Mucosal healing is the mainstream goal of modern treat-to-target strategy as it is associated with a significantly more favorable disease course in IBD patients with either ulcerative colitis or Crohn's disease. Recent advances in endoscopic imaging technologies have overcome the traditional concept of mucosal healing assessed with conventional white light imaging, allowing for multiple levels of endoscopic healing up to the boundaries of molecular and functional evaluation. In this review, we focused on conventional and emerging strategies to assess endoscopic healing in ulcerative colitis and ileocolonic Crohn's disease, examining their pros and cons in real life practice.

Artificial intelligence (AI) refers to computer-based methodologies that use data to teach a computer to solve pre-defined tasks; these methods can be applied to identify patterns in large multi-modal data sources. AI applications in inflammatory bowel disease (IBD) includes predicting response to therapy, disease activity scoring of endoscopy, drug discovery, and identifying bowel damage in images. As a complex disease with entangled relationships between genomics, metabolomics, microbiome, and the environment, IBD stands to benefit greatly from methodologies that can handle this complexity. We describe current applications, critical challenges, and propose future directions of AI in IBD.

Recent advances in the field of endoscopy have found fertile ground for application in inflammatory bowel diseases (IBD). Mucosal healing is a primary goal of IBD therapy, and current evidence shows that histologic remission (HR) is an additional desirable outcome. However, with the use of standard endoscopy, a considerable number of patients with histologically active disease go unrecognized. This narrative article examines the role, current or potential, of each endoscopic technique, from standard white-light endoscopy to molecular imaging, in the assessment of mucosal healing and HR in IBD.

Advanced endoscopic imaging including high-definition endoscopy, confocal laser endomicroscopy (CLE) and endocytoscopy (EC) serve as an adjunct to predict clinical outcomes in inflammatory bowel disease (IBD). CLE can identify gut barrier dysfunction which correlates with disease behavior and long-term disease outcome. EC allows the assessment of histologic activity. Future controlled studies are warranted to define a definite role of these novel technologies in the management of patients with IBD.

Ulcerative colitis (UC) is one of the two forms of inflammatory bowel disease. It affects 5 million people globally, and is a chronic and recurring inflammation of the gastrointestinal tract with clinical presentation of abdominal pain, chronic diarrhea, rectal bleeding, and weight loss. The cause and the etiology of UC remain poorly understood. There is no cure and no 'gold standard diagnostic' for UC. The existing treatments are ineffective, and UC patients have a lower life expectancy with a risk of colorectal cancer. Recent studies in pathophysiology, clinical presentation, and biomarkers have significantly improved our understanding of UC. In this review we summarize recent advances in identifying novel clinical biomarkers, diagnostics, treatment targets, and emerging therapeutics. These insights are expected to assist in developing effective treatments for UC.

Mounting evidence underscores the pivotal role of the intestinal barrier and its convoluted network with diet and intestinal microbiome in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC). Moreover, the bidirectional association of the intestinal barrier with the liver and brain, known as the gut-brain axis, plays a crucial role in developing complications, including extraintestinal manifestations of IBD and CRC metastasis. Consequently, barrier healing represents a crucial therapeutic target in these inflammatory-dependent disorders, with barrier assessment predicting disease outcomes, response to therapy and extraintestinal manifestations.New advanced technologies are revolutionising our understanding of the barrier paradigm, enabling the accurate assessment of the intestinal barrier and aiding in unravelling the complexity of the gut-brain axis. Cutting-edge endoscopic imaging techniques, such as ultra-high magnification endocytoscopy and probe-based confocal laser endomicroscopy, are new technologies allowing real-time exploration of the 'cellular' intestinal barrier. Additionally, novel advanced spatial imaging technology platforms, including multispectral imaging, upconversion nanoparticles, digital spatial profiling, optical spectroscopy and mass cytometry, enable a deep and comprehensive assessment of the 'molecular' and 'ultrastructural' barrier. In this promising landscape, artificial intelligence plays a pivotal role in standardising and integrating these novel tools, thereby contributing to barrier assessment and prediction of outcomes.Looking ahead, this integrated and comprehensive approach holds the promise of uncovering new therapeutic targets, breaking the therapeutic ceiling in IBD. Novel molecules, dietary interventions and microbiome modulation strategies aim to restore, reinforce, or modulate the gut-brain axis. These advancements have the potential for transformative and personalised approaches to managing IBD.

Ulcerative colitis (UC), characterized by its recurrent nature, imposes a significant disease burden and compromises the quality of life. Emerging evidence suggests that achieving clinical remission is not sufficient for long-term remission. In pursuit of a favorable prognosis, mucosal healing (MH) has been defined as the target of therapies in UC. This paradigm shift has given rise to the formulation of diverse endoscopic and histological scoring systems, providing distinct definitions for MH. Endoscopic remission (ER) has been widely employed in clinical practice, but it is susceptible to subjective factors related to endoscopists. And there's growing evidence that histological remission (HR) might be associated with a lower risk of disease flares, but the incorporation of HR as a routine therapeutic endpoint remains a debate. The integration of advanced technology has further enriched the definition of deep MH. Up to now, a universal standardized definition for deep MH in clinical practice is currently lacking. This review will focus on the definition of deep MH, from different dimensions, and analyze strengths and limitations, respectively. Subsequent multiple large-scale trials are needed to validate the concept of deep MH, offering valuable insights into potential benefits for UC patients.

A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician's subjective assessment of symptoms. However, choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy. The treatment endpoints for ulcerative colitis (UC), recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) consensus have changed somewhat over time. The latest STRIDE-II consensus advises immediate (clinical response), intermediate (clinical remission and biochemical normalisation) and long-term treatment (endoscopic healing, absence of disability and normalisation of health-related quality of life, as well as normal growth in children) endpoints in UC. However, achieving deeper levels of remission, such as histologic normalisation or healing of the gut barrier function, may further improve outcomes among UC patients. Generally, all medical therapy should seek to improve short- and long-term mortality and morbidity. Hence treatment endpoints should be chosen based on their ability to predict for improvement in short- and long-term mortality and morbidity. Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient. In addition, changing therapy that has achieved partial response may lead to worse outcomes, with failure to recapture response on treatment reversion. Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians, or may have strong opinions re certain therapies. Potential benefits and harms of therapies, incremental benefits of achieving deeper levels of remission, as well as uncertainties of the same, need to be discussed with individual patients, and a treatment endpoint agreed upon with the clinician. Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission, such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.

Artificial intelligence (AI) is quickly demonstrating the ability to address problems and challenges in the care of IBD. This review with commentary will highlight today's advancements in AI applications for IBD in image analysis, understanding text, and replicating clinical knowledge and experience.

Advancements in machine learning methods, availability of high-performance computing, and increasing digitization of medical data are providing opportunities for AI to assist in IBD care. Multiple groups have demonstrated the ability of AI to replicate expert endoscopic scoring in IBD, with expansion into automated capsule endoscopy, enterography, and histologic interpretations. Further, AI image analysis is being used to develop new endoscopic scoring with more granularity and detail than is possible using conventional methods. Advancements in natural language processing are proving to reduce laborious tasks required in the care of IBD, including documentation, information searches, and chart review. Finally, large language models and chatbots that can understand language and generate human-like replies are beginning to exhibit clinical intelligence that will revolutionize how we deliver IBD care. Today, AI is being deployed to replicate expert judgement in specific tasks where disagreement, subjectivity, and bias are common. However, the near future will herald contributions of AI doing what we cannot, including new detailed measures of IBD, enhanced analysis of images, and perhaps even fully automating care. As we speculate on future technologic capabilities that may improve how we care for IBD, this review will also consider how we will implement and fairly use AI in practice.

Confocal laser endomicroscopy (CLE) and endocytoscopy (EC) are ultra-high definition (HD) imaging modalities that enable real-time histological assessment. Although existent for nearly two decades, their role in current clinical decision making in inflammatory bowel disease management is not well defined.

We searched PubMed using keywords ("confocal" OR "CLE" OR "endocytoscopy") AND ("IBD" OR "inflammatory bowel" OR "Crohn*" OR "Crohn's" OR "colitis ulcerosa" OR "ulcerative colitis") between 2005 and March 2023. We identified 52 studies for detailed review.

Confocal laser endomicroscopy was useful in real-time assessment of histologic inflammation and dysplasia characterization in both ulcerative colitis (UC) and Crohn's disease. Although CLE was associated with higher per-biopsy yield for UC-associated neoplasia (UCAN), the benefit was offset by higher procedure time, frequent equipment failure, and conflicting results on incremental yield over chromoendoscopy. Assessment of barrier dysfunction by CLE did not correlate with disease/endoscopic activity but could predict major adverse outcomes. The implications of residual CLE abnormalities in endoscopic remission remain uncertain. Ex vivo binding of labeled biologics can help in predicting biologic response in UC. EC can discriminate mucosal inflammatory cells by morphology and allows assessment of histologic activity. EC combined with pit pattern was better than pit pattern alone for UCAN. Artificial intelligence-assisted EC in UCAN needs further study.

Ultra-HD imaging in inflammatory bowel disease can be useful in assessment of UCAN, barrier dysfunction, predicting histologic remission, and biologic response. Future controlled studies are warranted to define the role of these novel technologies in clinical decision making.

Several advanced imaging techniques are now available for endoscopists managing inflammatory bowel disease (IBD) patients. These tools, including dye-based and virtual chromoendoscopy, probe-based confocal laser endomicroscopy and endocytoscopy, are increasingly innovative applications in clinical practice. They allow for a more in-depth and refined evaluation of the mucosal and vascular bowel surface, getting closer to histology. They have demonstrated a remarkable ability in assessing intestinal inflammation, histologic remission, and predicting relapse and favorable long-term outcomes. In addition, the future application of molecular endoscopy to predict biological drug responses has yielded preliminary but encouraging results. Furthermore, these techniques are crucial in detecting and characterizing IBD-related dysplasia, assisting endoscopic mucosal resection and submucosal dissection towards a surgery-sparing approach. Artificial intelligence (AI) holds great potential in this promising landscape, as it can provide an objective and reproducible assessment of inflammation and dysplasia. Moreover, it can improve the prediction of outcomes and aid in subsequent therapeutic decision-making. This review aims to summarize the promising role of state-of-the-art advanced endoscopic techniques and related AI-enabled models for managing IBD, paving the way for precision medicine.

Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients.

Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance.

Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g = 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI.

As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.

Inflammatory bowel disease (IBD) comprises two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. In long-standing ulcerative colitis disease activity, histological persistent inflammation has been linked to an increased risk of relapse, and long-term corticosteroid use, even when endoscopic remission is reached. In Crohn's disease, the discontinuous nature of lesions and transmural inflammation have limited the standardized histological assessment. The current evidence from research proposes that besides clinical and endoscopic healing, the achievement of histological healing constitutes an endpoint to assess disease activity and remission in IBD patients concerning better long-term disease outcomes. Histological alterations may persist even in the absence of endoscopic lesions. For these reasons, new advanced techniques promise to revolutionize the field of IBD by improving the endoscopic and histologic assessment, disease characterization, and ultimately patient care, with an established role in daily practice for objective assessment of lesions. This review outlines the importance of including microscopic evaluation in IBD, highlighting the clinical benefits of a deep state of disease remission using validated diagnostic methods and scoring systems for daily clinical practice.

Mucosal healing on endoscopy has emerged as a key prognostic parameter in the management of patients with IBD (Crohn's disease, ulcerative colitis/UC) and can predict sustained clinical remission and resection-free survival. The structural basis for this type of mucosal healing is a progressive resolution of intestinal inflammation with associated healing of ulcers and improved epithelial barrier function. However, in some cases with mucosal healing on endoscopy, evidence of histological activity in mucosal biopsies has been observed. Subsequently, in UC, a second, deeper type of mucosal healing, denoted histological healing, was defined which requires the absence of active inflammation in mucosal biopsies. Both levels of mucosal healing should be considered as initial events in the resolution of gut inflammation in IBD rather than as indicators of complete transmural healing. In this review, the effects of anti-inflammatory, biological or immunosuppressive agents as well as small molecules on mucosal healing in clinical studies are highlighted. In addition, we focus on the implications of mucosal healing for clinical management of patients with IBD. Moreover, emerging techniques for the analysis of mucosal healing as well as potentially deeper levels of mucosal healing such as transmural healing and functional barrier healing of the mucosa are discussed. Although none of these new levels of healing indicate a definitive cure of the diseases, they make an important contribution to the assessment of patients' prognosis. The ultimate level of healing in IBD would be a resolution of all aspects of intestinal and extraintestinal inflammation (complete healing).

Endoscopic healing is recognized as a primary treatment goal in Inflammatory Bowel Disease (IBD). However, endoscopic remission may not reflect histological remission, which is crucial to achieving favorable long-term outcomes. The development of new advanced techniques has revolutionized the field of IBD assessment and management. These tools can accurately assess vascular and mucosal features, drawing endoscopy closer to histology. Moreover, they can enhance the detection and characterization of IBD-related dysplasia. Given the persistent challenge of interobserver variability, a more standardized approach to endoscopy is warranted, and the integration of artificial intelligence (AI) holds promise for addressing this limitation. Additionally, although molecular endoscopy is still in its infancy, it is a promising tool to forecast response to therapy. This review provides an overview of advanced endoscopic techniques, including dye-based and dye-less chromoendoscopy, and in vivo histological examinations with probe-based confocal laser endomicroscopy and endocytoscopy. The remarkable contribution of these tools to IBD management, especially when integrated with AI, is discussed. Specific attention is given to their role in improving disease assessment, detection, and characterization of IBD-associated lesions, and predicting disease-related outcomes.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the colon and rectum. Endoscopy plays a crucial role in the diagnosis and management of UC. Recent advancements in endoscopic technology, including chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and the use of artificial intelligence, have revolutionized the assessment and treatment of UC patients. These innovative techniques enable early detection of dysplasia and cancer, more precise characterization of disease extent and severity and more targeted biopsies, leading to improved diagnosis and disease monitoring. Furthermore, these advancements have significant implications for therapeutic decision making, empowering clinicians to carefully consider a range of treatment options, including pharmacological therapies, endoscopic interventions and surgical approaches. In this review, we provide an overview of the latest endoscopic technologies and their applications for diagnosing and monitoring UC. We also discuss their impact on treatment decision making, highlighting the potential benefits and limitations of each technique.

Accurate disease characterization is the pillar of modern treatment of inflammatory bowel disease (IBD) and endoscopy is the mainstay of disease assessment and colorectal cancer surveillance. Recent technological progress has enhanced and expanded the use of endoscopy in IBD. In particular, numerous artificial intelligence (AI)-powered systems have shown to support human endoscopists' evaluations, improving accuracy and consistency while saving time. Moreover, advanced optical technologies such as endocytoscopy (EC), allowing high magnification in vivo, can bridge endoscopy with histology. Furthermore, molecular imaging, through probe based confocal laser endomicroscopy allows the real-time detection of specific biomarkers on gastrointestinal surface, and could be used to predict therapeutic response, paving the way to precision medicine. In parallel, as the applications of AI spread, computers are positioned to resolve some of the limitations of human histopathology evaluation, such as interobserver variability and inconsistencies in assessment. The aim of this review is to summarize the most promising advances in endoscopic and histologic assessment of IBD.