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A novel method measures bowel damage in celiac disease rapidly with high accuracy

Published on 9.9.2020
Tampere University
ohutsuolen nukkalisäkkeitä
An endoscopic biopsy sample showing healthy villi in the small intestine
Researchers at Tampere University have developed a completely novel method for the three-dimensional imaging of small intestinal biopsies. Digital 3D images can be utilised to measure quickly and accurately the degree of intestinal damage caused by variable gastrointestinal diseases. The imaging is based on X-ray tomography microscopy (micro-CT) and it can be used, among other things, to improve the diagnosis of celiac disease and in pharmaceutical trials.

Currently, the diagnosis of celiac disease is still mainly based on the detection of damaged villi in mucosal biopsies extracted from the small bowel. For the reliable analysis of the degree of mucosal damage, endoscopy specimens taken from the patient should be carefully cut for microscopic examination to achieve the correct measurement direction, which is laborious and requires special expertise.

“Repeat sections must frequently be cut, and even then, reliable measurement results may not be obtained. Borderline cases are particularly difficult to assess, and in the worst cases, interpretation problems can lead to lifelong misdiagnosis. The traditional diagnostic approach is also not sufficiently sensitive for drug trials,” says professor Kalle Kurppa.

The X-ray-based micro-CT device can be used to create a 3D reconstruction of tissue samples with an accuracy of up to one micrometre over the entire sample.

The method was created when researchers at Tampere University’s Center for Child Health Research and Celiac Disease Research Center collaborated with the Computational Biophysics and Imaging Group to discover whether 3D images created with innovative micro-CT imaging methods could be used for small bowel imaging and diagnosis of celiac disease.

In addition to the villous structure, the researchers wanted to use 3D images to measure the mucosal surface area, as this parameter reflects better the absorption of nutrients and is biologically a more meaningful endpoint. For this purpose, the research team developed a computer-assisted point cloud analysis method.

The imaging method was tested in patients with untreated and treated celiac disease, as well as in individuals with positive celiac antibodies but a non-diagnostic biopsy (so-called potential celiac disease). In addition, samples from antibody-negative control subjects were included.

Digital 3D images were able to measure the degree of intestinal damage quickly and accurately. It turned out that the method could, in fact, have established a celiac disease diagnosis in some of the antibody-positive patients who had not been diagnosed by conventional methods.

“The measurement of the surface area of intestinal villi, which was tested as a completely new research method, succeeded excellently, and the results correlated with the clinical findings and blood test results in a logical manner,” Kurppa notes.

“In the 3D images, we also found that, as the disease progresses, the intestinal mucosa shows notable deformation and coalescence in addition to shortened villi, which may significantly affect the absorptive area in the bowel,” Kurppa adds.

The study was funded by the Academy of Finland, Sigrid Juselius Foundation, Foundation for Paediatric Research, Finnish Medical Foundation, Business Finland (TEKES) and competitive government funding from the special responsibility area of Tampere University Hospital.

The original publication:
Virta J, Hannula M, Tamminen I, Lindfors K, Kaukinen K, Popp A, Taavela J, Saavalainen P, Hiltunen P, Hyttinen J, Kurppa K. X-ray microtomography is a novel method for accurate evaluation of small-bowel mucosal morphology and surface area. Sci Rep 2020;10:13164.
https://pubmed.ncbi.nlm.nih.gov/32753621/
doi: http://dx.doi.org/10.1038/s41598-020-69487-w

A video related to the article

Computational Biophysics and Imaging Group (CBIG)
 

Enquiries:
Professor Kalle Kurppa, tel. +358 (0)41 544 8840, kalle.kurppa [at] tuni.fi
Bachelor of Medicine Johannes Virta; johannes.virta [at] tuni.fi