Utility of Abdominal Ultrasonography in the Diagnosis and Monitoring of Inflammatory Bowel Disease

REVIEW

Utility of abdominal ultrasonography in the diagnosis and monitoring of inflammatory bowel disease

Joaquín Poza-Cordón1 and Tomás Ripollés-González2

1Department of Gastroenterology. Hospital Universitario La Paz. Madrid, Spain. 2Department of Radiology. Hospital Dr. Peset. Valencia, Spain

ABSTRACT lished for examining the gastrointestinal tract, for three main reasons: Better technological development in other Abdominal ultrasonography has been undervalued for years as diagnostic techniques, a rejection by gastroenterologists technique used in examining the gastrointestinal tract. However, in the validity of its results, and the intestinal content it- thanks to the technological advances that have been seen in ultrasonography probes and the use of high frequency equipment, self, which has always been considered a limiting factor we are able to obtain high quality images of the intestinal wall. for exploration. However, in the last 20 years, it has been Moreover, due to the increased sensitivity of the colour Doppler, used with great diagnostic reliability to evaluate inflam- we can detect the parietal vascularization. Finally, in recent years, matory processes of the gastrointestinal tract (1-3) such as intravenous ultrasonography contrast agents have been used that infectious enterocolitis (4,5), diverticulitis (6-8), appendi- allow not only the inflammatory activity to be quantified but also the presence of complications with a diagnostic accuracy similar to citis (9) or ischemic colitis (10). Only in the last decade computed tomography (CT) and full magnetic resonance (full-RM), has it been accepted as a first-line technique in the diagno- without the associated radiation risk and at a lower cost. This article sis and monitoring of inflammatory bowel disease. reviews the utility of abdominal ultrasonography in inflammatory The diagnosis and assessment of patients with inflam- bowel disease, in particular Crohn’s disease, both during initial diagnosis and follow-up of the disease; the article also reviews the matory bowel disease is based on the combination of ability of the technique to be used in the detection of complications clinical symptoms and signs, laboratory tests, endoscopy (stenosis, fistulas and abscesses). and imaging techniques. Ileocolonoscopy has been considered the “gold standard” for the evaluation of inflam- Key words: Ultrasonography. Inflammatory bowel diseases. matory bowel disease (IBD), it is a non-invasive test used Crohn’s disease. Contrast agent BR1. on a regular basis and also provides information on the presence of lesions in the intestinal mucosa. As we know, in Crohn’s disease (CD) the involvement is transmural, INTRODUCTION so imaging tests must be used to give us information of the entire wall of the affected segments and to detect Abdominal ultrasonography is commonly used to transmural complications such as stenosis, fistulas and study hepatobiliary, pancreatic and urogenital pathology. abscesses. However, in the past, its utility has been less well estab- We also know that imaging techniques are necessary in the initial diagnosis and follow up of the disease. Howev- er, many of these techniques, such as chest and abdomen Poza-Cordón J, Ripollés-González T. Utility of abdominal ultrasonography in the diagnosis and monitoring of inflammatory radiographs, gastrointestinal transit, or CT, involve sub- bowel disease. Rev Esp Enferm Dig 2014;106:395-408. jecting these patients, usually young people of childbear- ing age, to repeated ionizing radiation. Furthermore, if we consider that many of these patients receive immuno- suppressive therapies, the deleterious effects thereof may Received: 18-02-2014 Accepted: 30-04-2014 even be higher. It is known that a cumulative dosage higher or equal to 50 millisieverts (mSv) is associated with Correspondence: Joaquín Poza-Cordón. Department of Gastoenterology. the development of tumours of the colon and urogenital Hospital Universitario La Paz. Paseo de la Castellana, 261. 28046. Madrid, tract (11). A meta-analyses published in 2012 was esti- Spain e-mail: [email protected] mated that up to around 11 % of patients with CD receive 396 J. POZA-CORDÓN AND T. RIPOLLÉS-GONZÁLEZ Rev Esp Enferm Dig (Madrid)

a dose at or above 50 mSv of ionizing radiation (12). This Concerning the use of intravenous contrast agents percentage rose to 20 % in a recently published Spanish in ultrasonography, a technique called CEUS (contrast retrospective study (13). agents-enhanced ultrasound), the only marketed in Spain Therefore, the intestinal ultrasonography and entero- is SonoVue® (Bracco, Italy). It is a second-generation MRI, given its diagnostic accuracy and safety, have been contrast agents formed by micro-bubbles consisting of proposed as the techniques of choice for the evaluation sulphuric hexafluoride, an inert and stable molecule. This and monitoring of the CD. molecule is removed through the airway without any ex- The main advantage of ultrasonography is that it is cretion involvement of the kidney or liver and does not re- available in all hospitals and is cheaper compared to other main in the body longer than 15 minutes. It is an entirely techniques. Furthermore, it provides us with real-time in- intravascular contrast agents, i.e., it does not diffuse into formation that is difficult to obtain using other types of the tissues. Its detection requires that specific programs imaging. However, it has a number of limitations such as are installed in the ultrasonography image that increase obesity (unusual in these patients), difficulty in assessing the difference between the signal emitting from the mi- the proximal and anorectal involvement and finally, it is cro-bubbles and the signal emitting from the tissues. An- an examination technique that is accurate dependent on a other important aspect for assessing of the response of the certain learning curve. micro-bubbles is the mechanical index (MI). The MI is the force with which the ultrasonography waves compress the micro-bubbles. Using low MI (< 0.2) minimises their GENERAL CONSIDERATIONS: TECHNICAL destruction and keeps a sufficient number of bubbles for ASPECTS AND ULTRASONOGRAPHY continuous evaluation in real-time over several minutes. CONTRASTS The bolus amount used ranges between 1.2-4.8 ml. The majority of the studies published use a 1.2 ml bolus with The exploration of the digestive tract requires some 3.5-5 MHz probes; however, high-frequency probes have degree of abdominal compression for three main reasons greater capacity for destruction of the bubbles so greater (14): contrast agents will be required. – It moves the intestinal content (gas, stool). – It decreases the distance between the transducer and the loop. This is especially important with the use of GENERAL CONSIDERATIONS: INTESTINAL high frequency probes that have less penetration, but WALL ECHOSTRUCTURE AND ANATOMY provide higher quality images. – It evaluates the stiffness of a tissue and its reaction The correlation between the anatomy and ultrasonog- with abdominal compression. raphy appearance has been considered adequate in clini- This compression should be gradual and comparable cal practice, although the different acoustic interfaces to that performed during abdominal palpation. We should produced by the ultrasonographic appearance of layers note that a marked abdominal compression can bring do not exactly correspond with the histological differ- about a change in the thickness of the intestinal wall and ences between the layers. However, there is evidence that influence the measurements made on the structures. the muscular and submucosal layers correspond to those The examination should begin with a standard abdomi- identified on the ultrasonography (17,18). We can differ- nal probe (3-5 MHz) that will give us an overall view on entiate sonographically up to 5 echogenic layers (Fig. 1). the distribution, location and relationship to neighbouring alternating a hyperechoic layer with another hypoechoic. structures of the small intestine and colon loops. Subse- Over thirty studies have been published in the last two quently, we will focus the examination on high-frequency decades to establish normal ranges of the thickness of probes (7-12 MHz) necessary for a detailed examina- the intestinal wall, with significant differences being pro- tion of the previously identified segments where pathol- duced between the studies, from 1 to 5 mm. These differ- ogy is suspected, as the intestinal wall is measured with ences are due to the equipment and frequencies used, the higher resolution. In fact, during it is relatively frequent different scanning techniques and the degree of abdomi- to change from one probe to another during the examina- nal compression during measurement. Currently, with the tion in order to obtain additional information from each use of high frequency probes, most authors consider when of them. a wall to be normal when it is below 3 mm, using a mid- It does not require specific intestinal preparation except line abdominal compression (19). fasting for 3-5 hours to reduce postprandial peristalsis and The small intestine (Fig. 2A) is differentiated from luminal air. Some authors propose the use of oral contrast the colon by its peristaltic capacity, its winding course agents, a technique known by the acronym SICUS (Small and by the presence of valvulae conniventes being more Intestine Contrast Ultrasonography) (15) which requires expressive when liquid content is present and in more the administration of an oral contrast agents, generally be- proximal segments (jejunum). As occurs in other imaging tween 200-2,000 ml of polyethylene glycol (16). techniques the jejunum and ileum loops cannot be differ-

Rev Esp Enferm Dig 2014; 106 (6): 395-408 Vol. 106, N.º 6, 2014 UTILITY OF ABDOMINAL ULTRASONOGRAPHY IN THE DIAGNOSIS AND MONITORING 397 OF INFLAMMATORY BOWEL DISEASE entiated. Topographical criteria is used during the ultrasonography to identify these sections, so that generally the loops that are located in the infraumbilical region are considered ileal and those that are located in the supra- umbilical region are considered the jejunum. The typical ultrasonographic appearance of the colon is differentiated from the small intestine by the arrangement of gas waves and the absence of peristalsis (Fig. 2B). The colon is located in the periphery of the abdomen (20). The ascending and descending colon, being retroperitoneal organs, their position is fixed, in the laterodor- sal portion of the abdomen. The rectum is easily identified by following the ascending colon. The hepatic flexure can be located just below the most caudal portion of the right lobe of the liver and the splenic flexure between spleen and left kidney. Both flexures are generally identifiable by subcostal approach by having the patient take in a deep breath, but sometimes we use an intercostal approach. Fig. 1. Echostructure of the intestinal wall of a healthy patient with However, the position of the transverse and sigmoid colon alternating hyperechogenic and echogenic layers. The distance between can vary significantly depending on the length of its mes- the marks indicating the wall thickness. entery. To explore the transverse colon we must start the ultrasonography scan from the subxiphoid epigastric part and follow caudally up to and through the infraumbilical tinuous versus discontinuous) and/or the involvement of region. The sigmoid colon, despite having a meso-colon, the terminal ileum than in the ultrasonography image, as can be located the majority of the time above the iliac there is enough overlap between the two diseases. vessels and the psoas muscle of the left inguinal region. As we know, in CD, the terminal ileum is affected in Abdominal ultrasonography is not an appropriate test to about 70 % of cases (21). It is characterised by a thick- assess the rectum due to its pelvic location. ening of the wall, characteristically transmural and discontinuous, thickening of the submucosa being frequently observed, especially if the disease has progressed over a SONOGRAPHIC FEATURES OF CROHN’S certain amount time (22). Moreover, by using high fre- DISEASE AND ULCERATIVE COLITIS quency probes, hyperechogenic or hypoechoic linear paths can be observed (containing gas or not) that pass Differentiation between ulcerative colitis (UC) and through the layers in depth, corresponding to ulcerations CD is based more on the distribution of the disease (con- which will affect the disintegration of the layer patterns

A B

Fig. 2. Echostructure of a small intestine loop (valvulae conniventes) (A) and colon (haustra) (B).

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only validated index, mainly uses clinical criteria, is only useful for the inflammatory pattern of the disease and its complexity is used only in the context of clinical trials. For all this, the decision-making of the clinician should be based not only on the tests conducted in the clinic, but also on lab tests and imaging to demonstrate the presence or absence of inflammatory activity and/or complications. Throughout the article we focus on the utility of ultrasonography in various aspects of CD. They are didacti- cally divided into six sections: – Initial evaluation of suspected CD. – Assessment of the extent of the disease. – Diagnosis of complications: abscesses, fistulas and stenosis. – Determining the inflammatory activity. – Monitoring of the medical treatment. – Postoperative recurrence.

INITIAL EVALUATION IN SUSPECTED CROHN’S DISEASE Fig. 3. Cross section of a bowel loop showing the sonographic data characteristic of CD affectation. There are many prospective studies comparing abdominal ultrasonography with other diagnostic techniques, such as endoscopy, barium studies, CT, entero-MRI or to varying degrees (Fig. 3) (23). Another fact that also capsule endoscopy. Most of them are controlled studies allows for differentiation between CD and UC and other with high prevalence in IBD and combine patients with processes that produce thickening of the intestinal wall, is known disease and patients with clinical suspicion. It the involvement of mesenteric fat adjacent to a thickened must be kept in mind that the differences in sensitivity loop which is generally identified by its almost homoge- and specificity will depend basically on the comparator neous appearance, almost isoechogenic to the submucosa. used, the cut-off used for the thickness of the intestinal Finally, the data that give greater specificity to the diag- wall, and the quality of ultrasonography equipment (24). nosis of CD, apart from the discontinuous involvement, is Thus the classic studies have a sensitivity of 53-81 % and the presence of stenosis, fistulas and abscesses. a specificity of 80-87 % (25-28). However, in more recent In UC only the mucosal layer echostructure is affected, studies the sensitivity is around 86-95 % and the specific- preserving the rest of the layers, except in severe out- ity of 93-97 % (29, 30). breaks or megacolon where the ulcers are more severe. Fraquelli et al. (19) published a meta-analyses aimed Unlike in CD, the disease is distributed continuously and at determining the sensitivity and specificity of different regularly from the rectum proximally, the extent of the cut-off points of the thickness of the intestinal wall in the disease varying, without affecting the terminal ileum. The diagnosis in CD. The authors concluded that using a cut- limitations of abdominal ultrasonography must be kept in off of more than 3 mm, the sensitivity and specificity were mind when assessing the rectum and as such, the diagnos- 88 % and 93 % respectively, whereas, when the cut-off tic accuracy in cases of proctitis is very low. was more than 4 mm, the sensitivity was 75 % and specificity of 97 %. This makes many authors use a 4 mm cut- off for the primary diagnosis of CD to reduce the number UTILITY OF ABDOMINAL ULTRASONOGRAPHY of false positives and 3 mm to monitor the disease. IN CROHN’S DISEASE Four studies have been published, including over a thousand patients, where the sensitivity and specificity for Many papers have been published regarding the utility the diagnosis of CD is performed in patients without pri- of ultrasonography in CD and very few make reference to or diagnosis of IBD (31-34) (Table I). The Parente et al. the UC. This is mainly because in UC, the clinical indices study (34) is worthy of note; it included 487 patients with used have very good correlation with the inflammatory symptoms and signs suggestive of IBD. Ultrasonography activity of the disease and are used to decide on the start was the first study that was performed on all patients and of treatment and monitoring its response. However, this achieved a sensitivity of 85 %. does not occur in CD where there are no good clinical Despite these data, we should note that even in expert indices. The CDAI (Crohn’s Disease Activity Index), the hands, there are false positives and false negatives since

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Table I. Sensitivity and specificity of ultrasonography in the diagnosis of inflammatory bowel disease Author n Comparator S E Bozkurt, 1994 (31) 240 Barium/endoscopy/ 76 100 surgery Hollerbach, 1998 (32) 227 Barium/endoscopy/ 84 Not used surgery Astegiano, 2001 (33) 313 Barium/endoscopy 84 98 Parente, 2003 (34) 487 Barium/endoscopy/ 88 Not used surgery the thickening of the intestinal wall is not specific to IBD and transverse colon with a 88 and 82 % respectively. The and is present in other inflammatory, neoplastic and in- jejunum was the most difficult location to diagnose with a fectious diseases (35). The ileal and segmental location, sensitivity of 72 %. In a recent series, Martinez et al. (43) involvement of mesenteric fat and the presence of fistulas compared the ultrasonography with entero-MRI in 30 in and abscesses are the most specific data. However, the fi- patients with a total of 119 segments evaluated, obtain- nal diagnosis should always, whenever possible, be done ing greater diagnostic sensitivity with ultrasonography, in the small intestine and the colon, accompanied by en- although the difference was not statistically significant. doscopic and histological diagnosis (36).

DIAGNOSIS OF COMPLICATIONS: ABSCESSES, ASSESSMENT OF THE EXTENT OF CD FISTULAS AND STENOSIS

To date we have published eight studies comparing ul- Abscesses trasonography with other imaging and/or endoscopy techniques in order to determine the extent of CD (34,37-43) Computerised tomography has been traditionally con- (Table II). A recently published systematic review (44) es- sidered the imaging test of choice. Because of its accessi- tablishes an overall sensitivity of 85 % (95 % CI 83-88 %) bility in all centres and its safety, ultrasonography should and a specificity of 94 % (95 % CI 93-95 %). be the first imaging test to be performed in a patient with However most of these studies were prospective, in- suspected abdominal abscess. cluded a series of small number of patients with CD lo- The utility of ultrasonography in the diagnosis of ab- calised to the ileum and as such, their results should be in- dominal abscesses has been evaluated in three studies terpreted with caution. In addition, we must consider the using surgery as a reference and includes a total of 41 le- comparator used as a benchmark. The Parente et al. study sions in 242 patients (45-47). Pooling the results of these (34) must again be noted, in which a comparative study studies (44), a sensitivity of 84 % (95 % CI 79-88 %) and was performed with endoscopic and radiological findings a specificity of 93 % (95 % CI 89-95 %) is defined. in 187 consecutive patients with CD. The study revealed In ultrasonography (Fig. 4) these are usually present- a sensitivity for ileal disease 95 %, smaller for the left ed as a hypo-anechoic image with undefined borders,

Table II. Sensitivity and specificity of ultrasonography in evaluating the extent of inflammatory bowel disease Authors n Test S E Maconi et al. 1996 (37) 115 Ileocolonoscopy/barium 89 94 Reimund et al. 1999 (38) 48 Ileocolonoscopy/barium 83 67 Bru et al. 2001 (39) 38 Ileocolonoscopy 83 87 Parente et al. 2002 (40) 296 Ileocolonoscopy/barium 93 97 Parente et al. 2003 (34) 187 Ileocolonoscopy/barium/CT/Surgery 77 95 Pascu et al. 2004 (41) 37 Ileocolonoscopy 74 97 Parente et al. 2004 (42) 102 Ileocolonoscopy/ enteroclysis 96 98 Martínez et al. 2009 (43) 30 entero-MRI 91 98

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A B

Fig. 4. A. Thickened intestinal loop with marked hyperaemia. Small intramural avascular hypoechoic nodule (arrow) representing an intramural abscess. B. Mesenteric hypoechoic mass (arrow) showing no enhancement after injection of contrast agents corresponding to an abdominal abscess.

which may or may not contain echogenic content (gas) vesical, fistulas, etc.) (Fig. 5) or mesenteric fat (entero- inside (Fig. 4B). With the use of high-frequency probes, mesenteric fistulas) (45,46). the presence of intramural abscesses can be identified as Currently there is no reliable technique for the diagno- generally well demarcated hypoechoic images (Fig. 4A). sis of this complication and intraoperative findings should Depending on their position in the abdominal cavity, they be considered a reference when assessing the utility of a can be classified into intraperitoneal (shallow or deep) or technique for the diagnosis of this complication (49). The retroperitoneal (47). barium studies, which have been considered as the gold It is sometimes difficult to distinguish between abscess standard for years, could lose more than 40 % of fistulas and phlegmon. For this, the use of colour Doppler can encountered during surgery (36). Only two prospective help differentiate between these. The abscess is usually studies have evaluated the role of ultrasonography in de- detected by Doppler signal in the vicinity of the lesion but termining the presence of internal fistulas using surgery as not within the same while the phlegmon is generally iden- a reference (46,47), the sensitivity can reach up to 87 % tified by an increase in the Doppler signal. The introduc- with a specificity of 90-96 % depending on the series. The tion of intravenous ultrasonography contrast agents has Martínez et al. (43) is worthy of note, which prospectively not only allowed for these lesions to be clearly differenti- compared the findings on ultrasonography and entero-MRI ated from each other, but we can also clearly define the without obtaining significant differences between the two limits of the abscess and therefore better define the size, techniques in the detection of fistulas, with a sensitivity of estimate its multilocularity and communication with other 82% for ultrasonography and 70 % for entero-MRI. intra-abdominal organs (48) (Fig. 4B). After injection of ultrasonography contrast agents there is an enhancement of the inflammatory mass corresponding to phlegmon, Stenosis however for abscesses there in no signal in the collection, with enhancement of the adjacent peripheral tissue. In ad- Stenosis are identified as segments of thickened walls, dition, it allows lesions up to 1 cm to be detected with aperistalsis, with narrowing of the lumen. There is pre- higher resolution than in CT which, because of its small stenotic dilatation identified by liquid distension or echo- size, does not allow for a distinction between fistulas or genic content in the previous loop (Fig. 6A). lymphadenopathy. To date, there have been four prospective studies that have evaluated the utility of ultrasonography in the diagnosis of stenosis (40,45,46,50). The sensitivity and speci- Fistulas ficity of ultrasonography will depend on the test used as the gold standard, so that when compared to surgery, ste- Fistulas are visualised as tracts or hypoechoic areas nosis are of a higher degree, will be ultrasonically more from a thickened intestinal loop, which may have echo- expressive and therefore easier to detect. genic contents inside (if they contain gas) and can blindly Some studies used oral contrast agents to increase the communicate with other structures (entero-enteric entero- detection rate of stenosis, especially those of a low de-

Rev Esp Enferm Dig 2014; 106 (6): 395-408 Vol. 106, N.º 6, 2014 UTILITY OF ABDOMINAL ULTRASONOGRAPHY IN THE DIAGNOSIS AND MONITORING 401 OF INFLAMMATORY BOWEL DISEASE

A B

Fig. 5. A. Entero-mesenteric fistula (arrow). B. Enteroenteric fistula (arrow), both displayed as hypoechoic tracts. gree. Parente et al. in their series revealed the diagnostic stenosis (51,52). Thus both stratification and increased in- sensitivity may increase to 10 % for a single stenosis and traparietal vascularization are present in stenoses that are 20 % for two or more stenosis (42). inflammatory in nature (Fig. 6B). While when stratifica- The echotexture of the intestinal wall as well as the tion is observed in stenoses, especially in the submucosa, density of vascularization of the stenotic segment can with vascular loss are more characteristic of predominant- give us an approximation of the histological changes and ly fibrotic stenoses. Intravenous ultrasonography contrast allow us to discriminate between fibrotic or inflammatory agents could help to differentiate between the degree of

A B

Fig. 6. Inflammatory stenosis. B-mode image (A), showing a thickened bowel wall segment (arrow) with abundant hyperaemia on colour Doppler ultrasonography (B).

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inflammation or fibrosis of these segments. Working with tivity are transmural complications, such as deep ulcers, the largest number of published patients is Ripollés et al. fistulas, boils or abscesses. (53) who correlated ultrasonography findings with histo- Multiple studies have focused on determining the utility of pathological findings in a series of 25 operated patients, the Doppler to show inflammatory activity. Thus, during the finding that transmural complications, the degree of co- 1990s, papers were published about the utility of pulsed Dop- lour Doppler and the percentage of contrast agents in- plers on the superior mesenteric artery (56-60). The results crease was significantly greater in inflammatory stenoses. obtained were contradictory without obtaining significant differences among the groups (healthy, CD in remission, and CD in an outbreak) in all the studies and their validity has DETERMINING THE INFLAMMATORY ACTIVITY not been confirmed in larger series. In addition, its measurement is influenced by many technical and other factors such The main criteria for determining inflammatory activ- as age, atherosclerosis, fasting, the territory of the affected ity in ultrasonography are wall thickening and the degree segment, which directly affect the results obtained (61). Sub- of parietal vascularization detected with colour Doppler. sequently published studies have focused on the vasculariza- Although there are other data that relate to the activity of tion on the affected intestinal segment. The index most used the disease, such as loss of echostructure wall (54), fibro- is semi-quantitative and graded the density of the parietal vas- fatty proliferation and the presence of lymphadenopathy cularization from 0 to 3 using colour Doppler, 0 being none, (55). Other criteria for the existence of inflammatory ac- 1 barely visible, 2 moderate and 3 intense (62) (Fig. 7). In

A B

C D

Fig. 7. Semiquantitative index used in the colour Doppler ultrasonography to assess the degree of hyperaemia in the wall of the bowel loop: 0 degree (A), 1 degree (B), 2 degree (C), 3 degree (D).

Rev Esp Enferm Dig 2014; 106 (6): 395-408 Vol. 106, N.º 6, 2014 UTILITY OF ABDOMINAL ULTRASONOGRAPHY IN THE DIAGNOSIS AND MONITORING 403 OF INFLAMMATORY BOWEL DISEASE this respect, the authors have correlated the Doppler activ- strong negative correlation between TTP and histopatho- ity with the clinical (63,64), endoscopic (62) and histological logical findings (r = -0.68, p < 0.01) so that the time from activity (65). Other studies have evaluated the utility of the the introduction of the contrast agents to the maximum resistance index obtained in the vessels of the intestinal wall peak decreased with greater inflammatory activity in the (66,67) (Table III). analysis of the surgical specimen (70). Franco et al. ana- In recent years studies have been published on the util- lysed (71) in a series of 54 patients with ileal CD two ity of intravenous ultrasonography contrast agents to as- quantization parameters obtained in the contrast agents sess the inflammatory activity of the disease with promis- measurement («Peak» and the coefficientβ ) obtaining a ing results. sensitivity to demonstrate ileal activity of 97 % for the Although some studies have been published that quali- “peak” and 86 % for the coefficient B, with a specificity tatively assess the parietal enhancement, most of the of 83 % for both. Finally, Ripollés et al. (72) obtained a authors performed quantitative analysis of the parietal correlation between the percentage of enhancement and enhancement (68) with specific programs, which allow endoscopic severity in a series of 61 patients with CD. for intensity/time curves for a region of interest (ROI). Patients with moderate or severe endoscopic activity, That is to say, for a manually selected area, the bright- measured by the CD Simple Endoscopic Score or Rut- ness intensity is analysed for a set amount of time (usually geerts Index, showed a significantly greater increase in 60 seconds) after administration of the contrast agents. enhancement than in patients with inactive disease (p < Through these curves, depending on the software used, 0.001). Using a 46 % increase in enhancement after con- different variables are analysed, such as: Max or Peak S.I. trast agents administration as the cut-off, the sensitivity (maximum signal intensity), mean S.I. (average signal in- was 96 % with a specificity of 73 % for detecting moder- tensity), percentage of enhancement ((max. S.I.-min. S.I.) ate or severe endoscopic activity. x 100/min. S.I.), MTT (mean transit time), TTP (Time to However, quantification of the contrast agents has a the peak), the coefficientβ (slope of the curve), the area number of limitations because the results are dependent under the curve and VRV (vascular redistribution vol- on the equipment since each ultrasonography works with ume) (Fig. 8). different programs. And sometimes, it is not possible In a study by Girlich et al. (69), they found in a series to clearly analyse the intestinal wall, even with modern of 20 patients with CD who were undergoing surgery, a equipment, if the wall is too thin.

Table III. Accuracy of the colour Doppler and the intramural resistance index in evaluating activity in Crohn’s disease Study n Parameters Finding Statistical significance Heyne, 2002 (63) 20 Controls Semiquantitative Correlation with clinical activity CD: NS 99 EII (CD 60, 39 UC p < 0.001 UC) Spalinger, 2000 (64) 119 (85 outbreaks) Semiquantitative Correlation with clinical activity S: 83; E: 88 p < 0.001 Esteban, 2001 (66) 79 (44 outbreaks) Resistance index Correlation with clinical activity Outbreak: 0.65-37.5 kg Relapse: 0.75-37.5 kg p < 0.001; S: 95 %; E: 69 % Neye, 2004 (62) 22 (126 segments) Semiquantitative Correlation with endoscopic Ileum (k: (0.82) Ascending (k: 0.75) Transverse (k: 0.78) Sigma (k: (0.81) Drews, 2009 (65) 32 Semiquantitative Correlation with histological p < 0.05 activity S: 95; E: 70 Ripollés, 2008 (75) 28 Semiquantitative Monitoring (0 and 4 weeks) ↓ vascular: p < 0,05 (22 outbreaks) residual hyperaemia 4 w: 81 % recurrence (p < 0.05) Sjekavica, 2007 (67) CD: Resistance index Correlation with clinical activity p < 0,001 Healthy: 67 Inflammatory bowel disease (IBD); Crohn’s disease (CD); ulcerative colitis (UC).

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SI PEAK

MTT Recirculation

A.U.C.

time TTP

Peak[%] = 37.3 TTP[s] = 9.521 RBV = 781.883 RBF = 48.205 MTT[s] = 16.22 50

10 SI max = 55 SI mean = 37 s.d. = 6.5 [Area = 0.9277 cm2] [%] s 4.120 8.240 12.360 16.480 20.600 24.720 28.840 32.960

Fig. 8. Intensity/time curve and parameters obtained with quantifi cation of contrast agents [Contrast (Esaote, Genoa, Italy)]. Max. or Peak S.I. (maximum signal intensity), mean S.I. (average signal intensity), mean transit time (MMT), time to peak (TTP), vascular redistribution volume (RDV).

MONITORING OF THE MEDICAL TREATMENT es in treatment have been evaluated with clinical signs. Several studies have used ultrasonography to assess the In order to assess the response to medical treatment the response to medical treatment, detecting in patients with same patient should be monitored frequently, and there- a good response, a reduction in both the thickness and the fore the monitoring technique should be non-invasive, not Doppler fl ow of the intestinal wall (74,75). However, in use ionizing radiation and be especially well tolerated by most of these studies there was no correlation between the patient. Ultrasonography meets all these requirements medical response evaluated with the CDAI or CRP and ul- and may reduce the use or for other invasive procedures trasonography changes. Relapses in patients with favour- or those that use ionizing radiation. able clinical response have been attributed to the persis- The literature has shown that there are patients with- tence of infl ammatory activity despite strong performance out symptoms who have infl ammatory activity confi rmed in relief of the symptoms. It has been demonstrated that during endoscopy. In the study conducted by Hirche et the residual hyperaemia evaluated with colour Doppler or al. (73) the ultrasonography was performed routinely on with contrast agents can identify patients with incomplete 255 patients with CD, revealing transmural complications histological remission refl ecting subclinical infl amma- in 18 % of patients, 37 % of those being asymptomatic, tion, with increased susceptibility to relapse (75,76). with CDAI < 150. These data highlight the importance of The introduction of anti-TNF in the treatment of CD is monitoring the effectiveness of the treatment with imag- changing the natural course of the disease; these therapies ing techniques. not only reduce the activity of the disease but also the rate The goal of traditional medical treatments has been to of long-term complications. In a recent study conducted control the symptoms of the patients. Relapses and chang- on patients treated with anti-TNF a decrease in wall thick-

Rev esp enfeRm Dig 2014; 106 (6): 395-408 Vol. 106, N.º 6, 2014 UTILITY OF ABDOMINAL ULTRASONOGRAPHY IN THE DIAGNOSIS AND MONITORING 405 OF INFLAMMATORY BOWEL DISEASE ness, degree of vascularization and transmural complica- high diagnostic accuracy in detection of postoperative re- tions was observed, a significant correlation existing be- currence, detecting almost all cases of severe recurrence tween these changes and the clinical response (77). Only as well as high sensitivity and specificity in differentiat- patients with partial response or remission showed an ing between mild and severe recurrence. The use of oral ultrasonographic improvement. Evolution (surgery, dose contrast agents may increase the diagnostic sensitivity of increase or change of anti-TNF) in the following year the test as reflected in the study conducted by Castiglione showed significant differences between patients with im- et al. (86). The use of intravenous contrast agents shows proved ultrasonography and those that did not improve. promising results, the study conducted by Paredes et al. Castiglione et al. (78) in a study conducted on 133 (87) achieving a sensitivity and specificity of 98 % and patients, 66 treated with anti-TNF and 67 with immune- 100 % respectively, including the criteria of thickness > suppressants, after 2 years of treatment, mucosal healing 5mm or enhancement > 46 %. was observed in 42 patients and transmural healing assessed by ultrasonography in 20 patients. The study found good correlation between mucosal and transmural healing UTILITY OF ABDOMINAL ULTRASONOGRAPHY (k = 0.63), mucosal healing existing in 18 of the 20 pa- IN ULCERATIVE COLITIS tients with transmural healing. In this study there was little correlation between clinical remission and mucosal As we know, UC exclusively affects the colon and ex- healing or transmural healing. tends from the rectum variably and proximally. Unlike Quantitative techniques in ultrasonography with con- CD, the pattern of layers is observed except in severe out- trast agents can measure changes in the mural enhance- breaks of the disease, in which there may be a destruction ment reflecting the response to therapy in monitoring the of their walls. Characteristically, the muscle and pericolic inflammatory disease. It has been proven that there is a fat are not usually affected. And finally, the wall thick- significant reduction in the enhancement in patients with ening depends on the first layer but occasionally may be clinical response to biological treatments (79). However, increased by submucosal oedema or fibrosis. to date there are no studies demonstrating that this as- The clinical utility of abdominal ultrasonography in UC sessment adds information to that provided by the colour is less well established than in CD since the resolution of Doppler ultrasonography. ultrasonography images does not establish the presence of lesions in the mucous layer. Moreover, as we have previously mentioned, the rectum cannot be properly assessed UTILITY IN POSTOPERATIVE RECURRENCE through abdominal ultrasonography. In this respect, some studies have failed to find cor- To date, eight studies have been published evaluating relation between wall thickening and clinical activity the utility of abdominal ultrasonography for postoperative (88,89). However, other authors found a higher correla- recurrence (80-84), two with oral contrast agents (85,86) tion between ultrasonography and endoscopic findings in and only one with intravenous contrast agents (87), using UC than in CD (41). In another more recently published endoscopy as the benchmark (Table IV). All studies show study, not only was a good correlation found between en-

Table IV. Accuracy of ultrasonography in the diagnosis of postoperative recurrence Study n Technique Recurrence S E DiCandio G (80) 32 US 5 mm 82 100 Andreoli A (81) 41 US 5 mm 81 86 Rispo A (82) 45 US 3 mm 79 95 Calabrese E (85) 72 SICUS 3 mm 92 20 dilatation > 25 mm stenosis < 10 Paredes JM (83) 33 US 5 mm 86 77 Doppler 2 or 3 Castiglione F (86) 40 US/SICUS 3 mm 77/82 94 Paredes JM (87) 60 CEUS 5 mm or 46 % enhancement 98 100 Ultrasonografía (US); Small Intestine Contrast Ultrasonography (SICUS).

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doscopic activity and ultrasonographic activity, but it was 5. Kawamoto S, Horton KM, Fishman EK. Pseudomembranous colitis: able to establish a predictor of poor progression if the ac- spectrum of imaging findings with clinical and pathologic correlation. Radiographics 1999;19:887-97. tivity data continued for 3 months from starting treatment 6. Ripollés T, Agramunt M, Martínez MJ, Costa S, Gómez-Abril SA, with corticosteroids (90). Richart J. The role of ultrasound in the diagnosis, management and In our opinion, the utility of abdominal ultrasound in evolutive prognosis of acute left-sided colonic diverticulitis: a review of 208 patients. Eur Radiol 2003;13:2587-95. ulcerative colitis may be of interest in three clinical situa- 7. Pradel JA, Adell JF, Taourel P, Djafari M, Monnin-Delhom E, Bruel tions: assessing the extent of the disease in cases of incom- JM. Acute colonic diverticulitis: prospective comparative evaluation plete colonoscopy such as in a serious onset of the disease, with US and CT. Radiology 1997;205:503-12. aid in the differential diagnosis in cases of indeterminate 8. Hollerweger A, Macheiner P, Rettenbacher T, Brunner W, Gritzmann N. Colonic diverticulitis: diagnostic value and appearance of inflamed colitis in order to rule out small intestine involvement diverticula-sonographic evaluation. Eur Radiol 2001;11:1956-63. and may eventually be an alternative to colonoscopy in 9. Lee JH. Sonography of acute appendicitis. Semin Ultrasound CT MR outbreaks of the disease in order to assess activity or the 2003;24:83-90. 10. Ripollés T, Simó L, Martínez-Pérez MJ, Pastor MR, Igual A, López extent of disease. However, ultrasonography is not useful A. Sonographic findings in ischemic colitis in 58 patients. 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