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Updated: Dec 22, 2025

Label-free, High-Resolution 3D Imaging and Machine Learning Analysis of Intestinal Organoids via Low-Coherence Holotomography
Published on: August 12, 2025
Detection of intestinal dysplasia using angle-resolved low coherence interferometry
Neil Terry1, Yizheng Zhu, Julie K M Thacker
1Duke University, Department of Biomedical Engineering, 136 Hudson Hall, Durham, North Carolina 27708, USA. neil.terry@duke.edu
Insights
Angle-resolved low coherence interferometry (a/LCI) can detect intestinal dysplasia by measuring cell nuclei size and density. This optical biopsy technique shows promise for identifying precancerous changes in the colon.
Area of Science:
- Biomedical Optics
- Optical Biopsy
- Gastrointestinal Pathology
Background:
- Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique.
- a/LCI enables label-free, depth-resolved measurement of cell nuclei.
- Previously used for Barrett's Esophagus dysplasia detection.
Purpose of the Study:
- Evaluate a/LCI for identifying intestinal dysplasia ex vivo.
- Assess correlation between nuclear morphology and dysplasia.
- Determine a/LCI's diagnostic performance in colonic tissues.
Main Methods:
- Pilot ex vivo study on 27 patients undergoing colonic resection.
- Collected a/LCI measurements from colonic tissues.
- Compared a/LCI data with histopathological assessment of biopsies.
Main Results:
- Significant correlation between increased nuclear size and reduced density with dysplasia.
- Dysplasia identified at the basal layer (200-300 μm depth).
- Achieved 92.9% sensitivity, 83.6% specificity, and 85.2% accuracy.
Conclusions:
- a/LCI effectively detects intestinal dysplasia in ex vivo colonic tissues.
- Demonstrates potential for optical biopsy in colorectal cancer screening.
- Highlights the need for future in vivo studies to validate findings.
Abstract:
Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has previously been used clinically to identify the presence of dysplasia in Barrett's Esophagus patients undergoing routine surveillance. We present the results of a pilot, ex vivo study of tissues from 27 patients undergoing partial colonic resection surgery, conducted to evaluate the ability of a/LCI to identify dysplasia. Performance was determined by comparing the nuclear morphology measurements with pathological assessment of co-located physical biopsies. A statistically significant correlation between increased average nuclear size, reduced nuclear density, and the presence of dysplasia was noted at the basal layer of the epithelium, at a depth of 200 to 300 μm beneath the tissue surface. Using a decision line determined from a receiver operating characteristic, a/LCI was able to separate dysplastic from healthy tissues with a sensitivity of 92.9% (13/14), a specificity of 83.6% (56/67), and an overall accuracy of 85.2% (69/81). The study illustrates the extension of the a/LCI technique to the detection of intestinal dysplasia, and demonstrates the need for future in vivo studies.
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