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A study was conducted to assess the validity of a simple sharp-kink approximation which relates the contact angle of a liquid on a surface to its density, its surface tension, and the effective molecule-surface potential. The equation might be applied to study the temperature-dependence of the contact angle for helium or alkali metal surfaces.

Purpose: Adaptive radiation therapy (ART) is the latest topic in a series of white papers published by the American Society for Radiation Oncology addressing quality processes and patient safety. ART widens the therapeutic index by improving precision of radiation dose to targets, allowing for dose escalation and/or minimization of dose to normal tissue. ART is performed via offline or online methods; offline ART is the process of replanning a patient's treatment plan between fractions, whereas online ART involves plan adjustment with the patient on the treatment table. This is achieved with in-room imaging capable of assessing anatomical changes and the ability to reoptimize the treatment plan rapidly during the treatment session. Although ART has occurred in its simplest forms in clinical practice for decades, recent technological developments have enabled more clinical applications of ART. With increased clinical prevalence, compressed timelines and associated complexity of ART, quality and safety considerations are an important focus area., Methods: ASTRO convened an interdisciplinary task force to provide expert consensus on key workflows and processes for ART. Recommendations were created using a consensus-building methodology and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters selecting "strongly agree" or "agree" indicated consensus. Content not meeting this threshold was removed or revised., Summary: Establishing and maintaining an adaptive program requires a team-based approach, appropriately trained and credentialed specialists as well as significant resources, specialized technology, and implementation time. A comprehensive quality assurance program must be developed, using established guidance, to make sure all forms of ART are performed in a safe and effective manner. Patient safety when delivering ART is everyone's responsibility and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to deliver the highest levels of quality and safety., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The purpose of this study was to investigate the technical feasibility of integrating the quantitative maps available from SyntheticMR into the head and neck adaptive radiation oncology workflow. While SyntheticMR has been investigated for diagnostic applications, no studies have investigated its feasibility and potential for MR-Simulation or MR-Linac workflow. Demonstrating the feasibility of using this technique will facilitate rapid quantitative biomarker extraction which can be leveraged to guide adaptive radiation therapy decision making., Approach: Two phantoms, two healthy volunteers, and one patient were scanned using SyntheticMR on the MR-Simulation and MR-Linac devices with scan times between four to six minutes. Images in phantoms and volunteers were conducted in a test/retest protocol. The correlation between measured and reference quantitative T1, T2, and PD values were determined across clinical ranges in the phantom. Distortion was also studied. Contours of head and neck organs-at-risk (OAR) were drawn and applied to extract T1, T2, and PD. These values were plotted against each other, clusters were computed, and their separability significance was determined to evaluate SyntheticMR for differentiating tumor and normal tissue., Main Results: The Lin's Concordance Correlation Coefficient between the measured and phantom reference values was above 0.98 for both the MR-Sim and MR-Linac. No significant levels of distortion were measured. The mean bias between the measured and phantom reference values across repeated scans was below 4% for T1, 7% for T2, and 4% for PD for both the MR-Sim and MR-Linac. For T1 vs. T2 and T1 vs. PD, the GTV contour exhibited perfect purity against neighboring OARs while being 0.7 for T2 vs. PD. All cluster significance levels between the GTV and the nearest OAR, the tongue, using the SigClust method was p < 0.001., Significance: The technical feasibility of SyntheticMR was confirmed. Application of this technique to the head and neck adaptive radiation therapy workflow can enrich the current quantitative biomarker landscape., Competing Interests: AD has received related research support from Elekta AB and unrelated royalties / licenses from Resoundant LLC. KH has received related investigational software / research support from SyntheticMR AB and unrelated research support from GE Healthcare. CDF has received related travel, speaker honoraria and/or registration fee waiver from: Elekta AB and unrelated travel, speaker honoraria and/or registration fee waiver from: The American Association for Physicists in Medicine; the University of Alabama-Birmingham; The American Society for Clinical Oncology; The Royal Australian and New Zealand College of Radiologists; The American Society for Radiation Oncology; The Radiological Society of North America; and The European Society for Radiation Oncology. CDF has received related direct industry grant/in-kind support, honoraria, and travel funding from Elekta AB and has served in an unrelated consulting capacity for Varian/Siemens Healthineers. Philips Medical Systems, and Oncospace, Inc.

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the acquisition. Iterative reconstruction with the subspace model and additional regularization of the signal representation in the subspace is performed to minimize the number of spokes and maintain matching quality and SNR. Reconstruction accuracy was assessed using the ISMRM NIST phantom. In-vivo validation was performed on two healthy subjects and two prostate cancer patients undergoing radiation therapy. The longitudinal repeatability was quantified using the concordance correlation coefficient (CCC) in one of the healthy subjects by repeated scans over 1 year. One prostate cancer patient was scanned at three time points, before initiating therapy and following brachytherapy and external beam radiation. Changes in the T1/T2 maps obtained with the proposed method were quantified. The prostate, peripheral and transitional zones, and visible dominant lesion were delineated for each study, and the statistics and distribution of the quantitative mapping values were analyzed. Significant image quality improvements compared with standard reconstruction methods were obtained with the proposed subspace reconstruction method. A notable decrease in the spread of the T1/T2 values without biasing the estimated mean values was observed with the subspace reconstruction and agreed with reported literature values. The subspace reconstruction enabled visualization of small differences in T1/T2 values in the tumor region within the peripheral zone. Longitudinal imaging of a volunteer subject yielded CCC of 0.89 for MRF T1, and 0.81 for MRF T2 in the prostate gland. Longitudinal imaging of the prostate patient confirmed the feasibility of capturing radiation treatment related changes. This work is a proof-of-concept for a high resolution and fast quantitative mapping using golden-angle radial MRF combined with a subspace reconstruction technique for longitudinal treatment response assessment in subjects undergoing radiation treatment., Competing Interests: Declaration of Competing Interest This work was performed as part of a master research agreement between MSKCC and Philips Healthcare. MB, MD, PM, and PK were employees of Philips Healthcare while making contributions to this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fragile X syndrome (FXS) is a pervasive developmental disorder and the most common monogenic cause of autism spectrum disorder (ASD). Female heterozygous (HET) carriers play a major role in the transmission of the pathology and present several FXS- and ASD-like behavioral alterations. Despite their clear genetic origins, FXS symptoms are known to be modulated by environmental factors, e.g., exposure to chronic stress, especially during critical life periods, such as pregnancy. Pregnancy, together with pups' care, constitutes maternal experience, i.e., another powerful environmental factor affecting several neurobehavioral functions in females. Here we investigated the impact of maternal experience on the long-term effects of stress in Fmr1 -HET female mice. Our findings demonstrated that the behavioral abnormalities of HET females, i.e., hyperactivity and memory deficits, were unaffected by stress or maternal experience. In contrast, stress, independently of maternal experience, induced the appearance of cognitive deficits in WT mice. Maternal experience increased anxiety levels in all mice and enhanced their corticosterone levels, concomitantly promoting the effects of stress on social communication and adrenal glands. In translational terms, these results advance our understanding of the environmental modulation of the behavioral alterations observed in FXS female carriers and highlight the long-term impact of maternal experience and its interactions with chronic stress.

Background: Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in radiation therapy for abdominal targets. Models for GI motility can improve the assessment of delivered dose and contribute to the development, testing, and validation of deformable image registration (DIR) and dose-accumulation algorithms., Purpose: To implement GI tract motion in the 4D extended cardiac-torso (XCAT) digital phantom of human anatomy., Materials and Methods: Motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery were identified based on literature research. Search criteria included amplitude changes larger than planning risk volume expansions and durations of the order of tens of minutes. The following modes were identified: peristalsis, rhythmic segmentation, high amplitude propagating contractions (HAPCs), and tonic contractions. Peristalsis and rhythmic segmentations were modeled by traveling and standing sinusoidal waves. HAPCs and tonic contractions were modeled by traveling and stationary Gaussian waves. Wave dispersion in the temporal and spatial domain was implemented by linear, exponential, and inverse power law functions. Modeling functions were applied to the control points of the nonuniform rational B-spline surfaces defined in the reference XCAT library. GI motility was combined with the cardiac and respiratory motions available in the standard 4D-XCAT phantom. Default model parameters were estimated based on the analysis of cine MRI acquisitions in 10 patients treated in a 1.5T MR-linac., Results: We demonstrate the ability to generate realistic 4D multimodal images that simulate GI motility combined with respiratory and cardiac motion. All modes of motility, except tonic contractions, were observed in the analysis of our cine MRI acquisitions. Peristalsis was the most common. Default parameters estimated from cine MRI were used as initial values for simulation experiments. It is shown that in patients undergoing stereotactic body radiotherapy for abdominal targets, the effects of GI motility can be comparable or larger than the effects of respiratory motion., Conclusion: The digital phantom provides realistic models to aid in medical imaging and radiation therapy research. The addition of GI motility will further contribute to the development, testing, and validation of DIR and dose accumulation algorithms for MR-guided radiotherapy., (© 2023 American Association of Physicists in Medicine.)

Background and Purpose: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps., Methods: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was formed to identify and evaluate failure modes for all the steps taken during a daily treatment workflow. Failure modes of high severity and overall score were isolated and addressed., Results: Mitigations were determined for high-ranking failure modes and implemented into the clinic. High-ranking failure modes existed in all steps of the workflow. Failure modes were then rescored to evaluate the effectiveness of the mitigations., Conclusion: Failure modes and effects analysis on the Unity MR-Linac highlighted areas in the ATP workflow that could be prone to failures and allowed our clinic to change the process to be more robust., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Introduction: Using an magnetic resonance linear accelerator (MR-Linac) may improve the precision of visible tumor boosting with ultra-hypofractionation by accounting for daily positional changes in the target and organs at risk (OAR)., Patients and Methods: Fifteen patients with prostate cancer and an MR-detected dominant lesion were treated on the MR-Linac with stereotactic body radiation (SBRT) to 40 Gy in 5 fractions, boosting the gross tumor volume (GTV) to 45 Gy with daily adaptive planning. Imaging was acquired again after initial planning (verification scan), and immediately after treatment (post-treatment scan). Prior to beam-on, additional adjustments were made on the verification scan. Contours were retrospectively adjusted on verification and post-treatment scans, and the daily plan recalculated on these scans to estimate the true dose delivered., Results: The median prostate D95% for plan 1, 2 and 3 was 40.3 Gy, 40.5 Gy and 40.3 Gy and DIL D95% was 45.7 Gy, 45.2 Gy and 44.6 Gy, respectively. Bladder filling was associated with reduced GTV coverage (p = 0.03, plan 1 vs 2) and prostate coverage (p = 0.03, plan 2 vs 3). The D0.035 cc constraint was exceeded on verification and post-treatment plans in 24 % and 33 % of fractions for the urethra, 31 % and 45 % for the bladder, and 35 % and 25 % for the rectum, respectively., Conclusion: MR-Linac guided, daily adaptive SBRT with focal boosting of the GTV yields acceptable planned and delivered dosimetry. Adaptive planning with a MR-Linac may reliably deliver the prescribed dose to the intended tumor target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Objective . To develop a respiratory motion-resolved four-dimensional (4D) magnetic resonance imaging (MRI) technique with high-isotropic-resolution (1.1 mm) using 3D radial sampling, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for lung cancer imaging. Approach . Free-breathing half- and full-spoke 3D golden-angle radial acquisitions were performed on eight healthy volunteers and eight patients with lung tumors of varying size. A back-and-forth k-space ordering between consecutive interleaves of the 3D radial acquisition was performed to minimize eddy current-related artifacts. Data were sorted into respiratory motion states using camera-based motion navigation and 4D images were reconstructed using temporal compressed sensing to reduce scan time. Normalized sharpness indices of the diaphragm, apparent signal-to-noise ratio (aSNR) and contrast-to-noise ratio (CNR) of the lung tumor (patients only), liver, and aortic arch were compared between half- and full-spoke 4D MRI images to evaluate the impact of respiratory motion and image contrast on 4D MRI image quality. Respiration-induced changes in lung volumes and center of mass shifts were compared between half- and full-spoke 4D MRI measurements. In addition, the motion measurements from 4D MRI and the same-day 4D CT were presented in one of the lung tumor patients. Main results . Half-spoke 4D MRI provides better visualization of the lung parenchyma, while full-spoke 4D MRI presents sharper diaphragm images and higher aSNR and CNR in the lung tumor, liver, and aortic arch. Lung volume changes and center of mass shifts measured by half- and full-spoke 4D MRI were not statistically different. For the patient with 4D MRI and same-day 4D CT, lung volume changes and center of mass shifts were generally comparable. Significance . This work demonstrates the feasibility of a motion-resolved 4D MRI technique with high-isotropic-resolution using 3D radial acquisition, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for treatment planning and motion monitoring in radiotherapy of lung cancer., (Creative Commons Attribution license.)

Background and Purpose: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy., Materials and Methods: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize spatial resolution and temporal blurring by limiting the extent of data sharing in the Fourier domain. Improvements in image quality are characterized by evaluating changes in signal-to-noise ratio (SNR), resolution, target detection, and level of artifact. The method is validated in simulations, in a dynamic phantom, and in-vivo imaging., Results: Sharing of high-frequency k-space data, driven by the average breathing curve, improves spatial resolution and reduces artifacts. Although equal sharing of k-space data improves resolution and SNR in stationary features, phases with large temporal changes accumulate significant artifacts due to averaging of high frequency features. In the absence of view-sharing, no averaging and detection artifacts are observed while spatial resolution is degraded., Conclusions: The use of a quasi-random sampling function, with view-sharing driven by the average breathing curve, provides a feasible method for self-navigated 4D-MRI at improved spatial resolution., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Fragile X syndrome (FXS) is a major neurodevelopmental disorder and the most common monogenic cause of autism spectrum disorder (ASD). FXS is caused by a mutation in the X-linked FMR1 gene leading to the absence of the FMRP protein, inducing several behavioral deficits, including motor, emotional, cognitive, and social abnormalities. Beside its clear genetic origins, FXS can be modulated by environmental factors, e.g., stress exposure: indeed the behavioral phenotype of FXS, as well as of ASD patients can be exacerbated by the repeated experience of stressful events, especially early in life. Here we investigated the long-term effects of prenatal exposure to unpredictable chronic stress on the behavioral phenotype of the Fmr1-knock-out (KO) mouse model for FXS and ASD. Mice were tested for FXS- and ASD-relevant behaviors first at adulthood (3 months) and then at aging (18 months), in order to assess the persistence and the potential time-related progression of the stress effects. Stress induced the selective emergence of behavioral deficits in Fmr1-KO mice that were evident in spatial memory only at aging. Stress also exerted several age-specific behavioral effects in mice of both genotypes: at adulthood it enhanced anxiety levels and reduced social interaction, while at aging it enhanced locomotor activity and reduced the complexity of ultrasonic calls. Our findings underline the relevance of gene-environment interactions in mouse models of neurodevelopmental syndromes and highlight the long-term behavioral impact of prenatal stress in laboratory mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Petroni, Subashi, Premoli, Memo, Lemaire and Pietropaolo.)

Purpose: To describe and report longitudinal quality assurance (QA) measurements for the magnetic resonance imaging (MRI) component of the Elekta Unity MR-linac during the first year of clinical use in our institution., Materials and Methods: The performance of the MRI component of Unity was evaluated with daily, weekly, monthly, and annual QA testing. The measurements monitor image uniformity, signal-to-noise ratio (SNR), resolution/detectability, slice position/thickness, linearity, central frequency, and geometric accuracy. In anticipation of routine use of quantitative imaging (qMRI), we characterize B0/B1 uniformity and the bias/reproducibility of longitudinal/transverse relaxation times (T1/T2) and apparent diffusion coefficient (ADC). Tolerance levels for QA measurements of qMRI biomarkers are derived from weekly monitoring of T1, T2, and ADC., Results: The 1-year assessment of QA measurements shows that daily variations in each MR quality metric are well below the threshold for failure. Routine testing procedures can reproducibly identify machine issues. The longitudinal three-dimensional (3D) geometric analysis reveals that the maximum distortion in a diameter of spherical volume (DSV) of 20, 30, 40, and 50 cm is 0.4, 0.6, 1.0, and 3.1 mm, respectively. The main source of distortion is gradient nonlinearity. Maximum peak-to-peak B0 inhomogeneity is 3.05 ppm, with gantry induced B0 inhomogeneities an order of magnitude smaller. The average deviation from the nominal B1 is within 2%, with minimal dependence on gantry angle. Mean ADC, T1, and T2 values are measured with high reproducibility. The median coefficient of variation for ADC, T1, and T2 is 1.3%, 1.1%, and 0.5%, respectively. The median bias for ADC, T1, and T2 is -0.8%, -0.1%, and 3.9%, respectively., Conclusion: The MRI component of Unity operates within the guidelines and recommendations for scanner performance and stability. Our findings support the recently published guidance in establishing clinically acceptable tolerance levels for image quality. Highly reproducible qMRI measurements are feasible in Unity., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Fragile X Syndrome (FXS) is the most common heritable form of mental retardation and monogenic cause of autism spectrum disorder (ASD). FXS is due to a mutation in the X-linked FMR1 gene and is characterized by motor, cognitive and social alterations, mostly overlapping with ASD behavioral phenotypes. The severity of these symptoms and their timing may be exacerbated and/or advanced by environmental adversity interacting with the genetic mutation. We therefore tested the effects of the prenatal exposure to unpredictable chronic stress on the behavioral phenotype of juveniles of both sexes in the Fmr1 knock-out (KO) mouse model of FXS. Mice underwent behavioral tests at 7-8 weeks of age, that is, when most of the relevant behavioral alterations are absent or mild in Fmr1-KOs. Stress induced the early appearance of deficits in spontaneous alternation in KO male mice, without exacerbating the behavioral phenotype of mutant females. In males stress also altered social interaction and communication, but mostly in WT mice, while in females it induced effects on locomotion and communication in mice of both genotypes. Our data therefore highlight the sex-dependent relevance of early environmental stressors to interact with genetic factors to influence the appearance of selected FXS- and ASD-like phenotypes., (© 2022. The Author(s).)

Purpose: The goal of this study was to evaluate the use of EBT-XD film for SRS/SBRT commissioning in a 1.5T hybrid MR-Linac (MRL)., Method: The output factors (S t ), from 1x1, 2x2, 3x3 cm 2 , were measured with film in solid water. The results were compared with (1) the measurements by a PTW diamond detector (CVD) and an Exradin® A26MR ion chamber in 3D water phantom; (2) Monte Carlo calculation by Monaco TPS (MTPS) in water. The inline (IN) and crossline (CR) profiles, measured by films and the CVD, were also compared. An SRS plan with two targets was created in MTPS and was measured with EBT-XD film in a StereoPHAN TM phantom serving as an end-to-end test. The 3x3 cm 2 was used for film calibration with doses ranging from 0 to 28 Gy. Water was added to the phantom-film-phantom interface to reduce the electron-return-effect (ERE). Films were calibrated with One-scan-dosimetry protocol., Results: The film S t were within 1.2% and 2.2% compared to other detectors and MTPS respectively. At the central B-field induced asymmetric region, films were within 0.6% between the CVD and the MTPS, but 5-8% differences were observed in the 40%-5% gradient region in CR due to ERE. The differences in localization and dose were found to be 0.6 mm and 3.3%. The γ(3%/2mm), γ (5%/2mm), γ (5%/1mm) were 97.7%, 99.3%, 94.6%., Conclusions: Films can provide accurate dosimetric results under ERE and are valuable for commissioning MRL. Using the One-scan-dosimetry protocol with EBT-XD film for MRL increases accuracy and efficiency in commissioning and QA of SRS/SBRT., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: Commercial independent monitor unit (IMU) check systems for high-magnetic-field MR-guided radiation therapy (RT) systems are lacking. We investigated the feasibility of adopting an existing treatment planning system (TPS) as an IMU check for online adaptive radiotherapy using 1.5-Tesla MR-Linac., Methods: The 7-MV flattening filter free (FFF) beam and multi-leaf collimator (MLC) models of a 1.5-T Elekta Unity MR-Linac within Monte Carlo-based Monaco TPS were used to generate an optimized beam model in Eclipse TPS. The MLC dosimetric leaf gap of the beam in Eclipse was determined by matching the dose distribution of Eclipse-generated intensity-modulated radiation therapy (IMRT) plans using the Analytical Anisotropic Algorithm (AAA) algorithm to Monaco plans. The plans were automatically adjusted for different source-to-axis distances (SADs) between the two systems. For IMU check, the treatment plans developed in Monaco were transferred to Eclipse to recalculate the dose using AAA. A plug-in within Eclipse was created to perform a 2D gamma analysis of the AAA and Monte Carlo dose distribution on a beam's eye view parallel plane. Monaco dose distribution was shifted laterally by 2 mm during gamma analysis to account for the impact of magnetic field on electron trajectories. Eclipse doses for posterior beams were corrected for both the Unity couch and the posterior MR coil attenuation. Thirteen patients, each with 4-5 fractions for a variety of tumor sites (pancreas, rectum, and prostate), were tested., Results: After thorough commissioning, the method was implemented as part of the standard clinical workflow. A total of 62 online plans, each with approximately 15 beams, were evaluated. The average per-beam gamma (3%/3 mm) pass rate for plans was 97.9% (range, 95.9% to 98.8%). The average pass rate per beam for all 932 beams used in these plans was 97.9% ± 1.9%, with the lowest per-beam gamma pass rate at 88.4%. The time for the process was within 3.2 ± 0.9 min., Conclusion: The use of a second planning system provides an efficient way to perform IMU checks with clinically acceptable accuracy for online adaptive plans on Unity MR-Linac. This is essential for meeting the safety requirements for second checks as outlined in American Association of Physicists in Medicine Task Group (AAPM TG) reports 114 and 219., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Zhang, Tyagi, Scripes, Subashi, Liang, Lovelock, Mechalakos, Li and Lim.)

Behavioral phenotyping devices have been successfully used to build ethograms, but many aspects of behavior remain out of reach of available phenotyping systems. We now report on a novel device, which consists in an open-field platform resting on highly sensitive piezoelectric (electromechanical) pressure-sensors, with which we could detect the slightest movements (up to individual heart beats during rest) from freely moving rats and mice. The combination with video recordings and signal analysis based on time-frequency decomposition, clustering, and machine learning algorithms provided non-invasive access to previously overlooked behavioral components. The detection of shaking/shivering provided an original readout of fear, distinct from but complementary to behavioral freezing. Analyzing the dynamics of momentum in locomotion and grooming allowed to identify the signature of gait and neurodevelopmental pathological phenotypes. We believe that this device represents a significant progress and offers new opportunities for the awaited advance of behavioral phenotyping., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background and Purpose: Stereotactic body radiation therapy (SBRT) of locally advanced pancreatic cancer (LAPC) is challenging due to significant motion of gastrointestinal (GI) organs. The goal of our study was to quantify inter and intrafraction deformations and dose accumulation of upper GI organs in LAPC patients., Materials and Methods: Five LAPC patients undergoing five-fraction magnetic resonance-guided radiation therapy (MRgRT) using abdominal compression and daily online plan adaptation to 50 Gy were analyzed. A pre-treatment, verification, and post-treatment MR imaging (MRI) for each of the five fractions (75 total) were used to calculate intra and interfraction motion. The MRIs were registered using Large Deformation Diffeomorphic Metric Mapping (LDDMM) deformable image registration (DIR) method and total dose delivered to stomach&#95;duodenum, small bowel (SB) and large bowel (LB) were accumulated. Deformations were quantified using gradient magnitude and Jacobian integral of the Deformation Vector Fields (DVF). Registration DVFs were geometrically assessed using Dice and 95th percentile Hausdorff distance (HD95) between the deformed and physician's contours. Accumulated doses were then calculated from the DVFs., Results: Median Dice and HD95 were: Stomach&#95;duodenum (0.9, 1.0 mm), SB (0.9, 3.6 mm), and LB (0.9, 2.0 mm). Median (max) interfraction deformation for stomach&#95;duodenum, SB and LB was 6.4 (25.8) mm, 7.9 (40.5) mm and 7.6 (35.9) mm. Median intrafraction deformation was 5.5 (22.6) mm, 8.2 (37.8) mm and 7.2 (26.5) mm. Accumulated doses for two patients exceeded institutional constraints for stomach&#95;duodenum, one of whom experienced Grade1 acute and late abdominal toxicity., Conclusion: LDDMM method indicates feasibility to measure large GI motion and accumulate dose. Further validation on larger cohort will allow quantitative dose accumulation to more reliably optimize online MRgRT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NT has received honorarium and travel support from Philips and Elekta healthcare. CHC have received travel support from Elekta healthcare., (© 2022 The Authors.)

Introduction: To investigate the impact of partial lateral scatter (LS), backscatter (BS) and presence of air gaps on optically stimulated luminescence dosimeter (OSLD) measurements in an acrylic miniphantom used for dosimetry audit on the 1.5 T magnetic resonance-linear accelerator (MR-linac) system., Methods: The following irradiation geometries were investigated using OSLDs, A26 MR/A12 MR ion chamber (IC), and Monaco Monte Carlo system: (a) IC/OSLD in an acrylic miniphantom (partial LS, partial BS), (b) IC/OSLD in a miniphantom placed on a solid water (SW) stack at a depth of 1.5 cm (partial LS, full BS), (c) IC/OSLD placed at a depth of 1.5 cm inside a 3 cm slab of SW/buildup (full LS, partial BS), and (d) IC/OSLD centered inside a 3 cm slab of SW/buildup at a depth of 1.5 cm placed on top of a SW stack (full LS, full BS). Average of two irradiated OSLDs with and without water was used at each setup. An air gap of 1 and 2 mm, mimicking presence of potential air gap around the OSLDs in the miniphantom geometry was also simulated. The calibration condition of the machine was 1 cGy/MU at SAD = 143.5 cm, d = 5 cm, G90, and 10 × 10 cm 2 ., Results: The Monaco calculation (0.5% uncertainty and 1.0 mm voxel size) for the four setups at the measurement point were 108.2, 108.1, 109.4, and 110.0 cGy. The corresponding IC measurements were 109.0 ± 0.03, 109.5 ± 0.06, 110.2 ± 0.02, and 109.8 ± 0.03 cGy. Without water, OSLDs measurements were ∼10% higher than the expected. With added water to minimize air gaps, the measurements were significantly improved to within 2.2%. The dosimetric impacts of 1 and 2 mm air gaps were also verified with Monaco to be 13.3% and 27.9% higher, respectively, due to the electron return effect., Conclusions: A minimal amount of air around or within the OSLDs can cause measurement discrepancies of 10% or higher when placed in a high b-field MR-linac system. Care must be taken to eliminate the air from within and around the OSLD., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: To describe and report longitudinal quality assurance (QA) measurements for the mechanical and dosimetric performance of an Elekta Unity MR-linac during the first year of clinical use in our institution., Materials and Methods: The mechanical and dosimetric performance of the MR-linac was evaluated with daily, weekly, monthly, and annual QA testing. The measurements monitor the size of the radiation isocenter, the MR-to-MV isocenter concordance, MLC and jaw position, the accuracy and reproducibility of step-and-shoot delivery, radiation output and beam profile constancy, and patient-specific QA for the first 50 treatments in our institution. Results from end-to-end QA using anthropomorphic phantoms are also included as a reference for baseline comparisons. Measurements were performed in water or water-equivalent plastic using ion chambers of various sizes, an ion chamber array, MR-compatible 2D/3D diode array, portal imager, MRI, and radiochromic film., Results: The diameter of the radiation isocenter and the distance between the MR/MV isocenters was (μ ± σ) 0.39 ± 0.01 mm and 0.89 ± 0.05 mm, respectively. Trend analysis shows both measurements to be well within the tolerance of 1.0 mm. MLC and jaw positional accuracy was within 1.0 mm while the dosimetric performance of step-and-shoot delivery was within 2.0%, irrespective of gantry angle. Radiation output and beam profile constancy were within 2.0% and 1.0%, respectively. End-to-end testing performed with ion-chamber and radiochromic film showed excellent agreement with treatment plan. Patient-specific QA using a 3D diode array identified gantry angles with low-pass rates allowing for improvements in plan quality after necessary adjustments., Conclusion: The MR-linac operates within the guidelines of current recommendations for linear accelerator performance, stability, and safety. The analysis of the data supports the recently published guidance in establishing clinically acceptable tolerance levels for relative and absolute measurements., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Objective: Adaptive radiation therapy (ART) is an integral part of MR-guided RT (MRgRT), requiring a new RT plan for each treatment fraction and resulting in a significant increase in patient-specific quality assurance (PSQA). This study investigates the possibility of using treatment log-file for automated PSQA., Method: All treatment plans were delivered in 1.5T Unity MR-Linac (Elekta). A Unity compatible version of LinacView (Standard Imaging) was commissioned to automatically monitor and analyze the log-files. A total of 220 fields were delivered and measured by ArcCheck ® -MR (Sun Nuclear) and LinacView. Thirty incorrectly matched fields were also delivered to check for error detection sensitivity. The gamma analysis, γ, with 3%, 3 mm criteria was used in both ArcCheck ® -MR and LinacView. Additionally, the gantry angle, jaws, and multileaf collimators (MLC) positions reported in the log-file were compared with plan positions using TG-142 criteria., Result: The γ (3%, 3 mm) for the 190 plans were found to be between the range of 72.5%-100.0% and 95.4%-100.0% for ArcCheck ® -MR and LinacVeiw, respectively. All the delivered gantry angle and jaws were found to be within 0.2° and 2 mm. MLCs that were outside the guard leaves or under the diaphragms were found to have more than 1.0 mm discrepancy. This was attributed to the linac internal override for these MLCs and had no dosimetric impact. Excluding these discrepancies, all MLC positions were found to be within 1.0 mm. The γ (3%, 3 mm) for the 30 incorrectly matched fields were found to be 3.9%-84.8% and 0.1%-64.4% for ArcCheck ® -MR and LinacVeiw, respectively., Conclusion: Significant ranked correlation demonstrates the automated log-file analysis can be used for PSQA and expedite the ART workflow. Ongoing PSQA will be compared with log-file analysis to investigate the longer term reproducibility and correlation., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background and Purpose: Stereotactic body radiation therapy delivered using MR-guided radiotherapy (MRgRT) and automatic breathold gating has shown to improve overall survival for locally advanced pancreatic cancer (LAPC) patients. The goal of our study was to evaluate feasibility of treating LAPC patients using abdominal compression (AC) and impact of potential intrafraction motion on planned dose on a 1.5T MR-linac., Methods & Materials: Ten LAPC patients were treated with MRgRT to 50 Gy in 5 fractions with daily online plan adaptation and AC. Three orthogonal plane cine MRI were acquired to assess stability of AC pressure in minimizing tumor motion. Three sets of T2w MR scans, pre-treatment (MRI pre ), verification (MRI ver ) and post-treatment (MRI post ) MRI, were acquired for every fraction. A total of 150 MRIs and doses were evaluated. Impact of intrafraction organ motion was evaluated by propagating pre-treatment plan and structures to MRI ver and MRI post , editing contours and recalculating doses. Gross tumor volume (GTV) coverage and organs-at-risk (OARs) doses were evaluated on MRI ver and MRI post ., Results: Median total treatment time was 75.5 (49-132) minutes. Median tumor motion in AC for all fractions was 1.7 (0.7-7), 2.1 (0.6-6.3) and 4.1 (1.4-10.0) mm in anterior-posterior, left-right and superior-inferior direction. Median GTV V50Gy was 78.7%. Median D5cm 3 stomach&#95;duodenum was 24.2 (18.4-29.3) Gy on MRI ver and 24.2 (18.3-30.5) Gy on MRI post . Median D5cm 3 small bowel was 24.3 (18.2-32.8) Gy on MRI ver and 24.4 (16.0-33.6) Gy on MRI post ., Conclusion: Dose-volume constraints for OARs were exceeded for some fractions on MRI ver and MRI post . Longer follow up is needed to see the dosimetric impact of intrafraction motion on gastrointestinal toxicity., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NT has received honorarium and travel support from Philips and Elekta healthcare. CHC and PBR have received travel support from Elekta healthcare., (© 2021 The Author(s).)

Purpose: As the utilization of brachytherapy procedures continues to decline in clinics, a need for accessible training tools is required to help bridge the gap between resident comfort in brachytherapy training and clinical practice. To improve the quality of intracavitary and interstitial high-dose-rate brachytherapy education, a multimaterial, modular, three-dimensionally printed pelvic phantom prototype simulating normal and cervical pathological conditions has been developed., Methods and Materials: Patient anatomy was derived from pelvic CT and MRI scans from 50 representative patients diagnosed with localized cervical cancer. Dimensions measured from patients' uterine body and uterine canal sizes were used to construct a variety of uteri based off of the averages and standard deviations of the subjects in our study. Soft-tissue anatomy was three-dimensionally printed using Agilus blends (shore 30 and 70) and modular components using Vero (shore 85)., Results: The kit consists of four uteri, a standard bladder, a standard rectum, two embedded gross tumor volumes, and four clip-on gross tumor volume attachments. The three anteverted uteri in the kit are based on the smallest, the average, and the largest dimensions from our patient set, whereas the retroverted uterus assumes average dimensions., Conclusions: This educational high-dose-rate gynecological pelvic phantom is an accessible and cost-effective way to improve radiation oncology resident training in intracavitary/interstitial brachytherapy cases. Implementation of this phantom in resident education will allow for more thorough and comprehensive physician training through its ability to transform the patient scenario. It is expected that this tool will help improve confidence and efficiency when performing brachytherapy procedures in patients., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the dosimetric impact of magnetic (B) field on varying air cavities in rectum patients treated on the hybrid 1.5 T MR-linac., Methods: Artificial air cavities of varying diameters (0.0, 1.0, 1.5, 2.0, 2.5, 3.0, and 5.0 cm) were created for four rectum patients (two prone and two supine). A total of 56 plans using a 7 MV flattening filter-free beam were generated with and without B-field. Reference intensity-modulated radiation therapy treatment plans without air cavity in the presence and absence of B-field were generated to a total dose of 45/50 Gy. The reference plans were copied and recalculated for the varying air cavities. D 95 (PTV 45 -PTV 50 ), D 95 (PTV 50 -aircavity), V 50 (PTV 50 -aircavity), D max (PTV 50 -aircavity), and V 110% (PTV 50 -aircavity) were extracted for each patient. Annulus rings of 1-mm-diameter step size were generated for one of the air cavity plans (3.0 cm) for all four patients to determine D max (%) and V 110% (cc) within each annulus., Results: In the presence of B-field, hot spots at the cavity interface start to become visible at ~1 cm air cavity in both supine and prone positioning due to electron return effect (ERE). In the presence of B-field D max and V 110% varied from 5523 ± 49 cGy and 0.09 ± 0.16 cc for 0 cm air cavity size to 6050 ± 109 cGy and 11.6 ± 6.7 cc for 5 cm air cavity size. The hot spots were located within 3 mm inside the rectal-air interface, where D max increased from 110.4 ± 0.5% without B-field to 119.2 ± 0.8 % with B-field., Conclusions: Air cavities inside rectum affects rectum plan dosimetry due ERE. Location and magnitude of hot spots are dependent on the size of the air cavity., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: This report describes a process for designing a 3D printed patient-specific applicator for HDR brachytherapy of the orbit., Case Presentation: A 34-year-old man with recurrent melanoma of the orbit was referred for consideration of re-irradiation. An applicator for HDR brachytherapy was designed based on the computed tomography (CT) of patient anatomy. The body contour was used to generate an applicator with a flush fit against the patient's skin while the planning target volume (PTV) was used to devise channels that allow for access and coverage of the tumor bed. An end-to-end dosimetric test was devised to determine feasibility for clinical use. The applicator was designed to conform to the volume and contours inside the orbital cavity. Support wings placed flush with the patient skin provided stability and reproducibility, while 16 source channels of varying length were needed for sufficient access to the target. A solid sheath, printed as an outer support-wall for each channel, prevented bending or accidental puncturing of the surface of the applicator., Conclusions: Quality assurance tests demonstrated feasibility for clinical use. Our experience with available 3D printing technology used to generate an applicator for the orbit may provide guidance for how materials of suitable biomechanical and radiation properties can be used in brachytherapy.

Purpose: Radiochromic film remains a useful and versatile clinical dosimetry tool. Current film options are single use. Here, we introduce a novel prototype two-dimensional (2D) radiochromic sheet, which optically clears naturally at room temperature after irradiation and can be reused. We evaluate the sheets for potential as a 2D dosimeter and as a radiochromic bolus with capability for dose measurement., Methods: A novel derivative of reusable Presage ® was manufactured into thin sheets of 5 mm thickness. The sheets contained 2% cumin-leucomalachitegreen-diethylamine (LMG-DEA) and plasticizer (up to 25% by weight). Irradiation experiments were performed to characterize the response to megavoltage radiation, including dose sensitivity, temporal decay rate, consistency of repeat irradiations, intra and inter-sheet reproducibility, multi-modality response (electrons and photons), and temperature sensitivity (22°C to 36°C). The local change in optical-density (ΔOD), before and after radiation, was obtained with a flat-bed film scanner and extracting the red channel. Repeat scanning enabled investigation of the temporal decay of ΔOD. Additional studies investigated clinical utility of the sheets through application to IMRT treatment plans (prostate and a TG119 commissioning plan), and a chest wall electron boost treatment. In the latter test, the sheet performed as a radiochromic bolus., Results: The radiation induced OD change in the sheets was found to be proportional to dose and to exponentially decay to baseline in ~24 h (R2 = 0.9986). The sheet could be reused and had similar sensitivity (within 1% after the first irradiation) for at least eight irradiations. Importantly, no memory of previous irradiations was observed within measurement uncertainty. The consistency of dose response from photons (6 and 15 MV) and electrons (6-20 MeV) was found to be within calibration uncertainty (~1%). The dose sensitivity of the sheets had a temperature dependence of 0.0012 ΔOD/°C. For the short (1 min) single field IMRT QA verification, good agreement was observed between the Presage sheet and EBT film (gamma pass rate 97% at 3% 3 mm dose-difference and distance-to-agreement tolerance, with a 10% threshold). For the longer (~13 min) TG-119 9-field IMRT verification the gamma agreement was lower at 93% pass rate at 5% 3 mm, 10% threshold, when compared with Eclipse. The lower rate is attributed to uncertainty arising from signal decay during irradiation and indicates a current limitation. For the electron cutout treatment, both Presage and EBT agreed well (within 2% RMS difference) but differed from the Eclipse treatment plan (~7% RMS difference) indicating some limitations to the Eclipse modeling in this case. The worst case estimates of uncertainty introduced by the signal decay for deliveries of 2, 5, and 10 min are 0.6%, 1.4%, and 2.8% respectively., Conclusions: Reusable Presage sheets show promise for 2D dose measurement and as a radiochromic bolus for in vivo dose measurement. The current prototype is suitable for deliveries of length up to 5 min, where the uncertainty introduced by signal decay is anticipated to be ~1% (worst case 1.4%), or for longer deliveries where there is no temporal modulation (e.g. physical compensators, or open beams). Additionally, spatial resolution is limited by sheet thickness and scanner resolution, resulting in a practical resolution of 0.8 mm., (© 2019 American Association of Physicists in Medicine.)

Purpose: To develop a spatiotemporal-constrained sorting technique for motion-robust 4 dimensional-magnetic resonance imaging., Methods and Materials: This sorting method implemented 2 new approaches for 4-dimensional imaging: (1) an optimized sparse k-space acquisition trajectory with self-gating signal derivation, and (2) a retrospective k-space sorting for reconstruction using a novel spatiotemporal-constrained strategy to minimize breathing variation-induced motion artifacts. Such sorting was regularized by a spatiotemporal index. Volumetric reconstruction was implemented iteratively with a secnd-order total generalized variation penalty. The proposed method was evaluated and compared with the conventional phase-sorting and amplitude-sorting methods in 2 studies. In a computer simulation study, 6 abdominal motion scenarios, including 2 cosine and 4 patient breathing motion patterns, were studied. Reconstruction accuracy was evaluated quantitatively in reference to the ground truth by average image relative error (IRE) in 10 phases and target Dice similarity coefficients (DSCs) in end-of-exhalation/inhalation phases. In addition, the proposed method was evaluated using a custom-made motion phantom. Reconstruction accuracy was evaluated by motion range measurement and image quality comparison in both fast and slow breathing motions., Results: In the simulation study, stitching motion artifacts in restricted images were lessened using the proposed method compared with those using the conventional methods. The average IRE and target DSC (end-of-exhalation/inhalation) were 0.031 and 0.95/0.94, respectively, suggesting better motion reconstruction accuracy than the phase-sorted method (IRE, 0.057; DSC, 0.89/0.89) and the amplitude-sorted method (IRE, 0.048; DSC, 0.91/0.88). In the phantom study, the moving target reconstructed by the proposed method demonstrated better rendering with less edge blurring. With fast breathing motion, the range measured using the proposed method was more accurate than that of the phase-sorted method and was comparable to the result of amplitude-sorted method and ground truths., Conclusions: Preliminary results suggested that the proposed sorting technique could reconstruct high-quality images and accurate motion estimation with reduced artifacts in 4 dimensional-magnetic resonance imaging., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In fragile X syndrome (FXS), sensory hypersensitivity and impaired habituation is thought to result in attention overload and various behavioral abnormalities in reaction to the excessive and remanent salience of environment features that would normally be ignored. This phenomenon, termed sensory defensiveness, has been proposed as the potential cause of hyperactivity, hyperarousal, and negative reactions to changes in routine that are often deleterious for FXS patients. However, the lack of tools for manipulating sensory hypersensitivity has not allowed the experimental testing required to evaluate the relevance of this hypothesis. Recent work has shown that BMS-204352, a BK Ca channel agonist, was efficient to reverse cortical hyperexcitability and related sensory hypersensitivity in the Fmr1-KO mouse model of FXS. In the present study, we report that exposing Fmr1-KO mice to novel or unfamiliar environments resulted in multiple behavioral perturbations, such as hyperactivity, impaired nest building and excessive grooming of the back. Reversing sensory hypersensitivity with the BK Ca channel agonist BMS-204352 prevented these behavioral abnormalities in Fmr1-KO mice. These results are in support of the sensory defensiveness hypothesis, and confirm BK Ca as a potentially relevant molecular target for the development of drug medication against FXS/ASD.

Purpose: Bolus-tracked multiphasic contrast computed tomography (CT) is often used in diagnostic radiology to enhance the visibility of pancreas tumors, but is uncommon in radiation therapy pancreas CT simulation, and its impact on gross tumor volume (GTV) delineation is unknown. This study evaluates the lesion conspicuity and consistency of pancreas stereotactic body radiation therapy (SBRT) GTVs contoured in the different contrast phases of triphasic CT simulation scans., Methods and Materials: Triphasic, bolus-tracked planning CT simulation scans of 10 consecutive pancreas SBRT patients were acquired, yielding images of the pancreas during the late arterial (LA), portal venous (PV), and either the early arterial or delayed phase. GTVs were contoured on each phase by a gastrointestinal-specialized radiation oncologist and reviewed by a fellowship-trained abdominal radiologist who specializes in pancreatic imaging. The volumes of the registered GTVs, their overlap ratio, and the 3-dimensional margin expansions necessary for each GTV to fully encompass GTVs from the other phases were calculated. The contrast difference between tumor and normal pancreas was measured, and 2 radiation oncologists rank-ordered the phases according to their value for the lesion-contouring task., Results: Tumor-to-pancreas enhancement was on average much larger for the LA and PV than the delayed phase or early arterial phases; the LA and PV phases were also consistently preferred by the radiation oncologists. Enhancement differences among the phases resulted in highly variable GTV volumes with no observed trends. Overlap ratios ranged from 18% to 75% across all 3 phases, improving to 43% to 91% when considering only the preferred LA and PV phases. GTV expansions necessary to encompass all GTVs ranged from 0.3 to 1.8 cm for all 3 phases, improving slightly to 0.1 to 1.4 cm when considering just the LA and PV phases., Conclusions: For pancreas SBRT, we recommend combining the GTVs from a multiphasic CT simulation with bolus-tracking, including, at a minimum, a Boolean "OR" of the LA and PV phases., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice. These studies have mostly focused on the hormonal responses to stress, using the acute exposure to a single type of stressor. Hence, little is known about the behavioral effects of stress in FXS, and the importance of the nature of the stressing procedure, especially in the context of a repeated exposure that more closely resembles real life conditions. Here we evaluated the effects of chronic exposure to different types of stress (i.e., either repeated restraint or unpredictable stress) on the behavioral phenotype of adult Fmr1 mice. Our results demonstrated that chronic stress induced deficits in social interaction and working memory only in WT mice and the impact of stress depended on the type of stressors and the specific behavior tested. Our data suggest that the behavioral sensitivity to stress is dramatically reduced in FXS, opening new views on the impact of gene-environment interactions in this pathology., (Copyright © 2016. Published by Elsevier B.V.)

This study compares the shutter-speed (SS) and the Tofts models as used in assessing therapeutic response in a longitudinal DCE-MRI experiment. Sixteen nu/nu mice with implanted colorectal adenocarcinoma cell line (LS-174T) were randomly assigned into treatment/control groups (n  =  8/group) and received bevacizumab/saline twice weekly (Day1/Day4/Day8). All mice were scanned at one pre- (Day0) and two post-treatment (Day2/Day9) time points using a high spatiotemporal resolution DCE-MRI pulse sequence. The CA extravasation rate constant [Formula: see text] from the Tofts/SS model and the mean intracellular water residence time [Formula: see text] from the SS model were analyzed. A biological subvolume (BV) within the tumor was identified based on the [Formula: see text] intensity distribution, and the SS model parameters within the BV ([Formula: see text] and [Formula: see text]) were analyzed. It is found that [Formula: see text] and [Formula: see text] have a similar spatial distribution in the tumor volume. The Bayesian information criterion results show that the SS model was a better fit for all scans. At Day9, the treatment group had significantly higher tumor mean [Formula: see text] (p  =  0.021), [Formula: see text] (p  =  0.021) and [Formula: see text] (p  = 0.045). When BV from transcytolemmal water exchange analysis was adopted, the treatment group had higher mean [Formula: see text] at both Day2 (p  =  0.038) and Day9 (p  =  0.007). Additionally, at Day9, the treatment group had higher mean [Formula: see text] (p  =  0.045) and higher [Formula: see text] spatial heterogeneity indices (Rényi dimensions) d 1 (p  = 0.010) and d 2 (p  = 0.021). When mean [Formula: see text] and its coefficient of variation (CV) were used to separate treatment/control group samples using supporting vector machine, the accuracy of treatment/control classification was 68.8% at Day2 and 87.5% at Day9; in contrast, the Day2/Day9 accuracy were 62.5%/87.5% using tumor mean [Formula: see text] and its CV and were 50.0%/87.5% using tumor mean [Formula: see text] and its CV, respectively. These results suggest that the SS model parameters outperformed the Tofts model parameters in terms of capturing bevacizumab therapeutic effect in this longitudinal experiment.

Purpose: To develop a dynamic fractal signature dissimilarity (FSD) method as a novel image texture analysis technique for the quantification of tumor heterogeneity information for better therapeutic response assessment with dynamic contrast-enhanced (DCE)-MRI., Methods: A small animal antiangiogenesis drug treatment experiment was used to demonstrate the proposed method. Sixteen LS-174T implanted mice were randomly assigned into treatment and control groups (n = 8/group). All mice received bevacizumab (treatment) or saline (control) three times in two weeks, and one pretreatment and two post-treatment DCE-MRI scans were performed. In the proposed dynamic FSD method, a dynamic FSD curve was generated to characterize the heterogeneity evolution during the contrast agent uptake, and the area under FSD curve (AUCFSD) and the maximum enhancement (MEFSD) were selected as representative parameters. As for comparison, the pharmacokinetic parameter K(trans) map and area under MR intensity enhancement curve AUCMR map were calculated. Besides the tumor's mean value and coefficient of variation, the kurtosis, skewness, and classic Rényi dimensions d1 and d2 of K(trans) and AUCMR maps were evaluated for heterogeneity assessment for comparison. For post-treatment scans, the Mann-Whitney U-test was used to assess the differences of the investigated parameters between treatment/control groups. The support vector machine (SVM) was applied to classify treatment/control groups using the investigated parameters at each post-treatment scan day., Results: The tumor mean K(trans) and its heterogeneity measurements d1 and d2 values showed significant differences between treatment/control groups in the second post-treatment scan. In contrast, the relative values (in reference to the pretreatment value) of AUCFSD and MEFSD in both post-treatment scans showed significant differences between treatment/control groups. When using AUCFSD and MEFSD as SVM input for treatment/control classification, the achieved accuracies were 93.8% and 93.8% at first and second post-treatment scan days, respectively. In comparison, the classification accuracies using d1 and d2 of K(trans) map were 87.5% and 100% at first and second post-treatment scan days, respectively., Conclusions: As quantitative metrics of tumor contrast agent uptake heterogeneity, the selected parameters from the dynamic FSD method accurately captured the therapeutic response in the experiment. The potential application of the proposed method is promising, and its addition to the existing DCE-MRI techniques could improve DCE-MRI performance in early assessment of treatment response.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.