Gastroenterology

Gastroenterology

Volume 141, Issue 3, September 2011, Pages 819-826.e1
Gastroenterology

Imaging and Advanced Technology
Ultrasound Elasticity Imaging for Detecting Intestinal Fibrosis and Inflammation in Rats and Humans With Crohn's Disease

https://doi.org/10.1053/j.gastro.2011.07.027Get rights and content

Background

Intestinal fibrosis causes many complications of Crohn's disease (CD). Available biomarkers and imaging modalities lack sufficient accuracy to distinguish intestinal inflammation from fibrosis. Transcutaneous ultrasound elasticity imaging (UEI) is a promising, noninvasive approach for measuring tissue mechanical properties. We hypothesized that UEI could differentiate inflammatory from fibrotic bowel wall changes in both animal models of colitis and humans with CD.

Methods

Female Lewis rats underwent weekly trinitrobenzene sulfonic acid enemas yielding models of acute inflammatory colitis (n = 5) and chronic intestinal fibrosis (n = 6). UEI scanning used a novel speckle-tracking algorithm to estimate tissue strain. Resected bowel segments were evaluated for evidence of inflammation and fibrosis. Seven consecutive patients with stenotic CD were studied with UEI and their resected stenotic and normal bowel segments were evaluated by ex vivo elastometry and histopathology.

Results

Transcutaneous UEI normalized strain was able to differentiate acutely inflamed (−2.07) versus chronic fibrotic (−1.10) colon in rat models of inflammatory bowel disease (IBD; P = .037). Transcutaneous UEI normalized strain also differentiated stenotic (−0.87) versus adjacent normal small bowel (−1.99) in human CD (P = .0008), and this measurement also correlated well with ex vivo elastometry (r = −0.81).

Conclusions

UEI can differentiate inflammatory from fibrotic intestine in rat models of IBD and can differentiate between fibrotic and unaffected intestine in a pilot study in humans with CD. UEI represents a novel technology with potential to become a new objective measure of progression of intestinal fibrosis. Prospective clinical studies in CD are needed.

Section snippets

Animal Models of Acute Colitis and Intestinal Fibrosis

Acute colitis and colonic fibrosis were generated in Lewis rats by rectal administration of TNBS enemas, a well-accepted model of colitis developed by Morris et al.13 A total of 15 female Lewis rats (Harlan Sprague–Dawley; Harlan, Indianapolis, IN; weight, 150–180 g) were separated into 3 groups: Acute colitis, chronic intestinal fibrosis, and phosphate-buffered saline (PBS) enema negative controls; 1 rat in the acute colitis group did not survive treatment. Rodents were fasted for 16–24 hours

Acute TNBS Enemas Induce Inflammatory Colitis, Whereas Chronic TNBS Enemas Induce Colonic Fibrosis in Rats

The objective of the animal portion of our study was to determine whether UEI measurements of the rat colon could distinguish inflammatory and fibrotic causes of bowel wall thickening. Biologic confirmation of the fibrotic and inflammatory phenotypes was performed by gross pathologic, histologic, and molecular methods. At sacrifice, gross colon morphology was consistent with inflammation and fibrosis (Figure 1A). The acute TNBS colitis group demonstrated distal colon thickening with areas of

Discussion

The monitoring and management of inflammation in IBD have undergone revolutionary advances in the past 20 years, but the development of methods of detection and treatment of fibrosis in CD have lagged behind. Fibrostenotic complications lead to frequent hospital admissions, operative interventions, and substantial costs in CD. At present, our armamentarium against fibrosis is limited to preventive, anti-inflammatory strategies. Antifibrotic therapies for other organs may hold promise for

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Cited by (136)

  • Bowel stiffness associated with histopathologic scoring of stenosis in patients with Crohn's disease

    2021, Acta Biomaterialia
    Citation Excerpt :

    Our study demonstrated a strong relationship between the tissue stiffness and histological change of the tissue in CD strictures, i.e. the severer the disease, the stiffer wall of the CD stricture. The finding is consistent with the trend identified in previous compression studies on the bowel wall stiffness in CD patients [10-12]. However, it is difficult to compare the mechanical constants obtained in this study with the bowel wall stiffness in CD patient in previously published studies since different mechanical tests and mechanical models were used.

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Conflicts of interest The authors disclose no conflicts.

Funding Supported by grants R21-DK081123-01 (KK, JX, PDRH, JMR); K08-DK080172-01 (PDRH), and T32-DK007367-01 (RWS).

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