Compression Optical Coherence Elastography for Assessing Lymph Node Status in Early Breast Cancer
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Keywords

compression optical coherence elastography (C-OCE)
stiffness (Young's modulus)
nonlinear elastic properties
lymph nodes
breast cancer
metastasis

How to Cite

Vorontsov , D. A., Krivorotko, P. V., Gladkova, N. D., Tabagua, T. T., Sovetsky, A. A., Bederina, E. L., Sirotkina, M. A., Vorontsov, A. Y., Gamayunov, S. V., Zaitsev , V. Y., & Gubarkova, E. V. (2023). Compression Optical Coherence Elastography for Assessing Lymph Node Status in Early Breast Cancer. Voprosy Onkologii, 69(5), 885–896. https://doi.org/10.37469/0507-3758-2023-69-5-885-896

Abstract

Introduction. Assessment of the state of the lymph nodes is an important factor in determining the stage of the disease and choosing the optimal treatment tactics for breast cancer. In traditional lymph node dissection, only a small proportion of lymph nodes are often found to be metastatic, and this fact must be weighed against potential complications of dissection, such as lymphedema. Biopsy of sentinel lymph nodes using radiopharmaceuticals is currently an important step in surgical treatment and the standard method of regional staging in patients with early stages of breast cancer throughout the world. However, the main limitations of this method are the administration of exogenous agents, postoperative histological analysis, and the possibility of false negative results. There remains a need for the development and application of new intraoperative high-resolution and label-free imaging that can detect lymph nodes, which removal will reliably determine the extent of the tumor process in regional lymphatic collectors without lymphadenectomy. Optical coherence tomography (OCT) with its new modality, compression OCT elastography (C-OCE), can become such a method, capable of quantitatively assessing the elastic properties of biological tissues, which can significantly change with metastatic lesions of the lymph nodes, with a spatial resolution of about 40-50 µm.

The aim of the study was to study linear (stiffness) and nonlinear elastic properties of lymph nodes in the presence and absence of breast cancer metastases with the histological verification of the main structural components of the lymph nodes using the C-OCE method.

Materials and methods. A total of 27 postoperative sentinel and axillary lymph nodes were examined in 24 patients. Patients aged 54-73 years included in this study had previously histologically confirmed breast cancer with clinical stage T1-2N0M0 stage IA-IIA, and they were scheduled for breast-conserving surgery or amputation of the breast with sentinel lymph node biopsy. All patients underwent intraoperative lymphoscintigraphy after injection of a radiopharmaceutical (technetium-99m).

The study was carried out using a high-speed spectral-domain multimodal OCT device (Institute of Applied Physics of the RAS, Russia), which provides C-OCE for visualization of linear and nonlinear elastic properties of the tissue, with the calculation of the absolute values of the stiffness (Young's modulus in kPa) and the elastic non-linearity parameter of the tissue. Verification of the obtained OCT data was carried out using a standard histological study, according to the results of which all lymph nodes were divided into: normal (inactive) (n=6), reactive with follicular hyperplasia (n=7), reactive with sinus histiocytosis (n=8) and metastatic (n=6) lymph nodes.

Results. It was found that normal lymph nodes on C-OCE images are characterized by the lowest stiffness values in the cortical area with preserved lymphoid follicles (<200 kPa). Reactive lymph nodes with follicular hyperplasia show moderately elevated stiffness values (200-300 kPa) in the cortical region and more pronounced stiffness values (400-600 kPa) in areas of sinus histiocytosis. Lymph nodes with total metastasis show the highest stiffness values (> 600 kPa). Concerning the Young's modulus, which defines the linear elastic properties of tissue, there remains a noticeable overlap in stiffness values between these types of lymph nodes. Therefore, we also estimated the parameters of their elastic nonlinearity. The complementary use of both linear and nonlinear elastic parameters made it possible to differentiate all four main conditions of the lymph nodes with high statistical significance (p<0.0001).

Conclusions. C-OCE allows differentiation of normal, reactive and metastatic lymph nodes with higher contrast compared to conventional structural OCT imaging. C-OCE imaging shows a high potential for future intraoperative use to determine the status of lymph nodes in real time and assess the extent of breast cancer in regional lymphatic collectors to preserve intact lymph nodes.

https://doi.org/10.37469/0507-3758-2023-69-5-885-896
pdf (Русский)

References

Lyman GH, Somerfield MR, Bosserman LD, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017;35(5):561-564. https://doi.org/10.1200/JCO.2016.71.0947.

Криворотько П.В., Табагуа Т.Т., Комяхов А.В., и др. Биопсия сигнальных лимфатических узлов при раннем раке молочной железе: опыт НИИ онкологии им. Н.Н. Петрова. Вопросы онкологии. 2017;63(2):267-273 [Krivorotko PV, Tabagua TT, Komyakhov AV, et al. Sentinel lymph node biopsy in early breast cancer: the experience of the N.N. Petrov National Medical Research Center of Oncology. Voprosy Onkologii. 2017;63(2):267-273 (In Russ.)]. https://doi.org/10.18027/2224-5057-2016-4s1-4-8.

Berrocal J, Saperstein L, Grube B, et al. Intraoperative injection of Technetium-99m sulfur colloid for sentinel lymph node biopsy in breast cancer patients: a single institution experience. Surg Res Pract. 2017;2017:5924802. https://doi.org/10.1155/2017/5924802.

Mazouni C, Koual M, De Leeuw F, et al. Prospective evaluation of the limitations of near-infrared imaging in detecting axillary sentinel lymph nodes in primary breast cancer. Breast J. 2018;24(6):1006-1009. https://doi.org/10.1111/tbj.13123.

Криворотько П.В., Канаев С.В., Семиглазов В.Ф., и др. Методологические проблемы биопсии сигнальных лимфатических узлов у больных раком молочной железы. Вопросы онкологии. 2015;61(3):418-423 [Krivorotko PV, Kanaev SV, Semiglazov VF, et al. Methodological problems of sentinel lymph node biopsy in breast cancer patients. Voprosy Onkologii. 2015;61(3):418-423 (In Russ.)].

Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: A metaanalysis. Cancer. 2006;106(1):4-16. https://doi.org/10.1002/cncr.21568.

Meric-Bernstam F, Rasmussen JC, Krishnamurthy S, et al. Toward nodal staging of axillary lymph node basins through intradermal administration of fluorescent imaging agents. Biomed Opt Express. 2013;5(1):183-96. https://doi.org/10.1364/BOE.5.000183.

Krivorotko P, Zhiltsov E, Tabagua T, et al. Immediate results of determining the sentinel lymph nodes in breast cancer patients using a combination of radioisotope and fluorescent methods. Eur J Cancer. 2018;92:s69-s70. https://doi.org/10.1016/S0959-8049(18)30433-7

Zhu Y, Fearn T, Chicken DW, et al. Elastic scattering spectroscopy for early detection of breast cancer: partially supervised Bayesian image classification of scanned sentinel lymph nodes. J Biomed Opt. 2018;23(8):1-9. https://doi.org/10.1117/1.JBO.23.8.085004.

McLaughlin RA, Scolaro L, Robbins P, et al. Imaging of human lymph nodes using optical coherence tomography: potential for staging cancer. Cancer Res. 2010;70(7):2579-84. https://doi.org/10.1158/0008-5472.CAN-09-4062.

Leitgeb R, Placzek F, Rank E, et al. Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography. J Biomed Opt. 2021;26(10):100601. https://doi.org/10.1117/1.JBO.26.10.100601.

Foo KY, Newman K, Fang Q, et al. Multi-class classification of breast tissue using optical coherence tomography and attenuation imaging combined via deep learning. Biomed Opt Express. 2022;13(6):3380-3400. https://doi.org/10.1364/BOE.455110.

Schmitt J. OCT elastography: imaging microscopic deformation and strain of tissue. Opt Express. 1998;3(6):199-211. https://doi.org/10.1364/oe.3.000199.

Sigrist RMS, Liau J, Kaffas AE, et al. Ultrasound elastography: review of techniques and clinical applications. Theranostics. 2017;7(5):1303-1329. https://doi.org/10.7150/thno.18650.

Бусько Е.А., Мищенко А.В., Семиглазов В.В., Табагуа Т.Т. Эффективность УЗИ и соноэластографии в диагностике непальпируемых и пальпируемых образований молочной железы. Вопросы онкологии. 2013;3:375-381 [Busko ЕА, Mishchenko АV, Semiglazov VV, Tabagua ТТ. Efficacy of ultrasound and sonoelastography in diagnosis of non-palpable and palpable breast lesions. Voprosy Onkologii. 2013;59 (3):375-381 (In Russ.)].

Ковалева Е.В., Данзанова Т.Ю., Синюкова Г.Т., и др. Мультипараметрическая ультразвуковая диагностика измененных лимфатических узлов при первичномножественных злокачественных опухолях, включающих рак молочной железы и лимфому. Злокачественные опухоли 2018;8(4):37-44 [Kovaleva EV, Danzanova TYu, Sinyukova GT, et al. Multiparametric ultrasound diagnosis of metastatic and lymphoproliferative changes in lymph nodes in primary-multiple malignant tumors, including breast cancer and lymphoma. Malignant Tumours. 2018;8(4):37-44 (In Russ.)]. https://doi.org/10.18027/2224-5057-2018-8-4-37-44.

Борсуков А.В., Морозова Т.Г., Ковалев А.В., и др. Тенденции развития компрессионной соноэластографии поверхностных органов и эндосонографии в рамках стандартизации методики. Вестник новых медицинских технологий. Электронное издание. 2015;2 [Borsukov AV, Morozova TG, Kovalev AV, at al. Trends in the development of compression sonoelastography superficial organs and endosonography in the field of the standardization methods. Journal of New Medical Technologies. eJournal. 2015;2 (In Russ.)]. https://doi.org/10.12737/10745.

Gong P, Chin SL, Allen WM, et al. Quantitative micro-elastography enables in vivo detection of residual cancer in the surgical cavity during breast-conserving surgery. Cancer Res. 2022;82(21):4093-4104. https://doi.org/10.1158/0008-5472.CAN-22-0578.

Gubarkova EV, Sovetsky AA, Zaitsev VY, et al. OCT-elastography-based optical biopsy for breast cancer delineation and express assessment of morphological/molecular subtypes. Biomed Opt Express. 2019;10(5):2244-2263. https://doi.org/10.1364/BOE.10.002244.

McLaughlin RA, Latham B, Sampson DD, et al. Investigation of optical coherence micro-elastography as a method to visualize micro-architecture in human axillary lymph nodes. BMC Cancer. 2016;16(1):874. https://doi.org/10.1186/s12885-016-2911-z.

Zaitsev VY, Matveyev AL, Matveev LA, et al. Strain and elasticity imaging in compression optical coherence elastography: The two-decade perspective and recent advances. J Biophotonics. 2021;14(2):e202000257. https://doi.org/10.1002/jbio.202000257.

Matveyev AL, Matveev LA, Sovetsky AA, et al. Vector method for strain estimation in phase-sensitive optical coherence elastography. Laser Phys. Lett. 2018;15:065603. https://doi.org/10.1088/1612-202X/aab5e9.

Sovetsky AA, Matveyev AL, Matveev LA, et al. Full-optical method of local stress standardization to exclude nonlinearity-related ambiguity of elasticity estimation in compressional optical coherence elastography. Laser Phys. Lett. 2020;17:065601. https://doi.org/10.1088/1612-202X/ab8794.

Gubarkova EV, Sovetsky AA, Matveev LA, et al. Nonlinear elasticity assessment with optical coherence elastography for high-selectivity differentiation of breast cancer tissues. Materials (Basel). 2022;15(9):3308. https://doi.org/10.3390/ma15093308.

Grieve K, Mouslim K, Assayag O, et al. Assessment of sentinel node biopsies with full-field optical coherence tomography. Technol Cancer Res Treat. 2016;15(2):266-74. https://doi.org/10.1177/1533034615575817.

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