Tomašić V, Ćaćić P, Baršić N, Bišćanin A. Beyond conventional endoscopy: Image-enhanced techniques in quiescent ulcerative colitis assessment. World J Gastrointest Endosc 2026; 18(1): 113749 [DOI: 10.4253/wjge.v18.i1.113749]
Corresponding Author of This Article
Vedran Tomašić, MD, PhD, Consultant, Lecturer, Department of Endoscopy and Day Hospital, Klinički bolnički Centar Sestre Milosrdnice, Vinogradska Cesta 29, Zagreb 10000, Croatia. tomasicvedran@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Author contributions: Tomašić V provided the review’s conceptualization; Tomašić V and Ćaćić P performed the data acquisition and wrote the original draft; Tomašić V, Ćaćić P, Baršić N, and Bišćanin A participated in the review and editing of all successive versions of the manuscript. All authors approval the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vedran Tomašić, MD, PhD, Consultant, Lecturer, Department of Endoscopy and Day Hospital, Klinički bolnički Centar Sestre Milosrdnice, Vinogradska Cesta 29, Zagreb 10000, Croatia. tomasicvedran@gmail.com
Received: September 2, 2025 Revised: October 11, 2025 Accepted: November 21, 2025 Published online: January 16, 2026 Processing time: 135 Days and 8 Hours
Abstract
Mucosal healing is an important therapeutic target in ulcerative colitis (UC) because it is associated with improved clinical outcomes and sustained remission. Conventional white-light endoscopy has limitations, including subjective interpretation, interobserver variability, and difficulty detecting residual microscopic inflammation despite an apparently healed mucosa. Image-enhanced endoscopy (IEE) techniques improve visualization of mucosal and vascular patterns, potentially enhancing the assessment of inflammation and healing in UC. Modalities such as narrow-band imaging, linked-color imaging, blue laser imaging, dual-red imaging, texture and color enhancement imaging, and iSCAN accentuate vascular structures and subtle color differences, allowing more precise differentiation between complete and partial healing. These methods correlate strongly with histological inflammation and better predict clinical relapse compared with conventional scoring systems such as the Mayo Endoscopic Subscore. Quantitative IEE-based indices, including the linked-color imaging index, Paddington International virtual ChromoendoScopy ScOre, and Mucosal Analysis of Inflammatory Gravity by iScan TE-c Image score, provide reproducible and objective measurements that reduce subjective variability. Next-generation endoscopic platforms combining advanced IEE technologies enable real-time, high-resolution evaluation of mucosal microarchitecture and vascular regeneration. This facilitates personalized management by detecting residual inflammation earlier, improving monitoring, optimizing treatment decisions, and ultimately enhancing long-term outcomes while lowering relapse rates in UC patients.
Core Tip: Endoscopic-histological correlations in ulcerative colitis were previously inconsistent because conventional white-light endoscopy often missed subtle mucosal and vascular changes, leading to underestimation of patchy inflammation. Discrepancies also arose from sampling variability, patchy healing, unstandardized protocols, and inconsistent scoring systems. Advanced endoscopic technologies now enhance visualization of mucosal and vascular features, allowing more accurate assessment of disease activity that aligns closely with histology and supports improved long-term outcomes. These advances are driving the field of precision endoscopy in ulcerative colitis, with the potential to improve diagnostic accuracy and monitoring of treatment response.
Citation: Tomašić V, Ćaćić P, Baršić N, Bišćanin A. Beyond conventional endoscopy: Image-enhanced techniques in quiescent ulcerative colitis assessment. World J Gastrointest Endosc 2026; 18(1): 113749
Several studies have shown that endoscopic healing (EH), rather than clinical remission alone, is associated with a reduced risk of ulcerative colitis (UC) relapse and related complications during follow-up[1-3]. Consequently, treatment strategies that prioritize EH have emerged as a key therapeutic goal due to their link with improved long-term outcomes[4]. As a result, assessing endoscopic activity has become a regulatory requirement to provide a more objective evaluation of disease severity and therapeutic response.
This review summarizes current and recent literature on image-enhanced endoscopy (IEE) for assessing mucosal healing in adult patients with quiescent UC. A comprehensive PubMed/MEDLINE search was conducted, including prospective and retrospective studies, randomized controlled trials, and observational cohort studies published within the past 20 years that evaluated correlations between IEE findings, endoscopic and histological healing, and relapse prediction. The most recent search was completed in August 2025. Animal studies, case reports, and non-English publications were excluded.
CONVENTIONAL EVALUATION OF MUCOSAL HEALING IN UC
Although advances in treatment targets have driven significant progress in UC management, complete disease control remains elusive for many patients. Conventional endoscopic scoring systems, such as the Mayo Endoscopic Subscore (MES) and the UC Endoscopic Index of Severity (UCEIS), are limited by subjectivity, resulting in substantial intra- and interobserver variability in UC assessment[5-8]. Despite these limitations, the MES remains widely used in clinical practice and trials due to its simplicity and practicality.
A validated definition of EH in UC has not yet been established. EH is commonly defined as either complete endoscopic remission (MES 0) or partial remission (MES 1). A systematic review and meta-analysis performed by Viscido et al[9] showed that patients achieving MES 0 have a significantly lower risk of clinical relapse, irrespective of length of follow-up or maintenance therapy (conventional or biological therapy). That same meta-analysis also found a trend toward reduced hospitalization rates in patients with MES 0 compared to those with MES 1, although the small sample size limited their ability to draw definite conclusions and no colectomy events were reported. Accordingly, MES 0 was suggested as a more optimal therapeutic target due to its association with a potentially more durable clinical course. Nonetheless, that analysis did not account for potential confounders such as the use of standard vs high-definition endoscopy in MES assessment, variability in clinical relapse definitions, nor differing indications for hospitalization. Additionally, baseline characteristics including disease extent, presence of extraintestinal manifestations and smoking status were not compared between the MES 0 and MES 1 groups, despite their known influence on UC relapse risk.
The MES was originally developed and validated using standard-definition white light endoscopy (WLE). However, increasing evidence underscores important limitations of WLE that reduce the precision and reliability of the MES in detecting subtle inflammatory changes. Notably, even patients achieving MES 0 have a relapse rate of 9.4% within 6 months of follow-up[10]. Moreover, nearly one-quarter of patients with endoscopically quiescent disease continue to show microscopic inflammation, which is associated with higher relapse risk[11]. In contrast, patients who achieve both endoscopic remission (MES 0 or MES 1) and histological remission [Geboes score (GS) of 0 or 1 or Nancy Histological Index (NHI) 0 or 1] demonstrate a 58% reduction in relapse rates compared with those with persistent microscopic inflammation[12].
This variability underscores the need for innovative strategies to improve the accuracy and consistency of endoscopic evaluation in UC management. Incorporating both endoscopic and histologic findings into the concept of “mucosal healing” strengthens the modeling of disease pathways and supports more personalized, precise patient care. Robust evidence from UC trials has further introduced the concept of “disease clearance,” which posits that controlling inflammation at the microscopic level with achievement of an NHI score of 0 could meaningfully alter the long-term disease trajectory[13]. As a result, treatment paradigms are expected to shift toward a more comprehensive, multi-dimensional approach that integrates clinical, biochemical, endoscopic, and histologic remission[14].
A major challenge in the histological assessment of UC is the lack of a universally accepted, standardized scoring system, leading to variability across clinicians and researchers[15]. Additional difficulties include inconsistent measurement targets and the absence of consensus on criteria for tool selection, training, and scoring[16]. Further research is needed to weigh the benefits of composite endoscopic-histologic healing against patient discomfort, procedural risks, environmental burden, and the increased costs associated with frequent endoscopies and biopsies.
ASSESSMENT OF UC MUCOSAL HEALING USING IEE
The advent of high-definition WLE, together with the development of IEE platforms, has transformed real-time characterization of mucosal inflammation. These advances enable point-of-care optical diagnosis that can approximate histological assessment, allowing more accurate prediction of underlying histology during endoscopic evaluation. By reducing the need for biopsies, advanced IEE techniques may offer a more sustainable alternative to conventional WLE with biopsies, lessening both environmental and economic impacts[17].
Recent innovations include “push-button” electronic enhancement and digital-optical methods, collectively termed virtual chromoendoscopy. When combined with high-definition WLE, virtual chromoendoscopy enhances image contrast through optical filtering or software-based processing. Notable IEE modalities, such as narrow-band imaging (NBI; Olympus, Tokyo, Japan), texture and color enhancement imaging (TXI; Olympus), red dichromatic imaging (RDI; Olympus), iSCAN (Pentax, Tokyo, Japan), flexible imaging color enhancement (Fujinon, Tokyo, Japan), and blue laser light (BLI)/Linked-color imaging (LCI; Fujifilm, Tokyo, Japan), have demonstrated accuracy in assessing UC activity[18]. A meta-analysis of 17 studies found that virtual chromoendoscopy is significantly superior to WLE in diagnosing histological remission and differentiating histologically active disease from remission in UC[19]. Key performance metrics for each IEE modality compared with MES/UCEIS are summarized in Table 1, and landmark studies evaluating histologic activity in UC via IEE are listed in Table 2.
Table 1 Key performance metrics for each image-enhanced endoscopy modality compared to Mayo Endoscopic Score/Ulcerative Colitis Endoscopic Index of Severity.
Acute inflammatory cell infiltrates (26% vs 0%) and goblet cell depletion (32% vs 5%) were more commonly found in segments with an obscure MVP compared to those with a clear MVP, while basal plasmacytosis was less frequent in the former (2% vs 21%)
Definitions for histological findings followed those of the Japanese Ministry of Health, Labour, and Welfare
Over 60% of mucosal areas with a normal appearance under white light exhibited BV-H on NBI, while two-thirds of mucosal areas showing scars on white light displayed BV-BB on NBI; a significant correlation was observed between magnified NBI findings and histological results
Overall iSCAN score showed a strong correlation with the ECAP score; its accuracy in detecting abnormalities based on ECAP was 80%, with a sensitivity of 78% and specificity of 100%; Both the iSCAN vascular and mucosal scores were also significantly correlated with ECAP; correlation between the overall iSCAN score and RHI was moderate, with an accuracy of 68% for detecting abnormalities by RHI (sensitivity 78%, specificity 50%); notably, most patients with MES 0 still exhibited abnormalities on iSCAN
PICaSSO score demonstrated a strong correlation with multiple histological indices, showing significantly higher correlation coefficients compared to those of MES and UCEIS with histology scores
There was no significant difference in the proportion of the LCI group nor the relapse rate between UC patients with histologically active disease and those with inactive disease, as determined by GS
NBI technology enhances endoscopists’ ability to visualize and differentiate mucosal vascular patterns (MVPs). In patients with endoscopically quiescent UC, magnified NBI enables detailed characterization of MVP subtypes, such as “clear vs obscure”, “honeycomb-like vs irregular”, and blood vessels shaped like “honeycombs, bare branches, or vines”. These distinctions may help detect subtle residual inflammation and predict relapse within 12 months by identifying incomplete vascular regeneration[20-22]. In a recent study, Stefanelli et al[23] demonstrated that NBI provides both high interrater reliability and strong accuracy in assessing UC disease activity. The consistently good-to-excellent inter-operator agreement underscores its ease of use and practicality in clinical practice. Moreover, the excellent concordance between NBI-assessed activity and histological inflammation measured by the NHI confirms its accuracy and clinical utility.
Challenges with NBI include difficulty in reliably assessing vascular patterns in patients with moderate to severe UC, where mucosal edema and intramucosal hemorrhage can obscure visualization. Another limitation is the challenge of extrapolating localized MVP findings obtained with magnified NBI to an assessment of the entire colonic mucosa.
TXI
Hayashi et al[24] conducted a prospective single-center study of 146 UC patients in endoscopic remission (MES 1) and developed a 3-grade TXI scoring system based on redness enhancement and vessel visibility (score 0 = no accentuated redness, score 1 = accentuated redness, score 2 = accentuated redness with poor deep-vessel visibility). This system successfully stratified risk within the MES 1 subgroup: Patients with TXI score 2 had significantly lower relapse-free survival and reduced histological remission rates compared with those scoring 0-1. On multivariate analysis, TXI score 2 emerged as an independent risk factor for UC relapse [hazard ratio (HR) = 4.16, 95% confidence interval (CI): 1.72-10.04, P < 0.01], while maintaining good interobserver agreement (κ = 0.597-0.823).
Mamiya et al[25] reported strong associations between TXI and conventional WLE scoring systems (MES and UCEIS, P < 0.001), fecal calprotectin levels (P = 0.015), and histologic activity assessed by the GS, with the GS 2B (neutrophil infiltration in the lamina propria) showing the strongest correlation. However, unlike conventional endoscopic scores, TXI did not significantly predict UC relapse in this cohort. The authors attributed this to the relatively low relapse rate of 13.3% during follow-up, which may have limited the statistical power to detect prognostic differences.
RDI
In contrast to NBI, RDI employs longer wavelengths to enhance visualization of deeper tissue structures, particularly submucosal blood vessels in patients with mild to moderate UC[26]. The RDI scoring system, first developed by Naganuma et al[27], has been validated in a study by Hashimoto et al[28]; in detail, it demonstrated strong correlations with conventional WLE-based scores, including MES (r = 0.78, P < 0.0001) and UCEIS (r = 0.74, P < 0.0001), as well as with histological inflammation assessed by NHI (r = 0.63, P < 0.0001). Notably, the RDI scores correlated more strongly with histological activity assessed by NHI than conventional endoscopic scores[28]. Mamiya et al[25] further reported significant correlations between RDI and MES, UCEIS, fecal calprotectin levels, and the GS. They also established the prognostic value of RDI for UC relapse, reporting that patients with RDI scores of 3-4 had a significantly higher relapse risk (HR = 3.56, 95%CI: 1.13-11.24, P = 0.03) compared to those with lower scores.
LCI
LCI enhances visualization of mucosal redness and vascular patterns associated with inflammation, with some studies reporting improved contrast and brightness compared to standard WLE, NBI, and BLI[29]. Several prospective studies have evaluated LCI-based classification systems, demonstrating correlations between LCI endoscopic patterns, disease activity, and clinical outcomes in UC[30-34].
In a pilot study, LCI demonstrated more than twice the color differentiation between inflamed and normal mucosa compared to WLE, thereby enhancing the detection of subclinical inflammation[30]. Uchiyama et al[31]reported that the LCI index strongly correlated with Matts histopathological grade and that the interobserver agreement for LCI classifications was comparable to or greater than that of the MES, with κ values remaining excellent even between expert and non-expert readers. Across studies by Kanmura et al[32], Takagi et al[33], and Matsumoto et al[34], LCI accurately identified patients in endoscopic remission (MES ≤ 1) who experienced favorable long-term outcomes over a 12-month follow-up. Moreover, LCI endoscopic patterns showed a strong correlation with histologic healing as assessed by the GS and were associated with lower clinical relapse rates[33,34]. In a recent study by Sugiyama et al[35], LCI demonstrated diagnostic accuracy for histologic healing comparable to autofluorescence imaging, showing higher sensitivity, while autofluorescence imaging exhibited higher specificity. A key advantage of LCI over other virtual chromoendoscopy technologies is its enhanced brightness, which allows comprehensive wide-angle inspection of the colon without the need for magnification or close-up imaging. This feature streamlines endoscopic evaluation by enabling rapid, high-contrast assessment of the entire mucosal surface, facilitating the detection of subtle inflammatory changes.
iSCAN
An initial study reported that iSCAN may provide improved assessment of UC disease activity and the extent of mucosal inflammation compared to conventional WLE[36]. iSCAN shows strong correlations with the MES and several established histological scoring systems, including the New York Mount Sinai system, Robarts Histopathology Index (RHI), and Extent, Chronicity, Activity, Plus score[37,38].
Notably, iSCAN has been shown to detect subtle mucosal and vascular abnormalities even in patients classified as MES 0. In a study by Iacucci et al[37], iSCAN identified such abnormalities in approximately one-third to two-thirds of MES 0 patients, enabling real-time risk stratification without the need for biopsy.
iSCAN technology was subsequently used to develop the Paddington International virtual ChromoendoScopy ScOre (PICaSSO), a standardized tool for evaluating mucosal and vascular patterns in inflammation[39]. PICaSSO demonstrates excellent interobserver agreement across varying levels of endoscopic experience and shows strong correlations with multiple histological indices, including RHI, NHI, Extent, Chronicity, Activity, Plus score, GS, and Villanacci scores[40,41].
A prospective study of 307 patients across 11 international centers validated PICaSSO’s ability to predict favorable clinical outcomes at 6 months and 12 months of follow-up[42]. Notably, endoscopic remission defined by the PICaSSO score alone was as effective as standard endoscopic-histological remission criteria in predicting 12-month outcomes, including therapy switches, hospitalizations, and colectomy.
The PICaSSO scoring system demonstrates excellent reproducibility across multiple virtual chromoendoscopy platforms beyond iSCAN. Validation studies have confirmed its successful application with NBI and LCI/BLI, showing strong correlations with histological scores (RHI and NHI) and accuracy comparable to MES and UCEIS in predicting histological remission[43].
Potential limitations of the aforementioned IEE technologies include longer procedural times, which may affect clinical workflow and patient comfort. In addition, their use often requires specialized equipment, software upgrades, and targeted training to ensure accurate image acquisition and interpretation.
AI-ENABLED ADVANCES IN ENDOSCOPIC DISEASE ASSESSMENT
Emerging AI-based models may offer an accessible, time-efficient, standardized, and objective approach to assessing UC activity, potentially reducing intra- and interobserver variability inherent to conventional human assessment. A cohort study of 110 patients followed for 12 months after colonoscopy reported that artificial intelligence (AI)-based MES assignments achieved high sensitivity (96.9%), specificity (78.4%), and overall accuracy (93.4%) in identifying EH[44]. These models also demonstrated superior performance in stratifying patients’ risk of clinical relapse compared to conventional methods. Notably, AI-based systems showed greater reproducibility, with consistently higher inter-observer and intra-observer agreement than human endoscopists alone.
AI-assisted IEE systems have been developed to help non-expert clinicians provide objective and accurate diagnostic predictions using advanced optical imaging. Notably, one AI system performs targeted mucosal characterization, classifying tissue as “vascular-active” or “vascular-healing” through sophisticated pattern recognition algorithms[45]. This system demonstrated strong prognostic capability, predicting clinical relapse in 104 UC patients with MES ≤ 1 over a 12-month follow-up. The relapse rate was significantly higher in the AI-classified vascular-active group (23.9%) compared with the vascular-healing group (3.0%).
Chat generative pre-trained transformer version 4 (open AI) has demonstrated performance comparable to trained gastroenterologists in grading 50 endoscopic images according to MES criteria in UC patients[46]. In comparative studies, chat generative pre-trained transformer version 4 achieved a mean accuracy of 78.9%, vs 81.1% for trained inflammatory bowel disease, with no statistically significant difference between groups (P = 0.71). Notably, this performance was achieved without prior configuration, fine-tuning, or specialized training, highlighting the potential of advanced multimodal language models for analyzing complex medical imagery.
Convolutional neural network models have been successfully trained to detect endoscopic remission and predict histological remission using the PICaSSO score[47]. Their risk stratification for disease flare was comparable to physician-assessed endoscopy score (UCEIS), demonstrating the clinical utility of automated assessment.
Recent developments have introduced a multimodal “AI-switching” model that combines PICaSSO with NBI technology[48]. This approach demonstrates high accuracy in predicting endoscopic and histological remission (81.3% and 89.6%, respectively), with area under the receiver operating characteristic curve values of 0.92 and 0.89 for UCEIS and PICaSSO assessments.
Another innovative approach is the Mucosal Analysis of Inflammatory Gravity by iScan TE-c Image score[49]. This AI-based system effectively stratifies patients with MES ≤ 1 according to histological activity without requiring biopsy. The Mucosal Analysis of Inflammatory Gravity by iScan TE-c Image score correlates significantly with the GS and demonstrates superior ability to distinguish between MES 0 and MES 1 patients in clinical remission. Integration into endoscopic workflows and regulatory challenges currently limit the routine clinical implementation of AI-assisted IEE systems.
VIRTUAL CHROMOENDOSCOPY IN ULCERATIVE COLITIS: APPLICATION AND OPTIMIZATION
Currently available virtual chromoendoscopy technologies enable real-time, point-of-care “optical biopsies”, enhancing the evaluation of endoscopic and histological activity in UC. LCI and TXI improve visualization of subtle mucosal inflammation across the colonic lumen using a “distant view” approach, whereas NBI, iSCAN, and BLI provide detailed “close-up” assessment of mucosal-vascular patterns. RDI further allows evaluation of deep vascular structures in the presence of mucosal edema and inflammation.
Quantitative scores derived from these virtual chromoendoscopy technologies have demonstrated validation and reproducibility, supporting their use in risk assessment for disease relapse and guiding monitoring and treatment strategies in UC. Nevertheless, further longitudinal studies are required to determine their impact on long-term outcomes. By reducing reliance on conventional mucosal biopsies, these technologies may also lower healthcare costs and improve the sustainability of endoscopic procedures. Computer-aided detection systems using AI have shown promise in providing more consistent and objective evaluations by reducing inter-observer and intra-observer variability in scoring, although broader clinical validation is still ongoing.
Virtual chromoendoscopy technologies are standardly available in current-generation endoscopic equipment, so there are no inherent barriers to wider implementation in UC diagnosis and monitoring. However, challenges remain, including limited access to the latest-generation endoscopes, variable virtual chromoendoscopy expertise among endoscopists, and the capacity or willingness to adopt new methods. Additional obstacles include longer procedure times that may affect patient comfort, an extended learning curve, limited standardized training programs, and high initial costs with minimal or absent reimbursement from regulatory authorities.
Addressing these challenges through targeted education, system-level policy improvements, and further research into cost-effectiveness and long-term outcomes is essential to support the integration of virtual chromoendoscopy technologies into routine clinical practice and optimize UC patient care.
CONCLUSION
IEE may serve as a valuable adjunct in evaluating quiescent UC by overcoming some limitations of conventional endoscopy. Its incorporation into routine practice has the potential to improve disease monitoring and guide therapeutic decision-making in UC.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Croatia
Peer-review report’s classification
Scientific Quality: Grade B, Grade B
Novelty: Grade C, Grade C
Creativity or Innovation: Grade C, Grade C
Scientific Significance: Grade B, Grade B
P-Reviewer: Petrousis G, MD, Researcher, Sweden S-Editor: Zuo Q L-Editor: A P-Editor: Xu J
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