Search

Sickle cell disease (SCD) decreases the oxygen-carrying capacity of red blood cells. Children with SCD have reduced/restricted cerebral blood flow, resulting in neurocognitive deficits. Hydroxyurea is the standard treatment for SCD; however, whether hydroxyurea influences such effects is unclear. A key area of SCD-associated neurocognitive impairment is working memory, which is implicated in other cognitive and academic skills. The neural correlates of working memory can be tested using n-back tasks. We analyzed functional magnetic resonance imaging (fMRI) data of patients with SCD (20 hydroxyurea-treated patients and 11 controls, aged 7-18 years) while they performed n-back tasks. Blood-oxygenation level-dependent (BOLD) signals were assessed during working memory processing at 2 time points: before hydroxyurea treatment and ~1 year after treatment was initiated. Neurocognitive measures were also assessed at both time points. Our results suggested that working memory was stable in the treated group. We observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- >0-back contrast. Searchlight-pattern classification of the 2 time points of the 2-back tasks identified greater changes in the pattern and magnitude of BOLD signals, especially in the posterior regions of the brain, in the control group than in the treated group. In the control group at 1-year follow-up, 2-back BOLD signals increased across time points in several clusters (e.g., right inferior temporal lobe, right angular gyrus). We hypothesize that these changes resulted from increased cognitive effort during working memory processing in the absence of hydroxyurea. In the treated group, 0- to 2-back BOLD signals in the right angular gyrus and left cuneus increased continuously with increasing working memory load, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. These findings suggest that hydroxyurea treatment helps maintain working memory function in SCD., Competing Interests: Dr. Akshay Sharma has received consultant fees from Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, Sangamo Therapeutics, and Editas Medicine. He has also received research funding from CRISPR Therapeutics and honoraria from Vindico Medical Education. Dr. Sharma is the St. Jude site principal investigator of clinical trials for genome editing for SCD sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907), and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trial, which includes salary support paid to our institution. Dr. Sharma has no direct financial interest in these therapies. Dr. Andrew M. Heitzer has received consulting fees from Global Blood Therapeutics. Neither Dr. Sharma nor Dr. Heitzer is an employee of any commercial entity. All other 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. This does not alter our adherence to PLoS ONE policies on sharing data and materials., (Copyright: © 2024 Lai 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.)

Purpose : Accurate detection of leptomeningeal metastasis (LM) is critical for risk stratification and treatment of pediatric brain tumors. Poor-quality staging MRI has been associated with decreased survival in this population, but technical factors differentiating good from poor quality screening MRIs remain undefined. To test the hypothesis that key technical factors are associated with accurate MRI diagnosis of leptomeningeal metastasis in children with leptomeningeal seeding brain tumors. Methods: MRIs acquired at outside facilities and repeated in our institution within 35 days for 75 children with leptomeningeal seeding tumors were assessed for slice thickness and gap; use of T2 FLAIR + Contrast, acquisition plane of 3DT1WI + Contrast (brain); axial T1 + Contrast sequence, and use of pre-contrast T1 images (spine). Reported findings were recorded as positive, negative, or equivocal for LM and classified as true positive (TP; unequivocal metastasis), false negative (FN; not reported), false positive (FP; resolved without treatment), or true negative. Wilcoxon signed-rank and Fisher's exact test were used to assess technical differences between TP and FN MRIs. Results: Rate of LM detection was greater with smaller interslice gap in brain (P = 0.003) and spine (P = 0.002); use of T2 FLAIR + Contrast (P = 0.005) and sagittal plane for 3DT1WI + Contrast (P = 0.028) in brain; and use of alternatives to axial TSE/FSE in spine (P = 0.048). Slice thickness was not significant. Pre-contrast T1WI did not contribute to LM diagnosis in spine. Conclusion: Using post-contrast T2 FLAIR and sagittal 3DT1 in brain, small/no interslice gap, and avoiding TSE/FSE axials in spine may facilitate leptomeningeal metastasis detection in children with brain tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]