Crohn disease is not a distinct histopathologic entity.

Although described and named after its author in 1932, Crohn disease was not clinically, histologically, or radiographically distinguished from ulcerative colitis until 1959. Currently, the diagnosis of Crohn disease entails an analysis of clinical, radiologic, endoscopic, pathologic, and stool specimen results. Contrast-enhanced radiography is used to localize the extent, severity, and contiguity of disease; CT scanning provides cross-sectional images for assessing mural and extramural involvement; endoscopy enables direct visualization of the mucosa and provides the ability to obtain a biopsy specimen for histopathologic correlation; and ultrasonography and MRI are adjuncts that provide alternative cross-sectional images in populations in whom radiation exposure is a concern. For excellent patient education resources, visit eMedicineHealth's Digestive Disorders Center. Also, see eMedicineHealth's patient education articles, Inflammatory Bowel Disease, Crohn Disease, and Crohn Disease FAQs. Examples of Crohn disease are provided in the images below.

Crohn disease. Aphthous ulcers. Double-contrast barium enema examination

in Crohn colitis demonstrates numerous aphthous ulcers. Crohn disease of the terminal ileum with CT and sonographic correlation. Small-bowel followthrough study demonstrates the string sign in the terminal ileum. Also note pseudodiverticula of the antimesenteric wall of the terminal ileum, secondary to greater distensibility of this

less-involved segment of the wall. Crohn disease of the terminal ileum with CT and sonographic correlation. Note terminal ileal-wall thickening and

adjacent mesenteric inflammatory stranding. Crohn disease. Mesenteric inflammation. CT scan demonstrates inflammatory mass in the right lower quadrant associated with thickening of the wall and narrowing of the lumen of the terminal

ileum. Crohn disease. Crohn colitis. Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right

colon. Crohn disease. MRI with CT correlation. MRI demonstrates thickening of the wall of the right colon with intramural increased signal on a T1-weighted image. This was believed to represent intramural fat deposition.

Pathophysiology
The etiology of Crohn disease is largely unknown. Genetic, infectious, immunologic, and psychological factors have all been implicated in influencing the development of the disease. The disease is characterized by chronic inflammation extending through all layers of the intestinal wall and involving mesentery as well as regional lymph nodes. Early mucosal involvement consists of longitudinal and transverse aphthous ulcerations, which are responsible for a cobblestone appearance. As the disease progress, deep fissures, sinuses, and fistulae develop. Eventually, communication between diseased bowel segments, the abdominal wall, retroperitoneal structures, and the urinary tract occurs. Because of the transmural nature of the disease, mesenteric and perianal manifestations are fairly common. Because of the inflammation, strictures resulting from edema, inflammation, and, ultimately fibrosis and scaring, are frequent. Crohn disease is pervasive. The basic pathologic process of disease can occur at any segment of the alimentary tract.

Crohn disease and ulcerative colitis share similar inflammatory changes. Cryptitis and subsequent crypt abscesses consisting of polymorphonuclear cells are identical for both diseases. However, during the inflammatory flare-ups, Crohn disease involves increases in the number of cells containing immunoglobulin G2 (IgG2) and ulcerative colitis involves a predominant increase in immunoglobulin G1 (IgG1) and immunoglobulin G3 (IgG3) cell types. The inflammatory infiltrate of the lamina propria in Crohn disease leads to loose aggregations of macrophages, and they organize into noncaseating granulomas, which involve all layers of the bowel wall from mucosa to serosa. Occasionally, they can be seen on laparoscopy as miliary nodules, and they function as contiguous spread of the disease from the intestine. With chronic inflammation, the bowel walls become thickened, fibrotic, and stenotic in Crohn disease, and an extension of inflammation and fistula formation often occurs as a result of a transmural fissure. In ulcerative colitis, hemorrhagic and ulcerative inflammation is mostly limited to the mucosa, with recurrence leading to atrophic mucosa. Ulcers often have irregular borders, giving rise to a collar-stud effect. In recurrent disease, inflammatory polyps develop from exuberant epithelial regeneration. When inflammation infiltrate extends into the submucosa and muscularis propria, it does so in a diffuse pattern, in contrast to Crohn disease, in which they appear as lymphoid aggregates. Why Crohn disease has a skip-distribution as opposed to that seen in ulcerative colitis is uncertain.

Epidemiology
Findings from studies in the United States and Western Europe indicate that the incidence of Crohn disease is 2 cases per 100,000 population. The prevalence is estimated to be 20-40 cases per 100,000 population. Recent data show that at least in Europe, rates in Southern European countries are catching up to those of their northern neighbors. Approximately 15% of the cases of Crohn disease appear in persons older than 50 years. The relative risk for adenocarcinoma of the ileum is at least 100-fold greater in Crohn disease patients compared with age- and sex-matched controls. Small-bowel cancers typically arise at sites of macroscopic disease after mean age of 18 years.

Mortality and morbidity

Crohn disease is associated with higher rate of mortality, as compared with that of the general population, independent of GI tract involvement. The excess mortality is most pronounced in the first few years after diagnosis. This observation has been attributed to complications of Crohn disease, which include abscesses, fistulas, intestinal obstructions and perforations, and colorectal cancer. Approximately 15% of the cases of Crohn disease appear in persons older than 50 years. In the older population, Crohn disease tends to involve the colon, and more obstructive and inflammatory complications tend to develop. However, despite this fact, older patients have been shown to tolerate medical and surgical therapy as well as young patients.

Abscesses develop in approximately 15-20% of patients with Crohn disease as a result of sinus track formation or as a complication of surgery. Abscesses can be found in the mesentery, peritoneal cavity, or retroperitoneum or in an extraperitoneal location. The most common sites of retroperitoneal abscesses are the ischiorectal fossa, the presacral space, and the iliopsoas region. The terminal ileum is the most common site of origin of abscesses. It is one of leading causes of mortality in Crohn disease. Obstruction occurs in 20-30% of patients during the course of the disease. Early in the disease, it appears as reversible intermittent postprandial obstruction due to edema and bowel spasm. Over several years, this persistent inflammation gradually progresses to fibrostenotic narrowing and stricture, which may require regional resection. Fistula formation is a frequent complication of Crohn disease of the colon. Fistulas can be categorized into 3 groups: benign, nuisance, and intractable. Benign fistulas are simple and include ileoileal, ileocecal, and ileosigmoid fistulas, which might produce only mild or moderate diarrhea. They may even remain asymptomatic for years without any treatment. Nuisance fistulas must be closed because of annoying symptoms and troublesome pathophysiologic consequences, but neither the complications nor the underlying bowel disease is severe enough to require surgery. This intermediate group includes enterovesicular, enterocutaneous, cologastric, and coloduodenal fistulas. Complicated fistulas with abscesses or severe underlying bowel disease (either ulcerating inflammation or distal obstruction) are the most difficult to manage. They occur in 50% of patients with Crohn disease. The role of medical therapy is simply to control the obstructing, inflammatory, or suppurative processes before definitive surgery is performed. The goal of the operation is evacuation of the abscess and, if not contraindicated by associated sepsis, resection of the diseased bowel. This form of fistula leads to spontaneous intestinal perforation in 1-2% of patients. GI cancer has been the leading cause of mortality in Crohn disease. Adenocarcinoma usually arises in areas of chronic disease. The cancer risk is higher in both the small intestine and the colon, as compared with that of general population. The relative risk for adenocarcinoma of the ileum is at least 100-fold greater in age- and sex-matched controls. Small-bowel cancers typically arise at sites of macroscopic disease after mean age of 18 years. Unfortunately, most cancers related to Crohn disease are not detected until advanced stages, and the patients have poor prognoses. Mounting evidence from studies indicates that Crohn disease is associated a cancer risk equal to that of ulcerative colitis. Some extraintestinal cancers (eg, squamous cell cancer in patients with chronic perianal, vulvar, or rectal disease) and Hodgkin or non-Hodgkin lymphomas have also been shown to be more common in patients with Crohn disease.

Preferred Examination
The preferred examinations are plain radiography, double-contrast barium enema examination, single-contrast upper GI series with small-bowel follow-though or enteroclysis with CT, and double-contrast evaluation of the small bowel. Ultrasonography and MRI can be used as adjuncts if radiation exposure is an issue in monitoring disease activity.[1, 2, 3]

In general, the clinician should select CT first in evaluation of Crohn disease. CT has is not as sensitive in delineating fissure or fistula as barium studies, but it is superior to barium studies in showing the extraluminal sequelae of Crohn disease. Residual contrast material from barium studies leads to severe streak artifact on CT scans due to hyperattenuating contrast suspension used in barium studies. On the other hand, CT contrast residue does not preclude a barium study. Barium contrast studies are limited in the evaluation of transluminal inflammation in Crohn disease; distention of small bowel with contrast material is required for proper evaluation. Slow passage of the contrast agent through the pylorus can result in nonvisualization of small-bowel lesions in small bowel series. Enteroclysis is one way to circumvent the dilemma by passing a catheter to the duodenal jejunal junction. Abdominal radiographic findings are not specific for Crohn disease. Radiography is useful in evaluation of bowel-loop distention and pneumoperitoneum. Sonographic findings have high variability because of operator dependence in detection of the bowel-wall changes seen in Crohn disease. Transmission of ultrasound waves through fatty tissues is limited, and detection may be severely limited by the patient's body habitus. Traditionally, MRI was limited in the evaluation of the abdomen and pelvis because of motion artifact. With stronger gradients, breath-hold imaging, and faster sequences, MRI of the abdomen and pelvis can be readily performed in most patients. It is currently actively used in routine assessment of pelvis fistulae and sinus tracks. In many medical centers, MRI enterography and enteroclysis are actively used in surveillance of small bowel disease and extraluminal mesenteric disease. MRI is an attractive alternative to traditional fluoroscopy and CT scanning, especially in pediatric population in which long-term radiation exposure is a concern.

CT-guided therapy
CT has become the procedure of choice not only in diagnosing Crohn disease but also in managing abscesses. A growing body of literature shows that CT-guided percutaneous abscess drainage may obviate surgery. In studies, CT percutaneous abscess drainage has shown great success either as a temporizing measure or as definitive therapy with a decreased rate of recurrence, as compared with that of surgery. Because about 70-90% of patients with regional enteritis eventually require surgery, avoiding an operation to treat an abscess is a tangible benefit of CT.[4]

Complications and contraindications

The oral administration of contrast material is to be avoided when moderate- or high-grade colonic obstruction is present. Double-contrast (air contrast) barium enema examination is contraindicated in patients with severe colitis, because injection of air with contrast agent may precipitate toxic megacolon or colonic perforation. Barium studies are contraindicated when there are signs and symptoms of peritonitis or when there are radiographic signs of gas in the bowel wall or pneumoperitoneum.[5] The intravenous injection of contrast material for CT studies should be avoided when chronic renal insufficiency is present, when there is continued use of Glucophage, or when there are signs and symptoms of acute renal failure. CT and barium studies use ionizing radiation,

which may result in considerable radiation burden. This exposure is a relative contraindication in pregnancy and childhood. Sonography and MRI may prove to be useful alternative imaging modalities.

Radiography
The role of plain radiography with barium studies in Crohn disease is fairly limited. The 2 major purposes that it serves are (1) to assess the presence of intestinal obstruction and (2) to evaluate pneumoperitoneum prior to further radiological workup. Additional extraintestinal findings of sacroiliitis or oxalate kidney stones may be present. These further support the diagnosis of Crohn disease.

Crohn disease versus ulcerative colitis

Double-contrast barium enema study is useful for diagnosing inflammatory bowel disease and for differentiating Crohn disease from ulcerative colitis, especially in the early phase of the disease. On double-contrast studies, early Crohn disease is characterized by discrete aphthoid ulcers, which are seen as punctate or slitlike collections of barium surrounded by radiolucent mounds of edema. The aphthoid ulcers are often separated by normal bowel and present as skip lesions. On the contrary, ulcerative colitis extends proximally at various degrees from the rectum as a continuous area of disease that eventually leads to pancolitis. Early ulcerative colitis is characterized by a granular appearance on double-contrast examination as a result of edema and hyperemia of the mucosa. Thus, the 2 diseases can be differentiated on basis of radiographic findings.[6] In a comparison of 23 patients with ulcerative colitis with 27 patients with Crohn disease, Laufer et al established the differentiating features the conditions using barium study. They found that ulcerative colitis involves granular mucosa, diffuse rectal involvement, and continuous inflammatory changes in the bowel with sparing of the terminal ileum. Crohn disease involves patchy rectal involvement with punched-out ulcers, ulcers on normal mucosa, and discontinuous bowel inflammation typically with involvement of the terminal ileum. These criteria are distinguishing in 95% of patients. The difficulty in differentiating the 2 illnesses occurs at later chronic stages, during which numerous remissions and exacerbations can result in discontinuous ulcerative colitis. Despite this difficulty, careful examination of the mucosal surface with barium study enables the distinction.[6]

Aphthoid ulcers
Aphthoid ulcers, as shown in the image below, are detected on barium studies in 25-50% of patients with Crohn disease. These are identified in as many as 75% of surgical specimens with Crohn disease. Endoscopy is slightly superior to barium studies in the demonstration of isolated or a few aphthoid ulcers.

Crohn disease. Aphthous ulcers. Double-contrast barium enema examination in Crohn colitis demonstrates numerous aphthous ulcers.

Severe Crohn disease

As more severe Crohn disease develops, the small ulcers become enlarged and deeper, and they connect to one another, forming stellate, serpiginous, and linear ulcers. These ulcers are found most frequently in terminal ileum along the mesenteric border. These are pathognomonic of Crohn disease. On small-bowel series or enteroclysis, a mesenteric border ulcer appears as a long 1- to 2-mm barium collection that parallels a short, straight mesenteric border. A radiolucent collar usually parallels the linear barium collection at the margin of the ulcer. The antimesenteric border of the bowel is usually uninvolved and pulled into the ulcer collar, creating radiating folds.

Cobblestoning
As inflammation penetrates the submucosa and muscularis layers, deep knifelike linear clefts form the basis of "cobblestoning" and fissure or fistula formation. They appear as a bariumfilled reticular network of grooves that surround round or ovoid radiolucent islands of mucosa. Eventually, transmural inflammation leads to decreased luminal diameter and limited distensibility. This leads to a radiographic string sign that represents long areas of circumferential inflammation and fibrosis resulting in long segments of luminal narrowing. See the images below.

Crohn disease. Cobblestoning. Spot view of the terminal ileum from a small-bowel follow-through study demonstrates linear longitudinal and transverse ulcerations that create a cobblestone appearance. Also note the relatively greater involvement of the mesenteric side of the terminal ileum and the displacement of the involved loop away from the normal small bowel secondary to mesenteric inflammation and

fibrofatty proliferation. Crohn disease. Spot view of the terminal ileum from a small-bowel follow-through study demonstrates several narrowing and stricturing, consistent with the string sign. Also note a sinus tract originating from the medial wall of the terminal ileum and the involvement of the medial wall of the cecum.

Enlarged villi
Chronic inflammation in the lamina propria of the small intestine results in enlarged villi radiographically manifested as 0.5- to 2-mm, round or polygonal nodules. This fine mucosal nodularity occurs in the small intestine and should not be confused with the mucosal granularity seen in the colon of patients with ulcerative colitis.

Limitations
Mucosal nodularity or granularity in a small-bowel series is a nonspecific finding that can be seen in diseases that infiltrate or inflame the lamina propria, such as amyloidosis or radiation enteritis. Small-bowel follow-though examination is limited by the speed of barium passage through the pylorus. If too slow, incomplete distention in the lumen of the bowel can cause short skip lesions, masses, or obstructing lesions in the small bowel to be missed. Additional barium studies images of Crohn disease are shown below.

Crohn disease. Crohn colitis. Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon.

Crohn disease. Single-contrast barium enema study demonstrates stricturing of

the caput cecum, the so-called coned cecum. Crohn disease. Enterocolic fistula. Double-contrast barium enema study demonstrates multiple fistulous tracts between the terminal ileum and the right colon adjacent to the ileocecal valve, the so-called double-

tracking of the ileocecal valve. Crohn disease. Small-bowel follow-through study demonstrates narrowing of the lumen and multiple enteroenteric

fistulae, but it fails to show the enterovesical fistula. Crohn disease. Cystogram demonstrates a filling defect and inflammatory changes of the dome of the bladder, but it fails to demonstrate the enterovesical fistula.

In general, 18-20% of findings are false-negative on barium study, as compared with endoscopic detection. However, barium enema has a 95% accuracy rate in distinguishing Crohn disease from ulcerative colitis.

Computed Tomography
The role of CT in the evaluation of Crohn disease is well accepted. The ability of CT to depict bowel involvement and extraluminal pathology (eg, abscess, obstruction, fistula) makes it an essential imaging tool for patient care. The earliest CT finding of Crohn disease is bowel wall thickening, which usually involves the distal small bowel and colon, although any segment of the GI tract can be affected. Typically, the luminal thickening is 5-15 mm.[7, 8,
9, 10]

CT should be the first radiologic procedure performed in patients with acute symptoms and suspected or known Crohn disease. The ability to directly demonstrate the bowel wall, adjacent abdominal organs, mesentery, and retroperitoneum makes CT superior to barium studies in diagnosing the complications of Crohn disease. CT directly demonstrates bowel wall thickening, mesenteric edema, and lymphadenopathy, as well as phlegmon and abscess. See the images below.

Crohn disease of the terminal ileum with CT and sonographic correlation. Small-bowel follow-through study demonstrates the string sign in the terminal ileum. Also note pseudodiverticula of the antimesenteric wall of the terminal ileum, secondary to greater distensibility of this less-involved segment of the wall.

Crohn disease of the terminal ileum with CT and sonographic correlation. Note terminal ileal-wall thickening and adjacent mesenteric inflammatory

stranding. Crohn disease. Active small-bowel inflammation. CT scan demonstrates small-bowel wall thickening, mesenteric inflammatory stranding, and

mesenteric adenopathy. Crohn disease. Mesenteric inflammation. CT scan demonstrates inflammatory mass in the right lower quadrant associated with thickening of the wall and narrowing of the lumen of the terminal ileum. Although barium is more sensitive in demonstrating the presence of fissures and fistulas, CT is superior in demonstrating the sequelae of these tracks (eg, air in the urinary bladder in enterovesical fistula). The sensitivity of CT for Crohn disease is estimated to be 71%, with lower detection of early mucosal disease as compared with barium studies. A recent study by Philpotts et al has shown that the CT findings of Crohn disease considerably overlap with those of infectious, radiation, ulcerative, and ischemic colitides.[11] Certain distinguishing features have been cited in delineating Crohn disease from other forms of enterocolitis, including differences in wall thickness and attenuation; the distribution of colonic wall involvement; and the presence or absence of abscesses, fistulas, small-bowel disease, and mesenteric fibrofatty proliferation. In using the mentioned features, CT can attain positive predictive value above 90% and a diagnostic accuracy as high as 93%.[11] See the image below.

Crohn disease. Fibrofatty proliferation. CT scan in a patient with Crohn colitis in the chronic phase demonstrates wall thickening of the right colon, an absence of adjacent mesenteric inflammatory stranding, and a large amount of fatty proliferation around the right colon separating the colon from the remainder of the gut, socalled creeping fat. The introduction of multidetector-row CT scanners with thinner collimation and faster intravenous injections of contrast material have allowed more detailed evaluation of the bowel. The enhancement of the bowel wall after intravenous contrast enhancement is correlated with the enlargement of the feeding vessel and hyperemia during active disease. In an article by Del Campo et al, patients with active disease had a bowel wall attenuation of 95 HU, as compared with 65 HU in patients with disease in remission.[12] The ability to measure bowel wall enhancement may prove valuable in treating patients with Crohn disease. One limitation of CT has been in the area of delineating active versus inactive disease. The presence of mesenteric stranding does not reliably signify active disease because residual mesenteric thickening can remain during remission.

Ulcerations
Ulcerations in the mucosa can be detected on thin-section CT, although small-bowel series or enteroclysis is more sensitive to the early mucosal changes of Crohn disease. In addition, mesenteric stranding, increase in mesenteric fat, local adenopathy, fistula, and abscess are readily and commonly identified on CT scans.

Hazy fat
Edema or mild inflammation of the mesenteric fat results in fat of increased attenuation, the so-called hazy fat on CT. Greater inflammation or fibrosis of fat results on CT in attenuating linear bands of soft tissue coursing through the mesentery. On CT, an ill-defined inflamed mass of mixed attenuation may represent a phlegmon or early abscess formation. Enlarged lymph nodes are usually seen in proximity to the bowel wall along the mesenteric course of the vascular bundle. See the image below.

Crohn disease. Mesenteric inflammation. CT scan demonstrates an inflammatory mass in the right lower quadrant associated with thickening of the wall and narrowing of the lumen of the terminal ileum.

Abscesses
On CT scans, abscesses appear as well-defined, round or oval masses of fluid attenuation, and they are often multilocular. Pockets or bubbles of gas usually result from fistulous communication with bowel or, less likely, from infection by gas-producing organisms.

Crohn disease versus ulcerative colitis

There is considerable overlap between CT findings of ulcerative colitis and Crohn disease. Despite this fact, certain defining features of each disease have been characterized. Ulcerative colitis is predominantly a mucosal disease. However, with progression of illness, there is hypertrophy of the muscularis often by 40-fold, increase submucosa fatty deposition, and thickening of the lamina propria from round cell infiltration, which all leads to bowel wall thickening. On average, thickening of the luminal wall is 7.8 mm in ulcerative colitis, which is less than the amount of wall thickening typically seen with Crohn disease. Submucosal fat is a prominent finding in chronic ulcerative colitis and is one of the defining features of the mural stratification seen in ulcerative colitis. In comparison, Crohn disease has transmural involvement that over time leads to replacement of submucosal fat with fibrosis and loss of mural stratification. In distinction to ulcerative colitis, Crohn disease also has several extraluminal CT findings, including mesenteric fibrofatty proliferation and abscess. Additional images of Crohn disease on CT scanning are provided below.

Crohn disease. CT with MRI correlation. CT scan in a patient with chronic inactive Crohn disease demonstrates thickening of the wall of the right colon with intramural lucency. This was believed to represent intramural fat deposition.

Crohn disease. MRI with CT correlation. MRI demonstrates thickening of the wall of the right colon with intramural increased signal on a T1-weighted image. This was believed to represent intramural fat deposition.

Crohn disease. Perianal abscesses. CT scan demonstrates multiple fluid, contrast material, and air collections around the anorectum. Note the presence

of a rectal tube. Crohn disease. Perianal abscesses. CT scan demonstrates multiple fluid, contrast agent, and air collections around the anorectum. Note

the presence of a rectal tube. Crohn disease. Small-bowel obstruction in a patient with recurrence proximal to an anastomosis. CT scan in a patient with a prior ileocolectomy demonstrates small-bowel dilatation and wall thickening of the small

bowel proximal to the anastomosis. Crohn disease. Enteroenteric fistula. CT scan demonstrates the tract of an enteroenteric fistula.

Crohn disease. Enterocutaneous fistula. CT scan demonstrates enterocutaneous and colocutaneous fistula formation.

Magnetic Resonance Imaging

Traditionally, MRI has had a well-defined role in evaluation of anorectal complications of Crohn disease. With a regular fast spin-echo technique, the pathologic entities of a fistula, a sinus tract, and an abscess can be detected in the static anorectal region by using MRI.[13] More recently, MRI enterography and enteroclysis has allowed detection of small bowel Crohn disease similar to the use of small bowel series, with the additional benefits for assessment of extraluminal disease.[14] High-resolution imaging with the current MRI technology has increased the accuracy of assessing the grade and severity of patient with Crohn disease.[14, 15, 16, 17, 18] Its increased use and availability will likely rival traditional imaging in the assessment of Crohn disease.

Perianal sinus tracts and fistulas

Sinus tracts and fistulas often appear hyperintense on T1-weighted images and hyperintense on T2-weighted images because of their fluid content. With fat suppression, the fluid signal is further intensified and easily seen as being hyperintense on T2-weighted images. An abscess

often appears as an isolated collection of high-signal-intensity areas on the T2-weighted image, especially in ischioanal fossa. Defining whether an abscess, fistula, or sinus tract is above or below the levator ani muscle is important for drainage, because any part of the abscess above the levator ani muscle will not drain adequately in the inferior direction, and vice versa.

MRI sequences
The development of faster pulse sequences (eg, single-shot fast spin-echo, steady-state free precession, and gradient-echo sequences) and higher-gradient systems has made T1- and T2weighted breath-hold imaging possible. This breath-hold imaging has been a major breakthrough in overcoming physiologic motion artifacts in abdominal imaging. It has made routine abdominal MRI feasible. The single-shot fast spin-echo sequence, in which T2-weighted images are acquired by using half-Fourier transformation and a long echo train. Each image section is acquired independently in less than 1 second, and the method eliminates physiologic motion from the bowel and the need for breath holds. Fat suppression can be added to increase specificity for bowel and mesenteric edema. The steady-state free precession imaging is based on a low flip angle gradient echo series with short repetition time. It is another series of sequences that is insensitive to motion artifacts and can provide T2-type imaging. It can have black boundary artifacts along the bowel wall that mask small lesions, but fat suppression can reduce the artifact. The major feature of the sequence is the ability to acquire an entire series within a single breath hold. In fact, MR fluoroscopy is performed with cine of steady-state free precession imaging and a frame rate of 0.5-2 sections per seconds along the long axis of the affected segments. Contrast evaluation is often imaged with 3-dimensional spoiled gradient echo T1 fatsuppressed sequences. Images are acquired with breath hold. For bowel imaging, series are taken after intravenous glucagon at 30 and 70 seconds post contrast. Because of a decrease in cumulative radiation exposure and because of the capability of attaining high-quality coronal images correlating with barium studies, MRI is currently an alternative for monitoring disease activity in Crohn disease.

MRI enterography and enteroclysis

With the development of faster imaging sequence and with the use of intravenous 0.2 mg glucagon to decrease bowel motility, the small bowel is distended in both MRI enterography or enteroclysis, often with 1.5-2 L of solution containing biphasic intraluminal contrast agents (low T1 and high T2). Some of these agents are Volumen (EZ-E-M; Westbury, NY), mannitol (2.5%), methylcellulose, sorbitol (2%), and polyethylene glycol. Image is performed for 40-60 minutes subsequent to luminal distension for MRI enterography and enteroclysis. Oral ingestion of the intraluminal contrast is performed in enterography, while nasojejunal intubation and infusion of intraluminal contrast is performed in enteroclysis. Nasojejunal intubation under fluoroscopy is required for MRI enteroclysis; it provides excellent bowel distention and provides detailed luminal information.[19] However, there is added procedure

time for the fluoroscopy nasojejunal intubation, along with increased invasiveness and patient discomfort.[20, 21] These factors can be major drawback, especially in pediatric population. MRI enterography has less patient discomfort, but the bowel preparation may not produce the uniform distention achieved with enteroclysis. Nevertheless, several studies have shown better patient tolerance of enterography over enteroclysis, and some studies have shown similar sensitivity for both techniques.[20] Initial imaging with serial coronal steady-state free precession for the small bowel can demonstrate decreased motility in areas of small bowel disease, along with luminal thickening (wall thickness >4 mm) while monitoring adequate distention of the ileocecal lumen. After adequate luminal distention, intravenous 0.2 mg of glucagon or 1 mg of intramuscular glucagon is administered to reduce motion artifacts, followed by T2-weighted single-shot fast spin-echo series. The coronal and axial T2-weighted single-shot fast spinecho images can show edema in the small bowel mesentery and small bowel wall deep ulcers, while fat-saturated images can determine chronic mural fat changes. Lastly, after administration of a gadolinium-based intravenous contrast agent, coronal volume gradientecho sequences are acquired to assess vascular engorgement, mucosal hyperemia, mural enhancement, inflammatory hyper-enhancing lymph nodes, abscess, and fistula. There are currently ongoing investigations into the use of MRI enterography and assessment of active disease in the colon.

Active Crohn disease

Assessment of inflammatory activity is fundamental to the managing Crohn disease. There is no single reference standard for defining active disease. Clinical scores such as the Crohn disease activity index and biochemical markers such as C-reactive protein are widely used, but they lack utility for assessment of the entire bowel.[17] Endoscopy is the current reference standard for evaluation of disease of the colon and terminal ileum. It has the key advantages of direct visualization and sampling of disease, but it is limited in its assessment of the entire small bowel. MRI currently serves as a viable method for global assessment. Many of MRI criteria of disease activity are based on luminal and extraluminal disease. In terms of luminal disease, active disease includes ulcer, wall thickening, mural and perimural T2 intensity, and bowel wall enhancement with gadolinium-based contrast agents.[17] Extraluminal active disease includes enlarged inflammatory lymph nodes, fibrofatty proliferation, and mesenteric edema. During active inflammation, gadolinium enhancement of the bowel wall can be seen on T1weighted images, and it is easily differentiated from normal adjacent bowel. There are 3 main patterns of enhancement in determining the level of disease. The layered or stratified enhancement is seen with enhancement of the mucosa, and relatively poor submucosal enhancement and submucosal edema are seen in active disease.[22, 23, 24] Diffuse intense homogenous enhancement of the entire bowel wall thickness occurs from transmural inflammation.[25] Low-level heterogeneous enhancement occurs with fibrosis.[26] See the image below.

MRI enterography 3-dimensional gradient postcontrast series demonstrates stratified hyperenhancement of the mucosa of the distal ileum in a patient with active Crohn disease. Wall thickening is variable in active disease, as described in many reports. The general consensus is that concentric bowel wall thickening greater than 4 mm is suggestive of active disease. In study by Maccioni et al, active disease is characterized by a thickened bowel wall with gadolinium enhancement, but inactive disease is not.[27] With the advent of MRI enteroclysis, and to a lesser degree optimal enterography, alteration of folds in early active Crohn disease can be seen as diffuse thickened folds as in a picket-fence pattern, reduction and distortion of folds secondary to ulceration, and cobblestoning on single-shot spin-echo series.[26] See the image below.

MRI enterography with coronal fat-saturated T2-weighted singleshot fast spin echo imaging demonstrates mesenteric edema and mural wall edema and thickening in a patient with active Crohn disease in the distal ileum. Fat-suppressed T2-weighted images can also be used for differentiation because they show high-signal intensity in active disease and low or absent signal intensity in nonactive disease. Mural T2 increased signal intensity is a well-validated marker of disease activity.[23, 27, 28, 29, 30, 31] In fact, the fat suppression in T2-weighted images helps differentiate fibrofatty changes of mural disease from mural wall edema. Ulceration in active Crohn disease is highly dependent on the quality of luminal distention and is best depicted by MRI enterography and enteroclysis. Deep ulcers appear as thin lines of high signal within a thickened bowel wall on single-shot fast spin-echo series and can be seen more readily on MRI enterography, whereas aphthous ulcer, with a nidus of high signal with surrounding intermediate signal, can be seen on high-resolution MRI enteroclysis. See the image below.

MRI enterography coronal single-shot fast spin-echo images in a patient with active Crohn disease demonstrates wall thickening and wall deep fissuring along an ascending limb of the distal ileum small bowel loop in the right lower quadrant of the abdomen. Fibrofatty proliferation is hyperintense on T2-weighted images and is related to regional mesenteritis or edema and dilatation of local vessels. The dilatation of the local vessels is seen supplying a local inflamed bowel segment, akin to the comb sign seen on CT examination; this finding is well depicted in postcontrast gradient-echo images and steadystate free-procession images. Inclusive in the term fibrofatty proliferation is fat wrapping, whereby there is chronic enlarged mesenteric fat leading to increased separation of the mesenteric bowel loops. Fat proliferation is a distinguishing feature of Crohn disease and is indicative of the diagnosis. See the image below.

MRI enterography, steady-state free-procession image, demonstrates vascular engorgement of the vasa recta or "comb" sign in a thickened ileum bowel loop during active disease. Mesenteric edema in active disease is seen accompanying bowel wall edema and hyperenhancement and is seen often with the comb sign of the mesentery. Active lymph nodes are enlarged, hyperenhancing, and edematous, typically along the vascular supply of affected bowel segment. The nodal enhancement is usually homogenous and is greater than or equal to one of the adjacent lymph node for active disease.[23] Low et al[32] and Marcos and Semelka[33] have found gradient-echo imaging to be more sensitive than other methods in determining the severity of Crohn disease, and they favor the use of gadolinium-enhanced gradient-echo MRI.

Gadolinium-enhanced spoiled gradient-echo MRI has a reported sensitivity of 85-89%, a specificity of 96-94%, and an accuracy of 94-91% for active disease, as compared with single-shot fast spin-echo MRI, which has a sensitivity of 51-52%, specificity of 98-96%, and accuracy of 83-84%.[32]

Chronic Crohn disease and complications of Crohn disease

There are 3 major forms of chronic Crohn disease: fistula and perforating disease, fibrostenotic disease, reparative or regenerative disease. Fistulae are sequelae of deep transmural ulcers that extend through the musculature, leading to the formation of small abscesses and sinus tracts. The sinus tract can involve and communicate with adjacent hollow organ and form fistulae. MRI depiction of fistulae is often seen as fibrotic star-shaped reactions of the mesentery, with tethering of the adjacent communicating structures. It has avid enhancement post contrast and, on occasion, shows a linear T2-hyperintense tract. The chronic mesenteric inflammation can eventually form fibrous bands with enhancement similar to sinuses and fistulas. However, they often lead to tenting and segmental obstruction with MR fluoroscopy, showing kinking and stretching of the adjacent bowel loops. Fibrostenotic disease is often depicted as bowel obstruction without bowel wall thickening. The bowel stricture has low T1 and T2 mural signal and has mild nonhomogenous enhancement. With asymmetric bowel wall involvement, pseudosacculation can occur. Regenerative disease is depicted on MRI as luminal narrowing without inflammation or obstruction. On steady-state free-procession imaging, filiform polyposis may be suggested without enhancement or obstruction. Neoplasia is also a concern in chronic disease, since Crohn disease patients are at increased risk of developing adenocarcinoma of the affected bowel segment.[34, 35] Eccentric bowel wall thickening or shouldering, mesenteric infiltration, and lymphadenopathy on MRI enterography or enteroclysis are often early signs of malignancy.

Warning about gadolinium-based contrast agents

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MR angiography scans.[36] NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

Degree of confidence and impact of MRI

Gadolinium-enhanced spoiled gradient-echo MRI has a reported sensitivity of 85-89%, a specificity of 96-94%, and an accuracy of 94-91% for active disease, as compared with single-shot fast spin-echo MRI, which has a sensitivity of 51-52%, a specificity of 98-96%, and an accuracy of 83-84%.[32] MRI enterography and enteroclysis compared with conventional imaging has sensitivity of 88-98% and specificity of 78-100%.[14] In a recent

retrospective study, MRI enterography has been confirmed to impact the management of patient care with additional information from endoscopy and clinical assessment. In a retrospective study of 120 MRI enterography patients, 53% underwent additional medical treatment of active disease and 16% underwent surgery with intraoperative findings concordant to MR enterography.[37]

Ultrasonography
Ultrasonography can be an alternative to CT in the evaluation of the intraluminal and extraluminal manifestations of Crohn disease. The normal GI wall appears as 5 concentric, alternating echogenic and hypoechoic layers; this appearance is known as the gut signature. The GI wall has an average thickness of less than 5 mm.[38, 39] In the case of active Crohn disease, the wall thickness can range from 5 mm to 2 cm with either partial or total loss of layering, which reflects transmural edema, inflammation, or fibrosis. With severe inflammation, the wall appears diffusely hypoechoic with a central hyperechoic line that corresponds to the narrowed lumen. Peristalsis is reduced or absent, and the diseased segment is noncompressible and rigid with a loss of haustra. Ultrasonography can depict ballooning of the less involved segments, which is seen as focal sacculation or outpouching. These findings reflect the skip lesions found in Crohn disease. The accuracy of ultrasonography is further improved with the use of color Doppler imaging. The use of Doppler imaging is helpful in the detection of hyperemia of an inflamed bowel wall and adjacent fat during active disease. With transmural inflammation, edema and fibrosis of the adjacent mesentery occurs, leading to fingerlike projections of mesenteric fat that creeps over the serosal surface of the bowel. This creeping fat eventually envelops the diseased bowel segment. On sonograms, this appears as a uniform hyperechoic mass, which is classically seen at the cephalic margin of the terminal ileum. With long-standing disease, this becomes more heterogeneous or even hypoechoic. In active Crohn disease, reactive mesenteric nodes are enlarged and may coalesce to form a conglomerate mass. On sonograms, enlarged nodes can be seen as oval hypoechoic masses in the mesentery. With confluence, they become lobulated masses of various sizes. Many complications of Crohn disease can also be seen in their ultrasonographic forms. Phlegmon appears as a hypoechoic mass with irregular borders and no identifiable wall or fluid. Abscess appears as a fluid collection with a thickened wall containing air or echogenic debris. Obstruction appears as dilated hyperperistaltic fluid filled segments. Perforation appears as bright echoes with distal acoustic shadows outside the boundaries of bowel loops. A fistula, on the other hand, appears as a hypoechoic tract. If gas is present in the fistulous tract, it contains hyperechoic foci with acoustic shadowing. Palpation of diseased loops during sonography enables tract identification. In addition, sonography should be able to identify gas bubbles in abnormal locations, such as air in the bladder or vaginal vault, the retroperitoneum, the subcutaneous tissue, and the urachal remnant.

The detection of bowel wall thickening varies widely. Detection rates range from 22-89%. The large variation presumably reflects differences in technique, operator experience, and ultrasound equipment. Determination of the extent of the disease is not always possible, and correlation between wall thickening and the clinical activity of disease is poor. The loss of gut signature and bowel wall thickening is a nonspecific finding. It is found in infectious, ischemic, neoplastic, and radiation-induced conditions. In addition, the detection of bowel wall changes in Crohn disease varies significantly because of operator dependence. See the images below.

Crohn disease of the terminal ileum with CT and sonographic correlation. Note terminal ileal-wall thickening and adjacent mesenteric inflammatory

stranding. Crohn disease of the terminal ileum with CT and sonographic correlation. Note hypoechoic wall thickening, loss of the gut signature, and the

hyperechoic line representing the narrowed lumen. Crohn disease of the terminal ileum with CT and sonographic correlation. Note hypoechoic wall thickening, loss of the gut signature, and the hyperechoic line representing the narrowed

lumen. Crohn disease. Sonogram of a thickened bowel wall demonstrates the so-called pseudokidney appearance.

The literature states that the differentiation between hypoechoic foci from creeping fat and that from phlegmon or edema may be difficult or nearly impossible. Proponents of CT have also stated that the specificity of color Doppler imaging is still unknown. In general, the confidence level of the radiologist in interpreting the results is operator dependent, and it is often lower than that of CT. For these reasons, ultrasonography has not been the favored modality for imaging Crohn disease.

Nuclear Imaging
Leukocytes labeled with either technetium-99m-HMPAO (hexamethylpropylamine oxime) or indium-111 can be used to assess for active bowel inflammation in inflammatory bowel disease. Compared to the111 In label, the99m Tc HMPAO label has better imaging characteristics and can be imaged much sooner after injection. However, imaging must typically be done within an hour after injection of99m Tc-HMPAO-labeled leukocytes, as there is normal excretion into the bowel after this time, unlike with111 -labeled leukocytes, which have no normal bowel excretion. Molnar et al found that a99m Tc-HMPAO leukocyte scan in active Crohn disease had a sensitivity of 76.1% and a specificity of 91.0%, as compared to CT sensitivity of 71.8% and specificity of 83.5%. While leukocyte scans may be better in the detection of segmental inflammatory activity, CT is superior for the detection of complications.[40] False-positive bowel activity can be seen with gastrointestinal bleeding, swallowed leukocytes (eg, from uptake related to sinusitis or nasogastric tubes), or activity related to indwelling enteric tubes. In addition, leukocyte uptake is not specific for Crohn disease and will be seen in most infectious or inflammatory bowel processes. As mentioned above, there is often normal bowel excretion of99m Tc-HMPAO leukocytes if imaging occurs within the first hour after injection.