Published online Jul 7, 2021. doi: 10.3748/wjg.v27.i25.3734
Peer-review started: January 25, 2021
First decision: March 29, 2021
Revised: April 9, 2021
Accepted: May 8, 2021
Article in press: May 8, 2021
Published online: July 7, 2021
Processing time: 161 Days and 9.9 Hours
The small intestine is located in the middle of the gastrointestinal tract, so small intestinal diseases are more difficult to diagnose than other gastrointestinal diseases. However, with the extensive application of artificial intelligence in the field of small intestinal diseases, with its efficient learning capacities and compu
Core Tip: Artificial intelligence has been widely used in the management of small intestinal diseases, which has greatly improved the diagnostic efficiency of capsule endoscopy and other examination methods, and at the same time, beneficial progression has also been obtained in the prognosis prediction of small intestinal diseases. Although AI still faces risks such as overfitting and black box effects, its stability and efficiency give it great potential in the management of small intestinal diseases. This article reviews the current application status of AI in small intestinal diseases. In addition, challenges and prospects in this field are discussed.
- Citation: Yang Y, Li YX, Yao RQ, Du XH, Ren C. Artificial intelligence in small intestinal diseases: Application and prospects. World J Gastroenterol 2021; 27(25): 3734-3747
- URL: https://www.wjgnet.com/1007-9327/full/v27/i25/3734.htm
- DOI: https://dx.doi.org/10.3748/wjg.v27.i25.3734
The small intestine is located in the middle of the gastrointestinal digestive system, with a total length of 5 m to 7 m, including the duodenum, jejunum and ileum, and is the longest organ of the digestive system. Small intestinal diseases (SIDs) mainly include celiac disease (CD), small intestinal Crohn’s disease (SICD), primary small intestinal tumor (PSIT), obscure gastrointestinal bleeding and so on. The traditional examination methods include X-ray barium enterography, computed tomography (CT), magnetic resonance imaging (MRI), balloon-assisted enteroscopy, deep enteroscopy and so on. In recent years, the emergence of capsule endoscopy (CE) has brought a revolutionary breakthrough for the diagnosis of SIDs. However, because of the special anatomical position of the small intestine (far away from the oral cavity and anus, overlap and peristalsis), there are still many problems in the diagnosis of SIDs, such as high technical requirements, low positive rate of diagnosis, inaccurate qualitative location of the disease, patient intolerance and so on. In addition, the onset of SIDs is insidious, the specificity of clinical symptoms is low, and the lesion site is not easy to explore, so the clinical diagnosis of SIDs has always been a difficult problem. With the emergence of artificial intelligence (AI) and its wide application in the medical field, it also provides new methods for the whole management process of SIDs and greatly improves the efficiency of SIDs management.
AI is a concept put forward in the 1950s. It is a frontier cross discipline developed on the basis of computer science, neuropsychology, philosophy, linguistics, cyber
This study used the keywords of “artificial intelligence” and “small intestine” to search the relevant literature in the databases of PubMed, Embase, Web of Science and Cochrane Library up to October 2020. Studies included in our review were required to meet the following inclusion criteria: (1) full-text paper available in English; and (2) studies that associated AI with the small intestinal diseases. We excluded descriptive papers without validation of methods. The application status of AI in SIDs was summarized, and the challenges and prospects in this field were discussed.
With the advent of AI, it is possible to perform computer-assisted organ segmentation in CT, MRI, endoscopy and other examination methods and has shown good application potential in the fields like assisted localization of radiotherapy. The following will introduce the research progress of this aspect in the field of the small intestine especially the duodenum (Table 1).
Ref. | Diagnostic method | AI technology | Training set | Validating set | Outcomes |
Tong et al[11] | CT | ML | 90 images | - | DSC of duodenum: 69.26% |
Kim et al[9] | CT | CNN | 80 images | 40 images | DSC of duodenum: 0.595 |
Peng et al[10] | CT | CNN | 43 images | - | DSC of duodenum: 0.61 |
Fu et al[12] | MRI | CNN | 100 images | 20 images | Dice coefficient of duodenum: 65.50% ± 8.90% |
Dice coefficient of bowel: 86.60% ± 2.69% | |||||
Chen et al[13] | MRI | DL | 66 images | 36 images | DSC of duodenum: 0.80 |
Takiyama et al[15] | EGD | CNN | 27335 images | 17081 images | AUCs: 0.99 |
Igarashi et al[16] | EGD | ML | 49174 images | 36072 images | Accuracy (Ts: 0.993, Vs: 0.965) |
CT: Some studies had used the CNN method to automatically segment duodenum and other abdominal organs from CT images, with clinically acceptable accuracy and efficiency[9,10]. Tong et al[11] proposed an end-to-end segmentation network for improving multiorgan segmentation performance using the ML method. The dice similarity coefficient and average surface distance were quantitatively evaluated, and the results confirmed this network had good accuracy and timeliness in the anatomical segmentation of abdominal organs including the duodenum.
MRI: Fu et al[12] conducted a retrospective analysis on 3D MR images of 120 patients and proposed a CNN model, which has been verified to accurately segment the abdominal organs including the duodenum and expedite the contouring process for MRI-guided adaptive radiotherapy. Chen et al[13] also conducted a similar study, and in their study, the inference process was completed within 1 min, indicating an obvious advantage of timeliness. The length of the small intestine is an important factor in the management of patients with short bowel syndrome. Some scholars designed a special software algorithm to calculate the length of small intestine based on magnetic resonance enterography images in mice. Compared with the measured results of anatomical specimens, the mean absolute difference between the two methods was 1.8 ± 3.8 cm (P = 0.24), and the mean percentage difference was 9.4% ± 6.0%[14].
Endoscopy: In a Japanese study based on GoogLeNet architecture, a CNN diagnostic program was constructed, using 27335 esophagogastroduodenoscopy (EGD) images for the training set and using 17081 EGD images for the independent validation set. The results showed that the CNN has a good effect to classify the anatomical location of EGD images for stomach and duodenum images, with an area under the curve of 0.99[15]. Igarashi et al[16] used AlexNet (a deep learning framework) to retrospectively analyze 85246 original images of EGD images in 441 patients with gastric cancer and developed an anatomical organ classifier. The accuracy rates of the training and validation sets were 0.993 and 0.965, respectively.
With the emergence of CE in 2000[17], it has revolutionized our understanding of small intestinal mucosa[18-20], enabling doctors to detect small intestinal mucosal erosion, ulcers, vascular disease, bleeding, polyps, parasite and other lesions more efficiently. However, reliable and rapid reading of video is still a challenge, but more and more studies have shown that the combination of AI and CE can greatly improve the efficiency of our evaluation of small intestinal mucosal lesions; the detection accuracy was above 90% in most studies[21-27].
Ulcer: Previous studies have confirmed that applying a CNN system of deep learning to the reading process of CE can reduce the reading time without decreasing the detection rate of erosion and ulcer lesions[28-32].
Angioectasias and bleeding: Intestinal angioectasias cause more than 8% of all gastrointestinal bleeding episodes[33]. Different studies have applied ML, CNN and computer algorithms to the differential diagnosis of intestinal angioectasias and have achieved high sensitivity and specificity[34-39]. AI is also applied to the direct examination of intestinal mucosal bleeding by CE, which can directly calculate the blood content in the digestive tract and infer whether there is active bleeding in the small intestinal mucosa[40-44].
Protruding lesions: There are a variety of small intestinal mucosal protruding lesions. CNN can help doctors describe their shape features, help analyze their nature and distinguish polyps, epithelial tumors, submucosal tumors, etc.[34,45,46].
Villous atrophy: Villous atrophy is a defining symptom of some digestive tract diseases such as CD. Some scholars combined AI methods with CE for the detection and measurement of villous atrophy and successfully mapped the extent of the diseased small intestine[47].
AI is also used in risk prediction and clinical treatment decisions of small intestinal mucosal lesions. For example, one study used CNN for the risk prediction of acute intestinal bleeding[48], and another study applied CNN to risk prediction and therapeutic tactics selection for duodenal ulcers[49]. Wong et al[50] built a ML model, based on data from 22854 patients with gastroduodenal ulcer including six clinical parameters to identify patients at high risk for recurrent ulcer bleeding within 1 year. Gastrointestinal bleeding is a common complication of left ventricular assist device treatment. Axelrad et al[51] developed an endoscopic algorithm. Compared with conventional cohorts, the implementation of the algorithm increased endoscopic diagnostic efficiency by 68%, treatment efficiency by 113%, the number of procedures per patient decreased by 27%, the length of hospital stay decreased by 33%, and the estimated cost decreased by 18%.
In addition, the interference of intestinal contents to CE can also be reduced by AI. Combined with support vector machine, Bashar et al[52] designed a classifier for separating useless frames that are highly contaminated by turbid fluids, fecal materials and/or residual foods. The accuracy of this classifier was more than 80%. Pietri et al[53] developed a computer algorithm to automatically evaluate the demeanor of small intestinal bubbles in CE images. The specificity of this algorithm was 95.79%, the sensitivity was 95.19%, and the calculation time was 0.037 s per frame. It can be used to reduce the interference of bubbles in CE images. Klein et al[54] created a computed algorithm based on the pixels in the color bar to score and classify the preparation of the small intestine for CE, and this automatic scoring method has a concordance rate of more than 90% with the assessment of clinicians.
CD is a complex autoimmune disease. Patients who ingest foods containing gluten will develop an autoimmune response that causes damage to the small intestine. CD is one of the most common chronic digestive diseases, with a prevalence rate of 1% worldwide[55]. Duodenal biopsy is the gold standard for diagnosis[56]. Noninvasive methods such as endoscopy and clinical features analysis are also widely used in diagnosis, but the diagnostic rate of CD is only 15%–20% through current strategies[57]. However, with the increasing application of AI in the diagnosis of CD, the accuracy and efficiency of diagnosis are greatly improved[58] (Table 2).
Ref. | Diagnostic method | AI technology | Training set | Testing set | Outcomes |
Chetcuti et al[62] | CE | ML | 81 patients | - | Accuracy: 75.3% |
Li et al[63] | CE | Computer-assisted recognition | Ep: 240, Cp: 220 | - | Accuracy: 93.9% |
Vicnesh et al[64] | CE | Computerized algorithm | 21 patients | - | Accuracy: 89.82% |
Zhou et al[65] | CE | CNN | Ep: 6, Cp: 5 | Ep: 5, Cp: 5 | Accuracy: 100% |
Gadermayr et al[59] | EGD | Computer-assisted | 290 patients (2835 images) | - | Accuracy: 94%-100% |
Das et al[67] | Mucosal biopsies | Computer-assisted | Ep: 124, Cp: 137 | Ep: 120, Cp: 105 | Sen: 90.3%, Spe: 93.5%, AUCs: 96.2% |
Wei et al[66] | Mucosal biopsies | DL | 212 images | - | Accuracy: 95.3%, AUCs > 0.95 |
Pastore et al[70] | Clinical data | Computer-assisted | 100 patients | - | Reliability: 0.813 |
Tenório et al[60] | Clinical data | Decision trees, Bayesian inference, k-nearest neighbor algorithm, support vector machines, artificial neural networks | 178 patients | 38 patients | Accuracy: 80.0%, Sen: 0.78, Spe: 0.80, AUCs: 0.84 |
Virta et al[68] | Micro-CT | Computer-assisted point cloud analysis | 81 patients | - | Accuracy: 100% |
Sangineto et al[69] | Gene expression in PBMCs | ML, random forest algorithm | Ep: 17, Cp: 20 | - | Accuracy: 100% |
Previous studies have confirmed that AI-assisted duodenoscope images analysis can greatly improve the diagnostic efficacy of CD, with the accuracy between 80% and 100% and specificity and sensitivity over 80%[59-61]. In the diagnosis of CD, the combination of AI and CE is closer, which can improve the accuracy of diagnosis and significantly save the diagnosis time[62-65]. AI was also used in the analysis of duodenal mucosa biopsy, which can help with qualitative analysis and play an important role in quantitative analysis[66,67]. At the same time, the application of AI with X-ray images[68], peripheral blood mononuclear cells[69] and clinical features[60,70] in the diagnosis and classification of CD have also achieved progress.
Crohn’s disease is a chronic nonspecific inflammatory bowel disease that affects the entire gastrointestinal tract, in which 30% of patients are confined to the small intestine, commonly known as small intestinal Crohn‘s disease[71]. SICD most often involves the distal ileum as well as the jejunum and the digestive tract above and has a higher incidence of intestinal strictures than colonic Crohn‘s disease[72,73]. The application of AI in the management of SICD is comprehensive, including diagnosis, risk prediction, extra-intestinal manifestation (EIM) prediction and so on (Table 3).
Ref. | Diagnostic method | AI technology | Training set | Testing set | Outcomes |
Yang et al[78] | Microultrasound | CNN | 43 mice | - | AUCs: 0.8831 |
Shen et al[80] | Clinical data | Computerized algorithm | Ep1: 61, Cp1: 78 | Ep2:42, Cp2: 57; Ep3:84, Cp3: 495 | AUCs: 0.92 |
Bottigliengo et al[81] | Clinical data | BMLTs (NB, BN, BART) | 152 patients | - | AUCs without genetic variables (NB: 0.71, BN: 0.50, BART: 0.76), AUCs with genetic variables (NB: 0.75, BN: 0.67, BART: 0.78) |
Taylor et al[79] | Clinical data | ML (elastic net and random forest) | 480 first-degree relatives | - | AUCs (elastic net): 0.80, AUCs (random forest): 0.87 |
Menti et al[82] | Clinical data | BMLTs | 152 patients | - | Accuracy without genetic variables: 82%, accuracy with genetic variables: 89% |
Klang et al[77] | CE | DL | 49 patients (17640 images) | - | AUCs: 0.94-0.99, accuracy: 95.4%-96.7% |
Parfеnov et al[76] | CE | Computerized algorithm | 25 patients | - | 44% patients confirmed only with the help of AI |
Lamash et al[74,75] | MRI | CNN | 15 patients | 8 patients | Dice coefficients: 75%-97% |
Diagnosis: Lamash et al[74,75] used CNN to analyze MRI images and construct an assessment model for SICD. Their model could effectively distinguish active and inactive inflammatory segments, distinguish segments with strictures and segments without strictures and could be used to measure the length of intestinal strictures. Parfеnov et al[76] used a software diagnostic algorithm to analyze the CE images of 25 SICD patients, preliminarily confirming that CE could be used to diagnose early SICD with intestinal mucosal inflammation. Klang et al[77] performed automatic analysis of CE images of 49 SICD patients using a CNN method, achieving diagnostic accuracy of more than 95% and significantly reducing reading time. Yang et al[78] also attempted to combine CNN with a microultrasound system for early diagnosis of SICD in mice and achieved good effectiveness in the identification of early inflammation.
Risk prediction of SICD: Taylor et al[79] used ML classifiers (elastic network and random forest) to classify small intestine inflammation in asymptomatic first-degree relatives of patients with SICD. They found that genetic variants associated with SICD, family history and fecal calprotectin together identified individuals with presymptomatic intestinal inflammation who are therefore at risk for SICD. Shen et al[80] developed a web-based SICD hazard stratification tool. Predicting high-risk populations for SICD based on altered bowel habit, abdominal pain, white blood cell count, albumin and platelet count abnormalities allowed clinicians to identify potential SICD earlier.
Risk prediction of EIMs: AI is controversial in the evaluation of the EIMs of SICD. In the study of Bottigliengo et al[81], based on Bayesian machine learning technology evaluation combined with genetic factors to predict the occurrence of EIMs in Crohn’s disease, it has no advantage over traditional statistical tools. Whereas Menti et al[82] used Bayesian machine learning technology to predict the risk of occurrence of EIMs in Crohn’s disease, and the prediction accuracy was 82% when considering only clinical factor and 89% combined with genetic factors, which was outperforming other prediction techniques.
The incidence of PSIT is about 5% of gastrointestinal tumors and 0.2% of all kinds of tumors[83,84]. The main site of PSIT is the duodenum, followed by the jejunum and ileum[85]. There are a variety of pathological types of malignant PSIT. Adenocarcinoma is the most common pathological type, up to 40%, followed by neuroendocrine tumors (25%), malignant lymphomas (10%-15%) and malignant stromal tumors (9%)[86]. PSIT lacks specific manifestations in the early stage, and they are faced with many problems in the clinic, such as difficult diagnosis, high misdiagnosis rate, nonstandard treatment and so on[87]. AI has been applied in the field of auxiliary diagnosis and prognostic analysis of PSIT, and has an important impact on the management (Table 4).
Ref. | Diagnostic method | AI technology | Training set | Testing set | Outcomes |
Inoue et al[88] | EGD | CNN | 531 images | 1080 images | Accuracy: 94.7%-100% |
Liu et al[90] | CE | SVM | 89 patients | - | Sen: 97.8%, Spe: 96.7% |
Vieira et al[89,91] | CE | SVM | 29 patients (936 images) | - | This SVM outperforms others by more than 5% |
Barbosa et al[93] | CE | CNN | Ep: 104, Cp: 100 | Ep: 92, Cp: 100 | Sen: 98.7%, Spe: 96.6% |
Panarelli et al[94] | MicroRNA sequencing | ML | 84 samples | - | Accuracy (Ts: 98.5%, Vs: 94.4%) |
Drozdov et al[95] | Gene expression profiling | ML | 73 samples | - | Differentiated from normal cells (Sen: 100%, Spe: 92%), metastases prediction (Sen: 100%, Spe: 100%) |
Kjellman et al[96] | Plasma protein multibiomarker | Random forestmodel | Ep:135, Cp: 143 | - | AUCs: 0.97 |
Yan et al[97] | CT | Random forestmodel | 213 patients | - | AUCs: 0.943 |
Diagnosis: Inoue et al[88] used CNN to analyze EGD images for the diagnosis of superficial nonampullary duodenal epithelial tumors. The overall diagnosis accuracy of CNN was 94.7%, including 94% for adenomas and 100% for high-grade dysplasias, and it only took 12-31 s for analysis. The method of support vector machine was applied to the automatic analysis of CE images, which greatly improved the accuracy and efficiency of diagnosis[89-92]. In addition, Barbosa et al[93] used the CNN to automatically analyze CE images for the diagnosis of PSIT, which also had high sensitivity and specificity, reaching 98.7% and 96.6%, respectively.
Risk stratification and prognosis prediction: In different studies, ML was used to analyze the pathological tissue samples, plasma protein multibiomarker and miRNA markers of patients with small intestinal neuroendocrine tumors[94-96]. Their studies provided some new and effective methods for early diagnosis, treatment strategy selection, prognosis prediction and recurrence risk prediction of small intestinal neuroendocrine tumors. In the study of Yan et al[97], random forest models were performed to evaluate the correlation of risk stratification for small intestinal stromal tumors. Their study suggested multidetector CT texture analysis may become an important comprehensive tool for preoperative risk stratification of small intestinal stromal tumors.
Small intestinal obstruction: Cheng et al[98,99] used CNN to analyze abdominal radiographs to assist in the diagnosis of small intestinal obstruction (SIO). The sensitivity and specificity of the CNN diagnostic system were 83.8% and 68.1%, respectively, based on the training set of 2210 abdominal radiographs. When the training set was expanded to 7768 abdominal radiographs, the diagnostic sensitivity and specificity were increased to 91.4% and 91.9%, respectively. Their study suggests that the accuracy of detection of SIO by CNN improves significantly with the increasing number of training radiographs. Lucas et al[100] explored the development of an ML tool for SIO detection based on CT images. They evaluated the accuracy of eye tracking in image centerline annotation of the small intestine as the first step in the development of an ML tool for SIO. Their results showed that the eye tracking-based annotation was accurate and precise enough for application in ML-based small intestinal centerline annotation.
Small intestinal motor dysfunction: Small bowel intestinal dysfunction (SIMD) can occur during the development of many diseases, so the evaluation of small intestinal motor function is an important means for the auxiliary diagnosis and severity evaluation of these diseases. AI is widely used to evaluate small intestinal motor function through CE images. Using intraintestinal manometry as the gold standard for the diagnosis of SIMD, Malagelada et al[101] proved that an ML model was reliable to evaluate CE images for the diagnosis of SIMD. Applying this model, they found that 29% of patients with functional intestinal disorders had SIMD, significantly higher than that of the healthy population (3%), confirming the pathophysiological changes in the intestine of functional intestinal disorders[102]. Furthermore, a classification method for classifying functional intestinal disorders according to small intestinal motor function was also proposed[103].
De Iorio et al[104] also demonstrated that ML can reliably detect reduced intestinal muscle activity and motion by CE images through the method of injecting intestinal muscle inhibition (glucagon) into healthy subjects. Moreover, the study of Seguí et al[105] suggested that CNN was also reliable in the description and classification of small intestine motor characteristics with the classification accuracy reaching 96%. Malagelada et al[106] also used ML to analyze CE and abdominal MRI images of patients with cystic fibrosis and confirmed that the delay in small bowel and colonic transit times in patients with cystic fibrosis is associated with known endocrine dysfunction and with SIMD.
Small intestinal ischemia-reperfusion injury: Intraoperative evaluation of intestinal viability in patients with acute intestinal ischemia is a critical factor for surgical decision making. In the pig jejunum experiment, Strand-Amundsen et al[107] attempted to apply ML to the analysis of multivariate time-series of bioimpedance sensor data to analyze intestinal viability after intestinal ischemia-reperfusion. The results suggested that the measurement should be made before the onset of reperfusion, and the prediction effect was better when the measurement was repeated continuously during ischemia and reperfusion. The detection accuracy of irreversible damage may be close to 100%.
Enteropathies associated with undernutrition: There is a significant histopathological overlap in duodenal biopsies of enteropathies associated with undernutrition such as environmental enteropathy and CD. Syed et al[108] used CNN to establish a histopathological analysis model, which can effectively distinguish environmental enteropathy, CD and normal intestinal mucosa. The detection accuracy was 93.4%, and the false-negative rate was 2.4%.
At present, in order to promote the application of AI in the field of SIDs, we still need to solve some problems and challenges: (1) Insufficiency of training sample size. The incidence of most SIDs is not high. For example, the incidence of PSIT is much lower than that of gastric tumors and colorectal tumors, which affects the amount of data in the training set. Measurement errors are easy to occur when the sample size is small[109], and as suggested by the continuity study of Cheng et al[98,99], expanding the sample size of the training set can significantly improve the inspection accuracy of AI model; (2) Lack of prospective data. Most of the studies used retrospective data, which have been artificially screened before AI model training and lack prospective studies; (3) Single source of data. Most of the training sets and verification sets used in the study come from single-center data, so it is still necessary to further improve the repeatability and stability of the model through multicenter data. As in Alzheimer‘s disease research, each single center should be encouraged to share data in anticipation of establishing large-scale and open databases[110]; (4) The interpretation of the results. Due to the inevitable problems of AI, like overfitting of training set data[111] and the “black box” characteristic of the algorithm[112], the accuracy and interpretation of the AI model are inconsistent, which may have a negative impact on clinical application[113]. More intensive basic research and extensive verification are needed to improve this deficiency; (5) Ethical and legal issues. Can we trust the results of AI? Once the AI diagnosis and treatment prediction fails, it will give rise to a series of social, ethical and legal problems[114,115]. It is necessary to combine human supervision with AI tools more reliably; and (6) AI has been widely researched in various fields. We should attach importance to learning experience from different research fields and try to carry out related research in the field of SIDs, so as to promote the continuous progress of AI research in the field of SIDs.
The advantages of AI in the diagnosis and prognosis analysis of SIDs have been increasingly recognized, and the high accuracy and efficiency of AI detection greatly reduce the workload of doctors. Although there are still various challenges in the application of AI, the potential of AI in improving the management efficiency of diseases cannot be ignored. Clinicians should work together with experts in various fields to promote the development of AI in SIDs.
Manuscript source: Invited manuscript
Specialty type: Gastroenterology and hepatology
Country/Territory of origin: China
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