Abstract
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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 (Hbtotal), deoxygenated (HbR), 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, Hbtotal 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 Hbtotal 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.