bluuebunny/crossref_metadata_2025_split huggingface dataset:
WE‐E‐BRC‐03: Interactive Anatomy Editing: Implicit Function Reshaping via RBF Management
Authors: Hibbard L 
Published: November 2011

Purpose: To efficiently visualize and accurately edit presegmented anatomies for radiotherapy planning in a fully 3D setting. Methods: Anatomy representations (contours, surfaces) derived from prior segmentations are recreated as implicit surfaces‐‐the zero level sets of implicit functions f(x,y,z)=k whose shapes are defined by radial basis functions (RBFs) centered on, and along normals to, the zero level (k=0). These smooth and continuous surfaces are re‐shaped by altering the number and arrangement of the RBFs. Using a standard contouring program, the user overdraws the surface profiles in any combination of transverse, sagittal, or coronal views, and the 2D curves comprising the differences between the original surface profiles and the user edit‐contours determine the arrangement of the new RBFs. Constructing smooth shape transitions between the new and old portions of the surface is a challenge‐‐several methods were developed to define that portion of the surface spanned by the edit curves and to insure that the geometric transition from the old to the new surface is smooth and accurately renders the intended change. The surface reconstructed between the user‐drawn edit contours is a form of spline interpolation, so that a few inputs can smoothly redefine a large surface. Extensive parallelization enables this expensive computation to run in nearly real time. Results: The management of RBFs removed from the original shape and added to the new shape is essential to obtain a comprehensible and correct updated surface. Such surfaces are smooth and continuous and accurately represent the anatomy viewed in the drawing program single plane views. The updates are computed in 1–3 s and the user can operate in those views that provide the greatest shape information. Conclusions: We present a novel method to efficiently edit 3D anatomic shapes by operating directly on the implicit surface representing the anatomy.This work was supported by Elekta.
WE‐E‐BRC‐07: Evaluate Reproducibility of 4DCT Registration‐Based Lung Ventilation Measurement with Gamma Comparison Method
Authors: Du K , Ding K , Cao K , Reinhardt J , Christensen G , Bayouth J 
Published: November 2011

Purpose: The regional lung pulmonary function can be calculated by computing the Jacobian of image registration deformation field. Radiation‐induced pulmonary function changes are assessed by comparing pulmonary function before and after radiation therapy (RT). Due to the probably different breath pattern and effort, uncertainties from 4DCT imaging and registration error, we need to first establish the measurement reproducibility. We also introduce gamma comparison method to compensate space disalignment in two distributions. Methods: Two repeated 4DCT data sets scanned with 30 minutes interval before RT from two patients are used in this study. Tissue volume preserving nonrigid registration algorithm with Laplacian regularization constraints was applied to register the maximum exhalation image to the maximum inhalation image for the calculation of local lung expansion as a measurement of regional pulmonary function in two scans. We compared the two pulmonary functions and analyzed the pulmonary function ratio map. Gamma comparison method is introduced to tolerate possible error in image acquisition and image registration. Mean and standard deviation of pulmonary function ratio map and gamma pass percent are calculated to measure reproducibility. Results: The registration accuracy analysis indicated our registration error is on the order of 1.0 mm. Most lung tissue has a reproducible pulmonary function. Reproducibility near the diaphragm is worse than other regions. The standard deviation of function ratio map is respectively 0.0352 and 0.0495. The gamma comparison pass percent is respectively 84% and 87%. Further plots suggest most of the lung function is reproducible in 2 scans. Conclusions: We analyzed the reproducibility to measure regional pulmonary function using 4DCT and image registration. We compared the regional lung function in two repeated 4DCT scan and discussed the function ratio map. We also introduced a gamma comparison method to quantify reproducibility.This work was supported in part by NIH grant HL079406 and EB004126.
WE‐E‐BRC‐08: Evaluation of a Probabilistic Non‐Rigid Registration Method for Improved Intra‐Operative Target Definition in 125‐I Permanent Prostate Implants
Authors: Pursley J , Risholm P , Fedorov A , Tuncali K , Fennessy F , Wells W 
Published: November 2011

Purpose: To evaluate the use of a non‐rigid registration method for improved intra‐operative target definition in 125‐I permanent prostate implants. Methods: The validation dataset was created from 10 MRI‐guided prostate biopsy patients with both diagnostic (with endorectal coil) and intra‐procedural (without endorectal coil) 3 Tesla MRI scans under an IRB approved protocol. A biomechanical‐based probabilistic non‐rigid registration method was adapted to register diagnostic to intra‐procedural images by matching the contoured prostate boundaries. The probabilistic framework provides a collection of prostate configurations under deformation, or a marginal probability map for a given location to be identified as inside the prostate by the registration. The marginal probability map was compared to the intra‐procedural prostate contour. 125‐I treatment plans were generated for the intra‐procedural scans. Results: In two cases we find that ∼5% of the prostate volume within the 50th percentile of the marginal deformed probability is not included in the intra‐procedural contour, and 3–4% of the intra‐procedural prostate volume is not included in any of the deformed configurations. Different regions of the prostate have varying uncertainties; preliminary results show margins of 1–2 mm near mid‐gland and 3–4 mm around the apex. We present geometric uncertainties and the resulting variation of dosimetric quantities in the base, mid‐gland, apex and peripheral zone of the prostate. Conclusions: We study the feasibility of using a probabilistic non‐rigid registration method for supplementing intra‐procedural images with diagnostic MR images. The method is evaluated geometrically and dosimetrically, which quantifies the methodˈs ability to provide intra‐procedural estimation of the accuracy of the deformed configurations. This method will be applied to registration of diagnostic MR with intra‐procedural transrectal ultrasound images to improve visualization of the prostate apex and substructure, which could provide improved prostate boundary definitions with uncertainty margins to guide the development of intra‐operative brachytherapy treatment plans.This work was supported by NIH grants 1U41RR019703‐01A2, 1R01CA111288‐01A1,P01‐CA67165,andU01CA151261.
WE‐E‐214‐03: Biology and Physiology of Targeted Radionuclide Therapy (TRT)
Authors: Williams L 
Published: November 2011

Radiolabeled agents are being developed for TRT (Targeted Radionuclide Therapy). Included in the 50 to 200 nm scale of this project are liposomes, short segments of DNA or RNA, nanoparticles and proteins. Because of possibly multiple lesion sites, these radiopharmaceuticals (RPs) are usually given by IV injection. Targeting, which requires a number of hours to days to accomplish, is effected by various means. The simplest method is to have the agent pass out of the blood and into the tumor space using the fenestrations in tumor capillaries. Liposomes are one such example whose membranes are dissolved in the lesion so as to release vesicle contents. Among the most specific localization processes is protein binding to a molecular marker on ‐ or near ‐ the tumor cell. Among such markers are Carcinoembryonic Antigen (CEA) and human epidermal growth factor receptor 2 (HER2). CEA is associated with colon, lung and some breast cancers, while HER2 is a breast cancer marker in approximately 25% of patients. These antigens are found in normal colon lumen and heart muscle respectively. A protein used in finding a molecular target may be something as simple as a mouse‐derived antibody or an engineered protein construct. One constraint is that proteins from alien species eventually generate their own human antibodies when repeatedly used in a given patient. This effect can be moderated by DNA manipulation of the alien antibody to change its structure to a more human‐like amino‐acid sequence. Use of a blood‐injection for the RP may result in sequestration by a normal tissue such as the liver or kidneys. In the renal case, small proteins (<25 kDa) would be very rapidly taken out of circulation so as to prevent significant tumor targeting. Various strategies have been developed to minimize sequestration; e.g., blocking or use of polyethylene glycol covering molecules (“stealth”) to prolong protein circulation. Because of the large numbers of possible RPs, it is necessary that preselection be done on any putative clinical RP. A figure of merit (FOM) may be used to choose one of a series of agents dedicated to the same tumor type; e.g., cognate antibodies to CEA. Both imaging and therapeutic FOMs have been developed. These indicators are used to differentiate RPs using animal data. This preferential ordering process is needed since the number of agents is large while volunteers for research studies are only a small fraction (2 to 5%) of the total patient population. One is still left with the question of the relationship between animal and clinical biodistribution data.Learning Objectives:1. Know the types of agents presently being studied for TRT.2. Understand the reasons for tumor targeting by engineered pharmaceuticals (RPs).3. Realize the importance of the RP blood curve for the targeting process.4. Use of Figures of Merit to select an optimal imaging or therapy agent.
WE‐E‐220‐01: Focused‐Ultrasound Mediated Blood‐Brain Barrier Disruption
Authors: McDannold N 
Published: November 2011

Purpose: Numerous studies have shown that ultrasound bursts combined with an ultrasound contrast agent results in a temporary disruption of the blood‐brain barrier (BBB). Combined with focused ultrasound systems that can precisely focus ultrasound through the human skull, a noninvasive means for targeted drug delivery becomes possible. As the BBB, which normally serves to protect the central nervous system, prevents most substances from being delivered to the brain from the circulation, this approach could have a large impact on treatments for brain tumors and other disorders. This talk will review recent results from recent studies testing the safety and efficacy of this approach. Methods: Ongoing studies at our institution are testing repeated BBB disruption sessions in nonhuman primates using a clinical MR‐guided focused ultrasound system (ExAblate 4000, InSightec). Additional studies are being performed to test whether combining BBB disruption with Herceptin, an antibody‐based drug for HER2‐positive breast cancer that often fails with brain metastases, can improve outcomes in rats implanted with human breast cancer cells. Relevant works on safety and efficacy of this technique from other research groups will also be presented. Results: We have found that BBB disruption can be achieved repeatedly in nonhuman primates without MRI‐based evidence of tissue damage or functional deficits. Furthermore, the disruption has been found to only occur at targeted locations in the brain. Tests in the breast cancer brain metastases model have shown improvement in tumor growth rate, with tumors in 4/10 animals in the Herceptin+BBB disruption group disappearing. This result was not achieved in the control groups. Conclusion: These and other similar studies, while still ongoing, are encouraging and supportive of preparing for initial human tests of this technique. Methods to control and monitor the procedure, however, are currently lacking and will be necessary for widespread use of the technique.Learning objectives:1. Learn how ultrasound and ultrasound contrast agents are applied for blood‐brain barrier disruption2. Learn about ongoing safety and efficacy studies of the technique3. Learn about need for methods to guide and monitor the ultrasound exposures
WE‐G‐BRA‐06: Radiotherapy Planning for Glioma Based on a Computational Tumor Growth Model
Authors: Unkelbach J , Menze B , Konukoglu E , Shih H , Ayache N , Bortfeld T 
Published: November 2011

Purpose: We investigate treatment planning for intensity‐modulated radiotherapy (IMRT) for glioma based on a computational tumor growth model. Currently, the target consists of the tumor mass visible on MRI plus a 1–2 centimeter isotropic expansion to account for tumor cell infiltration into adjacent brain tissue. Observations suggest that glioma primarily grow along white matter fiber tracts. Accounting for the anisotropic infiltration pattern may potentially improve the efficacy of radiotherapy and prolong survival. Methods: We assume that tumor growth is characterized by local proliferation of tumor cells and diffusion into neighboring tissue. Mathematically, this can be described via a partial differential equation of reaction‐diffusion type (Fisher‐Kolmogoroff‐Equation). Diffusion‐Tensor‐Imaging provides the spatial distribution of the diffusion tensor. Solution of the model equations yields a spatial distribution of the tumor cell density. Radiation‐induced cell kill is described via the linear‐quadratic cell survival model. Modification of current treatment planning procedures can be approached in three steps: 1) the target contour is adaped to match an isoline of the tumor cell density while keeping the total volume constant; 2) dose within the target can be redistributed to maximize overall cell kill while keeping the integral dose constant; 3) unavoidable dose outside the target can be redistributed to affect brain tissue more likely to be infiltrated by tumor cells. Results: Treatment planning studies suggest that overall cell survival can be reduced by 1–3 orders of magnitude compared to the isotropic margin approach — depending on model parameters. Accounting for uncertainties in model parameters reduces the expected benefit, but a sensitivity analysis over a range of realistic parameters suggests that substantial improvements can be expected. Conclusions: Since current planning procedures based on isotropic margins do not reflect known growth characteristics of glioma, computational tumor growth models have the potential to improve radiotherapy efficacy despite uncertainties in model parameters.J Unkelbach receives funding from Philips Medical Systems; E Konukoglu receives funding from Microsoft Research.
WE‐G‐BRA‐08: Evaluation of Dosimetric Parameters by ROC Curve with Radiation Induced Pneumonitis and Esophagitis of Non‐Small Cell Lung Cancer(NSCLC) Treated by Three‐Dimensional Conformal Radiotherapy(3DCRT)
Authors: Zhu S , Liu Z , Su J , Li J , Shen W , Wang Y 
Published: November 2011

Purpose: To understand the correlation between radiation induced pneumonitis (RIP) and esophagitis (RIE) with dosimetric parameters for patients treated using 3‐D conformal radiation therapy (3DCRT) for non‐small cell lung cancers (NSCLC). Methods: Dosimetric parameters of dose‐volume histograms from 3DCRT plans for 104 NSCLC patients treated between 2000 to 2004 from our hospital were retrospectively analyzed. The prescription doses ranged from 60–78Gy with a median dose of 66Gy. The RIP and RIE were assessed for each patient during the treatment and follow‐up within 3 months after treatment completion. The correlation between dosimetric parameters with RIP and RIE were evaluated by univariate and multivariate analysis using Logistic Regression Model of SPSS 11.0 software. The predictive ability of parameters was assessed with receiver operating characteristic (ROC)curves. The area under the curve (AUC) was used to filter cut‐off values for predictive RIP and RIE. Results: The rate of RIP>=2 grade was 38.3% for patients. Univariate analysis showed that the lung mean dose and volumes receiving doses from 5 to 40Gy (V5–V40)were important factors for predicting RIP. Multivariable analysis indicated that lung V35 was likely to be an independent factor. The optimal cut‐off value for lungV35 was 20.75%, corresponding to sensitivity of 66.10% and specificity of 81.00% in ROC curve. The rate of RIE was 46.2%. Multivariate analysis showed that both GTV and PTV of NSCLC, and esophagus V60 were the independent parameters for predicting RIE. The optimal cut‐off value for esophagus V60 was 12.50%, corresponding to sensitivity of 81.30% and specificity of 69.60% in ROC curve. It was found that there was significantly difference between AUC of ROC curve for esophagus V60 and those for GTVˈs and PTVˈs of NSCLC (P<0.05). Conclusions: lung V35 and esophagus V60 were likely to be the independent factors predicting of RIP and RIE, respectively.Our funding support received from National Natural Science Foundation of China (30870743).
WE‐G‐214‐02: Utility of 18F‐FDOPA PET for Radiotherapy Target Delineation in Glioma Patients
Authors: Pafundi D , Brinkmann D , Laack N , Sarkaria J , Yan E , Kemp B , Lowe V 
Published: November 2011

Purpose: To evaluate the impact of adding 18F‐FDOPA‐PET, an amino acid tracer, to standard of care MRI for radiotherapy target volume delineation for gliomas. Methods: 6 patients with newly diagnosed brain tumors were given 5.0 mCi +/− 10% of 3,4‐dihydroxy‐6‐[18F]‐fluoro‐L‐phenylalanine (18F‐FDOPA), and underwent a 10‐minute PET/CT acquisition. Overall pathology confirmed WHO grade 3 astrocytoma (n=3), grade 3 oligoastrocytoma (n=1), and glioblastoma (n=2). T1‐weighted post gadolinium (T1‐gad) and T2‐weighted/FLAIR MRI sequences were rigidly aligned to the 18F‐FDOPA‐PET/CT. Three experienced radiation oncologists contoured the T2/FLAIR abnormality, T1‐gad enhancement, and areas of 18F‐FDOPA uptake separately. An experienced nuclear medicine physician contoured 18F‐FDOPA uptake, which was considered as the gold standard for positive disease on PET imaging. Intersection, union, and exclusion boolean operators were performed to determine discordance and concordance between MRI and 18F‐FDOPA‐PET, along with interobserver variability defining 18F‐FDOPA‐PET volume. In addition, uniform expansions of the T1‐gad contours were performed in increments of 0.5 cm until 100% of the 18F‐FDOPA‐PET volume was covered. Results: 18F‐FDOPA‐PET uptake was observed in all patients, with interobserver delineation variability between radiation oncologists (RadOnc1‐RadOnc3) and the gold standard ranging from 47% less to 191% more volume. On average 9.5% (0.3%–29.1%) of the 18F‐FDOPA‐PET gold standard volume extended beyond the RadOnc T2/FLAIR volumes. Half of the cases had no enhancement, and of the remainder on average 77.8% (61.3%–93.1%) of the 18F‐FDOPA‐PET volume extended outside the T1‐gad enhancement. An average expansion of 2.0cm (1.0cm–5.0cm) beyond the T1‐gad contours was necessary to cover 100% of the 18F‐FDOPA‐PET volume. Conclusions: This work introduces the potential utilization of 18F‐FDOPA‐PET for identifying positive disease not visible with conventional MRI and the potential to customize radiotherapy target volumes to the active disease. Future studies will correlate pathology with concordant and discordant regions, and compare biopsy confirmed results with automatic segmentation techniques for 18F‐FDOPA‐PET.Funding has been provided by Brains Together for a Cure
WE‐G‐110‐01: Task‐Based Modeling and Optimization of a Dedicated Cone‐Beam CT Scanner for Musculoskeletal Imaging
Authors: Prakash P , Gang G , Zbijewski W , Yorkston J , Machado A , Carrino J , Siewerdsen J 
Published: November 2011

Purpose: Cascaded systems analysis (CSA) offers a quantitative basis to optimize design and operation of novel imaging systems. Considering a CBCT scanner under development for musculoskeletal imaging, we employed CSA for design and technique optimization in relation to specific imaging tasks. Methods and Materials: A comprehensive system model combined spatial‐frequency‐dependent noise transfer characteristics, “system” parameters such as focal spot size and x‐ray scatter, and “generalized” parameters of anatomical clutter — each in relation to task‐based detectability. System performance was computed as a function of system geometry (magnification, detector pixel size, focal spot size, etc.), anatomical site (upper and lower extremities), imaging technique (kVp and dose), and reconstruction technique (voxel size and reconstruction filter). The vast parameter space was investigated in multivariate analysis for tasks ranging from low‐contrast, low‐frequency, soft‐tissue discrimination to higher‐contrast, high‐frequency detectability. Theoretical predictions were validated versus measurements on an imaging bench, and qualitative verification was obtained in cadaver images. Results: The analysis identified distinct optima and key tradeoffs among factors of contrast, noise, resolution, and dose. System geometry was a critical parameter in terms of focal spot blur, dose, and scatter, and a multivariate optimum was identified at magnification ∼1.3. Other optima included: kVp (90 kVp + 0.3 mm Cu); pixel size (0.15–0.19 mm); binning (2×2 binning for soft‐tissue discrimination); and filter (Hann versus ramp for soft‐tissue and bone tasks). Results were qualitatively confirmed in cadaver images and guided the selection of components and physical design of the extremity scanner. Conclusions: A CSA model providing a comprehensive treatment of quantum noise with “system” and “generalized” parameters provided a powerful basis for design and optimization. The work identified distinct optima in system geometry and operation without costly experimental trial and error and guided the development of a prototype CBCT scanner for musculoskeletal imaging now in translation.Work supported by the National Institutes of Health grant R01‐CA‐112163 and research collaboration with Carestream Health Inc. (Rochester NY).