In the study the multimodal optical coherence tomography (MM OCT) including microstructural cross-polarization OCT (CP OCT) imaging with the application of attenuation coefficients combined with compression OCT-elastography (OCE) with quantitative morphological segmentation based on specific stiffness ranges for delineation of breast cancer margins was applied. The research was carried out on different morphological and molecular subtypes of human breast cancer. The findings of this study suggest that OCE and CP OCT of breast cancer images may, in the future, enable real-time feedback to the surgeon about accurate resection margin location in patients with breast cancer.
We demonstrate possibilities of multimodal OCT for quick distinguishing of uninformative necrotic zones from other morphological structures in freshly-excised breast cancer samples to improve information value of subsequent histological examination.
This report presents an overview of recent progress in the development of novel OCE-based technologies enabling non-invasive morphological segmentation of tumor tissues during their natural development and response to therapies. The approach is based on preliminary quantitative assessment of characteristic elasticity ranges corresponding to the segmented morphological constituents (“quasistatic elasto-spectroscopy”). It has been found that such constituents are characterized by fairly well separated ranges of the Young’s modulus, which makes it possible to automatically segment up to 4-6 such zones in OCE-based elasticity maps. High consistency of such OCE-based procedure with conventional morphological segmentation of histological slides in terms of percentages of the segmented-zone areas has been demonstrated. Unlike invasive, time-consuming and laborious histological studies the developed OCE-based segmentation is non-invasive and can be performed even in vivo. High accuracy and sensitivity of the OCE-based-segmentation was demonstrated in vivo for two different types of model tumors (4T1 and Ct26) treated by PDT and chemotherapies. The OCE-based analysis can readily be combined with such OCT-based extensions as texture analysis and OCT-based angiography. The latter opens the possibility to combine morphological assessment with functional characterization of tumor response to therapies. OCE-based characterization of mechanical heterogeneity and elasticity spectra of tumors has also proven to be efficient for express assessment of patients’ breast-cancer subtypes. Overall, the developed OCE-based assessment in many applications suggests a rapid and in vivo feasible alternative to conventional histology and can be efficiently used in a wide range of biomedical problems.
An important factor in assessing tumor status for determining therapeutic and surgical tactics is the study of its morphological structure. In particular, preoperative differentiation/grading of colorectal adenocarcinomas is very important for the adjustment of neoadjuvant therapy, surgical technique choice and survival prediction. To achieve the maximum benefit and to avoid unnecessary side effects, the ability to distinguish high-grade from low-grade colorectal adenocarcinoma, as well as identification of patients with high recurrence risk before the possible initiation of treatment will increase the quality and duration of patients' life. Taking into account the peculiarities of the biology of intestinal cancer, optical coherence elastography, as a method of studying tissue structure at a shallow depth, may be promising in the study of colorectal adenocarcinoma. Possibilities of optical coherence elastography in differentiating low-grade and high-grade types of colorectal adenocarcinoma are demonstrated in this study. The reported results are based on revealed qualitative criteria for assessment of OCE images in combination with quantitative statistically significant differences in characteristic stiffness values for low-grade and high-grade colorectal adenocarcinomas.
As was shown earlier in the animal experiments, compression optical coherence elastography (OCE) is a highly sensitive method for studying the morphological features of biological tissues. An attempt was made to study the possibilities of the OCE method for identifying and differentiating from each other various morphological structures in human tissues. Postoperative samples of human breast cancer and human colon cancer were studied. Histological examination identified areas of morphological structures - (I) adipose tissue, (II) stroma and (III) tumor tissue in breast cancer samples; and areas of (I) mucous membrane and (II) tumor tissue in colon cancer samples. For these areas, an accurate comparison was made with OCE images and stiffness ranges for morphological structures were obtained. This observation allows us to make a conclusion that OСE can be a promising method for studying the structure of human tissue in clinics.
This study presents results on application of compressional optical coherence elastography (OCE) for visualization of a transitional zone between peri-tumoral (normal) and tumor region of breast tissue. The assessment of non-tumor/tumor regions is made based on percentage of pixels with different characteristic stiffness (“stiffness spectrum”) in the OCE image, also taking into account spatial localization of different-stiffness regions. The OCE-based stiffness maps and corresponding histograms of normalized stiffness spectrum demonstrate clear the boundary between normal (peritumoral) tissue and an invasive tumor. The normal breast tissue is fairly heterogeneous on the OCE images with increased stiffness in the region of the lobular structures and lower stiffness in the surrounded soft fibrous and especially adipose tissue of the mammary gland. The invasive breast cancer includes mechanically more dense stiffer accumulations of tumor cells, as well as less stiffer hyalinized tumor stroma. The corresponding histograms of stiffness show clearly dominating and ever increasing percentage of stiff regions in the tumor tissue showing gradually diminishing share of the normal stromal component in tissue. Thus, analysis of the so-obtained normalized histograms (“stiffness spectrum”) may be used to assess the negative surgical margin of resection in the future.
We report a new application of compressional optical coherence elastography (OCE) to discriminate morphological constituents of biological tissues by analyzing OCE images obtained either in vivo or for freshly excised samples. The new technique enables quantitative morphological segmentation of OCE images with delineation of several (~4-6) tissue constituents. As the first step, the method uses compressional OCE to reconstruct stiffness maps for a pre-chosen standardized pressure over the entire area of the OCE image. Then specific stiffness ranges (characteristic "stiffness spectra") are initially determined by careful comparison of the OCE-based stiffness maps with the results of segmentation of "gold-standard" histological slices. After such pre-calibration, the stiffness maps can be automatically segmented into regions, for which the Young’s modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. The results of such automated segmentation of OCE-images demonstrate a striking correlation with the results of conventional segmentation of histological slices in terms of percentages of the segmented zones. High sensitivity of the OCE-method to histological alterations was demonstrated in vivo in comparative studies of various types of anti-tumor therapies using murine tumor models. Studies of >100 samples of freshly excised breast cancer samples revealed strong correlation between the tumor-tissue subtype and its morphological composition determined by the developed OCE method. Thus, the developed approach can be used as a basis for express OCE-based biopsy (feasible intraoperatively). Longitudinal in vivo monitoring of morphological alterations in tumors under therapy or during natural development is also possible for locations accessible to OCT.
Development of noninvasive diagnostic techniques in clinical practice, especially sufficiently fast methods suitable for intraoperative use, remains a topical and challenging problem in modern medicine. Compressional Optical Coherence Elastography (OCE) that has a high potential to be intraoperatively applied. This study reports preliminary results on application of compressional OCE for identification of tumor margins and even differentiation of breast cancer types with low- and high- histological grades, i.e., a step towards creation of a kind of OCE-based optical biopsy. The reported variant of OCE utilized B-scans with scales ~2-4 mm comparable with typical scales of histological samples. The approach is based on the ability of OCE to quantitatively visualize distribution of the Young modulus (stiffness) in studied tissue samples, which then is used to perform "elasto-spectroscopy" generically resembling the massspectroscopy procedures. The procedures of the OCE examination do not require any special preparation of tissue samples and thus can be applied intraoperatively on time intervals ~ a few minutes with immediately available results. In the reported study, the samples after OCE examinations were subjected to histological studies and classification made by an experienced histopathologist. Comparison between the OCE results and histological data made it possible not only to distinguish between normal tissue and tumor (for determining resection boundary), but also to formulate OCE-based criteria allowing for differentiation between carcinomas of low grades and fairly good treatment prognosis and highgrade invasive tumors with poor prognosis. Similarly, identification of not only invasive breast tumors, but also benign breast lesions, intermediate between norm and malignant tumors can be made.
Normal and pathological tissues are different in their elastic properties. Thus, elastic characteristics of tissues can serve as an additional diagnostic marker to distinguish altered tissues. A number of studies have demonstrated advantages of using optical coherent tomography in clinical practice and research. Here we report the application of optical coherence elastography (OCE) for studying elastic properties of murine breast cancer 4T1. It is known that 4T1 model is convenient for in vivo tumor imaging and is highly relevant to studies of tumor process. In this study the therapy was performed with a cytostatic chemotherapeutic drug cisplatin. We developed the protocol of compressional OCT elastography for long-term in vivo monitoring of tumor response to anti-tumor therapy. The ear tumor model was chosen as optimal for this task. Histological analysis demonstrated good agreement with OCE-based stiffness-mapping results.
In this report we present a scanning system and signal processing for three-dimensional strain mapping based on optical coherence tomography. This approach allows evaluating the tissue deformation in 3D for both quasistatic elastography (OCE) and monitoring of slowly relaxing strains (mechanical relaxations, creeps, etc.). Experimental demonstrations of 3D OCE are performed using silicone layer with known structure located on excised breast cancer tissue. It is important to note that in the described variant of OCE we perform aperiodic loading of the tissue not-synchronized with scanning. Because entire 3D datasets are acquired only twice (before and after deformation) it is crucial to ensure that there is already no tissue creep in the deformed state. Experimental demonstrations of monitoring slow processes are performed for visualization of drying of cartilaginous sample. Slow deformation may be undetectable on inter-B-scan intervals because such strain values may be well below minimal detectable level. However, for wider intervals (typical for 3D datasets acquisition), strains can attain an order of magnitude higher level that can be detectable and used for further relaxation parameters calculations. We discuss the applicable scanning patterns and signal processing optimizations.
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