What Is Crohn’s Disease?

Crohn’s disease is a form of inflammatory bowel disease. People with Crohn’s disease have long-term (chronic) inflammation and sores (ulcers) that can occur anywhere in the gut (from the mouth and stomach to the large intestine), and in any of the layers that make up the gut wall. Crohn’s disease is a progressive, “relapsing and remitting” condition, which means that there are times when the symptoms of a person living with Crohn’s disease get worse (known as flare-ups or relapses) and others when they partly or completely go away (remission).

What Causes Crohn’s Disease?

The exact causes of Crohn’s disease are not yet fully understood, but it is known that a combination of factors causes inflammation to be activated by the immune system. Inflammation is a normal process through which the body responds to an injury or a perceived threat, such as a bacterial infection. In Crohn’s disease, a high level of inflammation taking place for too long results in tissue damage in the gut, and can sometimes cause inflammation-related complications outside the gut as well, such as in the skin, joints, and eyes.

Crohn’s disease is thought by some to be an autoimmune condition, which means that the body’s immune system wrongly attacks normal, healthy tissue. Other researchers think that it’s caused by the immune system mistakenly identifying harmless bacteria inside the gut as a threat and starting to attack them, causing it to become inflamed. The gut contains hundreds of different species of bacteria and although some can cause illness, many are essential to our health and wellbeing, playing key roles in digestion, metabolism (the chemical reactions in the body that produce energy from food), regulation of the immune system, and mood. Genetic factors like changes in genes and environmental factors are also known to be involved in the development of Crohn’s disease.

What Is an Anastomotic Stricture?

In addition to the main symptoms of Crohn’s disease, other complications can make the management of the disease more difficult and the quality of life of the person living with it poorer. One such complication is anastomotic stricture. “Anastomosis” is the term given to a surgical procedure that involves the connection of two channels together that were not previously connected. For example, some people with Crohn’s disease have surgery to remove part of their colon and the remaining part of the colon is then connected to the small intestine.

An “anastomotic stricture” occurs if scar tissue on the intestinal wall in that part of the intestine starts to narrow it. This narrowing can reduce the ability of waste to pass through the small intestine and colon, and if it becomes completely blocked is a medical emergency that requires immediate treatment.

How Do Strictures Form in Crohn’s Disease?

Strictures form as a result of a combination of overactive inflammation and excessive “fibrosis” (a normal process by which connective tissue is formed as a response to repair damage or injury, but that can result in too much tissue, or hardened or scarred tissue, if it occurs at levels that are too high). The exact composition of a stricture (whether it is inflammatory or fibrotic) affects which treatment approach is most likely to be effective against it.

Strictures that are mostly inflammatory benefit from intensified medical therapy (such as an increase in the dosage of a drug or the number of drugs prescribed), while fibrotic strictures are best treated by surgery or the use of a “balloon” device to widen the affected area of the intestine (there are currently no approved drug therapies that are able to specifically target fibrotic intestinal strictures). However, diagnostic approaches are currently unable to assess the extent to which a stricture is fibrotic or inflammatory, something that is needed to ensure that patients with Crohn’s disease get the treatment they need.

What Did This Study Investigate?

Several different imaging methods can be used to assess the state of the intestinal wall if a person has a stricture, but they are not able to quantify to what extent a stricture is caused by inflammation or fibrosis. Computed tomography (CT) scanning uses a series of X-rays to create detailed images of inside the body. In contrast, positron emission tomography (PET) involves a tracer drug being injected into a vein that emits positrons (usually ¹⁸F-fluorodeoxyglucose, ¹⁸F-FDG), which collects in areas with higher levels of biochemical or metabolic activity. These areas can then be visualized, and the technique is particularly useful in detecting cancers or decreased blood flow in the heart. CT and PET scanning can be combined to produce detailed three-dimensional images with areas of cellular activity highlighted.

Although PET/CT using ¹⁸F-FDG-PET/CT is useful in visualizing inflammation, it cannot distinguish areas of fibrosis. However, a molecule called “fibroblast activating protein” (FAP) has recently been reported to play a role in the process by which fibrosis occurs in response to tissue damage and therefore the development of fibrosis in patients with Crohn’s disease. Researchers have developed inhibitors that target and bind to FAP (FAPI), and by tagging these inhibitors with a tracer molecule called gallium-68 (⁶⁸Ga), areas of fibrosis in the body can be visualized and measured.

In this study, the authors investigated whether combining ¹⁸F-FDG-PET/CT and ⁶⁸Ga-FAPI-46-PET/CT could be used to differentiate between areas of inflammation and fibrosis in intestinal strictures in patients with Crohn’s disease. Three patients who had previously undergone Crohn’s disease-related surgery underwent both imaging techniques, and also underwent two other imaging procedures for verification of the results (which included colonoscopy). Two of the patients also underwent surgery and tissue samples taken from their strictures were analyzed to determine the levels of inflammation and fibrosis.

The results of the tests showed that the level of ⁶⁸Ga-FAPI-46 taken up correlated with the level and severity of fibrosis in strictures, with different uptake patterns in each patient, while the level of ¹⁸F-FDG taken up correlated with the level of inflammation. Several medications that target fibrosis are currently being evaluated for the treatment of Crohn’s disease-associated strictures. The combination of the two imaging techniques may be useful in assessing strictures in patients with Crohn’s disease with the aim of selecting the best individualized treatment approach, and in assessing progression over time.

Note: The authors of this paper make a declaration about grants, research support, consulting fees, lecture fees, etc. received from pharmaceutical companies. It is normal for authors to declare this in case it might be perceived as a conflict of interest. For more detail, see the Conflict of Interest Statement at the end of the paper.