Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography

Abstract

Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young’s modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer – low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors.

Tissue Elasticity as a Diagnostic Marker of Molecular Mutations in Morphologically Heterogeneous Colorectal Cancer

“…The stiffness values of mucinous and solid pattern areas were not statistically significantly different (p = 0.29). However, as was described above, visual C-OCE image assessment of these patterns allows for their distinction (Figure 2B), as we have shown previously in a paper [43].…”

“…In our previous studies, we demonstrated the capabilities of C-OCE for highly sensitive imaging of the CRC tissue structure based on the differences in the elastic properties of individual morphological components [42,43]. This research is the next step toward C-OCE application to CRC screening in terms of understanding the relationship between molecular mutations in cancer and their elasticity/stiffness.…”

“…The frequency of driver mutations in high-grade CRC cases was much higher (77%) compared to low-grade CRC cases in which driver mutations were significantly less common (30%) (Table 1). A statistically significant association (p = 0.0073, Fisher's exact Subsequent quantitative analysis of stiffness values was carried out only for C-OCE image zones with stiffness > 520 kPa (from yellow to dark-blue) because this threshold was previously established for identifying CRC cells [43]. Consequently, quantification of these three CRC morphological patterns by ROIs turned out to be quite different: complex tubular pattern had the lowest stiffness values (mean ± standard deviation) of 770 ± 164 kPa (Figure 2C), which were statistically significantly different from stiffness values of mucinous pattern of 968 ± 234 kPa and stiffness values of solid pattern of 1039 ± 270 kPa (p < 0.0001, Mann-Whitney U test).…”

“…Further, the application of ultrasound elastography has been successful in visualizing the depth of CRC invasion [53]. The combination of OCT and elastography in one technology-C-OCE-allowed getting closer to the CRC morphology and made it possible to distinguish the CRC morphological patterns of the tumor node [43]. In the current study, as well as in [43], CRC morphological patterns are also analyzed, but the groups include a larger number of ROIs, which allows for slight correction of the mean stiffness values for each of the CRC morphological patterns and proposes a stiffness value of 857 kPa for reliable differentiation of solid patterns from the complex tubular one.…”

“…However, some limitations of the presented study considering the prospects for using the C-OCE as a diagnostic tool in clinical practice need to be recognized: (i) the established diagnostic parameters require mandatory testing on a larger number of CRC cases; (ii) the implementation of C-OCE diagnostics is currently possible only in ex vivo study of CRC tissue for the following reasons: in compression C-OCE, direct access to the contact between the probe and the tissue being examined is needed, and there are no certified endoscopic options for C-OCE-they are still in the process of development and testing [43]; (iii) relatively small field of view (~4 × 1 mm) and required post-processing time per OCE image (~2 min) may significantly increase the time of examination of a large tumor node.…”