II.2.2.2. Ultrasound in the diagnosis and follow-up of patients with inflammatory bowel disease

Dr. Tomás Ripollés Sabater
Hospital Universitari Doctor Peset. Valencia

 

For many years, it was believed that intestinal gas and peristalsis prevented ultrasound evaluation of intestinal loops, as this is often the case in normal intestinal loops. However, in the diseased intestine, the wall is thickened and rigid, with typically decreased peristalsis and little intraluminal gas. These factors allow satisfactory ultrasound assessment of the affected segments in most patients with inflammatory bowel disease (IBD). Obesity is also a limitation in ultrasound evaluation; however, IBD patients are usually thin, which favours the use of ultrasound, allowing proper evaluation and interpretation of the findings.

 

TECHNIQUE

There are several requirements for proper ultrasound examination of the digestive tract: this is a technique that requires skill and a certain amount of experience, both of which can be acquired through prior training; there is a learning curve, so the results obtained improve with experience. Moreover, examination requires a meticulous technique and time, unlike a standard ultrasound to measure the kidneys or detect stones. Another key aspect to ensure a good diagnostic yield is the use of high-frequency probes; an initial general examination of the abdominal cavity can be performed with 3–5 MHz convex probes, but for a thorough examination of the intestinal loops and surrounding tissues, it is essential to use higher frequency (>5 MHz) convex or linear probes, as these provide a higher resolution assessment of the intestinal wall.

In 1986, Puylaert1 described the so-called “gradual compression” technique whereby pressure is gradually increased in order to shift intestinal gas and reduce the distance between the transducer and the area of interest, thus allowing for the use of high frequency probes with a lower depth of penetration. Fasting before an ultrasound scan makes the examination easier as it reduces gas, but there is no need for any other special preparation. Some authors advocate the use of large amounts of nonabsorbable oral isotonic solution for better dilation of the intestinal lumen, although this unduly prolongs the examination. Moreover, Bru et al. described using ultrasound with a physiological saline enema to assess involvement of the colon2. In women, transvaginal ultrasound is ideal for assessing the involvement of the rectosigmoid colon and pelvic intestinal loops.

The procedure used to examine the intestinal loops varies depending on the publication, but it must be thorough and orderly so as not to leave out a single intestinal segment. To ensure a comprehensive assessment, each affected segment of the colon or small intestine should be explored both transversely and longitudinally.

Ultrasound examination of the abdominal cavity must begin with a B-mode examination (greyscale) to detect intestinal segments with a thickened wall, determining the length and distribution of the affected segments. Other parameters to be analysed include changes in the local fat, transmural complications (fistulas or abscesses) and the presence of stenoses and dilatations. The use of colour Doppler ultrasound as a complement to B-mode ultrasound allows to evaluate parietal vascularisation, a parameter which reflects the degree of inflammation. Lastly, in some cases, ultrasound contrast agents may be used to assess the enhancement of inflamed segments or to differentiate between abscesses and phlegmons.

 

B-mode ultrasound

• A normal intestine wall has a layered structure, with a morphology that varies during ultrasound examination as a result of peristalsis. In ideal conditions, up to five layers are visible in the intestinal wall (Fig. 1)3.

• Measured from the mid-line to the serosa, the thickness of the normal wall should be less than 3 mm. Ultrasound diagnosis of IBD relies mainly on the detection of wall thickening in an intestinal segment (Fig. 1 and 2).

• In addition to wall thickness, the persistence or loss of the layered structure of the wall, whether its involvement is continuous or discontinuous, whether the involvement is symmetrical or asymmetrical, and the degree of compressibility of the loop should also be analysed.

FIGURA 1. Corte trasversal de un asa intestinal en ecografía modo B en un paciente con EC.

Colour Doppler ultrasound

• Allows the microscopic vessels of the intestinal loop wall to be visualised. These small vessels are characterised by slow flow and low speeds. In order to evaluate the vascularity of the loops, the Doppler parameters must be optimised, setting the ultrasound equipment colour to the maximum sensitivity using a special preset program.

• To reduce inter- and intraobserver variability in the interpretation, settings should be kept the same throughout the examination.

• The vascularity of the intestinal loop wall is measured using a semiquantitative scale: no flow (grade 0), weak flow (grade 1) or easily visible flow (grade 2)4.

 

Contrast-enhanced ultrasound

• Intravenous ultrasound contrast agents have recently been introduced into clinical practice. These contrast agents allow the microvasculature of multiple abdominal organs such as the liver, kidneys, pancreas, intestine or spleen to be examined in a manner similar to computed tomography (CT) or magnetic resonance imaging (MRI). Currently, their most widespread application is the detection and characterisation of focal lesions in the liver and other solid organs. These contrast agents can also be used to study the microvasculature of the wall of the intestinal loops. Various histological studies have demonstrated that in diseased intestinal loops, neovascularisation occurs in the early stages of active disease, in the form of small vessels that can be assessed using contrast media5.

• Unlike those used in CT or MRI, so-called second-generation ultrasound contrast agents are completely intravascular and do not cross into the interstitium.

• Specific image contrast enhancement software must be installed on the ultrasound machine in order to visualise microbubbles after injection of the ultrasound contrast agent. The use of low mechanical indices prevents breakage of the microbubbles and facilitates the evaluation of the enhancement in real time over several minutes.

• We used SonoVue®, a second generation ultrasound contrast agent injected into a peripheral vein as a 2.4 ml bolus through a 20 G catheter, followed by the injection of 10 ml of normal saline (0.9% NaCl). Enhancement of the inflamed intestinal loop wall becomes visible about 15–20 seconds after injection of the contrast agent. The degree of enhancement can be assessed either subjectively or objectively using time-signal intensity curves, measuring enhancement in a region of interest (ROI) in the wall over a specific period of time (Fig. 3 and 4).

• Ultrasound contrast enhancement assesses parietal microvasculature while colour Doppler evaluates the macroscopic vessels. In addition, contrast agents have other advantages over colour Doppler: the analysis of time-signal intensity curves is more reproducible than the semiquantitative or subjective measurement of the number of vessels; it does not depend on the ultrasound device used and, lastly, motion artefacts caused by peristalsis or intestinal contents do not prevent the evaluation of parietal enhancement as is the case with colour Doppler6,7.

FIGURA 3. Imagen longitudinal ecográfica en modo B del íleon terminal.

CROHN’S DISEASE

Crohn’s disease (CD) is a chronic IBD characterised by alternating episodes of inflammatory activity and periods of remission. In order to plan treatment, symptomatic patients require repeated assessments of disease activity and intensity, as well as monitoring for transmural complications (abscesses, fistulas, stenoses) that may occur in the clinical course. CD is typically diagnosed in young adults and exhibits a chronic relapsing clinical course, so that where imaging techniques such as CT are used for monitoring purposes, patients are at a significant risk of cumulative exposure to ionising radiation over the course of their lives. The absence of radiation, high patient acceptance and availability make ultrasonography an attractive technique in the management of this disease. In our hospital, ultrasound is the standard technique used to assess patients with CD.

CD is an inflammatory process that affects all layers of the intestinal wall, often showing changes in perienteric tissues. As a result, cross-sectional imaging techniques play an important role in both the diagnosis and follow-up of CD. Along with the medical records, laboratory data and endoscopic data, ultrasound imaging, just like CT or MRI is helpful in establishing a sound initial diagnosis of CD. The information given by the radiologist allows the location, extension (detection of lesions not reachable by the endoscope), inflammatory activity and severity of the disease to be determined, in order to rule out penetrating or stenosing forms, or to monitor treatment effectiveness. This information is important to guide the therapeutic strategy and also has prognostic value. The report of an ultrasound examination performed in a patient with CD should include the presence or absence of ultrasound findings, allowing it to be classified into one of the subtypes defined by the Montreal classification, i.e. inflammatory, stenosing or fistulising. However, in clinical practice, more than one disease subtype may be observed in a given intestinal segment or in multiple adjacent segments in the same patient.

 

Diagnosis of Crohn’s disease

The findings published in the literature show that ultrasound is an accurate technique for the initial diagnosis of patients with suspected CD. A meta-analysis and a systematic review of the literature, which aimed to evaluate the accuracy of ultrasound in the detection of IBD, were recently published. In both studies, the technique was concluded to be appropriate to either confirm or rule out the diagnosis8,9. The diagnosis of CD relies primarily on the measurement of wall thickness. Based on the criterion of a wall thickness >3 mm, the published results are:  accuracy: 90–93%, sensitivity: 83–90%, and specificity: 95–99%. The best results were obtained in the detection of the disease in the ileum (Fig. 2) and the ascending or descending colon, while the lowest sensitivity was observed in relation to lesions located in the jejunum and in the rectum. Sensitivity also decreases in cases with initial mucous lesions or aphthoid ulcers, as these do not cause significant wall thickening. Several studies conducted with ultrasound contrast agents have shown that the presence of enhancement in the wall of intestinal segments with a wall thickness <3 mm increases sensitivity in the diagnosis of CD7,10.

CD affects the digestive tract in a discontinuous manner; thus, various segments may be affected, with areas of normal intestine between them. When evaluating the exact extent of involvement, namely via intestinal segments, ultrasound results are inferior, with a sensitivity and specificity of 83–88% and 93–95%, respectively, although there are no significant differences with respect to CT or MRI9. From a practical point of view, the detection of more or fewer segments does not generally affect the treatment plan. Nevertheless, it is advisable to perform MR-enterography studies in cases of extensive involvement, suspected lesions of the upper intestine, or when surgery is planned. Hydrosonography with the ingestion of large amounts (1.5 l) of nonabsorbable oral solutions or a hydrocolonic ultrasound with rectal enema can improve the results of ultrasound in detecting diseased segments2,11.

Involvement of the appendix in CD is observed in up to 21% of cases in surgical series. Simultaneous involvement of the terminal ileum is nearly always present, whereas caecum thickening is observed in only about 50% of cases. In our experience, the presence of a hyperaemic appendix is very common (73%), with no significant difference with respect to the percentage of cases with hyperaemia found in acute appendicitis12. In the Emergency Department, when a patient has right iliac fossa pain and thickening of the appendix on ultrasound, the signs suggestive of CD are:

• Involvement of other intestinal segments.

• Fibrofatty proliferation around the ileum.

• Marked and irregular thickening of the submucosal ileum, ileal parietal thickness
>5 mm.

• Hyperaemia in the terminal ileum (the presence of the latter two signs had a positive predictive value of 96% and a negative predictive value of 73% for the diagnosis of CD)12.

A hyperaemic appendix with no colour Doppler flow in the terminal ileum suggests acute appendicitis. Ultrasound findings in the caecum or the appendix overlap in both conditions, namely acute appendicitis and appendiceal involvement in CD, making them useless for differentiation.

 

Transmural complications

A characteristic feature of CD is the transmural extension of inflammation that gradually affects the entire intestinal wall. Transmural complications (fistulas or abscesses) occur in 20–40% of patients at some stage of disease13.

Cross-sectional imaging techniques, including ultrasound, do not usually detect mucosal changes caused by the disease. However, echogenic images produced by ulcers can sometimes be seen in the thickened wall; these are visible as dots or fixed and constant echogenic lines in the wall during peristalsis of the intestinal loop. Linear ulcers can penetrate deep into the wall to form sinus tracts or fissures, which are initially intramural but run the risk of spreading extramurally as hypoechoic tracts outside the serosa in the tissue adjacent to the inflamed loops (Fig. 5 and Fig. 6)14. Fissures may end abruptly in the mesentery (blind fissures) or form an inflammatory mass. The differentiation between a fissure and a fistula is merely academic, since these display the same biological behaviour. The term fistula implies communication between organs covered by epithelium or skin; fistulas may occur between loops, especially the ileum and caecum (enteroenteral) (Fig. 5 and Fig. 6) or involve adjacent structures, such as the bladder (enterovesical) (Video 1), abdominal wall (enterocutaneous) or psoas muscle (retroperitoneal). When fissures or fistulas contain gas bubbles, they are identified as echogenic lines in the mesenteric fat.

FIGURA 5. Afectación transmural en paciente con EC.

According to the review by Panés et al., the accuracy of ultrasound imaging in detecting fistulas has been evaluated in four studies that found a sensitivity of 67–87% and a specificity of 90–100%, concluding that ultrasound is highly sensitive and specific, with no significant differences in relation to CT or MRI9. In a recent study conducted in our hospital that compared ultrasound and surgical findings, the former showed a sensitivity and specificity of 91 and 100%, respectively15.

As a consequence of “covered perforations” caused by fissures or fistulas, poorly defined inflammatory masses or phlegmons develop in the mesentery adjacent to the intestinal loop, which may contain fluid collections or abscesses. The distinction between phlegmon and abscess has important implications for patient management, as abscesses may require percutaneous or surgical drainage, while phlegmons usually respond to medical treatment. On an ultrasound, phlegmons appear as ill-defined hypoechoic masses, and abscesses appear as well-defined, thick-walled hypoechoic or cystic collections with a complex inner content that may feature echogenic areas due to the presence of gas. Abscesses that contain a lot of gas are hard to detect. The use of colour Doppler helps to differentiate these, as phlegmons exhibit internal flow whereas no internal flow is detected in abscesses, only vessels in the periphery of the mass. However, in daily clinical practice, if no gas or liquid is visible within a well-defined collection, it can be difficult to differentiate them.

According to the review by Panés et al.9, ultrasound has a high sensitivity of 81–100% for detecting abscesses, and a specificity of 92–94%. The deep pelvis is the most difficult area to evaluate, unless a vaginal transducer is used. In the study by Maconi et al.16, while ultrasound and CT correctly detected the presence of abscesses in a high percentage of cases, the former was less accurate, yielding a higher number of false positives. The use of ultrasound contrast agents is extremely useful to differentiate between phlegmons and abscesses, with a safety similar to that of CT or MRI and, therefore, helps avoid false ultrasound-based abscess diagnoses. Injection of ultrasound contrast enhances the inflammatory mass if it is a phlegmon; conversely, with abscesses there is no signal, with enhancement of the adjacent peripheral tissue (Fig. 7 and Fig 8). In addition, the contrast agent allows better definition of abscess size, which can be important in deciding whether or not the collection should be drained17.

FIGURA 7. Absceso en paciente con EC.

Stenosis

Stenosis occur in 12–54% of patients with CD and are associated with increased morbidity and decreased quality of life. In cases of obstruction, the stenotic segment is seen as an area with wall thickening and a central narrowed intestinal lumen, which is fixed and echogenic, accompanied by dilatation and hyperperistalsis of the proximal loops (Fig. 9 and Fig. 10). The sensitivity of ultrasound imaging in the diagnosis of CD stenoses is of 74–100%, with a specificity of 89–93%. Higher-grade stenoses are easier to evaluate9. However, ultrasound is not a suitable technique for ruling out asymptomatic stenoses before capsule endoscopy, as its sensitivity in detecting low-grade stenosis is lower than for high-grade stenosis. CT or MRI studies such as CT or MR enterography to evaluate the intestine are conducted after giving the patient 1–1.5 l of an oral contrast agent to distend the intestinal lumen, which facilitates the detection of the affected intestinal segments and helps to differentiate those with a low-grade stenosis from those in which the intestinal lumen is distended. However, ultrasound examination is performed fasting and with no oral contrast agent, for which reason it is not always possible to distinguish whether an area with wall thickening also has a stenosed lumen. The use of an oral contrast agent significantly improves the sensitivity of the technique for the diagnosis of low-grade stenosis11,18.

FIGURA 9. Estenosis inflamatoria en paciente con EC.

When obstruction is clinically suspected in a patient with CD, a CT scan is usually performed, especially in Emergency settings. However, while the sensitivity of ultrasound imaging in the diagnosis of intestinal obstruction is >85%, where obstruction is suspected, a preliminary ultrasound should be performed19, taking into account that the assessment of the inner diameter of the intestinal loops does not

require a great deal of experience (Video 2).
CT scans ordered by non-specialist doctors in an Emergency Department and/or carried out by radiologists with no experience in ultrasound are one of the main contributors to irradiation in CD patients20.

In the event of obstruction, it is important to determine whether the stenosis is predominantly inflammatory or fibrotic (scar tissue), as the former responds to medical treatment while the latter may require surgery or endoscopic dilation. Although colonoscopy is considered the gold standard to assess stenosis, this technique only provides information on the mucosa; in many cases, it cannot reach the stenotic area when located in the small intestine. Colour Doppler ultrasound, especially when used with an echo signal enhancer (first-generation ultrasound contrast agents), helps to differentiate between hypervascular inflammatory stenoses and poorly vascularised fibrotic stenoses21. The injection of second-generation ultrasound contrast agents has shown inflammatory stenoses to exhibit intense parietal enhancement, which can also be measured by the quantitative analysis of mural signal intensity curves (Fig. 9 and Fig. 10). In a study that analysed various ultrasound parameters in order to evaluate mural inflammation, using a histological analysis of the specimen as the reference technique, it was shown that after injection of a contrast agent, wall enhancement was significantly greater in inflamed stenotic segments than in fibrotic segments15. Other signs associated with inflammation included the presence of fistulas or abscesses, or hyperaemia on colour Doppler. However, as reported in recent articles, in many cases, histopathological examination of the resected part of the stenotic segment shows a combination of inflammation and fibrosis, making differential diagnosis nearly impossible. In summary, the absence of signs of inflammation in the stenosis always indicates fibrosis; however, the presence of signs of inflammation does not rule out the presence of fibrosis associated with inflammation.

 

Evaluation of inflammatory disease activity

CD is characterised by a chronic recurrent course, for which reason an appropriate therapeutic approach requires periodic evaluations of inflammatory activity. This can be done based on clinical or laboratory tests, or macroscopic data, measured either by endoscopy or imaging tests.

If we review the literature, the relationship between parietal vascularisation evaluated using colour Doppler and inflammatory activity is controversial. Several studies have shown a significant correlation between vascularisation of the intestinal wall and either clinical activity measured using the Crohn’s disease activity index (CDAI)22, or physiological function as measured by serum C-reactive protein (CRP) levels. In our experience23, which is consistent with that of other authors24, hyperaemia is a common finding in patients with a high CDAI score (sensitivity >93%) or elevated CRP, although many asymptomatic patients also have hyperaemia (poor specificity: about 45%). On the other hand, this is not surprising, since clinical activity indices are primarily based on the patient’s symptoms, which do not necessarily reflect the same things as ultrasound abnormalities, or endoscopic or histological findings.

Inflammatory activity can also be evaluated by measuring speed or flow in the superior mesenteric artery (SMA) or inferior mesenteric artery (IMA) via Doppler ultrasound, based on the fact that neovascularisation of the inflamed wall causes an increased flow in the mesenteric arteries and veins25,26. The results are also disputed; in addition, Doppler ultrasound of the mesenteric vessels is a long, technically difficult examination with a high failure rate, for which reason it is not routinely used in the evaluation of CD patients.

There is a better consensus in the literature on the correlation between ultrasound parameters and endoscopic or histological activity. Wall thickness, the colour Doppler grade and parietal enhancement after injection of the contrast agent are all parameters that exhibit a significant positive correlation with the degree of endoscopic activity. The presence of transmural complications, fistulas or abscesses also indicates inflammatory activity. According to Panés et al.9, based on six reviewed studies in the literature, the sensitivity of ultrasound for the detection of disease activity was 63–100% (total 85%), with a specificity of 77–100% (total 91%). The study by Neye et al.4 found a high concordance between the colour Doppler evaluation of the parietal and the degree of activity observed on ileocolonoscopy, with a precise correlation of the degree of activity in 67% of segments, and a difference of only one degree in 31% of segments. The best results were obtained in the descending colon.

A correlation has been shown between the degree of hyperaemia determined via colour Doppler and the degree of enhancement determined via an ultrasound contrast agent27. A high correlation was also confirmed between the degree of ultrasound enhancement and gadolinium uptake on MRI28, indicating that both techniques objectively measure the increase in microvessels in the inflamed intestinal wall.

Several studies have shown a higher correlation between the CDAI score and enhancement in the intestinal loop after injection of the contrast agent than with the degree of hyperaemia measured by colour Doppler 29,30.

A recent study30 found that the enhancement pattern of the intestinal loop wall after injection of the ultrasound contrast agent allowed active and inactive patients to be differentiated based on their CDAI score. It considered patients as active in the presence of intense enhancement, observed as complete wall enhancement or the enhancement of the inner layers (mucosa and submucosa). A sensitivity and specificity of 81% and 63%, respectively, was obtained in distinguishing between active and inactive disease. In the study by Migaleddu et al.31, contrast-enhanced ultrasound showed better results in detecting endoscopic activity than either wall thickness or the degree of hyperaemia, with a sensitivity and specificity of 93.5 and 93.7%, respectively.

The quantitative evaluation of intestinal wall enhancement based on the analysis of time-signal intensity curves is more objective. A significant correlation was observed between these measures and endoscopic inflammatory activity (Fig. 3 and Fig. 4). In the study by Franco et al.32, peak enhancement intensity in the ileum showed a sensitivity of 97% and a specificity of 83% in differentiating patients with active disease, demonstrating that measuring enhancement allows inflammatory activity to be predicted and quantified. In a study conducted in our centre33 with 65 patients, parietal enhancement in patients with moderate or severe endoscopic activity was significantly greater than in patients with mild or absent endoscopic activity. Using a cut-off value of 46% of the increase in signal intensity, a sensitivity of 96% and specificity of 73% were obtained for the detection of moderate or severe endoscopic activity (Fig. 3 and Fig. 4). Contrast enhancement is significantly better at predicting endoscopic severity (90% accuracy) than the other two ultrasound variables, namely, wall thickness (79%) or the degree of hyperaemia on colour Doppler ultrasound (69%), which is consistent with the results of previous studies conducted with MRI or CT34.

 

Medical treatment monitoring

For the evaluation of the response to medical treatment, the same patient should be monitored frequently; therefore, the follow-up technique should be non-invasive, not use ionising radiation and, most of all, be well tolerated by the patient. Ultrasound meets all these requirements, as it can reduce the use of other invasive techniques or those involving ionising radiation.

There is ample evidence in the literature that there are asymptomatic patients in whom endoscopy confirms inflammatory activity. On the other hand, the number of CD patients with typical symptoms such as diarrhoea or abdominal pain in the context of quiescent disease is high. In addition, a substantial number of patients who initially respond to biologics lose their response over time. In the study by Hirsch et al.35, ultrasound was routinely performed in 255 patients with CD, revealing transmural complications in 18%, 37% of whom were asymptomatic with CDAI < 150. This data highlights the importance of monitoring treatment effectiveness using imaging techniques.

Conventional treatment approaches do not modify the natural course of the disease, which often progresses from inflammatory to stenosing and/or fistulising forms. The aim of traditional medical treatments over the years has been to control patient symptoms. Relapses and treatment changes have been evaluated with clinical signs such as diarrhoea, abdominal pain, the patient’s general condition or extraintestinal manifestations. Several studies have used ultrasound to evaluate the response to medical treatment, detecting a reduction in both thickness and Doppler flow in patients with good response36,37. However, most of these studies showed no significant correlation between medical response evaluated using CDAI or CRP and ultrasound changes. Relapses in cases with a favourable clinical response have been attributed to the persistence of inflammatory activity despite good progress with symptom relief.

Residual hyperaemia evaluated by colour Doppler or contrast-enhanced ultrasound has been shown to identify patients with incomplete histological remission, reflecting subclinical inflammation with an increased susceptibility to relapse29,37. Patients with quiescent disease after medical treatment in whom hyperaemia or parietal enhancement persists after the injection of an ultrasound contrast agent are at a greater risk for clinical relapse or requiring surgery in the medium term. These facts may have implications for treatment: subjects in clinical remission with persistent hyperaemia should be monitored more closely or maintain a longer treatment course, while the absence of hyperaemia would reinforce the decision to either reduce or discontinue treatment, as well as the need for a less intensive follow-up, thus reducing  costs.

The introduction of anti-tumour necrosis factor (anti-TNF) therapy in the management of CD is changing the natural course of disease; these therapies not only reduce disease activity, but also the rate of long-term complications. After the introduction of immunomodulators (azathioprine, and methotrexate) and, especially, biologics (anti-TNF monoclonal antibodies), endoscopic mucosal healing was proposed as a treatment goal, as it is associated with lower rates of hospitalisation and surgery38.

Endoscopic examination is invasive and uncomfortable, for which reason most patients are unaccepting of repeat examinations. In addition, it cannot be used to assess proximal segments of the small intestine. It is also unclear whether mucosal healing is synonymous with transmural healing of the intestinal wall.

In a study conducted in our hospital in which response to anti-TNF therapy was evaluated using Doppler ultrasound in 24 patients, a decrease in wall thickness, in the degree of vascularisation and in transmural complications was observed, with a significant correlation between these changes and the clinical response39. Only patients with partial response or remission showed improvement on ultrasound. Transmural healing was observed with normalisation of ultrasound findings (both thickness and parietal hyperaemia) in eight (47%) of 17 patients with response/remission versus none of the patients with no clinical response (Fig. 11). Over the following year, there were significant differences in clinical course (surgery, dose increase or change of anti-TNF) between patients with ultrasound improvement and those with no improvement (25% vs 92%), and between patients who showed ultrasound normalisation and those in whom ultrasound findings persisted (12% vs 81%).

FIGURA 11. Ecografía en la monitorización del tratamiento con antiTNF.

After two years of treatment in a study of 133 patients, 66 of whom were treated with immunosuppressants and 67 with anti-TNF, Castiglione et al.40 observed mucosal healing in 42 patients and transmural healing evaluated by intestinal ultrasound in 20 patients. The study showed a good agreement between mucosal and transmural healing (k = 0.63), with mucosal healing being observed in 18 of the 20 patients with transmural healing. This study showed little agreement between clinical remission and mucosal (k = 0.34) or transmural healing (k = 0.27).

Quantitative techniques in contrast-enhanced ultrasound can measure changes in mural enhancement, which reflect the response to therapy in the follow-up of inflammatory disease. A significant reduction in enhancement has been demonstrated in patients with a clinical response to biological treatments41. However, there are currently no studies demonstrating that this evaluation adds to the information obtained by colour Doppler.

 

ULCERATIVE COLITIS

Ulcerative colitis (UC) is always restricted to the colon, with continuous involvement from the rectum to the proximal colon, making it easy to assess via colonoscopy. in addition, the disease affects only the superficial layers; as a result, ultrasound is far less useful in UC than in CD. The sensitivity of ultrasound in diagnosing initial changes is low, as these are below its spatial resolution threshold. In later stages, mural thickening can be detected, allowing adequate assessment of the extent and severity of disease. Wall thickening is concentric, continuous and, except in very severe cases, less pronounced than in CD. While there may be thickening of the surface layers (mucosa and submucosa), the muscularis, serosa and pericolic fat are not affected, and the layer structure is always retained. Nor are there transmural complications such as fistulas or abscesses. Although parietal hyperaemia is observed in the most severe cases of colitis, to date, no studies have examined the relationship between the degree of vascularisation on colour Doppler and the inflammatory activity in UC. Several studies have found a correlation between inflammatory activity in the left colon and an increased flow in the LMA measured by Doppler ultrasound26.

Differentiation between UC and CD is based more on the pattern of distribution of the disease (continuous vs discontinuous) and/or involvement of the terminal ileum than on ultrasound imaging, as there is a fair amount of overlap between the two diseases.

In UC, the role of ultrasound is to evaluate the extension of disease in cases of incomplete colonoscopy, and to support the differential diagnosis in cases of indeterminate colitis. It can also serve an alternative to colonoscopy during disease relapses, in order to assess their extent and severity. By contrast, ultrasound is of no use to evaluate the colon when toxic megacolon or the complications thereof are suspected.

 

CONCLUSIONS

• The above-mentioned data justifies the use of ultrasound as first-line technique for the assessment of patients with CD, whether for routine monitoring or for evaluation when a flare-up occurs.

• Ultrasound has advantages over CT as it does not use ionising radiation and is noninvasive, and over MRI because it is more accessible and less expensive, because scanning time is shorter and, above all, because it is very well tolerated by patients, allowing for repeat examinations during follow-up.

• Ultrasound could be used as a substitute for endoscopy in the evaluation of transmural healing, as the accessibility of the technique allows for frequent monitoring while facilitating quick treatment adjustments.

 

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