Digestive and Liver Disease
Volume 42, Issue 10 , Pages 667-674, October 2010

Diagnostic value and clinical utility of contrast enhanced ultrasound in intestinal diseases

  • Barbara Braden

      Affiliations

    • Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 1865 228760; fax: +44 1865 228561.
    • ,
  • Andre Ignee

      Affiliations

    • Medical and Imaging Department, Caritas - Krankenhaus, Bad Mergentheim, Germany
    • ,
  • Michael Hocke

      Affiliations

    • Medical and Imaging Department, Caritas - Krankenhaus, Bad Mergentheim, Germany
    • Klinikum Meiningen, Meiningen, Germany
    • ,
  • Rebecca M. Palmer

      Affiliations

    • Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
    • ,
  • Christoph Dietrich

      Affiliations

    • Medical and Imaging Department, Caritas - Krankenhaus, Bad Mergentheim, Germany

Received 1 January 2010; accepted 26 May 2010. published online 05 July 2010.

Article Outline

Abstract 

Contrast enhanced ultrasound (CEUS) has recently gained increasing attention as it clearly improves the visualisation of perfusion in various tissues. The development of second generation contrast enhancing agents used in low-mechanical-index harmonic ultrasound has enabled real-time assessment of the microvascular circulation and quantification of bowel wall vascularity.

For this review Medline was searched for clinical studies using CEUS to investigate the gastrointestinal tract.

Many studies demonstrate that acute or chronic inflammation of the intestinal wall is accompanied by increased perfusion of the mesentery, which can be displayed semi-quantitatively using contrast enhanced ultrasound analyzing time intensity curves. In contrast, ischemia is characterized by hypoperfusion of the mesenteric arteries and the bowel wall. The most promising sonographic approach in assessing splanchnic arteries and the bowel wall is combining the analysis of superior and inferior mesenteric inflow by pulsed Doppler scanning (systolic and diastolic velocities, resistance index) with the end-organ vascularity by CEUS.

CEUS at a preliminary stage has been described as clinically important in a variety of gastrointestinal disorders, particularly in patients with Crohn's disease. CEUS facilitates the detection of disease extent and activity, and its luminal and extraluminal complications.

Abbreviation: ceus, contrast enhanced ultrasound

Keywords: Bowel wall, Contrast agent, Complication, Inflammatory bowel disease

 

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1. Introduction 

Transabdominal ultrasound is widely regarded as a clinically valuable, non-invasive imaging modality in initial diagnosis and for follow-up monitoring in a variety of gastrointestinal diseases. Ultrasound has gained acceptance, particularly in inflammatory bowel disease (IBD), as it can provide important information, including: the extent and activity of the disease, presence of complications (fistula, abscess, obstruction) and helps in differential diagnosis [1], [2].

Both color and power Doppler ultrasound are applied to demonstrate intramural vessels in the bowel wall to detect hypo- or hypervascularization in gastrointestinal disease [3], [4]. Contrast enhancement increases the accuracy of the Doppler ultrasound in evaluating bowel wall vascularization [5]. New sonographic technologies combined with the application of contrast agents allow the continuous monitoring of the intramural perfusion using low mechanic index without the Doppler mode (contrast harmonic imaging). This avoids artifacts, e.g., by bowel peristalsis (tissue motion artifacts) and/or transmural vessel perfusion below the detection threshold.

1.1. Technical aspects 

First generation ultrasound contrast agents contain air, while the micro-bubbles used as second generation ultrasound contrast agents contain inert gases (e.g. sulfur hexafluoride) in a phospholipid shell and have an improved stability. Due to their small size of 1–7μm, these micro-bubbles stay in the circulation and can also pass into micro-vessels and capillaries. Micro-bubbles act as strong scattering objects due to the difference in impedance between air and liquid, and the acoustic response is optimized at the resonant frequency of a micro-bubble. Their shape and gaseous content explains the non-linear, harmonic response which differs from the tissue signal in contrast harmonic ultrasound [6]. The mechanical index is an estimate of the maximum amplitude of the pressure pulse in tissue. At low acoustic power, the acoustic response is considered as linear, the micro-bubbles undergo oscillation with compression and rarefaction that are equal in amplitude and no special contrast enhanced signal is created. At higher acoustic power (mechanical index between 0.2 and 0.5), non-linear oscillation occurs. Ultrasound waves are created at harmonics of the delivered frequency. The harmonic response frequencies are different from that of the incident (fundamental frequency) with subharmonics (half of the fundamental frequency), harmonics (including the second harmonic response at twice the fundamental frequency), and ultra-harmonics obtained at 1.5 or 2.5 times the fundamental frequency. These contrast enhanced ultrasound signals are micro-bubble specific.

Contrast enhanced ultrasound shares the limitations of ultrasound in general. The gastrointestinal tract cannot be visualised over its entire length. Obtaining and interpreting the (echo-enhanced) sonographic images are highly investigator dependent. Obesity can render high frequency ultrasound difficult or impossible. Furthermore, the micro-bubbles of contrast media do not last very long in the circulation and the investigation must be performed in a limited time frame after contrast injection. The micro-bubbles burst at high mechanical indices (MI) which are a measure of the acoustic power output of the ultrasound system. On the other hand, image quality is best at high mechanical indices, but this would result in micro-bubble destruction.

SonoVue® micro-bubbles resonate best at a relatively low insonation frequency. High frequency probes which are commonly used to examine the bowel wall have some limitations resulting in a lower sensitivity, requiring higher acoustic power for satisfying results. This may lead to a lower image quality; this has been also controversially discussed in the literature. The acoustic response of ultrasound micro-bubbles is defined by the micro-bubble diameter and the stiffness of the micro-bubble shell. SonoVue® micro-bubbles have a size distribution between 1 and 10μm, corresponding to a resonance frequency of about 1–10MHz. The smaller micro-bubbles in the suspension respond more strongly to higher insonation frequencies, whereas the larger micro-bubbles respond more strongly to lower insonation frequencies [7]. For ultrasound of the bowel wall frequencies above 7.5MHz are preferred to allow differentiation of the wall layers. As fewer micro-bubbles resonate at these frequencies, higher doses of contrast agents are recommended (e.g. SonoVue® 4.8ml).

Because ultrasound is a dynamic investigation in real-time mode, additional information about the tissue can be deduced from the quantification of influx and washout of the contrast media. Special software can generate graphs that depict the change in signal intensity over time within a particular region of interest (time intensity curves) [8].

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2. Inflammatory bowel disease 

2.1. Crohn's disease 

Transabdominal ultrasound helps to determine the extent and localization of inflammation in Crohn's disease by demonstrating (asymmetric) bowel wall thickening. Intramural, but also peri-intestinal inflammatory reaction in addition to extraluminal complications including fistula, abscesses, or ileus can be depicted [1], [2], [9]. This technique has also proved to be useful as a screening imaging modality in patients with symptoms or clinical signs that strongly indicate inflammatory bowel disease. Therefore, transabdominal ultrasound is widely used as first line diagnostic method to assess disease activity and presence of complications in patients with Crohn's disease, but also for follow-up investigations. Findings of transabdominal ultrasound help guide therapeutic decisions and allow monitoring of the individual disease course.

2.2. Changes in mesenteric flow 

Doppler ultrasound techniques enable the measurement of changes in mesenteric flow that is related to the severity of the inflammation, the localization of the inflammation, the length of the involved bowel section. In Crohn's disease patients, correlation has been described between the volume of blood flow in the superior mesenteric artery [3] with changes in enteroclysis and clinical parameters, the Crohn's disease activity index (CDAI) as well as 1-antitrypsine stool clearance. The correlation with CDAI has been rejected by other groups. The literature has been recently summarized [10].

The most relevant changes are seen in vessels which deliver the largest volume of blood to the involved bowel region. Therefore, changes in the blood flow in the superior mesenteric artery are observed [3] when the small bowel, cecum, ascending or transverse colon are affected. Inflammation of the left sided colon causes changes in the blood flow in the inferior mesenteric artery.

Typically, major changes are found in the superior mesenteric artery in patients with Crohn's disease and in the inferior mesenteric artery in patients with ulcerative colitis. Similar changes in the inferior mesenteric artery may also be apparent in patients with left sided Crohn's colitis. On the other hand, changes in the superior mesenteric artery can be seen in patients with ulcerative pancolitis or even backwash ileitis. Increasing portal vein blood flow is found to correlate with the increased mesenteric inflow especially in patients with CD.

2.3. Prognosis 

Investigations by Ludwig et al. indicate that the pulsatility index measured postprandially as well as in the fasting state allows estimation of the risk of relapse. Positive and negative predictive values range between 0.77 and 0.89 [11], [12], [13]. The clinical significance of this phenomenon remains unclear. It can be helpful to monitor the changes of the blood flow of the mesenteric vessels in context to the severity of the disease. In isolation these changes in blood flow are unlikely to influence therapeutic management. Combination of the measurement of blood inflow and wall changes in the bowel segments is likely to give the most clinically relevant information. It has yet to be determined if changes in the mesenteric vessels give an earlier indication of therapeutic success or failure when compared to the sonographic normalization of the bowel wall or even the clinical situation. Contrast enhanced ultrasound with analysis of time intensity curves might be an additional step [14].

2.4. Disease extent 

Bowel wall ultrasound reliably describes the localization and extent of the affected intestinal segments. In a study comparing dynamic magnetic resonance imaging and echo-signal enhanced low-mechanical-index ultrasound in wideband harmonic imaging the length of sonographically documented bowel wall alterations correlated significantly with the length of thickened bowel segments in magnetic resonance imaging. Echo-enhanced bowel wall ultrasound and MRI were capable of objectively evaluating the local vascularization in the bowel wall [15].

2.5. Disease activity 

CEUS can visualise intramural blood vessels in the affected bowel wall [3], [16], [17]. Doppler ultrasound enables the assessment of disease activity in inflammatory bowel disease. Doppler imaging in splanchnic vessels can detect inflammatory hyperemia and hypervascularization in terms of increased flow volume and velocity, or resistance and pulsatility index on spectral analysis. The density of small vessels in the affected bowel loop is a Doppler ultrasound indicator of inflammatory hyperemia. Power Doppler ultrasound increases the sensitivity to detect flow in intramural vessels. The application of ultrasound contrast agents improves the image quality of color Doppler investigations by increasing the backscattered echo-signal within the vessels. Thus, the discrimination between hyperemia in active inflammation and normal intestinal wall is facilitated. The use of echo-contrast agents further increases the accuracy of color Doppler ultrasound in diagnosis and follow-up of patients with Crohn's disease [5], [16], [18], [19]. This might also be useful for predicting early relapse and for monitoring the response to treatment.

Contrast enhanced power Doppler analysis proved superior to conventional power Doppler ultrasound in assessing activity in a study investigating 15 patients with active ileal Crohn's disease and correlated with clinical and biochemical indices for disease activity [20]. The analysis of contrast enhancement in second harmonic B-mode imaging proved useful for follow-up in a series by Robotti including 52 patients with Crohn's disease [21]. Plikat et al. could demonstrate an increase of the gray scale values within the region of interest after contrast injection in all patients with segments of inflamed intestine [22]. In a study by Rapaccini et al. intestinal wall thickness did not show concordance with the activity of Crohn's disease, rather active disease was indicated by the presence of vascular signals in the affected loops during color Doppler ultrasound in the affected loops after injection of Levovist® [5]. In a recent study, Migaleddu et al. tested the diagnostic accuracy of conventional US, color Doppler US and CEUS in the assessment of inflammatory activity in 47 patients with Crohn's disease in the small bowel and/or the colon by using the endoscopic and histological findings as reference standards. CEUS showed the highest performance with 93.5% sensitivity, 93.7 specificity, 93.6% overall accuracy, and the strongest correlation to the Crohn's disease activity index (0.74) [23]. Contrast enhancement was assessed for the site of initial enhancement and the direction and behavior of enhancement (minimal or submucosal enhancement, and outward and inward transparietal enhancement).

Serra et al. report 81% sensitivity and 63% specificity for the diagnosis of active disease using CEUS in 48 patients with ileal wall thickening [24]. Findings were classified into four different patterns of contrast enhancement in the bowel wall: (1) complete enhancement of the entire wall, (2) absence of enhancement in the outer muscularis propria, (3) enhancement only of the intermediate layer, and (4) absence of enhancement. “Poor” bowel enhancement (patterns 3 and 4) and “abundant” enhancement (patterns 1 and 2) discriminated active – defined as Crohn's disease activity index >150 – and inactive disease. The studies by Migaleddu and by Serra analyzed CEUS only by perfusion pattern evaluation which is of subjective character.

In a recent study including 61 patients with Crohn's disease, the CEUS assessed activity was prospectively compared to the severity grade determined at ileocolonoscopy. Measurement of contrast enhancement was quantitatively assessed as the increase in wall brightness with respect to the baseline brightness. A threshold brightness value of percentage of increase of 46% had a sensitivity of 96% and specificity of 73% in prediction of moderate or severe grade for inflammation at endoscopy [25]. Therefore, the evaluation of bowel wall vascularization using contrast enhanced ultrasound seems to be a useful non-invasive diagnostic tool for distinguishing between active and inactive disease.

Kunihiro et al. could prove that loss of stratification in the involved bowel segment in B-mode ultrasound and a high echo-intensity in harmonic flash imaging predict the need for surgery [26].

Furthermore, the ultrasound contrast agent SonoVue® has been successfully used to assess disease activity, and also the response to infliximab treatment in a preliminary Italian study. The authors recommend CEUS as a relatively low cost imaging modality for the clinical monitoring of small bowel Crohn's disease [27]. In another study, including six patients with active inflammation of the terminal ileum, gray scale analysis from the region of interest in the affected loop correlated with the clinical disease activity (Crohn's disease activity). Clinical improvement after 6 months of infliximab treatment was clearly reflected by parallel alterations in the pattern of the contrast enhanced echo-signal [28].

2.6. Inflammatory masses 

Esteban et al. investigated 28 patients with suspected abdominal inflammatory masses using power Doppler ultrasound before and after intravenous administration of the ultrasound contrast agent Levovist®. The contrast enhanced ultrasound evaluation within and around the inflammatory masses allowed distinction between abscesses (without post-contrast vascular signal within the lesion) and phlegmonous tissue (with intense vascularity, Fig. 1) [29]. The spatial resolution and sensitivity of signal-enhancing power Doppler ultrasound also enabled the detection of small inflammatory masses less than 15mm which were not detected in computed tomography. Levovist®-enhanced power Doppler ultrasound proved to be sensitive and specific in the detection of inflammatory masses in patients with Crohn's disease.

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  • Fig. 1. 

    Contrast enhanced ultrasound can facilitate the diagnosis of inflammatory mass causing stenosis and stricture. (a) The hypoechoic mass on the right side of the image was suspicious for abscess formation but contrast enhancement proved inflammatory mass lesion, hypovascular stricture shown in the arterial phase (b) and abscess formation shown by conventional B-mode (c) and using CEUS (d).

The early diagnosis of inflammatory complications such as abscesses, phlegmonae and fistula is probably the most crucial aspect in the management of patients with Crohn's disease. This is because medical therapy may still be effective in the initial stages of disease, thus preventing progression and need for surgical intervention. The study by Esteban et al. demonstrated that smaller inflammatory masses below 18mm healed with medical therapy. (Contrast enhanced) Doppler ultrasound was useful in the follow-up of these inflammatory complications. Since there is no concern of radiation exposure to the patient, multiple and serial examinations may be performed facilitating the assessment of disease progression and close monitoring of response to medical treatment [30]. Transurethral injection of ultrasound contrast media might help to visualise vesico-intestinal fistulae in Crohn's disease [31].

2.7. Inflammatory or fibrotic strictures 

Conventional transabdominal bowel ultrasound can depict dilated bowel loops and is often able to identify and locate the cause of intestinal obstruction [9], [32]. In patients with Crohn's disease, reliable differentiation between inflammatory or cicatricial-fibroid stenosis might be crucial for further surgical or medical management. Whether the ultrasonographical analysis of the vascularity in the stenosis can accurately answer this diagnostic challenge is still controversially discussed [2], [33], [34], [35].

The longitudinal extent of wall thickness in the stenotic segment appears to be a discriminative criterion: inflammatory stenoses usually extend more than 3cm whereas cicatricial-fibroid strictures are found in short segments (<20–30mm) of thickened intestinal walls.

Contrast enhanced ultrasound has been successfully applied in differentiation between inflammatory or fibrotic stenosis (Fig. 1). Hypervascularity of stenosed segments in contrast enhanced ultrasound indicates inflammatory cause for intestinal obstruction, while hypovascularity is found in cicatricial stenosis. These vascularity criteria have been confirmed by histological examination after surgery or response to conservative therapy in follow-up [34].

However, lack of hypervascularity might be caused by technical problems: inadequately chosen Doppler parameters, depth penetration >40mm and insensitive equipment. Contrast enhanced bowel ultrasound might overcome the problem of depth penetration as it is less depth dependent than Doppler techniques. Nevertheless only high end ultrasound equipment enables sufficient visualisation of bowel contrast enhanced ultrasound.

Quantitative analysis of time intensity curves using contrast enhanced techniques might provide additional information to color Doppler imaging alone [19].

2.8. Ulcerative colitis 

Most studies on contrast enhanced ultrasound in inflammatory bowel disease investigated patients with Crohn's disease. Reports on CEUS findings in ulcerative colitis are mostly anecdotal. After contrast injection the hyperemia in the thickened submucosal layer can be depicted in the affected colon segment (Fig. 2). The region of interest for the gray scale analysis can be placed exactly within the submucosal layer [22]. The use of ultrasound is mostly the correct identification of the extent in patients with known ulcerative colitis and detection of complications, e.g., perforation. CEUS in that regard might be a scientifically fascinating tool but the use in daily routine has not been established so far.

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  • Fig. 2. 

    In patients with ulcerative colitis and left sided colitis the bowel wall is thickened (a). The hyperperfusion of the inflamed colonic segment becomes visible after injection of the contrast agent (b).

Yamaguchi et al. evaluated different patterns of CEUS findings in steroid refractory or dependent ulcerative colitis as predictors for response to granulocyte and monocyte adsorption apharesis and leukocytapheresis [36].

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3. Potential applications for CEUS in other gastrointestinal diseases 

3.1. Appendicitis and diverticulitis 

Sonographic signs of appendicitis include: a non-compressible tubular structure with a diameter of more than 6mm at the base of the cecum at the confluence of the three tenia coli with or without luminal distension, concentric thickening of the inflamed appendiceal wall (>1–2mm) with corresponding pain on pressure, free fluid and inflammatory fat changes [37], [38]. Color Doppler imaging [39] and especially CEUS [40] are helpful in displaying the architecture of the appendix (Fig. 3). Inflammation of the appendiceal wall may be followed by localized ischemia [41] which may also be visualised by CEUS. In a study including 50 patients with suspected appendicitis, CEUS had an accuracy of 98% and a sensitivity of 100% in the diagnosis of acute appendicitis when compared to the surgical and histological findings [42].

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  • Fig. 3. 

    Color Doppler imaging is helpful in the understanding of the bowel wall architecture in gastrointestinal diseases, e.g., clearly delineating the submucosal vessels. Gray scale ultrasound depicts the normal sized appendix (5mm) (a), but color Doppler imaging allows a better understanding of the vessel architecture within the submucosa (b) indicating initial inflammation in the very early stage of appendicitis. Due to the improved sensitivity the same is true for contrast enhanced ultrasound also in difficult cases (c and d).

The typical sonographic features in patients with acute diverticulitis include; peri-diverticular inflammatory reaction, mural and peri-diverticular abscess formation and concomitant segmental mural bowel wall thickening (greater than 3–4mm) with hypervascularity. A recent metanalysis did not reveal a significant difference in accuracy between graded compression ultrasound and computed tomography in diagnosing acute colonic diverticulitis [43].

Complications of both diseases, e.g., pyephlebitis and abscesses can be recognized by CEUS as well. In doubt, the differential diagnosis of inflammation and abscess can be nicely demonstrated by CEUS as demonstrated for Crohn's disease [29].

Appendicitis epiploica (also known as epiploic appendagitis) is perhaps a more common but rarely recognized disease of the colonic epiploicae. Its main clinical feature is acute abdominal pain often mistaken for appendicitis or diverticulitis. The disorder can be recognized sonographically by the presence of small hypo- and hyperechoic structures next to the colon wall in addition to slightly enlarged mesenteric lymph nodes. The transverse colon is rarely involved. Ultrasound can establish the diagnosis, although computed tomography is more commonly used due to the contrast features. CEUS has been shown to be helpful in the detection of circumscribed necrosis by demonstrating a central area of non-enhancement within the fatty tissue mass [44].

3.2. Antibiotic associated colitis 

Most patients with antibiotic-related diarrhea do not have enteritis and thus have no detectable sonographic abnormalities. On the other hand, patients who develop penicillin-induced colitis and pseudomembranous colitis, have typical sonographic abnormalities with prognostic implications [45]. The characteristic sonographic feature of penicillin-induced segmental hemorrhagic colitis is the appearance of partially asymmetric wall thickening of the colon (typically in the right colon) with loss of intestinal wall layers due to localized ischemia, histologically demonstrated by edema and bleeding. Hypovascularization can be detected by contrast enhanced ultrasound. High resistance flow pattern is found at a very early stage in the superior mesenteric artery. In later stages (at least >12h after onset of symptoms) hypervascular low resistance flow pattern is found. The surrounding colon and ileocecal region often appear normal [10], [45].

In contrast the most common finding in patients with pseudomembranous colitis caused by Clostridium difficile is symmetric wall thickening, which is often most prominent in the left colon but can also be apparent in other parts of the colon [46]. However, sonographic findings are not sufficiently specific to distinguish pseudomembranous colitis from other bacterial causes of colitis [47]. In our experience, both present uncharacteristic low resistance hyperdynamic flow pattern and hyperperfusion using CEUS. In severe cases, the colonic wall thickening may resemble diffuse infiltrating neoplasia (intestinal lymphoma). Other sonographic features of severe infection include transmural inflammatory reactions, free pericolic fluid, and intramural gas echoes [48].

3.3. Neutropenic enterocolitis 

Neutropenic enterocolitis is a potentially fatal complication of severe neutropenia. It typically affects the ileocecal region, which on ultrasound may reveal a distinct hyperechoic edematous hemorrhagic thickening of the intestinal wall. The presence of intramural gas and pericolic free fluid should raise concerns about imminent perforation [49]. In our experience, CEUS can help to delineate early necrosis and abscess formation.

3.4. Graft versus host disease (GvHD) 

Recently sonographic findings in acute graft versus host disease (GvHD) have been described as prognostic factors for the outcome of the disease [50]. All patients had thickened submucosal bowel wall segments in the ileocecal region. This pattern might help to differentiate together with the clinical symptoms between an infection (e.g. pseudomembranous colitis or cytomegaly virus colitis) and a GvHD of the bowel. In patients with a high grade a GvHD (daily stool volume >1500ml) sonographic characteristics of secretory diarrhea similar to the findings in endemic sprue such as a reduced frequency and uniformity of Kerckring's plicae circulares and an increased motility were observed. GvHD patients with only a moderate diarrhea or without intestinal symptoms had no sonographic signs of this type of involvement of the small intestine. By color Doppler imaging an increased arterial perfusion of the bowel wall and SMA was detectable in the majority of GvHD patients as a typical but nonspecific sign of an inflammatory bowel process. In contrast, all patients who had ischemic bowel wall lesions as evidenced by a high resistance flow pattern in the SMA did not respond to immunosuppressive therapy and ultimately died. Thus, the assessment of arterial blood flow in the SMA and bowel wall can be suggested as a prognostic marker in a GvHD [50]. In our experience (unpublished data), CEUS has been helpful to improve the detection of bowel wall ischemia.

3.5. Intussusception 

The typical ultrasound image of intussusception is a “target” or “bull's eye” lesion, representing layers of the intestine within the intestine. The sonographic finding of intramural gas indicates a low chance of reducibility [51]. Prognostically, a lack of perfusion in the intussusceptum [52], [53] detected with CEUS might indicate the development of ischemia and, therefore, the need for surgery.

3.6. Intestinal ischemia 

Contrast enhanced ultrasound can detect intestinal ischemia (caused by bowel strangulation, superior mesenteric artery embolism and non-occlusive mesenteric ischemia) in patients presenting with bowel obstruction (Fig. 4). A diminished or absent color signal after contrast injection in the least peristaltic and/or the most dilated bowel segment indicated intestinal ischemia (sensitivity 85–94%, specificity 100% compared to surgical findings), while simple obstruction without intestinal ischemia was characterized by normal color signals within the bowel wall [54], [55], [56].

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  • Fig. 4. 

    Contrast enhanced ultrasound can facilitate the identification of ischemic intestinal wall thickening (“ischämisch”) also in patients with inconclusive findings using color duplex imaging. Asymmetric bowel wall and “dirty bowel appearance” with loss of wall layer structure are indicative. Tissue contrast ultrasound signals are reduced or completely absent. Analysis of arterial enhancement is most important.

In patients with abdominal angina contrast application facilitated the adequate visualisation of the visceral arteries. The diagnostic efficiency of Doppler examinations of the mesenteric arteries is much higher using contrast enhancement. Levovist® injection in combination with color and spectral Doppler allowed an unequivocal diagnosis of visceral artery stenosis in most patients with abdominal angina [56].

Typical symptoms of chronic intestinal ischemia are postprandial abdominal pain and weight loss. This is often caused by stenotic or occlusive alterations of the celiac and/or mesenteric arteries. Significant stenosis is assumed if duplex scanning measures PV>200cm/s and EVD>55cm/s in the celiac artery, PV>275–300cm/s and EDV>45cm/s in superior mesenteric artery. However, angiography still is required for definitive diagnosis [10].

The interpretation of Duplex scan is difficult in acute ischemia of the small bowel. A few hours after the acute thromboembolic event, dilated bowel loops and bowel wall thickening can be observed. Sometimes an arterial occlusion can be detected, but Doppler ultrasound usually fails to demonstrate distal embolization.

3.7. Gastrointestinal tumors 

In a small study including 13 patients with gastrointestinal stromal tumor, the vascular imaging pattern in contrast enhanced coded phase inversion harmonic ultrasound differed between benign and malignant stromal tumors [57]. We know from tumors in other organs that dynamic contrast enhanced ultrasound (DCEUS) and vascular recognition imaging software enables the detection of micro-vessels and quantitative assessment of solid tumor perfusion. DCEUS can be used to monitor the anticancer efficacy of anti-angiogenic treatment. Reduction in tumor vascularization is observed in responders and is correlated with progression-free survival [58]. Similar clinical trials are being undertaken in colon cancer patients as well.

To our experience, contrast enhanced ultrasound can delineate necrosis even in small gastrointestinal stromal tumors (GIST)<15mm which is of importance for differential diagnosis and also during therapy monitoring. In a study involving 24 patients with GIST, CEUS allowed early prediction of tumor response to imatinib treatment [59].

3.8. Gastrointestinal hematoma 

Sonographically, hematoma may be recognized as echo poorly circumscribed bowel wall thickening. A similar picture may be seen in Schoenlein Henoch Purpura involving the gastrointestinal tract and with small or large bowel tumors. CEUS is decisive.

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4. Role of CEUS 

Computed tomography, magnetic resonance imaging, (capsule) endoscopy and enteroclysma are applied as effective imaging modalities to assess gastrointestinal disease. Endoscopy is invasive and can provide only the intraluminal aspect of the (transmural) disease. Poor patient compliance renders endoscopy difficult for follow-up. Parts of the small bowel are only accessible with advanced techniques (balloon enteroscopy, capsule endoscopy).

Computed tomography and (CT) enteroclysis involve radiation exposure and are therefore not indicated for patient follow-up, particularly not in young patients of fertile age who might require frequent monitoring in chronic intestinal disease.

Contrast enhanced ultrasound is a repeatable, well tolerated modality and, therefore, suitable for follow-up, predicting relapse and treatment control. Dedicated contrast-specific software can objectively assess signal quantity and overcome subjective interpretation of perfusion pattern. Motion artefacts caused by peristalsis, respiration or pulse do not impair CEUS to the same degree as they impair color Doppler ultrasound.

Recently bowel ultrasonography reproducibility was assessed in 20 patients with Crohn's disease by six experienced ultrasonographers using eight parameters: bowel wall thickness, bowel wall pattern, bowel wall blood flow, enlarged mesenteric lymph nodes, mesenteric hypertrophy, abdominal free fluid, and stenosis or fistulae. k values were best for bowel wall thickness (0.72–1) and stenosis (0.81–1) which are most important in daily routine but worse for other parameters, e.g., for bowel wall blood flow (0.53–0.89) and fistula [60].

The costs of CEUS have been recently addressed by Italian and German studies [61], [62], [63], [64], [65] showing the cost effectiveness of CEUS but so far no specific data have been published on CEUS of the gastrointestinal tract.

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5. Conclusion 

Using second harmonic imaging and new generations of stable contrast agents contrast enhanced ultrasound of the bowel wall appears to be a non-invasive diagnostic tool to investigate the macro- and most importantly – in contrast to Doppler techniques – also the microcirculation. In bowel diseases, the combination of both Doppler ultrasound, high resolution B-mode ultrasound as well as subtle usage of Duplex techniques and CEUS are a useful tool with certain indications:

-Improved imaging of the intestinal wall demonstrating inflammatory hyperemia in affected bowel segments.

-To assess the therapeutic efficacy of anti-inflammatory therapy.

-Imaging of the arterial and portal venous mesenteric vessels in patients with suspected acute or chronic gastrointestinal disease.

-Detection of typical sonographic patterns in the bowel wall suggestive of ischemic bowel disease and the detection and exclusion of stenoses or occlusion in mesenteric vessels.

-Assessment of typical changes in acute and chronic inflammatory bowel diseases concerning the localization (and more importantly) severity of the disease.

-Monitoring of typical changes in patients after bone marrow transplantation suggestive for acute GvHD (prognosis).

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Conflict of interest 

None.

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Funding 

None.

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PII: S1590-8658(10)00200-8

doi:10.1016/j.dld.2010.05.018

Digestive and Liver Disease
Volume 42, Issue 10 , Pages 667-674, October 2010

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