Inflamm Bowel Dis. 2025 Jan 24:izae319. doi: 10.1093/ibd/izae319. Online ahead of print.

Jonathan R Dillman ¹, Jean A Tkach ¹, Joel G Fletcher ², David H Bruining ³, Aiming Lu ², Subra Kugathasan ⁴, Adina L Alazraki ^4 5, Jack Knight-Scott ⁵, Ryan W Stidham ⁶, Jeremy Adler ⁷, Phillip Minar ⁸, Bruce C Trapnell ⁹, Erin L Bonkowski ⁸, Holden Jurrell ⁸, Oscar Lopez-Nunez ¹⁰, Margaret H Collins ¹⁰, Scott D Swanson ¹¹, Lin Fei ¹², Lucia Qian ^12 13, Alexander J Towbin ¹, Murat Kocaoglu ¹, Christopher G Anton ¹, Rebecca A Imbus ¹⁴, Jonathan A Dudley ¹⁴, Lee A Denson ⁸

Author information

¹Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

²Department of Radiology, Mayo Clinic, Rochester, MN, USA.

³Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

⁴Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

⁵Department of Radiology, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA.

⁶Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA.

⁷Division of Pediatric Gastroenterology, Department of Pediatrics, C. S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI, USA.

⁸Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

⁹Departments of Medicine and Pediatrics, Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

¹⁰Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

¹¹Department of Radiology, Michigan Medicine, Ann Arbor, MI, USA.

¹²Division of Biostatistics and Epidemiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

¹³University of Michigan, Ann Arbor, MI, USA.

¹⁴Department of Radiology, Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Abstract

Background: We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn's disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content.

Methods: Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers. Circulating CD64, extracellular matrix protein 1 (ECM1), GM-CSF autoantibodies (GM-CSF Ab), and fecal calprotectin were measured by ELISA. Ileal 3-dimensional magnetization transfer ratio (3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, diffusion-weighted intravoxel incoherent motion (IVIM), and the simplified magnetic resonance index of activity (sMaRIA) were measured by MRI. Ileal resection specimen acute inflammation was graded, and collagen content was measured quantitatively using second harmonic imaging microscopy. Associations between biomarkers and ileal collagen content were tested.

Results: Median (interquartile range [IQR]) age was 19.5 (16-33) years. We observed an inverse relationship between ileal acute inflammation and collagen content (r = -0.39 [95% confidence interval {CI}: -0.61, -0.10], P = .008). Most patients (33 [66%]) received biologics, with no variation in collagen content with treatment exposures. In the univariate analysis, CD64, GM-CSF Ab, fecal calprotectin, and sMaRIA were positively associated with acute inflammation and negatively associated with collagen content (P < .1). The multivariable model for ileal collagen content (R2 = 0.31 [95% CI: 0.11, 0.52]) included log CD64 (β = -.27; P = .19), log ECM1 (β = .47; P = .06), log GM-CSF Ab (β = -.15; P = .01), IVIM f (β = .29, P = .10), and IVIM D* (β = 1.69, P = .13).

Conclusions: Clinically available and exploratory circulating and MRI biomarkers are associated with the degree of inflammation versus fibrosis in CD ileal resections. With further validation, these biomarkers may be used to guide medical and surgical decision-making for refractory CD.