Intestinal ultrasound in inflammatory bowel disease.

Intestinal ultrasound (IUS) is non-invasive, fast, cheap, and well-tolerated and requires no preparation and is thus applicable as a point-of-care monitoring tool of inflammatory bowel disease (IBD). Evidence suggests that IUS is comparable to other standard monitoring modalities, i.e., endoscopy, MRI, calprotectin, and C-reactive protein and might be more accurate in predicting response to treatment at an early stage consequently allowing for timely optimised treatment. This review finds that integrating IUS as the standard of care in every IBD outpatient clinic and as the primary outcome in future medical trials seems inevitable.

The role of molecular imaging in detecting fibrosis in Crohn's disease.

Fibrosis is a pathological process that occurs due to chronic inflammation, leading to the proliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM). The process of long-term fibrosis initiates with tissue hypofunction and progressively culminates in the ultimate manifestation of organ failure. Intestinal fibrosis is a significant complication of Crohn's disease (CD) that can result in persistent luminal narrowing and strictures, which are difficult to reverse. In recent years, there have been significant advances in our understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in inflammatory bowel disease (IBD). Significant progress has been achieved in the fields of pathogenesis, diagnosis, and management of intestinal fibrosis in the last few years. A significant amount of research has also been conducted in the field of biomarkers for the prediction or detection of intestinal fibrosis, including novel cross-sectional imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). Molecular imaging represents a promising biomedical approach that enables the non-invasive visualization of cellular and subcellular processes. Molecular imaging has the potential to be employed for early detection, disease staging, and prognostication in addition to assessing disease activity and treatment response in IBD. Molecular imaging methods also have a potential role to enabling minimally invasive assessment of intestinal fibrosis. This review discusses the role of molecular imaging in combination of AI in detecting CD fibrosis.

Study of ischemic progression in different intestinal tissue layers during acute intestinal ischemia using swept-source optical coherence tomography angiography.

In acute intestinal ischemia, the progression of ischemia varies across different layers of intestinal tissue. We established a mouse model and used swept-source optical coherence tomography (OCT) to observe the intestinal ischemic process longitudinally in different tissue layers. Employing a method that combines asymmetric gradient filtering with adaptive weighting, we eliminated the vessel trailing phenomenon in OCT angiograms, reducing the confounding effects of superficial vessels on the imaging of deeper vasculature. We quantitatively assessed changes in vascular perfusion density (VPD), vessel length, and vessel average diameter across various intestinal layers. Our results showed a significant reduction in VPD in all layers during ischemia. The mucosa layer experienced the most significant impact, primarily due to disrupted capillary blood flow, followed by the submucosa layer, where vascular constriction or decreased velocity was the primary factor.

Clinical Application of Intestinal Ultrasound in Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Intestinal ultrasound (IUS) is a non-invasive, accurate, and well-tolerated tool that provides real-time assessment of inflammatory bowel disease (IBD) activity and is therefore an ideal monitoring tool. This review describes the evolving role of IUS in each phase of clinical management of IBD. RECENT FINDINGS: Accumulating evidence has demonstrated that IUS is an excellent tool for the assessment of suspected IBD, with a very high negative predictive value. It accurately assesses disease activity, disease complications, and in the pre-treatment phase, provides a benchmark for subsequent follow-up. IUS can detect early therapeutic response and correlates well with other established monitoring modalities with arguably superior predictive capabilities and ability to assess a deeper degree of remission, transmural healing (TH). IUS has a crucial role in the management of IBD and has ushered in a new era of monitoring with more rapid evaluation and the opportunity for early optimization, deeper therapeutic targets, and improved outcomes.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Photoacoustic Imaging as a Novel Non-invasive Biomarker to Assess Intestinal Tissue Oxygenation and Motility in Neonatal Rats.

BACKGROUND: Within the premature infant intestine, oxygenation and motility play key physiological roles in healthy development and disease such as necrotizing enterocolitis. To date, there are limited techniques to reliably assess these physiological functions that are also clinically feasible for critically ill infants. To address this clinical need, we hypothesized that photoacoustic imaging (PAI) can provide non-invasive assessment of intestinal tissue oxygenation and motility to characterize intestinal physiology and health. METHODS: Ultrasound and photoacoustic images were acquired in 2-day and 4-day old neonatal rats. For PAI assessment of intestinal tissue oxygenation, an inspired gas challenge was performed using hypoxic, normoxic, and hyperoxic inspired oxygen (FiO2). For intestinal motility, oral administration of ICG contrast agent was used to compare control animals to an experimental model of loperamide-induced intestinal motility inhibition. RESULTS: PAI demonstrated progressive increases in oxygen saturation (sO2) as FiO2 increased, while the pattern of oxygen localization remained relatively consistent in both 2-day and 4-day old neonatal rats. Analysis of intraluminal ICG contrast enhanced PAI images yielded a map of the motility index in control and loperamide treated rats. From PAI analysis, loperamide significantly inhibited intestinal motility, with a 32.6% decrease in intestinal motility index scores in 4-day old rats. CONCLUSION: These data establish the feasibility and application of PAI to non-invasively and quantitatively measure intestinal tissue oxygenation and motility. This proof-of-concept study is an important first step in developing and optimizing photoacoustic imaging to provide valuable insight into intestinal health and disease to improve the care of premature infants.

Performance of three predictive scores to avoid delayed diagnosis of significant blunt bowel and mesenteric injury: A 12-year retrospective cohort study.

BACKGROUND: Avoiding missed diagnosis and therapeutic delay for significant blunt bowel and mesenteric injuries (sBBMIs) after trauma is still challenging despite the widespread use of computed tomography (CT). Several scoring tools aiming at reducing this risk have been published. The purpose of the present work was to assess the incidence of delayed (>24 hours) diagnosis for sBBMI patients and to compare the predictive performance of three previously published scores using clinical, radiological, and laboratory findings: the Bowel Injury Prediction Score (BIPS) and the scores developed by Raharimanantsoa Score (RS) and by Faget Score (FS). METHODS: A population-based retrospective observational cohort study was conducted; it included adult trauma patients after road traffic crashes admitted to Lausanne University Hospital, Switzerland, between 2008 and 2019 (n = 1,258) with reliable information about sBBMI status (n = 1,164) and for whom all items for score calculation were available (n = 917). The three scores were retrospectively applied on all patients to assess their predictive performance. RESULTS: The incidence of sBBMI after road traffic crash was 3.3% (38 of 1,164), and in 18% (7 of 38), there was a diagnostic and treatment delay of more than 24 hours. The diagnostic performances of the FS, the RS, and the BIPS to predict sBBMI, expressed as the area under the receiver operating characteristic curve, were 95.3% (95% confidence interval [CI], 92.7-97.9%), 89.2% (95% CI, 83.2-95.3%), and 87.6% (95% CI, 81.8-93.3%) respectively. CONCLUSION: The present study confirms that diagnostic delays for sBBMI still occur despite the widespread use of abdominal CT. When CT findings during the initial assessment are negative or equivocal for sBBMI, using a score may be helpful to select patients for early diagnostic laparoscopy. The FS had the best individual diagnostic performance. However, the BIPS or the RS, relying on clinical and laboratory variables, may be helpful to select patients for early diagnostic laparoscopy when there are unspecific CT signs of bowel or mesenteric injury. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Gastroschisis ultrasound bowel characteristics demonstrate minimal impact on perinatal outcomes.

BACKGROUND: Bowel dilation and bowel wall thickness are common prenatal ultrasound measurements for fetuses with gastroschisis. Data regarding antenatal sonographic bowel findings and postnatal outcomes are conflicting. Our objective was to evaluate the impact of in utero bowel measurements on perinatal outcomes in gastroschisis pregnancies. METHODS: Retrospective cohort study of 116 pregnancies complicated by gastroschisis between 2011 and 2020. We reviewed ultrasounds documenting fetal bowel measurements. To evaluate the association of these measurements with antepartum and delivery outcomes, we ran logistic and linear models using generalized estimating equations. RESULTS: Eleven perinatal outcomes reached statistical significance, although with minimal clinical impact given small magnitude of effect. Intra-abdominal bowel dilation was associated with a 0.5 week decrease in delivery gestational age (GA) (95% CI -0.07, -0.03) and a 6.93 g increase in birth weight (95% CI 1.54, 28.73). Intra-abdominal bowel wall thickness was associated with later GA of non-stress test (NST) start of 0.22 weeks (95% CI 0.07, 0.37), increased delivery GA of 0.08 weeks (95% CI 0.02, 0.15), 0.006 decrease in umbilical artery (UA) pH (95% CI -0.009, -0.003), 0.26 increase in UA base deficit (95% CI 0.09, 0.43), and decreased odds of cesarean delivery (OR = 0.83, 95% CI 0.70, 0.99). Extra-abdominal bowel wall thickness was associated with a 0.1 increase in UA base deficit (95% CI 0.02, 0.19) and a 0.05 increase in 5-min APGAR score (95% CI 0.01, 0.09). Stomach cross-section was associated with a 0.01 week decrease in delivery GA (95% CI -0.02, -0.001) and increased odds of receiving betamethasone (OR = 1.02, 95% CI 1.01, 1.04). CONCLUSIONS: In utero bowel characteristics reached statistical significance for several outcomes, but with minimal meaningful clinical differences in outcomes.

Recent advances in the use of ultrasound in Crohn's disease.

INTRODUCTION: A clear consensus exists on the role of IUS for the assessment and monitoring of Crohn's disease (CD) in the 'treat-to-target' strategy. AREAS COVERED: IUS is an accurate tool for the management of CD. It is noninvasive and well tolerated. IUS has good-to-optimal inter-operator reliability either for assessing disease activity or for evaluating treatment response, especially combining Bowel Wall Thickness (BWT) and Color Doppler Signals (CDS). IUS is able to evaluate transmural remission (TR), the ultimate goal of the 'treat-to-target' strategy. Several studies confirmed its accuracy in the assessment of the post-operative recurrence (POR). Thanks to recent advances in trans-perineal ultrasound technique (TPUS), it allows to characterize peri-anal disease and its complications. Small intestine contrast ultrasound (SICUS) and contrast-enhancement ultrasound (CEUS) may improve IUS performance, particularly in stricturing or penetrating CD. Ultrasound elastography (USE) is raising interest for its accuracy in differentiating CD phenotypes (fibrotic versus inflamed). EXPERT OPINION: IUS is a pivotal step in the management of CD, in early assessment as in therapeutic monitoring, with advantages of evaluating transmural response. Development and validation of novel ultrasound biomarkers of activity and fibrosis, especially those linked to advanced ultrasound techniques, are expected in the coming years.

Dye-free visualisation of intestinal perfusion using laser speckle contrast imaging in laparoscopic surgery: a prospective, observational multi-centre study.

INTRODUCTION: Intraoperative perfusion imaging may help the surgeon in creating the intestinal anastomoses in optimally perfused tissue. Laser speckle contrast imaging (LSCI) is such a perfusion visualisation technique that is characterized by dye-free, real-time and continuous imaging. Our aim is to validate the use of a novel, dye-free visualization tool to detect perfusion deficits using laparoscopic LSCI. METHODS: In this multi-centre study, a total of 64 patients were imaged using the laparoscopic laser speckle contrast imager. Post-operatively, surgeons were questioned if the additional visual feedback would have led to a change in clinical decision-making. RESULTS: This study suggests that the laparoscopic laser speckle contrast imager PerfusiX-Imaging is able to image colonic perfusion. All images were clear and easy to interpret for the surgeon. The device is non-disruptive of the surgical procedure with an average added surgical time of 2.5 min and no change in surgical equipment. The potential added clinical value is accentuated by the 17% of operating surgeons indicating a change in anastomosis location. Further assessment and analysis of both white light and PerfusiX perfusion images by non-involved, non-operating surgeons showed an overall agreement of 80%. CONCLUSION: PerfusiX-Imaging is a suitable laparoscopic perfusion imaging system for colon surgery that can visualize perfusion in real-time with no change in surgical equipment. The additional visual feedback could help guide the surgeons in placing the anastomosis at the most optimal site.

NAD(P)H Fluorescence Lifetime Imaging for the Metabolic Analysis of the Murine Intestine and Parasites During Nematode Infection.

Parasites generally have a negative effect on the health of their host. They represent a huge health burden, as they globally affect the health of the infested human or animal in the long term and, thus, impact agricultural and socio-economic outcomes. However, parasite-driven immune-regulatory effects have been described, with potential therapeutic relevance for autoimmune diseases. While the metabolism in both the host and parasites contributes to their defense and is the basis for nematode survival in the intestine, it has remained largely understudied due to a lack of adequate technologies. We have developed and applied NAD(P)H fluorescence lifetime imaging to explanted murine intestinal tissue during infection with the natural nematode Heligmosomoides polygyrus to study the metabolic processes in both the host and parasites in a spatially resolved manner. The exploitation of the fluorescence lifetime of the co-enzymes nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), hereafter NAD(P)H, which are preserved across species, depends on their binding status and the binding site on the enzymes catalyzing metabolic processes. Focusing on the most abundantly expressed NAD(P)H-dependent enzymes, the metabolic pathways associated with anaerobic glycolysis, oxidative phosphorylation/aerobic glycolysis, and NOX-based oxidative burst, as a major defense mechanism, were distinguished, and the metabolic crosstalk between the host and parasite during infection was characterized.

Wide field-of-view fluorescence imaging for organ-level lineage tracing of rare intestinal stem cell populations.

Significance: Lineage tracing using fluorescent reporters is a common tool for monitoring the expression of genes and transcription factors in stem cell populations and their progeny. The zinc-binding protein 89 (ZBP-89/Zfp148 mouse gene) is a transcription factor that plays a role in gastrointestinal (GI) stem cell maintenance and cellular differentiation and has been linked to the progression of colon cancer. While lineage tracing is a useful tool, it is commonly performed with high-magnification microscopy on a small field of view within tissue sections, thereby limiting the ability to resolve reporter expression at the organ level. Furthermore, this technique requires extensive tissue processing, which is time consuming and requires euthanizing the animal. Further knowledge could be elucidated by measuring the expression of fluorescent reporters across entire organs with minimal tissue processing. Aim: We present the application of wide-field fluorescence imaging for whole-organ lineage tracing of an inducible Zfp148-tdTomato-expressing transgenic mouse line to assess the expression of ZBP-89/Zfp148 in the GI tract. Approach: We measured tdTomato fluorescence in ex vivo organs at time points between 24 h and 6 months post-induction. Fluctuations in tdTomato expression were validated by fluorescence microscopy of tissue sections. Results: Quantification of the wide field-of-view images showed a statistically significant increase in fluorescent signal across the GI tract between transgenic mice and littermate controls. The results also showed a gradient of decreasing reporter expression from proximal to distal intestine, suggesting a higher abundance of ZBP-89 expressing stem cells, or higher expression of ZBP-89 within the stem cells, in the proximal intestine. Conclusions: We demonstrate that wide-field fluorescence imaging is a valuable tool for monitoring whole-organ expression of fluorescent reporters. This technique could potentially be applied in vivo for longitudinal assessment of a single animal, further enhancing our ability to resolve rare stem cell lineages spatially and temporally.

The Role of Noninvasive Surrogates of Inflammation in Monitoring Pediatric Inflammatory Bowel Diseases: The Old and the New.

Effectiveness of limited available therapies for pediatric inflammatory bowel disease has reached stagnation. Previous non-invasive monitoring strategies have relied upon cumbersome tools to evaluate clinical symptoms and biochemical markers that do not reflect endoscopic activity or respond quickly to treatments. Novel, patient-centric, and highly accurate, monitoring strategies with a focus on intestinal ultrasound for a direct, precise monitoring of activity to achieve disease modification are now possible. Ultimately, research on the optimal tight control monitoring strategies, individualized to each pediatric inflammatory bowel disease patient, are in development and offer a hope to potential therapeutic ceiling breakthrough on the horizon.

Prognostic role of intestinal ultrasound in Crohn's disease.

The majority of patients affected by Crohn's disease (CD) develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel, resulting in stricturing or penetrating complications in around 50% of patients during the natural history of the disease. Surgery is frequently needed to treat complicated disease when pharmacological therapy failes, with a high risk of repeated operations in time. Intestinal ultrasound (IUS), a non-invasive, cost-effective, radiation free and reproducible method for the diagnosis and follow-up of CD, in expert hands, allow a precise assessment of all the disease manifestations: Bowel characteristics, retrodilation, wrapping fat, fistulas and abscesses. Moreover, IUS is able to assess bowel wall thickness, bowel wall stratification (echo-pattern), vascularization and elasticity, as well as mesenteric hypertrophy, lymph-nodes and mesenteric blood flow. Its role in the disease evaluation and behaviour description is well assessed in literature, but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative recurrence. The availability of a low cost exam as IUS, able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications, could be a very useful instrument in the hands of IBD physician. The aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment, disease progression, risk of surgery and risk of post-surgical recurrence in CD.

Intestinal ultrasound may be a useful tool in monitoring acute rejection following intestinal transplantation.

BACKGROUND: Acute rejection is the leading cause of mortality and morbidity for children following intestinal transplantation. Rapid detection and prompt treatment are critical; however, the only reliable method of diagnosis and monitoring is endoscopic graft biopsies. The required regular anesthetics are particularly problematic in children, and non-invasive strategies are needed. METHODS: We describe the intestinal ultrasound findings of three children before and after treatment for rejection. Ultrasounds were performed within 24 h of endoscopically obtained biopsies which were used to establish a diagnosis of rejection and to define severity. A single sonographer performed the ultrasounds and was blinded to biopsy results at the time of the scanning. These findings are provided in the context of the ultrasound appearance of seven children who had no features of rejection on surveillance biopsies. RESULTS: Intestinal ultrasound demonstrated increased bowel wall thickness, vascularity, and mesenteric inflammation during moderate to severe rejection episodes. The submucosal layer was particularly thickened, which may represent a finding more specific for rejection. All patients demonstrated improvement in all quantitative ultrasound features correlating with the resolution of acute cellular rejection on histology. Patients with no evidence of rejection on biopsy had a bowel wall thickness range of 0.9-2.8 mm, suggesting a normal upper limit of 3 mm. CONCLUSION: Moderate and severe acute rejection may be detected and response to treatment can be monitored by intestinal ultrasound and, correlating with clinical improvement, can aid in follow-up.

Intestinal and Multivisceral Transplantation: Indications and Surgical Techniques.

Intestinal transplantation and multivisceral transplantation are technically challenging and complex procedures mainly performed on patients with irreversible and non-medically manageable end-stage intestinal failure. Increasingly, other organs besides small intestines are included in the allograft for which the terms "composite intestinal transplantation" and "multivisceral transplantation" are used. Commonly, complex vascular reconstructions are used for these procedures. Knowledge of surgical anatomy hence is essential for accurate interpretation of postoperative imaging in these patients. This article reviews the indications and most common surgical techniques for intestinal and multivisceral transplantations.

Intestinal and Multivisceral Transplantation: Complications.

Advancements in immunosuppression protocols, surgical techniques, and postoperative care in the last few decades have improved outcomes of intestinal transplant patients. Normal immediate postoperative imaging appearance can simulate pathology. Intestinal transplant recipients are prone for several postoperative complications due to the complex surgical technique, which involves multiple anastomoses, and immunogenic nature of the allograft intestine. Imaging plays a crucial role in detection of several major complications including infectious, immunologic, vascular, gastrointestinal, pancreaticobiliary, genitourinary, and neoplastic complications. The awareness of the posttransplant anatomy and normal imaging appearances helps radiologists anticipate and accurately detect posttransplant complications.

Insights into acute mesenteric ischaemia: an up-to-date, evidence-based review from a mesenteric stroke centre unit.

Radiologists play a central role in the diagnostic and prognostic evaluation of patients with acute mesenteric ischaemia (AMI). Unfortunately, more than half of AMI patients undergo imaging with no prior suspicion of AMI, making identifying this disease even more difficult. A confirmed diagnosis of AMI is ideally made with dynamic contrast-enhanced CT but the diagnosis may be made on portal-venous phase images in appropriate clinical settings. AMI is diagnosed on CT based on the identification of vascular impairment and bowel ischaemic injury with no other cause. Moreover, radiologists must evaluate the probability of bowel necrosis, which will influence the treatment options.AMI is usually separated into different entities: arterial, venous, non-occlusive and ischaemic colitis. Arterial AMI can be occlusive or stenotic, the dominant causes being atherothrombosis, embolism and isolated superior mesenteric artery (SMA) dissection. The main finding in the bowel is decreased wall enhancement, and necrosis can be suspected when dilatation >25 mm is identified. Venous AMI is related to superior mesenteric vein (SMV) thrombosis as a result of a thrombophilic state (acquired or inherited), local injury (cancer, inflammation or trauma) or underlying SMV insufficiency. The dominant features in the bowel are hypoattenuating wall thickening with submucosal oedema. Decreased enhancement of the involved bowel suggests necrosis. Non-occlusive mesenteric ischaemia (NOMI) is related to impaired SMA flow following global hypoperfusion associated with low-flow states. There are numerous findings in the bowel characterised by diffuse extension. An absence of bowel enhancement and a thin bowel wall suggest necrosis in NOMI. Finally, ischaemic colitis is a sub-entity of arterial AMI and reflects localised colon ischaemia-reperfusion injury. The main CT finding is a thickened colon wall with fat stranding, which seems to be unrelated to SMA or inferior mesenteric artery lesions. A precise identification and description of vascular lesions, bowel involvement and features associated with transmural necrosis is needed to determine patient treatment and outcome.