EFSUMB Recommendations and Clinical Guidelines for Intestinal Ultrasound (GIUS) in Inflammatory Bowel Diseases

Key words

Gastrointestinal tract - inflammatory bowel diseases - guidelines - ultrasound - Crohn’s disease - ulcerative colitis - IBD - ultrasonography

Introduction

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) with increasing incidence and prevalence worldwide [1]. The onset of IBD may occur in different decades of life with CD being more frequent in the second and third decade. Many patients are still faced with a diagnostic delay [2] [3].

Diagnostic imaging in the management of IBD

IBD patients need clinical, biochemical, endoscopic, and cross-sectional assessment to confirm the diagnosis and flares of the disease, to detect complications and to guide treatment. To date, endoscopy remains the main diagnostic procedure since it allows biopsy and histological evaluation [4]. However, it has limitations with respect to the assessment of the complications and proximal ileal extension of CD [5]. Furthermore, European guidelines on diagnostics in IBD have recommended complementary imaging methods, such as gastrointestinal ultrasound (GIUS), computed tomography enterography (CTE) and magnetic resonance enterography (MRE) for the diagnosis and determination of the location, extent and complications of CD [6].

Gastrointestinal ultrasound and other imaging tools in IBD

Systematic reviews and meta-analyses have shown that GIUS, CTE and MRE have comparable diagnostic accuracy for the initial assessment of CD, the monitoring of disease activity and progression, and for assessing its main complications (stenoses, fistulae and abscesses) [7] [8] [9] [10] The latest consensus guidelines by the European Crohn’s and Colitis Organization (ECCO) and European Society of Gastrointestinal Radiology (ESGAR) for imaging in IBD have recommended GIUS, CTE, or MRE to detect small bowel CD at its first presentation, to assess disease activity of the terminal ileum, to diagnose stenoses of the small bowel and to assess penetrating complications [11]. Among these techniques, GIUS has the advantage of being well-tolerated, radiation-free, repeatable, generally available and less expensive [12].

Advantages and limitations of GIUS

The increasing worldwide interest in GIUS for IBD has been recently pointed out [12] [13] [14], but issues need to be faced before widespread use, such as standardization and general agreement regarding the definition of the intestinal and extra-intestinal features, and the criteria for the detection of IBD, which are still not well defined. Indeed the sensitivity and specificity of the technique may vary according to the criteria and cut-offs used [7] [8] [15] [16] [17] [18] [19].

For this reason our international team of GIUS experts, under the umbrella of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), cooperated in order to establish GIUS recommendations for assessing IBD.

Methodological structure and classification of the consensus levels

The creation of the Task Force Group (TGF) of GIUS experts, the development of guidelines according to a modified Delphi method and all steps that have led to the statements regarding the definition criteria and landmarks of the US features of IBD, with their Level of Evidence (LoE) and Grade of Recommendation (GoR) [20] have been reported in detail in the online version of this issue. All statements in this issue include an agreement/disagreement level that has been scored on a five-point Likert scale as follows: A+: agree; A-: rather agree; I: indecisive; D-: rather disagree; D+: disagree.

Features of Crohn’s disease

Crohn’s disease, especially when located in the small bowel, can be difficult to detect and challenging to follow-up, since it presents with both intestinal and extra-intestinal features. Transabdominal GIUS can assess luminal, parietal and extra-parietal features of CD and allows the detection and assessment of its severity.

Luminal and parietal features

Thickening

Bowel wall thickening (BWT) is by far the most important and most used parameter when diagnosing CD, and it is the most consistently used parameter in systematic reviews and meta-analyses to detect the disease [7] [8]. Indeed, BWT is also a reproducible parameter between investigators [21]. We recommend measuring wall thickness in the anterior wall of the bowel (or where it is better visible) in the longitudinal direction, avoiding haustrations and mucosal folds. The cursor/calipers should be placed at the end of the interface echo between the serosa and the proper muscle to the start of the interface echo between the lumen and the mucosa [22] [23].

The cut-off for the detection of CD varies among studies. However, the latest meta-analysis, which included 15 prospective studies, showed that a cut-off value of 3 mm had a sensitivity and specificity of 89 % and 96 %, respectively, while other cut-off values (4 mm or more) yielded a sensitivity of 87 % and a specificity of 98 % [16]. Moreover, this study also showed that increased BWT is the best parameter to detect CD located in the small bowel.

The thickening of each single layer of the bowel wall and its clinical significance in CD have been poorly investigated so far. It seems that the proper muscle layer and submucosal layer are thicker in patients with poor response to medical treatment and higher risk of surgery [24] [25] and that the increased thickening of the submucosa is associated with active CD [26]. Overall the degree of BWT is correlated with clinical and biochemical activity of CD, but the correlation is weak [27] [28] [29] [30]. The increased BWT is also the most common parameter to detect CD recurrence after surgery and its degree seems to be correlated with the severity of endoscopic recurrence (see below).

Furthermore, improvement or even normalization of BWT after immunosuppressive treatment takes a long time and occurs only in a small percentage of patients [27] [31] [32] [33]. Conversely, the lack of improvement or the increase of BWT after treatment is correlated with high risk of surgery [33] [34].

Echo pattern

The bowel wall echo pattern may have variable features in CD. The wall layers may be intact and all clearly visible with preserved stratification but may also be focally or extensively disrupted (disrupted or hypoechoic echo pattern). The diseased bowel may also show tracts with preserved stratification alternating with a disrupted echo pattern.

Changes in the predominance of the layers or loss of stratification may be related to different disease aspects [26] [35] [36]. The loss of mural stratification (the disrupted or hypoechoic echo pattern) correlates with clinical and biochemical CD activity [27] [37] [38] with prevalent histological inflammation [39] and with increased risk of surgery [40] [41] [42]. In vitro studies revealed that the focal disappearance sign or focal destruction of wall stratification is caused by deep longitudinal ulcerations [43] [44] [45].

Vascularity

Splanchnic vascularity in CD

Crohn’s disease affects the in- and outflow of splanchnic vessels that can be assessed using pulse wave Doppler. Clinical disease activity, namely disease activity established by clinical indices such as Crohn’s Disease Activity Index (CDAI) or Harvey Bradshow Index (HBI), is associated with increased flow in the mesenteric and portal vein or mesenteric arteries, either shown as increased maximum velocity, time-averaged mean velocity, flow volume or reduced resistive index in fasting patients in some studies [46] [47] [48] [49] [50] [51] [52], but with more controversial results in other studies [52] [53] [54]. Studies have also compared Doppler US of mesenteric blood flow with endoscopic activity of CD or a combination of clinical, endoscopic and radiological findings with conflicting results [55] [56] [57] [58].

The rather disappointing results indicated by measuring flow parameters in splanchnic vessels are probably related to the extensive physiological variability in the flow, also well-known in the healthy population [59] [60]. Furthermore the intra-subject, inter-observer and inter-equipment variability of color Doppler imaging (CDI) measurements are well documented [61] [62] [63].

Color Doppler assessment of bowel wall in CD

A more focused approach on CD is the measurement of the vascularity in the affected bowel wall. Bowel wall vascularity can be determined at the level of the most thickened segments, by color or power Doppler US, using special presets optimized for slow flow detection [23]. Color Doppler flow is usually semi-quantitative and graded subjectively. There are scoring systems assessing the degree of vascularity based on thickening of the bowel wall coupled with the number, size and extent of the power Doppler signals [64] [65].

This subjective assessment of vascularity seems to reflect vessel density and inflammatory activity in the histologically examined bowel wall [66] [67] [68] [69]. Furthermore, bowel wall vascularity seems to be correlated with endoscopic activity [67] [69] [70] [71] and clinical activity (e. g., Harvey-Bradshaw index score of ≥ 4 or Crohn’s disease activity index ≥ 150) [27] [33] [58] [68] [71] [72] [73] [74] [75] and to a lesser degree with biochemical activity (e. g., C-reactive protein or fecal calprotectin) of CD [58]. Moreover, persistence of increased vascularity despite clinical remission after treatment may suggest an increased risk of relapse [74].

Contrast-enhanced US assessment of bowel wall in CD

Despite the capabilities of US color Doppler to suggest CD activity, its accuracy in detecting slow-moving blood flow in small vessels and vascularity in deep-lying bowel wall segments is low. Contrast-enhanced ultrasound (CEUS) overcomes these limitations, improving the detection of hypervascularity and perfusion, also in the deep-seated bowel wall and in the capillaries.

Assessing contrast-enhanced blood flow in the bowel wall is more complex [23]. Studies show considerable heterogeneity with regard to CEUS techniques and contrast parameters to assess bowel wall vascularity in CD [76] [77] [78]. The main parameters could be simply subdivided into qualitative, semi-quantitative and quantitative. The main qualitative and semi-quantitative parameters include different patterns of contrast enhancement, such as variation of layer enhancement of the bowel wall [79] and patterns of perfusion, such as submucosal enhancement and inward and outward transparietal enhancement [71]. Among the several quantitative parameters investigated, the relative peak enhancement and the area under the curve seem to be most reproducible, reliable and widely used to discriminate disease activity and to assess the histological features of the bowel wall [25] [78] [80].

Several studies and meta-analyses have shown that CEUS has high accuracy in the detection of active CD using endoscopy or clinical index as the reference standard [18] [19]. CEUS also seems to provide relevant prognostic information regarding treatment efficacy in patients with CD. In fact, improvement of several perfusion parameters, such as peak contrast enhancement, rate of wash-in and wash-out and, in particular, the area under the time intensity curve of the intestinal wall, 4 – 6 weeks after starting anti-inflammatory treatment (anti-TNF-alpha), correlated with a favorable response [25] [80].

Furthermore, CEUS showed excellent accuracy for the diagnosis of postoperative CD recurrence. In particular, the peak contrast enhancement > 46 % over baseline showed a 10 % increase in accuracy compared with conventional parameters such as BWT > 3 mm and the assessment of color Doppler flow [81]. Likewise, the pattern of enhancement showed a sensitivity and specificity of 94 % for identifying endoscopic recurrence compared with a modified endoscopic Rutgeerts score [71].

Several studies assessed the accuracy of CEUS for evaluating various aspects of disease activity. The endoscopic activity has been assessed by CEUS using parameters derived by the time enhancement intensity curves, such as maximum peak intensity or relative peak enhancement, showing a sensitivity of 68 – 100 % and a specificity of 73 – 96 % for discriminating endoscopically active from inactive disease [70] [82] [83] [84] [85]. In contrast, the correlation between CEUS and clinical and biochemical activity of CD is more controversial [71] [79] [85] [86] [87] [88].

Extraintestinal features

Lymph nodes

Mesenteric loco-regional lymph nodes are a common finding in healthy subjects, particularly in children [89], and in CD patients. Enlarged inflammatory mesenteric lymph nodes related to CD are usually described at US as oval or elongated with lesser diameter > 5 mm and seem to be correlated with young age, early disease, or disease with shorter duration, and with the presence of fistulae and abscesses [90] [91] [92]. However, enlarged mesenteric lymph nodes do not seem to be strongly correlated with clinical disease activity and also appear in other intestinal disorders [27] [90].

Mesenteric fat hypertrophy

Mesenteric fat hypertrophy or creeping fat is a common feature of active CD. Although it seems to be associated with transmural inflammation, fibrosis, muscular hypertrophy and stricture, its role in the onset and development of CD is not fully understood [93]. Creeping fat appears on US as hyperechoic tissue or “mass effect” encircling the diseased bowel. It is found by US in approximately 40 – 50 % of CD patients with a reported sensitivity and specificity > 83 % compared to multi-detector CT scan [94] [95] [96]. However, this finding is associated with clinical and biochemical disease activity, and it may disappear or improve in patients who have responded to medical treatment [27] [96].

Abdominal free fluid

A small amount of free fluid, close to the affected bowel segments, is a common, easily detectable and reproducible US finding in CD patients, but its prevalence and significance have not been fully investigated [21]. However, it seems to be a nonspecific finding, as it can been found in most patients irrespective of their underlying disease [97].

Appendiceal involvement

As CD at its onset may clinically mimic acute appendicitis, the sonographic recognition of these entities is important to avoid unnecessary laparotomies. Primary involvement of the appendix in CD is rare, sonographically indistinguishable from simple acute appendicitis. It is characterized by markedly thickened and hyperemic walls, frequently associated with a thickened terminal ileum and cecum [98] [99] [100].

Complications in Crohn’s disease

The main abdominal complications of CD are stenoses, fistulae and abscesses. These are the main indications for surgical intervention. Surgery is a frequent treatment in the natural history of CD patients [101] [102].

Stenoses

Stenoses represent the more frequent abdominal complications and the main cause of surgical intervention (70 – 90 %) and their prevalence increases over the course of the disease [103] [104]. Several US diagnostic criteria for stenosis have been described [105]. However, the main ones are: thickened and stiff bowel wall, narrowing of the lumen (diameter less than 1 cm), proximal dilatation (> 25 – 30 mm) and hyperperistalsis of the prestenotic gut [106] [107].

The higher diagnostic accuracy of US is obtained when surgery is considered the reference standard. In a systematic review of literature, US has demonstrated a sensitivity for the diagnosis of stenosis from 74 % to 100 %, with a specificity in the range of 89 % to 93 % [8] [10] [12] [106] [107] [108] [109] [110]. Irrespective of the gold standard used, X-ray or intraoperative findings, the ingestion of an oral contrast agent such as polyethylene glycol (PEG) solution (500 – 800 ml) drunk approximately 30 minutes before the US examination [also called Small Intestine Contrast US (SICUS)] has been shown to improve the sensitivity of US for identifying patients with at least 1 stenosis (74 % vs. 89 – 98 %) and those with 2 or more strictures (55 % vs. 75 – 77 %) with an overall good specificity (> 93 %) [109] [111]. Moreover, there is a good correlation between the extent of small bowel strictures measured by means of US and X-ray, and between the extent of the disease measured at surgery [109] [112].

Stenoses in CD are often the result of a combination of fibrosis and inflammation, although they are usually classified as predominantly inflammatory or fibrotic. Patients with strictures with prominent inflammation can potentially be managed with medical treatment, whereas patients with narrowed bowel segments and with prevalent fibrosis, in particular if associated with obstructive symptoms, frequently require endoscopic dilatation or surgery [113]. Despite the fact that this issue is much more complicated and likely also involves smooth muscle hyperplasia/hypertrophy that may be correlated with chronic inflammation [114], the US pattern of the bowel wall can help to differentiate between inflammatory and fibrotic stenosis. The hypoechoic pattern is more typical of inflammatory stenosis, while the stratified or nonhomogeneous echo pattern indicates fibrosis [24] [39]. Several studies have shown that the degree of vascularization and hyperemia on color Doppler and CEUS is correlated with the histologically proven degree of inflammation [24] [105] [115]. In particular, CEUS is useful for distinguishing inflammatory from fibrostenotic lesions in CD. Most studies showed that the contrast enhancement of the bowel wall of inflammatory strictures (using surgical pathological specimens as the reference standard) is significantly greater compared to that of fibrotic strictures [24] [82] [116] [117] [118] [119].

Recent studies reported a significant correlation between the measurement of transabdominal bowel wall stiffness assessed by sonoelastography and the degree of bowel fibrosis at histology [118] [120] [121] [122] [123].

Intestinal fistulae

Fistulae, sinus tracts and fissures are hallmarks of CD and lead to peri-intestinal abscesses, loop adhesions and stricture formation. Extramural fissures originating from deep ulcerations of the intestinal wall are visualized as subtle hypoechoic irregularities of the bowel surface, in correspondence with hypoechoic segments of the bowel wall. Fissures result in the formation of sinus tracts and fistulae. Sinus tracts are linear extensions of inflammation that may have a blind end or finish in an inflammatory mesenteric mass [94] [124] [125] [126] [127] [128].

Abdominal fistulae in CD are classified as internal and external. The internal can be entero-enteric, entero-mesenteric or entero-vesical [129]. The US diagnostic criteria of sinus tracts and fistulae are similar and include: hypoechoic areas or tracts between ileal loops with or without internal gaseous artifacts; hypoechoic peri-intestinal tracts with or without gas within; hypoechoic peri-intestinal areas with a diameter < 2 cm [107] [108] [109] [110] [129] [130] [131] [132] [133]. The sensitivity of US for the diagnosis of fistulizing lesions ranged from 67 % to 87 %, with a specificity in the range of 90 % to 100 % [8], similar to CT and MR. The latest consensus guidelines by the ECCO and ESGAR for imaging in IBD have recommended GIUS as one of the diagnostic procedures to assess perforating complications [11].

Abdominal abscesses

In 12 – 30 % of CD patients, an abscess occurs as a result of a fistula or surgical intervention. The US appearance is characterized by: hypo-anechoic lesions containing fluid and gaseous artifacts; posterior enhancement; irregular margins sometimes within hypertrophic mesentery [107] [108] [109] [110] [129] [130] [131] [132] [134].

The sensitivity of US for the diagnosis of abdominal abscesses ranges from 81 % to 100 %, with a specificity in the range of 92 % to 94 % [8], similar to CT and MR, although certain anatomic areas, such as the deep pelvis and left hypochondrium, are difficult to assess by GIUS and lesions can be missed. Abscesses and inflammatory masses or phlegmons can have a similar appearance on conventional US. This limit can be overcome using CEUS [135]. CEUS can demonstrate diffusely increased enhancement in phlegmons, while abscesses enhance only in the peripheral zone, with an avascular central portion, due to the fluid collection. To minimize radiation exposure, US should be preferred over CT for the detection of complications [8] [12]. Particularly, it is useful to monitor CD patients under treatment with biologic agents, which are contraindicated in patients with intra-abdominal abscesses, but may be effective in those with phlegmons [136].

Postoperative recurrence in Crohn’s disease

Despite advancement in medical therapy, surgery is still required in more than half of CD patients and reoperation in up to 60 % of these patients [137]. The identification of predictive factors of recurrence and ileo-colonoscopic assessment of postoperative recurrence (Rutgeerts score) within the first year after surgery are crucial to optimize therapeutic management [138].

Several studies and systematic reviews have assessed the role of bowel US in postoperative follow-up, showing that the detection of increased bowel wall thickening > 3 mm of the anastomosis or neoterminal ileum is an accurate indicator for recurrence, with a sensitivity > 80 % and specificity > 88 % [8] [12]. In this regard, prospective studies have shown that the use of PEG solution (SICUS) [139] [140] [141] [142] [143] and color Doppler or CEUS [81] [144] can increase the sensitivity up to 90 – 98 %, albeit with a decrease in specificity. This is valid for US assessment performed 1 year after surgery. With shorter follow-up, e. g. 3 months, the sensitivity of US in assessing and predicting postoperative recurrence appears inaccurate [141] [145].

Moreover, both GIUS and SICUS, adopting different cut-off levels for bowel thickness (> 5 mm for conventional sonography and > 4 mm for SICUS), can suggest severe endoscopic postoperative recurrence and accordingly could replace endoscopy in the postsurgical follow-up [146]. In CD patients treated with conservative surgery (e. g. stricturoplastics or minimal bowel resections), GIUS is useful to monitor the postoperative behavior of bowel wall thickness and provides prognostic information. US detection of unchanged or worsened wall thickness 6 months after surgery or the postoperative persistence of wall thickness > 6 mm is predictive of a high risk of recurrence [147] [148].

Sonographic scores in Crohn’s disease

The various US mural and extramural features of CD may have relevant prognostic implications and have been used to build sonographic indexes. The US detection of bowel wall thickness > 7 mm has been shown to be an independent risk of surgery (OR = 19.5, 95 % CI: 5.362 – 71.065) [34]. The short-term risk of surgery has also been evaluated with a score that included weighted parameters such as: wall thickness (> 4.5 mm), wall echo pattern (“disrupted stratification”) and presence of fistulae/abscesses and stenoses. Although not validated, this score was able to correctly identify up to 84 % of patients requiring short-term surgery [40]. Following this trend, a numerical index, quantitating small bowel damage as detected by SICUS in CD patients, has been developed more recently with the aim of converting qualitative sonographic images into a numerical index for CD (Sonographic Lesion Index for CD – SLIC). Also this index was able to identify patients with higher lesion indices who underwent surgery more frequently than those with lower indices after one-year follow-up [149], and can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD [150]. An attempt to develop an ultrasonographic index of inflammatory activity for CD was proposed on the basis of wall thickness and wall stratification of the gut, subdivided into eight segments. The results of this index showed a correlation (r² = 0.62, P  < 0.01) with endoscopic/radiological score, but, given its complexity and lack of validation, it has remained unused [38].

Ulcerative colitis

Ulcerative colitis, unlike CD, involves only the colonic mucosa starting from the rectum (proctitis) often ascending to the rest of the colon. Nowadays, colonoscopy is the method of choice and the reference standard in UC [151] [152]. Intestinal US is an accurate tool to detect and assess the extension of active UC and to define disease activity. The typical grayscale US finding in active UC is moderate thickening of the intestinal wall (usually below 9 mm), involving the mucosa and submucosa, sometimes with increased echogenicity of the submucosal layer, without involvement of the proper muscle layer or surrounding fat. Typical findings may be the irregular mucosal surface caused by gas bubbles entrapped among pseudopolyps and in deep ulcerations and the loss of haustration [153]. Because the lesions in UC are not transmural, the colonic wall stratification is usually preserved [154], although it may be disrupted in patients with severe activity. In particular, the diagnosis of ulcerative colitis relies in most studies on the detection of bowel wall thickness > 4 mm in adults [153] [154] [155] [156] and > 3 mm in children [157] [158] [159]. Intestinal US can be used to assess UC extension, but is more challenging for rectal involvement, where the sensitivity is approximately 15 %. For the remaining colon the sensitivity is higher than 70 %, i. e., up to 97 % for the sigmoid and descending colon [156].

Wall thickness correlates well with clinical activity [153] [158] [159] [160] [161] [162] [163] [164], with biological tests like C-reactive protein values [155] [159] [163] and also with endoscopy findings [153] [155] [158] [163] [164]. Loss of bowel wall stratification (hypoechoic pattern) was associated with moderate (55 % of cases) and severe forms (100 % of cases) [165], while normal wall stratification was present in 87 % of mild cases in another study [166]. Increased vascularity assessed by Doppler US of the bowel wall (increased Doppler signals with low resistance) was also associated with both clinical and endoscopic activity of UC [158] [159] [166] [168]. Attempts have been made to establish an ultrasonic activity score. One of these, based on extension and degree of colonic wall thickness, showed that it is possible to discriminate severe and moderately severe attacks with a sensitivity of 90 % and a specificity of 96 % [160], but it was not validated due to a lack of large cohort studies.

Transabdominal US can also be used for the assessment of UC response to treatment by assessing wall thickness [160] [163] [169] [170], and vascularity changes by CEUS [171] [172]. Regarding response to treatment, published data are contradictory. One study concluded that color and power Doppler are useful [173], while another showed no correlation [172]. Furthermore, CEUS quantification can be used for noninvasive assessment of activity in UC [172] [174] and for treatment response [171] [172]. Strain elastography of the colonic wall may provide information that correlates with endoscopic and clinical disease activity [175].

Appendiceal involvement is seen in 15 % to 86 % of patients with UC and is more common in proctosigmoiditis, than in more extensive UC. It seems to be related to a better response to therapy and higher risk of pouchitis after ileo-colic anastomosis [152] [176].

Complications of ulcerative colitis

Ultrasound may detect extra-intestinal complications of UC (e. g., primary sclerosing cholangitis) [177], but findings of intestinal complications have not been validated in prospective studies. Toxic megacolon combines abnormal colonic dilatation (> 6 cm), thin colonic walls (< 2 mm) and fluid-filled bowel [178] [179]. Massive pseudopolyposis as well as cancer in IBD may show irregular thickening of the wall [180] or a pseudokidney sign. However, GIUS does not play a major role in diagnosing these complications. Portomesenteric vein thrombosis may be detected by color Doppler imaging and CEUS in up to 26 % of acute or quiescent IBD patients [76] [181] [182].

Differential diagnosis among inflammatory colitides

GIUS has limited value compared to histology in differentiating various enterocolitides. However, GIUS assessment of the area of gut involvement and of mural and transmural changes of the bowel and vascularity may help to differentiate CD from UC [36] [156] [183] [184] [185] [186], and other infectious (e. g. tuberculous, bacterial, pseudomembranous and parasitic) [187] [188] [189] [190] [191], vascular and inflammatory enterocolitides (e. g. ischemic, NSAID, Henoch-Schönlein purpura) [192] [193] [194] [195] [196] and to suggest the nature of lesions in most patients [166] [197] [198] [199].

• References

• 1 Molodecky NA, Soon IS, Rabi DM. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142: 46-54 .e42
• 2 Schoepfer AM, Dehlavi MA, Fournier N. et al. Diagnostic delay in Crohn’s disease is associated with a complicated disease course and increased operation rate. Am J Gastroenterol 2013; 108: 1744-53
• 3 Ott C, Obermeier F, Thieler S. et al. The incidence of inflammatory bowel disease in a rural region of Southern Germany: a prospective population-based study. Eur J Gastroenterol Hepatol 2008; 20: 917-23
• 4 Annese V, Daperno M, Rutter MD. European Crohn’s and Colitis Organisation European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis 2013; 7: 982-1018
• 5 Wilkens R, Novak KL, Lebeuf-Taylor E. et al. Impact of Intestinal Ultrasound on Classification and Management of Crohn’s Disease Patients with Inconclusive Colonoscopy. Can J Gastroenterol Hepatol 2016; 2016
• 6 Gomollón F, Dignass A, Annese V. et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and Medical Management. J Crohns Colitis 2017; 11: 3-25
• 7 Horsthuis K, Bipat S, Bennink RJ. et al. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology 2008; 247: 64-79
• 8 Panés J, Bouzas R, Chaparro M. et al. Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn’s disease. Alim Pharmacol Ther 2011; 34: 125-145
• 9 Puylaert CA, Tielbeek JA, Bipat S. et al. Grading of Crohn’s disease activity using CT, MRI, US and scintigraphy: a meta-analysis. Eur Radiol 2015; 25: 3295-313
• 10 Greenup AJ, Bressler B, Rosenfeld G. Medical Imaging in Small Bowel Crohn’s Disease-Computer Tomography Enterography, Magnetic Resonance Enterography, and Ultrasound: “Which One Is the Best for What?”. Inflamm Bowel Dis 2016; 22: 1246-61
• 11 Panes J, Bouhnik Y, Reinisch W. et al. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based con, sensus guidelines. J Crohns Colitis 2013; 7: 556-585
• 12 Calabrese E, Maaser C, Zorzi F. et al. Bowel Ultrasonography in the Management of Crohn’s Disease. A Review with Recommendations of an International Panel of Experts. Inflamm Bowel Dis 2016; 22: 1168-83
• 13 Asthana AK, Friedman AB, Maconi G. et al. Failure of gastroenterologists to apply intestinal ultrasound in inflammatory bowel disease in the Asia-Pacific: a need for action. J Gastroenterol Hepatol 2015; 30: 446-452
• 14 Atkinson NS, Bryant RV, Dong Y. et al. WFUMB Position Paper. Learning Gastrointestinal Ultrasound: Theory and Practice. Ultrasound Med Biol 2016; 42: 2732-42
• 15 Fraquelli M, Colli A, Casazza G. et al. Role of US in detection of Crohn disease: meta-analysis. Radiology 2005; 236: 95-101
• 16 Dong J, Wang H, Zhao J. et al. Ultrasound as a diagnostic tool in detecting active Crohn’s disease: a meta-analysis of prospective studies. Eur Radiol 2014; 24: 26-33
• 17 Zhu C, Ma X, Xue L, Xu J, Li Q, Wang Y, Zhang J. Small intestine contrast ultrasonography for the detection and assessment of Crohn disease: A meta-analysis. Medicine (Baltimore) 2016; 95 (31) e4235 , doi:10.1097/MD.0000000000004235.
• 18 Serafin Z, Białecki M, Białecka A. et al. Contrast-enhanced Ultrasound for Detection of Crohn’s Disease Activity: Systematic Review and Meta-analysis. J Crohns Colitis 2016; 10: 354-62
• 19 Ma X, Li Y, Jia H. et al. Contrast-enhanced ultrasound in the diagnosis of patients suspected of having active Crohn’s disease: meta-analysis. Ultrasound Med Biol 2015; 41: 659-68
• 20 Howick J, Chalmers I, Glasziou P. et al. The Oxford Levels of Evidence 2. OCEBM Levels of Evidence Working Group, Oxford Centre for EvidenceBased Medicine. Available from: 2009 http://www.cebm.net/index.aspx?o=5653
• 21 Fraquelli M, Sarno A, Girelli C. et al. Reproducibility of bowel ultrasonography in the evaluation of Crohn’s disease. Dig Liver Dis 2008; 40: 860-866
• 22 Nylund K, Hausken T, Odegaard S. et al. Gastrointestinal wall thickness measured with transabdominal ultrasonography and its relationship to demographic factors in healthy subjects. Ultraschall in Med 2012; 33: E225-E232
• 23 Nylund K, Maconi G, Hollerweger A. et al. EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound – Part 1: Examination Techniques and Normal Findings (Short version). Ultraschall in Med 2017; 38: 273-284
• 24 Nylund K, Jirik R, Mezl M. et al. Quantitative contrast-enhanced ultrasound comparison between inflammatory and fibrotic lesions in patients with Crohn’s disease. Ultrasound Med Biol 2013; 39: 1197-1206
• 25 Saevik F, Nylund K, Hausken T. et al. Bowel perfusion measured with dynamic contrast-enhanced ultrasound predicts treatment outcome in patients with Crohn’s disease. Inflammatory bowel diseases 2014; 20: 2029-2037
• 26 Ellrichmann M, Wietzke-Braun P, Dhar S. et al. Endoscopic ultrasound of the colon for the differentiation of Crohn’s disease and ulcerative colitis in comparison with healthy controls. Alim Pharmacol Ther 2014; 39: 823-833
• 27 Kucharzik T, Wittig BM, Helwig U. et al. Use of Intestinal Ultrasound to Monitor Crohn’s Disease Activity. Clin Gastroenterol Hepatol 2016; pii: S1542-S3565 (16)31058–8
• 28 Maconi G, Parente F, Bollani S. et al. Abdominal ultrasound in the assessment of extent and activity of Crohn’s disease: clinical significance and implication of bowel wall thickening. Am J Gastroenterol 1996; 91: 1604-1609
• 29 Mayer D, Reinshagen M, Mason RA. et al. Sonographic measurement of thickened bowel wall segments as a quantitative parameter for activity in inflammatory bowel disease. Z Gastroenterol 2000; 38: 295-300
• 30 Hirche TO, Russler J, Schroder O. et al. The value of routinely performed ultrasonography in patients with Crohn disease. Scand J Gastroenterol 2002; 37: 1178-1183
• 31 Castiglione F, Testa A, Rea M. et al. Transmural healing evaluated by bowel sonography in patients with Crohn’s disease on maintenance treatment with biologics. Inflamm Bowel Dis 2013; 19: 1928-1934
• 32 Civitelli F, Nuti F, Oliva S. et al. Looking Beyond Mucosal Healing: Effect of Biologic Therapy on Transmural Healing in Pediatric Crohn’s Disease. Inflamm Bowel Dis 2016; 22: 2418-2424
• 33 Ripollés T, Paredes JM, Martínez-Pérez MJ. et al. Ultrasonographic Changes at 12 Weeks of Anti-TNF Drugs Predict 1-year Sonographic Response and Clinical Outcome in Crohn’s Disease: A Multicenter Study. Inflamm Bowel Dis 2016; 22: 2465-2473
• 34 Castiglione F, de Sio I, Cozzolino A. et al. Bowel wall thickness at abdominal ultrasound and the one-year-risk of surgery in patients with Crohn’s disease. Am J Gastroenterol 2004; 99: 1977-1983
• 35 Limberg B. Sonographic features of colonic Crohn’s disease: comparison of in vivo and in vitro studies. J Clini Ultrasound 1990; 18: 161-166
• 36 Limberg B, Osswald B. Diagnosis and differential diagnosis of ulcerative colitis and Crohn’s disease by hydrocolonic sonography. Am J Gastroenterol 1994; 89: 1051-1057
• 37 Bozkurt T, Rommel T, Stabenow-Lohbauer U. et al. Sonographic bowel wall morphology correlates with clinical and endoscopic activity in Crohn’s disease and ulcerative colitis. Eur J Ultrasound 1996; 4: 27-33
• 38 Futagami Y, Haruma K, Hata J. et al. Development and validation of an ultrasonographic activity index of Crohn’s disease. Eur J Gastroenterol Hepatol 1999; 11: 1007-1012
• 39 Maconi G, Carsana L, Fociani P. et al. Small bowel stenosis in Crohn’s disease: clinical, biochemical and ultrasonographic evaluation of histological features. Alim Pharmacol Ther 2003; 18: 749-756
• 40 Rigazio C, Ercole E, Laudi C. et al. Abdominal bowel ultrasound can predict the risk of surgery in Crohn’s disease: proposal of an ultrasonographic score. Scand J Gastroenterol 2009; 44: 585-593
• 41 Kunihiro K, Hata J, Manabe N. et al. Predicting the need for surgery in Crohn’s disease with contrast harmonic ultrasound. Scand J Gastroenterol 2007; 42: 577-585
• 42 Rosenbaum DG, Conrad MA, Biko DM. et al. Ultrasound and MRI predictors of surgical bowel resection in pediatric Crohn disease. Pediatr Radiol 2017; 47: 55-64
• 43 Hata J, Haruma K, Yamanaka H. et al. Ultrasonographic evaluation of the bowel wall in inflammatory bowel disease: comparison of in vivo and in vitro studies. Abdom Imaging 1994; 19: 395-399
• 44 Kunihiro K, Hata J, Haruma K. et al. Sonographic detection of longitudinal ulcers in Crohn disease. Scand J Gastroenterol 2004; 39: 322-326
• 45 Nylund K, Leh S, Immervoll H. et al. Crohn’s disease: Comparison of in vitro ultrasonographic images and histology. Scand J Gastroenterol 2008; 43: 719-726
• 46 Bolondi L, Gaiani S, Brignola C. et al. Changes in splanchnic hemodynamics in inflammatory bowel disease. Non-invasive assessment by Doppler ultrasound flowmetry. . Scand J Gastroenterol 1992; 27: 501-507
• 47 Erden A, Cumhur T, Olcer T. Superior mesenteric artery Doppler waveform changes in response to inflammation of the ileocecal region. Abdom Imaging 1997; 22: 483-486
• 48 Giovagnorio F, Diacinti D, Vernia P. Doppler sonography of the superior mesenteric artery in Crohn’s disease. Am J Roentgenol 1998; 170: 123-126
• 49 Mirk P, Palazzoni G, Gimondo P. Doppler sonography of hemodynamic changes of the inferior mesenteric artery in inflammatory bowel disease: preliminary data. Am J Roentgenol 1999; 173: 381-387
• 50 Yekeler E, Danalioglu A, Movasseghi B. et al. Crohn disease activity evaluated by doppler ultrasonography of the superior mesenteric artery and the affected small-bowel segments. J Ultrasound Med 2005; 24: 59-65
• 51 Sjekavica I, Barbaric-Babic V, Krznaric Z. et al. Assessment of Crohn’s disease activity by Doppler ultrasound of superior mesenteric artery and mural arteries in thickened bowel wall: Cross-sectional study. Croatian Med J 2007; 48: 822-830
• 52 Karoui S, Nouira K, Serghini M. et al. Assessment of activity of Crohn’s disease by Doppler sonography of superior mesenteric artery flow. J Crohns Colitis 2010; 4: 334-340
• 53 Maconi G, Imbesi V, Bianchi PorroG. Doppler ultrasound measurement of intestinal blood flow in inflammatory bowel disease. Scand J Gastroenterol 1996; 31: 590-593
• 54 Maconi G, Parente F, Bollani S. et al. Factors affecting splanchnic haemodynamics in Crohn’s disease: a prospective controlled study using Doppler ultrasound. Gut 1998; 43: 645-650
• 55 van Oostayen JA, Wasser MN, Griffioen G. et al. Diagnosis of Crohn’s ileitis and monitoring of disease activity: value of Doppler ultrasound of superior mesenteric artery flow. Am J Gastroenterol 1998; 93: 88-91
• 56 Byrne MF, Farrell MA, Abass S. et al. Assessment of Crohn’s disease activity by Doppler sonography of the superior mesenteric artery, clinical evaluation and the Crohn’s disease activity index: a prospective study. Clin58 Radiol 2001; 56: 973-978
• 57 Ludwig D, Wiener S, Bruning A. et al. Mesenteric blood flow is related to disease activity and risk of relapse in Crohn’s disease: a prospective follow-up study. Am J Gastroenterol 1999; 94: 2942-2950
• 58 Thomson M, Rao P, Berger L. et al. Graded compression and power Doppler ultrasonography versus endoscopy to assess paediatric Crohn disease activity pre- and posttreatment. J Pediatr Gastroenterol Nutr 2012; 54: 404-408
• 59 Dietrich CF, Jedrzejczyk M, Ignee A. Sonographic assessment of splanchnic arteries and the bowel wall. Eur J Radiol 2007; 64: 202-212
• 60 Ignee A, Boerner N, Bruening A. et al. Duplex sonography of the mesenteric vessels – a critical evaluation of inter observer variability. Z Gastroenterol 2016; 54: 304-311
• 61 Sacerdoti D, Gaiani S, Buonamico P. et al. Interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis. J Hepatol 1997; 27: 986-992
• 62 Zoli M, Merkel C, Sabbà C. et al. Interobserver and inter-equipment variability of echo-Doppler sonographic evaluation of the superior mesenteric artery. J Ultrasound Med 1996; 15: 99-106
• 63 Sabbà C, Merkel C, Zoli M. et al. Interobserver and interequipment variability of echo-Doppler examination of the portal vein: effect of a cooperative training program. Hepatology 1995; 21: 428-433
• 64 Limberg B. Diagnosis of chronic inflammatory bowel disease by ultrasonography. Z Gastroenterol 1999; 37: 495-508
• 65 Jenssen C, Tuma J, Moller K. et al. Ultrasound artifacts and their diagnostic significance in internal medicine and gastroenterology – part 2: color and spectral Doppler artifacts. Z Gastroenterol 2016; 54: 569-578
• 66 Sasaki T, Kunisaki R, Kinoshita H. et al. Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn’s disease. BMC Res Notes 2014; 7: 363
• 67 Sasaki T, Kunisaki R, Kinoshita H. et al. Use of color Doppler ultrasonography for evaluating vascularity of small intestinal lesions in Crohn’s disease: correlation with endoscopic and surgical macroscopic findings. Scand J Gastroenterol 2014; 49: 295-301
• 68 Drews BH, Barth TF, Hänle MM. et al. Comparison of sonographically measured bowel wall vascularity, histology, and disease activity in Crohn’s disease. Eur Radiol 2009; 19: 1379-1386
• 69 Epifanio M, Baldisserotto M, Spolidoro JV. et al. Grey-scale and colour Doppler sonography in the evaluation of children with suspected bowel inflammation: correlation with colonoscopy and histological findings. Clin Radiol 2008; 63: 968-978
• 70 Ripollés T, Martínez MJ, Paredes JM. et al. Crohn disease: correlation of findings at contrast-enhanced US with severity at endoscopy. Radiology 2009; 253: 241-248
• 71 Migaleddu V, Scanu AM, Quaia E. et al. Contrast-enhanced ultrasonographic evaluation of inflammatory activity in Crohn’s disease. Gastroenterology 2009; 137: 43-52
• 72 Carnevale MaffèG, Brunetti L, Formagnana P. et al. Ultrasonographic findings in Crohn’s disease. J Ultrasound 2014; 18: 37-49
• 73 Paredes JM, Ripollés T, Cortés X. et al. Abdominal sonographic changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn’s Disease. Dig Dis Sci 2010; 55: 404-410
• 74 Ripollés T, Martínez MJ, Barrachina MM. Crohn’s disease and color Doppler sonography: response to treatment and its relationship with long-term prognosis. J Clin Ultrasound 2008; 36: 267-272
• 75 Spalinger J, Patriquin H, Miron MC. et al. Doppler US in patients with Crohn disease: vessel density in the diseased bowel reflects disease activity. Radiology 2000; 217: 787-791
• 76 Piscaglia F, Nolsøe C, Dietrich CF. et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall in Med 2012; 33: 33-59
• 77 Cheng W, Gao X, Wang W. et al. Preliminary Analysis of Clinical Situations Involved in Quantification of Contrast-Enhanced Ultrasound in Crohn’s Disease. Ultrasound Med Biol 2016; 42: 1784-1791
• 78 Zink F, Kratzer W, Schmidt S. et al. Comparison of Two High-End Ultrasound Systems for Contrast-Enhanced Ultrasound Quantification of Mural Microvascularity in Crohn’s Disease. Ultraschall in Med 2016; 37: 74-81
• 79 Serra C, Menozzi G, Labate AM. et al. Ultrasound assessment of vascularization of the thickened terminal ileum wall in Crohn’s disease patients using a low-mechanical index real-time scanning technique with a second generation ultrasound contrast agent. Eur J Radiol 2007; 62: 114-121
• 80 Quaia E, Sozzi M, Angileri R. et al. Time-Intensity Curves Obtained after Microbubble Injection Can Be Used to Differentiate Responders from Nonresponders among Patients with Clinically Active Crohn Disease after 6 Weeks of Pharmacologic Treatment. Radiology 2016; 281: 606-616
• 81 Paredes JM, Ripollés T, Cortés X. et al. Contrast-enhanced ultrasonography: usefulness in the assessment of postoperative recurrence of Crohn’s disease. J Crohns Colitis 2013; 7: 192-201
• 82 Ripolles T, Rausell N, Paredes JM. et al. Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal inflammation in Crohn’s disease: a comparison with surgical histopathology analysis. J Crohns Colitis 2013; 7: 120-128
• 83 Moreno N, Ripolles T, Paredes JM. et al. Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn’s disease: changes following treatment with immunomodulators and/or anti-TNF antibodies. J Crohns Colitis 2014; 8: 1079-1087
• 84 Horjus TalaburHorje CS, Bruijnen R, Roovers L. et al. Contrast Enhanced Abdominal Ultrasound in the Assessment of Ileal Inflammation in Crohn’s Disease: A Comparison with MR Enterography. PloS one 2015; 10: e0136105-52
• 85 De Franco A, Di Veronica A, Armuzzi A. et al. Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity. Radiology 2012; 262: 680-688
• 86 Girlich C, Schacherer D, Jung EM. et al. Comparison between a clinical activity index (Harvey-Bradshaw-Index), laboratory inflammation markers and quantitative assessment of bowel wall vascularization by contrast-enhanced ultrasound in Crohn’s disease. Eur J Radiol 2012; 81: 1105-1109
• 87 Girlich C, Jung EM, Huber E. et al. Comparison between preoperative quantitative assessment of bowel wall vascularization by contrast-enhanced ultrasound and operative macroscopic findings and results of histopathological scoring in Crohn’s disease. Ultraschall in Med 2011; 32: 154-159
• 88 Wong DD, Forbes GM, Zelesco M. et al. Crohn’s disease activity: Quantitative contrast-enhanced ultrasound assessment. Abdom Imaging 2012; 37: 369-376
• 89 Dietrich CF, Zeuzem S, Caspary WF. et al. Sonographische Lymphknotendarstellung im Abdomen bei gesunden Probanden. Ultraschall in Med 1998; 19: 265-269
• 90 Maconi G, Di Sabatino A, Ardizzone S. et al. Prevalence and clinical significance of sonographic detection of enlarged regional lymph nodes in Crohn’s disease. Scand J Gastroenterol 2005; 40: 1328-1333
• 91 Dietrich CF, Hocke M, Jenssen C. Ultrasound for abdominal lymphadenopathy. Dtsch Med Wochenschr 2013; 138: 1001-1018
• 92 Chiorean L, Barr RG, Braden B. et al. Transcutaneous Ultrasound: Elastographic Lymph Node Evaluation. Current Clinical Applications and Literature Review. Ultrasound Med Biol 2016; 42: 16-30
• 93 Peyrin-Biroulet L, Chamaillard M, Gonzalez F. et al. Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander?. Gut 2007; 56: 577-583
• 94 Sarrazin J, Wilson SR. Manifestations of Crohn disease at US. Radiographics 1996; 16: 499-520
• 95 Gaitini D, Kreitenberg AJ, Fischer D. et al. Color-coded duplex sonography compared to multidetector computed tomography for the diagnosis of crohn disease relapse and complications. J Ultrasound Med 2011; 30: 1691-1699
• 96 Maconi G, Greco S, Duca P. et al. Prevalence and clinical significance of sonographic evidence of mesenteric fat alterations in Crohn’s disease. Inflamm Bowel Dis 2008; 14: 1555-1561
• 97 Smereczynski A, Starzynska T, Kolaczyk K. Ultrasound of selected pathologies of the small intestine. J Ultrasonography 2013; 13: 155-166
• 98 Agha FP, Ghahremani GG, Panella JS. et al. Appendicitis as the initial manifestation of Crohn’s disease: Radiologic features and prognosis. Am J Roentgenol 1987; 149: 515-518
• 99 Puylaert JBCM, Van Der Werf SDJ, Ulrich C. et al. Crohn disease of the ileocecal region: US visualization of the appendix. Radiology 1988; 166: 741-743
• 100 Ripolles T, Martinez MJ, Morote V. et al. Appendiceal involvement in Crohn’s disease: gray-scale sonography and color Doppler flow features. Am J Roentgenol 2006; 186: 1071-1078
• 101 Munkholm P, Langholz E, Davidsen M. et al. Intestinal cancer risk and mortality in patients with Crohn’s disease. Gastroenterology 1993; 105: 1716-1723
• 102 Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Ann Surg 2000; 231: 38-45
• 103 Cosnes J, Cattan S, Blain A. et al. Long-term evolution of disease behaviour of Crohn’s disease. Inflamm Bowel Dis 2002; 8: 244-250
• 104 Cosnes J, Gower-Rousseau C, Seksik P. et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140: 1785-1794
• 105 Coelho R, Ribeiro H, Maconi G. Bowel Thickening in Crohn’s Disease: Fibrosis or Inflammation?. Diagnostic Ultrasound Imaging Tools. Inflamm Bowel Dis 2017; 23: 23-34
• 106 Calabrese E, Zorzi F, Onali S. et al. Accuracy of small-intestine contrast ultrasonography, compared with computed tomography enteroclysis, in characterizing lesions in patients with Crohn’s disease. Clin Gastroenterol Hepatol 2013; 11: 950-955
• 107 Castiglione F, Mainenti PP, De Palma GD. et al. Noninvasive diagnosis of small bowel Crohn’s disease: direct comparison of bowel sonography and magnetic resonance enterography. Inflamm Bowel Dis 2013; 19: 991-998
• 108 Onali S, Calabrese E, Petruzziello C. et al. Small intestine contrast ultrasonography vs computed tomography enteroclysis for assessing ileal Crohn’s disease. World J Gastroenterol 2012; 18: 6088-6095
• 109 Pallotta N, Vincoli G, Montesani C. et al. Small intestine contrast ultrasonography (SICUS) for the detection of small bowel complications in Crohn’s disease: a prospective comparative study versus intraoperative findings. Inflamm Bowel Dis 2012; 18: 74-84
• 110 Kumar S, Hakim A, Alexakis C. et al. Small intestinal contrast ultrasonography for the detection of small bowel complications in Crohn’s disease: correlation with intraoperative findings and magnetic resonance enterography. J Gastroenterol Hepatol 2015; 30: 86-91–72
• 111 Parente F, Greco S, Molteni M. et al. Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn’s disease. A prospective comparison with conventional ultrasound, × ray studies, and ileocolonoscopy. Gut 2004; 53: 1652-1657
• 112 Parente F, Maconi G, Bollani S. et al. Bowel ultrasound in assessment of Crohn’s disease and detection of related small bowel strictures: a prospective comparative study versus × ray and intraoperative findings. Gut 2002; 50: 490-495
• 113 Dignass A, Van AsscheG, Lindsay JO. et al. European Crohn’s and Colitis Organisation (ECCO). The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Current management. J Crohns Colitis  2010; 4: 28-62
• 114 Chen W, Lu CG, Lindsay JO. et al. Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn’s Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme. J Crohns Colitis 2017; 11: 92-104
• 115 Kratzer W, von Tirpitz C, Mason R. et al. Contrast-enhanced power Doppler sonography of the intestinal wall in the differentiation of hypervascularized and hypovascularized intestinal obstructions in patients with Crohn’s disease. J Ultrasound Med 2002; 21: 149-157
• 116 Quaia E, de Paoli L, Stocca T. et al. The value of small bowel wall contrast enhancement after Sulfur hexafluoride-filled microbubble injection to differentiate inflammatory from fibrotic strictures in patients with Crohn’s disease. Ultrasound Med Biol 2012; 38: 1324-1332
• 117 Schirin-Sokhan R, Winograd R, Tischendorf S. et al. Assessment of inflammatory and fibrotic stenoses in patients with Crohn’s disease using contrast-enhanced ultrasound and computerized algorithm: a pilot study. Digestion 2011; 83: 263-268
• 118 Lu C, Gui X, Chen W. et al. Ultrasound Shear Wave and Contrast Enhancement: Effective Biomarkers in Crohn’s Disease Strictures. Inflamm Bowel Dis 2017; 23: 421-430
• 119 Braden B, Ignee A, Hocke M. et al. Diagnostic value and clinical utility of contrast enhanced ultrasound in intestinal diseases. Dig Liver Dis 2010; 42: 667-674
• 120 Baumgart DC, Müller HP, Grittner U. et al. US-based Real-time Elastography for the Detection of Fibrotic Gut Tissue in Patients with Stricturing Crohn Disease. Radiology 2015; 275: 889-899
• 121 Fraquelli M, Branchi F, Cribiù FM. et al. The Role of Ultrasound Elasticity Imaging in Predicting Ileal Fibrosis in Crohn’sDisease Patients. Inflamm Bowel Dis 2015; 21: 2605-2612
• 122 Dillman JR, Stidham RW, Higgins PD. et al. Ultrasound shear wave elastography helps discriminate low-grade from high-grade bowel wall fibrosis in ex vivo human intestinal specimens. J Ultrasound Med 2014; 33: 2115-2123
• 123 Sconfienza LM, Cavallaro F, Colombi V. et al. In-vivo Axial-strain Sonoelastography Helps Distinguish Acutely-inflamed from Fibrotic Terminal Ileum Strictures in Patients with Crohn’s Disease: Preliminary Results. Ultrasound Med Biol 2016; 42: 855-863
• 124 Di Mizio R, Maconi G, Romano S. et al. Small bowel Crohn disease: sonographic features. Abdom Imaging 2004; 29: 23-35
• 125 Hollerweger A. Colonic diseases: the value of US examination. Eur J Radiol 2007; 64: 239-249
• 126 Nylund K, Hausken T, Gilja OH. Ultrasound and inflammatory bowel disease. Ultrasound Q 2010; 26: 3-15
• 127 Nylund K, Ødegaard S, Hausken T. et al. Sonography of the small intestine. World J Gastroenterol 2009; 15: 1319-1330
• 128 Maconi G, Radice E, Greco S. et al. Bowel ultrasound in Crohn’s disease. Best Pract Res Clin Gastroenterol 2006; 20: 93-112
• 129 Maconi G, Sampietro GM, Parente F. et al. Contrast radiology, computed tomography and ultrasonography in detecting internal fistulas and intra-abdominal abscesses in Crohn’s disease: a prospective comparative study. Am J Gastroenterol 2003; 98: 1545-1555
• 130 Maconi G, Bollani S, Bianchi PorroG. Ultrasonographic detection of intestinal complications in Crohn’s disease. Dig Dis Sci 1996; 41: 1643-1648
• 131 Gasche C, Moser G, Turetschek K. et al. Transabdominal bowel sonography for the detection of intestinal complications in Crohn’s disease. Gut 1999; 44: 112-117
• 132 Martínez MJ, Ripollés T, Paredes JM. et al. Assessment of the extension and the inflammatory activity in Crohn’s disease: comparison of ultrasound and MRI. Abdom Imaging 2009; 34: 141-148
• 133 Neye H, Ensberg D, Rauh P. et al. Impact of high-resolution transabdominal ultrasound in the diagnosis of complications of Crohn’s disease. Scand J Gastroenterol 2010; 45: 690-695
• 134 Maconi G, Sampietro GM, Russo A. et al. The vascularity of internal fistulae in Crohn´s disease: an in vivo power Doppler ultrasonography assessment. Gut 2002; 50: 496-500
• 135 Ripollés T, Martínez-Pérez MJ, Paredes JM. et al. Contrast-enhanced ultrasound in the differentiation between phlegmon and abscess in Crohn’s disease and other abdominal conditions. Eur J Radiol 2013; 82: e525-e531
• 136 Cullen G, Vaughn B, Ahmed A. et al. Abdominal phlegmons in Crohn’s disease: outcomes following antitumor necrosis factor therapy. Inflamm Bowel Dis 2012; 18: 691-696
• 137 Buisson A, Chevaux JB, Allen PB. et al. Review article: the natural history of postoperative Crohn’s disease recurrence. Aliment Pharmacol Ther 2012; 35: 625-633
• 138 Gionchetti P, Dignass A, Danese S. et al. ECCO. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 2: Surgical Management and Special Situations. J Crohns Colitis 2017; 11: 135-149
• 139 Onali S, Calabrese E, Petruzziello C. et al. Endoscopic vs ultrasonographic findings related to Crohn’s disease recurrence: a prospective longitudinal study at 3 years. J Crohns Colitis 2010; 4: 319-328
• 140 Calabrese E, Petruzziello C, Onali S. et al. Severity of postoperative recurrence in Crohn’s disease: correlation between endoscopic and sonographic findings. Inflamm Bowel Dis 2009; 15: 1635-1642
• 141 Biancone L, Calabrese E, Petruzziello C. et al. Wireless capsule endoscopy and small intestine contrast ultrasonography in recurrence of Crohn’s disease. Inflamm Bowel Dis 2007; 13: 1256-1265
• 142 Pallotta N, Giovannone M, Pezzotti P. et al. Ultrasonographic detection and assessment of the severity of Crohn’s disease recurrence after ileal resection. BMC Gastroenterol 2010; 10: 69
• 143 Onali S, Calabrese E, Petruzziello C. et al. Post-operative recurrence of Crohn’s disease: A prospective study at 5 years. Dig Liver Dis 2016; 48: 489-494
• 144 Paredes JM, Ripollés T, Cortés X. et al. Non-invasive diagnosis and grading of postsurgical endoscopic recurrence in Crohn’s disease: usefulness of abdominal ultrasonography and (99m)Tc-hexamethylpropylene amineoxime-labelled leucocyte scintigraphy. J Crohns Colitis 2010; 4: 537-545
• 145 Orlando A, Modesto I, Castiglione F. et al. The role of calprotectin in predicting endoscopic post-surgical recurrence in asymptomatic Crohn’s disease: a comparison with ultrasound. Eur Rev Med Pharmacol Sci 2006; 10: 17-22
• 146 Castiglione F, Bucci L, Pesce G. et al. Oral contrast-enhanced sonography for the diagnosis and grading of postsurgical recurrence of Crohn’s disease. Inflamm Bowel Dis 2008; 14: 1240-1245
• 147 Parente F, Sampietro GM, Molteni M. et al. Behaviour of the bowel wall during the first year after surgery is a strong predictor of symptomatic recurrence of Crohn’s disease: a prospective study. Aliment Pharmacol Ther 2004; 20: 959-968
• 148 Maconi G, Sampietro GM, Cristaldi M. et al. Preoperative characteristics and postoperative behavior of bowel wall on risk of recurrence after conservative surgery in Crohn’s disease: a prospective study. Ann Surg 2001; 233: 345-352
• 149 Calabrese E, Zorzi F, Zuzzi S. et al. Development of a numerical index quantitating small bowel damage as detected by ultrasonography in Crohn’s disease. J Crohns Colitis 2012; 6: 852-860
• 150 Zorzi F, Stasi E, Bevivino G. et al. A sonographic lesion index for Crohn’s disease helps monitor changes in transmural bowel damage during therapy. Clin Gastroenterol Hepatol 2014; 12: 2071-2077
• 151 Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med 2011; 365: 1713-1725
• 152 Magro F, Gionchetti P, Eliakim R. et al. Third European Evidence-Based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis 2017; 11: 649-670
• 153 Bru C, Sans M, Defelitto MM. et al. Hydrocolonic sonography for evaluating inflammatory bowel disease. Am J Roentgenol 2001; 177: 99-105
• 154 Strobel D, Goertz RS, Bernatik T. Diagnostics in inflammatory bowel disease: Ultrasound. World J Gastroenterol 2011; 17: 3192-3197
• 155 Antonelli E, Giuliano V, Casella G. et al. Ultrasonographic assessment of colonic wall in moderate-severe ulcerative colitis: comparison with endoscopic findings. Dig Liver Dis 2011; 43: 703-706
• 156 Parente F, Greco S, Molteni M. et al. Role of early ultrasound in detecting inflammatory intestinal disorders and identifying their anatomical location within the bowel. Aliment Pharmacol Ther 2003; 18: 1009-1016
• 157 Bremner AR, Griffiths M, Argent JD. et al. Sonographic evaluation of inflammatory bowel disease: a prospective, blinded, comparative study. Pediatr Radiol 2006; 36: 947-953
• 158 Civitelli F, Di Nardo G, Oliva S. et al. Ultrasonography of the colon in pediatric ulcerative colitis: a prospective, blind, comparative study with colonoscopy. J Pediatr 2014; 165: 78-84
• 159 Ruess L, Blask AR, Bulas DI. et al. Inflammatory bowel disease in children and young adults: correlation of sonographic and clinical parameters during treatment. Am J Roentgenol 2000; 175: 79-84
• 160 Arienti V, Campieri M, Boriani L. et al. Management of severe ulcerative colitis with the help of high resolution ultrasonography. Am J Gastroenterol 1996; 91: 2163-2169
• 161 Schwerk WB, Beckh K, Raith M. A prospective evaluation of high resolution sonography in the diagnosis of inflammatory bowel diasease. Eur J Gastroenterol Hepatol 1992; 4: 173-182
• 162 Worlicek H, Lutz H, Heyder N. et al. Ultrasound findings in Crohn’s disease and ulcerative colitis: a prospective study. J Clin Ultrasound 1987; 15: 153-163
• 163 Maconi G, Ardizzone S, Parente F. et al. Ultrasonography in the evaluation of extension, activity, and follow-up of ulcerative9 colitis. Scand J Gastroenterol 1999; 34: 1103-1107
• 164 Parente F, Molteni M, Marino B. et al. Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis? a prospective study. Am J Gastroenterol 2010; 105: 1150-1157
• 165 Haber HP, Busch A, Ziebach R. et al. Ultrasonographic findings correspond to clinical, endoscopic, and histologic findings in inflammatory bowel disease and other enterocolitides. J Ultrasound Med 2002; 21: 375-382
• 166 Dixit R, Chowdhury V, Kumar N. Hydrocolonic sonography in the evaluation of colonic lesions. Abdom Imaging 1999; 24: 497-505
• 167 Heyne R, Rickes S, Bock P. et al. Non-invasive evaluation of activity in inflammatory bowel disease by power Doppler sonography. Z Gastroenterol 2002; 40: 171-175
• 168 Bavil AS, Somi MH, Nemati M. et al. Ultrasonographic evaluation of bowel wall thickness and intramural blood flow in ulcerative colitis. ISRN Gastroenterol 2012; 2012: 370495
• 169 Parente F, Molteni M, Marino B. et al. Bowel ultrasound and mucosal healing in ulcerative colitis. Dig Dis 2009; 27: 285-290
• 170 Yoshida A, Kobayashi K, Ueno F. et al. Possible role of early transabdominal ultrasound in patients undergoing cytapheresis for active ulcerative colitis. Intern Med 2011; 50: 11-15
• 171 Socaciu M, Ciobanu L, Diaconu B. et al. Non-Invasive Assessment of Inflammation and Treatment Response in Patients with Crohn’s Disease and Ulcerative Colitis using Contrast-Enhanced Ultrasonography. Quantification. J Gastrointestin Liver Dis 2015; 24: 457-465
• 172 Yamaguchi T, Yoshida S, Tanaka S. et al. Predicting the clinical response to cytapheresis in steroid-refractory or dependent ulcerative colitis using contrast-enhanced ultrasonography. Scand J Gastroenterol 2009; 44: 831-837
• 173 Rogoveanu I, Săftoiu A, Cazacu S. et al. Color Doppler transabdominal ultrasonography for the assessment of the patients with inflammatory bowel disease during treatment. Rom J Gastroenterol 2003; 12: 277-281
• 174 Girlich C, Schacherer D, Jung EM. et al. Comparison between quantitative assessment of bowel wall vascularization by contrast-enhanced ultrasound and results of histopathological scoring in ulcerative colitis. Int J Colorectal Dis 2012; 27: 193-198
• 175 Ishikawa D, Ando T, Watanabe O. et al. Images of colonic real-time tissue sonoelastography correlate with those of colonoscopy and may predict response to therapy in patients with ulcerative colitis. BMC Gastroenterol 2011; 11: 29
• 176 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.; Colitis Foundation of America., Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr 2007; 44: 653-674
• 177 Hirche TO, Russler J, Braden B. et al. Sonographic detection of perihepatic lymphadenopathy is an indicator for primary sclerosing cholangitis in patients with inflammatory bowel disease. Int J Colorectal Dis 2004; 19: 586-594
• 178 Dietrich CF. Ultrasonography of the small and large intestine. In: Rose BD. (Ed) UpToDate. Wellesley MA: 2015
• 179 Maconi G, Sampietro GM, Ardizzone S. et al. Ultrasonographic detection of toxic megacolon in inflammatory bowel diseases. Dig Dis Sci 2004; 49: 138-142
• 180 de Barros N, Cerri GG, de Souza RochaM. et al. Sonographic appearances of conglomerated polyps (giant polyposis) in patients with Crohn’s disease. J Clin Ultrasound 2000; 28: 199-205
• 181 Maconi G, Bolzacchini E, Dell’Era A. et al. Portal vein thrombosis in inflammatory bowel diseases: a single-center case series. J Crohns Colitis 2012; 6: 362-367
• 182 Landman C, Nahon S, Cosnes J. et al. Portomesenteric vein thrombosis in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 582-589
• 183 Ziech ML, Hummel TZ, Smets AM. et al. Accuracy of abdominal ultrasound and MRI for detection of Crohn disease and ulcerative colitis in children. Pediatr Radiol 2014; 44: 1370-1378
• 184 Pera A, Cammarota T, Comino E. et al. Ultrasonography in the detection of Crohn’s disease and in the differential diagnosis of inflammatory bowel disease. Digestion 1988; 41: 180-184
• 185 Hata J, Haruma K, Suenaga K. et al. Ultrasonographic assessment of inflammatory bowel disease. Am J Gastroenterol 1992; 87: 443-447
• 186 Valette PJ, Rioux M, Pilleul F. et al. Ultrasonography of chronic inflammatory bowel diseases. Eur Radiol 2001; 11: 1859-1866
• 187 Puylaert JB, Lalisang RI, van der Werf SD. et al. Campylobacter ileocolitis mimicking acute appendicitis: differentiation with graded-compression US. Radiology 1988; 166: 737-740
• 188 Puylaert JB, Van der Zant FM, Mutsaers JA. Infectious ileocecitis caused by Yersinia, Campylobacter, and Salmonella: clinical, radiological and US findings. Eur Radiol 1997; 7: 3-9
• 189 Ros PR, Buetow PC, Pantograg-Brown L. et al. Pseudomembranous colitis. Radiology 1996; 198: 1-9
• 190 Kedar RP, Shah PP, Shivde RS. et al. Sonographic findings in gastrointestinal and peritoneal tuberculosis. Clin Radiol 1994; 49: 24-29
• 191 Mathis G, Metzler J. Sonography in salmonella enterocolitis. Ultraschall in Med 1992; 13: 106-109
• 192 Siegel MJ, Friedland JA, Hildebolt CF. Bowel wall thickening in children: differentiation with US. Radiology 1997; 203: 631-635
• 193 Lim JH, Ko YT, Lee DH. et al. Sonography of inflammatory bowel disease: findings and value in differential diagnosis. Am J Roentgenol 1994; 163: 343-347
• 194 Dietrich CF, Lembcke B, Jenssen C. et al. Intestinal ultrasound in rare gastrointestinal diseases, update, part 1. Ultraschall in Med 2014; 35: 400-421
• 195 Ripollés T, Simó L, Martínez-Pérez MJ. et al. Sonographic findings in ischemic colitis in 58 patients. Am J Roentgenol 2005; 184: 777-785
• 196 Nuernberg D, Ignee A, Dietrich CF. Current status of ultrasound in gastroenterology--bowel and upper gastrointestinal tract--part 2. Z Gastroenterol 2008; 46: 355-366
• 197 Aideyan UO, Smith WL. Inflammatory bowel disease in children. Radiol Clin North Am 1996; 34: 885-902
• 198 O’Malley ME, Wilson SR. US of gastrointestinal tract abnormalities with CT correlation. Radiographics 2003; 23: 59-72
• 199 Truong M, Atri M, Bret PM. et al. Sonographic appearance of benign and malignant conditions of the colon. Am J Roentgenol 1998; 170: 1451-1455