High-Frequency (30 MHz-6 GHz) Breast Tissue Characterization Stabilized by Suction Force for Intraoperative Tumor Margin Assessment

Abstract

A gigahertz (GHz) range antenna formed by a coaxial probe has been applied for sensing cancerous breast lesions in the scanning platform with the assistance of a suction tube. The sensor structure was a planar central layer and a metallic sheath of size of 3 cm² connected to a network analyzer (keySight FieldFox N9918A) with operational bandwidth up to 26.5 GHz. Cancer tumor cells have significantly higher water content (as a dipolar molecule) than normal breast cells, changing their polarization responses and dielectric losses to incoming GHz-based stimulation. Principal component analysis named S₁₁, related to the dispersion ratio of the input signal, is used as a parameter to identify malignant tumor cells in a mouse model (in vivo) and tumor specimens of breast cancer patients (in vitro) (both central and marginal parts). The results showed that S₁₁ values in the frequency range from 5 to 6 GHz were significantly higher in cancer-involved breast lesions. Histopathological analysis was the gold standard for achieving the S₁₁ calibration to distinguish normal from cancerous lesions. Our calibration on tumor specimens presented 82% positive predictive value (PPV), 100% negative predictive value (NPV), and 86% accuracy. Our goal is to apply this system as an in vivo non-invasive tumor margin scanner after further investigations in the future.

Keywords: GHz spectroscopy; breast cancer; dipolar polarization; scattering; tumor margin.

Figure 1

GHz measurement system. (a) The used network analyzer (KeySight FieldFox N9918A). (b) The open-ended coaxial cable (Semi-Flexible Cable 670-086 SXE). (c) Magnified view of the coaxial cable. (d) A Foley catheter modified for applying suction thoroughly. (e) Suction pump.

Figure 2

GHz measurement on a mouse model. (a) Tumor tissue and applying the GHz probe on it. (b) Normal mouse tissue with H&E assay representing the fibrotic connective tissue and cancerous mouse tissue with H&E assay representing a hypercellular region and high nucleus-to-cytoplasm size ratio. (c) Frequency-dependent behaviour of S₁₁ parameter for normal and cancerous tissues with or without applying suction force.

Figure 3

(a) mean values of S₁₁ magnitude in three categories of fatty, benign, and malignant breast tissues. (b) Differences of each category versus tumor spectrum. (c) Variation of measured S₁₁ by the time after dissection with magnification. (d) The ROC curve for different cut-offs.

Figure 4

GHz spectroscopy on human tumor margins. (a) H&E assay of a measured margin sample, 2.7 × 2.7 cm. (b) S₁₁ magnitude measurements on the selected margin in 18 points. Pathologically negative and positive points are represented in green and red, respectively. The obtained pattern is completely matched with the H&E assay.

Figure 5

(a) Schematic view of an electrical network with two ports in a high-frequency region to describe scattering parameter, S₁₁. (b) Schematic view of protein content and water distribution of a normal cell, which results in an increased S₁₁ parameter in normal tissue due to less resonant membrane-bound waters associated with decreased expression of membrane proteins. (c) Schematic view of protein content and water distribution of a cancer cell, which results in a decreased S₁₁ parameter in cancerous tissue due to more resonant membrane-bound waters associated with increased expression of membrane proteins.