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Background: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST)., Purpose: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST., Study Type: Prospective., Population: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR)., Field Strength/sequence: 3.0 T/reduced field of view single-shot echo-planar DTI sequence., Assessment: Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery., Statistical Tests: Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant., Results: 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm 2 /s)., Data Conclusion: Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC., Evidence Level: 1 TECHNICAL EFFICACY: Stage 4., (© 2024 International Society for Magnetic Resonance in Medicine.)

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.

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from time-intensity curves (TICs), and 107 radiomic features were derived. Statistical analyses compared R vs. PR/NR. At PRT, 79% of R displayed a "Capsular" morphology (P = 1.49 × 10 -7 ), and 100% demonstrated a TIC-type II (P = 8.32 × 10 -7 ). 80% of PR showed "Unipolar" morphology (P = 1.03 × 10 -5 ), and 60% expressed a TIC-type V (P = 0.06). Semiquantitative wash-in rate (WiR) was able to separate R vs. PR/NR (P = 0.0078). The WiR radiomics displayed significant differences in the first&#95;order&#95;10 percentile (P = 0.0178) comparing R vs. PR/NR at PRT. The PWI/DCE TIC-type II curve, low WiR, and "Capsular" enhancement represent PRT patterns typically observed in successfully treated UPS and demonstrate potential for UPS treatment response assessment., (© 2024. The Author(s).)

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) affects patients after recovering from acute coronavirus disease 2019 (COVID-19). This study investigates the impact of SARS-CoV-2 vaccination on PASC symptoms in children in Taiwan during the Omicron pandemic., Methods: We enrolled children under 18 years with PASC symptoms persisting for more than 4 weeks. Data collected included demographics, clinical information, vaccination status, and symptom persistence. We used logistic regression models to compare symptoms in the acute and post-COVID-19 phases and to assess the association between vaccination and these symptoms., Results: Among 500 PASC children, 292 (58.4%) were vaccinated, 282 (52.8%) were male, and the mean (SD) age was 7.6 (4.6) years. Vaccinated individuals exhibited higher odds of experiencing symptoms in the previous acute phase, such as cough (adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI]: 1.02-2.42), rhinorrhea/nasal congestion (AOR = 1.74; 95% CI: 1.13-2.67), sneezing (AOR = 1.68; 95% CI: 1.02-2.76), sputum production (AOR = 1.91; 95% CI: 1.15-3.19), headache/dizziness (AOR = 1.73; 95% CI: 1.04-2.87), and muscle soreness (AOR = 2.33; 95% CI: 1.13-4.80). In contrast, there were lower odds of experiencing abdominal pain (AOR = 0.49; 95% CI: 0.25-0.94) and diarrhea (AOR = 0.37; 95% CI: 0.17-0.78) in children who had received vaccination during the post-COVID-19 phase., Conclusions: This study revealed clinical features and vaccination effects in PASC children in Taiwan. Vaccination may reduce some gastrointestinal symptoms in the post-COVID-19 phase.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC., (© 2024. The Author(s).)

Purpose: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping., Methods: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions on each scanner (total scans = 100). To evaluate the feasibility of 3D-QALAS, nine patients with multiple sclerosis (nine women; mean age ± SD, 48.2 ± 11.5 y) underwent imaging examination on two 3T MRI systems from different manufacturers., Results: Quantitative maps obtained with 3D-QALAS showed high linearity (R 2  = 0.998 and 0.998 for T1 and T2, respectively) with respect to reference measurements. The mean intra-scanner coefficients of variation for each scanner and structure ranged from 0.4% to 2.6%. The mean structure-wise test-retest repeatabilities were 1.6%, 1.1%, and 0.7% for T1, T2, and PD, respectively. Overall, high inter-vendor reproducibility was observed for all parameter maps and all structure measurements, including white matter lesions in patients with multiple sclerosis., Conclusion: The vendor-agnostic multiparametric mapping technique 3D-QALAS provided reproducible measurements of T1, T2, and PD for human tissues within a typical physiological range using 3T scanners from four different MRI manufacturers., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Multiparametric MR imaging of the prostate is an essential diagnostic study in the evaluation of prostate cancer. Several entities including normal anatomic structures, benign lesions, and posttreatment changes can mimic prostate cancer. An in depth understanding of the pitfalls is important for accurate interpretation of prostate MR imaging., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Early prediction of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) patients could help oncologists select individualized treatment and avoid toxic effects associated with ineffective therapy in patients unlikely to achieve pathologic complete response (pCR). The objective of this study is to evaluate the performance of radiomic features of the peritumoral and tumoral regions from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquired at different time points of NAST for early treatment response prediction in TNBC. This study included 163 Stage I-III patients with TNBC undergoing NAST as part of a prospective clinical trial (NCT02276443). Peritumoral and tumoral regions of interest were segmented on DCE images at baseline (BL) and after two (C2) and four (C4) cycles of NAST. Ten first-order (FO) radiomic features and 300 gray-level-co-occurrence matrix (GLCM) features were calculated. Area under the receiver operating characteristic curve (AUC) and Wilcoxon rank sum test were used to determine the most predictive features. Multivariate logistic regression models were used for performance assessment. Pearson correlation was used to assess intrareader and interreader variability. Seventy-eight patients (48%) had pCR (52 training, 26 testing), and 85 (52%) had non-pCR (57 training, 28 testing). Forty-six radiomic features had AUC at least 0.70, and 13 multivariate models had AUC at least 0.75 for training and testing sets. The Pearson correlation showed significant correlation between readers. In conclusion, Radiomic features from DCE-MRI are useful for differentiating pCR and non-pCR. Similarly, predictive radiomic models based on these features can improve early noninvasive treatment response prediction in TNBC patients undergoing NAST., Competing Interests: KKH serves on the medical advisory boards for ArmadaHealth and AstraZeneca and receives research funding from Cairn Surgical, Eli Lilly and Company, and Lumicell. K-PH is currently receiving research funding from Siemens Healthineers and has received research funding from GE. JKL received grant or research support from Novartis, Medivation/Pfizer, Genentech, GSK, EMD-Serono, AstraZeneca, Medimmune, Zenith, and Merck; participated in the Speaker’s Bureau for MedLearning, Physicians’ Education Resource, Prime Oncology, Medscape, Clinical Care Options, and Medpage and receives royalty from UpToDate and Certis. DT declares research contracts with Pfizer, Novartis, and Ployphor and is a consultant of AstraZeneca, GlaxoSmithKline, OncoPep, Gilead, Novartis, Pfizer, Personalis, and Sermonix. WY receives royalties from Elsevier. GR receives research funding from GE Healthcare. JM is an inventor of United States patents licensed to Siemens Healthineers and GE Healthcare and is a consultant for C4 Imaging. 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 Panthi, Mohamed, Adrada, Boge, Candelaria, Chen, Hunt, Huo, Hwang, Korkut, Lane, Le-Petross, Leung, Litton, Pashapoor, Perez, Son, Sun, Thompson, Tripathy, Valero, Wei, White, Xu, Yang, Zhou, Yam, Rauch and Ma.)

Accurate tumor segmentation is required for quantitative image analyses, which are increasingly used for evaluation of tumors. We developed a fully automated and high-performance segmentation model of triple-negative breast cancer using a self-configurable deep learning framework and a large set of dynamic contrast-enhanced MRI images acquired serially over the patients' treatment course. Among all models, the top-performing one that was trained with the images across different time points of a treatment course yielded a Dice similarity coefficient of 93% and a sensitivity of 96% on baseline images. The top-performing model also produced accurate tumor size measurements, which is valuable for practical clinical applications.

Purpose To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC). Materials and Methods In this prospective study, 181 women diagnosed with stage I-III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting in 930 features per scan. Radiomic features were compared between pCR and non-pCR groups by using Wilcoxon rank sum test. To build a multivariable predictive model, logistic regression with elastic net regularization and cross-validation was performed for texture feature selection using 119 participants (median age, 52 years [range, 26-77 years]). An independent testing cohort of 62 participants (median age, 48 years [range, 23-74 years]) was used to evaluate and compare the models by area under the receiver operating characteristic curve (AUC). Results Univariable analysis identified 15 T1, 10 T2, and 12 PD radiomic features at midtreatment that predicted pCR with an AUC greater than 0.70 in both the training and testing cohorts. Multivariable radiomics models of maps acquired at midtreatment demonstrated superior performance over those acquired at baseline, achieving AUCs as high as 0.78 and 0.72 in the training and testing cohorts, respectively. Conclusion SyMRI-based radiomic features acquired at midtreatment are potentially useful for identifying early NAST responders in TNBC. Keywords: MR Imaging, Breast, Outcomes Analysis ClinicalTrials.gov registration no. NCT02276443 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Houser and Rapelyea in this issue.

Background: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success. We pursue a universal (pan-SARS-CoV-2) vaccine against Delta, Omicrons and ever-emergent new mutants., Methods and Findings: We explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation (N = 1,478) of infection-free participants (aged 18-85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6-8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). This UB-612 booster vaccination is safe and well tolerated without SAEs., Conclusions: By targeting conserved epitopes on viral S2, M and N proteins, UB-612 could provide potent, broad and long-lasting B-cell and T-cell memory immunity and offers the potential as a universal vaccine to fend off Omicrons and new VoCs without resorting to Omicron-specific immunogens., Trial Registration: ClinicalTrials.gov ID: NCT04773067; ClinicalTrials.gov ID: NCT05293665; ClinicalTrials.gov ID: NCT05541861., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CYW and WJP are co-inventors on related patent applications. CYW, WJP, BSK, YHH, MSW, YTY, and PYC are employees of UBI Asia., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bacterial coinfections have been widely recognized in adults with coronavirus disease 2019 (COVID-19). However, bacterial coinfections in hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been sufficiently researched. This study aimed to determine the clinical presentations and risk factors for bacterial coinfections of pediatric inpatients during the SARS-CoV-2 Omicron BA.2 variant pandemic., Methods: This retrospective, observational study included patients younger than 18 years of age who were hospitalized for COVID-19 confirmed by polymerase chain reaction (PCR) or antigen rapid tests during the SARS-CoV-2 Omicron BA.2 variant pandemic. Data and outcomes of these patients with or without bacterial coinfections were compared., Results: During this study period, 161 children with confirmed COVID-19 were hospitalized. Twenty-four had bacterial coinfections. The most frequently reported concurrent diagnosis was bacterial enteritis, followed by lower respiratory tract infections. Children with bacterial coinfections had higher white blood cell (WBC) counts and PCR cycle threshold values. The bacterial coinfection group comprised a relatively greater proportion of patients who required high-flow nasal cannula oxygen and remdesivir. The length of stay in the hospital and that in the intensive care unit were longer for children with COVID-19 with bacterial coinfections. Mortality was not observed in either group. Abdominal pain, diarrhea, and comorbidity with neurologic illnesses were risk factors for bacterial coinfections with COVID-19., Conclusion: This study provides clinicians with reference points for the detection of COVID-19 in children and its possible association with bacterial infections. Children with COVID-19 and neurologic diseases who present with abdominal pain or diarrhea are at risk of bacterial coinfections. Prolonged fever duration and higher PCR test cycle threshold values, WBC levels, and high-sensitivity C-reactive protein (hsCRP) levels may indicate bacterial coinfections in children with COVID-19., 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 © 2023 Lai, Hsu, Lin, Wei, Chen, Low, Chiu, Lin and Hwang.)

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann-Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 ( p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Introduction: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies., Areas Covered: Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines., Expert Opinion: Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

Background: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC., Purpose: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC., Study Type: Prospective., Population/subjects: A total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020., Field Strength/sequence: A 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI)., Assessment: Three scans were acquired longitudinally (pretreatment, after two cycles of NAST, and after four cycles of NAST). For each scan, 11 ADC histogram features (minimum, maximum, mean, median, standard deviation, kurtosis, skewness and 10th, 25th, 75th, and 90th percentiles) were extracted from tumors and from PTRs of 5 mm, 10 mm, 15 mm, and 20 mm in thickness with inclusion and exclusion of fat-dominant pixels., Statistical Tests: ADC features were tested for prediction of pCR, both individually using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC), and in combination in multivariable models with k-fold cross-validation. A P value < 0.05 was considered statistically significant., Results: Fifty-one patients (47%) had pCR. Maximum ADC from PTR, measured after two and four cycles of NAST, was significantly higher in pCR patients (2.8 ± 0.69 vs 3.5 ± 0.94 mm 2 /sec). The top-performing feature for prediction of pCR was the maximum ADC from the 5-mm fat-inclusive PTR after cycle 4 of NAST (AUC: 0.74; 95% confidence interval: 0.64, 0.84). Multivariable models of ADC features performed similarly for fat-inclusive and fat-exclusive PTRs, with AUCs ranging from 0.68 to 0.72 for the cycle 2 and cycle 4 scans., Data Conclusion: Quantitative ADC features from PTRs may serve as early predictors of the response to NAST in TNBC., Evidence Level: 1 TECHNICAL EFFICACY: Stage 4., (© 2022 International Society for Magnetic Resonance in Medicine.)

Background: Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort., Methods: This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children's Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs., Results: Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was Mycoplasma pneumoniae., Conclusions: FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, diffusion-weighted imaging, and multiphase contrast-enhanced imaging is the mainstay for imaging assessment of endometrial cancer. Identification of important prognostic factors at MRI improves both treatment selection and posttreatment follow-up. MRI also plays a crucial role for fertility-preserving strategies and in patients who are not surgical candidates by helping guide therapy and identify procedural complications. This review is a product of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease-Focused Panel and reflects a multidisciplinary international collaborative effort to summarize updated information highlighting the role of MRI for endometrial cancer depiction and delineation, treatment planning, and follow-up. The article includes information regarding dedicated MRI protocols, tips for MRI reporting, imaging pitfalls, and strategies for image quality optimization. The roles of MRI-guided radiation therapy, hybrid PET/MRI, and advanced MRI techniques that are applicable to endometrial cancer imaging are also discussed. Online supplemental material is available for this article. © RSNA, 2022.

Background: The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on., Methods: This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis., Results: In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively)., Conclusion: BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome., Competing Interests: Declaration of competing interest All authors have no conflicts of interest or financial relationships relevant to this article to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. While primary series vaccination rates are generally high in Southeast Asian (SEA) countries, various factors have limited the rollout and impact of booster doses., Areas Covered: We reviewed 79 studies in the International Vaccine Access Center (IVAC) VIEW-hub platform on vaccine effectiveness (VE) after primary immunizations with two-dose schedules. VE data were reported for SARS-CoV-2 infection, COVID-19-related hospitalizations and deaths, and stratified across variants of concern, age, study design and prior SARS-CoV-2 infection for mRNA vaccines (BNT162b2, mRNA-1273, and combinations of both), vector vaccines (AstraZeneca, AZD1222 [ChAdOx1 nCoV-19] 'Vaxzevria'), and inactivated virus vaccines (CoronaVac)., Expert Opinion: The most-studied COVID-19 vaccines provide consistently high (>90%) protection against serious clinical outcomes like hospitalizations and deaths, regardless of variant. Additionally, this protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222, as supported by our analysis of Asian and relevant international data, and by insights from SEA experts. Given the continued impact of COVID-19 hospitalizations and deaths on health-care systems worldwide, encouraging vaccination strategies that reduce this burden is more relevant than attempting to prevent broader but milder infections with specific variants, including Omicron.

The task group (TG) on magnetic resonance imaging (MRI) implementation in high-dose-rate (HDR) brachytherapy (BT)-Considerations from simulation to treatment, TG 303, was constituted by the American Association of Physicists in Medicine's (AAPM's) Science Council under the direction of the Therapy Physics Committee, the Brachytherapy Subcommittee, and the Working Group on Brachytherapy Clinical Applications. The TG was charged with developing recommendations for commissioning, clinical implementation, and on-going quality assurance (QA). Additionally, the TG was charged with describing HDR BT workflows and evaluating practical consideration that arise when implementing MR imaging. For brevity, the report is focused on the treatment of gynecologic and prostate cancer. The TG report provides an introduction and rationale for MRI implementation in BT, a review of previous publications on topics including available applicators, clinical trials, previously published BT-related TG reports, and new image-guided recommendations beyond CT-based practices. The report describes MRI protocols and methodologies, including recommendations for the clinical implementation and logical considerations for MR imaging for HDR BT. Given the evolution from prescriptive to risk-based QA, an example of a risk-based analysis using MRI-based, prostate HDR BT is presented. In summary, the TG report is intended to provide clear and comprehensive guidelines and recommendations for commissioning, clinical implementation, and QA for MRI-based HDR BT that may be utilized by the medical physics community to streamline this process. This report is endorsed by the American Brachytherapy Society., (© 2022 American Association of Physicists in Medicine.)

Purpose: To develop a rigid real-time prospective motion-corrected multiparametric mapping technique and to test the performance of quantitative estimates., Methods: Motion tracking and correction were performed by integrating single-shot spiral navigators into a multiparametric imaging technique, three-dimensional quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS). The spiral navigator was optimized, and quantitative measurements were validated using a standard system phantom. The effect of motion correction on whole-brain T1 and T2 mapping under different types of head motion during the scan was evaluated in 10 healthy volunteers. Finally, six patients with Parkinson's disease, which is known to be associated with a high prevalence of motion artifacts, were scanned to evaluate the effectiveness of our method in the real world., Results: The phantom study demonstrated that the proposed motion correction method did not introduce quantitative bias. Improved parametric map quality and repeatability were shown in volunteer experiments with both in-plane and through-plane motions, comparable to the no-motion ground truth. In real-life validation in patients, the approach showed improved parametric map quality compared to images obtained without motion correction., Conclusions: Real-time prospective motion-corrected multiparametric relaxometry based on 3D-QALAS provided robust and repeatable whole-brain multiparametric mapping., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Current clinical MR imaging practices rely on the qualitative assessment of images for diagnosis and treatment planning. While contrast in MR images is dependent on the spin parameters of the imaged tissue, pixel values on MR images are relative and are not scaled to represent any tissue properties. Synthetic MR is a fully featured imaging workflow consisting of efficient multi-parameter mapping acquisition, synthetic image generation, and volume quantitation of brain tissues. As the application becomes more widely available on multiple vendors and scanner platforms, it has also gained widespread adoption as clinicians begin to recognize the benefits of rapid quantitation. This review will provide details about the sequence with a focus on the physical principles behind its relaxometry mechanisms. It will present an overview of the products in their current form and some potential issues when implementing it in the clinic. It will conclude by highlighting some recent advances of the technique, including a 3D mapping method and its associated applications., (© 2022 American Association of Physicists in Medicine.)

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Background: The causative pathogen of pediatric osteomyelitis is often unidentified despite culturing attempts. This study evaluated and compared the clinical characteristics, therapeutic approach, and outcomes of osteomyelitis caused by unknown pathogens and identified microorganisms., Method: This 17-year retrospective study was conducted at a tertiary hospital in central Taiwan. Medical records of children aged less than 18 years with a diagnosis of osteomyelitis between 2003 and 2019 were reviewed., Result: In total, 70 patients (median age = 6.4 years; male = 65.7%) fulfilled the inclusion criteria, of whom 33 (47.1%) were culture negative. Staphylococcus aureus was the main pathogen (67.6% of identified bacteria). The proportion of methicillin-resistant S. aureus (MRSA) was 44% and 54.5% of the MRSA isolates exhibited clindamycin resistance. Compared to children with culture-positive osteomyelitis, those with culture-negative osteomyelitis had a lower rate of concomitant septic arthritis (40.5% vs. 15.2%, p = 0.019) and leukocytosis on presentation (45.9% vs. 21.2%, p = 0.030); they also required fewer surgical interventions (56.8% vs. 24.2%, p = 0.006) and received a shorter course of total antibiotic therapy (49.0 vs. 43.0 days, p = 0.045). In the culture-negative group, the MRSA coverage rate was 18.8% during initial empirical therapy and increased to 59.4% during further adjusted therapy. The overall complication rate was 18.6% and was lower in the culture-negative group (32.4% vs. 3.0%, p = 0.002)., Conclusion: In areas where community-associated MRSA and clindamycin resistance strains are a concern, empirical glycopeptide-based therapy is suggested in pediatric osteomyelitis, particularly in those with culture-negative infections., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Background: MVC-COV1901, a recombinant protein vaccine containing pre-fusion-stabilised spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide, has been shown to be well tolerated with a good safety profile in healthy adults aged 20-49 years in a phase 1 trial, and provided a good cellular and humoral immune responses. We present the interim safety, tolerability, and immunogenicity results of a phase 2 clinical trial of the MVC-COV1901 vaccine in Taiwan., Methods: This is a large-scale, double-blind, randomised, placebo-controlled phase 2 trial done at ten medical centres and one regional hospital in Taiwan. Individuals aged 20 years or older who were generally healthy or had stable pre-existing medical conditions were eligible for enrolment. Exclusion criteria included (but were not limited to) travel overseas within 14 days of screening, intention to travel overseas within 6 months of the screening visit, and the absence of prespecified medical conditions, including immunosuppressive illness, a history of autoimmune disease, malignancy with risk to recur, a bleeding disorder, uncontrolled HIV infection, uncontrolled hepatitis B and C virus infections, SARS-CoV-1 or SARS-CoV-2 infections, an allergy to any vaccine, or a serious medical condition that could interfere with the study. Study participants were randomly assigned (6:1) to receive two doses of either MVC-COV1901 or placebo, administered via intramuscular injection on day 1 and day 29. MVC-COV1901 contained 15 μg of S-2P protein adjuvanted with 750 μg CpG 1018 and 375 μg aluminium hydroxide in a 0·5 mL aqueous solution, and the placebo contained the same volume of saline. Randomisation was done centrally by use of an interactive web response system, stratified by age (≥20 to <65 years and ≥65 years). Participants and investigators were masked to group assignment. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from day 1 (the day of the first dose) to day 57 (28 days after the second dose). Safety was assessed in all participants who received at least one dose. Immunogenicity was assessed by measuring geometric mean titres (GMTs) and seroconversion rates of neutralising antibody and antigen-specific IgG in the per-protocol population. This study is registered with ClinicalTrials.gov, NCT04695652., Findings: Of 4173 individuals screened between Dec 30, 2020, and April 2, 2021, 3854 were enrolled and randomly assigned: 3304 to the MVC-COV1901 group and 550 to the placebo group. A total of 3844 participants (3295 in the MVC-COV1901 group and 549 in the placebo group) were included in the safety analysis set, and 1053 participants (903 and 150) had received both doses and were included in the per-protocol immunogenicity analysis set. From the start of this phase 2 trial to the time of interim analysis, no vaccine-related serious adverse events were recorded. The most common solicited adverse events in all study participants were pain at the injection site (2346 [71·2%] of 3295 in the MVC-COV1901 group and 128 [23·3%] of 549 in the placebo group), and malaise or fatigue (1186 [36·0%] and 163 [29·7%]). Fever was rarely reported (23 [0·7%] and two [0·4%]). At 28 days after the second dose of MVC-COV1901, the wild-type SARS-CoV-2 neutralising antibody GMT was 662·3 (95% CI 628·7-697·8; 408·5 IU/mL), the GMT ratio (geometric mean fold increase in titres at day 57 vs baseline) was 163·2 (155·0-171·9), and the seroconversion rate was 99·8% (95% CI 99·2-100·0)., Interpretation: MVC-COV1901 has a good safety profile and elicits promising immunogenicity responses. These data support MVC-COV1901 to enter phase 3 efficacy trials., Funding: Medigen Vaccine Biologics and Taiwan Centres for Disease Control, Ministry of Health and Welfare., Competing Interests: Declaration of interests CC, CEL, and I-CT are employees of Medigen Vaccine Biologics (Taipei, Taiwan) and they report receiving grants from Taiwan Centres for Disease Control, Ministry of Health and Welfare, during the conduct of the study. CC also has a patent pending relating to the MVC-COV1901 vaccine against SARS-CoV-2 (US17/351,363). All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Precise correlation between three-dimensional (3D) imaging and histology can aid biomechanical modeling of the breast. We develop a framework to register ex vivo images to histology using a novel cryo-fluorescence tomography (CFT) device., Methods: A formalin-fixed cadaveric breast specimen, including chest wall, was subjected to high-resolution magnetic resonance (MR) imaging. The specimen was then frozen and embedded in an optimal cutting temperature (OCT) compound. The OCT block was placed in a CFT device with an overhead camera and 50 μm thick slices were successively shaved off the block. After each shaving, the block-face was photographed. At select locations including connective/adipose tissue, muscle, skin, and fibroglandular tissue, 20 μm sections were transferred onto cryogenic tape for manual hematoxylin and eosin staining, histological assessment, and image capture. A 3D white-light image was automatically reconstructed from the photographs by aligning fiducial markers embedded in the OCT block. The 3D MR image, 3D white-light image, and photomicrographs were rigidly registered. Target registration errors (TREs) were computed based on 10 pairs of points marked at fibroglandular intersections. The overall MR-histology registration was used to compare the MR intensities at tissue extraction sites with a one-way analysis of variance., Results: The MR image to CFT-captured white-light image registration achieved a mean TRE of 0.73 ± 0.25 mm (less than the 1 mm MR slice resolution). The block-face white-light image and block-face photomicrograph registration showed visually indistinguishable alignment of anatomical structures and tissue boundaries. The MR intensities at the four tissue sites identified from histology differed significantly (p < 0.01). Each tissue pair, except the skin-connective/adipose tissue pair, also had significantly different MR intensities (p < 0.01)., Conclusions: Fine sectioning in a highly controlled imaging/sectioning environment enables accurate registration between the MR image and histology. Statistically significant differences in MR signal intensities between histological tissues are indicators for the specificity of correlation between MRI and histology., (© 2021 American Association of Physicists in Medicine.)

Purpose To determine if amide proton transfer-weighted chemical exchange saturation transfer (APT W CEST) MRI is useful in the early assessment of treatment response in persons with triple-negative breast cancer (TNBC). Materials and Methods In this prospective study, a total of 51 participants (mean age, 51 years [range, 26-79 years]) with TNBC were included who underwent APT W CEST MRI with 0.9- and 2.0-µT saturation power performed at baseline, after two cycles (C2), and after four cycles (C4) of neoadjuvant systemic therapy (NAST). Imaging was performed between January 31, 2019, and November 11, 2019, and was a part of a clinical trial (registry number NCT02744053). CEST MR images were analyzed using two methods-magnetic transfer ratio asymmetry (MTR asym ) and Lorentzian line shape fitting. The APT W CEST signals at baseline, C2, and C4 were compared for 51 participants to evaluate the saturation power levels and analysis methods. The APT W CEST signals and their changes during NAST were then compared for the 26 participants with pathology reports for treatment response assessment. Results A significant APT W CEST signal decrease was observed during NAST when acquisition at 0.9-µT saturation power was paired with Lorentzian line shape fitting analysis and when the acquisition at 2.0 µT was paired with MTR asym analysis. Using 0.9-µT saturation power and Lorentzian line shape fitting, the APT W CEST signal at C2 was significantly different from baseline in participants with pathologic complete response (pCR) (3.19% vs 2.43%; P = .03) but not with non-pCR (2.76% vs 2.50%; P > .05). The APT W CEST signal change was not significant between pCR and non-pCR at all time points. Conclusion Quantitative APT W CEST MRI depended on optimizing acquisition saturation powers and analysis methods. APT W CEST MRI monitored treatment effects but did not differentiate participants with TNBC who had pCR from those with non-pCR. © RSNA, 2021 Clinical trial registration no. NCT02744053 Supplemental material is available for this article. Keywords Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, MR-Imaging, Breast, Technical Aspects, Tumor Response, Technology Assessment.

Background: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6-35 months of age., Methods: One hundred eighty-five children randomized into 5 groups [1.9 µg hemagglutinin (HA)/AS03B, 0.9 µg HA/AS03C, 1.9 µg HA/AS03C, 3.75 µg HA/AS03C or 3.75 µg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03B the highest amount. One year later, all subjects were to receive unadjuvanted 3.75 µg HA as antigen challenge. Immunogenicity was assessed 21 days after primary vaccination (day 42) and 7 days after antigen challenge (day 392). Immunogenicity-fever index, based on hemagglutination inhibition and microneutralization antibody titers at day 42 and fever 7 days after each vaccination, was used to guide the selection of an acceptable formulation., Results: After primary vaccination, formulations elicited strong homologous immune responses with all subjects' hemagglutination inhibition titers ≥1:40 post-vaccination. Immunogenicity-fever index based on hemagglutination inhibition and microneutralization assays showed that 1.9 µg HA/AS03B ranked the highest. Antibody levels persisted >4 times above baseline 12 months after primary vaccination with all formulations (day 385). Antibodies increased >4-fold after antigen challenge (day 392/day 385) with 1.9 µg HA/AS03B, 0.9 µg HA/AS03C and 1.9 µg HA/AS03C formulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 µg HA/AS03D) to 60.5% (1.9 µg HA/AS03B)., Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 µg HA/AS03B providing the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age., Competing Interests: J.H.K., M.D., J.D., D.F. and B.S. are employees of the GSK group of companies. W.W., D.W.V., B.I. and A.S. were employees of the GSK group of companies during the conduct of the study. J.H.K., B.S., M.D., J.D., W.W. and A.S. hold shares from the GSK group of companies. T.P., N.-C.C., K.S. and L.-M.H. received funds from the GSK group of companies through their institution for the conduct of the study. L.-M.H. received personal fees from the GSK group of companies for educational lectures. J.H.K., M.D., T.P., N.-C.C., K.S., L.-M.H., J.D., D.F., B.S., W.W., D.W.V., B.I. and A.S. declare no other financial and nonfinancial relationships and activities. K.-P.H., P.-Y.C. and C.-H.C. declare no financial and nonfinancial relationships and activities and no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Dynamic contrast-enhanced (DCE) MRI is useful for diagnosis and assessment of treatment response in breast cancer. Fast DCE MRI offers a higher sampling rate of contrast enhancement curves in comparison to conventional DCE MRI, potentially characterizing tumor perfusion kinetics more accurately for measurement of functional tumor volume (FTV) as a predictor of treatment response., Purpose: To investigate FTV by fast DCE MRI as a predictor of neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC)., Study Type: Prospective., Population/subjects: Sixty patients with biopsy-confirmed TNBC between December 2016 and September 2020., Field Strength/sequence: A 3.0 T/3D fast spoiled gradient echo-based DCE MRI ASSESSMENT: Patients underwent MRI at baseline and after four cycles (C4) of NAST, followed by definitive surgery. DCE subtraction images were analyzed in consensus by two breast radiologists with 5 (A.H.A.) and 2 (H.S.M.) years of experience. Tumor volumes (TV) were measured on early and late subtractions. Tumors were segmented on 1 and 2.5-minute early phases subtractions and FTV was determined using optimized signal enhancement thresholds. Interpolated enhancement curves from segmented voxels were used to determine optimal early phase timing., Statistical Tests: Tumor volumes were compared between patients who had a pathologic complete response (pCR) and those who did not using the area under the receiver operating curve (AUC) and Mann-Whitney U test., Results: About 26 of 60 patients (43%) had pCR. FTV at 1 minute after injection at C4 provided the best discrimination between pCR and non-pCR, with AUC (95% confidence interval [CI]) = 0.85 (0.74,0.95) (P < 0.05). The 1-minute timing was optimal for FTV measurements at C4 and for the change between C4 and baseline. TV from the early phase at C4 also yielded a good AUC (95%CI) of 0.82 (0.71,0.93) (P < 0.05)., Data Conclusion: FTV and TV measured at 1 minute after injection can predict response to NAST in TNBC., Level of Evidence: 1 TECHNICAL EFFICACY: 4., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR guided radiation therapy systems is providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. The purpose of this report is to provide an educational resource describing MR biomarkers, the techniques used to quantify them, their strengths and weakness within the context of their application to radiation oncology so as to ensure their appropriate use and application within this field., (© 2021 American Association of Physicists in Medicine.)

Purpose: Chronic susceptibility lesions in the brain can be either hemorrhagic (potentially dangerous) or calcific (usually not dangerous) but are difficult to discriminate on routine imaging. We proposed to develop quantitative diagnostic criteria for single-energy computed tomography (SECT), dual-energy computed tomography (DECT), and quantitative susceptibility mapping (QSM) to distinguish hemorrhage from calcium., Materials and Methods: Patients with positive susceptibility lesions on routine T2*-weighted magnetic resonance of the brain were recruited into this prospective imaging clinical trial, under institutional review board approval and with informed consent. The SECT, DECT, and QSM images were obtained, the lesions were identified, and the regions of interest were defined, with the mean values recorded. Criteria for quantitative interpretation were developed on the first 50 patients, and then applied to the next 45 patients. Contingency tables, scatter plots, and McNemar test were applied to compare classifiers., Results: There were 95 evaluable patients, divided into a training set of 50 patients (328 lesions) and a validation set of 45 patients (281 lesions). We found the following classifiers to best differentiate hemorrhagic from calcific lesions: less than 68 Hounsfield units for SECT, calcium level of less than 15 mg/mL (material decomposition value) for DECT, and greater than 38 ppb for QSM. There was general mutual agreement among the proposed criteria. The proposed criteria outperformed the current published criteria., Conclusions: We provide the updated criteria for the classification of chronic positive susceptibility brain lesions as hemorrhagic versus calcific for each major clinically available imaging modality. These proposed criteria have greater internal consistency than the current criteria and should likely replace it as gold standard., Competing Interests: Conflicts of interest and sources of funding: In kind funding through the Center for Advanced Biomedical Imaging at MD Anderson Cancer Center, from GE Healthcare. This clinical trial was physician-initiated, designed and executed by the authors. GE Healthcare's role was limited to funding and the supply of equipment. The company had no role in trial design, execution, or analysis. The company also had no role in writing or editing the study, other than approving the manuscript for release., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Gram-positive (GP) pathogens are less accounted for in pediatric urinary tract infection (UTI), and their clinical impact is underrecognized. This study aimed to identify predictors of GP uropathogens in pediatric UTI. In this 14-year retrospective cohort of pediatric patients with UTI, we classified first-time UTIs cases into those caused by GP or Gram-negative (GN) bacteria. We constructed a multivariable logistic regression model to predict GP UTI. We evaluated model performance through calibration and discrimination plots. We developed a nomogram to predict GP UTI that is clinically feasible. Of 3783 children with first-time UTI, 166 (4.4%) were infected by GP and 3617 (95.6%) by GN bacteria. Among children with GP UTI, the most common uropathogens were vancomycin-resistant Enterococcus faecalis (VRE) (27.1%), Staphylococcus saprophyticus (26.5%), and coagulase-negative Staphylococci (12.7%). Eight independent risk factors were associated with GP UTI: Age ≥ 24 months (odds ratio [OR]: 3.21), no prior antibiotic use (OR: 3.13), serum white blood cell (WBC) count < 14.4 × 10 3 /μL (OR: 2.19), high sensitivity C-reactive protein (hsCRP) < 3.4 mg/dL (OR: 2.18), hemoglobin ≥ 11.3 g/dL (OR: 1.90), negative urine leukocyte esterase (OR: 3.19), negative urine nitrite (OR: 4.13), and urine WBC < 420/μL (OR: 2.37). The model exhibited good discrimination (C-statistic 0.879; 95% CI 0.845-0.913) and calibration performance. VR E. faecalis, the leading GP uropathogen causing pediatric UTI, requires early detection for infection control. Our model for predicting GP UTI can help clinicians detect GP uropathogens and administer antibiotic regimen early.

Objectives: The aims of this study were to develop an accelerated multiparametric magnetic resonance imaging method based on 3D-quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) combined with compressed sensing (CS) and to evaluate the effect of CS on the quantitative mapping, tissue segmentation, and quality of synthetic images., Materials and Methods: A magnetic resonance imaging system phantom, containing multiple compartments with standardized T1, T2, and proton density (PD) values; 10 healthy volunteers; and 12 patients with multiple sclerosis were scanned using the 3D-QALAS sequence with and without CS and conventional contrast-weighted imaging. The scan times of 3D-QALAS with and without CS were 5:56 and 11:11, respectively. For healthy volunteers, brain volumetry and myelin estimation were performed based on the measured T1, T2, and PD. For patients with multiple sclerosis, the mean T1, T2, PD, and the amount of myelin in plaques and contralateral normal-appearing white matter (NAWM) were measured. Simple linear regression analysis and Bland-Altman analysis were performed for each metric obtained from the datasets with and without CS. To compare overall image quality and structural delineations on synthetic and conventional contrast-weighted images, case-control randomized reading sessions were performed by 2 neuroradiologists in a blinded manner., Results: The linearity of both phantom and volunteer measurements in T1, T2, and PD values obtained with and without CS was very strong (R2 = 0.9901-1.000). The tissue segmentation obtained with and without CS also had high linearity (R2 = 0.987-0.999). The quantitative tissue values of the plaques and NAWM obtained with CS showed high linearity with those without CS (R2 = 0.967-1.000). There were no significant differences in overall image quality between synthetic contrast-weighted images obtained with and without CS (P = 0.17-0.99)., Conclusions: Multiparametric imaging of the whole brain based on 3D-QALAS can be accelerated using CS while preserving tissue quantitative values, tissue segmentation, and quality of synthetic images., Competing Interests: Conflicts of interest and sources of funding: N.T. is an employee of GE Healthcare Japan. This work was supported by Japan Agency for Medical Research and Development under grant number JP19lk1010025h9902; JSPS KAKENHI grant numbers 19K17150, 19K17177, 18H02772, and 18K07692; Health, Labor and Welfare Policy Research Grants for Research on Region Medical; and a grant-in-aid for special research in subsidies for ordinary expenses of private schools from The Promotion and Mutual Aid Corporation for Private Schools of Japan; Brain/MINDS beyond program from Japan Agency for Medical Research and Development grant numbers JP19dm0307024 and JP19dm0307101., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/purpose: Urinary tract infections (UTIs) are one of the most common pediatric infections. Our objective in this study is to investigate the association between urine pH and uropathogens in pediatric patients., Methods: The source population comprised 26 066 paired urinalysis (UA) and urine culture (UC) samples obtained from pediatric patients. We classified the paired UA-UC samples into UTI positive (N = 6348) and UTI negative (N = 19 718) according to the colony forming units corresponding to the sampling source. We included UTI positive patients with infection caused by a single species of pathogen (N = 5201) and frequency matched them with UTI negative patients (N = 4729) by age, sex, sampling source, and visit type., Results: This study included 5201 pediatric patients with UTIs and found that urine with Proteus mirabilis or Pseudomonas aeruginosa demonstrated the least acidic pH (mean pH = 6.72 and 6.62, respectively), whereas urine with Escherichia coli or Klebsiella pneumoniae exhibited the most acidic pH (pH = 6.21 and 6.18). After stratifying the UTI samples by their pH range (<6, 6-6.9, 7-7.9, and ≥8). The prevalence of P. mirabilis increased significantly across increasing pH categories., Conclusion: This research is the first epidemiological study that linked urine pH to specific uropathogens in a pediatric population. Both urine pH and age are associated with certain causative uropathogens. Urine that grew P. mirabilis or P. aeruginosa had the least acidic pH. Additional studies should validate the role of urine pH in predicting uropathogens and UTI., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest relevant to the manuscript that is being submitted to the Journal of Microbiology, Immunology and Infection., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: To determine if tumor necrosis by pretreatment breast MRI and its quantitative imaging characteristics are associated with response to NAST in TNBC., Methods: This retrospective study included 85 TNBC patients (mean age 51.8 ± 13 years) with MRI before NAST and definitive surgery during 2010-2018. Each MRI included T2-weighted, diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging. For each index carcinoma, total tumor volume including necrosis (TTV), excluding necrosis (TV), and the necrosis-only volume (NV) were segmented on early-phase DCE subtractions and DWI images. NV and %NV were calculated. Percent enhancement on early and late phases of DCE and apparent diffusion coefficient were extracted from TTV, TV, and NV. Association between necrosis with pathological complete response (pCR) was assessed using odds ratio (OR). Multivariable analysis was used to evaluate the prognostic value of necrosis with T stage and nodal status at staging. Mann-Whitney U tests and area under the curve (AUC) were used to assess performance of imaging metrics for discriminating pCR vs non-pCR., Results: Of 39 patients (46%) with necrosis, 17 had pCR and 22 did not. Necrosis was not associated with pCR (OR, 0.995; 95% confidence interval [CI] 0.4-2.3) and was not an independent prognostic factor when combined with T stage and nodal status at staging (P = 0.46). None of the imaging metrics differed significantly between pCR and non-pCR in patients with necrosis (AUC < 0.6 and P > 0.40)., Conclusion: No significant association was found between necrosis by pretreatment MRI or the quantitative imaging characteristics of tumor necrosis and response to NAST in TNBC.

Acquisition parameter selection is currently performed empirically for many quantitative MRI (qMRI) acquisitions. Tuning parameters for different scan times, tissues, and resolutions requires some amount of trial and error. There is an opportunity to quantitatively optimize these acquisition parameters in order to minimize variability of quantitative maps and post-processing techniques such as synthetic image generation. The objective of this work is to introduce and evaluate a quantitative method for selecting parameters that minimize image variability. An information theory framework was developed for this purpose and applied to a 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) signal model for qMRI. In this framework, mutual information is used to measure the information gained by a measurement as a function of acquisition parameters, quantifying the information content of potential acquisitions and allowing informed parameter selection. The information theory framework was tested on artificial data generated from a representative mathematical phantom, measurements acquired on a qMRI multiparametric imaging standard phantom, and in vivo measurements in a human brain. The phantom measurements showed that higher mutual information calculated by the model correlated with smaller coefficient of variation in the reconstructed parametric maps, and in vivo measurements demonstrated that information-based calibration of acquisition parameters resulted in a decrease in parametric map variability consistent with model predictions.

Magnetic resonance imaging (MRI) offers outstanding soft tissue contrast that may reduce uncertainties in target and organ-at-risk delineation and enable online adaptive image-guided treatment. Spatial distortions resulting from non-linearities in the gradient fields and non-uniformity in the main magnetic field must be accounted for across the imaging field-of-view to prevent systematic errors during treatment delivery. This work presents a modular phantom and software application to characterize geometric distortion (GD) within the large field-of-view MRI images required for radiation therapy simulation. The modular phantom is assembled from a series of rectangular foam blocks containing high-contrast fiducial markers in a known configuration. The modular phantom design facilitates transportation of the phantom between different MR scanners and MR-guided linear accelerators and allows the phantom to be adapted to fit different sized bores or coils. The phantom was evaluated using a 1.5 T MR-guided linear accelerator (MR-Linac) and 1.5 T and 3.0 T diagnostic scanners. Performance was assessed by varying acquisition parameters to induce image distortions in a known manner. Imaging was performed using T1 and T2 weighted pulse sequences with 2D and 3D distortion correction algorithms and the receiver bandwidth (BW) varied as 250-815 Hz pixel -1 . Phantom set-up reproducibility was evaluated across independent set-ups. The software was validated by comparison with a non-modular phantom. Average geometric distortion was 0.94 ± 0.58 mm for the MR-Linac, 0.90 ± 0.53 mm for the 1.5 T scanner, and 1.15 ± 0.62 mm for the 3.0 T scanner, for a 400 mm diameter volume-of-interest. GD increased, as expected, with decreasing BW, and with the 2D versus 3D correction algorithm. Differences in GD attributed to phantom set-up were 0.13 mm or less. Differences in GD for the two software applications were less than 0.07 mm. A novel modular phantom was developed to evaluate distortions in MR images for radiation therapy applications.

Objectives: Quantitative synthetic magnetic resonance imaging (MRI) enables synthesis of various contrast-weighted images as well as simultaneous quantification of T1 and T2 relaxation times and proton density. However, to date, it has been challenging to generate magnetic resonance angiography (MRA) images with synthetic MRI. The purpose of this study was to develop a deep learning algorithm to generate MRA images based on 3D synthetic MRI raw data., Materials and Methods: Eleven healthy volunteers and 4 patients with intracranial aneurysms were included in this study. All participants underwent a time-of-flight (TOF) MRA sequence and a 3D-QALAS synthetic MRI sequence. The 3D-QALAS sequence acquires 5 raw images, which were used as the input for a deep learning network. The input was converted to its corresponding MRA images by a combination of a single-convolution and a U-net model with a 5-fold cross-validation, which were then compared with a simple linear combination model. Image quality was evaluated by calculating the peak signal-to-noise ratio (PSNR), structural similarity index measurements (SSIMs), and high frequency error norm (HFEN). These calculations were performed for deep learning MRA (DL-MRA) and linear combination MRA (linear-MR), relative to TOF-MRA, and compared with each other using a nonparametric Wilcoxon signed-rank test. Overall image quality and branch visualization, each scored on a 5-point Likert scale, were blindly and independently rated by 2 board-certified radiologists., Results: Deep learning MRA was successfully obtained in all subjects. The mean PSNR, SSIM, and HFEN of the DL-MRA were significantly higher, higher, and lower, respectively, than those of the linear-MRA (PSNR, 35.3 ± 0.5 vs 34.0 ± 0.5, P < 0.001; SSIM, 0.93 ± 0.02 vs 0.82 ± 0.02, P < 0.001; HFEN, 0.61 ± 0.08 vs 0.86 ± 0.05, P < 0.001). The overall image quality of the DL-MRA was comparable to that of TOF-MRA (4.2 ± 0.7 vs 4.4 ± 0.7, P = 0.99), and both types of images were superior to that of linear-MRA (1.5 ± 0.6, for both P < 0.001). No significant differences were identified between DL-MRA and TOF-MRA in the branch visibility of intracranial arteries, except for ophthalmic artery (1.2 ± 0.5 vs 2.3 ± 1.2, P < 0.001)., Conclusions: Magnetic resonance angiography generated by deep learning from 3D synthetic MRI data visualized major intracranial arteries as effectively as TOF-MRA, with inherently aligned quantitative maps and multiple contrast-weighted images. Our proposed algorithm may be useful as a screening tool for intracranial aneurysms without requiring additional scanning time.