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The British Journal of Radiology logoLink to The British Journal of Radiology
. 2020 Apr 13;93(1109):20190614. doi: 10.1259/bjr.20190614

Correlation between ultrasound consolidated score and simple endoscopic score for determining the activity of Crohn’s disease

Chang Liu 1,2,1,2, Shi-Si Ding 1,2,1,2, Kun Zhang 1,2,1,2, Lin-Na Liu 1,2,1,2, Le-Hang Guo 1,2,1,2, Li-Ping Sun 1,2,1,2, Yi-Feng Zhang 1,2,1,2, Xiao-Min Sun 3, Wei-Wei Ren 1,2,1,2, Chong-Ke Zhao 1,2,1,2, Xiao-Long Li 1,2,1,2, Qiao Wang 1,2,1,2, Xiao-Rong Xu 3, Hui-Xiong Xu 1,2,1,2,✉
PMCID: PMC7217571  PMID: 32101466

Abstract

Objectives:

The aim of this study was to develop an ultrasound consolidated score (UCS) in determining the activity of Crohn’s disease (CD) and evaluate it with reference to simple endoscopic score (SES).

Methods:

From June 2014 to June 2017, 66 patients with CD were retrospectively enrolled in this study. Each patient underwent endoscopy and transabdominal ultrasound (US) examination. The morphological symmetry, echogenicity of bowel wall, bowel wall layer structure, echogenicity of peri-bowel fat, bowel wall thickness (BWT), and Limberg type on power Doppler US were assessed with transabdominal US, and an UCS scoring system was developed based on these characteristics. Endoscopic results were used as the reference standard and SES was calculated to determine the CD activity. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance for determining CD activity and the correlation between UCS and SES was assessed using Spearman correlation analysis.

Results:

330 intestinal segments in 66 patients were included. The UCS of the segments in the remission phase ranged from 3.0 to 9.0 (mean, 3.6 ± 0.9) whereas in the active phase from 3.0 to 20.0 (mean, 10.6 ± 4.0) (p < 0.001). The cut-off value of UCS was 6. The associated area under ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.980, 88.3%, 95.5%, 93.8%, 91.3%, and 92.3%, respectively. The correlation coefficient between UCS and SES was 0.90, which was higher than the correlation coefficient of 0.83 between BWT and SES.

Conclusions:

The newly developed UCS with transabdominal US has a good performance and potentially provides an effective alternative for evaluating the activity of CD.

Advances in knowledge:

UCS is an effective method to evaluate the activity of CD because it provides comprehensive information of the disease. Therefore, it could be employed as an alternative for diagnosis of CD.

Introduction

Crohn’s disease (CD) is a chronic, non-specific inflammatory disease caused by intestinal immune dysfunction that can affect the entire intestinal wall.1–5 CD usually presents complications such as fistulas, stenosis, and intestinal obstruction.6–9 The inflammatory lesions of CD are transmural, segmental, and asymmetrically distributed in the intestine.10 Of all inflammatory bowel segments, the terminal ileum and right colon are the most commonly involved segments in this entity. CD also affects the small bowel in some cases. CD is characterized by alternating active and remission phases and cannot be cured.11,12 Recurrent episodes, lifelong morbidity, and long treatment time are usual for patients with CD.13 Therefore, assessment of disease severity is crucial to determine the therapeutic strategy and to evaluate the prognosis. Patients with CD need follow-up and dynamic evaluation before and after treatment. A diagnosis modality that can accurately assess the activity and severity of CD is very important for selection of treatment method, assessment of treatment efficacy, and timely adjustment of treatment strategy.

The severity of CD is often evaluated by endoscopy, which provides direct information of the inner mucosal layers and is considered the gold standard for the determination of CD severity.14,15 However, endoscopy is an invasive and painful procedure that is not always well tolerated by patients. Repeated endoscopy examinations are not suitable for patients who need surveillance in short periods..16,17 In addition, endoscopy is not suitable for patients with primary intestinal stenosis or postoperative stenosis.18 Moreover, endoscopy observes only the surface of intestinal wall, mostly the mucosal layer lesions, and cannot provide an accurate evaluation of the transmural inflammation, while ultrasound (US) is able to observe the five-layer structure of the intestinal wall, which includes mucosa, muscularis mucosa, submucosa, muscularis propria, and serosa. In addition, the surrounding changes of abdominal structures are also observable with US, such as fat change, abscess, fistula, and so on. Nowadays, US is widely employed as an objective, accurate, non-invasive, and convenient examination method for evaluating CD. US has gained increasing attention in assessing the activity, complications of CD, and the efficiency of treatment.19

Conventionally, the bowel wall thickness (BWT) is the most regular parameter used for assessing CD activity with US. However, US not only facilitates measurement of BWT, but also provides information such as morphological symmetry, echogenicity of the bowel walls, bowel wall layer structure, echogenicity of peri-bowel fat, and Limberg type on power Doppler US. Therefore, we hypothesized that a semi-quantitative analysis including these characteristics, that is, a new scoring system named US consolidated score (UCS), would be more beneficial for assessment of CD activity, in comparison with BWT alone. To confirm the hypothesis, this study was carried out to evaluate whether UCS could be used as an alternative method for assessment of CD. The aim of this study was to evaluate the correlation between UCS and simple endoscopic score (SES) in determining the activity of CD. The study might provide a more comprehensive non-invasive US-based method for evaluating CD activity.

Methods and materials

Patients

The study was approved by the ethics committee of the university hospital and written informed consent was waived due to the retrospective nature of the study. All the procedures in the study complied with the World Medical Association Declaration of Helsinki.20

Between June 2014 and June 2017, 66 patients diagnosed with CD were retrospectively enrolled in this study (Figure 1). The inclusion criteria were as follows: patients were diagnosed with CD by clinicians; patients had been hospitalized, and the records of all examinations were complete; both the US and endoscopy results were stored and the time interval between endoscopy and US was less than 24 h; and US and endoscopy were carried out before treatment during hospitalization. Patients with following conditions were excluded from the study: diagnosed as UC; diagnosed as intestinal tuberculosis; unconfirmed to have CD; and incomplete image data. Finally, there were 66 patients involved in this study: 34 males and 32 females (age range 18–77 years, mean age 39.4 ± 15.4 years). Of these 66 cases, the time interval from initial diagnosis of CD to the latest examination of US or endoscopy ranged from 1 month to 360 months, with the median value of 24.0 months. Six patients were diagnosed with CD for the first time, and the other 60 patients had recurrent disease. 313 segments in 66 patients were analyzed, with endoscopy as the reference standard.

Figure 1.

Figure 1.

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Patients enrollment method flow chart in this study.

Conventional US examination

66 enrolled patients underwent conventional US examination (Table 1). The patients were fasted for 8 h and enemas were performed by taking the cathartic agent of polyethylene glycol electrolyte powder solution for intestinal preparation the day before the examinations.21

Table 1.

Conventional US examination steps

Description procedure Step Detail
Bowel preparation Fasted 8 h and took cathartic agent of polyethylene glycol electrolyte powder solution for enema.

  1. First dosage: 600–1000 ml

    Every 10–15 min: 250 ml

    Total: 2,000–3000 ml

  2. Standard: Watery stool observed
US preparation Orally took 2.5% isotonic mannitol 60 min prior to US.

  1. 1,000 ml of 2.5% isotonic mannitol;

  2. Endoscopy was scheduled after US examination on the same day or on the following day.
US examination

  1. Perform a full abdominal scan for overall condition.

  2. The terminal ileum, right colon, transverse colon, left colon, and rectum were carefully examined.

  1. The convex array transducer was used to exam the terminal ileum, right colon, transverse colon, left colon, and rectum.

  2. The linear array high-frequency transducer was used to examine the bowel clockwise, starting from terminal ileum, followed by right colon, transverse colon, left colon, and rectum.
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On the day of US examination, approximately 1,000 ml of 2.5% isotonic mannitol was orally administered to each patient 60 min before US examination. The purpose was to reduce intestinal peristalsis and intestinal gas.

The Logiq E9 US scanner (GE Healthcare, Milwaukee, WI, USA), equipped with convex array transducer C1-5 (frequency range, 2–5 MHz) and linear-array transducer L4-9 (frequency range, 4–9 MHz), was employed in this study. In addition, S2000 (Siemens Medical Solutions, Mountain View, CA, USA) with a convex array transducer (frequency range, 1–4 MHz) and a linear-array transducer (frequency range, 4–9 MHz) was also used.

The US examinations were performed by a physician with 7 years of experience in CD US examination. The conventional US examination took 20–30 min. First, the convex array transducer was used to perform a full abdominal scan to observe the patient’s overall condition. Then, the linear array high-frequency transducer was used to examine the details of segments. Continuous dynamic observation was performed on each segment of the intestinal wall.

Conventional US was used to observe the thickness of the intestinal wall on both the transverse and longitudinal sections. The symmetry of the involved segments was assessed to determine whether they were symmetric thickening or asymmetric thickening. The intestinal wall echogenicity, the intestinal wall layers, hierarchical structure in the wall, echogenicity of peri-bowels fat, the peristalsis of intestine, the dilation or stricture of intestine cavity, as well as Limberg type on power Doppler US were also observed. In general, five layers could be recognized by conventional US for normal bowel wall. From the internal cavity outwards, the five layers are as follows: hyperechoic mucosa, hypoechoic muscularis mucosa, hyperechoic submucosa, hypoechoic muscularis propria, and hyperechoic serosa. Limberg types are as follows: Limberg type 0, normal bowel wall; Limberg type Ⅰ, thickened bowel wall without vascularity; Limberg type Ⅱ, thickened bowel wall with short blood vessels; Limberg type Ⅲ, thickened bowel wall with longer blood vessels; and Limberg type Ⅳ, thickened bowel wall with long blood vessels connected with mesenteries. Higher Limberg levels represent more active disease.

The morphological symmetry, echogenicity of the bowel wall, bowel wall layer structure, echogenicity of peri-bowel fat, BWT, and Limberg type on power Doppler US were analyzed and were included in the proposed UCS for the diagnosis of CD. The calculation of UCS was as follows: UCS = S1 (score for symmetry)+S2 (score for the echogenicity of peri-bowel fat)+S3 (Limberg type)+S4 (score for bowel wall layer structure)+S5 (score for the echogenicity of the bowel walls)+S6 (score for BWT). Specifically, for the score of symmetry, if the anterior and posterior bowel wall layers are symmetrical, S1 = 0 point; otherwise S1 = 1 point. For S2, if the echogenicity of peri-bowel fat is high, S2 = 1 point; otherwise S2 = 0 point. For S3, if bowel walls are determined as Limberg type 0, IorII, S3 = 0; if they are Limberg type III or IV, S3 = 1. For S4, if the five-layer structure of the intestinal wall is clearly visible, S4 = 0 point; if the bowel wall layers are less clear but the inside and outside layers can be distinguished, S4 = 1 point; and if all layers are unclear, S4 = 2 points. For S5, if the thickness of the hyperechoic submucosa is smaller than the thickness of the hypoechoic muscularis mucosa, or all layers are hypoechoic, S5 = 0 point; if the thickness of the hyperechoic submucosa is similar to the thickness of the hypoechoic muscularis mucosa, S5 = 1 point; and if the thickness of the submucosa is larger than the thickness of the muscularis mucosa, or all layers are hyperechoic, S5 = 2 points. For S6, S6 = rounding value of the BWT (mm). For instance, if the BWT was 3.1 mm, three points were allocated for S6; if the BWT was 3.6 mm, four points were allocated (Table 2)(Figures 2–6).

Table 2.

UCS scoring system (UCS = S1 (score for symmetry)+S2 (score for the echogenicity of peri-bowel fat)+S3 (Limberg Classification)+S4 (score for bowel wall layer structure)+S5 (score for the echogenicity of the bowel walls)+S6 (score for BWT), points)

UCS Factor 0 1 2
Symmetry Symmetrical Asymmetrical -
Echo of peri-bowels fat Not increased Increased -
Limberg Type Type 0, Ⅰ,Ⅱ Type Ⅲ,Ⅳ -
Bowel wall layers structure Clear Less clear Unclear
Echo of the bowel walls Thickness of submucosa with hyperechogenicity is smaller than thickness of hypoechoic muscularis mucosa. Thickness of submucosa with hyperechogenicity is similar to thickness of hypoechoic muscularis mucosa. Thickness of submucosa with hyperechogenicity is larger than thickness of hypoechoic muscularis mucosa.
BWT Score = N points (rounded using 0.5 cut off)
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UCS, ultrasound consolidated score; BWT, bowel wall thickness.

Figure 2.

Figure 2.

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Ultrasound images show the morphological symmetry of bowel walls. The solid yellow line is the boundary between the serosal layer of the intestinal wall and the surrounding tissue, and the white solid line distinguishes the anterior and posterior walls of the bowel. (A) The anterior and posterior bowel walls are symmetrical and the UCS is 0. (B) The anterior and posterior bowel walls are asymmetrical and the UCS is 1.

Figure 3.

Figure 3.

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Ultrasound images show the echogenicity of peri-bowel fat in a patient with Crohn’s disease. The solid yellow line is the boundary between the serosal layer of the intestinal wall and the surrounding tissue, and the white solid line distinguishes the anterior and posterior walls (in B1, the part between the two white lines is the intestinal tract). (A) The echogenicity of peri-bowel fat in the area outside the yellow solid line is not increased and the UCS is 0. (B) The echogenicity of peri-bowel fat in the area “H” outside the yellow solid line is increased significantly and the UCS is 1.

Figure 4.

Figure 4.

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Ultrasound images show the Limberg types of bowel walls in a patient with Crohn’s disease. The solid yellow line is the boundary between the serosal layer of the intestinal wall and the surrounding tissue, and the white solid line distinguishes the anterior and posterior walls. (A) Limberg type 0 indicating normal bowel wall. (B) Limberg type Ⅰ indicating thickened bowel wall. (C) Limberg type Ⅱ indicating thickened bowel wall with short blood vessels. (D) Limberg type Ⅲ indicating thickened bowel wall with longer blood vessels. (E) Limberg type Ⅳ indicating thickened bowel wall with long blood vessels connected with mesenteries.

Figure 5.

Figure 5.

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Ultrasound images show the bowel wall layer structure. The solid yellow line is the boundary between the serosal layer of the intestinal wall and the external tissue, and the white solid line distinguishes the anterior and posterior walls (in A1, the part between the two white lines is the intestinal tract). (A) A1 and A2 show that the five-layer structure of the intestinal wall is clearly visible: the mucosal layer is hyperechoic, the mucosal muscle layer is hypoechoic, the submucosa is hyperechoic, the muscular layer is hypoechoic, and the serosa layer is hyperechoic; the UCS is 0. (B) B1 and B2 show that only the inside and outside layers can be clearly visualized inside bowel wall layers and the UCS is 1. (C) C1 and C2 show that all five layers are too blurry to differentiate and the UCS is 2.

Figure 6.

Figure 6.

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Ultrasound images show the echogenicity of the bowel walls. The solid yellow line is the boundary between the serosal layer of the intestinal wall and the external tissue, and the white solid line distinguishes the anterior and posterior walls (in A1 and C1, the part between the two white lines is the intestinal tract). (A) A1 and A2 show that the thickness of the hyperechoic submucosa is less than the that of the hypoechoic muscularis mucosa thus the UCS is 0. (B) B1 and B2 show that the thickness of the hyperechoic submucosa is similar to the thickness of the hypoechoic muscularis mucosa and the UCS is 1. (C) C1 and C2 show that the thickness of hyperechoic submucosa is larger than the thickness of hypoechoic muscularis mucosa and the UCS is 2.

All the US evaluation was performed by two US physicians independently with consensus and they were blinded to the patient history and relevant data. The qualitative features evaluated including symmetry, the echogenicity of peri-bowel fat, bowel wall layer structure, the echogenicity of the bowel walls, and Limberg types by the first observer was compared to that evaluated by the second observer.

Endoscopy examination

On the same day or the next day after US examination, the terminal ileum, right colon, transverse colon, left colon, and rectum were observed by endoscopy (Olympus, probe CE-H180AI/L, Hamburg, Germany), and a multisite biopsy of living tissue for pathological and cytological examination was performed. The endoscope first reached the end of the ileum, and the characteristics of the lesion as well as the extent and location of each segment of the lesion were slowly examined by retreating the endoscopy and the images were collected. The endoscopist was blinded to the US findings and they were different doctors.

The endoscopy results were taken as the reference standard to determine the extent and activity of CD. The whole intestine was divided into five segments: terminal ileum, right colon, transverse colon, left colon, and rectum. SESs (ulcer size +ulcer area+lesion ratio +intestinal stenosis, range 0–12 points) were generated on the five segments based on the literature.22

According to previous studies, cases scored with 0–2 points at endoscopy are considered to be in the remission period, while 3–12 points indicate the active period.22 The degree of activity of each patient was determined by two senior physicians from the Department of Gastroenterology who were familiar with all parameters of the SES scoring system. They independently scored and calculated SESs and reached a consensus if the results were widely varied. The clinical and histopathological severity of the patient was anonymous at the time of evaluation to avoid influence on the results. In addition, both UCS and SES were analyzed at a segment level.

Statistical analysis

Statistical analysis was performed using the SPSS V.18.0 statistical software (V.18.0, SPSS Inc., Chicago, IL, USA). Descriptive data were expressed as mean ± standard deviation. An independent t test was used for continuous variables analysis, and the chi-square test was used for qualitative variables. Receiver operating characteristic (ROC) curve analysis was performed and the area under the ROC (AUROC) curve was calculated. AUROC, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated, with endoscopy as the reference standard. Sensitivity and specificity were calculated as following: Sensitivity = true positive (TP)/ (TP +false negative [FN]); Specificity = true negative (TN)/ (TN +false positive [FP]).

In addition, z test was performed to find difference in diagnostic performance between BWT and UCS. Correlation analysis between SES with endoscopy and UCS with US was evaluated using Spearman correlation analysis after all results were adjusted by K-means cluster which they were divided into four groups: remission, mild, medium and severe groups. A correlation coefficient of 0.00–0.25 was considered negligible, 0.26–0.49 low correlation, 0.50–0.69 moderate correlation, 0.70–0.89 high correlation (strong correlation), and 0.90–1.00 highly consistent. Interobserver consistency for the qualitative analysis was assessed by using a κ value. κ values were interpreted as slight agreement (κ = 0.00–0.20), fair agreement (κ = 0.21–0.40), moderate agreement (κ = 0.41–0.60), substantial agreement (κ = 0.61–0.80), and almost perfect agreement (κ = 0.80–1.00).

Results

Endoscopy results

Due to severe intestinal stenosis, endoscopy could not be completed in eight patients with a total of 17 bowel segments. Therefore, 313 segments in 66 patients were scored with SES (Tables 3 and 4) (Figure 7). 178 segments were in the remission phase (SES range: 0–2), while 135 segments were in the active phase (SES range: 3–12). Among the 135 segments of active intestine, 50 (37.0%) were found at terminal ileum, 28 (20.7%) right colon, 17 (12.6%) transverse colon, 27 (20.0%) left colon, and 13 (9.6%) rectums. Totally, 57.7% of the involved segments were terminal ileum and right colon.

Table 3.

SES scoring system (SES = Ulcer size+Ulcer area+Lesion ratio +Intestinal stenosis, range 0–12 points)22

SES factor 0 1 2 3
Ulcer size 0 <0.5 cm, 0.5–2 cm, >2 cm,
Aphtha Large ulcers Giant ulcers
Ulcer area ratio 0 <10% 10–30% >30%
Lesion area ratio 0 <50% 50–75% >75%
Intestinal stenosis 0 Single, More than one, Endoscopy cannot pass
Endoscopy can pass Endoscopy can pass
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SES, simple endoscopic score

Table 4.

Characteristics of enrolled bowel segments with Crohn’s disease

SES UCS factor 0–2
(Remission phase)		 3–12
(Active phase)		 Pa
Number of segments 176 137 N/A
Symmetry score = 0 score = 1 163
13		 71
66		 <0.001
Echo of peri-bowels fat score = 0
score = 1		 165
11		 36
101		 <0.001
Limberg
Score = 0
Score = 1		 0
176
0		 1
81
56		 <0.001
Bowel wall layers score = 0
Score = 1
Score = 2		  153
 23
 0		 64
63
10		 <0.001
Echo of the bowel walls
Score = 0
Score = 1
Score = 2		 153
14
6		 37
64
39		 <0.001
BWT
range (mm)
mean (mm)		 2–7.8
2.34 ± 1.62		 2–15
8.18 ± 3.09		 <0.001
UCS
range
mean		 3.0–9.0
3.35 ± 0.93		 3.0–20.0
10.55 ± 4.04		 <0.001
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SES, simple endoscopic score; UCS, ultrasound consolidated score; BWT, bowel wall thickness.

a

<0.01 was considered to be statistically significant.

Figure 7.

Figure 7.

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The histogram shows SESCD scores distribution of 313 cases.

US results

For the 66 patients with CD, a total of 330 bowel segments were examined using transabdominal US with respect to the wall thickness, morphological symmetry, bowel wall layers, echogenicity of the bowel walls, echogenicity of peri-bowel fat, and Limberg types (Figure 8). Endoscopy could not pass the intestines due to stenosis in 17 intestinal segments, thus they were excluded for the analysis in this study. Finally, only the 313 segments visible on endoscopy were analyzed with US since endoscopy was the reference standard.

Figure 8.

Figure 8.

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Ultrasound (US) and endoscopy images of a 32-year-old female (A), 45-year-old male (B), and a 36-year-old male (C) with Crohn’s diseases (CD). Images A1, B1, and C1 with US show the wall symmetry and peri-bowel fat echogenicity; Images A2, B2, and C2 show enlarged view of the bowel walls; Images A3, B3, and C3 show the endoscopy characteristics. (A) Refers to one intestinal segment (right colon) with SES = 2, BWT = 3.3 mm, and UCS = 4. The CD is in the remission phase. (B) Refers to one intestinal segment (right colon) with SES = 5, BWT = 5.2 mm, and UCS = 8. The CD is in the active phase. (C) Refers to one intestinal segment (transverse colon) with SES = 11, BWT = 12.4 mm, and UCS = 18. The CD is in the active phase.

117 of 135 segments in active phase were detected by transabdominal US. The detection rates for terminal ileum, right colon, transverse colon, left colon, and rectum were 96.0% (48/50), 92.0% (26/28), 82.4% (14/17), 88.9% (24/27), and 38.46% (5/13), respectively.

The BWT of the segments in the remission phase ranged from 2.0 to 7.8 mm (mean, 2.4 ± 1.0 mm), whereas BWT in the active phase ranged from 2.0 to 15.0 mm (mean, 7.6 ± 2.9 mm) (P ＜0.001). With SES as the reference standard, the cut-off value of BWT was 3.0 mm. The associated AUROC, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for BWT were 0.977, 92.0%, 90.3%, 88.1%, 93.5% and 91.1%, respectively (Figure 9).

Figure 9.

Figure 9.

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ROC curve for BWT shows that AUROC = 0.977, p < 0.001.

The UCS of the segments in the remission phase ranged from 3 to 9 (mean, 3.4 ± 0.9), whereas UCS in the active phase ranged from 3 to 20 (mean, 10.6 ± 4.0) (P＜0.001). The cut-off value of UCS was 6. The associated AUROC, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.980, 88.3%, 95.5%, 93.8%, 91.3%, and 92.3% (Figure 10). No significant difference in diagnostic performance between BWT and UCS was found (z test, p = 0.4137).

Figure 10.

Figure 10.

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ROC curve for UCS shows that AUROC = 0.980, p < 0.001.

Correlation between endoscopy and US

The correlation between BWT measured by transabdominal US and SES with endoscopy was assessed for the 313 intestinal segments and the correlation coefficient was 0.83 (95% CI: 0.787–0.857, p < 0.001), indicating that BWT with US and SES with endoscopy were significantly consistent in determining the activity of CD (Figure 11). In addition, the correlation between UCS with US and SES with endoscopy for the 313 intestinal segments was assessed, and the correlation coefficient after adjustment for clustering was 0.90 (95% CI: 0.111–1.000, p < 0.05), which was higher than that between BWT and SES (Figure 11).

Figure 11.

Figure 11.

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(A) Correlation scatter plot of SES and BWT with correlation coefficient r = 0.83 and CI of 0.787–0.857 (p < 0.001). (B) Correlation scatter plot of SES and UCS, with correlation coefficient r = 0.90 and I 0.111–1.000 (p < 0.05).

Interobserver agreement for UCS

The κ values of symmetry, the echogenicity of peri-bowel fat, bowel wall layer structure, the echogenicity of the bowel walls, and Limberg types were 0.747, 0.932, 0.869, 0.649, and 0.851, respectively, for interobserver agreement (p < 0.001). The total κ value for UCS was 0.652 (p < 0.001).

Discussion

In this study, the correlation between UCS and SES was evaluated for determining the inflammatory activity in CD. Our results found that UCS with US is able to reflect the activity of inflammatory lesions in the intestinal wall in patients with CD, which can be used as an alternative method for endoscopic examination when endoscopy is inappropriate or is not available.

Currently, the most commonly used scoring system for CD in clinical practice is the Crohn's Disease Activity Index (CDAI), which uses clinical symptoms such as the frequency of diarrheas, the degree of abdominal pain, and the general conditions of the patient as the basis for evaluation.23 However, the patients’ complaints for symptoms are subjective. Studies had showed that CDAI had a weak correlation with mucosal inflammation on endoscopy.24 Cross-sectional imaging, including CT, MRI, and US, can observe both the intestinal and abdominal lesions and they complement each other for detecting and measuring disease activity. However, CT and MRI are not suitable for repeated use and long-term surveillance because of radiation, inconvenience, low availability, and increased cost. In a recent multicenter clinical trial, both magnetic resonance enterography (MRE) and US are confirmed to have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations.25 Transabdominal US, however, is a non-invasive, convenient, and accurate method with low cost, which can be used repeatedly during the treatment and surveillance process.26 Although the sensitivity and specificity of MRE exceed US significantly in the METRIC (MREnterography or ulTRasound in CD) study,25 in China, the waiting time for MRE is nearly two weeks, whereas only 2 days for US examination. In addition, MRE costs about 80–90 US dollars, whereas less than 20 US dollars for US examination. Therefore, US is more cost-effective and more suitable for long-term surveillance. In the past studies, conventional US combined with color Doppler US or contrast-enhanced US (CEUS) was proven to be capable of determining the severity of CD.27 Novak et al found that the BWT and color Doppler signal correlated significantly with CD activity with a Simple Sonographic Score (SSS).28 For strictures, endoscopy can only score intestinal segments before strictures while US is able to exam segments on and after strictures. Moreover, most strictures contain fibrosis and inflammation, and it was regarded that differentiation of inflammatory from fibrotic strictures was achievable with new US techniques such as CEUS and elastography.29–34

In this study, a new scoring system, UCS, was proposed. The correlation coefficient between UCS and the SES was higher than that between BWT and SES, which suggested that this new scoring system could be better than BWT alone for evaluating the activity of CD since the former includes more information about the inflammation change in CD patients. Interobserver analysis also showed that this method had a substantial consistency.35

Patients with CD often have edema and ulcers in the bowel wall. The edema of the intestinal wall can be well reflected by the thickness of the intestinal wall, which is one of the most important changes for CD patients. The measurement of intestinal wall thickness on US is convenient and repeatable and there is a significant correlation between BWT on US with SES on endoscopy. However, the information about the ulcers is hardly available by BWT measurement. A longitudinal ulceration of the intestinal wall often causes asymmetric thickening of the intestinal wall. Inflammation in the ulcerated area is heavier than surrounding areas, which increased inflammatory infiltration and tissue hyperplasia around the ulcer. The more severe the ulcer is, the more severe edema of the intestinal wall, and the intestinal wall thickness increases substantially. In addition, due to the long-term process of repeated inflammation onset and remission in the intestinal wall, tissue inflammatory edema, connective tissue hyperplasia, and fibrotic changes often occur, thus segmental irregular thickening of the intestinal wall could be observed. UCS provides the information about bowel wall symmetry whereas only the widest portion is measured with BWT.

Second, the layering of the intestinal wall also has been considered to have a substantial relationship with the activity of CD.36 For lesions with more severe inflammatory exudation, the lining of the intestinal wall would disappear and the layers could not be distinguished. For mild lesions, the bowel wall layers would reappear as the condition was relieved. These different conditions are hard to be reflected by BWT alone whereas can be revealed with the UCS scoring system. Therefore, UCS provides more details about the severity of CD in comparison with BWT alone.

Regarding the echogenicity of the bowel walls, the hypoechoic mucosal layer and the hyperechoic submucosal layer are the most often affected layers, which can be easily observed by US. BWT alone does not provide such information. However, with regard to UCS, hypoechoic thickening of the mucosal muscle layer is defined as 0 point on S5, one point is assigned if the thickness of the two layers is similar, and two points if the hyperechogenic submucosa is highly thickened. The latter indicates that the inflammation is more severe that the infiltration of inflammation is not limited to the inner wall of the intestine but is transmural. UCS is able to provide this detailed information whereas BWT is not able to reveal it. In addition, κ value of interobserver agreement is smaller than others, the possible soot cause might be the subjectivity of the scoring. We need to make the definition more explicit in future study.

Regarding the echogenicity of peri-bowel fat, increased peri-intestinal fat echogenicity indicates that the inflammation involves peri-bowel fat thus is more severe, which is also to be reflected by the UCS scoring system whereas is unavailable by measurement of BWT alone.

We also included Limberg types in the UCS to determine CD activity because power Doppler US is a well-applied tool in the clinical practice. To be specific, intestines with Limberg I and Limberg II are considered to be in remission phase while Limberg III and Limberg IV are in active phase, therefore, they were assigned by score 0 and 1, respectively.

The study has several limitations. First, this was a retrospective study and thus the results should be validated in future studies with prospective design. Second, US of CD needs many experiences and thus the results in this single center study might not necessarily be repeatable in other centers. Multicenter studies with more cases are needed to validate the results in this study. Third, all the patients were hospitalized in this study since endoscopy was scheduled for all of them and the patient history data were complete for the hospitalized patients. This might limit the generalizability of the results. In addition, the scores were analyzed at a segment level. It is hard to perform analysis on the basis of patient level, because the same patient might have segments in both active phase and remission phase. The study was looking at the colon and terminal ileum only as correlated purely with colonoscopy. Small bowel capsule as an emerging tool has advantages in detecting more bowel segments and reducing pains for patients while it is not widely available and was not a routine procedure. SES was used as the gold standard instead of histology from biopsy since biopsy might have sampling error. SES is a qualitative method open to the same biases as US interpretation, whereas two independent readers with consensus would solve this problem. Moreover, the UCS should be compared to the standardized imaging protocols such as MRE or CT as well as a qualitative US score in future studies particularly should be correlated with the MRE scores for example in the METRIC study.25 Finally, more parameters and respective weighing of individual parameters using multivariate regress analysis should be studied in future research to improve UCS in evaluating activity of CD.

In summary, UCS with transabdominal US is consistent with SES with endoscopy. In comparison with conventional BWT measurement alone, UCS provides more comprehensive information about the inflammation conditions in CD patents.

Footnotes

Acknowledgment: This work was supported by the Fundamental Research Funds for the Central Universities (Grants 22120180376 and 22120190021) and the National Natural Science Foundation of China (Grants 81601502, 81671695 and 81725008).

†Chang Liu and Shi-Si Ding contributed equally to this study.

Contributor Information

Chang Liu, Email: liuchang0907@tongji.edu.cn.

Shi-Si Ding, Email: dingshisi@163.com.

Kun Zhang, Email: zhang1986kun@126.com.

Lin-Na Liu, Email: liulinna61@163.com.

Le-Hang Guo, Email: gopp1314@hotmail.com.

Li-Ping Sun, Email: sunliping_s@126.com.

Yi-Feng Zhang, Email: zhangyifeng@tongji.edu.cn.

Xiao-Min Sun, Email: sxmglcly@163.com.

Wei-Wei Ren, Email: rww9456@163.com.

Chong-Ke Zhao, Email: zhaochongke123@163.com.

Xiao-Long Li, Email: 15275388623@163.com.

Qiao Wang, Email: wangqiao078@163.com.

Xiao-Rong Xu, Email: xuxr@tongji.edu.cn.

Hui-Xiong Xu, Email: xuhuixiong@126.com.

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