Multimodal Optical Coherence Tomography for Intraoperative Evaluation of Tumor Margins and Surgical Margins in Breast-Conserving Surgery.

The aim of the study: We compare the effectiveness of multimodal optical coherence tomography (MM OCT) in the traditional structural OCT mode and the OCT elastography (OCE) mode in addressing two clinically important tasks: (1) detecting groups of tumor cells at surgical margins during breast-сonserving surgery (BСS) in breast cancer (BC) and (2) identifying breast tumor margins. The obtained results were correlated with corresponding histological sections. Materials and Methods: The study was performed on 100 surgical margin samples (top, bottom, medial, and lateral - four samples from each patient in total) obtained from 25 patients with BC who underwent BCS (lumpectomy), and on 25 postoperative tumor samples (to determine tumor margins). With MM OCT method, we visually and numerically assessed the scattering (level and depth of OCT signal penetration) and elastic (stiffness values, or Young's modulus (kPa)) properties of the tumor and non-tumor breast tissue and the obtained values were compared with the results of postoperative histological examination. Results: In 4 surgical margin samples (out of 100), with the OCE method we identified groups of histologically confirmed tumor cells ("positive" resection margins) at the distance of about 5 mm from the visible tumor margin. The identified zones were larger than 0.5 mm with stiffness of more than 400 kPa in all these cases. However, the structural OCT could not identify these groups of tumors and they were not distinguishable from the surrounding fibrous tissue.In the areas of tumor into non-tumor tissue transition, structural OCT images detected tumor margins only if they were adjacent to adipose tissue and did not detect them if there were adjacent to non-tumor fibrous tissue. OCE images with high stiffness values (more than 400 kPa) and high contrast showed a clear tumor margin with both adipose and fibrous tissue. Conclusion: The study demonstarets the potential of MM OCT, particularly its OCE mode, as a real-time method for intraoperative tumor margin and surgical margin assessment in BCS. OCE images compared to structural OCT images visualize higher contrast between different types of breast tissue (adipose tissue, fibrous stroma, hyalinized stroma, tumor cell clusters), as well as more accurate identification of the tumor border and detection of small groups of tumor cells at surgical margins. An algorithm for intraoperative MM OCT examination of the state of the resection margin is proposed in accordance with standard clinical guidelines for achieving clean surgical margins in breast cancer patients.

Combined Application of Dual-Wavelength Fluorescence Monitoring and Contactless Thermometry during Photodynamic Therapy of Basal Cell Skin Cancer.

The aim of the study was to assess the capabilities of combined application of dual-wavelength fluorescence visualization and contactless skin thermometry during photodynamic therapy monitoring (PDT) of basal cell cancer. MATERIALS AND METHODS: The study was performed at the University Clinic of Privolzhsky Research Medical University (Nizhny Novgorod). Nine clinically, dermatoscopically, and histologically verified foci of basal cell skin cancer were exposed to PDT sessions (wavelength of 662 nm, light dose density of 150 J/cm2) with systemic application of chlorin-based photosensitizer Fotoditazin. A semiconductor laser system Latus-T (Russia) was employed for irradiation. Dual-wavelength fluorescence visualization and contactless thermometry with an IR pyrometer were used to monitor the PDT sessions. RESULTS: The PDT sessions of nine foci of basal cell cancer were carried out under the control of fluorescence imaging and contactless thermometry. Photosensitizer photobleaching in all foci amounted to 40% signifying a percent of photosensitizer involved in the photodynamic reaction. It has been shown that the combined employment of dual-wavelength fluorescence monitoring and contactless thermometry during the PDT of basal cell skin cancer allows oncologists to control simultaneously the degree of photosensitizer photobleaching and the depth of the photodynamic effect in tissues, the extent of involving the mechanisms associated with hyperthermia as well as the correctness of the procedure conducting. In the course of 9-month dynamic follow-up after the treatment, no clinical and dermatoscopic signs of recurrence were found. CONCLUSION: A bimodal control of PDT enables the assessment of the correctness and efficacy of the procedure performance. The contactless control of tissue heating allows ensuring the temperature mode for hyperthermia realization, while the fluorescence monitoring makes it possible to evaluate the accumulation of the photosensitizer in the tumor and the depth of the PDT action as well as to predict the procedure efficacy based on the photobleaching data. The complementary use of these techniques allows the adjustment of the mode directly in the course of the PDT procedure. The acquisition of the sufficient statistical data on the combined monitoring will result in the development of a novel PDT protocol.

Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study.

Microvascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.

Photodynamic therapy monitoring with optical coherence angiography.

Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement.