The possibility to assess molecular-biological and morphological features of particular breast cancer types can improve the precision of resection margin detection and enable accurate determining of the tumor aggressiveness, which is important for treatment selection. To enable reliable differentiation of breast-cancer subtypes and evaluation of resection margin, without performing conventional histological procedures, here we apply cross-polarization optical coherence tomography (CP-OCT) and compare it with a novel variant of compressional optical coherence elastography (C-OCE) in terms of the diagnostic accuracy (Ac) with histological verification. The study used 70 excised breast cancer specimens with different morphological structure and molecular status (Luminal A, Luminal B, Her2/Neo+, non-luminal and triple-negative cancer). Our first aim was to formulate convenient criteria of visual assessment of CP-OCT and C-OCE images intended (i) to differentiate tumorous and non-tumorous tissues and (ii) to enable more precise differentiation among different malignant states. We identified such criteria based on the presence of heterogeneities and characteristics of signal attenuation in CP-OCT images, as well as the presence of inclusions/mosaic structures combined with visually feasible assessment of several stiffness grades in C-OCE images. Secondly, we performed a blinded reader study of the Ac of C-OCE versus CP-OCT, for delineation of tumorous versus non-tumorous tissues followed by identification of breast cancer subtypes. For tumor detection, C-OCE showed higher specificity than CP-OCT (97.5% versus 93.3%) and higher Ac (96.0 versus 92.4%). For the first time, the Ac of C-OCE and CP-OCT were evaluated for differentiation between non-invasive and invasive breast cancer (90.4% and 82.5%, respectively). Furthermore, for invasive cancers, the difference between invasive but low-aggressive and highly-aggressive subtypes can be detected. For differentiation between non-tumorous tissue and low-aggressive breast-cancer subtypes, Ac was 95.7% for C-OCE and 88.1% for CP-OCT. For differentiation between non-tumorous tissue and highly-aggressive breast cancers, Ac was found to be 98.3% for C-OCE and 97.2% for CP-OCT. In all cases C-OCE showed better diagnostic parameters independently of the tumor type. These findings confirm the high potential of OCT-based examinations for rapid and accurate diagnostics during breast conservation surgery.

Soft biological tissues, breast cancer tissues in particular, often manifest pronounced nonlinear elasticity, i.e., strong dependence of their Young’s modulus on the applied stress. We showed that compression optical coherence elastography (C-OCE) is a promising tool enabling the evaluation of nonlinear properties in addition to the conventionally discussed Young’s modulus in order to improve diagnostic accuracy of elastographic examination of tumorous tissues. The aim of this study was to reveal and quantify variations in stiffness for various breast tissue components depending on the applied pressure. We discussed nonlinear elastic properties of different breast cancer samples excised from 50 patients during breast-conserving surgery. Significant differences were found among various subtypes of tumorous and nontumorous breast tissues in terms of the initial Young’s modulus (estimated for stress < 1 kPa) and the nonlinearity parameter determining the rate of stiffness increase with increasing stress. However, Young’s modulus alone or the nonlinearity parameter alone may be insufficient to differentiate some malignant breast tissue subtypes from benign. For instance, benign fibrous stroma and fibrous stroma with isolated individual cancer cells or small agglomerates of cancer cells do not yet exhibit significant difference in the Young’s modulus. Nevertheless, they can be clearly singled out by their nonlinearity parameter, which is the main novelty of the proposed OCE-based discrimination of various breast tissue subtypes. This ability of OCE is very important for finding a clean resection boundary. Overall, morphological segmentation of OCE images accounting for both linear and nonlinear elastic parameters strongly enhances the correspondence with the histological slices and radically improves the diagnostic possibilities of C-OCE for a reliable clinical outcome.

We present a real-time realization of OCT-based elastographic mapping local strains and distribution of the Young’s modulus in biological tissues, which is in high demand for biomedical usage. The described variant exploits the principle of Compression Optical Coherence Elastography (C-OCE) and uses processing of phase-sensitive OCT signals. The strain is estimated by finding local axial gradients of interframe phase variations. Instead of the popular least-squares method for finding these gradients, we use the vector approach, one of its advantages being increased computational efficiency. Here, we present a modified, especially fast variant of this approach. In contrast to conventional correlation-based methods and previously used phase-resolved methods, the described method does not use any search operations or local calculations over a sliding window. Rather, it obtains local strain maps (and then elasticity maps) using several transformations represented as matrix operations applied to entire complex-valued OCT scans. We first elucidate the difference of the proposed method from the previously used correlational and phase-resolved methods and then describe the proposed method realization in a medical OCT device, in which for real-time processing, a “typical” central processor (e.g., Intel Core i7-8850H) is sufficient. Representative examples of on-flight obtained elastographic images are given. These results open prospects for broad use of affordable OCT devices for high-resolution elastographic vitalization in numerous biomedical applications, including the use in clinic.

The aims of this study are (i) to compare ultrasound strain elastography (US-SE) and compression optical coherence elastography (C-OCE) in characterization of elastically linear phantoms, (ii) to evaluate factors that can cause discrepancy between the results of the two elastographic techniques in application to real tissues, and (iii) to compare the results of US-SE and C-OCE in the differentiation of benign and malignant breast lesions. On 22 patients, we first used standard US-SE for in vivo assessment of breast cancer before and then after the lesion excision C-OCE was applied for intraoperative visualization of margins of the tumors and assessment of their type/grade using fresh lumpectomy specimens. For verification, the tumor grades and subtypes were determined histologically. We show that in comparison to US-SE, quantitative C-OCE has novel capabilities due to its ability to locally control stress applied to the tissue and obtain local stress-strain curves. For US-SE, we demonstrate examples of malignant tumors that were erroneously classified as benign and vice versa. For C-OCE, all lesions are correctly classified in agreement with the histology. The revealed discrepancies between the strain ratio given by US-SE and ratio of tangent Young’s moduli obtained for the same samples by C-OCE are explained. Overall, C-OCE enables significantly improved specificity in breast lesion differentiation and ability to precisely visualize margins of malignant tumors compared. Such results confirm high potential of C-OCE as a high-speed and accurate method for intraoperative assessment of breast tumors and detection of their margins.

A computationally efficient and fairly realistic model of OCT-scan formation in spectral-domain optical coherence tomography is described. The model is based on the approximation of discrete scatterers and ballistic character of scattering, these approximations being widely used in literature. An important feature of the model is its ability to easily account for arbitrary scatterer motions and computationally efficiently generate large sequences of OCT scans for gradually varying configurations of scatterers. This makes the proposed simulation platform very convenient for studies related to the development of angiographic processing of OCT scans for visualization of microcirculation of blood, as well as for studies of decorrelation of speckle patterns in OCT scans due to random (Brownian type) motions of scatterers. Examples demonstrating utilization of the proposed model for generation OCT scans imitating perfused vessels in biological tissues, as well as evolution of speckles in OCT scans due to random translational and rotational motions of localized (but not-point-like) scatterers are given. To the best of our knowledge, such numerical simulations of large series of OCT scans in the presence of various types of motion of scatterers have not been demonstrated before.

This paper presents a recently developed variant of phase-resolved Optical Coherence Elastography (OCE) enabling non-contact visualization of transient local strains of various origins in biological tissues and other materials. In this work, we demonstrate the possibilities of this new technique for studying dynamics of osmotically-induced strains in cartilaginous tissue impregnated with optical clearing agents (OCA). For poroelastic water-containing biological tissues, application of non-isotonic OCAs, various contrast additives, as well as drug solutions administration, may excite transient spatially-inhomogeneous strain fields of high magnitude in the tissue bulk, initiating mechanical and structural alterations. The range of the strain reliably observed by OCE varied from ±10⁻³ to ±0.4 for diluted and pure glycerol, correspondingly. The OCE-technique used made it possible to reveal previously inaccessible details of the complex spatio-temporal evolution of alternating-sign osmotic strains at the initial stages of agent diffusion. Qualitatively different effects produced by particular hydrophilic OCAs, such as glycerol and iohexol, are discussed, as well as concentration-dependent differences. Overall, the work demonstrates the unique abilities of the new OCE-modality in providing a deeper insight in real-time kinetics of osmotically-induced strains relevant to a broad range of biomedical applications.