Deep-Learning Models for Abdominal CT Organ Segmentation in Children: Development and Validation in Internal and Heterogeneous Public Datasets.

Background: Deep-learning abdominal organ segmentation algorithms have shown excellent results in adults; validation in children is sparse. Objective: To develop and validate deep-learning models for liver, spleen, and pancreas segmentation on pediatric CT examinations. Methods: This retrospective study developed and validated deep-learning models for liver, spleen, and pancreas segmentation using 1731 CT examinations (1504 training, 221 testing), derived from three internal institutional pediatric (age ≤18) datasets (n=483) and three public datasets comprising pediatric and adult examinations with various pathologies (n=1248). Three deep-learning model architectures (SegResNet, DynUNet, and SwinUNETR) from the Medical Open Network for AI (MONAI) framework underwent training using native training (NT), relying solely on institutional datasets, and transfer learning (TL), incorporating pre-training on public datasets. For comparison, TotalSegmentator (TS), a publicly available segmentation model, was applied to test data without further training. Segmentation performance was evaluated using mean Dice similarity coefficient (DSC), with manual segmentations as reference. Results: For internal pediatric data, DSC for normal liver was 0.953 (TS), 0.964-0.965 (NT models), and 0.965-0.966 (TL models); normal spleen, 0.914 (TS), 0.942-0.945 (NT models), and 0.937-0.945 (TL models); normal pancreas, 0.733 (TS), 0.774-0.785 (NT models), and 0.775-0.786 (TL models); pancreas with pancreatitis, 0.703 (TS), 0.590-0.640 (NT models), and 0.667-0.711 (TL models). For public pediatric data, DSC for liver was 0.952 (TS), 0.876-0.908 (NT models), and 0.941-0.946 (TL models); spleen, 0.905 (TS), 0.771-0.827 (NT models), and 0.897-0.926 (TL models); pancreas, 0.700 (TS), 0.577-0.648 (NT models), and 0.693-0.736 (TL models). For public primarily adult data, DSC for liver was 0.991 (TS), 0.633-0.750 (NT models), and 0.926-0.952 (TL models); spleen, 0.983 (TS), 0.569-0.604 (NT models), and 0.923-0.947 (TL models); pancreas, 0.909 (TS), 0.148-0.241 (NT models), and 0.699-0.775 (TL models). DynUNet-TL was selected as the best-performing NT or TL model and was made available as an opensource MONAI bundle (https://github.com/cchmc-dll/pediatric_abdominal_segmentation_bundle.git). Conclusion: TL models trained on heterogeneous public datasets and fine-tuned using institutional pediatric data outperformed internal NT models and TotalSegmentator across internal and external pediatric test data. Segmentation performance was better in liver and spleen than in pancreas. Clinical Impact: The selected model may be used for various volumetry applications in pediatric imaging.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

BACKGROUND: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. METHODS: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ±â€…13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). CONCLUSION: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Despite advances in medical therapy, many patients with ileal Crohn's disease progress to fibrostenosis requiring surgery. Our study has shown that GM-CSF autoantibodies and MRI biomarker sequences are associated with the need for ileal resection and may help guide management decisions.

Localized alterations in cortical thickness and sulcal depth of the cingulo-opercular network in relation to lower reading fluency skills in children with dyslexia.

The traditional models of reading development describe how language processing and word decoding contribute to reading comprehension and how impairments in word decoding, a defining feature of dyslexia, affect reading comprehension outcomes. However, these models do not include word and sentence reading (contextual reading) fluency, both of which engage executive functions, with notably decreased performance in children with dyslexia. In the current study, we compared cortical thickness and sulcal depth (CT/SD) in the cingulo-opercular (CO) executive functions brain network in children with dyslexia and typical readers and examined associations with word vs. contextual reading fluency. Overall, CT was lower in insular regions and higher in parietal and caudal anterior cingulate cortex regions in children with dyslexia. Children with dyslexia showed positive correlations between word reading fluency and CT/SD in insular regions, whereas no significant correlations were observed in typical readers. For sentence reading fluency, negative correlations with CT/SD were found in insular regions in children with dyslexia, while positive correlations with SD were found in insular regions in typical readers. These results demonstrate the differential relations between word and sentence reading fluency and anatomical circuitry supporting executive functions in children with dyslexia vs. typical readers. It also suggests that word and sentence reading fluency, relate to morphology of executive function-related regions in children with dyslexia, whereas in typical readers, only sentence reading fluency relates to morphology of executive function regions. The results also highlight the role of the insula within the CO network in reading fluency. Here we suggest that word and sentence reading fluency are distinct components of reading that should each be included in the Simple View of Reading traditional model.

Machine learning to detect the SINEs of cancer.

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid.

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

Augmented pain-evoked primary sensorimotor cortex activation in adolescent girls with juvenile fibromyalgia.

ABSTRACT: Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM. Thirty-three adolescent girls with JFM and 33 healthy adolescent girls underwent functional magnetic resonance imaging scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm 2 and rated pain intensity and unpleasantness on a computerized Visual Analogue Scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses. The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities ( P < 0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm 2 (Z > 3.1, cluster-corrected P < 0.05), and the peak S1 activation magnitudes significantly correlated with the scores on the Widespread Pain Index ( r = 0.35, P = 0.048) with higher activation associated with more widespread pain. We also found that greater primary sensorimotor cortex activation in response to 4 kg/cm 2 mediated the between-group differences in pain intensity ratings ( P < 0.001). In conclusion, we found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input.

Maternal education as an environmental factor related to reading in children with reading difficulties: A functional magnetic resonance imaging study.

The expanded simple view of reading (SVR) model suggests that word decoding, language comprehension and executive functions are necessary for reading comprehension. Children with reading difficulties (RDs) often have deficits in critical components of reading established in the expanded SVR model and alterations in brain function of reading-related regions. Maternal education could provide children with advantageous educational opportunities or resources that support reading acquisition. The primary goal of this study was to examine the contributions of maternal education to the behavioural and neurobiological correlates of the expanded SVR model. Seventy-two 8- to 12-year-old children with RDs and typical readers (TRs) completed reading, behavioural and an functional magnetic resonance imaging stories-listening task to determine the functional connectivity of the receptive language network to the whole brain in association with maternal education. Higher maternal education was associated with better vocabulary in children with RDs and positive functional connectivity between the receptive language network and regions related to visual processing in children with RDs versus TRs. These data suggest that maternal education supports the ability to comprehend oral language and engagement of neural networks that support imagination/visualization in children with RDs.

Visuo-vestibular and cognitive connections of the vestibular neuromatrix are conserved across age and injury populations.

BACKGROUND AND PURPOSE: Given the prevalence of vestibular dysfunction in pediatric concussion, there is a need to better understand pathophysiological disruptions within vestibular and associated cognitive, affective, and sensory-integrative networks. Although current research leverages established intrinsic connectivity networks, these are nonspecific for vestibular function, suggesting that a pathologically guided approach is warranted. The purpose of this study was to evaluate the generalizability of the previously identified "vestibular neuromatrix" in adults with and without postconcussive vestibular dysfunction to young athletes aged 14-17. METHODS: This retrospective study leveraged resting-state functional MRI data from two sites. Site A included adults with diagnosed postconcussive vestibular impairment and healthy adult controls and Site B consisted of young athletes with preseason, postconcussion, and postseason time points (prospective longitudinal data). Adjacency matrices were generated from preprocessed resting-state data from each sample and assessed for overlap and network structure in MATLAB. RESULTS: Analyses indicated the presence of a conserved "core" network of vestibular regions as well as areas subserving visual, spatial, and attentional processing. Other vestibular connections were also conserved across samples but were not linked to the "core" subnetwork by regions of interest included in this study. CONCLUSIONS: Our results suggest that connections between central vestibular, visuospatial, and known intrinsic connectivity networks are conserved across adult and pediatric participants with and without concussion, evincing the significance of this expanded, vestibular-associated network. Our findings thus support this network as a workable model for investigation in future studies of dysfunction in young athlete populations.

Colorectal cancer in patients of advanced age is associated with increased incidence of BRAF p.V600E mutation and mismatch repair deficiency.

Introduction: The highest incidence of colorectal cancer (CRC) is in patients diagnosed at 80 years or older highlighting a need for understanding the clinical and molecular features of these tumors. Methods. In this retrospective cohort study, 544 CRCs underwent next generation sequencing and mismatch repair (MMR) evaluation. Molecular and clinical features were compared between 251 patients with traditional-onset CRC (50-69 years at diagnosis) and 60 with late-onset CRC (>80 years at diagnosis). Results: Late-onset CRC showed a significantly higher rate of right-sided tumors (82% vs 35%), MMR deficiency (35% vs. 8%) and BRAF p.V600E mutations (35% vs. 8%) and a significantly lower rate of stage IV disease (15% vs 28%) and APC mutations (52% vs. 78%). Association of these features with advanced age was supported by stratifying patients into 6 age groups (<40, 40-49, 50-59, 60-69, 70-79 and >80 years). However, the age-related rise in MMR deficient (dMMR) CRC was only seen in the female patients with an incidence of 48% (vs. 10% in the male patient) in the >80y group. In addition, BRAF p.V600E was significantly enriched in MMR deficient CRC of advanced age (67% in late-onset CRC). Categorizing CRC by mutational profiling, late-onset CRC revealed a significantly higher rate of dMMR/BRAF + APC - (18% vs. 2.0%), dMMR/BRAF - APC - (8.3% vs. 1.2%) and MMR proficient (pMMR)/BRAF + APC - (12% vs. 4.0%) as compared to traditional-onset CRC. Discussion: In summary, there was a higher rate of dMMR and BRAF p.V600E in late-onset CRC, independently or in combination. The higher incidence of dMMR in late-onset CRC in females is most likely predominantly driven by BRAF p.V600E induced hypermethylation. Prospective studies with treatment plans designed specifically for these older patients are warranted to improve their outcomes.

Liver T1 Relaxation Quantification Using a 3-Dimensional Interleaved Look-Locker Acquisition With T2 Preparation Pulse Sequence (3D-QALAS): Comparison With Conventional 2-Dimensional MOLLI.

BACKGROUND: Changes in liver magnetic resonance imaging T1 relaxation times are associated with histologic inflammation and fibrosis. OBJECTIVE: To compare liver T1 measurements obtained using a novel single-breath-hold 3-dimensional (3D) whole-liver T1 estimation method (3D-QALAS) to standard-of-care 2-dimensional (2D) modified Look-Locker (2D-MOLLI) measurements. METHODS: With institutional review board approval, research magnetic resonance imaging examinations were performed in 19 participants at 1.5 T. T1 relaxometry of the liver was performed using a novel 3D whole-liver T1 estimation method (3D-QALAS) as well as a 2D modified Look-Locker (2D-MOLLI) method. The 3D method covered the entire liver in a single breath hold, whereas 2D imaging was performed at 4 anatomic levels in 4 consecutive breath holds. T1 measurements from parametric maps were obtained by a single operator, and region-of-interest area-weighted mean T1 values were calculated. Pearson correlation ( r ) was used to assess correlation between T1 estimation methods, and the paired t test and Bland-Altman analysis were used to compare agreement in T1 measurements. RESULTS: In 18 participants (1 participant was excluded from analysis because of respiratory motion artifacts on 3D-QALAS images), 2D-MOLLI and 3D-QALAS mean T1 measurements were strongly correlated ( r = 0.95, [95% CI: 0.87-0.98]; P < 0.0001). 2D-MOLLI T1 values were significantly longer than 3D-QALAS values (647.2 ± 87.3 milliseconds vs. 554.7 ± 75.8 milliseconds; P < 0.0001) with mean bias = 92.5 milliseconds (95% limits of agreement, 36.8, 148.2 milliseconds). CONCLUSION: Whole-liver T1 measurements obtained using a novel single-breath-hold 3D T1 estimation method correlate with a standard-of-care multiple consecutive-breath-hold 2D single-slice method but demonstrate systematic bias that should be considered or corrected when used in a clinical or research setting.

Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules.

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.

ABCD_Harmonizer: An Open-source Tool for Mapping and Controlling for Scanner Induced Variance in the Adolescent Brain Cognitive Development Study.

Data from multisite magnetic resonance imaging (MRI) studies contain variance attributable to the scanner that can reduce statistical power and potentially bias results if not appropriately managed. The Adolescent Cognitive Brain Development (ABCD) study is an ongoing, longitudinal neuroimaging study acquiring data from over 11,000 children starting at 9-10 years of age. These scans are acquired on 29 different scanners of 5 different model types manufactured by 3 different vendors. Publicly available data from the ABCD study include structural MRI (sMRI) measures such as cortical thickness and diffusion MRI (dMRI) measures such as fractional anisotropy. In this work, we 1) quantify the variance attributable to scanner effects in the sMRI and dMRI datasets, 2) demonstrate the effectiveness of the data harmonization approach called ComBat to address scanner effects, and 3) present a simple, open-source tool for investigators to harmonize image features from the ABCD study. Scanner-induced variance was present in every image feature and varied in magnitude by feature type and brain location. For almost all features, scanner variance exceeded variability attributable to age and sex. ComBat harmonization was shown to effectively remove scanner induced variance from all image features while preserving the biological variability in the data. Moreover, we show that for studies examining relatively small subsamples of the ABCD dataset, the use of ComBat harmonized data provides more accurate estimates of effect sizes compared to controlling for scanner effects using ordinary least squares regression.

Examining reaction time variability on the stop-signal task in the ABCD study.

OBJECTIVE: Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined interrelationships among these performance indices in childhood, and the use of reaction time (RT) computational models has been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the interrelationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs. METHOD: This study utilized trial-level data from the stop signal task from 8916 children (9-10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined interrelations among these indicators, temporal patterns, and sex differences. RESULTS: There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while nondecisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls' wide boundary separation. CONCLUSIONS: Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.

Associations between digital media use and brain surface structural measures in preschool-aged children.

The American Academy of Pediatrics recommends limits on digital media use ("screen time"), citing cognitive-behavioral risks. Media use in early childhood is ubiquitous, though few imaging-based studies have been conducted to quantify impacts on brain development. Cortical morphology changes dynamically from infancy through adulthood and is associated with cognitive-behavioral abilities. The current study involved 52 children who completed MRI and cognitive testing at a single visit. The MRI protocol included a high-resolution T1-weighted anatomical scan. The child's parent completed the ScreenQ composite measure of media use. MRI measures included cortical thickness (CT) and sulcal depth (SD) across the cerebrum. ScreenQ was applied as a predictor of CT and SD first in whole-brain regression analyses and then for regions of interest (ROIs) identified in a prior study of screen time involving adolescents, controlling for sex, age and maternal education. Higher ScreenQ scores were correlated with lower CT in right-lateralized occipital, parietal, temporal and fusiform areas, and also lower SD in right-lateralized inferior temporal/fusiform areas, with substantially greater statistical significance in ROI-based analyses. These areas support primary visual and higher-order processing and align with prior findings in adolescents. While differences in visual areas likely reflect maturation, those in higher-order areas may suggest under-development, though further studies are needed.

Helmet Technology, Head Impact Exposure, and Cortical Thinning Following a Season of High School Football.

The purpose of this study was to compare the effects of wearing older, lower-ranked football helmets (LRank) to wearing newer, higher-ranked football helmets (HRank) on pre- to post-season changes in cortical thickness in response to repetitive head impacts and assess whether changes in cortical thickness are associated with head impact exposure for either helmet type. 105 male high-school athletes (NHRank = 52, NLRank = 53) wore accelerometers affixed behind the left mastoid during all practices and games for one regular season of American football to monitor head impact exposure. Pre- and post-season magnetic resonance imaging (MRI) were completed to assess longitudinal changes in cortical thickness. Significant reductions in cortical thickness (i.e., cortical thinning) were observed pre- to post-season for each group, but these longitudinal alterations were not significantly different between the LRank and HRank groups. Further, significant group-by-head impact exposure interactions were observed when predicting changes in cortical thickness. Specifically, a greater frequency of high magnitude head impacts during the football season resulted in greater cortical thinning for the LRank group, but not for the HRank group. These data provide preliminary in vivo evidence that HRank helmets may provide a buffer between the specific effect of high magnitude head impacts on regional thinning by dissipating forces more evenly throughout the cortex. However, future research with larger sample sizes, increased longitudinal measures and additional helmet technologies is warranted to both expand upon and further validate the present study findings.

Velocity-Encoded Phase-Contrast MRI for Measuring Mesenteric Blood Flow in Patients With Newly Diagnosed Small-Bowel Crohn Disease.

BACKGROUND. Intestinal inflammation is associated with radiologic and histologic hyperemia. A paucity of studies have used MRI to measure mesenteric blood flow in patients with Crohn disease. OBJECTIVE. The purpose of this study was to evaluate the application of velocity-encoded phase-contrast MRI for measuring mesenteric blood flow in patients with newly diagnosed small-bowel Crohn disease. METHODS. This prospective study included 20 patients with ileal Crohn disease newly diagnosed between December 2018 and October 2021 (eight female participants, 12 male participants; median age, 14.0 years), and 15 healthy control participants (eight female participants, seven male participants; median age, 17.0 years). Patients with Crohn disease underwent investigational MRI and laboratory assessments at diagnosis and at 6 weeks and 6 months after initiating anti-tumor necrosis factor-α medical therapy; control participants underwent a single investigational MRI examination. All MRI examinations included a velocity-encoded phase-contrast acquisition, which was used to measure blood flow in the abdominal aorta, superior mesenteric artery (SMA), and superior mesenteric vein (SMV). Mann-Whitney U test was used to compare blood flow measurements (ratios of SMA and SMV blood flow to aorta blood flow [hereafter, SMA-to-aorta and SMV-to-aorta blood flow, respectively]) between groups; Friedman test was used to evaluate temporal changes in blood flow. Spearman correlation was used to assess relationships between blood flow measurements and laboratory markers of intestinal inflammation. Diagnostic performance was assessed by ROC analysis. RESULTS. At baseline, SMA-to-aorta blood flow in patients versus control participants was 0.44 versus 0.30 (p = .003), and SMV-to-aorta blood flow was 0.36 versus 0.21 (p = .002). At 6 weeks and 6 months, SMA-to-aorta blood flow in patients decreased to 0.30 and 0.27 (p < .001), and SMV-to-aorta blood flow decreased to 0.27 and 0.21 (p = .02), respectively. SMA-to-aorta and SMV-to-aorta blood flow were positively correlated with C-reactive protein (rho, 0.34 [p = .01] and 0.35 [p = .008], respectively) and fecal calprotectin (rho, 0.34 [p = .01] vs 0.47 [p < .001]). AUCs for differentiating patients from controls were 0.79 for SMA-to-aorta (sensitivity, 60%; specificity, 100%) and 0.82 for SMV-to-aorta (sensitivity, 75%; specificity, 87%) blood flow. CONCLUSION. Mesenteric blood flow is quantifiable using velocity-encoded phase-contrast MRI. The measurements differ between patients with ileal Crohn disease and healthy control participants and change in response to medical therapy. CLINICAL IMPACT. MRI-based mesenteric blood flow measurements provide a potential novel marker of intestinal inflammation.

Does central nervous system dysfunction underlie patellofemoral pain in young females? Examining brain functional connectivity in association with patient-reported outcomes.

Patellofemoral pain (PFP) is defined as retro- or peri-patellar knee pain without a clear structural abnormality. Unfortunately, many current treatment approaches fail to provide long-term pain relief, potentially due to an incomplete understanding of pain-disrupted sensorimotor dysfunction within the central nervous system. The purposes of this study were to evaluate brain functional connectivity in participants with and without PFP, and to determine the relationship between altered brain functional connectivity in association with patient-reported outcomes. Young female patients with PFP (n = 15; 14.3 ± 3.2 years) completed resting-state functional magnetic resonance imaging (rs-fMRI) and patient-reported outcome measures. Each patient with PFP was matched with two controls (n = 30, 15.5 ± 1.4 years) who also completed identical rs-fMRI testing. Six bilateral seeds important for pain and sensorimotor control were created, and seed-to-voxel analyses were conducted to compare functional connectivity between the two groups, as well as to determine the relationship between connectivity alterations and patient-reported outcomes. Relative to controls, patients with PFP exhibited altered functional connectivity between regions important for pain, psychological functioning, and sensorimotor control, and the connectivity alterations were related to perceived disability, dysfunction, and kinesiophobia. The present results support emergent evidence that PFP is not localized to structural knee dysfunction, but may actually be resultant to altered central neural processes. Clinical significance: These data provide potential neuro-therapeutic targets for novel therapies aimed to reorganize neural processes, improve neuromuscular function, and restore an active pain-free lifestyle in young females with PFP.

Effect of Subconcussive Head Impact Exposure and Jugular Vein Compression on Behavioral and Cognitive Outcomes after a Single Season of High-School Football: A Prospective Longitudinal Trial.

This prospective longitudinal trial aimed to (1) determine the role of head impact exposure on behavioral/cognitive outcomes, and (2) assess the protective effect(s) of a jugular vein compression (JVC) collar on behavioral/cognitive outcomes after one season of high-school football. Participants included 284 male high-school football players aged 13-18 years enrolled from seven Midwestern high-schools. Schools were allocated to the JVC collar intervention (four teams, 140 players) or no collar/no intervention control (three teams, 144 players) condition. Head impact exposure was measured throughout the season using CSx accelerometers. Outcome measures included post-season parent and adolescent report on Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Scale (SWAN) and Post-Concussion Symptom Inventory (PCSI), as well as adolescent performance on Attention Network Task (ANT), digital Trail Making Task (dTMT), and Cued Switching task. No significant effect of head impact exposure or JVC collar use on post-season SWAN or PCSI scores or performance on dTMT and Cued Switching task were noted. There was no effect of head impact exposure on ANT performance; however, the JVC collar group had greater post-season Alerting network scores than the no collar group (p = 0.026, d = 0.22). Findings provide preliminary evidence that the JVC collar may provide some protection to the alerting attention system. These findings should be interpreted cautiously as a greater understanding of the long-term sequelae of head impact exposure and the role of cumulative head impact exposure behavioral/cognitive outcomes is required.