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Background: Point-of-care ultrasound (POCUS) has transformed inflammatory bowel disease (IBD) management, but the cost to purchase high-end equipment can be prohibitive., Aim: To assess prospectively the feasibility of POCUS using pre-existing mid-end ultrasound equipment without incurring additional cost., Methods: Consecutive IBD patients underwent POCUS with or without faecal calprotectin (FCP) using a mid-end ultrasound machine. If POCUS with or without FCP could not guide management, we performed additional ileocolonoscopy or cross-sectional imaging. We evaluated the impact of POCUS on IBD management and its correlation with ileocolonoscopy or cross-sectional imaging. We analysed pregnant, paediatric and post-operative patients separately., Results: Among 508 patients with IBD, we analysed 419 (60.4% Crohn's disease [CD]; 61.3% male, age [years]: 36 [18-78]) undergoing 556 POCUS sessions. POCUS with or without FCP independently influenced clinical management in 42.8% of patients with CD and 49.7% with ulcerative colitis (UC). POCUS helped avoid colonoscopy in 51.4% of patients with CD and 51.8% with UC, and cross-sectional imaging in 38.1% of suspected active small bowel CD. In patients with additional diagnostics, POCUS-based decisions remained unchanged in 81.2% with CD and 85% with UC. Sensitivity and specificity of POCUS compared to ileocolonoscopy were 80% and 94.4% for CD and 80.8% and 92.8% for UC, respectively. Sensitivity and specificity compared to cross-sectional imaging were 87.2% and 87.5%, respectively., Conclusion: POCUS using existing mid-end ultrasound equipment in low-resource settings influenced IBD clinical decision-making with excellent accuracy, often avoiding colonoscopy and cross-sectional imaging., (© 2024 John Wiley & Sons Ltd.)

Description: In the past 3 years, the use of intestinal ultrasound (IUS) for monitoring inflammatory bowel disease in clinical practice has grown substantially in the United States. This American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) aims to review the available evidence and guidance regarding the role of intestinal ultrasound in inflammatory bowel disease care., Methods: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important and recently published studies in this field, and it reflects the experiences of the multidisciplinary group of authors composed of adult and pediatric gastroenterologists., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Bismuth (Bi)-based computed tomography (CT) imaging contrast agents (CAs) hold significant promise for diagnosing gastrointestinal diseases due to their cost-effectiveness, heightened sensitivity, and commendable biocompatibility. Nevertheless, substantial challenges persist in achieving an easy synthesis process, remarkable water solubility, and effective targeting ability for the potential clinical transformation of Bi-based CAs. Herein, we show Bi drug-inspired ultra-small dextran coated bismuth oxide nanoparticles (Bi 2 O 3 -Dex NPs) for targeted CT imaging of inflammatory bowel disease (IBD). Bi 2 O 3 -Dex NPs are synthesized through a simple alkaline precipitation reaction using bismuth salts and dextran as the template. The Bi 2 O 3 -Dex NPs exhibit ultra-small size (3.4 nm), exceptional water solubility (over 200 mg mL -1 ), high Bi content (19.75 %), excellent biocompatibility and demonstrate higher X-ray attenuation capacity compared to clinical iohexol. Bi 2 O 3 -Dex NPs not only enable clear visualization of the GI tract outline and intestinal loop structures in CT imaging but also specifically target and accumulate at the inflammatory site in colitis mice after oral administration, facilitating a precise diagnosis and enabling targeted CT imaging of IBD. Our study introduces a novel and clinically promising strategy for synthesizing high-performance Bi 2 O 3 -Dex NPs for diagnosing gastrointestinal diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric IBD patients. Patient level structured data include IBD diagnosis, 12- and 52-week steroid use and name, and remission status. Each slide is labelled with biopsy site and normal or abnormal classification per the surgical pathology report. Each tissue section scan from an abnormal slide is further classified by an experienced pathologist. Researchers utilizing this dataset may select from the provided outcomes or add labels and annotations from their own institutions., (© 2024. The Author(s).)

Developing a noninvasive imaging method to detect immune system activation with a high temporal resolution is key to improving inflammatory bowel disease (IBD) management. In this study, granzyme B (GZMB), typically released from cytotoxic T and natural killer cells, was targeted using PET with 68 Ga-NOTA-GZP (where GZP is β-Ala-Gly-Gly-Ile-Glu-Phe-Asp-CHO) to detect early intestinal inflammation in murine models of colitis. Methods: Bioinformatic analysis was used to assess the potential of GZMB as a biomarker for detecting IBD and predicting response to treatment. Human active and quiescent Crohn disease and ulcerative colitis tissues were stained for GZMB. We used IL-10 -/- mice treated with dextran sulfate sodium (DSS) as an IBD model, wild-type C57BL/6J mice as a control, and anti-tumor necrosis factor as therapy. We used a murine GZMB-binding peptide conjugated to a NOTA chelator (NOTA-GZP) labeled with 68 Ga as the PET tracer. PET imaging was conducted at 1, 3, and 4 wk after colitis induction to evaluate temporal changes. Results: Bioinformatic analysis showed that GZMB gene expression is significantly upregulated in human ulcerative colitis and Crohn disease compared with the noninflamed bowel by 2.98-fold and 1.92-fold, respectively; its expression is lower by 2.16-fold in treatment responders than in nonresponders. Immunofluorescence staining of human tissues demonstrated a significantly higher GZMB in patients with active than with quiescent IBD ( P = 0.032). 68 Ga-NOTA-GZP PET imaging showed significantly increased bowel uptake in IL-10 -/- mice with DSS-induced colitis compared with vehicle-treated IL-10 -/- mice (SUV mean , 0.75 vs. 0.24; P < 0.001) and both vehicle- and DSS-treated wild-type mice (SUV mean , 0.26 and 0.37; P < 0.001). In the IL-10 -/- DSS-induced colitis model, the bowel PET probe uptake decreased in response to treatment with tumor necrosis factor-α (SUV mean , 0.32; P < 0.001). There was a 4-fold increase in colonic uptake of 68 Ga-NOTA-GZP in the colitis model compared with the control 1 wk after colitis induction. The uptake gradually decreased to approximately 2-fold by 4 wk after IBD induction; however, the inflamed bowel uptake remained significantly higher than control at all time points (week 4 SUV mean , 0.23 vs. 0.08; P = 0.001). Conclusion: GZMB is a promising biomarker to detect active IBD and predict response to treatment. This study provides compelling evidence to translate GZMB PET for imaging IBD activity in clinical settings., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Aims: Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA., Methods: We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control., Results: Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA., Conclusions: To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD.

Background: Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in this population., Methods: 153 consecutive patients were included, 100 in the training cohort and 53 in the study cohort. Three superficial muscles (rectus femoris = RF, rectus abdominis = RA, and biceps brachii = BB) were selected for the detection of sarcopenia using muscle ultrasound (US). The training cohort consisted of consecutive patients with or without IBD and was used to evaluate the feasibility and inter- and intra-observer variability of the US measurement. The study cohort consisted of only IBD patients and served to test US diagnostic accuracy. In the latter, muscle US, bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were used to measure muscle parameters., Results: Sarcopenia prevalence in IBD patients was 50%. Muscle US showed excellent inter-rater and intra-rater reliability (ICC >0.95) and a good diagnostic accuracy in detecting sarcopenia compared to BIA with area under the receiver operating characteristic curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined as the sum of the RA, BB, and RF thickness divided by the square of the patient's height, resulting in an AUROC of 81%. Muscle thresholds for sarcopenia were detected, with RA and USMI values correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Additionally, the agreement between the US and MRI measurements of RA was excellent (ICC 0.96)., Conclusions: The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. This research has significant implications for disease management in IBD patients and underscores the need for further investigations to validate these findings in larger cohorts., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Blood-based biomarkers that reliably indicate disease activity in the intestinal tract are an important unmet need in the management of patients with IBD. Extracellular vesicles (EVs) are cell-derived membranous microparticles, which reflect the cellular and functional state of their site of site of origin. As ultrasound waves may lead to molecular shifts of EV contents, we hypothesized that application of ultrasound waves on inflamed intestinal tissue in IBD may amplify the inflammation-specific molecular shifts in EVs like altered EV-miRNA expression, which in turn can be detected in the peripheral blood. 26 patients with IBD were included in the prospective clinical study. Serum samples were collected before and 30 min after diagnostic transabdominal ultrasound. Differential miRNA expression was analyzed by sequencing. Candidate inducible EV-miRNAs were functionally assessed in vitro by transfection of miRNA mimics and qPCR of predicted target genes. Serum EV-miRNA concentration at baseline correlated with disease severity, as determined by clinical activity scores and sonographic findings. Three miRNAs (miR-942-5p, mir-5588, mir-3195) were significantly induced by sonography. Among the significantly regulated EV-miRNAs, miR-942-5p was strongly induced in higher grade intestinal inflammation and correlated with clinical activity in Crohn's disease. Prediction of target regulation and transfection of miRNA mimics inferred a role of this EV-miRNA in regulating barrier function in inflammation. Induction of mir-5588 and mir-3195 did not correlate with inflammation grade. This proof-of-concept trial highlights the principle of induced molecular shifts in EVs from inflamed tissue through transabdominal ultrasound. These inducible EVs and their molecular cargo like miRNA could become novel biomarkers for intestinal inflammation in IBD., (© 2024. The Author(s).)

Background: Enteropathic spondyloarthritis is underdiagnosed and inflammatory biomarkers and ultrasonography (US) could be useful for screening inflammatory bowel disease (IBD) patients. The objective of this study was to evaluate the prevalence of spondyloarthritis (SpA) in IBD patients, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria and the correlation of results of US of entheses and joints with plasma calprotectin levels., Methods: This was an observational cross-sectional study. Patients from the IBD outpatient clinic of a reference center were evaluated according to ASAS criteria classification, results of US of entheses and joints, and inflammatory biomarker measurements (erythrocyte sedimentation rates, C-reactive protein levels, fecal and plasma calprotectin levels). A p value lower than 0.05 was considered significant., Results: A total of 30.5% of the studied sample (n = 118) of patients with IBD presented at least one inflammatory musculoskeletal manifestation. The overall prevalence of enteropathic SpA was 13.55%, with 10.16% axial SpA and 4.23% peripheral SpA according to the ASAS criteria. A total of 42.1% of patients had an MASEI score greater than 18, 35.2% had synovitis, and 14.7% had tenosynovitis on US, increasing the frequency of diagnosis of enteropathic SpA to 22.8%. Plasma calprotectin levels were similar to those in healthy controls, and correlated only with the fecal calprotectin level (p 0.041)., Conclusions: A total of 13.5% of patients met the criteria in accordance with the ASAS criteria for enteropathic SpA, which increased to 22.8% with the addition of US. The prevalence of enthesitis, synovitis and tenosynovitis by US of symptomatic joints and entheses were 42%, 35% and 14.7% respectively. Plasma calprotectin was correlated with fecal calprotectin but not with inflammatory biomarkers or US or ASAS criteria., (© 2024. The Author(s).)

Background: Inflammatory bowel diseases (IBD) are associated with important changes in nutritional status., Objective: The aim of the study was to compare body fat composition between two anthropometric methods: skinfolds and ultrasonography, in patients with IBD., Methods: Single-center cross-sectional study with IBD patients in remission or active disease. For the agreement analysis between the body fat assessment methods, the Bland Altman method was used., Results: A total of 101 patients with IBD were included, 75 with Crohn's disease and 26 with ulcerative colitis. Approximately 56% of the patients with Crohn's disease and 65.4% of those with ulcerative colitis had a body fat composition above normal levels, with no significant difference between the diseases (P=0.63). The Bland-Altman concordance analysis showed that the methods for assessing the percentage of fat by the adipometer and ultrasound were not in full agreement (P=0.001), despite both presented good correlation (CC 0.961; P=0.000)., Conclusion: The analysis of body fat percentage in patients with IBD was different between the skinfolds and ultrasound. Both methods can be used to assess the of body fat percentage of patients with IBD. However, monitoring of body fat sequentially and longitudinally should always be performed using the same method throughout the disease course. Prospective longitudinal studies are warranted to precisely define the role of these two methods of measuring body composition in patients with IBD., Background: • Inflammatory bowel diseases are associated with changes in nutritional status., Background: • Skinfolds measurements and ultrasound are valid methods for assessing body composition and body fat., Background: • These methods despite comparable are not identical and are useful in clinical nutritional practices in IBD.

Intestinal fibrosis is one of the major complications of inflammatory bowel disease (IBD) and a pathological process that significantly impacts patient prognosis and treatment selection. Although current imaging assessment and clinical markers are widely used for the diagnosis and stratification of fibrosis, these methods suffer from subjectivity and limitations. In this study, we aim to develop a radiomics diagnostic model based on multi-slice computed tomography (MSCT) and clinical factors. MSCT images and relevant clinical data were collected from 218 IBD patients, and a large number of quantitative image features were extracted. Using these features, we constructed a radiomics model and transformed it into a user-friendly diagnostic nomogram. A nomogram was developed to predict fibrosis in IBD by integrating multiple factors. The nomogram exhibited favorable discriminative ability, with an AUC of 0.865 in the validation sets, surpassing both the logistic regression (LR) model (AUC = 0.821) and the clinical model (AUC = 0.602) in the test set. In the train set, the LR model achieved an AUC of 0.975, while the clinical model had an AUC of 0.735. The nomogram demonstrated superior performance with an AUC of 0.971, suggesting its potential as a valuable tool for predicting fibrosis in IBD and improving clinical decision-making. The radiomics nomogram, incorporating MSCT and clinical factors, demonstrates promise in stratifying fibrosis in IBD. The nomogram outperforms traditional clinical models and offers personalized risk assessment. However, further validation and addressing identified limitations are necessary to enhance its applicability., (© 2024. The Author(s).)

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis and Crohn disease, is a chronic inflammatory disorder resulting from an aberrant immune response, though its exact cause is unknown. The current mainstay standard of care for the diagnosis and surveillance of IBD is endoscopy. However, this methodology is invasive and images only superficial tissue structures, revealing very little about the molecular drivers of inflammation. Accordingly, there is an unmet need for noninvasive imaging tools that provide reliable and quantitative visualization of intestinal inflammation with high spatial and molecular specificity. In recent years, several PET agents for imaging IBD have been reported. Such agents allow noninvasive visualization and quantification of dynamic molecular inflammatory processes in vivo. This review focuses on recent advancements in the development of PET tracers for imaging biomarkers of interest in IBD pathogenesis, such as cell-surface molecules that are overexpressed on immune cells and cytokines that perpetuate inflammatory signaling., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Inflammatory bowel disease (IBD), which includes both Crohn disease and ulcerative colitis, is a relapsing inflammatory disease of the gastrointestinal tract. Long-term chronic inflammatory conditions elevate the patient's risk of colorectal cancer (CRC). Currently, diagnosis requires endoscopy with biopsy. This procedure is invasive and requires a bowel-preparatory regimen, adding to patient burden. Interleukin 12 (IL12) and interleukin 23 (IL23) play key roles in inflammation, especially in the pathogenesis of IBD, and are established therapeutic targets. We propose that imaging of IL12/23 and its p40 subunit in IBD via immuno-PET potentially provides a new noninvasive diagnostic approach. Methods: Our aim was to investigate the potential of immuno-PET to image inflammation in a chemically induced mouse model of colitis using dextran sodium sulfate by targeting IL12/23p40 with a 89 Zr-radiolabeled anti-IL12/23p40 antibody. Results: High uptake of the IL12/23p40 immuno-PET agent was exhibited by dextran sodium sulfate-administered mice, and this uptake correlated with increased IL12/23p40 present in the sera. Competitive binding studies confirmed the specificity of the radiotracer for IL12/23p40 in the gastrointestinal tract. Conclusion: These promising results demonstrate the utility of this radiotracer as an imaging biomarker of IBD. Moreover, IL12/23p40 immuno-PET can potentially guide treatment decisions for IBD management., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background/aims: In the past, dye-spraying chromoendoscopy was the technique of choice for colonic surveillance in patients with long-standing extensive inflammatory bowel disease. Recent evidence suggests that virtual chromoendoscopy is an equally acceptable technique., Materials and Methods: Eleven gastroenterologists were given a survey with 20 pairs of pictures from inflammatory bowel disease surveillance colonoscopies (10 with nondysplastic lesions, 5 with dysplastic lesions, and 5 with no lesions). Each pair contained the same image captured during colonoscopy using indigo carmine and narrow-band imaging. For each picture, the gastroenterologist assessed the presence/absence of lesion and, when a lesion was identified, assessed the presence/absence of dysplasia and delineated its margins. To compare lesion and dysplasia detection between techniques, sensitivity, specificity, and interobserver agreement were calculated. The chi-square test was used to assess the accuracy of margins delineation., Results: When assessing lesion and dysplasia detection, similar sensitivity and specificity values were obtained for both techniques. Interobserver agreement analysis revealed that dye-spraying chromoendoscopy and virtual chromoendoscopy had a moderate agreement in lesion detection but, for dysplasia detection, dye-spraying chromoendoscopy had a slight agreement [K = 0.11 (0.03-0.18), P < .01] and virtual chromoendoscopy a fair agreement [K = 0.30 (0.22-0.37), P < .01]. Margin delineation was similar between techniques., Conclusion: Sensitivity and specificity for lesion and dysplasia detection, as well as the accuracy of margins delineation, were similar between dye-spraying chromoendoscopy and virtual chromoendoscopy. Interobserver agreement for dysplasia detection was suboptimal in both techniques; however, it was superior when using virtual chromoendoscopy. These findings suggest that virtual chromoendoscopy constitutes a valid alternative for dysplasia screening in inflammatory bowel disease.

A growing body of evidence from neuroimaging studies suggests that inflammatory bowel disease (IBD) is associated with functional and structural alterations in the central nervous system and that it has a potential link to emotional symptoms, such as anxiety and depression. However, the neurochemical underpinnings of depression symptoms in IBD remain unclear. We hypothesized that changes in cortical gamma-aminobutyric acid (GABA+) and glutamine (Glx) concentrations are related to cortical thickness and resting-state functional connectivity in IBD as compared to healthy controls. To test this, we measured whole-brain cortical thickness and functional connectivity within the medial prefrontal cortex (mPFC), as well as the concentrations of neurotransmitters in the same brain region. We used the edited magnetic resonance spectroscopy (MRS) with the MEGA-PRESS sequence at a 3 T scanner to quantitate the neurotransmitter levels in the mPFC. Subjects with IBD (N = 37) and healthy control subjects (N = 32) were enrolled in the study. Compared with healthy controls, there were significantly decreased GABA+ and Glx concentrations in the mPFC of patients with IBD. The cortical thickness of patients with IBD was thin in two clusters that included the right medial orbitofrontal cortex and the right posterior cingulate cortex. A seed-based functional connectivity analysis indicated that there was higher connectivity of the mPFC with the left precuneus cortex (PC) and the posterior cingulate cortex, and conversely, lower connectivity in the left frontal pole was observed. The functional connectivity between the mPFC and the left PC was negatively correlated with the IBD questionnaire score (r = -0.388, p = 0.018). GABA+ concentrations had a negative correlation with the Hamilton Depression Scale (HAMD) score (r = -0.497, p = 0.002). Glx concentration was negatively correlated with the HAMD score (r = -0.496, p = 0.002) and positively correlated with the Short-Form McGill Pain Questionnaire score (r = 0.330, p = 0.046, uncorrected). There was a significant positive correlation between the ratio of Glx to GABA+ and the HAMD score (r = 0.428, p = 0.008). Mediation analysis revealed that GABA+ significantly mediated the main effect of the relationship between the structural and functional alterations and the severity of depression in patients with IBD. Our study provides initial evidence of neurochemistry that can be used to identify potential mechanisms underlying the modulatory effects of GABA+ on the development of depression in patients with IBD., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Objectives : Inflammatory bowel disease (IBD) is a condition characterized by chronic intestinal inflammation. We can identify two major forms: Crohn's disease (CD) and ulcerative colitis (UC). One of the extraintestinal manifestations of IBD is nonalcoholic fatty liver disease (NAFLD). IBD and NAFLD share common pathogenetic mechanisms. Ultrasound (US) examination is the most commonly used imaging method for the diagnosis of NAFLD. This cross-sectional observational retrospective study aimed to evaluate the US prevalence of NAFLD in IBD patients and their clinical features. Materials and Methods : A total of 143 patients with IBD underwent hepatic US and were divided into two different groups according to the presence or absence of NAFLD. Subsequently, new exclusion criteria for dysmetabolic comorbidities (defined as plus) were applied. Results : The US prevalence of NAFLD was 23% (21% in CD and 24% in UC, respectively). Most IBD-NAFLD patients were male and older and showed significantly higher values for body mass index, waist circumference, disease duration, and age at onset than those without NAFLD. IBD-NAFLD patients showed a significantly higher percentage of stenosing phenotype and left-side colitis. Regarding metabolic features, IBD-NAFLD patients showed a significantly higher percentage of hypertension and IBD plus dysmetabolic criteria. Also, higher values of alanine aminotransferase and triglycerides and lower levels of high-density lipoproteins are reported in these patients. Conclusions : We suggest performing liver US screening in subjects affected by IBD to detect NAFLD earlier. Also, patients with NAFLD present several metabolic comorbidities that would fall within the new definition of metabolic-associated fatty liver disease. Finally, we encourage larger longitudinal studies, including healthy controls, to provide further confirmation of our preliminary data.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by inflammation of the gastrointestinal tract and is a disorder of the brain-gut axis. Neuroimaging studies of brain function and structure have helped better understand the relationships between the brain, gut, and comorbidity in IBD. Studies of brain structure have primarily employed voxel-based morphometry to measure grey matter volume and surface-based morphometry to measure cortical thickness. Far fewer studies have employed other surface-based morphometry metrics such as gyrification, cortical complexity, and sulcal depth. In this study, brain structure differences between 72 adults with IBD and 90 healthy controls were assessed using all five metrics. Significant differences were found for cortical thickness with the IBD group showing extensive left-lateralized thinning, and for cortical complexity with the IBD group showing greater complexity in the left fusiform and right posterior cingulate. No significant differences were found in grey matter volume, gyrification, or sulcal depth. Within the IBD group, a post hoc analysis identified that disease duration is associated with cortical complexity of the right supramarginal gyrus, albeit with a more lenient threshold applied., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The use of intestinal ultrasound (IUS) in the management of inflammatory bowel disease (IBD) is emerging. We aim to determine the performance of IUS in the assessment of disease activity in IBD., Methods: This is a prospective cross-sectional study of IUS performed on IBD patients in a tertiary centre. IUS parameters including intestinal wall thickness, loss of wall stratification, mesenteric fibrofatty proliferation, and increased vascularity were compared with endoscopic and clinical activity indices., Results: Among the 51 patients, 58.8% were male, with a mean age of 41 years. Fifty-seven percent had underlying ulcerative colitis with mean disease duration of 8.4 years. Against ileocolonoscopy, IUS had a sensitivity of 67% (95% confidence interval (CI): 41-86) for detecting endoscopically active disease. It had high specificity of 97% (95% CI: 82-99) with positive and negative predictive values of 92% and 84%, respectively. Against clinical activity index, IUS had a sensitivity of 70% (95% CI: 35-92) and specificity of 85% (95% CI: 70-94) for detecting moderate to severe disease. Among individual IUS parameters, presence of bowel wall thickening (>3 mm) had the highest sensitivity (72%) for detecting endoscopically active disease. For per-bowel segment analysis, IUS (bowel wall thickening) was able to achieve 100% sensitivity and 95% specificity when examining the transverse colon., Conclusions: IUS has moderate sensitivity with excellent specificity in detecting active disease in IBD. IUS is most sensitive in detecting a disease at transverse colon. IUS can be employed as an adjunct in the assessment of IBD., Competing Interests: None

The diagnosis of gastrointestinal (GI) diseases currently relies primarily on invasive procedures like digestive endoscopy. However, these procedures can cause discomfort, respiratory issues, and bacterial infections in patients, both during and after the examination. In recent years, nanomedicine has emerged as a promising field, providing significant advancements in diagnostic techniques. Nanoprobes, in particular, offer distinct advantages, such as high specificity and sensitivity in detecting GI diseases. Integration of nanoprobes with advanced imaging techniques, such as nuclear magnetic resonance, optical fluorescence imaging, tomography, and optical correlation tomography, has significantly enhanced the detection capabilities for GI tumors and inflammatory bowel disease (IBD). This synergy enables early diagnosis and precise staging of GI disorders. Among the nanoparticles investigated for clinical applications, superparamagnetic iron oxide, quantum dots, single carbon nanotubes, and nanocages have emerged as extensively studied and utilized agents. This review aimed to provide insights into the potential applications of nanoparticles in modern imaging techniques, with a specific focus on their role in facilitating early and specific diagnosis of a range of GI disorders, including IBD and colorectal cancer (CRC). Additionally, we discussed the challenges associated with the implementation of nanotechnology-based GI diagnostics and explored future prospects for translation in this promising field., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Yue et al.)

Objectives: The study sought to explore and better understand the perceptions and experiences of stakeholders in relation to the use of ultrasound for the assessment of inflammatory bowel disease (IBD) in adults in the UK., Design: A qualitative semistructured interview study, using template analysis and normalisation process theory, was undertaken., Setting: Interviews were conducted using virtual meeting software., Results: Fourteen participants were enrolled between 2nd of June 2021 and 6th of September 2021. Participants were from the following roles: medical gastroenterology and radiology doctors, IBD nurse specialists, patients living with IBD, healthcare service managers. Participants reported that perceived barriers included reliance on established imaging and care pathways, reluctance to change, lack of trust in ultrasound in relation to perceived lack of precision and the initial financial and time outlay in establishing an ultrasound service. Participants were enthusiastic for the uptake of ultrasound and discussed enablers to ultrasound uptake including the benefits to patients in terms of reduction in waiting times and earlier diagnosis and treatment allocation, reduced number of hospital appointments and patients having better understanding of their health., Conclusion: There are perceived barriers to achieving implementation of ultrasound. There is scant literature to effectively assess these reported barriers. Therefore, there is further research required in the areas of the impact of the use of ultrasound for the assessment of IBD in the UK., Competing Interests: Competing interests: GM is in receipt of research funding from Janssen, Arla foods and AstraZeneca, and is a consultant for Alimentiv., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Optoacoustic imaging (OAI) enables microscale imaging of endogenous chromophores such as hemoglobin at significantly higher penetration depths compared to other optical imaging technologies. Raster-scanning optoacoustic mesoscopy (RSOM) has recently been shown to identify superficial microvascular changes associated with human skin pathologies. In animal models, the imaging depth afforded by RSOM can enable entirely new capabilities for noninvasive imaging of vascular structures in the gastrointestinal tract, but exact localization of intra-abdominal organs is still elusive. Herein the development and application of a novel transrectal absorber guide for RSOM (TAG-RSOM) is presented to enable accurate transabdominal localization and assessment of colonic vascular networks in vivo. The potential of TAG-RSOM is demonstrated through application during mild and severe acute colitis in mice. TAG-RSOM enables visualization of transmural vascular networks, with changes in colon wall thickness, blood volume, and OAI signal intensities corresponding to colitis-associated inflammatory changes. These findings suggest TAG-RSOM can provide a novel monitoring tool in preclinical IBD models, refining animal procedures and underlines the capabilities of such technologies to address inflammatory bowel diseases in humans., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Intestinal ultrasound (IUS) is a non-invasive, real-time, cross-sectional imaging tool that can be used at the point-of-care to assess disease activity in patients with Crohn's disease or ulcerative colitis. IUS promotes quick and impactful treatment decisions that can modify disease progression and enhance patient compliance. This review will summarize the technical aspects of IUS, the evidence to support the use of IUS in disease activity monitoring, the comparison of IUS to current standard of care monitoring modalities such as colonoscopy and calprotectin, and the optimal positioning of IUS in a tight-control monitoring strategy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet., Results: In this study, dextran-coated cerium oxide (D-CeO 2 ) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO 2 could efficiently scavenge reactive oxide species (ROS) as well as downregulate the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and iNOS) to protect cells from H 2 O 2 -induced oxidative damage. Moreover, D-CeO 2 could suppress the expression of fibrosis-related gene levels, such as α-SMA, and Collagen 1/3, demonstrating the anti-fibrotic effect. In both TBNS- and DSS-induced colitis models, oral administration of D-CeO 2 in chitosan/alginate hydrogel alleviated intestinal inflammation, reduced colonic damage by scavenging ROS, and decreased inflammatory factor levels. Notably, our findings also suggested that D-CeO 2 reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO 2 could also be employed as a CT contrast agent for noninvasive gastrointestinal tract (GIT) imaging., Conclusion: We introduced cerium oxide nanozyme as a novel therapeutic approach with computed tomography (CT)-guided anti-inflammatory and anti-fibrotic therapy for the management of IBD. Collectively, without appreciable systemic toxicity, D-CeO 2 held the promise of integrated applications for diagnosis and therapy, pioneering the exploration of nanozymes with ROS scavenging capacity in the anti-fibrotic treatment of IBD., (© 2023. The Author(s).)

Cross-sectional imaging-ultrasonography, computed tomography enterography, and magnetic resonance enterography-is a routine and indispensable tool for patients with Crohn's disease (CD) that helps to detect or monitor disease characteristics before, during, and after CD treatment. New emerging radiological technologies may have further clinical applications in the management of CD. In this review article, we focus on the latest developments in cross-sectional imaging in CD research, including its role in intra- and extra-luminal lesion detection, intestinal inflammation and fibrosis grading, therapeutic response assessment and outcome prediction, postoperative recurrence detection and prediction, and the gut-brain axis., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

We aimed to explore whether the imaging of antiporter system x C - of immune cells with (4 S )-4-(3- 18 F-fluoropropyl)-l-glutamate ( 18 F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18 F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x C - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18 F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18 F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18 F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18 F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68 + xCT + and CD3 + xCT + cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68 + xCT + cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system x C - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18 F-FSPG PET imaging of system x C - activity may noninvasively assess the IBD activity., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Intestinal ultrasound (IUS) is a non-invasive modality for monitoring disease activity in inflammatory bowel diseases (IBD). IUS training currently lacks well-defined standards and international consensus on competency criteria., Aim: To achieve international consensus on what competencies should be expected from a newly certified IUS practitioner., Methods: A three-round, iterative Delphi process was conducted among 54 IUS experts from 17 countries. Round 1 was a brainstorming phase with an open-ended question to identify the knowledge and skills that experts believe a newly certified IUS practitioner should possess. The experts' suggestions were then organised into statements by a Steering Committee. In round 2, the experts commented upon and rated the statements, which were revised accordingly. In round 3, the experts rated the revised statements. Statements meeting the pre-defined consensus criterion of at least 70% agreement were included in the final list of statements., Results: In total, 858 items were suggested by the experts in the first round. Based on these suggestions, 55 statements were organised into three categories: knowledge, technical skills and interpretation skills. After the second round, 53 revised statements remained. After the final round, a total of 41 statements had achieved consensus., Conclusions: We established international, expert consensus on the knowledge and skills that should be expected from newly certified IUS practitioners. These consensus statements are the first step towards mastery learning for IUS training. Educators can utilise these statements to design training programmes and evaluate the competencies of trainees before they engage in independent practice., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Breaking through the biologic therapy efficacy plateau for inflammatory bowel disease requires the strategic development of personalized biomarkers in the tight control model. After risk stratification early in the disease course, targeted serial monitoring consistently to assess clinical outcomes in response to therapy allows for quick therapeutic adjustments before bowel damage can occur. Point-of-care intestinal ultrasound performed by the treating gastroenterologist is an accurate cross- sectional biomarker that monitors intestinal inflammation in real-time, enhances patient care, and increases shared understanding to help achieve common treatment goals. Combining intestinal ultrasound during a clinic visit with existing serum and stool biomarkers in a home testing setup with electronic health monitoring allows for an optimized, patient-centered personalized treatment algorithm that may improve treatment outcomes. Here, we review the current state, pragmatic considerations, and future implications of point-of-care testing and home testing for noninvasive inflammatory bowel disease monitoring in the tight control model., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Transabdominal ultrasound (TAUS) is useful in all aspects of lesion screening, monitoring activity, or treating/diagnosing any related complications of inflammatory bowel disease. Its ability to screen or diagnose complications is almost the same as that of other methods, such as CT or MRI. Moreover, its noninvasiveness makes it a first-line examination method. A TAUS image depicting ulcerative colitis will show large intestinal wall thickening that is continuous from the rectum, which is mainly due to mucosal layer thickening, while for Crohn's disease, a TAUS image is characterized by a diversity in the areas affected, distribution, and layer structure. Indicators of activity monitoring include wall thickness, wall structure, and vascular tests that use Doppler ultrasound or contrast agents. While all of these have been reported to be useful, at this time, no single parameter has been established as superior to others; therefore, a comprehensive evaluation of these parameters is justified. In addition, evaluating the elasticity of lesions using elastography is particularly useful for distinguishing between fibrous and inflammatory stenoses. However, the lack of objectivity is the biggest drawback of using ultrasound. Standardizing and popularizing the ultrasound process will be necessary, including scanning methods, equipment settings, and image analysis., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 The Korean Society of Radiology.)

Intestinal ultrasound (IUS) is a non-invasive and accurate tool to assess inflammatory bowel disease. The ECCO-ESGAR guideline recommends the use of IUS for the assessment of disease activity and complications in Crohn's disease (CD). In addition, an increasing body of evidence suggests the use of IUS as alternative to colonoscopy in monitoring CD and in assessing disease activity of ulcerative colitis. Early responsiveness of IUS findings by the first weeks of treatment and the advantage to perform the procedure in real time may dramatically change frequency of the assessment of treatment response in the future and speed up the clinical decision-making process. Development of validated and reproducible sonographic scores to measure disease activity and therapeutic response and spread of knowledge of IUS remain relevant issues for the future in which current researchers and the International Bowel Ultrasound (IBUS) Group are actively engaged., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Inflammatory bowel disease (IBD) is typically diagnosed by exclusion years after its onset. Current diagnostic methods are indirect, destructive, or target overt disease. Screening strategies that can detect low-grade inflammation in the colon would improve patient prognosis and alleviate associated healthcare costs. Here, we test the feasibility of fluorescence lifetime imaging (FLIm) to detect inflammation from thick tissue in a non-destructive and label-free approach based on tissue autofluorescence. A pulse sampling FLIm instrument with 355 nm excitation was coupled to a rotating side-viewing endoscopic probe for high speed (10 mm/s) intraluminal imaging of the entire mucosal surface (50-80 mm) of freshly excised mice colons. Current results demonstrate that tissue autofluorescence lifetime was sensitive to the colon anatomy and the colonocyte layer. Moreover, mice under DSS-induced colitis and 5-ASA treatments showed changes in lifetime values that were qualitatively related to inflammatory markers consistent with alterations in epithelial bioenergetics (switch between β-oxidation and aerobic glycolysis) and physical structure (colon length). This study demonstrates the ability of intraluminal FLIm to image mucosal lifetime changes in response to inflammatory treatments and supports the development of FLIm as an in vivo imaging technique for monitoring the onset, progression, and treatment of inflammatory diseases.

Background and Aims: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients., Methods: One hundred seventeen IBD patients (89 Crohn's disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59)., Results: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin., Conclusion: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD.

Background: One of the most important complications in inflammatory Bowel Disease (IBD) are musculoskeletal manifestations that are reported in more than 50% of patients., Objectives: In this study, we aimed to evaluate the musculoskeletal and radiologic manifestations in our IBD patients., Methods: In this cross-sectional study on 96 mild-to-moderate IBD patients (76 UC, 18 CD and 2 undifferentiated IBD) with mean (SD) age of 39.28 (11.42) years, 44 (45.8%) were males and 52 were (54.2%) females. Patients were examined by an expert rheumatologist and their musculoskeletal symptoms were assessed. The musculoskeletal system was evaluated by Modified Schober test, Thoracic expansion (TE), Occiput to wall distance (OWD), and Patrick's or FABER test. Peripheral joints were also examined in all four extremities. Then patients were referred for pelvic and lumbosacral x-ray. Sacroiliitis grading was performed using the New York criteria., Results: Inflammatory low back pain was reported in 5 (5.2%), enthesopathy in 6 (6.5%) and dactylitis in 1 (1.1%). Positive Schober test was recorded in 5 (5.2%) and Patrick test in 3 (3.1%). Forty-nine (51%) cases had normal imaging with no sacroiliitis, endplate sclerosis was seen in 33 cases (34.4%), grade 3 and grade 4 were seen in 10 cases (10.4%)., Conclusions: In the present study, 34.4% of the IBD patients had mild radiologic changes as endplate sclerosis and 95% had a normal physical examination., (© 2021. The Author(s).)

Background: While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MB TNF-α ) to quantitatively detect mTNF-α expression in the intestinal mucosa., Methods: MB TNF-α was synthesized via a biotin-streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MB TNF-α to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging., Results: On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 10 6 a.u.) compared to that of the controls ([0.56 ± 0.21] × 10 6 a.u., P < 0.001). Targeted US signal intensities and inflammatory lesions were topographically coupled in mouse colons. Linear regression analyses in specimens of mice and patients demonstrated significant correlations between the targeted ultrasound signal intensity and mTNF-α expression (both P < 0.001). Furthermore, TNF-α-targeted ultrasound imaging qualitatively distinguished the varying inflammatory severity in intestinal specimens from IBD patients., Conclusion: Intracolic ultrasound molecular imaging with MB TNF-α enables quantitative assessment of mTNF-α expression. It may be a potential tool for facilitating the implementation of personalized medicine in IBD., (© 2021. The Author(s).)

Background: Gastrointestinal ultrasound is increasingly used for point of care assessment of inflammatory bowel disease., Aims: To explore the utility of gastrointestinal ultrasound as a point-of-care assessment tool from the perspectives of the clinician and patient., Methods: A prospective, observational cohort study was designed utilising routine outpatient consultations. Adult patients with inflammatory bowel disease were allocated to receive gastrointestinal ultrasound or not at the discretion of their treating clinician. Patients completed self-reported session experience questionnaires at study entry, immediately after their consultation, and 4 and 16 weeks later. Clinicians reported disease activity status, therapeutic decisions and clinical management., Results: Of 259 participants, mean age 40 (SD: 13) years, 54% male, 73 (28%) underwent ultrasound. Time since diagnosis was 9.2 (8.5) years (ultrasound) and 11.3 (9.2) years (no ultrasound). Immediately after ultrasound, patients who self-reported active disease reported better understanding of all aspects of their disease and disease symptoms were more confident in their ability to make informed decisions about managing their disease and had improved knowledge domain scores compared with the non-ultrasound group (all P < 0.05). Ultrasound had no influence over the patients' ability to manage their own healthcare but tended to be associated with transient improvement in medication adherence. After the ultrasound, the clinician's assessment of patient's disease activity changed in 22% (16/73) and management was altered in 56% (41/73) with anti-inflammatory therapy escalated in 33. About 47% (23/49) patients with Crohn's disease had their medication changed in the ultrasound group, compared to only 22% (25/112) in the nonultrasound group (P = 0.002). For patients with ulcerative colitis, medications were altered in 68% (15/22) compared to 26% (24/70) in the nonultrasound group (P = 0.005) When stratified for disease activity, medication change was more likely in those having ultrasound (P = 0.024)., Conclusions: Point-of-care gastrointestinal ultrasound has the potential to enhance the clinical management of inflammatory bowel disease by contributing to clinician decision-making and education of patients regarding their disease., (© 2021 John Wiley & Sons Ltd.)

NF-κB, a critical cytokine of inflammatory bowel diseases (IBD), is a viable marker to reflect the inflammatory activity of the intestine. We aimed to develop NF-κB-targeted microbubbles (MBs) and perform molecular contrast-enhanced ultrasound (CEUS) to quantify NF-κB expressions on the intestinal wall in IBD mice in vivo. In this study, NF-κB-targeted MBs were fabricated by connecting biotin-loaded NF-κB antibodies and avidin-loaded MBs. NF-κB-targeted MBs presented as transparent and round bubbles with an average diameter of 1.03/μm±0.01. The specific binding of targeted MBs and inflammatory cells was validated by in vitro experiments, including flow cytometry, Western blot and immunofluorescence, which revealed the specific binding of targeted MBs and inflammatory cells. Subsequently, NF-κB-targeted CEUS imaging was performed on mice with chemical-induced colitis, and the peak intensity (PI) and time-to-peak (TTP) were quantified. Pathological and immunohistochemical (IHC) examinations were further implemented. For the target CEUS group, fast enhancement followed by slow subsiding was observed. The PI of target CEUS of the IBD mice was significantly higher than that of non-target CEUS of the IBD mice, healthy controls and target CEUS of the treated IBD mice (34835%[13379-73492%] VS 437%[236-901%], 130%[79-231%], 528%[274-779%], p<0.0001), in accordance with the IHC results of NF-κB expressions. The TTP of target CEUS of the treated mice was significantly higher than that of untreated mice (35.7s [18.1-49.5s] VS 8.3s [4.2-12.5s], p<0.0001). Therefore, we suggested that NF-κB-targeted CEUS could accurately detect and quantify NF-κB expressions on the intestinal walls of IBD, enabling the evaluation of intestinal inflammation., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Contrast-enhanced ultrasonography (CEUS) is used to evaluate vascularity of the gastrointestinal wall in neoplastic and inflammatory diseases., Objective: To assess the feasibility of CEUS for the evaluation of duodenal perfusion in dogs with inflammatory bowel disease (IBD)., Animals: Forty-two dogs with IBD and 20 clinically healthy dogs., Methods: All CEUS studies of the duodenum were analyzed to obtain time-intensity curves and perfusion parameters. The procedure was repeated in 12 IBD dogs 2 months after a standardized treatment., Results: On CEUS, the duodenal wall showed a typical perfusion pattern characterized by a radial and simultaneous enhancement of the wall in all dogs. On qualitative assessment, no differences were observed in contrast medium distribution between healthy and affected dogs, or between dogs with IBD before and after treatment. Peak intensity (PI) and area under the curve (AUC) significantly differed between healthy (PI = 3.58 arbitrary units [au; 1.86-4.93 au] and AUC = 47.63 au seconds [aus, 22.68-62.15]) and affected dogs (PI = 5.10 au [0.63-15.16 au] and AUC = 63.62 aus [5.31-212.20 aus]; P = .03 and .03, respectively). No significant differences were found for the perfusion parameters before and after treatment., Conclusions and Clinical Importance: We showed that CEUS allows discrimination between IBD affected dogs and healthy dogs by evaluation of time-intensity curves, but did not provide useful information for monitoring therapeutic response. The qualitative assessment identified no significant differences between healthy and affected dogs, or between dogs before and after treatment., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background and Aim: this study aimed to compare carotid intima media (CIMT) and epicardial adipose tissue (EAT) measurements, which are considered as markers for the detection of early atherosclerosis in healthy controls and inflammatory bowel disease (IBD) cases., Methods: a total of 60 IBD patients (25 Crohn's disease and 35 ulcerative colitis) and 60 healthy patients (as a control group) were included in the study. The measurements of CIMT and EAT were performed using echocardiography and ultrasonography, respectively. Statistical analysis was used to determine the relationship between the parameters., Results: the thickness of bilateral (right and left) CIMT and EAT were significantly higher in IBD than in the control group (p < 0.05). There was a positive correlation between EAT and bilateral (right and left) CIMT in IBD patients (p < 0.05)., Conclusion: IBD is associated with an increased thickness of EAT and CIMT. Chronic inflammation in IBD may increase the risk of atherosclerotic heart disease. Thus, only measuring the thickness of EAT and CIMT can be used as an objective, easy, simple, affordable, non-invasive and accessible assessment method in order to screen for this risk.

Background & Aims: The accuracy of ultrasound for evaluation of individual colorectal segments in patients with inflammatory bowel diseases (IBD) has not been evaluated in a systematic review. We evaluated the diagnostic accuracy of ultrasound in different colorectal segments of patients with IBD., Methods: We searched publication databases from inception through March 2019 for studies that assessed the accuracy of ultrasound in detection of inflammation in right, transverse, and left colon and in rectum in patients with IBD, using findings from colonoscopy as the reference standard. Subgroup analyses were performed including IBD type, patient age, body mass index, and study design. The risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool., Results: Nineteen studies (1101 patients) were included in the qualitative synthesis. After we assessed the risk of bias, 7 studies (comprising 84 patients with Crohn's disease and 420 patients with ulcerative colitis) were included in the meta-analysis. Bowel wall thickness ≥ 3 mm identified colorectal segments with inflammation with 86.4% pooled sensitivity (95% CI, 76.1%-92.7%) and 88.3% pooled specificity (95% CI, 58.1%-97.6%). In rectum only, bowel wall thickness ≥ 3 mm identified inflammation with 74.5% sensitivity (95% CI, 53.0%-88.3%) and 69.5% specificity (95% CI, 33.6%-91.1%). Diagnostic accuracy was comparable among subgroups. Increased bowel wall flow and loss of stratification had higher true-positive odds ratios., Conclusions: Based on meta-analysis of patient-level data, ultrasound has higher diagnostic accuracy for detecting inflammation in colon than rectum in patients with IBD. Studies are needed to increase the accuracy of ultrasound detection of inflammation in rectum., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Intestinal ultrasound is a non-invasive, inexpensive, accessible imaging technique that is appropriate for the study of patients with inflammatory bowel disease (IBD). It provides an assessment of inflammatory activity and complications with a diagnostic accuracy similar to that of magnetic resonance imaging (MRI) and computed tomography (CT). Furthermore, it has proven to be of great value for the follow-up and monitoring of these patients. The addition of contrast enhancement has improved the diagnostic ability of intestinal ultrasound in the assessment of both inflammatory activity and complications. The development of dynamic studies able to quantify contrast arrival and determine a number of parameters in time-intensity curves (TICs) has increased the capability of intestinal ultrasound to identify inflammation and predict response to biologic therapy.

The incidence of inflammatory bowel disease (IBD) has increased over the past few decades. Also, the management of patients with IBD is associated with a relevant use of healthcare resources, and requires a multidisciplinary approach, with patients being cared for in monographic units. The umbrella term IBD includes ulcerative colitis (UC) and Crohn's disease (CD). The former condition involves the colonic mucosa alone, from the rectum in a cephalad direction with a variable extent, whereas the latter is a segmental transmural condition that may involve any portion of the gastrointestinal (GI) tract. Ileocolonoscopy is the gold standard for the diagnosis and follow-up of IBD, but can only assess intraluminal findings, hence it must be supplemented with techniques capable of transmural evaluation and of exploring scarcely accessible bowel segments, namely gastrointestinal ultrasound (GIUS), computed tomography (CT), and MR enterography (MRE).

CARMIL2 is required for CD28-mediated co-stimulation of NF-κB signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelic CARMIL2 variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the same CARMIL2 null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missense CARMIL2 variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations. CARMIL2 should be included in the diagnostic work-up of patients with suspected monogenic IBD.

Purpose: Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci., Materials and Methods: We generated a nanodevice composed of PLGA-PEG coupled with anti-MAdCAM-1 antibody half-chains and loaded with quantum dots (P@QD-MdC NPs). Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt. Specificity for diseased bowel regions was also assessed ex vivo in human specimens from patients with IBD. Potential for development as contrast agent in magnetic resonance imaging was assessed by preliminary study on animal model., Results: Synthesized nanoparticles revealed good stability and monodispersity. Molecular targeting properties were analyzed in vitro in a cell culture model. Upon intravenous injection, P@QD-MdC NPs were localized in the bowel of colitic mice, with enhanced accumulation at 24 h post-injection compared to untargeted nanoparticles (p<0.05). Nanoparticles injection did not induce histologic lesions in non-target organs. Ex vivo exposure of human bowel specimens to P@QD-MdC NPs revealed specific recognition of the diseased regions vs uninvolved tracts (p<0.0001). After loading with appropriate contrast agent, the nanoparticles enabled localized contrast enhancement of bowel mucosa in the rectum of treated mice., Conclusion: P@QD-MdC NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis., Competing Interests: The authors have no conflict of interest to declare regarding this study., (© 2020 Truffi et al.)

Background: Bowel ultrasound and magnetic resonance enterography (MRE) are decisive medical imaging modalities for diagnosing and locating bowel lesions with its extramural extent and complications. They assess the degree of activity, help clinicians to identify patients in need of surgery, and can be used for patient follow-up., Aim: To compare the role of MRE and bowel ultrasound in diagnosis and follow-up of inflammatory bowel disease (IBD) patients in Egypt., Methods: The study was conducted on 40 patients with IBD. All patients were subjected to clinical assessment, laboratory investigations, bowel ultrasound, MRE, and colonoscopy up to the terminal ileum with biopsies for histopathological examination., Results: This study was conducted on 14 patients (35%) with ulcerative colitis and 26 patients (65%) with Crohn's disease; 34 (85%) of these patients had active disease. Bowel ultrasound detected different bowel lesions with the following accuracies: ileum (85%), large bowel (70%), fistula (95%), stricture and proximal dilatation (95%) and abscesses (100%). Also, it showed that statistically significance of bowel ultrasound in differentiation between remission and activity of IBD in comparison to MRE and colonoscopy., Conclusion: In comparison to MRE, bowel ultrasound is a useful, non-invasive, and feasible bedside imaging tool for the detection of inflammation, detection of complications, and follow-up of IBD patients when performed by the attending physician., Competing Interests: Conflict-of-interest statement: None to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Contrast material-enhanced US is a technique that is approved by the U.S. Food and Drug Administration for the characterization of liver lesions and intravesicular applications in children; however, contrast-enhanced US has several other pediatric applications in clinical practice. The most common application is for patients with inflammatory bowel disease (IBD). Contrast-enhanced US can be used to diagnose IBD, distinguish regions of active or chronic inflammation of the bowel wall, and evaluate associated complications such as abscesses, fistulas, and strictures. Dynamic contrast material evaluation provides qualitative and quantitative information about mural and mesenteric blood flow, which is essential in the determination of disease activity in these patients. It also has the potential to provide a means of monitoring the response to therapy beyond endoscopy or MR enterography. In addition to its use for IBD, contrast-enhanced US can be used to assess for bowel perfusion when problem solving in patients with necrotizing enterocolitis, neonatal bowel infarction, or intussusception. It is a useful imaging technique to fortify diagnoses that may otherwise be indeterminate, such as appendicitis, epiploic appendagitis, intraluminal bowel masses, and complex cysts. Finally, innovative applications such as shear-wave elastography have the potential to provide information about the stiffness of the bowel wall. Online supplemental material is available for this article. © RSNA, 2020 See discussion on this article by Watson and Humphries.