Design and Development of Opto-ThermoAcoustic (OTA) Measurement System to Differentiate Cancer from Adjacent Normal Breast Biopsy Tissue

Abstract

Breast cancer is the most common cancer accounting for almost 11.7% of all cancer incidences and 6.9% of cancer-related deaths globally in 2020, as per Globocan 2020 report. Diagnosis of breast cancer requires microscopic examination of tissue taken by a needle-core biopsy. These core biopsy tissues are then sliced to a few hundred micrometers, mounted on glass slides, and stained using hematoxylin and eosin. These glass slides are examined by an expert pathologist under a microscope to diagnose the cancer pathology. This thesis proposes an opto-thermal-acoustic (OTA) multimodal system (Hybrid Spectral-IRDx) that can quantify the bulk optical, thermal, and acoustic property of these tissues to aid the pathologist with additional information. This tool can provide immediate feedback over the adequacy of tumor resection in the operating room, potentially guiding the pathologist to make an informed decision. In this thesis, the Hybrid Spectral-IRDx Tool with the ability to quantify the bulk optical, thermal, and acoustic properties of the breast biopsy tissue is designed and developed. The Hybrid Spectral-IRDx system can quantify the optical attenuation coefficient (µa), reduced scattering coefficient (µs`), thermal conductivity (k), heat capacity (Cp), and acoustic attenuation coefficient (α), of breast biopsy tissue. This system was used to characterize ex-vivo deparaffinized and formalin-fixed cancerous and adjacent normal tissues. The measurement on the formalin-fixed (FF) and deparaffinized (DP) breast biopsy tissues from a total of N = 30 subjects was performed. The ultrasound and optical measurements were performed on cancerous/fibroadenoma and its adjacent normal tissues from the same patients (N=19). The acoustic attenuation coefficient (α) and reduced scattering coefficient (µs`) (at 850, 940, and 1060 nm) for the cancerous/fibroadenoma tissues from N = 14 patients were reported to be higher compared to adjacent normal tissues, a basis of delineation. Comparing FF cancerous and adjacent normal tissue, the difference in µs` at 850 nm and 940 nm were statistically significant (p=3.17e-2 and 7.94e-3 respectively). The difference in α between the cancerous and adjacent normal tissues for DP and FF tissues was also statistically significant (p=2.85e-2 and 7.94e-3, respectively). Combining multimodal parameters α and µs` (at 940 nm) show the highest statistical significance (p=6.72e-4) between FF cancerous/fibroadenoma and adjacent normal tissues. With the combined optical and thermal measurements performed on N = 5 patients, it was observed that thermal conductivity (k) and reduced-scattering-coefficient (µs`) for both the cancerous and normal tissues reduced with the rise in tissue temperature. The thermal conductivity (k) of the adjacent normal tissues was found to be higher than the cancerous tissues, a basis of delineation. Comparing cancerous and adjacent normal tissue, the difference in k and µs` (at 940nm) were statistically significant (p=7.94e-3), while combining k and µs` achieved the highest statistical significance (p=6.74e-4). Finally, performing the combined Opto-Thermo-Acoustic modality experiment on N = 6 subjects yielded the highest statistical significance (p = 2.60 e-5) by considering the optical reduced scattering coefficient (µ's at 850 nm and 940 nm), thermal conductivity (k), and acoustic attenuation (α) results together. Hence considering multiple modalities increases the accuracy of the breast cancer diagnosis. The designed system can enhance the efficacy of cancer resection and optimize the workflow of cancer margin assessment. The results obtained establish the proof-of-principle and large-scale testing of this multimodal breast cancer diagnostic platform for core biopsy diagnosis.