Search

Extracting avalanche distributions from experimental microplasticity data can be hampered by limited time resolution. We compute the effects of low time resolution on avalanche size distributions and give quantitative criteria for diagnosing and circumventing problems associated with low time resolution. We show that traditional analysis of data obtained at low acquisition rates can lead to avalanche size distributions with incorrect power-law exponents or no power-law scaling at all. Furthermore, we demonstrate that it can lead to apparent data collapses with incorrect power-law and cutoff exponents. We propose new methods to analyze low-resolution stress-time series that can recover the size distribution of the underlying avalanches even when the resolution is so low that naive analysis methods give incorrect results. We test these methods on both downsampled simulation data from a simple model and downsampled bulk metallic glass compression data and find that the methods recover the correct critical exponents. [ABSTRACT FROM AUTHOR]

(1) Background: Proton therapy, a precise form of radiation treatment, can be significantly affected by variations in bowel content. The purpose was to identify the most beneficial gantry angles that minimize deviations from the treatment plan quality, thus enhancing the safety and efficacy of proton therapy for Wilms' tumor patients. (2) Methods: Thirteen patients with Wilms' tumor, enrolled in the SJWT21 clinical trial, underwent proton therapy. The variations in bowel gas were systematically monitored using daily Cone Beam Computed Tomography (CBCT) imaging. Air cavities identified in daily CBCT images were analyzed to construct daily verification plans and measure water equivalent path length (WEPL) changes. A worst-case scenario simulation was conducted to identify the safest beam angles. (3) Results: The study revealed a maximum decrease in target dose (ΔD100%) of 8.0%, which corresponded to a WEPL variation (ΔWEPL) of 11.3 mm. The average reduction in target dose, denoted as mean ΔD100%, was found to be 2.8%, with a standard deviation (SD) of 3.2%. The mean ΔWEPL was observed as 3.3 mm, with an SD of 2.7 mm. The worst-case scenario analysis suggested that gantry beam angles oriented toward the patient's right and posterior aspects from 110° to 310° were associated with minimized WEPL discrepancies. (4) Conclusions: This study comprehensively evaluated the influence of bowel gas variability on treatment plan accuracy and proton range uncertainties in pediatric proton therapy for Wilms' tumor.

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1-1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.

Hematoxylin and eosin (H&E) staining has been widely used as a fundamental and essential tool for diagnosing diseases and understanding biological phenomena by observing cellular arrangements and tissue morphological changes. However, conventional staining methods commonly involve solution-based, complex, multistep processes that are susceptible to user-handling errors. Moreover, inconsistent staining results owing to staining artifacts pose real challenges for accurate diagnosis. This study introduces a solution-free H&E staining method based on agarose hydrogel patches that is expected to represent a valuable tool to overcome the limitations of the solution-based approach. Using two agarose gel-based hydrogel patches containing hematoxylin and eosin dyes, H&E staining can be performed through serial stamping processes, minimizing color variation from handling errors. This method allows easy adjustments of the staining color by controlling the stamping time, effectively addressing variations in staining results caused by various artifacts, such as tissue processing and thickness. Moreover, the solution-free approach eliminates the need for water, making it applicable even in environmentally limited middle- and low-income countries, while still achieving a staining quality equivalent to that of the conventional method. In summary, this hydrogel-based H&E staining method can be used by researchers and medical professionals in resource-limited settings as a powerful tool to diagnose and understand biological phenomena., Competing Interests: Authors JhK, WC, DY, MK, and K-HC were employed by Noul Co., Ltd. The remaining 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 © 2023 Kim, Choi, Yoo, Kim, Cho, Sung, Choi, Uh, Kim, Go and Choi.)

(1) Background: The most significant cause of an unacceptable deviation from the planned dose during respiratory motion is the interplay effect. We examined the correlation between the magnitude of splenic motion and its impact on plan quality for total lymphoid irradiation (TLI); (2) Methods: Static and 4D CT images from ten patients were used for interplay effect simulations. Patients' original plans were optimized based on the average CT extracted from the 4D CT and planned with two posterior beams using scenario-based optimization (±3 mm of setup and ±3% of range uncertainty) and gradient matching at the level of mid-spleen. Dynamically accumulated 4D doses (interplay effect dose) were calculated based on the time-dependent delivery sequence of radiation fluence across all phases of the 4D CT. Dose volume parameters for each simulated treatment delivery were evaluated for plan quality; (3) Results: Peak-to-peak splenic motion (≤12 mm) was measured from the 4D CT of ten patients. Interplay effect simulations revealed that the ITV coverage of the spleen remained within the protocol tolerance for splenic motion, ≤8 mm. The D100% coverage for ITV spleen decreased from 95.0% (nominal plan) to 89.3% with 10 mm and 87.2% with 12 mm of splenic motion; (4) Conclusions: 4D plan evaluation and robust optimization may overcome problems associated with respiratory motion in proton TLI treatments. Patient-specific respiratory motion evaluations are essential to confirming adequate dosimetric coverage when proton therapy is utilized.

(1) Background: Synthetic CT images of the pelvis were generated from daily CBCT images to monitor changes in water equivalent path length (WEPL) and determine the dosimetric impact of anatomy changes along the proton beam's path; (2) Methods: Ten pediatric patients with pelvic tumors treated using proton therapy with daily CBCT were included. The original planning CT was deformed to the same-day CBCT to generate synthetic CT images for WEPL comparison and dosimetric evaluation; (3) Results: WEPL changes of 20 proton fields at the distal edge of the CTV ranged from 0.1 to 12 mm with a median of 2.5 mm, and 75th percentile of 5.1 mm for (the original CT-rescanned CT) and ranged from 0.3 to 10.1 mm with a median of 2.45 mm and 75th percentile of 4.8 mm for (the original CT-synthetic CT). The dosimetric impact was due to proton range pullback or overshoot, which led to reduced coverage in CTV Dmin averaging 12.1% and 11.3% in the rescanned and synthetic CT verification plans, respectively; (4) Conclusions: The study demonstrated that synthetic CT generated by deforming the original planning CT to daily CBCT can be used to quantify proton range changes and predict adverse dosimetric scenarios without the need for excessive rescanned CT scans during large interfractional variations in adaptive proton therapy of pediatric pelvic tumors.

Objective . This study aimed to develop a novel method for generating synthetic CT (sCT) from cone-beam CT (CBCT) of the abdomen/pelvis with bowel gas pockets to facilitate estimation of proton ranges. Approach . CBCT, the same-day repeat CT, and the planning CT (pCT) of 81 pediatric patients were used for training ( n = 60), validation ( n = 6), and testing ( n = 15) of the method. The proposed method hybridizes unsupervised deep learning (CycleGAN) and deformable image registration (DIR) of the pCT to CBCT. The CycleGAN and DIR are respectively applied to generate the geometry-weighted (high spatial-frequency) and intensity-weighted (low spatial-frequency) components of the sCT, thereby each process deals with only the component weighted toward its strength. The resultant sCT is further improved in bowel gas regions and other tissues by iteratively feeding back the sCT to adjust incorrect DIR and by increasing the contribution of the deformed pCT in regions of accurate DIR. Main results . The hybrid sCT was more accurate than deformed pCT and CycleGAN-only sCT as indicated by the smaller mean absolute error in CT numbers (28.7 ± 7.1 HU versus 38.8 ± 19.9 HU/53.2 ± 5.5 HU; P ≤ 0.012) and higher Dice similarity of the internal gas regions (0.722 ± 0.088 versus 0.180 ± 0.098/0.659 ± 0.129; P ≤ 0.002). Accordingly, the hybrid method resulted in more accurate proton range for the beams intersecting gas pockets (11 fields in 6 patients) than the individual methods (the 90th percentile error in 80% distal fall-off, 1.8 ± 0.6 mm versus 6.5 ± 7.8 mm/3.7 ± 1.5 mm; P ≤ 0.013). The gamma passing rates also showed a significant dosimetric advantage by the hybrid method (99.7 ± 0.8% versus 98.4 ± 3.1%/98.3 ± 1.8%; P ≤ 0.007). Significance . The hybrid method significantly improved the accuracy of sCT and showed promises in CBCT-based proton range verification and adaptive replanning of abdominal/pelvic proton therapy even when gas pockets are present in the beam path., (© 2023 Institute of Physics and Engineering in Medicine.)

Background: The Patient Health Questionnaire-2 (PHQ-2) and Insomnia Severity Index-2 (ISI-2) are screening assessments that reflect the past 2-week experience of depression and insomnia, respectively. Retrospective assessment has been associated with reduced accuracy owing to recall bias., Objective: This study aimed to increase the reliability of responses by validating the use of the PHQ-2 and ISI-2 for daily screening., Methods: A total of 167 outpatients from the psychiatric department at the Yongin Severance Hospital participated in this study, of which 63 (37.7%) were male and 104 (62.3%) were female with a mean age of 35.1 (SD 12.1) years. Participants used a mobile app ("Mental Protector") for 4 weeks and rated their depressive and insomnia symptoms daily on the modified PHQ-2 and ISI-2 scales. The validation assessments were conducted in 2 blocks, each with a fortnight response from the participants. The modified version of the PHQ-2 was evaluated against the conventional scales of the Patient Health Questionnaire-9 and the Korean version of the Center for Epidemiologic Studies Depression Scale-Revised., Results: According to the sensitivity and specificity analyses, an average score of 3.29 on the modified PHQ-2 was considered valid for screening for depressive symptoms. Similarly, the ISI-2 was evaluated against the conventional scale, Insomnia Severity Index, and a mean score of 3.50 was determined to be a valid threshold for insomnia symptoms when rated daily., Conclusions: This study is one of the first to propose a daily digital screening measure for depression and insomnia delivered through a mobile app. The modified PHQ-2 and ISI-2 were strong candidates for daily screening of depression and insomnia, respectively., (©Jae Won Oh, Sun Mi Kim, Deokjong Lee, Nak-Hoon Son, Jinsun Uh, Ju Hong Yoon, Yukyung Choi, San Lee. Originally published in JMIR Mental Health (https://mental.jmir.org), 22.05.2023.)

With the impact of the COVID-19 pandemic, the number of patients suffering from depression is rising around the world. It is important to diagnose depression early so that it may be treated as soon as possible. The self-response questionnaire, which has been used to diagnose depression in hospitals, is impractical since it requires active patient engagement. Therefore, it is vital to have a system that predicts depression automatically and recommends treatment. In this paper, we propose a smartphone-based depression prediction system. In addition, we propose depressive features based on multimodal sensor data for predicting depressive mood. The multimodal depressive features were designed based on depression symptoms defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The proposed system comprises a "Mental Health Protector" application that collects data from smartphones and a big data-based cloud platform that processes large amounts of data. We recruited 106 mental patients and collected smartphone sensor data and self-reported questionnaires from their smartphones using the proposed system. Finally, we evaluated the performance of the proposed system's prediction of depression. As the test dataset, 27 out of 106 participants were selected randomly. The proposed system showed 76.92% on an f1-score for 16 patients with depression disease, and in particular, 15 patients, 93.75%, were successfully predicted. Unlike previous studies, the proposed method has high adaptability in that it uses only smartphones and has a distinction of evaluating prediction accuracy based on the diagnosis.

Purpose: To generate synthetic relative proton stopping power (sRPSP) images from magnetic resonance imaging (MRI) sequence(s) and develop an online quality assurance (QA) tool for sRPSP to facilitate safe integration of magnetic resonance (MR)-only proton planning into clinical practice., Materials and Methods: Planning computed tomography (CT) and MR images of 195 pediatric brain tumor patients were utilized (training: 150, testing: 45). Seventeen consistent-cycle generative adversarial network (ccGAN) models were trained separately using paired CT-converted RPSP and MRI datasets to transform a subject's MRI into sRPSP. T1-weighted (T1W), T2-weighted (T2W), and FLAIR MRI were permutated to form 17 combinations, with or without preprocessing, for determining the optimal training sequence(s). For evaluation, sRPSP images were converted to synthetic CT (sCT) and compared to the real CT in terms of mean absolute error (MAE) in Hounsfield units (HU). For QA, sCT was deformed and compared to a reference template built from training dataset to produce a flag map, highlighting pixels that deviate by >100 HU and fall outside the mean ± standard deviation reference intensity. The gamma intensity analysis (10%/3 mm) of the deformed sCT against the QA template on the intensity difference was investigated as a surrogate of sCT accuracy., Results: The sRPSP images generated from a single T1W or T2W sequence outperformed that generated from multi-MRI sequences in terms of MAE (all p < 0.05). Preprocessing with N4 bias and histogram matching reduced MAE of T2W MRI-based sCT (54 ± 21 HU vs. 42 ± 13 HU, p = 0.002). The gamma intensity analysis of sCT against the QA template was highly correlated with the MAE of sCT against the real CT in the testing cohort (r = -0.89 for T1W sCT; r = -0.93 for T2W sCT)., Conclusion: Accurate sRPSP images can be generated from T1W/T2W MRI for proton planning. A QA tool highlights regions of inaccuracy, flagging problematic cases unsuitable for clinical use., (© 2022 American Association of Physicists in Medicine.)

Purpose: To train a deep neural network for correcting abdominal and pelvic cone-beam computed tomography (CBCT) of children and young adults in the presence of diverse patient size, anatomic extent, and scan parameters., Materials and Methods: Pretreatment CBCT and planning/repeat CT image pairs from 64 children and young adults treated with proton therapy (aged 1-23 years) were analyzed. To evaluate the impact of anatomic extent in CBCT and data size in the training data, we compared the performance of three cycle-consistent generative adversarial network models that were separately trained by three datasets comprising abdominal (n = 21), pelvic (n = 29), and combined abdominal-pelvic image pairs (n = 50), respectively. The maximum body width of each patient was normalized to a fixed width before training and model application to reduce the impact of variations in body size. The corrected CBCT images by the three models were comparatively evaluated against the repeat CT closest in time to the CBCT (median gap, 0 days; range, 0-6 days) in HU accuracy, estimated dose distribution, and proton range., Results: The network model trained by the combined dataset significantly outperformed the abdomen and pelvis models in mean absolute HU error of the corrected CBCT from 14 testing patients (47 ± 7 HU versus 51 ± 8 HU; paired Wilcoxon signed-rank test, P < 0.01). The larger error (60 ± 7 HU) without the body-size normalization confirmed the efficacy of the preprocessing. The model trained with the combined dataset resulted in gamma passing rates of 98.5 ± 1.9% (2%/2 mm criterion) and the range (80% distal fall-off) differences from the reference within ±3 mm for 91.2 ± 11.5% beamlets., Conclusion: Combining data from adjacent anatomic sites and normalizing age-dependent body sizes in children and young adults were beneficial in training a neural network to accurately estimate proton dose from CBCT despite limited training data size and anatomic diversities., 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 © 2021 Elsevier B.V. All rights reserved.)

Purpose: Assessment of the blood-brain barrier (BBB) permeability without the need for contrast agent is desirable, and the ability to measure the permeability to small molecules such as water may further increase the sensitivity in detecting diseases. This study proposed a time-efficient, noncontrast method to measure BBB permeability to water, evaluated its test-retest reproducibility, and compared it with a contrast agent-based method., Methods: A single-delay water extraction with phase-contrast arterial spin tagging (WEPCAST) method was devised in which spatial profile of the signal along the superior sagittal sinus was used to estimate bolus arrival time, and the WEPCAST signal at the corresponding location was used to compute water extraction fraction, which was combined with global cerebral blood flow to estimate BBB permeability surface area product to water. The reliability of WEPCAST sequence was examined in terms of intrasession, intersession, and inter-vendor (Philips [Ingenia, Best, the Netherlands] and Siemens [Prisma, Erlangen, Germany]) reproducibility. Finally, we compared this new technique to a contrast agent-based method., Results: Single-delay WEPCAST reduced the scan duration from approximately 20 min to 5 min. Extract fraction values estimated from single-delay WEPCAST showed good consistency with the multi-delay method (R = 0.82, P = .004). Group-averaged permeability surface area product values were found to be 137.5 ± 9.3 mL/100 g/min. Intrasession, intersession, and inter-vendor coefficient of variation of the permeability surface area product values were 6.6 ± 4.5%, 6.9 ± 3.7%, and 8.9 ± 3.0%, respectively. Finally, permeability surface area product obtained from WEPCAST MRI showed a significant correlation with that from the contrast-based method (R = .73, P = .02)., Conclusion: Single-delay WEPCAST MRI can measure BBB permeability to water within 5 min with an intrasession, intersession, and inter-vendor test-retest reproducibility of 6% to 9%. This method may provide a useful marker of BBB breakdown in clinical studies., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: To determine whether self-attention cycle-generative adversarial networks (cycle-GANs), a novel deep-learning method, can generate accurate synthetic computed tomography (sCT) to facilitate adaptive proton therapy in children with brain tumors., Materials and Methods: Both CT and T1-weighted magnetic resonance imaging (MRI) of 125 children (ages 1-20 years) with brain tumors were included in the training dataset. A model introducing a self-attention mechanism into the conventional cycle-GAN was created to enhance tissue interfaces and reduce noise. The test dataset consisted of 7 patients (ages 2-14 years) who underwent adaptive planning because of changes in anatomy discovered on MRI during proton therapy. The MRI during proton therapy-based sCT was compared with replanning CT (ground truth)., Results: The Hounsfield unit-mean absolute error was significantly reduced with self-attention cycle-GAN, as compared with conventional cycle-GAN (65.3 ± 13.9 versus 88.9 ± 19.3, P  < .01). The average 3-dimensional gamma passing rates (2%/2 mm criteria) for the original plan on the anatomy of the day and for the adapted plan were high (97.6% ± 1.2% and 98.9 ± 0.9%, respectively) when using sCT generated by self-attention cycle-GAN. The mean absolute differences in clinical target volume (CTV) receiving 95% of the prescription dose and 80% distal falloff along the beam axis were 1.1% ± 0.8% and 1.1 ± 0.9 mm, respectively. Areas of greatest dose difference were distal to the CTV and corresponded to shifts in distal falloff. Plan adaptation was appropriately triggered in all test patients when using sCT., Conclusion: The novel cycle-GAN model with self-attention outperforms conventional cycle-GAN for children with brain tumors. Encouraging dosimetric results suggest that sCT generation can be used to identify patients who would benefit from adaptive replanning., Competing Interests: Conflicts of Interest: Sahaja Acharya, MD, receives grant funding from Conquer Cancer, the American Society for Clinical Oncology Foundation, outside of this submitted work. Chia-ho Hua, PhD, receives grant funding from Philips Healthcare, outside of this submitted work. The other authors have no relevant conflicts of interest to disclose., (©Copyright 2021 The Author(s).)

Purpose: To determine the preirradiation baseline association of white matter integrity with neurocognitive function and to assess posttreatment changes in pediatric patients with craniopharyngioma treated with proton therapy., Methods and Materials: Ninety children and adolescents (2-20 years old) with craniopharyngioma were treated with proton therapy (54 Gy[RBE]) in a prospective therapeutic trial. Neurocognitive performance at the postoperative baseline before proton therapy and diffusion tensor imaging (DTI) data acquired at baseline and at annual follow-up were analyzed. Tract-based spatial statistics and structural connectomics were used to derive global and local white matter features from DTI. Baseline DTI features were compared for patients with average and below-average neurocognitive performance. Longitudinal DTI data were analyzed to determine the proton dose effect on white matter structures in relation to the irradiated brain volume and baseline age., Results: Before proton therapy, patients with below-average working memory, processing speed, verbal fluency, verbal learning, or fine motor dexterity exhibited more globally degraded white matter structures compared with their counterparts with average performance, as indicated by lower mean fractional anisotropy, decreased global efficiency, or higher modularity. Surgery, obstructive hydrocephalus, and preoperative hypothalamic involvement appeared to be related to this degradation. In local analyses, tract-based spatial statistics revealed left-lateralized associations with verbal and motor functions, which supported surgical approaches to midline tumors via the right hemisphere. The mean fractional anisotropy of the brain and the global efficiency derived from DTI increased over the 5 years after proton therapy. The rate of increase was lower with larger irradiated brain volumes and in older children., Conclusions: Below-average baseline neurocognitive performance in patients with craniopharyngioma before proton therapy appeared to be related to structural degradation of white matter tracts. Posttherapy longitudinal DTI showed improving trends in global integrity and efficiency measures, particularly in children in whom a smaller brain volume was irradiated., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Pencil-beam scanning proton therapy is particularly sensitive to anatomic changes, which may affect the delivered dose distribution. This study examined whether offline adaptation using on-treatment magnetic resonance imaging (MRI) scan during proton therapy could improve plan quality for pediatric patients., Methods and Materials: Pediatric patients with at least 1 MRI scan in the treatment position (MRI tx ) during proton therapy between January 2017 and July 2019 were retrospectively reviewed. Patients underwent MRI and computed tomography simulation. Cases were planned with scenario-based optimization with 3 mm/3% positional/range uncertainty. Patients demonstrating anatomic change on MRI tx were recontoured. The original plans were applied to the anatomy-of-the-day for dose recalculation (delivered plans). Plans were subsequently reoptimized offline, using original beam angles and dose-volume constraints (adapted plans). Delivered plans were compared with adapted plans to detect significant changes in plan quality, defined as a ≥5% decrease in the clinical target volume (CTV) receiving 95% of the prescription dose (V95) or a ≥5% increase in the dose-volume parameter used as an organ-at-risk constraint., Results: Seventy-three pediatric patients were eligible, with 303 MRI scans (73 simulation and 230 MRI tx scans) available for analysis. The median MRI tx scans per patient was 3 (range, 1-7). Twenty patients (27%) showed anatomic change, with 11 (55%) demonstrating a significant change in delivered plan quality. Significant changes were noted on MRI tx from week 2 (n = 3) or week 3 (n = 8). Seven of these 11 patients (64%) had a significantly reduced CTV V95 (median decrease, 7.6%; range, 5%-16%). Four (36%) had a significantly increased dose to the brain stem, hippocampus, and/or optic apparatus. Eight had a suprasellar low-grade glioma or head and neck rhabdomyosarcoma., Conclusion: On-treatment MRI was useful in detecting anatomic changes during proton therapy. MRI-based offline adaptation improved plan quality for most patients with anatomic changes. Further studies should determine the clinical value of MRI-based adaptive therapy for pediatric patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Four-dimensional magnetic resonance imaging (4D MRI) has advanced recently by incorporating prospective gating, but its performance on pediatric populations has not been investigated. This study aimed to determine the age-related performance of prospective gating, as compared with retrospective sorting., Materials and Methods: Prospectively gated 4D MRI scans were acquired on a motion phantom driven by real respiratory waveforms obtained from 23 pediatric and young adult patients (aged 5-24 years). The correlations between patient-specific breathing characteristics and the performance of 4D MRI were comparatively evaluated against retrospective sorting for the same scan time. For six patients who underwent both 4D MRI and 4D CT, the internal target volumes (ITVs) determined by the two modalities were compared., Results: Longer scan time and greater sorting error were most highly correlated ( P  < 0.001) with breathing irregularity and extent of diaphragm motion, but age was not a strong covariate because of interindividual variation. Prospective gating was more accurate than retrospective sorting except for those patients with severe breathing irregularity (peak-to-peak coefficient of variation >30%). The ITVs of 4D MRI and 4D CT were comparable (Dice similarity: >90%) unless the breathing characteristics changed between the two imaging sessions., Conclusions: For most patients analyzed in this study, prospective gating provided more accurate 4D MRI (95th percentile of deviation: <1.5 mm) than did retrospective sorting within a clinically feasible scan time (median: 5.9 min). The 4D MRI tended to take longer and to give larger sorting errors with deeper and irregular breathers., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: St. Jude Children’s Research Hospital has a research agreement with Philips Healthcare., (© 2019 The Authors.)

A patient with Hepatitis A virus (HAV) infection was notified to the public health authority. The identical HAV was found at a water dispensing outlet at the ground water facility and the toilet close to the facility. Serosurveillance in the community was conducted. Suspicious individuals were asked to visit city public health center and had a serologic test for anti-HAV Ig M. Overall, 100 individuals were tested, and all were negative for the anti-HAV Ig M. In our study cohort, we could not identify additional case of HAV infection., Competing Interests: No conflicts of interest., (Copyright © 2019 by The Korean Society of Infectious Diseases and Korean Society for Antimicrobial Therapy.)

Background and Purpose: The role of perfusion imaging in the management of pediatric high grade glioma is unclear. We evaluated the ability of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) to determine grade, evaluate post-treatment response and predict treatment failure., Material and Methods: In this study 22 patients with high-grade glioma underwent biopsy and were treated with concurrent and sequential radiotherapy and erlotinib as part of a phase I/II clinical trial (NCT00124657). Preradiotherapy, immediate postradiotherapy, 6‑month and treatment failure DSC MR images were reviewed, registered, and processed for the ratio of cerebral blood flow (CBF) and cerebral blood volume (CBV). Processed, derived perfusion, and T1-weighted images (T1WI), T2WI, and fluid attenuation inversion recovery (FLAIR) MRI sequences were used for segmentation and extraction of tumor perfusion parameters at all time points. Patient, tumor, treatment, and outcome data were summarized and related to perfusion data., Results: Regional CBF in tumors increased from diagnosis to postradiotherapy, while they decreased to levels below those at diagnosis from postradiotherapy to 6‑month follow-up. At 6 months, the median regional CBF was higher in tumors that progressed (median 1.16) than in those that did not (median, 0.95; P < 0.05). Patients with regional CBF ratios above 1.4 at diagnosis had shorter survival times than did those with regional CBF ratios below 1.4 (P = 0.77). Tumors with a regional CBV above 1.15 at the postradiotherapy (1-3 months) follow-up scan were associated with an earlier time to death than that of tumors with a regional CBV below 1.15 (P < 0.05)., Conclusion: Posttreatment perfusion characteristics are prognostic and may help predict survival. Overall, perfusion MRI is useful for managing pediatric high-grade glioma and should be incorporated into future clinical trials.

Purpose: To investigate the effect of interplay between spot-scanning proton beams and respiration-induced tumor motion on internal target volume coverage for pediatric patients., Materials and Methods: Photon treatments for 10 children with representative tumor motions (1-13 mm superior-inferior) were replanned to simulate single-field uniform dose- optimized proton therapy. Static plans were designed by using average computed tomography (CT) data sets created from 4D CT data to obtain nominal dose distributions. The motion interplay effect was simulated by assigning each spot in the static plan delivery sequence to 1 of 10 respiratory-phase CTs, using the actual patient breathing trace and specifications of a synchrotron-based proton system. Dose distributions for individual phases were deformed onto the space of the average CT and summed to produce the accumulated dose distribution, whose dose-volume histogram was compared with the one from the static plan., Results: Tumor motion had minimal impact on the internal target volume hot spot (D2), which deviated by <3% from the nominal values of the static plans. The cold spot (D98) was also minimally affected, except in 2 patients with diaphragmatic tumor motion exceeding 10 mm. The impact on tumor coverage was more pronounced with respect to the V99 rather than the V95. Decreases of 10% to 49% in the V99 occurred in multiple patients for whom the beam paths traversed the lung-diaphragm interface and were, therefore, more sensitive to respiration-induced changes in the water equivalent path length. Fractionation alone apparently did not mitigate the interplay effect beyond 6 fractions., Conclusion: The interplay effect is not a concern when delivering scanning proton beams to younger pediatric patients with tumors located in the retroperitoneal space and tumor motion of <5 mm. Children and adolescents with diaphragmatic tumor motion exceeding 10 mm require special attention, because significant declines in target coverage and dose homogeneity were seen in simulated treatments of such patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose.

Aim: To describe the clinical implementation and optimization of magnetic resonance imaging (MRI) systems installed in a radiation oncology department for dedicated use in radiotherapy (RT) simulation and treatment planning for pediatric patients., Methods: Two wide-bore MRI systems were installed and commissioned in 2016. Patient setups, coil placements, and scan protocols were developed to image various anatomic sites in children. Patients with brain tumors were routinely imaged using a pair of flexible loop coils and a posterior receiver coil integrated into the patient couch. The integrated posterior coil and the flexible anterior torso coil supported by the coil bridge were used together when imaging the abdomen, pelvis, or spine. A three-dimensional acquisition was most often performed, given the benefit of high-resolution multiplanar reformation as well as elimination of B0-related distortions in the slice selection direction., Results: We performed 542 MRI studies (265 for planning and 277 for monitoring on-treatment tumor changes) on pediatric patients in the first year after system installation. Multisequence images of pediatric RT patients with ependymoma, medulloblastoma, craniopharyngioma, rhabdomyosarcoma, or Ewing sarcoma were shown to illustrate the image quality obtainable with optimized planning sequences., Conclusions: Magnetic resonance imaging (MRI) of pediatric patients in their treatment positions with setup devices in place can be performed with coil arrangements that include flexible coils. The resulting image quality is suitable for treatment planning and on-treatment monitoring. We provide optimized site-specific sequence parameters to support the continued improvement of MRI for pediatric RT planning., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To evaluate the feasibility of using on-treatment magnetic resonance imaging (MRI) to detect proton range changes during treatment courses., Methods: MRI-based virtual computed tomography (vCT) was generated to calculate water-equivalent path length (WEPL) at the distal surface of a clinical target volume. T2-weighted MR images with and without fat suppression were processed by thresholding and fuzzy c-mean clustering to assign a bulk HU (Hounsfield Unit) to each segment of fat, water, and air. Bony tissues in vCT were transferred from planning CT via a region-based registration. We validated this method using images from three patients (aged 9, 12, and 17 yr old) with pelvic sarcomas who underwent proton therapy. MRI-based WEPL was evaluated against those of repeat CT (rCT) and cone beam CT (CBCT)., Results: The vCT agreed well with the rCT, wherein the use of bulk HU and imperfect bone registration contributed to discrepancies. The 99th percentile error of the MRI-based WEPL was up to 3.3 mm for posterior fields when we compensated the effect of mobile air. The gamma index (2-mm WEPL/2-mm pixel distance) was greater than 99% for those fields. We observed larger errors for anterior fields, which were due to bowel gas movement, mismatched respiratory motion, and differences in patient posture between the vCT and rCT. Applied to multiple on-treatment MRI of a patient, the estimated WEPL demonstrated an underrange trend, which was consistent with the CBCT results and the increased patient body circumference., Conclusions: The MRI-based vCT produced highly accurate WEPL estimates, demonstrating the potential of using on-treatment MRI for detecting changes in proton ranges., (© 2018 American Association of Physicists in Medicine.)

Purpose: To characterize respiration-induced abdominal organ motion in children receiving radiation treatment with a 4-dimensional (4D) magnetic resonance imaging (MRI) method., Methods and Materials: We analyzed free-breathing coronal 4D MRI datasets acquired from 35 patients (aged 1-20 years) with abdominal tumors. A deformable image registration of the 4D MRI datasets was performed to derive motion trajectories of selected anatomic landmarks, from which organ motions were quantified. The association between organ motion and patient characteristics was investigated and compared with previous studies. The relation between patient height and organ motion was further investigated to predict organ motion in prospective patients., Results: Organ motion and its individual variation were reduced in younger patients (eg, kidney peak-to-peak motion <5 mm for all but 1 patient aged ≤8 years), although special motion management may be warranted in some adolescents. The liver and spleen exhibited greater motion than did the kidneys, while intraorgan variation was present. The motions in the liver and kidneys agreed with those reported by the previous 4D computed tomography studies. Individual variations of organ motion in younger patients were due, in part, to changes in respiration rate, which ostensibly reflected the effect of anesthesia. The prediction of organ motion was limited by large individual variations, particularly for older patients., Conclusions: The 4D MRI acquisition method and motion analysis described in this study provide a nonionizing approach to understand age-associated organ motion, which aids in the planning of abdominal radiation therapy for pediatric patients. Use of 4D MRI facilitates monitoring of changes in target motion patterns during treatment courses and in various studies of the effect of organ motion on radiation treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study aimed to develop a practical and accurate 4-dimensional (4D) magnetic resonance imaging (MRI) method using a non-navigator, image-based internal respiratory surrogate derived by dimensionality reduction (DR). The use of DR has been previously suggested but not implemented for reconstructing 4D MRI, despite its practical advantages. We compared multiple image-acquisition schemes and refined a retrospective-sorting process to optimally implement a DR-derived surrogate. The comparison included an unconventional scheme that acquires paired slices alternately to mitigate the internal surrogate's dependency on a specific slice location. We introduced 'target-oriented sorting', as opposed to conventional binning, to quantify the coherence in retrospectively sorted images, thereby determining the minimal scan time needed for sufficient coherence. This study focused on evaluating the proposed method using digital phantoms which provided unequivocal gold standard. The evaluation indicated that the DR-based respiratory surrogate is highly accurate: the error in amplitude percentile of the surrogate signal was less than 5% with the optimal scheme. Acquiring alternating paired slices was superior to the conventional scheme of acquiring individual slices; the advantage of the unconventional scheme was more pronounced when a substantial phase shift occurred across slice locations. The analysis of coherence across sorted images confirmed the advantage of higher sampling efficiencies in non-navigator respiratory surrogates. We determined that a scan time of 20 s per imaging slice was sufficient to achieve a mean coherence error of less than 1% for the tested respiratory patterns. The clinical applicability of the proposed 4D MRI has been demonstrated with volunteers and patients. The diaphragm motion in 4D MRI was consistent with that in dynamic 2D imaging which was regarded as the gold standard (difference within 1.8 mm on average).

Homotopy reflects the intrinsic functional architecture of the brain through synchronized spontaneous activity between corresponding bilateral regions, measured as voxel mirrored homotopic connectivity (VMHC). Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO2 ) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS-fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory-motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS-fMRI is affected by arterial CO2 levels suggests that caution should be used when comparing RS-fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease., (Copyright © 2015 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy., Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51 atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect., Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non-surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect., Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect., Competing Interests: Notification: No actual or potential conflicts of interest exist., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The calibratable relationship between blood oxygenation (Y) and T(2) allows quantification of cerebral venous oxygenation. We aim to establish a calibration plot between blood T(2) , Y, and hematocrit at 7 T, and using T(2) -relaxation-under-spin-tagging MRI, determine human venous blood oxygenation in vivo., Methods: In vitro experiments were performed at 7 T on bovine blood samples using a Carr-Purcell-Meiboom-Gill-T2 sequence, from which we characterized the relationship among T(2) , Y, and hematocrit. T(2) -relaxation-under-spin-tagging MRI was implemented at 7 T to measure venous blood T2 in vivo, from which oxygenation was estimated using the in vitro calibration plot. Hyperoxia was performed to test the sensitivity of the method to oxygenation changes, and the 7 T results were compared with those at 3 T., Results: In vitro data showed that arterial and venous T(2) at 7 T are 68 and 20 ms, respectively, at a typical hematocrit of 0.42. In vivo measurement showed a cerebral venous oxygenation of 64.7 ± 5.0% and a test-retest coefficient-of-variation of 3.6 ± 2.4%. Hyperoxia increased Yv by 9.0 ± 1.4% (P = 0.001) and the 3 and 7 T results showed a strong correlation (R = 0.95) across individuals., Conclusion: We provided an in vitro calibration plot for conversion of blood T(2) to oxygenation at 7 T and demonstrated its utility in vivo., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To evaluate the feasibility and accuracy of magnetic resonance imaging (MRI)-based treatment planning using pseudo CTs generated through atlas registration., Methods: A pseudo CT, providing electron density information for dose calculation, was generated by deforming atlas CT images previously acquired on other patients. The authors tested 4 schemes of synthesizing a pseudo CT from single or multiple deformed atlas images: use of a single arbitrarily selected atlas, arithmetic mean process using 6 atlases, and pattern recognition with Gaussian process (PRGP) using 6 or 12 atlases. The required deformation for atlas CT images was derived from a nonlinear registration of conjugated atlas MR images to that of the patient of interest. The contrasts of atlas MR images were adjusted by histogram matching to reduce the effect of different sets of acquisition parameters. For comparison, the authors also tested a simple scheme assigning the Hounsfield unit of water to the entire patient volume. All pseudo CT generating schemes were applied to 14 patients with common pediatric brain tumors. The image similarity of real patient-specific CT and pseudo CTs constructed by different schemes was compared. Differences in computation times were also calculated. The real CT in the treatment planning system was replaced with the pseudo CT, and the dose distribution was recalculated to determine the difference., Results: The atlas approach generally performed better than assigning a bulk CT number to the entire patient volume. Comparing atlas-based schemes, those using multiple atlases outperformed the single atlas scheme. For multiple atlas schemes, the pseudo CTs were similar to the real CTs (correlation coefficient, 0.787-0.819). The calculated dose distribution was in close agreement with the original dose. Nearly the entire patient volume (98.3%-98.7%) satisfied the criteria of chi-evaluation (<2% maximum dose and 2 mm range). The dose to 95% of the volume and the percentage of volume receiving at least 95% of the prescription dose in the planning target volume differed from the original values by less than 2% of the prescription dose (root-mean-square, RMS < 1%). The PRGP scheme did not perform better than the arithmetic mean process with the same number of atlases. Increasing the number of atlases from 6 to 12 often resulted in improvements, but statistical significance was not always found., Conclusions: MRI-based treatment planning with pseudo CTs generated through atlas registration is feasible for pediatric brain tumor patients. The doses calculated from pseudo CTs agreed well with those from real CTs, showing dosimetric accuracy within 2% for the PTV when multiple atlases were used. The arithmetic mean process may be a reasonable choice over PRGP for the synthesis scheme considering performance and computational costs.