bluuebunny/crossref_metadata_2025_split huggingface dataset:
WE‐E‐BRE‐02: BEST IN PHYSICS (THERAPY) – Stereotactic Radiotherapy for Renal Sympathetic Ablation for the Treatment of Refractory Hypertension
Authors: Maxim P , Wheeler M , Maguire P , Loo B 
Published: July 2014

Purpose:To determine the safety and efficacy of stereotactic radiotherapy as a novel treatment for patients with refractory hypertension in a swine model. Uncontrolled hypertension is a significant contributor to morbidity and mortality, substantially increasing the risk of ischemic stroke, ischemic heart disease, and kidney failure.Methods:High‐resolution computed tomography (CT) images of anesthetized pigs were acquired and treatment plans for each renal artery and nerve were developed using our clinically implemented treatment planning system. Stereotactic radiotherapy, 40Gy in single fraction was delivered bilaterally to the renal nerves using a state‐of‐the‐art medical linear accelerator under image guidance utilizing dynamic conformal arcs. Dose to nearby critical organs was evaluated by dosevolume histogram analysis and correlated to toxicity data obtained through follow up pathology analysis. The animals were observed for six months with serial measurements of blood pressure, urine analysis, serum laboratories, and overall clinical and behavioral status.Results:All animals survived to the follow‐up point without evidence of renal dysfunction (stable serum creatinine), skin changes, or behavioral changes that might suggest animal discomfort. Plasma norepinephrine levels (ng/ml) were followed monthly for 6 months. The average reduction observed was 63%, with the median reduction at 73.5%. Microscopic evaluation 4–6 weeks after treatment showed evidence of damage to the nerves around treated renal arteries. Considerable attenuation in pan neurofilament expression by immunohistochemistry was observed with some vacuolar changes indicative of injury. There was no histological or immunohistochemical evidence of damage to nearby spinal cord or spinal nerve root structures.Conclusion:Our preclinical studies have shown stereotactic radiotherapy to the renal sympathetic plexus to be safe and effective in reducing blood pressure, thus this approach holds great promise as a novel treatment modality for patients with refractory hypertension.This study was funded by the Stanford University Cardiovascular Institute. B. Loo and P. Maxim have received funding from RaySearch Laboratories.
WE‐E‐BRE‐03: Biological Validation of a Novel High‐Throughput Irradiator for Predictive Radiation Sensitivity Bioassays
Authors: Fowler TL , Martin JA , Shepard AJ , Bailey AM , Nickel KP , Kimple RJ , Bednarz BP 
Published: July 2014

Purpose:The large dose‐response variation in both tumor and normal cells between individual patients has led to the recent implementation of predictive bioassays of patient‐specific radiation sensitivity in order to personalize radiation therapy. This exciting new clinical paradigm has led us to develop a novel high‐throughput, variable dose‐rate irradiator to accompany these efforts. Here we present the biological validation of this irradiator through the use of human cells as a relative dosimeter assessed by two metrics, DNA double‐strand break repair pathway modulation and intercellular reactive oxygen species production.Methods:Immortalized human tonsilar epithelial cells were cultured in 96‐well micro titer plates and irradiated in groups of eight wells to absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy. High‐throughput immunofluorescent microscopy was used to detect γH2AX, a DNA double‐strand break repair mechanism recruiter. The same analysis was performed with the cells stained with CM‐H2DCFDA that produces a fluorescent adduct when exposed to reactive oxygen species during the irradiation cycle.Results:Irradiations of the immortalized human tonsilar epithelial cells at absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy produced excellent linearity in γH2AX and CM‐H2DCFDA with R2 values of 0.9939 and 0.9595 respectively. Single cell gel electrophoresis experimentation for the detection of physical DNA double‐strand breaks in ongoing.Conclusions:This work indicates significant potential for our high‐throughput variable dose rate irradiator for patient‐specific predictive radiation sensitivity bioassays. This irradiator provides a powerful tool by increasing the efficiency and number of assay techniques available to help personalize radiation therapy.
WE‐E‐BRE‐07: High‐Throughput Mapping of Proton Biologic Effect
Authors: Bronk L , Guan F , Kerr M , Dinh J , Titt U , Mirkovic D , Lin S , Mohan R , Grosshans D 
Published: July 2014

Purpose:To systematically relate the relative biological effectives (RBE) of proton therapy to beam linear energy transfer (LET) and dose.Methods:Using a custom irradiation apparatus previously characterized by our group, H460 NSCLCs were irradiated using a clinical 80MeV spot scanning proton beam. Utilizing this system allowed for high‐throughput clonogenic assays performed in 96‐well tissue culture plates as opposed to the traditional 6‐well technique. Each column in the 96‐well plate received a set LET‐dose combination. By altering the total number of dose repaintings, numerous dose‐LET configurations were examined to effectively generate surviving fraction (SF) data over the entire Bragg peak. The clonogenic assay was performed post‐irradiation using an INCell Analyzer for colony quantification. SF data were fit to the linear‐quadratic model for analysis.Results:Irradiation with increasing LETs resulted in decreased cell survival largely independent of dose. A significant correlation between LET and SF was identified by two‐way ANOVA and the extra sum‐of‐squares F test. This trend was obscured at the lower LET values in the plateau region of the Bragg peak; however, it was clear for LET values at and beyond the Bragg peak. Data fits revealed the SF at a dose of 2Gy (SF2) to be 0.48 for the lowest tested LET (1.55keV/um), 0.47 at the end of the plateau region (4.74keV/um) and 0.33 for protons at the Bragg peak (10.35keV/um). Beyond the Bragg peak we measured SF2s of 0.16 for 15.01keV/um, 0.02 for 16.79keV/um, and 0.004 for 18.06keV/um.Conclusion:We have shown that our methodology enables high‐content automated screening for proton irradiations over a range of LETs. The observed decrease in cellular SF in high LET regions confirms an increased RBE of the radiation and suggests further evaluation of proton RBE values is necessary to optimize clinical outcomes.Rosalie B. Hite Graduate Fellowship in Cancer Research, NIH Program Project Grant P01CA021239
WE‐E‐BRE‐08: Impact of IUdR in Rat 9L Glioma Cell Survival for 25–35 KeV Photo‐Activated Auger Electron Therapy
Authors: Alvarez D , Hogstrom K , Brown T , Dugas J , Matthews K , Varnes M 
Published: July 2014

Purpose:To determine the biological effect from Auger electrons with 9% and 18% iododeoxyuridine (IUdR) incorporated into the DNA of rat 9L glioma cells at photon energies above and below the K‐edge of iodine (33.2 keV).Methods:Rat 9L glioma cell survival versus dose curves with 0%, 9%, and 18% thymidine replacement with IUdR were measured using four irradiation energies (4 MV x‐rays; monochromatic 35, 30, and 25 keV synchrotron photons). For each of 11 conditions (Energy, %IUdR) survival curves were fit to the data (826 cell cultures) using the linear‐quadratic model. The ratio of doses resulting in 10% survival gave sensitization enhancement ratios (SER10) from which contributions due to linear‐energy transfer (LET), radiosensitization (RS), and Auger effect (AE) were extracted.Results:At 35, 30, and 25 keV, SER10,LET values were 1.08±0.03, 1.22±0.02, and 1.37±0.02, respectively. At 4 MV SER10,RS values for 9% and 18% IUdR were 1.28±0.02 and 1.40±0.02, respectively. Assuming LET effects are independent of %IUdR and radiosensitization effects are independent of energy, SER10,AE values for 18% IUdR at 35, 30, and 25 keV were 1.35±0.05, 1.06±0.03, and 0.98±0.03, respectively; values for 9% IUdR at 35 and 25 keV were 1.01±0.04 and 0.82±0.02, respectively.Conclusion:For 18% IUdR the radiosensitization effect of 1.40 and the Auger effect of 1.35 at 35 keV are equally important to the combined effect of 1.90. No measureable Auger effect was observed for energies below the K‐edge at 20 and 25 keV, as expected. The insignificant Auger effect at 9% IUdR was not expected. Additional data (40–70 keV) and radiobiological modeling are being acquired to better understand the energy dependence of Auger electron therapy with IUdR.Funding support in part by the National Science Foundation Graduate Research Fellowship Program and in part by Contract No. W81XWH‐10‐1‐0005 awarded by the U.S. Army Research Acquisition Activity. This paper does not necessarily reflect the position or policy of the Government, and no official endorsement should be inferred.
WE‐E‐BRE‐09: Investigation of the Association Between Radiation‐Induced Pain and Radiation Dose in Head and Neck Cancer Patients
Authors: Gay H , Oh J , Apte A , Dyk P , Mullen D , Eschen L , Fergus S , Chin R , Thorstad W , Deasy J 
Published: July 2014

Purpose:Patients with head and neck cancer who undergo radiotherapy often experience several undesirable side‐effects, including xerostomia, trismus, and pain in the head and neck area, but little is know about the dose‐volume predictors of such pain. We investigated the association between radiation dose and both throat and esophagus pain during radiotherapy.Methods:We analyzed 124 head and neck patients who received radiotherapy at the Washington University School of Medicine in Saint Louis. For these patients, weekly PROs were recorded, including 16 pain and anatomical location questions. In addition, 17 observational symptoms were recorded. Patients were asked to describe their pain at each site according to a four‐level scale: none (0), mild (1), moderate (2), and severe (3). We explored the association between throat pain and the mean dose received in oral cavity and between esophageal pain and the mean dose received in the esophagus. The severity of pain was determined by the difference between the baseline (week 1) pain score and the maximum pain score during treatment. The baseline pain score was defined as the first available pain score before receiving 10 Gy because radiotherapy pain originates later during treatment. Dose‐volume metrics were extracted from treatment plans using CERR. To evaluate the correlation between pain and radiation dose, Spearman's correlation coefficient (Rs) was used.Results:The associations between throat pain and the mean dose to the oral cavity, and between esophagus pain and the mean dose to the esophagus, were both statistically significant, with Rs=0.320 (p=0.003) and Rs=0.424 (p<0.0001), respectively. Mean dose, for each structure, was a better predictor of pain than total integral dose.Conclusion:We demonstrated that pain during radiotherapy in head and neck patients highly correlates with the dose delivered. We will further investigate the association between other pain locations and relevant normal tissue dose characteristics.
WE‐E‐17A‐02: Predictive Modeling of Outcome Following SABR for NSCLC Based On Radiomics of FDG‐PET Images
Authors: Li R , Aguilera T , Shultz D , Rubin D , Diehn M , Loo B 
Published: July 2014

Purpose:This study aims to develop predictive models of patient outcome by extracting advanced imaging features (i.e., Radiomics) from FDG‐PET images.Methods:We acquired pre‐treatment PET scans for 51 stage I NSCLC patients treated with SABR. We calculated 139 quantitative features from each patient PET image, including 5 morphological features, 8 statistical features, 27 texture features, and 100 features from the intensity‐volume histogram. Based on the imaging features, we aim to distinguish between 2 risk groups of patients: those with regional failure or distant metastasis versus those without. We investigated 3 pattern classification algorithms: linear discriminant analysis (LDA), naive Bayes (NB), and logistic regression (LR). To avoid the curse of dimensionality, we performed feature selection by first removing redundant features and then applying sequential forward selection using the wrapper approach. To evaluate the predictive performance, we performed 10‐fold cross validation with 1000 random splits of the data and calculated the area under the ROC curve (AUC).Results:Feature selection identified 2 texture features (homogeneity and/or wavelet decompositions) for NB and LR, while for LDA SUVmax and one texture feature (correlation) were identified. All 3 classifiers achieved statistically significant improvements over conventional PET imaging metrics such as tumor volume (AUC = 0.668) and SUVmax (AUC = 0.737). Overall, NB achieved the best predictive performance (AUC = 0.806). This also compares favorably with MTV using the best threshold at an SUV of 11.6 (AUC = 0.746). At a sensitivity of 80%, NB achieved 69% specificity, while SUVmax and tumor volume only had 36% and 47% specificity.Conclusion:Through a systematic analysis of advanced PET imaging features, we are able to build models with improved predictive value over conventional imaging metrics. If validated in a large independent cohort, the proposed techniques could potentially aid in identifying patients who might benefit from adjuvant therapy.
WE‐E‐17A‐08: Prediction of Response to Neoadjuvant Chemotherapy Using a Mechanically Coupled Reaction‐Diffusion Model
Authors: Weis J , Miga M , Li X , Arlinghaus L , Chakravarthy A , Abramson V , Farley J , Yankeelov T 
Published: July 2014

Purpose:To develop a clinically‐relevant patient‐specific modeling framework for oncology that is amenable to readily available clinical imaging data and yet retains the most salient features of response prediction. We use a mechanically coupled mathematical model of tumor growth that is initialized and constrained by MRI data early in the course of therapy, to guide the determination of model parameters and predict the response of breast cancers to neoadjuvant chemotherapy (NAC).Methods:We adopt a patient‐scale spatiotemporal tumor growth modeling framework and apply patient‐specific predictive modeling, constrained by quantitative imaging data, to a group of 26 patients exhibiting a varying degree of response to NAC. Dynamic contrast enhanced MRI, diffusion weighted MRI, and anatomical T1‐weighted MRI volumes were acquired prior to beginning NAC, after one cycle of NAC, and at the conclusion of NAC. Tumor response is parameterized using data from before and after the first cycle of therapy, and the model is driven forward in time to predict tumor burden at the conclusion of therapy. Model reconstructed parameters and predictions are retrospectively assessed for prognostic value in predicting patients that eventually respond or do not respond to NAC.Results:Using our mechanics‐coupled modeling approach, we are able to discriminate, after the first cycle of therapy, breast cancer patients that would eventually achieve a complete pathological response and those who would not, with an area under the receiver operator characteristic curve of 0.81, sensitivity of 90%, and specificity of 56%.Conclusion:We show the potential for model‐predictions at the conclusion of therapy for use as a prognostic indicator of response to therapy. This work provides considerable promise for predictive modeling centered on integrating quantitative in vivo imaging data with biomechanical models of tumor growth.National Institutes of Health NCI 1U01CA142565, NCI U01CA174706, NCI R25CA092043, NCI 1P50 098131, NCI P30CA68485, NCI R01CA138599, NINDS R01NS049251. The Vanderbilt initiative in Surgery and Engineering Pilot Award Program and the Whitaker Foundation.
WE‐G‐18A‐07: Clinical Evaluation of Normalized Metal Artifact Reduction in KVCT Using MVCT Prior Images (MVCT‐NMAR) Technique in Radiotherapy
Authors: Paudel M , MacKenzie M , Fallone B , Rathee S 
Published: July 2014

Purpose:To evaluate the metal artifacts in diagnostic kVCT images of patients that are corrected using a normalized metal artifact reduction method with MVCT prior images, MVCT‐NMAR.Methods:An MVCTNMAR algorithm was developed and applied to five patients: three with bilateral hip prostheses, one with unilateral hip prosthesis and one with dental fillings. The corrected images were evaluated for visualization of tissue structures and their interfaces, and for radiotherapy dose calculations. They were also compared against the corresponding images corrected by a commercial metal artifact reduction technique, O‐MAR, on a Phillips™ CT scanner.Results:The use of MVCT images for correcting kVCT images in the MVCT‐NMAR technique greatly reduces metal artifacts, avoids secondary artifacts, and makes patient images more useful for correct dose calculation in radiotherapy. These improvements are significant over the commercial correction method, provided the MVCT and kVCT images are correctly registered. The remaining and the secondary artifacts (soft tissue blurring, eroded bones, false bones or air pockets, CT number cupping within the metal) present in O‐MAR corrected images are removed in the MVCT‐NMAR corrected images. Large dose reduction is possible outside the planning target volume (e.g., 59.2 Gy in comparison to 52.5 Gy in pubic bone) when these MVCT‐NMAR corrected images are used in TomoTherapy™ treatment plans, as the corrected images no longer require directional blocks for prostate plans in order to avoid the image artifact regions.Conclusion:The use of MVCT‐NMAR corrected images in radiotherapy treatment planning could improve the treatment plan quality for cancer patients with metallic implants.Moti Raj Paudel is supported by the Vanier Canada Graduate Scholarship, the Endowed Graduate Scholarship in Oncology and the Dissertation Fellowship at the University of Alberta. The authors acknowledge the CIHR operating grant number MOP 53254.
WE‐G‐18A‐08: Axial Cone Beam DBPF Reconstruction with Three‐Dimensional Weighting and Butterfly Filtering
Authors: Tang S , Wang W , Tang X 
Published: July 2014

Purpose:With the major benefit in dealing with data truncation for ROI reconstruction, the algorithm of differentiated backprojection followed by Hilbert filtering (DBPF) is originally derived for image reconstruction from parallel‐ or fan‐beam data. To extend its application for axial CB scan, we proposed the integration of the DBPF algorithm with 3‐D weighting. In this work, we further propose the incorporation of Butterfly filtering into the 3‐D weighted axial CB‐DBPF algorithm and conduct an evaluation to verify its performance.Methods:Given an axial scan, tomographic images are reconstructed by the DBPF algorithm with 3‐D weighting, in which streak artifacts exist along the direction of Hilbert filtering. Recognizing this orientation‐specific behavior, a pair of orthogonal Butterfly filtering is applied on the reconstructed images with the horizontal and vertical Hilbert filtering correspondingly. In addition, the Butterfly filtering can also be utilized for streak artifact suppression in the scenarios wherein only partial scan data with an angular range as small as 270° are available.Results:Preliminary data show that, with the correspondingly applied Butterfly filtering, the streak artifacts existing in the images reconstructed by the 3‐D weighted DBPF algorithm can be suppressed to an unnoticeable level. Moreover, the Butterfly filtering also works at the scenarios of partial scan, though the 3‐D weighting scheme may have to be dropped because of no sufficient projection data are available.Conclusion:As an algorithmic step, the incorporation of Butterfly filtering enables the DBPF algorithm for CB image reconstruction from data acquired along either a full or partial axial scan.
WE‐G‐18C‐01: Novel Method for Geometrically Undistorted B0 Inhomogeneity Field Map Estimation and Image Correction
Authors: Matakos A , Balter J , Cao Y 
Published: July 2014

Purpose:To develop and evaluate a method to estimate undistorted B0 inhomogeneity field maps of MRI and to correct susceptibility‐induced geometrical and intensity distortions in clinical images in order to support precision RT planning.Methods:The proposed method consisted of two major steps. First, undistorted B0 inhomogeneity field maps and images were estimated from k‐space data of a 3D dual gradient‐echo (GRE) acquisition using a novel joint reconstruction algorithm. After linearizing the cost function that includes two spatial regularizations, the algorithm iteratively estimated the undistorted field maps and images. Second, clinical images acquired with a low readout‐bandwidth in the same imaging session, e.g., 180 Hz/pixel in clinical brain T1‐weighted images, were corrected for geometrical and intensity distortions by using the undistorted field map. The method was evaluated through simulation, and studies of a geometric phantom with air‐water interfaces and human brain on a 3T scanner.Results:Simulation showed that our method reduced field map errors (RMS and maximum error) in the undistorted field maps ten‐fold compared to the distorted ones, and geometric and intensity artifacts in the jointly reconstructed images. In the phantom study, the 2‐mm distortion near the air‐water interface was fully corrected using the undistorted field map, but only partially corrected using the distorted field map with approximately 1‐mm residual distortion. In the patient study, there was >2 mm distortion near the sinus in the distorted field map. The geometrically accurate field map obtained by our method resulted in improved correction of geometry and intensity in both GRE and clinical T1‐weighted images at the air/tissue interface.Conclusion:Our method can correct geometrical distortion in clinical images, create a geometrical accurate image template, or provide a means for quality assurance of individual patient images, to enable MRI as a primary modality in precision RT planning.Work supported by: NIH R01 EB016079
WE‐G‐18C‐06: Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?
Authors: Yang J , Cai J , Wang H , Zheng C , Czito B , Bashir M , Palta M , Yin F 
Published: July 2014

Purpose:To investigate whether diaphragm motion is a good surrogate for liver tumor motion by comparing their motion trajectories obtained from cine‐MRI.Methods:Fourteen patients with hepatocellular carcinoma (10/14) or liver metastases (4/14) undergoing radiation therapy were included in this study. All patients underwent single‐slice 2D cine‐MRI simulations across the center of the tumor in three orthogonal planes. Tumor and diaphragm motion trajectories in the superior‐inferior (SI), anteriorposterior (AP), and medial‐lateral (ML) directions were obtained using the normalized cross‐correlation based tracking technique. Agreement between tumor and diaphragm motions was assessed by calculating the phase difference percentage (PDP), intra‐class correlation coefficient (ICC), Bland‐Altman analysis (Diffs) and paired t‐test. The distance (D) between tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between tumor and diaphragm motions.Results:Of all patients, the means (±standard deviations) of PDP were 7.1 (±1.1)%, 4.5 (±0.5)% and 17.5 (±4.5)% in the SI, AP and ML directions, respectively. The means of ICC were 0.98 (±0.02), 0.97 (±0.02), and 0.08 (±0.06) in the SI, AP and ML directions, respectively. The Diffs were 2.8 (±1.4) mm, 2.4 (±1.1) mm, and 2.2 (±0.5) mm in the SI, AP and ML directions, respectively. The p‐values derived from the paired t‐test were < 0.02 in SI and AP directions, whereas were > 0.58 in ML direction primarily due to the small motion in ML direction. Tumor and diaphragmatic motion had high concordance when the distance between the tumor and tracked diaphragm areas was small.Conclusion:Preliminary results showed that liver tumor motion had good correlations with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be a reliable surrogate for liver tumor motion.NIH (1R21CA165384‐01A1), Golfers Against Cancer (GAC) Foundation, The China Scholarship Council (CSC)