Introduction: Crohn’s disease (CD) is a chronic inflammatory disease characterized by transmural bowel wall inflammation that may progress to fibrosis leading to intestinal strictures and obstruction over time [1]. Clinically, precisely detecting the fibrotic severity within CD strictures is crucial due to the current lack of anti-fibrotic medicines for fibrosis-predominant strictures, which can only be relieved by endoscopic or surgical treatment [2]. Quantitative magnetic resonance imaging (MRI), such as diffusion-weighted imaging (DWI) has demonstrated efficacy for the detection of bowel fibrosis in CD [3]. As a specialized MRI technique that maps the diffusion of water molecules in biological tissues, DWI probably reflects the restricted diffusion of water molecules in the extracellular space caused by the presence of fibrotic tissue in the diseased lesion with a decreased apparent diffusion coefficient (ADC) [4]. However, traditionally ADC is only an overall measure of the water diffusivity that is determined by multiple microstructural features, such as intra- and extra-cellular space, cell size and intrinsic diffusivity. The recent development of time-dependent diffusion MRI (TD-dMRI) has demonstrated unique advantages in depicting cellular microstructures by characterizing the diffusion time dependence of restricted water diffusion and relating the diffusion time dependence to specific microstructural parameters [5,6]. Therefore, the aim of this study was to investigate the feasibility and efficacy of TD-dMRI-based microstructural mapping for noninvasively characterizing cellular properties of CD and for discriminating between moderate-to-severe fibrosis and non-to-mild fibrosis.

Methods: This prospective observational study enrolled 13 CD patients with 45 resected intestinal strictures between May 2023 and October 2023, who underwent TD-dMRI and were scheduled for surgery within 4 weeks. TD-dMRI were acquired by using a combination of pulsed and oscillating gradient spin-echo sequences (Siemens research sequence) at an equivalent diffusion time of 4.2-12.0 msec on a 3T MR scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany). TD-dMRI-based microstructural parameters, including cell diameter, extracellular diffusivity, intracellular volume fraction, cellularity, and diffusivities with different effective diffusion time, were estimated using a two-compartment (limited spectrally edited diffusion, IMPULSED) model of the least square curve fitting toolbox in MATLAB (MathWorks, Inc.). Conventional ADC was also calculated for comparison with these parameters. Region-by-region correlations with the surgical specimens were performed to determine the histologic degree of fibrosis. The accuracy of these microstructural imaging parameters was confirmed through their correlations with histopathologic measurements. One-way analysis of variance test, Spearman rank correlation, and receiver operating characteristic curve were used for statistical analysis.

Results: According to TD-dMRI measurements, there were significant correlations of higher cell diameter (mean cell diameter=6.47, 8.03, 11.30, 14.56, and 17.31 μm for fibrosis scores 0-4, respectively; r=0.53; p＜0.001), increased intracellular volume fraction (mean intracellular volume fraction=0.17, 0.19, 0.21, 0.25, and 0.29 for fibrosis scores 0-4, respectively; r=0.34; p＜0.01), and decreased cellularity (mean cellularity=16.15, 11.04, 7.79, 4.87, and 3.66, respectively; r=0.55; p＜0.01) with elevated pathological fibrosis scores. Among all measurements derived from TD-dMRI, cell diameter achieved the highest diagnostic performance with an area under the receiver operating characteristic curve (AUC) of 0.87 (p＜0.001) in discriminating moderate-to-severe fibrosis from non-to-mild fibrosis, followed by cellularity (AUC=0.82, p=0.001), intracellular volume fraction (AUC=0.75, p＜0.01), diffusivity at oscillating frequencies of 25 Hz (AUC=0.62, p=0.21), extracellular diffusivity (AUC=0.61, p=0.24), diffusivity at oscillating frequencies of 50Hz (AUC=0.51, p=0.93) and ADC (AUC=0.45, p=0.50). Microstructural mapping was supported by positive correlations between TD-dMRI-based and pathologic examination-based intracellular volume fraction (r=0.83, p＜0.001).

Conclusion: TD-dMRI allows for the characterization of microstructural features of intestinal strictures in CD patients, especially those related to fibrosis. Cell diameter shows great potential as a promising biomarker for noninvasive detection of varying degrees of bowel fibrosis.

Acknowledgements

No acknowledgement found.