Fig. 20.1
Fig. 20.2
Fig. 20.3
First layer: hyperechoic, interface between the lumen and superficial mucosa.
Second layer: hypoechoic, interface between the deep and superficial mucosa.
Third layer: hyperechoic, interface between submucosa and the muscularis propria.
Fourth layer: hypoechoic, muscularis propria.
Fifth layer: hyperechoic, the superficial interface of the perivisceral serosa
The typical and constant features of CD revealed via B-mode ultrasound are the presence of thickened and stiff bowel wall, modification or disappearance of echo stratification of the bowel wall, loss of peristalsis in the small bowel, and loss of haustrae coli in the colon [16] (Figs. 20.4 and 20.5). Disease activity can be accompanied by mesenterial fat hypertrophy and enlargement of surrounding lymph nodes. B-mode ultrasound revealed a high sensitivity and specificity in the detection of CD (73–96 % and 90–100 %, respectively) compared with other methods such as endoscopy and/or radiological imaging [17]. The diagnostic accuracy and costs of noninvasive diagnostic strategies including magnetic resonance imaging, intestinal ultrasonography, ileocolonoscopy, and video-capsule endoscopy in suspected CD were analyzed in a recent study [18]. The authors found that both accuracy and costs depend on the pretest probability of CD and vary according to the first test used. Ileocolonoscopy plus ultrasonography was the most accurate and least expensive initial diagnostic strategy. Many studies differed in terms of study design, population characteristics, and reference standard, as did the accuracy of ultrasound as a diagnostic tool in CD. Fraquelli et al. demonstrated that raising the bowel wall thickness threshold from 3 to 4 mm increased specificity (93–97 %) at the extent of sensitivity (88–75 %) [19], without any differences between adults and children [20].
Fig. 20.4
Fig. 20.5
Assessment of Disease Activity
Several sonomorphological findings of disease activity in CD are commonly used in daily practice: degree of bowel wall thickening, echo pattern, luminal narrowing, fibro-fatty proliferation, and mesenteric lymphadenopathy.
A Japanese study established a strong correlation between the maximum bowel wall thickness and the histological findings of surgical specimens and also between the echo pattern and histopathological disease activity. A loss of stratification (hypoechoic echo pattern) predicted the prevalence of severe inflammation [21]. Another study described a blurred wall layer more frequently in active disease than in inactive disease (62.0 vs. 5 %; p < 0.05) [17]. One of the first attempts to create a sonographic score to describe disease activity in CD was published by Futagami [22]. The sonographic score showed a good correlation to endoscopic findings, but the implemented sonomorphological features—bowel wall thickness and wall stratification—correlated weakly with CDAI or biological indices of inflammation (C-reactive protein, erythrocyte sedimentation rate). Many studies have demonstrated a marginal correlation between disease activity measured by CDAI and sonographic findings [23]. The CDAI is widely used as a reference standard, even if it mirrors the subjective complaints of the patient without necessarily reflecting sonomorphological abnormalities or endoscopic or histological findings [24].
Assessment of Disease Location
Several studies have compared the accuracy of bowel ultrasound to various radiological techniques in defining the anatomical location of CD [25–28]. One of the largest studies (n = 296) demonstrated sensitivity and specificity according to the location of the affected bowel segment (overall: sensitivity 93 %, specificity 97 %). The highest accuracy was achieved when examining the terminal ileum (sensitivity 95 %). The upper small bowel was much more difficult to assess correctly (jejunum 72 %). In particular, the detection of lesions in the pelvic area via transabdominal ultrasound remained poor. Proctitis was diagnosed correctly in only 15 % of patients [25]. Alternative ultrasound techniques such as small bowel contrast ultrasound (SICUS) and perianal ultrasound (PAUS) enriched the noninvasive arsenal for evaluating the upper small bowel or pelvic region. These examination techniques are discussed later.
Detection of Complications
Pediatric patients with CD and adults with childhood onset CD are at increased risk of developing comorbidities and complications [29]. In approximately 50–70 % of cases, CD patients are affected by complications such as bowel strictures, fistulae, and abscesses during the course of their disease [30]. Complications of CD that effect further treatment can often be found even in asymptomatic patients. High-resolution transabdominal ultrasound has an excellent diagnostic accuracy in the diagnosis of complications in patients with Crohn’s disease [31].
In a study by Hirche et al. [32], routine ultrasound detected transmural inflammation in 17 out of 255 patients without clinical signs of active disease (CD activity index 150). Eleven patients from this group had interenteric, enteromesenteric, or perirectal fistula, whereas six patients displayed a transmural mesenteric inflammation reaction without fistulae. In another series of 100 consecutive patients without active disease, fistulae were detected in 4 % of cases, mostly interenteric [17].
Detection of Abscesses
An abscess develops in 15–20 % of Crohn’s patients during the course of their illness. Identifying this complication is essential for the right management choice. Abscesses require surgical or percutaneous drainage [16] and are seen as a contraindication for numerous modern medical approaches. Abscesses appear as hypoechoic lesions with an irregular wall in transabdominal ultrasound. Internal echoes are a sign of debris, and a posterior echo enhancement can show liquid compartments of the structure (Figs. 20.6 and 20.7). The detection of vascular signs in the lesion is a sign of inflammatory masses and allows it to be differentiated from an abscess [33, 34]. Most studies evaluating the accuracy of ultrasound in the detection of abscesses use computed tomography or surgico-pathological findings as the gold standard. Sensitivity and specificity range between 90 % and 100 % [26, 31, 35, 36]. In a head-to-head comparison of ultrasound and CT scans, using only surgical findings as reference, no significant difference in sensitivity was detected (US 91 %, CT 86 %) [36]. Ultrasound lacks accuracy when detecting abdominal abscesses deep in the pelvis or retroperitoneal collections obscured by overlying bowel gas. One advantage of ultrasound is in the detection of small intraparietal or para-intestinal abscesses, which can be missed or misinterpreted as short fistulous tracts or hypoechoic lymph nodes in CT scans [37].
Fig. 20.6
Fig. 20.7
Detection of Fistula
Fistulae either connect the gut with abdominal organs (e.g., enterovesical, enterovaginal, interenteric), reach the cutaneous surface (enterocutaneous), or end blindly in the mesentery (enteromensenteric). The most common fistulae are enteroenteric (50 %); these connect two bowel loops and often develop in the presence of stenosis (Fig. 20.8). Fistulae appear as hypoechoic ducts or hypoechoic areas arising from a thickened bowel wall.
Fig. 20.8
Fistulae can show signs of air, debris, or intestinal material in the form of stationary or moving echoic spots [26, 35] (Fig. 20.9). The gold standard in fistulae detection is a surgical specimen. CT scan miss fistulae in up to 40 % of cases. Therefore, CT scans cannot be recommended as a reference standard in clinical trials [38]. The sensitivity and specificity of ultrasound in the detection of surgically proven fistulae varies between 70 and 87 % and 90 and 96 %, respectively [35, 39]. Fistulae connecting bowel segments often show a greater wall thickness and the wall stratification appears blurred with a loss of layer architecture [17].
Fig. 20.9
Detection of Strictures
Strictures are a common cause of surgery in CD and develop in 21 % of patients with ileal disease and 8 % of those with ileocolic disease [40]. Significant strictures are marked by prestenotic bowel dilatation above 3 cm. The stricture itself shows a thickened bowel wall with an associated narrowed lumen (Fig. 20.10). Peristalsis in the prestenotic bowel loop is often increased [41]. The accuracy of the detection of bowel wall strictures via transabdominal ultrasound varies between 74 and 91 % sensitivity and 93 and 100 % specificity compared to radiological or surgical findings [26, 28, 31, 35, 42]. The differentiation between inflammatory and fibrotic strictures is of major interest in clinical practice. Inflammatory changes can be targeted by anti-inflammatory agents, whereas fibrotic strictures are treated surgically or via endoscopic intervention. A stricture length of >30 mm increases the chance of inflammation [43]. The loss of stratification of the affected bowel wall has also been associated with inflammatory stenosis. The hypoechoic echo pattern is due to hyperemia and neovascularization related to the inflammatory response [39] (Fig. 20.11). Conversely, preserved bowel wall layers, especially with a pronounced third layer (submucosa), suggest that the stricture is fibrotic (Fig. 20.12). An increase in bowel wall thickness within the third layer seems to represent increased collagen deposition in the submucosa [44].
Fig. 20.10
Fig. 20.11
Fig. 20.12
Extraluminal Findings
The extraluminal findings of CD which can be seen via ultrasound are ascites , lymphadenopathy, and mesenteric fat hypertrophy . Enlarged lymph nodes and free fluid are commonly seen in active CD but it has not been possible to show a correlation with disease activity [17]. Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have long been recognized as characteristic features of Crohn’s disease on surgical specimens. Mesenteric fat hypertrophy appears in transabdominal ultrasound as a hyperechoic area surrounding the bowel wall, predominantly along the mesenteric side of the bowel [45, 46]. Different studies have shown that mesenteric fatty alterations, as evaluated by CT scan or MRI, correlate with biological activity [47–49]. One of the few studies into mesenteric fatty alterations found via ultrasound showed a significant correlation to biochemical/clinical CD activity, the presence of internal fistulae, and increased bowel wall thickness [50]. However, prediction of clinical relapse based on the presence of mesenteric fat hypertrophy was not successful. There are few studies into extraluminal findings of CD via ultrasound. The clinical significance and implication of these findings need further investigation.
Detection of Postsurgical Recurrence
Postoperative recurrence after ileocolonic resection is a common feature of CD. The recurrence rates evaluated by endoscopy after 1 and 3 years are 73 % and 90 %, respectively [51–54]. The diagnostic gold standard for the detection of early signs of recurrence is conventional ileocolonoscopy, with the severity of the lesions graded using Rutgeert’s score [54]. Numerous studies have evaluated noninvasive techniques for the detection of postoperative recurrence in CD. One approach is to measure the bowel wall thickness of the anastomosis after bowel resection via ultrasound. It has been shown that an increase in bowel wall thickness is not due to physiological healing of the anastomosis, because cancer patients did not show any increase in bowel wall thickness of the anastomosis [55]. Similar to the ultrasound findings in active CD, an increase in bowel wall thickness (>3–5 mm) can be interpreted as a recurrence of the disease. The sensitivity and specificity of ultrasound in the detection of postsurgical recurrence of CD is about 80 % and 85–100 %, respectively [55, 56]. A more recent study by Rispo et al. [57] used a cutoff level in bowel wall thickness of 5 mm to differentiate between mild and severe disease recurrence. A bowel wall thickness above 5 mm predicted a severe postsurgical recurrence with sensitivity and specificity of 94 % and 100 %, respectively. The author concluded that these methods were sufficiently accurate to detect a clinically significant postsurgical recurrence that would need specific treatment. Different studies have already stressed the value of ultrasound in the prediction of postsurgical recurrence in CD. In a study of 127 consecutive patients, 90 % of patient in the group with an unchanged or worsened bowel wall thickness in month 12 after the operation measured by transabdominal ultrasound developed clinical recurrence within 5 years [58]. Only 33 % of patients with improved bowel wall thickness relapsed over this same period. Similar data were shown a few years earlier by Maconi et al., evaluating bowel wall thickness before and 6 months after bowel resection [59].
Color/Power Doppler Ultrasound
As stated in current guidelines, color Doppler imaging increases the sensitivity and specificity of transabdominal ultrasound, in particular for CD limited to the ileum [60]. In particular, disease activity has been studied by visualizing the extent of bowel wall vascularity. The examination techniques using color/power Doppler ultrasound are:
Semi quantitative documentation of the intensity of color signals and/or the analysis of Doppler curves obtained from the vessels detected within the bowel wall.
Quantitative measurement of flow parameters of the superior and inferior mesenteric arteries.
Studies correlating clinical (CDAI) or biochemical (e.g., CRP/ESR) parameters with color/power Doppler ultrasound findings did not produce conclusive results. Numerous studies have described increased bowel wall vascularity more often in active than in quiescent CD, but these results rarely reached clinical significance [61–63]. On the other hand, recent studies have shown a significant correlation between endoscopic and color/power Doppler ultrasound activity scores in CD [64, 65]. The prognostic significance of color/power Doppler ultrasound findings was demonstrated by Ripolles [66]. Patients in clinical remission after treatment with residual hyperemia on sonographic examination (week 4) had an unfavorable clinical course compared with patients with no or barely visible residual hyperemia. In a prospective study by Paredes et al. ultrasound was used to assess changes (thickness and Doppler flow grade of the bowel wall) caused by biological therapy and its relationship with the clinical-biological response in 23 patients with CD . They found that sonographic changes were significantly more marked in patients who achieved clinical and biological response compared to those patients who did not respond to treatment [67].
In order to achieve optimal results in daily practice, it is essential to use the right color Doppler ultrasound settings. The settings should be optimized for slow flow detection (pulse repetition frequencies of 800–1500 Hz, wall filter of 40–50 Hz, maximal color signal gain immediately below the noise threshold). Color Doppler flow is considered present when color pixels persist throughout the examination. The blood flow can be confirmed by visualizing an arterial or venous flow pattern at the location of the color pixel on spectral analysis. Vascularity is graded subjectively as absent (grade 0), barely visible (grade 1), or marked (grade 3) (Fig. 20.13). Another access to disease activity via color/power Doppler ultrasound is the analysis of quantitative parameters. In active disease, the end-diastolic blood flow in bowel wall vessels disproportionately increases, which leads to a drop in the resistance index. Power Doppler ultrasound has been suggested to improve the diagnostic accuracy of transabdominal ultrasound in discriminating inflammatory from fibrotic strictures [5, 19, 65].
Fig. 20.13
The decreased resistance index in active CD has been described several times in the literature [61, 63, 68] (Fig. 20.14a and b). CD manly affects bowel segments supplied by the superior mesenteric artery (SMA). In active CD, the SMA flow volume was found to be greater than 500 ml/min and the resistance index was significantly lower than in the reference group with quiescent disease [69]. The pulsatility index of the SMA can also help predict a relapse in CD when it is repeatedly evaluated [70, 71]. The decrease in the pulsatility index of the SMA is associated with remission in CD. However, measuring the quantitative pulsed Doppler indices is time-consuming and highly demanding. Therefore, it still is not established in daily practice.
Fig. 20.14
Special Ultrasound Method in Crohn’s Disease
Small Bowel Contrast Ultrasound
The extent of Crohn’s lesions , especially in the upper small bowel, is sometimes underestimated by transabdominal ultrasound because of the insufficient distention of the bowel lumen. An isosmolar solution containing a nondigestible, nonabsorbable, and non-fermentable hydrophilic macro molecule, such as polyethylene glycol (PEG ), was used to distend the small bowel walls, which allowed for a more detailed assessment of the wall thickness and lumen diameter [72]. A follow-up study showed that the entire small intestine could be visualized on ultrasonography about 45 min after the ingestion of 600 ml or less of contrast solution without any significant side effects [73]. In daily practice, 300–500 ml of PEG is sufficient to achieve an optimal distention of the small bowel walls (Fig. 20.15). If stenosis is absent, the examination will be completed in 10–20 min. In comparison to small bowel follow through, SICUS reached a sensitivity of 72–100 % and specificity of 97–100 % in the detection of small bowel pathologies [3, 74–76]. False negative findings in the study by Cittadini et al. were mainly due to lymphoid hyperplasia, which is a feature of unknown significance in adults. As expected, the advantage of SICUS over conventional ultrasound was particularly clear in the detection of pathologies in the upper small bowel (jejunum: conventional ultrasound 80 % vs. SICUS 100 % detection rate) [77]. The sensitivity of identifying multiple strictures increased from 55 % to 78 % using SICUS [78] (Fig. 20.16a and b). In a recently published study, SICUS was able to detect all fistulae and stenosis initially diagnosed via CT [3]. Other convincing features of SICUS are a good interobserver agreement [72, 77, 79, 80] and ease of use for inexperienced ultrasound users, reaching even higher accuracy rates than those of an experienced examiner using conventional ultrasound [78]. SICUS has been the topic of several studies evaluating accuracy in predicting postsurgical recurrence [81–83]. A study on 40 patients with CD with previous bowel resection showed a sensitivity and specificity of 77 % and 94 % for transabdominal ultrasound and 82 % and 94 % for SICUS [81].
Fig. 20.15
Fig. 20.16
Endoanal and Perianal Ultrasound
Perianal disease is a common manifestation in complicated CD, occurring in 20–40 % of patients in the course of their disease [84]. Pelvic magnetic resonance imaging (MRI) and endoanal ultrasound are the established methods for the assessment of perianal inflammatory lesions in patients with CD. MRI and EAUS are especially recommended by German S3 Guidelines for CD in patients with perianal disease [85]. The combination of MRI and EAUS is capable of detecting perianal fistulae with a sensitivity of 100 % [86, 87]. These methods require specialized and fairly expensive equipment and experienced investigators. Furthermore, MRI is not applicable in patients with metallic clips or suffering from claustrophobia, and EAUS can be painful or impossible to perform in patients with anal stenosis. PAUS was introduced into clinical practice as an alternative. It can be performed using regular ultrasound probes [3.5–7.5 MHz]. The ultrasound probe is wrapped with a latex glove after applying contact gel on the surface of the probe. No patient preparation is required prior to the examination. Patient lies down in the left lateral decubitus position, and the ultrasound probe is then placed near the anal opening.
Contrast Enhanced Ultrasound
Contrast enhanced ultrasound (CEUS) is the next logical step after color Doppler ultrasound in the assessment of bowel wall vascularization . The accuracy of power Doppler ultrasound is limited by tissue motion artifacts and a possible transmural vessel perfusion below the detection threshold [92]. CEUS combines second-generation ultrasound contrast-enhancing agents with low mechanical index real-time harmonic ultrasound. It permits a real-time visualization of the small vessels in the bowel wall with image contrast similar to that of computed tomography and MRI [93]. The absence of established CEUS parameters has led to the development of different semi quantitative and quantitative approaches to predict disease activity in CD. One study by Migaleddu et al. was highly recommended by the medical community [94]. It defined three major enhancement patterns : submucosal enhancement or transmural enhancement with an outward or inward flow direction. Using endoscopic and histologic findings as reference standards, CEUS showed higherperformance than conventional ultrasound or color Doppler ultrasound in the detection of active disease (93.5 % sensitivity, 93.7 % specificity, and 93.6 % overall accuracy). Despite the impact of the study, the enhancement pattern remained a semi quantitative approach that is highly influenced by the subjective assessment of the ultrasound examiner. Using the increase in bowel wall enhancement after contrast application in relation to the baseline enhancement showed promising results. In a population of 61 patients, the sensitivity and specificity to predict moderate and severe disease were 96 % and 73 %, respectively [9].
Dynamic quantitative CEUS is currently the subject of scientific investigations in patients with CD. Three studies indicated that the time to peak in CEUS examinations could be a parameter worth measuring to evaluate disease activity . An increase in time to peak was connected to a decrease in clinical activity [10, 95]. Furthermore, Bataille et al. [96] found a negative correlation between histopathological score and the time to peak [97]. A more recent study quantitatively assessed microvascular activation in the thickened ileal walls of 54 patients with CD by using CEUS and evaluated its correlation with CDAI [98]. The authors analyzed the maximum peak intensity (MPI) and the wash-in slope coefficient (beta) and evaluated their correlation with the composite index of CD activity (CICDA), the CD activity index (CDAI), and the simplified endoscopic score for CD (SES-CD) for the terminal ileum. The sensitivity/specificity to detect active CD were 97 %/83 % for MPI and 86 %/83 % for beta coefficients. Both parameters significantly correlated with the CDAI (p = 0.0005, 0.0011) and the endoscopic SES-CD (p = 0.0052, 0.0011).
The differentiation of fibrotic and inflammatory strictures could be a beneficial application of CEUS in clinical practice, but there is still no established approach to solving this puzzle. One study focused on this question and evaluated the accuracy of several ultrasound parameters, especially of contrast-enhanced ultrasound, for evaluation of mural inflammation versus fibrostenonic changes in 25 patients with CD undergoing elective bowel resection [99]. Histopathology was used as reference. When the pathology score was dichotomized into two groups (inflammatory and fibrostenotic) 23 out of 28 stenoses were correctly classified via ultrasound, with substantial agreement (kappa = 0.632). There was a good correlation between the sonographic and pathology scores, both inflammation (Spearman’s rank, r = 0.53) and fibrostenosis (Spearman’s rank, r = 0.50). Thus, ultrasound, including CEUS is a useful tool for distinguishing inflammatory lesions from fibrostenotic ones in CD and small bowel follow-through (SBFT) is regarded obsolete due to the high radiation exposure, particularly in children with IBD Sauer CG, Inflamm Bow dis 2011.
CEUS was also evaluated in the context of postoperative recurrence of CD [100]. Classic ultrasound parameters, such as wall thickness >3 mm and color Doppler flow revealed an accuracy of 88.3 % for recurrence detection compared to the endoscopic results. A sonographic score of 2, including thickness >5 mm or contrast enhancement >46 %, improved the diagnosis of endoscopic recurrence a sensitivity, specificity and accuracy of 98 %, 100 % and 98.3 %, respectively. The use of CEUS in the detection and localization of fistulae and abscesses [101] needs further studies (Fig. 20.17a and b).
Fig. 20.17
Ulcerative Colitis
The regions of interest in patients with ulcerative colitis (UC) are far more accessible via endoscopy than in patients with CD. Most cases see a continuous inflammation from the anus that can extend up to the cecum. Rectal sparing and backwash ileitis can be detected in rare cases of UC . Early and mild cases of UC can show unspecific signs of an inner hypoechoic layer . It has been postulated that the hypoechoic layer represents the endoscopic findings of the swollen mucosa. In more severe to fulminant cases, a transmural bowel wall thickening similar to CD has been described. Normally the bowel wall stratification is preserved [17]. In active UC, the thickened mucosa can be explained by the round cell infiltration in the lamina propria, whereas the submucosa swells with oedema development. Unfortunately, no correlation between sonographic activity parameters of UC (wall thickness, symmetry of thickness, transmural reaction, and extraluminal findings, e.g., more than two lymph nodes) and endoscopic disease activity (Colitis activity index, CAI) has been found [17]. Two studies from Parente et al. [102, 103] contradict these common findings. These studies suggest that an ultrasound score based on bowel wall thickness and intramural blood flow, graded via color Doppler ultrasound, can be used as a surrogate of colonoscopy in assessing the short-term response of severe forms of UC to therapy. Furthermore, it was possible to using three-month ultrasound results to predict the outcome at 15 months after steroid treatment. These are very interesting data which need to be reproduced in further studies before transabdominal ultrasound can be recommended more strongly in the management of UC. Two studies have evaluated the extent of the inflammation in UC measured via ultrasound. The sensitivity varied according to the bowel segment. The best results were achieved in the left colon (>95 %) [104, 105].
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