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DOE OSTI2022

Multi-channel front-end ASIC for a 3D position-sensitive detector

Arrays of 3D position-sensitive detectors (3DPSD), operating at room temperature and using cadmium zinc telluride (CZT) and thallium bromide (TIBr) sensors, are suitable for gamma-ray spectrometry in many applications. One detector configuration, the 3D position-sensitive Virtual Frisch-Grid detector (VFG), is particularly advantageous for integrating into large area arrays. The signals generated inside each detector of the array are captured with the anode, cathode and four pads that enable the reconstruction of the position and energy of the ionizing interaction by measurements of amplitude and timing of the signals. For these applications, a low-noise front-end ASIC has been developed, capable of processing bipolar signals (needed because of AC-coupling of certain electrodes). The ASIC can be coupled to an ADC in order to form a compound “waveform digitizer” capable of post-processing the analog signals and determining amplitude and timing information. This paper describes a 32-channel front-end ASIC that is suitable for reading out a 3 × 3 or 4 × 4 element matrix in the VFG configuration. Each channel is composed of a low-noise charge amplifier with an adaptive continuous reset feedback circuit suitable for both positive and negative charge, a first order shaper and a single-to-differential converter output stage. Voltage and current references are all internally generated by 10-bit DACs and the chip is fully controllable with the I 2 C communication protocol. The readout channel response has been verified using the implemented injection circuit. Linear behavior up to ~75 ke ± with the gain of ~80 mV/fC, and up to ~200 ke ± with the gain of ~30 mV/fC was demonstrated. In conclusion, the first test result waveforms using a 137 Cs radioactive source on a 5 × 5 × 12 mm 3 TIBr crystal are reported.

47 OTHER INSTRUMENTATION↗

DOE OSTI2025

Improved laser-plasma accelerator stability via high-bandwidth longitudinal focal position stabilization of a 100 TW-class laser system

Laser-plasma accelerators (LPAs) offer an attractive alternative to conventional accelerators for the development of compact electron sources and next-generation light sources. Due to orders-of-magnitude larger accelerating gradients, LPAs enable the acceleration of high-brightness electron beams to ultrarelativistic energies in millimeter- to centimeter-scale distances. However, LPA stability is limited by shot-to-shot fluctuations of the driving laser system. Specifically, fluctuations in the final-focus longitudinal position result in correlated instability in LPA electron beam qualities, including total beam charge, average beam energy, and energy spread. We demonstrate active stabilization of the longitudinal focal position for a 100 TW-class laser system. This repetition-rate scalable stabilization system leverages noninvasive wave front monitoring of a copropagating, unamplified kHz pulse train to guide corrective adjustments to the focal position of a 1 Hz amplified drive laser via an upstream telescope on millisecond timescales. In this demonstration, the approach limits standard deviation fluctuations of the amplified drive beam’s longitudinal focal position to ±0.22⁢ mm (representing at least a 53% reduction), achieved with a correction bandwidth that reaches the Nyquist frequency limit. Consequently, we observe marked improvements in both long-term and shot-to-shot LPA stability in terms of charge and spectrum.

Beam control↗

DOE OSTI2017

Dynamic X-ray diffraction sampling for protein crystal positioning

A sparse supervised learning approach for dynamic sampling (SLADS) is described for dose reduction in diffraction-based protein crystal positioning. Crystal centering is typically a prerequisite for macromolecular diffraction at synchrotron facilities, with X-ray diffraction mapping growing in popularity as a mechanism for localization. In X-ray raster scanning, diffraction is used to identify the crystal positions based on the detection of Bragg-like peaks in the scattering patterns; however, this additional X-ray exposure may result in detectable damage to the crystal prior to data collection. Dynamic sampling, in which preceding measurements inform the next most information-rich location to probe for image reconstruction, significantly reduced the X-ray dose experienced by protein crystals during positioning by diffraction raster scanning. The SLADS algorithm implemented herein is designed for single-pixel measurements and can select a new location to measure. In each step of SLADS, the algorithm selects the pixel, which, when measured, maximizes the expected reduction in distortion given previous measurements. Ground-truth diffraction data were obtained for a 5 µm-diameter beam and SLADS reconstructed the image sampling 31% of the total volume and only 9% of the interior of the crystal greatly reducing the X-ray dosage on the crystal. Furthermore, by using in situ two-photon-excited fluorescence microscopy measurements as a surrogate for diffraction imaging with a 1 µm-diameter beam, the SLADS algorithm enabled image reconstruction from a 7% sampling of the total volume and 12% sampling of the interior of the crystal. When implemented into the beamline at Argonne National Laboratory, without ground-truth images, an acceptable reconstruction was obtained with 3% of the image sampled and approximately 5% of the crystal. The incorporation of SLADS into X-ray diffraction acquisitions has the potential to significantly minimize the impact of X-ray exposure on the crystal by limiting the dose and area exposed for image reconstruction and crystal positioning using data collection hardware present in most macromolecular crystallography end-stations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2016

Mobile Emergency Generator Pre-Positioning and Real-Time Allocation for Resilient Response to Natural Disasters

Truck-mounted mobile emergency generators (MEGs) are critical flexibility resources of distribution systems (DSs) for resilient emergency response to natural disasters. However, they are currently under-utilized. For better utilization, this paper proposes dispatching MEGs as distributed generators in DSs to restore critical loads by forming multiple microgrids (MGs). As the travel time of MEGs on road networks (RNs) can greatly influence the outage duration of critical loads, a two-stage dispatch framework consisting of pre-positioning and real-time allocation is introduced, and the traffic issue is considered via the vehicle routing problem. Pre-positioning places MEGs in staging locations prior to a natural disaster, while real-time allocation sends MEGs from staging locations to restore critical loads by forming MGs in DSs after the natural disaster strikes. Specifically, with the objective of minimizing the expected outage duration of loads considering their priorities and demand sizes, pre-positioning is done via a scenario-based two-stage stochastic optimization problem, in which the first-stage pre-positioning decisions are evaluated by numbers of second-stage real-time allocation problems corresponding to considered scenarios of DS damage and RN damage/congestion. A scenario decomposition algorithm is applied to solve this problem. Illustrative cases demonstrate the effectiveness of the proposed dispatch scheme and algorithm.

Lei, Shunbo (ORCID:0000000181690821)↗

DOE OSTI2024

Positioning Accuracy in a Concurrent Robot-CNC Hybrid Manufacturing System

Abstract Additive manufacturing (AM) has gained notoriety for offering advantages over traditional manufacturing methods, such as increased design complexity and flexibility. However, it has not found widespread use beyond rapid prototyping. One hindrance to the acceptance of AM processes in industry is the time and cost of fabrication per component. While metal AM by itself can be inexpensive, extra manufacturing steps in the form of subtractive manufacturing (SM) may need to be performed to reach final part tolerances, leading to hybrid additive-subtractive manufacturing (HASM) of a part, which increases time and cost. A potential area to reduce cost is through increasing the efficiency of the HASM process by conducting additive and subtractive manufacturing simultaneously. Usually, HASM is performed in a process where AM is completed in one machine or cell and transferred to another machine or cell for SM in a sequential assembly line process. This efficiency decreases part cost, but high aspect ratio parts or parts with internal geometry that require interleaved additive deposition and machining cannot be produced. One unexplored solution to simultaneous HASM that allows for interleaved operations is to operate the deposition head and machining spindle concurrently within the same machine envelope, known as concurrent HASM (CHASM). In this type of process, both AM and SM occur simultaneously on a batch of small parts or a single large part, maintaining a high efficiency without sacrificing the full range of complex geometries that AM allows for. A potential approach to the single-machine method could be to combine a robot and mill within the same envelope. A challenge to this approach, however, is control of both systems. Most machine controllers have limited external communication or, if a robot has been integrated, only offer movement of either the robot or mill at any given time. As a result, systems must pause either the AM or SM process to switch between them rather than working simultaneously. The present work investigates the positional accuracy of such a CHASM system comprised of a robotic arm and a 3-axis mill. Open-loop tests with limited communication between machines are performed on the system to verify positional error during concurrent robot-mill movements. Under certain conditions, it is demonstrated that position error can stay within 2 mm for the duration of a single layer; however, these tests show that, generally, the open-loop positioning performance of the system is inadequate for CHASM without part-specific hand-tuning of parameters. Based on these results, a set of requirements for successful robot-CNC CHASM is proposed for future integrations.

Goodwin, Jesse↗

DOE OSTI2013

Toward correcting drift in target position during radiotherapy via computer-controlled couch adjustments on a programmable Linac

Purpose: Real-time tracking of respiratory target motion during radiation therapy is technically challenging, owing to rapid and possibly irregular breathing variations. The authors report on a method to predict and correct respiration-averaged drift in target position by means of couch adjustments on an accelerator equipped with such capability. Methods: Dose delivery is broken up into a sequence of 10 s field segments, each followed by a couch adjustment based on analysis of breathing motion from an external monitor as a surrogate of internal target motion. Signal averaging over three respiratory cycles yields a baseline representing target drift. A Kalman filter predicts the baseline position 5 s in advance, for determination of the couch correction. The method's feasibility is tested with a motion phantom programmed according to previously recorded patient signals. Computed couch corrections are preprogrammed into a research mode of an accelerator capable of computer-controlled couch translations synchronized with the motion phantom. The method's performance is evaluated with five cases recorded during hypofractionated treatment and five from respiration-correlated CT simulation, using a root-mean-squared deviation (RMSD) of the baseline from the treatment planned position. Results: RMSD is reduced in all 10 cases, from a mean of 4.9 mm (range 2.7-9.4 mm) before correction to 1.7 mm (range 0.7-2.3 mm) after correction. Treatment time is increased {approx}5% relative to that for no corrections. Conclusions: This work illustrates the potential for reduction in baseline respiratory drift with periodic adjustments in couch position during treatment. Future treatment machine capabilities will enable the use of 'on-the-fly' couch adjustments during treatment.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

Sci—Fri PM: Topics — 02: Evaluation of Dosimetric Variations in Partial Breast Seed Implant (PBSI) due to Patient Arm Position (Up vs. Down)

The planning for PBSI is done with the patient's ipsilateral arm raised, however, anatomical changes and variations are unavoidable as the patient resumes her daily activities, potentially resulting in significant deviations in implant geometry from the treatment plan. This study aims to quantify the impact of the ipsilateral arm position on the geometry and dosimetry of the implant at eight weeks, evaluated on post-plans using the MIM Symphony™ software (MIM Software, Cleveland, OH). The average dose metrics for the three patients treated at the TBCC thus far using rigid fusion and contour transfer for the arms up position were 76% for the CTV V100, 61% for the PTV V100, and 37% for the PTV V200; and for the arms down position 81% for the CTV V100, 64% for the PTV V100, and 42% for the PTV V200. Qualitative analysis of the post-implant CT for one of the three patients showed poor agreement between the seroma contour transferred from the pre-implant CT and the seroma visible on the post-implant CT. To obtain a clinically accurate plan for that patient, contour modifications were used, yielding improved dose metric averages for the arms-up position for all three patients of 87% for the CTV V100, 68% for the PTV V100, and 39% for the PTV V200. Overall, the data available shows that dosimetric parameters increase with the patient's arm down, both in terms of coverage and in terms of the hot spot, and accrual of more patients may confirm this in a larger population.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-C-210-06: Quantitative Evaluation of Dosimetric Effects Resulting From Positional Variations of Pancreatic Tumor Volumes

Purpose: The aim of this study is to quantify dosimetric effects resulting from variation in pancreatic tumor position assessed by bony anatomy and implanted fiducial markers Methods: Twelve pancreatic cancer patients were retrospectively analyzed for this study. All patients received modulated arc therapy (VMAT) treatment using fiducial-based Image Guided Radiation Therapy (IGRT) to the intact pancreas. Using daily orthogonal kV and/or Cone beam CT images, the shift needed to co-register the daily pre-treatment images to reference CT from fiducial to bone (Fid-Bone) were recorded as Left-Right (LR), Anterior-Posterior (AP) and Superior-Inferior (SI). The original VMAT plan iso-center was shifted based on KV bone matching positions at 5 evenly spaced fractions. Dose coverage of the planning target volumes (PTVs) (V100%), mean dose to liver, kidney and stomach/duodenum were assessed in the modified plans. Results: A total of 306 fractions were analyzed. The absolute fiducial-bone positional shifts were greatest in the SI direction, (AP = 2.7 ± 3.0, LR = 2.8 ± 2.8, and SI 6.3 ± 7.9 mm, mean ± SD). The V100% was significantly reduced by 13.5%, (Fid-Bone = 95.3 ± 2.0 vs. 82.3 ± 11.8%, p=0.02). This varied widely among patients (Fid-Bone V100% Range = 2–60%), where 33% of patients had a reduction in V100% of more than 10%. The impact on OARs was greatest to the liver (Fid-Bone= 14.6 vs. 16.1 Gy, 10%), and stomach, (Fid-Bone = 23.9 vx. 25.5 Gy, 7%), however was not statistically significant (p=0.10 both). Conclusion: Compared to matching by fiducial markers, matching by bony anatomy would have substantially reduced the PTV coverage by 13.5%. This reinforces the importance of online position verification based on fiducial markers. Hence, implantation of fiducial markers is strongly recommended for pancreatic cancer patients undergoing intensity modulated radiation therapy treatments.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-P-21: Impact of MLC Position Errors On Simultaneous Integrated Boost Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma

Purpose: To investigate the impact of MLC position errors on simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with nasopharyngeal carcinoma. Methods: To compare the dosimetric differences between the simulated plans and the clinical plans, ten patients with locally advanced NPC treated with SIB-IMRT were enrolled in this study. All plans were calculated with an inverse planning system (Pinnacle3, Philips Medical System{sub )}. Random errors −2mm to 2mm{sub )},shift errors{sub (} 2mm,1mm and 0.5mm) and systematic extension/ contraction errors (±2mm, ±1mm and ±0.5mm) of the MLC leaf position were introduced respectively into the original plans to create the simulated plans. Dosimetry factors were compared between the original and the simulated plans. Results: The dosimetric impact of the random and system shift errors of MLC position was insignificant within 2mm, the maximum changes in D95% of PGTV,PTV1,PTV2 were-0.92±0.51%,1.00±0.24% and 0.62±0.17%, the maximum changes in the D0.1cc of spinal cord and brainstem were 1.90±2.80% and −1.78±1.42%, the maximum changes in the Dmean of parotids were1.36±1.23% and −2.25±2.04%.However,the impact of MLC extension or contraction errors was found significant. For 2mm leaf extension errors, the average changes in D95% of PGTV,PTV1,PTV2 were 4.31±0.67%,4.29±0.65% and 4.79±0.82%, the averaged value of the D0.1cc to spinal cord and brainstem were increased by 7.39±5.25% and 6.32±2.28%,the averaged value of the mean dose to left and right parotid were increased by 12.75±2.02%,13.39±2.17% respectively. Conclusion: The dosimetric effect was insignificant for random MLC leaf position errors up to 2mm. There was a high sensitivity to dose distribution for MLC extension or contraction errors.We should pay attention to the anatomic changes in target organs and anatomical structures during the course,individual radiotherapy was recommended to ensure adaptive doses.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-189: Determination of Markerless Lung Tumor Position in Real Time: A Feasibility Study Using a Novel Tomo-Cinegraphy Imaging

Purpose: A Tomo-Cinegraphy (TC) is a method to generate a series of temporal tomographic images from projection images of the on-board imager (OBI) while gantry is moving. It is to test if this technique is useful to determine a lung tumor position during treatments. Methods: Tomographic image via background subtraction, TIBS uses a priori anatomical information from a previous CT scan to isolate a SOI from a planar kV image by factoring out the attenuations by tissues outside the SOI (background). This idea was extended to a TC, which enables to generate tomographic images of same geometry from the projection of different gantry angles and different breathing phases. Projection images of a lung patient for CBCT acquisition are used to generate TC images. A region of interest (ROI) is selected around a tumor adding 2cm margins. Center of mass (COM) of the ROI is traced to determine tumor position for every projection images. Results: Tumor is visible in the TC images while the OBI projections are not. The coordinates of the COMs represent the temporal tumor positions. While, it is not possible to trace the tumor motion using the projection images. A source of time delay is the time to acquire projection images, which is always less than a second. Conclusion: TC allows tracking the tumor positions without fiducial markers in real time for some lung patients, if the projection images are acquired during treatments. Partially supported by NIH R01CA133539.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-459: Impact of Source Position and Traveling Time On HDR Skin Surface Applicator Dosimetry

Purpose: Observed dosimetric discrepancy between measured and treatment planning system (TPS) predicted values, during applicator commissioning, were traced to source position uncertainty in the applicator. We quantify the dosimetric impact of this geometric uncertainty, and of the source traveling time inside the applicator, and propose corrections for clinical use. Methods: We measured the dose profiles from the Varian Leipzig-style (horizontal) HDR skin applicator, using EBT3 film, photon diode, and optically stimulated luminescence dosimeter (OSLD) and three different GammaMed HDR afterloders. The dose profiles and depth dose of each aperture were measured at several depths (up to about 10 mm, depending on the dosimeter). The measured dose profiles were compared with Acuros calculated profiles in BrachyVision TPS. For the impact of the source position, EBT3 film measurements were performed with applicator, facing-down and facing-up orientations. The dose with and without source traveling was measured with diode detector using HDR timer and electrometer timer, respectively. Results: Depth doses measured using the three dosimeters were in good agreement, but were consistently higher than the Acuros dose calculations. Measurements with the applicator facing-up were significantly lower than those in the facing-down position with maximum difference of about 18% at the surface, due to source sag inside the applicator. Based on the inverse-square law, the effective source sag was evaluated to be about 0.5 mm from the planned position. The additional dose from the source traveling was about 2.8% for 30 seconds with 10 Ci source, decreasing with increased dwelling time and decreased source activity. Conclusion: Due to the short source-to-surface distance of the applicator, the small source sag inside the applicator has significant dosimetric impact, which should be considered before the clinical use of the applicator. Investigation of the effect for other applicators that have relatively large source lumen inner diameter may be warranted. Christopher Barker and Gil’ad Cohen are receiving research support for a study of skin surface brachytherapy from Elekta.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Continuous monitoring of prostate position using stereoscopic and monoscopic kV image guidance

Purpose: To demonstrate continuous kV x-ray monitoring of prostate motion using both stereoscopic and monoscopic localizations, assess the spatial accuracy of these techniques, and evaluate the dose delivered from the added image guidance. Methods: The authors implemented both stereoscopic and monoscopic fiducial localizations using a room-mounted dual oblique x-ray system. Recently developed monoscopic 3D position estimation techniques potentially overcome the issue of treatment head interference with stereoscopic imaging at certain gantry angles. To demonstrate continuous position monitoring, a gold fiducial marker was placed in an anthropomorphic phantom and placed on the Linac couch. The couch was used as a programmable translation stage. The couch was programmed with a series of patient prostate motion trajectories exemplifying five distinct categories: stable prostate, slow drift, persistent excursion, transient excursion, and high frequency excursions. The phantom and fiducial were imaged using 140 kVp, 0.63 mAs per image at 1 Hz for a 60 s monitoring period. Both stereoscopic and monoscopic 3D localization accuracies were assessed by comparison to the ground-truth obtained from the Linac log file. Imaging dose was also assessed, using optically stimulated luminescence dosimeter inserts in the phantom. Results: Stereoscopic localization accuracy varied between 0.13 ± 0.05 and 0.33 ± 0.30 mm, depending on the motion trajectory. Monoscopic localization accuracy varied from 0.2 ± 0.1 to 1.1 ± 0.7 mm. The largest localization errors were typically observed in the left–right direction. There were significant differences in accuracy between the two monoscopic views, but which view was better varied from trajectory to trajectory. The imaging dose was measured to be between 2 and 15 μGy/mAs, depending on location in the phantom. Conclusions: The authors have demonstrated the first use of monoscopic localization for a room-mounted dual x-ray system. Three-dimensional position estimation from monoscopic imaging permits continuous, uninterrupted intrafraction motion monitoring even in the presence of gantry rotation, which may block kV sources or imagers. This potentially allows for more accurate treatment delivery, by ensuring that the prostate does not deviate substantially from the initial setup position.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-I-19: MRI Positive Contrast Visualization of Prostate Brachytherapy Seeds Using An Integrated Laplacian-Based Phase Processing

Purpose: To propose a new method that provides a positive contrast visualization of the prostate brachytherapy seeds using the phase information from MR images. Additionally, the feasibility of using the processed phase information to distinguish seeds from calcifications is explored. Methods: A gel phantom was constructed using 2% agar dissolved in 1 L of distilled water. Contrast agents were added to adjust the relaxation times. Four iodine-125 (Eckert & Ziegler SML86999) dummy seeds were placed at different orientations with respect to the main magnetic field (B0). Calcifications were obtained from a sheep femur cortical bone due to its close similarity to human bone tissue composition. Five samples of calcifications were shaped into different dimensions with lengths ranging between 1.2 – 6.1 mm.MR imaging was performed on a 3T Philips Achieva using an 8-channel head coil. Eight images were acquired at eight echo-times using a multi-gradient echo sequence. Spatial resolution was 0.7 × 0.7 × 2 mm, TR/TE/dTE = 20.0/2.3/2.3 ms and BW = 541 Hz/pixel. Complex images were acquired and fed into a two-step processing pipeline: the first includes phase unwrapping and background phase removal using Laplacian operator (Wei et al. 2013). The second step applies a specific phase mask on the resulting tissue phase from the first step to provide the desired positive contrast of the seeds and to, potentially, differentiate them from the calcifications. Results: The phase-processing was performed in less than 30 seconds. The proposed method has successfully resulted in a positive contrast of the brachytherapy seeds. Additionally, the final processed phase image showed difference between the appearance of seeds and calcifications. However, the shape of the seeds was slightly distorted compared to the original dimensions. Conclusion: It is feasible to provide a positive contrast of the seeds from MR images using Laplacian operator-based phase processing.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-34: Automatic Target-Based Patient Positioning Framework for Image-Guided Radiotherapy in Prostate Cancer Treatment

Purpose: Current image-guided radiotherapy (IGRT) procedure is bonebased patient positioning, followed by subjective manual correction using cone beam computed tomography (CBCT). This procedure might cause the misalignment of the patient positioning. Automatic target-based patient positioning systems achieve the better reproducibility of patient setup. Our aim of this study was to develop an automatic target-based patient positioning framework for IGRT with CBCT images in prostate cancer treatment. Methods: Seventy-three CBCT images of 10 patients and 24 planning CT images with digital imaging and communications in medicine for radiotherapy (DICOM-RT) structures were used for this study. Our proposed framework started from the generation of probabilistic atlases of bone and prostate from 24 planning CT images and prostate contours, which were made in the treatment planning. Next, the gray-scale histograms of CBCT values within CTV regions in the planning CT images were obtained as the occurrence probability of the CBCT values. Then, CBCT images were registered to the atlases using a rigid registration with mutual information. Finally, prostate regions were estimated by applying the Bayesian inference to CBCT images with the probabilistic atlases and CBCT value occurrence probability. The proposed framework was evaluated by calculating the Euclidean distance of errors between two centroids of prostate regions determined by our method and ground truths of manual delineations by a radiation oncologist and a medical physicist on CBCT images for 10 patients. Results: The average Euclidean distance between the centroids of extracted prostate regions determined by our proposed method and ground truths was 4.4 mm. The average errors for each direction were 1.8 mm in anteroposterior direction, 0.6 mm in lateral direction and 2.1 mm in craniocaudal direction. Conclusion: Our proposed framework based on probabilistic atlases and Bayesian inference might be feasible to automatically determine prostate regions on CBCT images.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-43: Positional Variation of Implanted Fiducial Markers Over the Course of Image Guided Radiotherapy for Pancreatic Cancer

Purpose: Pancreas is a soft-tissue organ, implanted fiducials can change positions due to migration or tissue deformation. This study quantified positional variation of fiducials in IGRT for pancreatic cancer. Methods: 20 patients had at least 3 gold fiducials implanted in pancreas under EUS guidance. Patients had 4D-CT simulation for gated treatment. Daily gated OBI kV images (Turebeam) were used for positional alignment with fiducials for total of 25 or 28 fractions. Relative distances among 3 fiducials (d{sub 1–} {sub 2}, d{sub 1–3}, d{sub 2–3}) were measured from 4D-CT end-of-expiration phase bin; and from gated kV images in first, mid, and last fraction (n=180). Results: The median duration between implant and simulation was 11 (range 0–41) days. The median duration between simulation and first fraction was 17 (range 8–24) days. The median relative distance was 12 (range 4–78) mm for d{sub 1–2}, 24 (range 6–80) mm for d{sub 1–3}, and 19 (range 5–63) mm for d{sub 2–3}. The median deviation was 1 mm for d{sub 1–2}, d{sub 1–3}, d{sub 2–3} between simulation and first fraction, first and mid fraction, mid and last fraction (n=180). Two patients (10%) had deviation >= 5 mm (5, 11 mm) between simulation and first fraction. One patient (5%) had deviation >= 5 mm (11 mm) between first and mid fraction. No patient (0%) had deviation >= 5 mm between mid and last fraction. In all 3 cases with deviation >=5 mm, only one fiducial was significantly deviated. No clear evidence that deviation size was associated with time interval between implant and first fraction. Conclusion: Implanted gold fiducials were quite stable over time in their relative positions in pancreas. Our data suggested at least 3 fiducials are needed. In cases that one fiducial was significantly deviated in daily kV images, this fiducial should be excluded in image guidance.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-131: Reproducibility of Positioning Error Due to Temporarily Indwelled Urethral Catheter for Urethra-Sparing Prostate IMRT

Purpose: The purpose of this study was to prospectively assess the reproducibility of positioning errors due to temporarily indwelled catheter in urethra-sparing image-guided (IG) IMRT. Methods: Ten patients received urethra-sparing prostate IG-IMRT with implanted fiducials. After the first CT scan was performed in supine position, 6-Fr catheter was indwelled into urethra, and the second CT images were taken for planning. While the PTV received 80 Gy, 5% dose reduction was applied for the urethral PRV along the catheter. Additional CT scans were also performed at 5th and 30th fraction. Positions of interests (POIs) were set on posterior edge of prostate at beam isocenter level (POI1) and cranial and caudal edge of prostatic urethra on the post-indwelled CT images. POIs were copied into the pre-indwelled, 5th and 30th fraction’s CT images after fiducial matching on these CT images. The deviation of each POI between pre- and post-indwelled CT and the reproducibility of prostate displacement due to catheter were evaluated. Results: The deviation of POI1 caused by the indwelled catheter to the directions of RL/AP/SI (mm) was 0.20±0.27/−0.64±2.43/1.02±2.31, respectively, and the absolute distances (mm) were 3.15±1.41. The deviation tends to be larger if closer to the caudal edge of prostate. Compared with the pre-indwelled CT scan, a median displacement of all POIs (mm) were 0.3±0.2/2.2±1.1/2.0±2.6 in the post-indwelled, 0.4±0.4/3.4±2.1/2.3±2.6 in 5th, and 0.5±0.5/1.7±2.2/1.9±3.1 in 30th fraction’s CT scan with a similar data distribution. There were 6 patients with 5-mm-over displacement in AP and/or CC directions. Conclusion: Reproducibility of positioning errors due to temporarily indwelling catheter was observed. Especially in case of patients with unusually large shifts by indwelling catheter at the planning process, treatment planning should be performed by using the pre-indwelled CT images with transferred contour of the urethra identified by post-indwelled CT images.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-208: Prompt Gamma Imaging-Based Prediction of Bragg Peak Position for Realistic Treatment Error Scenarios

Purpose: To quantify the accuracy in predicting the Bragg peak position using simulated in-room measurements of prompt gamma (PG) emissions for realistic treatment error scenarios that combine several sources of errors. Methods: Prompt gamma measurements by a knife-edge slit camera were simulated using an experimentally validated analytical simulation tool. Simulations were performed, for 143 treatment error scenarios, on an anthropomorphic phantom and a pencil beam scanning plan for nasal cavity. Three types of errors were considered: translation along each axis, rotation around each axis, and CT-calibration errors with magnitude ranging respectively, between −3 and 3 mm, −5 and 5 degrees, and between −5 and +5%. We investigated the correlation between the Bragg peak (BP) shift and the horizontal shift of PG profiles. The shifts were calculated between the planned (reference) position and the position by the error scenario. The prediction error for one spot was calculated as the absolute difference between the PG profile shift and the BP shift. Results: The PG shift was significantly and strongly correlated with the BP shift for 92% of the cases (p<0.0001, Pearson correlation coefficient R>0.8). Moderate but significant correlations were obtained for all cases that considered only CT-calibration errors and for 1 case that combined translation and CT-errors (p<0.0001, R ranged between 0.61 and 0.8). The average prediction errors for the simulated scenarios ranged between 0.08±0.07 and 1.67±1.3 mm (grand mean 0.66±0.76 mm). The prediction error was moderately correlated with the value of the BP shift (p=0, R=0.64). For the simulated scenarios the average BP shift ranged between −8±6.5 mm and 3±1.1 mm. Scenarios that considered combinations of the largest treatment errors were associated with large BP shifts. Conclusion: Simulations of in-room measurements demonstrate that prompt gamma profiles provide reliable estimation of the Bragg peak position for complex error scenarios. Yafei Xing and Luiza Bondar are funded by BEWARE grants from the Walloon Region. The work presents simulations results for a prompt gamma camera prototype developed by IBA.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Characterization of a monoclonal antibody specific to California serogroup orthobunyaviruses and development as a chimeric immunoglobulin M-positive control in human diagnostics

ABSTRACT California serogroup viruses (CSGVs) of medical importance in the United States include La Crosse virus, Jamestown Canyon virus (JCV), California encephalitis virus, and snowshoe hare virus. Current diagnosis of CSGVs relies heavily on serologic techniques for detecting immunoglobulin M (IgM), an indication of a recent CSGV infection. However, human-positive control sera reactive to viruses in the serogroup are scarce because detection of recent infections is rare. Here, we describe the development of new murine monoclonal antibodies (MAbs) reactive to CSGVs and the engineering of a human-murine chimeric antibody by combining the variable regions of the broadly CSGV cross-reactive murine MAb, 3-3B6/2-3B2 and the constant region of the human IgM. MAb 3-3B6/2-3B2 recognizes a tertiary epitope on the Gn/Gc heterodimer, and epitopes important in JCV neutralization were mapped to the Gc glycoprotein. This engineered human IgM constitutively expressed in a HEK-293 stable cell line can replace human-positive control sera in diagnostic serological techniques such as IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Compared to the parent murine MAbs, the human-chimeric IgM antibody had identical serological activity to CSGVs in ELISA and demonstrated equivalent reactivity compared to human immune sera in the MAC-ELISA. Importance Orthobunyaviruses in the California serogroup cause severe neurological disease in children and adults. While these viruses are known to circulate widely in North America, their occurrence is rare. Serological testing for CSGVs is hindered by the limited availability and volumes of human-positive specimens needed as controls in serologic assays. Here, we described the development of a murine monoclonal antibody cross-reactive to CSGVs engineered to contain the variable regions of the murine antibody on the backbone of human IgM. The chimeric IgM produced from the stably expressing HEK293 cell line was evaluated for use as a surrogate human-positive control in a serologic diagnostic test.

Microbiology↗