The aim of this study is to compare the results of tissue stiffness estimates given by compression (strain) ultrasound elastography (S-USE) and compression optical coherence elastography (C-OCE) beyond the difference in resolution and penetration depth. Namely, the focus of this work is on the contribution of elastic nonlinearity and mechanical inhomogeneity of the tissues to the stiffness estimates and resultant diagnostic performance of these techniques. We demonstrate that in comparison with S-USE despite basically the same compression principle, the applied realization of quantitative C-OCE have novel capabilities due to its ability to obtain spatially-resolved local pressure control and the local stress-strain curve mapping within the tissue.
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.
The aim of this study was to evaluate the application of attenuation coefficients calculated from the cross-polarization optical coherence tomography (CP OCT) data for differentiation of breast cancer from non-tumorous breast tissues. For this purpose, surgically obtained breast specimens from 45 patients were examined using CP OCT in order to construct color-coded en-face OCT maps based on calculation of three optical coefficients (the commonly used rate of attenuation in the co- polarization channel; and, additionally, the attenuation in the cross- polarization channel; and the interchannel attenuation difference). It was shown that the use of these optical coefficients significantly increased the amount of obtained information from the OCT data in comparison with unprocessed images, enabling objective quantification for differentiating non-tumorous and tumorous tissue (adipose tissue, normal stroma, tumor stroma and agglomerates of tumor cells). The attenuation in the cross- polarization channel and the interchannel attenuation difference provided greater contrast for the visualization of the different breast cancer structures compared to the attenuation coefficient in the co- polarization channel. The findings of this study suggest that assessment of CP OCT images of breast cancer based on optical coefficients calculation may in perspective enable real-time feedback about accurate resection margin in patient with breast cancer to the surgeon.
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.
Breast cancer is a genetically heterogeneous disease characterized by various biomolecular and morphological features that affect the diagnosis, prognosis, and treatment response. In this study we combined cross-polarization optical coherence tomography (CP OCT) and multiphoton tomography (MPT), based on second harmonic generation (SHG), and two-photon-excited fluorescence (TPEF) to visualize tumor stroma and tumor cells in specimens of a human breast tissue. The data obtained by both techniques were compared with histopathology. The CP OCT and MPT images were quantitatively assessed to distinguish a breast normal tissue from a cancer as well as between a low and a high grade of cancer. Quantitative assessment of the CP OCT image included the calculation of signal attenuation coefficients separately for co- and cross- polarization channels and the formation the color-coded en-face distribution maps of these coefficients. The attenuation coefficient in cross- polarization channel showed better difference between breast cancer of low and high grades and distinguish them from normal tissue. The SHG images were processed using texture analysis techniques to quantify the density of collagen fibers in normal tissue and tumor. Thus, both imaging techniques have great potential to distinguish nontumorous and tumorous human breast tissue of varying degrees of malignancy and could provide identifying breast cancer margins for in surgery.
A multimodal optical coherence tomography (MM OCT) combining microstructural cross-polarization (CP) imaging and compression OCT-elastography (OCE) was employed in this study. The research was carried out on the noninvasive and invasive subtypes of human breast cancer. This study demonstrates how CP OCT combined with OCTelastography identifies an example of DCIS cancer that progresses into invasive breast cancer. OCE images more clearly show the cross sections of the ducts filled with tumor cells for DCIS (high-contrast structures with clear boundaries and high stiffness values) surrounded by areas with lower stiffness corresponding to fibrous stroma regions. The regions of invasive breast cancer in OCE-scans look as zones with strongly increased stiffness, which well agrees with the histology. Percentage of pixels with different characteristic stiffness ("stiffness spectrum") in the OCTelastography images was assessed to quantitatively visualize stiffness of tumor. The demonstrated ability of MM OCT imaging for breast cancer subtypes differentiation and breast cancer margin assessment is important for improved managements of patients.
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.
Elastic properties of soft biological tissues may reflect their functional state and be a sensitive indicator of important pathological processes occurring in them. Using compressional optical coherent elastography (OCE) we revealed significant differences not only in the value of the Young modulus, but also in the character of elastic responses of biological tissues in different pathological states (including such key states as inflammatory, oncological and degenerative processes) in ex vivo human tissues. Here, we demonstrate a bright example of such qualitatively and quantitatively different trends: unlike breast cancer characterized by strongly elevated (in comparison with norm) stiffness that pronouncedly increases with compression, stiffness of pelvic organ prolapse is strongly decreased and weakly varies with compression.
In this study we combined cross-polarization optical coherence tomography (CP OCT), multiphoton tomography (MPT), based on second harmonic generation, and two-photon-excited fluorescence to visualize collagen fibers and tumor cells in the various morphological subtypes of breast cancer. The ability of CP OCT to visualize tissue birefringence and cross-scattering adds new information about the microstructure of such breast cancers, while the MPT provides verification of this microstructure. Mammary glands, both normal and tumorous, were assessed by MPT and CP OCT to establish the relationships between spatial organization features of the cellular component and the intercellular matrix. It was shown, that such multimodal optical imaging has great potential for distinguishing various breast cancer morphological subtypes and could provide useful tools for identifying positive breast cancer margins for surgery.
Introduction of innovative noninvasive diagnostic techniques in clinical practice remains an actual topic of modern medicine. In the study, we assessed feasibility of multimodal OCT (MM OCT) that combines crosspolarization imaging and elastographic stiffness mapping to assess spatial structural organization and heterogeneity of breast cancer in the tumor center in comparison with normal mammary gland tissue. The research was carried out using human breast tissue mastectomy surgical samples including different histological types of breast cancer: ductal carcinoma in situ, invasive lobular and ductal carcinoma, fibroadenoma and normal tissue. The histological subtypes of breast cancer showed different structural and stiffness features of tumor tissue. In the case of invasive ductal carcinoma, the cross-polarization OCT image shows a more heterogeneous high-level OCT signal and higher stiffness in comparison with lobular breast cancer or fibroadenoma. These results indicate that assessing microstructures and elasticity changes yields complementary information about the microstructural features of breast cancer, which is important for selection of treatment tactics.
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