase‐specific DRRs. The maximum similarity is found by computing the minimum distance between the images so the phase‐specific DRR and in‐treatment EPID image are matched. Results: We were able to attribute the phase information to at least 75 % of the acquired in‐treatment images. The methodology was tested on the DRR images alone with 90 % phase recovery. Conclusion: We have developed a PCA‐based algorithm that enabled us to quantify the differences between the tumor motion within the planning 4DCT and the actual tumor motion during the treatment. Conflict of Interest: This work was partially supported by Varian Medical Systems, Inc.
TU‐C‐332‐03: Automatic Definition of Radiation Targets Using Textural Characteristics of Both Co‐Registered PET and CT Images
Authors: Caldwell C , Mah K , Yu H
Published: July 2008

Purpose: To automatically segment the radiation target for treatment of head and neck cancer (HNC) from FDG‐PET/CT images using a textural classifier and to compare the automated results with contours defined by expert observers. Method and Materials: 27 image features, including textural features from Spatial Gray‐Level Dependence Matrices and Neighborhood Gray‐Tone‐Difference Matrices, as well as statistical and structural features were calculated for 476 head and neck regions of interest (ROIs) in PET/CT images of 20 patients with HNC and 20 patients with lung cancer. A voxel based automated segmentation method using a Decision Tree (DT) based K nearest neighbors (KNN) classifier was developed based on the features in these ROIs. PET/CT images of another 10 head and neck patients who had all primary tumors and positive nodes manually segmented by three radiation oncologists were used to evaluate the method. Features were calculated for each voxel from corresponding PET and CT images within a window centered on the voxel. All voxels of head and neck soft tissues from the below the eye to the apex of the lung were automatically segmented. Results: The specificity was 95% ± 2% when all “true negative” voxels were considered to be all soft tissue voxels excluding the ROIs considered abnormal by one or more of three radiation oncologists. Sensitivity was 84% ± 19% when “true positive” was considered the intersection of at least two physicians' abnormal ROIs and sensitivity was 90% ± 16% when all “true positive” was the intersection of the abnormal ROIs of all three physicians. Conclusion: This work suggests that an automated segmentation method based on texture classification of FDG‐PET/CT images has potential to provide accurate delineation of HNC. This could potentially lead to reduction in inter‐observer variability in target delineation and improved accuracy of treatment delivery.
TU‐C‐332‐04: Pilot Patient Studies Using a Dedicated Dual‐Modality SPECT‐CT System for Breast Imaging
Authors: Madhav P , Cutler S , Crotty D , Perez K , McKinley R , Marcom P , Wong T , Tornai M
Published: July 2008

Purpose: Acknowledging the limitations/discomfort of mammography has inspired the development of a dedicated SPECT‐CT system to detect breast cancer, monitor therapeutic responses, and improve patient comfort. This system provides semi‐quantitative 3D functional/anatomical imaging of a pendant, uncompressed breast. Fused images can potentially provide more valuable clinical information than independent systems alone. Method and Materials: The SPECT subsystem permits fully‐3D complex acquisition trajectories around the breast, avoiding physical hindrances, overcoming distortions due to inadequate sampling, and allowing lesion detection on the chest wall. The CT subsystem, restricted to circular rotation, uses a quasi‐monochromatic, cone‐beam x‐ray source, which allows for reduced radiation dose and increased contrast between similar soft tissue attenuation coefficients. With no breast compression and an open, common field‐of‐view geometry system, the patient lies prone on a customized patient bed while the hybrid device non‐invasively acquires 3D data underneath. A preliminary investigation on the clinical performance of the hybrid system was done by imaging women with biopsy confirmed breast cancer Results: SPECT patient images can clearly visualize the tracer uptake by the tumor and view into the chest wall. Physical system constraints limit chest wall visualization in the CT patient images and thus patient positioning is under modification. Eliminating overlapping tissues through 3D imaging, the CT images improve lesion isolation versus 2D imaging modalities. Complementary functional and anatomical image information helps localize suspicious areas for subsequent analysis. Conclusion: Implementation of the world's first dedicated SPECT‐CT system promises greatly improved visualization of the 3D breast volume. Complementary information from functional and anatomical imaging can guide lesion localization for subsequent analysis. Conflict of Interest: MPT is an inventor of this technology, and is named as an inventor on the patent for this technology applied for by Duke. If this technology becomes commercially successful, he and Duke could benefit financially.
TU‐C‐332‐09: Effects of Mild Temperature Hyperthermia On Rat HT29 Xenograft Hypoxia Measured with a Dual‐Radiolabel Hypoxia Marker
Authors: Zhang M , Li X , Suehiro M , Zhao Z , Gagne D , Pizzonia J , Li G , Ling C , Humm J
Published: July 2008

Purpose: Quantitative measurements to directly determine the tumor hypoxia response following a mild temperature hyperthermia (MTH) treatment were conducted in a rat HT29 colorectal xenograft model. Method and Materials: A hypoxia marker iodoazomycin galactopyranoside (IAZGP) was labeled with two radioisotopes of iodine and . The two distinct IAZGP tracers were injected into HT29 tumor‐bearing nude rats 4‐hour before and immediately after 41.5°C, 45‐munite hyperthermia treatment respectively. The animals were sacrificed 3‐hour post hyperthermia, tumors resected, frozen and cryo‐sectioned for digital autoradiography on phosphor imaging plate. Novel methods were developed to acquire and analyze the dual‐isotope digital autoradiographic images, to unfold the pixel contribution of tracers administered before and after hyperthermia, thus providing quantitative information of the hypoxia change at the microscopic (50‐micron) level. Results: The results showed that, immediately following MTH treatment, there was a significant reduction in hypoxia tracer binding, indicating a reduction in the tumor hypoxic fraction, and that re‐oxygenation had taken place in this rat HT29 xenograft model. Pixel‐by‐pixel analysis of the data revealed a decline in hypoxia tracer uptake after hyperthermia in most regions, but with the concomitant emergence of some new regions of hypoxia identified by increased tracer uptake post treatment. In the body‐temperature control group, the overall hypoxic fraction remained almost constant, with some hypoxic tracer redistribution (putative acute hypoxia) observed. In conclusion, the pretreatment hypoxic fraction changed from between 18–42% to post‐hyperthermia values of between 7%–20% (spread among 5 animals). Conclusion: This study provided evidence for reoxygenation immediately following MTH treatment in the rat HT29 xenograft, with a preponderance of microscopic regional decreased radiotracer uptake. However, a few areas did exhibit increased hypoxia specific tracer uptake indicating the possible emergence of new hypoxia.
TU‐D‐352‐02: Magnetic Resonance Imaging to Track Mesenchymal Stem Cells (MSCs) in a Murine Myocardial Infarction Model
Authors: Yang Y , Yang Y , Klein B , Yanasak N , Shi X , Hill W , Hu T
Published: July 2008

Purpose: To track the migration and engraftment of the mesenchymal stem cells (MSCs) with micrometer‐sized particles of iron oxide (MPIO) labeling into myocardial infarcted site using MRI in mice. Method and Materials: MSCs with GFP fluorescence were labeled with MPIO. Mice were irradiated with a dose of 8 Gy and received rescuing bone marrow transplantation 24 hrs later. The labeled MSCs (∼3–7×105 cells) were then transplanted into the tibial modullary space of mice. The mice were randomly divided into two groups. At 14 days post‐MSCs transplantation, one group underwent myocardial infarction (MI; n=4; open chest with ligation of the left anterior descending coronary artery (LAD)) and the other group underwent sham‐operated surgery (Sham; n=2; open chest without ligating the LAD). MRI was performed at baseline, 3 days (D3), 7 days (D7) and 14 days (D14) post‐surgery. Short‐axis cardiac images were acquired using T2*‐weighted imaging and T2 mapping technique. The results were confirmed by fluorescent microscopy. The contrast‐to‐noise ratio (CNR) at the MI zone was calculated. For the Sham group, a CNR at a region of interest (ROI) designated in the left ventricular anterior wall was also calculated and compared with the MI group. Results: Pronounced signal intensity attenuation at the MI zone was observed by MRI at D7 and D14, potentially due to the accumulation of MPIO labeled stem cells. Both accumulation of stem cells with GFP signal and MPIO deposition in the heart were detected in the fluorescent microscopic images. The CNR were significantly different between the MI and Sham groups at D7 and D14 (p<0.05). Conclusion: Hypointense signal was observed at the MI zone in MRI, suggesting the infiltration of labeled MSCs. Current study may support a potential approach in cell therapy to noninvasive monitor migration of labeled cells post myocardial injury.
TU‐D‐352‐03: A Design of Compton Cameras for Imaging Gamma Emission in Proton Therapy
Authors: Feng Y , Baciak J , Haghighat A
Published: July 2008

Purpose: To design a Compton camera to image gamma‐ray emission during the treatment of proton therapy as a possible method to verify dose delivering. Method and Materials The pixilated (Ce) crystal was investigated as both scattering and absorbing detectors. In this design each crystal module used in front layer has the size of 2.5cm × 2.5cm × 0.5cm that was segmented into 4mm × 4mm × 2mm on its top to enhance the spatial resolution based on the differential response of PSPMT that receives scintillation light. Each detector in the rear layer has the size of 2.5cm × 2.5cm × 3.0cm and was segmented into 4mm × 4mm × 10mm. The position resolution in locating interaction is about 2mm laterally and 2.5mm vertically in the front detectors while the resolutions are 2mm and 15 mm in the rear detectors. The efficiency and angular uncertainty of this Compton camera was investigated based on numerical calculation. The geometry of the detectors and distance between detectors were optimized to achieve high efficiency or high angular resolution. Results: Angular uncertainty of ∼0.1 radians was the low limit for us to image 511 keV gamma rays because of the Doppler broadening. However, the angular uncertainty below 0.05 radians was achievable by observing the scattered photons at about 25°–60° scattering angle for 10 cm distance between detectors. Conclusion: Based on numerical calculation, we proposed a Compton camera with two layers. The potential angular resolution in imaging 511 keV gamma rays was about 0.3 radians while it was 0.05 radians or less from gamma rays above 2 MeV. The angular uncertainty is relevant to resolution, but higher resolution can potentially be achieved with proper image reconstruction algorithms that will be developed and evaluated in future.
TU‐D‐352‐05: The Effect of Magnetic Interference On a Coupled MR‐Linac System: 3D Modeling of RF in a Linac
Authors: St. Aubin J , Steciw S , Carlone M , Fallone B
Published: July 2008

Purpose: In order to provide real‐time Image Guided Radiotherapy (IGRT), the coupling of a 0.2T bi‐planar Magnetic Resonance Imager (MRI) and medical linear accelerator (linac) is proposed. This integration forces the linac to be within the fringe fields of the bi‐planar magnets causing magnetic interference. Appropriate shielding must be designed and optimized in order to reduce the fringe field magnitudes to a point where a clinically useful radiation beam is produced. Method and Materials: A first step to designing shielding is the full 3D radio‐frequency (rf) modeling of the linac waveguide using the Finite Element Method (FEM). The main accelerating cavities were modeled in 3D using COMSOL Multiphysics and compared to the widely used program Poisson Superfish. The full waveguide was then modeled in 3D and the coupling coefficients were determined. Results: A comparison of linac important parameters (i.e. resonant frequency, power dissipation, stored energy, Q value, shunt impedance and transit time factor) were made between the 3D model in COMSOL and that of Poisson Superfish. All values were found to be within 0.8% where the differences are attributed to differences in meshing between the two programs. A linac model consisting of 5 and one half accelerating cavities with 5 coupling cavities was then generated. A 3D instead of a 2D model was used since it is more accurate in determining the coupling coefficients between the accelerating and coupling cavities. Conclusion: This work is the first step to determining the magnetic shielding required in producing a clinically useful radiation beam from a coupled MR‐Linac system. The extracted parameters from the 3D model were found to be less than 1% different from the benchmarked program Poisson Superfish. This 3D model is however inherently more accurate since the full modeling of coupling between accelerating and coupling cavities has been achieved.
TU‐D‐352‐06: Modeling the Effect of Different Oxygenation Levels On Radiation Therapy Response Using Kinetic Parameters Derived From PET/CT Imaging
Authors: Titz B , Jeraj R
Published: July 2008

Purpose: Although tumor hypoxia is frequently related to increased radioresistance, the interplay between hypoxia and the time course of tumor response is not well understood. This study investigates effects of different oxygenation levels on therapeutic response using an imaging‐based tumor simulation model. Method and Materials: A multiscale tumor model was developed employing cell‐line‐specific input variables and kinetic parameters derived from pre‐therapy and PET/CT scans, which provided information on cellular proliferation and tumor hypoxia. For each tumor voxel, stochastic simulations were performed by modeling cellular growth and therapeutic response based on the linear quadratic formalism including the oxygen enhancement ratio. Model parameters were fitted to published in‐vitro and animal models of head and neck squamous cell carcinoma (HNSCC) cells. Using the obtained parameters, the model was applied to a human HNSCC case to investigate effects of different uniform and non‐uniform oxygenation levels. Resulting virtual images were compared for treatment efficacy under various hypoxic conditions. Results: Simulating cell cycle redistribution of cultured cells among the phases of the cell cycle after a single irradiation event yielded excellent agreement (within 3.8 %) with in‐vitro data, showing complete redistribution after 50 hours. In comparison to growth and response curves obtained in experiments with murine HNSCC xenografts, the model quantitatively and qualitatively reproduced macroscopic tumor behavior within experimental uncertainties. Simulations of the clinical case showed increased radioresistance with decreasing oxygen levels. Consideration of the uptake resulted in heterogeneous tumor response, featuring pronounced radioresistance below 2.5 mmHg pO2. Conclusion: Our results suggest that hypoxia adversely affects tumor response, especially when applying uniform dose prescriptions to heterogeneous tumors. The developed model is a valuable prospective tool for transforming voxel‐based information into patient‐specific parameters for outcome modeling and investigating biologically based non‐uniform dose prescriptions, thus helping to identify a biologically optimized treatment regimen.
TU‐D‐352‐07: Enhanced Energy Transfer From Mega‐Voltage Radiation to the Tumor Cell Killing Singlet Oxygen by Semiconductive Nanoparticles
Authors: Yang W , Mi J , Read P , Larner J , Helmke B , Sheng K
Published: July 2008

Purpose: To investigate a novel energy transfer pathway from 6 MV therapeutic X‐rays to Quantum dots (QDs), which further activates Photofrin to produce reactive singlet oxygen species by a process known as Foster Resonance Energy Transfer, and subsequently enhances cell kill. Method and Materials: The photon emission efficiency of QDs upon excitation by 6 MV X‐rays was measured as a function of the dose rate from 100 cGy/min to 600 cGy/min. A conjugate was synthesized based on the conjugation of Photofrin and QDs. The quenching of the photon emission was measured with the conjugate. The energy transferred to the photofrin was calculated based on the principle of Foster Resonance Energy Transfer (FRET) that the energy transfer efficiency is proportional to the degree of quenching. The cell kill enhancement with the conjugates was studied using A549 human lung carcinoma cells and an optical density based assay. The cellular distribution of the conjugates was imaged by a confocal microscope. Results: QDs were found to be excited by the 6 MV radiation and the number of visible photons generated from QD depended linearly on the radiation dose rate. The FRET efficiency increases as the number of Photofrin molecules conjugated to the quantum dots increases. The conjugate resulted in a statistical significant 34% increased cell kill at 24 pmol/ml conjugate concentration compared to radiation alone with minimal toxicity in non‐irradiated controls. Fluorescence microscopy revealed that the conjugates were distributed within the cytoplasm. Conclusion: This conjugate shows distinct properties as a novel media for generating singlet oxygen and enhanced tumor cell killing, which is achieved synergistically with radiation through a physical and linear interaction between QDs and X‐ray; the conjugate itself shows minimal dark toxicity at nM concentration, thus can be readily targeted by conformal radiotherapy with high geometrical specificity.
TU‐D‐352‐09: Development of a Carbon‐Nanotube Field Emission Based Multi‐Pixel Microbeam Cellular Irradiation System
Authors: Bordelon D , Zhang J , Graboski S , Cox A , Schreiber E , Zhou O , Chang S
Published: July 2008

Purpose: High spatial and temporal resolution cellular microbeam irradiation is important in studying dynamic radiation response at the cellular level. Existing systems include charged particle, x‐ray, and electron single beam irradiators. We have proposed a multi‐pixel electron microbeam array irradiator based on carbon nanotube (CNT) field emission with individually controllable beams to irradiate cellular scale regions in a Petri dish under real time microscope observation. Method and Materials: We have developed and tested a prototype single pixel 30keV electron irradiator utilizing a CNT field emission cathode. The cathode is temporally modulated to deliver a calibrated electron dose to the target. Microfabrication methods are used to develop beam collimators of fine aperture. Dosimetry is performed using GAFCHROMIC film, and system feasibility is demonstrated via Rat‐1 cell line irradiation. A multi‐pixel system with a cathode chip and electron transparent window has been built, and the multi‐pixel method has been demonstrated via field emission testing. Results: Preliminary data show the CNT electron microbeam irradiator is capable of 100 Gy/sec dose rate and 23um beam diameter. An “L” shaped irradiation pattern was used in feasibility demonstration using plated Rat‐1 cells. Irradiation was visualized via Gamma‐H2AX fluorescence marking of DNA damage. The multi‐pixel microbeam concept has been demonstrated through fabrication and testing of a 5×5 microbeam array cathode. A 2.5mA field emission current was achieved with all pixels emitting. Conclusion: We have demonstrated the feasibility of a carbon nanotube field emission based single microbeam cellular irradiation system as well as the cathode fabrication for the multi‐pixel microbeam prototype system still under development. The CNT microbeam irradiator is capable of delivering radiation over a large dynamic dose rate range with high temporal resolution. The eventual CNT based cellular irradiator is expected to be compact and made available for broad application.
TU‐D‐AUD B‐02: Volumatric Modulated Arc Therapy: Implementation and Evaluation for Prostate Cancer Cases
Authors: Zhang P , Happersett L , Mageras G
Published: July 2008

Purpose: Volumetric modulated arc therapy (VMAT) (Otto K, Medical Physics, 2008) is an emerging treatment paradigm which modulates MLC aperture and dose rate during gantry rotation. The purpose of this study is to implement and evaluate VMAT relative to the standard IMRT approach. Method and Materials: A gantry rotation up to 360° is modeled as 360 evenly divided beams. Beam apertures and dose rate are optimized with respect to gantry angles under a DVH constraints based objective. Differences between our VMAT implementation and previous VMAT are: using gradient search for dose rate optimization rather than random search, and sampling multiple MLC leaf positions within the allowed leaf speed constraints rather than a single one in each iteration. A planning study including 5 prostate patients with a prescription dose of 86.4Gy was performed to evaluate VMAT verse the standard 5‐field IMRT approach. VMAT treatment plans are normalized such that certain critical organ dose limits are met, and are comparable to IMRT plans. V95, D95 and mean dose of PTV are used to evaluate plans, while monitor unit (MU) and delivery time are used to assess delivery efficiency. Results: The PTV V95, D95 and mean dose in VMAT plans are 97.0±0.8%, 96.4±0.5%, and 101.7±0.4%, respectively, vs 97.1±0.8%, 97.5±1.0% and 103.0±0.7% in IMRT plans. VMAT and IMRT plans are indistinguishable measured by these dose indices. The advantage that VMAT presents is it reduces MU by 49.8±7.4%. Secondary scatter dose to patient is reduced accordingly. A typical prostate treatment is shortened from about 5 minutes for IMRT to 2.6±0.2 minutes for VMAT. The better delivery efficiency of VMAT is accomplished by having a larger time averaged beam aperture: 49.1±5.2cm2 vs 19.5±1.5 cm2 in IMRT. Conclusion: VMAT technique can reduce treatment time by up to 50% while maintaining comparable dosimetric quality to standard IMRT approach.
TU‐D‐AUD C‐02: An Investigation of the Consistency and Robustness of the PRESAGE/optical‐CT 3D Dosimetry System
Authors: Sakhalkar H , Adamovics J , Gluckman G , Oldham M
Published: July 2008

Purpose: The potential of the PRESAGE™/Optical‐CT system as a comprehensive 3D dosimetry tool has been demonstrated. Detailed characterization of intra‐dosimeter uniformity, temporal stability, inter‐dosimeter reproducibility and robustness have yet to be performed, and is the focus of this study. Method and Materials: Four identical PRESAGE™ dosimeters (10cm diameter and 7cm height cylinders) were irradiated with same treatment plan using a Varian accelerator. The treatment consisted of a symmetric arrangement of 9 small open‐fields (1×3 cm2) impinging on the upper flat surface of the cylindrical dosimeter. The nine beams consisted of 3 groups, corresponding to low medium and high dose. Beams in the same group delivered the same dose to the phantom. The significance of this beam arrangement is that a completely symmetric distribution is achieved at all depths in the phantom, with multiple regions at different spatial positions, receiving identical doses, thereby enabling rigorous investigation of consistency within the dosimeter. All dosimeters were scanned by optical‐CT at daily intervals to study temporal stability. Dose comparisons were made between PRESAGE, Eclipse, and independent measurement with EBT film at select depths. Results: The use of improved optics and acquisition technique yielded substantially higher quality 3D dosimetry data from PRESAGE than has been achieved previously (noise reduced to ∼1%, accuracy to within 3%). Excellent intra‐dosimeter uniformity (2% dose‐difference, 1mm distance‐to‐agreement) was observed even at low dose‐levels. Excellent temporal stability of response (1% dose‐difference, 1mm distance‐to‐agreement) was evident for >90 hrs post‐irradiation. Excellent inter‐dosimeter reproducibility (2% dosedifference, 2mm distance‐to‐agreement) of dose readout was observed between all four dosimeters. The PRESAGE™ dose‐distribution was found to agree better with EBT than with Eclipse calculations especially in penumbral regions. Conclusion: The results demonstrate excellent consistency and robustness characteristics of the PRESAGE™/optical‐CT dosimetry system for relative 3D‐dosimetry and represent a significant step towards incorporation in the radiation oncology clinic.
TU‐D‐AUD C‐06: Direct RBE Determination of Therapeutic Protons Using a DE‐E Telescope
Authors: Wroe A , Schulte R , Rosenfeld A
Published: July 2008

Purpose: A new monolithic silicon ΔE‐E telescope was evaluated for hadron therapy applications by converting the physical data provided by the detector to relative biological effect (RBE) for both modulated and un‐modulated therapeutic proton beams. Method and Materials: The ΔE‐E telescope provides information on lineal energy and particle identification that is based on energy depositions within the ΔE and E stages of the detector, collected in coincidence. Thus, this detector provides additional information on the quality of radiation fields over existing microdosimetry systems. Since different particles with the same LET or lineal energy are known to have different RBE values, the combined lineal‐energy particle identification data provided by the ΔE‐E telescope is likely to be of radiobiological value. To investigate this, an RBE matrix based on established in‐vitro V79 radiobiology data was developed linking the output of the device directly to radiobiological effect for two biological endpoints, RBE (10%) and low‐dose‐limit RBE(α). Experimental data was collected and analyzed for 100MeV modulated and un‐modulated therapeutic proton beams within a homogeneous polystyrene phantom. Results: Proximal to the spread‐out Bragg peak (SOBP), RBE(10%) and RBE(α) values of 1.2 and 3.2 respectively were determined from the measured response of the device. The high spatial resolution of the ΔE‐E telescope allows for data collection in rapidly changing radiation fields, which is demonstrated with derived RBE(10%) and RBE(α) values of 1.82 and 4.85 obtained from the measured response of the device at the SOBP distal edge. Conclusion: This work has demonstrated the ability of the ΔE‐E telescope to provide RBE data for proton radiation fields that is based on experimental in‐vitro data for V79 cells. This system could have an application to both hadron therapy and radiation protection as it provides a means for estimation of RBE in “real‐time” and verification of Monte Carlo simulations.
TU‐D‐332‐02: Abdominal Fat Quantification Accuracy Using Water Saturated B‐SSFP MRI Sequences: A Verification Study
Authors: Peng Q , Zhou A , Ding Y
Published: July 2008

Purpose: To verify the fat quantification accuracy of abdominal fat quantification results on images acquired with a Water Saturated b‐SSFP (WS b‐SSFP) MRI Sequence. Method and Materials: 10 healthy (5 female and 5 male) volunteers underwent both WS T1W TSE and WS b‐SSFP scans with breath hold on a 1.5 T clinical MR scanner. For the WS T1W TSE sequence, the parameters were as follows: TR/TE/flip angle = 500 ms/5 ms/90°, turbo factor = 7 and readout bandwidth = 128 KHz. For the WS 3D b‐SSFP sequences, the imaging parameters were as follows: TR/TE/flip angle = 2.9 ms/1.2 ms/55°, ETL = 128 with 12 dummy echoes, and readout bandwidth = 200 KHz. For WS T1W TSE sequence, 6 axial slices centered at L2‐L3 level were acquired in two consecutive expired breath‐holds, with 14 seconds each. Since WS b‐SSFP is a much faster scan, 8 slices (with slice 2–7 imaged at the same positions of the 6 TSE slices) were obtained in 11 seconds in one breath‐hold. For each subject, fat volumes from six common slices of WS TSE and WS b‐SSFP were measured and summed. Total abdominal fat (TAF), intra‐abdominal fat (IAF), and subcutaneous abdominal fat (SAF) volumes from images of both scans were measured and compared. Results: The TAF, IAF, and SAF mean differences of the fat volume measured from images of the two scans are only 0.34%, −0.25%, and 0.91%, respectively. The Bland‐Altman plots show that all the measurement differences between WS b‐SSFP and WS TSE are within the 95% of difference. Conclusion: The two methods are the same in terms of the measurement accuracy for human abdominal imaging. Therefore, WS b‐SSFP MRI can be used for abdominal fat quantification to reduce imaging and post‐processing difficulties and ultimately reduce research cost in abdominal fat distribution studies.
TU‐D‐332‐09: Estimating Temperature From the Magnetic Nanoparticle Magnetization
Authors: Weaver J , Hansen E , Rauwerdink A
Published: July 2008

Purpose: We present a method of non‐invasively estimating the temperature of magnetic nanoparticles in vivo. The method has wide application including monitoring magnetic nanoparticle hyperthermia to obtain effective thermal doses. Method and Materials: The signal from magnetic nanoparticles is generated by applying a pure sinusoidal magnetic field and observing the signal at the harmonic frequencies produced by the nanoparticles. The Langevin function model of the nanoparticle magnetization predicts a balance between the forces induced by the applied magnetic field and thermal motion of the nanoparticles. The ratio of the fifth and third harmonics is uniquely related to the temperature if the saturation magnetization and particle size distribution remain constant. Therefore, when the ratio of the harmonics is known at one calibration temperature, subsequent temperature changes can be assessed from the ratio of the harmonics. The method was tested using samples of Feridex™ at temperatures between 0°C and 100°C. After the sample reached equilibrium with a water bath of known temperature, the fifth and third harmonics of a 10mT, 9kHz sinusoidal field were measured using a pickup coil and a lockin amplifier. The temperature was estimated numerically using a spline interpolation of the Langevin function with a sinusoidal argument. Results: The ratio of the fifth to the third harmonics was shown numerically and experimentally to increase monotonically with increasing amplitude of the sinusoid in the Langevin function and the amplitude is inversely related to the temperature, P‐value of 0.0053. However, the intercept was not zero as expected, probably an artifact of the size distribution. The error in the calculated temperature estimate depends on the size distribution and temperature range used but the error was small: the standard deviation was 0.44 degrees. Conclusion: The temperature of magnetic nanoparticles can be estimated in the physiologic range using the ratio of the harmonics.