Multispectral Optoacoustic Tomography in Crohn’s disease - A First-in-human Diagnostic Clinical Trial

Objectives: Crohn’s disease (CD) is a lifelong chronic inflammatory condition resulting in a requirement for frequent clinical and endoscopic reassessment. Multispectral optoacoustic tomography (MSOT), a new technique for analysis of haemoglobin and oxygenation in tissues, was tested in patients with CD as a non-invasive alternative to predict intestinal disease activity.

Methods: In this single center, investigator-initiated, cross-sectional diagnostic study, n=108 patients with confirmed CD were imaged by MSOT. The ethics committee of the University of Erlangen-Nürnberg granted approval for the study, it was registered at clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT02622139), and all patients signed informed consent to participate. Imaging was performed at six single wavelengths (700, 730, 760, 800, 850, and 900 nm) and MSOT parameters, total (Hb_total), deoxygenated (Hb_R), oxygenated haemoglobin (HbO₂), and saturation, were derived by spectral unmixing. Diagnostic performance was gauged by comparison to clinical (Harvey-Bradshaw Index, HBI), endoscopic (Simplified Endoscopic Score for Crohn’s Disease, SES-CD), and histologic (modified Riley score) scoring systems.

Results: B-Mode ultrasound imaging identified inflamed intestine and MSOT was performed with scan times of approximately 5 minutes per patient. While patients with clinical remission or active disease showed no differences in MSOT parameters, Hb_total was higher in endoscopic/histologic active disease (87.1 a.u. [77.2-91.6], p<0.001/87.1 [IQR 78.4-91.9], p=0.001) compared to remission (69.0 [62.5-78.8]/73.5 [68.6-79.2]). Similarly, in active disease, oxygenated (p=0.001/p=0.007) and deoxygenated haemoglobin (p<0.001/p=0.002) was increased compared to remission. MSOT provided higher diagnostic performance compared to Harvey-Bradshaw Index (AUROC: 0.59), C-reactive protein (0.79), and ultrasound (Limberg score, 0.76) reaching a maximum for detection of endoscopic disease activity at 900 nm with a sensitivity of 100.0% (95%CI 89.1-100) and a specificity of 77.8% (40.0-97.2, AUROC 0.92). Increased Hb_total signals correlated directly with low (p=0.016/p=0.034) and moderate (p<0.001/p=0.001) endoscopic/histologic activity and high endoscopic activity (p<0.001).

Conclusion: MSOT is the first non-invasive, isotope- and contrast-agent-free, bed-side imaging modality to predict endoscopic/histologic disease activity in patients with CD. This preliminary study suggests that MSOT-based assessment of haemoglobin levels in the intestinal wall may be able to assess remission and active disease in CD without the need for more invasive procedures. Research Support: German Research Foundation, Graduate School in Advanced Optical Technologies, Center for Clinical Research, and the Emerging Fields Initiative of the Friedrich-Alexander-Universität Erlangen-Nürnberg.