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At least 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Quantifying the accuracy of the tumor motion and area as a function of acceleration factor for the simulation of the dynamic keyhole magnetic resonance imaging method

Purpose: The dynamic keyhole is a new MR image reconstruction method for thoracic and abdominal MR imaging. To date, this method has not been investigated with cancer patient magnetic resonance imaging (MRI) data. The goal of this study was to assess the dynamic keyhole method for the task of lung tumor localization using cine-MR images reconstructed in the presence of respiratory motion. Methods: The dynamic keyhole method utilizes a previously acquired a library of peripheral k-space datasets at similar displacement and phase (where phase is simply used to determine whether the breathing is inhale to exhale or exhale to inhale) respiratory bins in conjunction with central k-space datasets (keyhole) acquired. External respiratory signals drive the process of sorting, matching, and combining the two k-space streams for each respiratory bin, thereby achieving faster image acquisition without substantial motion artifacts. This study was the first that investigates the impact of k-space undersampling on lung tumor motion and area assessment across clinically available techniques (zero-filling and conventional keyhole). In this study, the dynamic keyhole, conventional keyhole and zero-filling methods were compared to full k-space dataset acquisition by quantifying (1) the keyhole size required for central k-space datasets for constant image quality across sixty four cine-MRI datasets from nine lung cancer patients, (2) the intensity difference between the original and reconstructed images in a constant keyhole size, and (3) the accuracy of tumor motion and area directly measured by tumor autocontouring. Results: For constant image quality, the dynamic keyhole method, conventional keyhole, and zero-filling methods required 22%, 34%, and 49% of the keyhole size (P < 0.0001), respectively, compared to the full k-space image acquisition method. Compared to the conventional keyhole and zero-filling reconstructed images with the keyhole size utilized in the dynamic keyhole method, an average intensity difference of the dynamic keyhole reconstructed images (P < 0.0001) was minimal, and resulted in the accuracy of tumor motion within 99.6% (P < 0.0001) and the accuracy of tumor area within 98.0% (P < 0.0001) for lung tumor monitoring applications. Conclusions: This study demonstrates that the dynamic keyhole method is a promising technique for clinical applications such as image-guided radiation therapy requiring the MR monitoring of thoracic tumors. Based on the results from this study, the dynamic keyhole method could increase the imaging frequency by up to a factor of five compared with full k-space methods for real-time lung tumor MRI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

4D-CT scans reveal reduced magnitude of respiratory liver motion achieved by different abdominal compression plate positions in patients with intrahepatic tumors undergoing helical tomotherapy

Purpose: While abdominal compression (AC) can be used to reduce respiratory liver motion in patients receiving helical tomotherapy for hepatocellular carcinoma, the nature and extent of this effect is not well described. The purpose of this study was to evaluate the changes in magnitude of three-dimensional liver motion with abdominal compression using four-dimensional (4D) computed tomography (CT) images of several plate positions. Methods: From January 2012 to October 2015, 72 patients with intrahepatic carcinoma and divided into four groups underwent 4D-CT scans to assess respiratory liver motion. Of the 72 patients, 19 underwent abdominal compression of the cephalic area between the subxiphoid and umbilicus (group A), 16 underwent abdominal compression of the caudal region between the subxiphoid area and the umbilicus (group B), 11 patients underwent abdominal compression of the caudal umbilicus (group C), and 26 patients remained free breathing (group D). 4D-CT images were sorted into ten-image series, according to the respiratory phase from the end inspiration to the end expiration, and then transferred to treatment planning software. All liver contours were drawn by a single physician and confirmed by a second physician. Liver relative coordinates were automatically generated to calculate the liver respiratory motion in different axial directions to compile the 10 ten contours into a single composite image. Differences in respiratory liver motion were assessed with a one-way analysis of variance test of significance. Results: The average respiratory liver motion in the Y axial direction was 4.53 ± 1.16, 7.56 ± 1.30, 9.95 ± 2.32, and 9.53 ± 2.62 mm in groups A, B, C, and D, respectively, with a significant change among the four groups (p < 0.001). Abdominal compression was most effective in group A (compression plate on the subxiphoid area), with liver displacement being 2.53 ± 0.93, 4.53 ± 1.16, and 2.14 ± 0.92 mm on the X-, Y-, and Z-axes, respectively. There was no significant difference in respiratory liver motion between group C (displacement: 3.23 ± 1.47, 9.95 ± 2.32, and 2.92 ± 1.10 mm on the X-, Y-, and Z-axes, respectively) and group D (displacement: 3.35 ± 1.55, 9.53 ± 2.62, and 3.35 ± 1.73 mm on the X-, Y-, and Z-axes, respectively). Abdominal compression was least effective in group C (compression on caudal umbilicus), with liver motion in this group similar to that of free-breathing patients (group D). Conclusions: 4D-CT scans revealed significant liver motion control via abdominal compression of the subxiphoid area; however, this control of liver motion was not observed with compression of the caudal umbilicus. The authors, therefore, recommend compression of the subxiphoid area in patients undergoing external radiotherapy for intrahepatic carcinoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-D-207A-07: The Effects of Inter-Cycle Respiratory Motion Variation On Dose Accumulation in Single Fraction MR-Guided SBRT Treatment of Renal Cell Carcinoma

Purpose: To assess the dose deposition in simulated single-fraction MR-Linac treatments of renal cell carcinoma, when inter-cycle respiratory motion variation is taken into account using online MRI. Methods: Three motion characterization methods, with increasing complexity, were compared to evaluate the effect of inter-cycle motion variation and drifts on the accumulated dose for an SBRT kidney MR-Linac treatment: 1) STATIC, in which static anatomy was assumed, 2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, based on the respiratory phase and 3) PCA, in which 3D volumes were generated using a PCA-model, enabling the detection of inter-cycle variations and drifts. An experimental ITV-based kidney treatment was simulated in a 1.5T magnetic field on three volunteer datasets. For each volunteer a retrospectively sorted 4D-MRI (ten respiratory phases) and fast 2D cine-MR images (temporal resolution = 476ms) were acquired to simulate MR-imaging during radiation. For each method, the high spatio-temporal resolution 3D volumes were non-rigidly registered to obtain deformation vector fields (DVFs). Using the DVFs, pseudo-CTs (generated from the 4D-MRI) were deformed and the dose was accumulated for the entire treatment. The accuracies of all methods were independently determined using an additional, orthogonal 2D-MRI slice. Results: Motion was most accurately estimated using the PCA method, which correctly estimated drifts and inter-cycle variations (RMSE=3.2, 2.2, 1.1mm on average for STATIC, AVG-RESP and PCA, compared to the 2DMRI slice). Dose-volume parameters on the ITV showed moderate changes (D99=35.2, 32.5, 33.8Gy for STATIC, AVG-RESP and PCA). AVG-RESP showed distinct hot/cold spots outside the ITV margin, which were more distributed for the PCA scenario, since inter-cycle variations were not modeled by the AVG-RESP method. Conclusion: Dose differences were observed when inter-cycle variations were taken into account. The increased inter-cycle randomness in motion as captured by the PCA model mitigates the local (erroneous) hotspots estimated by the AVG-RESP method.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-P-32: A Phantom Study of Accuracy of Four-Dimensional Cone-Beam CT (4D-CBCT) Vs. Three-Dimensional Cone Beam CT (3D-CBCT) in Image Guided Radiotherapy

Purpose: SymmetryTM 4D IGRT system of Elekta has been installed at our institution, which offers the 4D CBCT registration option. This study is to evaluate the accuracy of 4D CBCT system by using the CIRS 4D motion phantom and to perform a feasibility study on the implementation of 4D-CBCT as image guidance for SBRT treatment. Methods: The 3D and 4D CT image data sets are acquired using the CIRS motion phantom on a Philips large bore CT simulator. The motion was set as 0.5 cm superior and inferior directions with 6 seconds recycle time. The 4D CT data were sorted as 10 phases. One identifiable part of the 4D CT QA insert from CIRS phantom was used as the target. The ITV MIP was drawn based on maximum intensity projection (MIP) and transferred as a planning structure into 4D CBCT system. Then the 3D CBCT and 4D CBCT images were taken and registered with the free breath (3D), MIP (4D) and average intensity projection (AIP)(4D) reference data sets. The couch shifts (X, Y, Z) are recorded and compared. Results: Table 1 listed the twelve couch shifts based on the registration of MIP, AIP and free breath CT data sets with 3D CBCT and 4D CBCT for both whole body and local registration. X, Y and Z represent couch shifts in the direction of the right-left, superior-inferior and anterior-posterior. The biggest differences of 0.73 cm and 0.57 cm are noted in the free breath CT data with 4D CBCT and 3D CBCT data registration. Fig. 1 and Fig. 2 are the shift analysis in diagram. Fig. 3 shows the registration. Conclusion: Significant differences exist in the shifts corresponding with the direction of target motion. Further investigations are ongoing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-R-46: Predicting Distant Failure in Lung SBRT Using Multi-Objective Radiomics Model

Purpose: To predict distant failure in lung stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC) by using a new multi-objective radiomics model. Methods: Currently, most available radiomics models use the overall accuracy as the objective function. However, due to data imbalance, a single object may not reflect the performance of a predictive model. Therefore, we developed a multi-objective radiomics model which considers both sensitivity and specificity as the objective functions simultaneously. The new model is used to predict distant failure in lung SBRT using 52 patients treated at our institute. Quantitative imaging features of PET and CT as well as clinical parameters are utilized to build the predictive model. Image features include intensity features (9), textural features (12) and geometric features (8). Clinical parameters for each patient include demographic parameters (4), tumor characteristics (8), treatment faction schemes (4) and pretreatment medicines (6). The modelling procedure consists of two steps: extracting features from segmented tumors in PET and CT; and selecting features and training model parameters based on multi-objective. Support Vector Machine (SVM) is used as the predictive model, while a nondominated sorting-based multi-objective evolutionary computation algorithm II (NSGA-II) is used for solving the multi-objective optimization. Results: The accuracy for PET, clinical, CT, PET+clinical, PET+CT, CT+clinical, PET+CT+clinical are 71.15%, 84.62%, 84.62%, 85.54%, 82.69%, 84.62%, 86.54%, respectively. The sensitivities for the above seven combinations are 41.76%, 58.33%, 50.00%, 50.00%, 41.67%, 41.67%, 58.33%, while the specificities are 80.00%, 92.50%, 90.00%, 97.50%, 92.50%, 97.50%, 97.50%. Conclusion: A new multi-objective radiomics model for predicting distant failure in NSCLC treated with SBRT was developed. The experimental results show that the best performance can be obtained by combining all features.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-J-115: Target Volume and Artifact Evaluation of a New Device-Less 4D CT Algorithm

Purpose: 4DCT is often used in radiation therapy treatment planning to define the extent of motion of the visible tumor (IGTV). Recent available software allows 4DCT images to be created without the use of an external motion surrogate. This study aims to compare this device-less algorithm to a standard device-driven technique (RPM) in regards to artifacts and the creation of treatment volumes. Methods: 34 lung cancer patients who had previously received a cine 4DCT scan on a GE scanner with an RPM determined respiratory signal were selected. Cine images were sorted into 10 phases based on both the RPM signal and the device-less algorithm. Contours were created on standard and device-less maximum intensity projection (MIP) images using a region growing algorithm and manual adjustment to remove other structures. Variations in measurements due to intra-observer differences in contouring were assessed by repeating a subset of 6 patients 2 additional times. Artifacts in each phase image were assessed using normalized cross correlation at each bed position transition. A score between +1 (artifacts “better” in all phases for device-less) and −1 (RPM similarly better) was assigned for each patient based on these results. Results: Device-less IGTV contours were 2.1 ± 1.0% smaller than standard IGTV contours (not significant, p = 0.15). The Dice similarity coefficient (DSC) was 0.950 ± 0.006 indicating good similarity between the contours. Intra-observer variation resulted in standard deviations of 1.2 percentage points in percent volume difference and 0.005 in DSC measurements. Only two patients had improved artifacts with RPM, and the average artifact score (0.40) was significantly greater than zero. Conclusion: Device-less 4DCT can be used in place of the standard method for target definition due to no observed difference between standard and device-less IGTVs. Phase image artifacts were significantly reduced with the device-less method.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-J-117: Impact of Motion Artifacts On Image Quality and Accuracy of Tumor Motion Reconstruction in 4D CT-On-Rails and MV-CBCT Scans: A Phantom Study

Purpose: To compare and quantify respiratory motion artifacts in images from free breathing 4D-CT-on-Rails(CTOR) and those from MV-Cone-beam-CT(MVCB) and facilitate respiratory motion guided radiation therapy. Methods: 4D-CTOR: Siemens Somatom CT-on-Rails system with Anzai belt loaded with pressure sensor load cells. 4D scans were performed in helical mode, pitch 0.1, gantry rotation time 0.5s, 1.5mm slice thickness, 120kVp, 400 mAs. Normal and fast breathing (>12rpm) scanning protocols were investigated. Helical scan, AIP(average intensity projection) and MIP(maximum intensity projection) were generated from 4D-CTOR scans with amplitude sorting into 10 phases.MVCB: Siemens Artiste diamond view(1MV)MVCB was performed with 5MU thorax protocol with 60 second of full rotation.Phantom: Anzai AZ-733V respiratory phantom. The settings were set to normal and resp. modes with repetition rates at 15 rpm and 10 rpm. Surgical clips, acrylic, wooden, rubber and lung density, total six mock-ups were scanned and compared in this study.Signal-to-noise ratio(SNR), contrast-to-noise ratio(CNR) and reconstructed motion volume were compared to different respiratory setups for the mock-ups. Results: Reconstructed motion volume was compared to the real object volume for the six test mock-ups. It shows that free breathing helical in all instances underestimates the object excursions largest to −67.4% and least −6.3%. Under normal breathing settings, MIP can predict very precise motion volume with minimum 0.4% and largest −13.9%. MVCB shows underestimate of the motion volume with −1.11% minimum and −18.0% maximum. With fast breathing, AIP provides bad representation of the object motion; however, the MIP can predict the motion volume with −2.0% to −11.4% underestimate. Conclusion: Respiratory motion guided radiation therapy requires good motion recording. This study shows that regular CTOR helical scans provides bad guidance, 4D CTOR AIP cannot represent the fast breathing pattern, MIP can represent the best motion volume, MVCBCT can only be used for normal breathing with acceptable uncertainties.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-96: A New Paradigm of Weekly Chart Checking for Radiation Therapy Clinics

Purpose: To put forth an innovative clinical paradigm for weekly chart checking so that treatment status is periodically checked accurately and efficiently. This study also aims to help optimize the chart checking clinical workflow in a busy radiation therapy clinic. Methods: It is mandated by the Texas Administrative code to check patient charts of radiation therapy once a week or every five fractions, however it varies drastically among institutions in terms of when and how it is done. Some do it every day, but a lot of efforts are wasted on opening ineligible charts; some do it on a fixed day but the distribution of intervals between subsequent checks is not optimal. To establish an optimal chart checking procedure, a new paradigm was developed to achieve 1) charts are checked more accurately and more efficiently; 2) charts are checked on optimal days without any miss; 3) workload is evened out throughout a week when multiple physicists are involved. All active charts will be accessed by querying the R&V system. Priority is assigned to each chart based on the number of days before the next due date followed by sorting and workload distribution steps. New charts are also taken into account when distributing the workload so it is reasonably even throughout the week. Results: Our clinical workflow became more streamlined and smooth. In addition, charts get checked in a more timely fashion so that errors would get caught earlier should they occur. Conclusion: We developed a new weekly chart checking diagram. It helps physicists check charts in a timely manner, saves their time in busy clinics, and consequently reduces possible errors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-121: Abdominal Compression Effectively Reduces the Interplay Effect and Enables Pencil Beam Scanning Proton Therapy of Liver Tumors

Purpose: To study if abdominal compression can reduce breathing motion and mitigate interplay effect in pencil beam scanning proton therapy (PBSPT) treatment of liver tumors in order to better spare healthy liver volumes compared with photon therapy. Methods: Ten patients, six having large tumors initially treated with IMRT and four having small tumors treated with SBRT, were replanned for PBSPT. ITV and beam-specific PTVs based on 4D-CT were used to ensure target coverage in PBSPT. The use of an abdominal compression belt and volumetric repainting was investigated to mitigate the interplay effect between breathing motion and PBSPT dynamic delivery. An in-house Matlab script has been developed to simulate this interplay effect. The dose is computed on each phase individually by sorting all spots according to their simulated delivery timing. The final dose distribution is then obtained by accumulating all dose maps to a reference phase. Results: For equivalent target coverage PBSPT reduced average healthy liver dose by 9.5% of the prescription dose compared with IMRT/SBRT. Abdominal compression of 113.2±42.2 mmHg was effective for all 10 patients and reduced average motion by 2.25 mm. As a result, the average ITV volume decreased from 128.2% to 123.1% of CTV volume. Similarly, the average beam-specific PTV volume decreased from 193.2% to 183.3%. For 8 of the 10 patients, the average motion was reduced below 5 mm, and up to 3 repainting were sufficient to mitigate interplay. For the other two patients with larger residual motion, 4–5 repainting were needed. Conclusion: We recommend evaluation of the 4DCT motion histogram following simulation and the interplay effect following treatment planning in order to personalize the use of compression and volumetric repainting for each patient. Abdominal compression enables safe and more effective PBS treatment of liver tumors by reduction of motion and interplay effect. Kevin Souris is supported by IBA and Televie Grant from F.R.S.-FNRS. Liyong Lin is partially supported by Varian.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-463: Light-Field Based Dynalog Verification

Purpose: To independently verify leaf positions in so-called dynalog files for a Varian iX linac with a Millennium 120 MLC. This verification provides a measure of confidence that the files can be used directly as part of a more extensive intensity modulated radiation therapy / volumetric modulated arc therapy QA program. Methods: Initial testing used white paper placed at the collimator plane and a standard hand-held digital camera to image the light and shadow of a static MLC field through the paper. Known markings on the paper allow for image calibration. Noise reduction was attempted with removal of ‘inherent noise’ from an open-field light image through the paper, but the method was found to be inconsequential. This is likely because the environment could not be controlled to the precision required for the sort of reproducible characterization of the quantum noise needed in order to meaningfully characterize and account for it. A multi-scale iterative edge detection algorithm was used for localizing the leaf ends. These were compared with the planned locations from the treatment console. Results: With a very basic setup, the image of the central bank A leaves 15–45, which are arguably the most important for beam modulation, differed from the planned location by [0.38±0.28] mm. Similarly, for bank B leaves 15–45 had a difference of [0.42±0.28] mm Conclusion: It should be possible to determine leaf position accurately with not much more than a modern hand-held camera and some software. This means we can have a periodic and independent verification of the dynalog file information. This is indicated by the precision already achieved using a basic setup and analysis methodology. Currently, work is being done to reduce imaging and setup errors, which will bring the leaf position error down further, and allow meaningful analysis over the full range of leaves.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-G-BRA-11: Tumor Tracking in An Iterative Volume of Interest Based 4D CBCT Reconstruction

Purpose: 4D CBCT can allow evaluation of tumor motion immediately prior to radiation therapy, but suffers from heavy artifacts that limit its ability to track tumors. Various iterative and compressed sensing reconstructions have been proposed to reduce these artifacts, but are costly time-wise and can degrade the image quality of bony anatomy for alignment with regularization. We have previously proposed an iterative volume of interest (I4D VOI) method which minimizes reconstruction time and maintains image quality of bony anatomy by focusing a 4D reconstruction within a VOI. The purpose of this study is to test the tumor tracking accuracy of this method compared to existing methods. Methods: Long scan (8–10 mins) CBCT data with corresponding RPM data was collected for 12 lung cancer patients. The full data set was sorted into 8 phases and reconstructed using FDK cone beam reconstruction to serve as a gold standard. The data was reduced in way that maintains a normal breathing pattern and used to reconstruct 4D images using FDK, low and high regularization TV minimization (λ=2,10), and the proposed I4D VOI method with PTVs used for the VOI. Tumor trajectories were found using rigid registration within the VOI for each reconstruction and compared to the gold standard. Results: The root mean square error (RMSE) values were 2.70mm for FDK, 2.50mm for low regularization TV, 1.48mm for high regularization TV, and 2.34mm for I4D VOI. Streak artifacts in I4D VOI were reduced compared to FDK and images were less blurred than TV reconstructed images. Conclusion: I4D VOI performed at least as well as existing methods in tumor tracking, with the exception of high regularization TV minimization. These results along with the reconstruction time and outside VOI image quality advantages suggest I4D VOI to be an improvement over existing methods. Funding support provided by CPRIT grant RP110562-P2-01.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-DE-207A-06: ECG-Gated CT Reconstruction for a C-Arm Inverse Geometry X-Ray System

Purpose: To obtain ECG-gated CT images from truncated projection data acquired with a C-arm based inverse geometry fluoroscopy system, for the purpose of cardiac chamber mapping in interventional procedures. Methods: Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system with a scanned multisource x-ray tube and a photon-counting detector mounted to a C-arm. In the proposed method, SBDX short-scan rotational acquisition is performed followed by inverse geometry CT (IGCT) reconstruction and segmentation of contrast-enhanced objects. The prior image constrained compressed sensing (PICCS) framework was adapted for IGCT reconstruction to mitigate artifacts arising from data truncation and angular undersampling due to cardiac gating. The performance of the reconstruction algorithm was evaluated in numerical simulations of truncated and non-truncated thorax phantoms containing a dynamic ellipsoid to represent a moving cardiac chamber. The eccentricity of the ellipsoid was varied at frequencies from 1–1.5 Hz. Projection data were retrospectively sorted into 13 cardiac phases. Each phase was reconstructed using IGCT-PICCS, with a nongated gridded FBP (gFBP) prior image. Surface accuracy was determined using Dice similarity coefficient and a histogram of the point distances between the segmented surface and ground truth surface. Results: The gated IGCT-PICCS algorithm improved surface accuracy and reduced streaking and truncation artifacts when compared to nongated gFBP. For the non-truncated thorax with 1.25 Hz motion, 99% of segmented surface points were within 0.3 mm of the 15 mm diameter ground truth ellipse, versus 1.0 mm for gFBP. For the truncated thorax phantom with a 40 mm diameter ellipse, IGCT-PICCS surface accuracy measured 0.3 mm versus 7.8 mm for gFBP. Dice similarity coefficient was 0.99–1.00 (IGCT-PICCS) versus 0.63–0.75 (gFBP) for intensity-based segmentation thresholds ranging from 25–75% maximum contrast. Conclusions: The PICCS algorithm was successfully applied to reconstruct truncated IGCT projection data with angular undersampling resulting from simulated cardiac gating. Research supported by the National Heart, Lung, and Blood Institute of the NIH under award number R01HL084022. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-FG-CAMPUS-JeP3-05: Evaluation of 4D CT-On-Rails Target Localization Methods for Free Breathing Liver Stereotactic Body Radiotherapy (SBRT)

Purpose: Liver SBRT patients unable to tolerate breath-hold for radiotherapy are treated free-breathing with image guidance. Target localization using 3D CBCT requires extra margins to accommodate the respiratory motion. The purpose of this study is to evaluate the accuracy and reproducibility of 4D CT-on-rails in target localization for free-breathing liver SBRT. Methods: A Siemens SOMATOM CT-on-Rails 4D with Anzai Pressure Belt system was used both as the simulation and the localization CT. Fiducial marker was placed close to the center of the target prior to the simulation. Amplitude based sorting was used in the scan. Eight or sixteen phases of reconstructed CT sets (depends on breathing pattern) can be sent to Velocity to create the maximum intensity projection (MIP) image set. Target ITV and fiducial ITV were drawn based on the MIP image. In patient localization, a 4D scan was taken with the same settings as the sim scan. Images were registered to match fiducial ITVs. Results: Ten liver cancer patients treated for 50Gy over 5 fractions, with amplitudes of breathing motion ranging from 4.3–14.5 mm, were analyzed in this study. Results show that the Intra & inter fraction variability in liver motion amplitude significantly less than the baseline inter-fraction shifts in liver position. 90% of amplitude change is less than 3 mm. The differences in the D99 and D95 GTV dose coverage between the 4D CT-on-Rails and the CBCT plan were small (within 5%) for all the selected cases. However, the average PTV volume by using the 4D CT-on-Rails is 37% less than the CBCT PTV volume. Conclusion: Simulation and Registration using 4D CT-on-Rails provides accurate target localization and is unaffected by larger breathing amplitudes as seen with 3D CBCT image registration. Localization with 4D CT-on-Rails can significantly reduce the PTV volume with sufficient tumor.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TH-AB-202-04: Auto-Adaptive Margin Generation for MLC-Tracked Radiotherapy

Purpose: To develop an auto-adaptive margin generator for MLC tracking. The generator is able to estimate errors arising in image guided radiotherapy, particularly on an MR-Linac, which depend on the latencies of machine and image processing, as well as on patient motion characteristics. From the estimated error distribution, a segment margin is generated, able to compensate errors up to a user-defined confidence. Method: In every tracking control cycle (TCC, 40ms), the desired aperture D(t) is compared to the actual aperture A(t), a delayed and imperfect representation of D(t). Thus an error e(t)=A(T)-D(T) is measured every TCC. Applying kernel-density-estimation (KDE), the cumulative distribution (CDF) of e(t) is estimated. With CDF-confidence limits, upper and lower error limits are extracted for motion axes along and perpendicular leaf-travel direction and applied as margins. To test the dosimetric impact, two representative motion traces were extracted from fast liver-MRI (10Hz). The traces were applied onto a 4D-motion platform and continuously tracked by an Elekta Agility 160 MLC using an artificially imposed tracking delay. Gafchromic film was used to detect dose exposition for static, tracked, and error-compensated tracking cases. The margin generator was parameterized to cover 90% of all tracking errors. Dosimetric impact was rated by calculating the ratio between underexposed points (>5% underdosage) to the total number of points inside FWHM of static exposure. Results: Without imposing adaptive margins, tracking experiments showed a ratio of underexposed points of 17.5% and 14.3% for two motion cases with imaging delays of 200ms and 300ms, respectively. Activating the margin generated yielded total suppression (<1%) of underdosed points. Conclusion: We showed that auto-adaptive error compensation using machine error statistics is possible for MLC tracking. The error compensation margins are calculated on-line, without the need of assuming motion or machine models. Further strategies to reduce consequential overdosages are currently under investigation. This work was funded by the SoRTS consortium, which includes the industry partners Elekta, Philips and Technolution.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Serial-femtosecond crystallography reveals how a phytochrome variant couples chromophore and protein structural changes

The photoreaction and commensurate structural changes of a chromophore within biological photoreceptors elicit conformational transitions of the protein promoting the switch between deactivated and activated states. We investigated how this coupling is achieved in a bacterial phytochrome variant, Agp2-PAiRFP2. Contrary to classical protein crystallography, which only allows probing (cryo-trapped) stable states, we have used time-resolved serial femtosecond x-ray crystallography (tr-SFX) and pump-probe techniques with various illumination and delay times with respect to photoexcitation of the parent Pfr state. Thus, structural data for seven time frames were sorted into groups of molecular events along the reaction coordinate. They range from chromophore isomerization to the formation of Meta-F, the intermediate that precedes the functional relevant secondary structure transition of the tongue. Structural data for the early events were used to calculate the photoisomerization pathway to complement the experimental data. Late events allow identifying the molecular switch that is linked to the intramolecular proton transfer as a prerequisite for the following structural transitions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Magnetically responsive nanocultures for direct microbial assessment in soil environments

Cultivating microorganisms in native-like conditions is vital for bioprospecting and accessing now unculturable species. However, there remains a gap in scalable tools that can both mimic native microenvironments and enable targeted recovery of microbes from complex settings. Such approaches are essential to advance our understanding of microbial ecology, predict community functions, and discover previously unidentified biotherapeutics. We present magnetic nanocultures—a high-throughput microsystem for isolating and growing environmental microbes under near-native conditions. These nanoliter-scale bioreactors are encapsulated in semipermeable membranes that form magnetic polymeric microcapsules using iron oxide nanoparticles within polydimethylsiloxane-based shells. This design offers mechanical stability and magnetic actuation, enabling efficient retrieval from soil-like environments. The nanocultures are optimized for optical and biological properties to support microbial encapsulation, growth, and sorting. Our study demonstrates the feasibility of using magnetically responsive microenvironments to cultivate elusive microbes, offering a promising platform for bioprospecting previously uncultured or unknown microbial species.

Usman, Huda [Department of Chemical Engineering, C↗
DOE OSTI2017

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma

Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1–specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1–infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains. external region (MPER) have extensive neutralization breadth, and one of these, 10E8, reactive to the distal MPER, is one of the most broadly reactive HIV-1–neutralizing antibodies isolated to date (1–3). Two other MPER-binding gp41 bnAbs, 2F5 and 4E10, are both polyreactive, and their expression is limited by immune tolerance control in bnAb knock-in mice (4–7). In contrast, the 10E8 bnAb, in addition to potency and breadth, has lower reactivity with host molecules than 2F5 and 4E10 (1, 8–10). Thus, vaccine strategies for induction of 10E8-like antibodies are key to the development of an HIV-1 vaccine that can induce multiple broad and potent neutralizing antibody specificities. Here, we have isolated a clonal lineage (DH511) of broad and potent Env gp41 distal MPER bnAbs from both memory B cells and plasma from an HIV-1–infected African individual, defined the DH511 developmental pathway, and demonstrated the reactivity of the DH511 unmutated common ancestor (UCA) with the A subunit of the autoantigen ribonucleoprotein (RNP), providing a mechanism of bnAb induction. Finally, plasma DH511 bnAb lineage members were equally as potent neutralizers of HIV-1 as were bnAbs derived from memory B cells. Moreover, a chimeric DH511 lineage antibody consisting of memory bnAb V H [variable region of immunoglobulin (Ig) heavy chain] and plasma bnAb V L (variable region of Ig light chain) was broader than 10E8 and neutralized 99% of the HIV-1 isolates tested.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Community Structure and Microbial Associations in Sediment-Free Methanotrophic Enrichment Cultures from a Marine Methane Seep

We report Syntrophic consortia of anaerobic methanotrophic archaea (ANME) and sulfate-reducing bacteria (SRB) consume large amounts of methane and serve as the foundational microorganisms in marine methane seeps. Despite their importance in the carbon cycle, research on the physiology of ANME-SRB consortia has been hampered by the slow growth and complex physicochemical environment the consortia inhabit. Here, we report successful sediment-free enrichment of ANME-SRB consortia from deep-sea methane seep sediments in the Santa Monica Basin, California. Anoxic Percoll density gradients and size-selective filtration were used to separate ANME-SRB consortia from sediment particles and single cells to accelerate the cultivation process. Over a 3-year period, a subset of the sediment-associated ANME and SRB lineages, predominantly comprised of ANME-2a/2b (“Candidatus Methanocomedenaceae”) and their syntrophic bacterial partners, SEEP-SRB1/2, adapted and grew under defined laboratory conditions. Metagenome-assembled genomes from several enrichments revealed that ANME-2a, SEEP-SRB1, and Methanococcoides in different enrichments from the same inoculum represented distinct species, whereas other coenriched microorganisms were closely related at the species level. This suggests that ANME, SRB, and Methanococcoides are more genetically diverse than other members in methane seeps. Flow cytometry sorting and sequencing of cell aggregates revealed that Methanococcoides, Anaerolineales, and SEEP-SRB1 were overrepresented in multiple ANME-2a cell aggregates relative to the bulk metagenomes, suggesting they were physically associated and possibly interacting. Overall, this study represents a successful case of selective cultivation of anaerobic slow-growing microorganisms from sediments based on their physical characteristics, introducing new opportunities for detailed genomic, physiological, biochemical, and ecological analyses. Biological anaerobic oxidation of methane (AOM) coupled with sulfate reduction represents a large methane sink in global ocean sediments. Methane consumption is carried out by syntrophic archaeal-bacterial consortia and fuels a unique ecosystem, yet the interactions in these slow-growing syntrophic consortia and with other associated community members remain poorly understood. The significance of this study is the establishment of sediment-free enrichment cultures of anaerobic methanotrophic archaea and sulfate-reducing bacteria performing AOM with sulfate using selective cultivation approaches based on size, density, and metabolism. By reconstructing microbial genomes and analyzing community composition of the enrichment cultures and cell aggregates, we shed light on the diversity of microorganisms physically associated with AOM consortia beyond the core syntrophic partners. These enrichment cultures offer simplified model systems to extend our understanding of the diversity of microbial interactions within marine methane seeps.

59 BASIC BIOLOGICAL SCIENCES↗