Intraradiological pathology-calibrated electrical impedance spectroscopy in the evaluation of excision-required breast lesions.

PURPOSE: Evaluating a real-time complementary bioelectrical diagnostic device based on electrical impedance spectroscopy (EIS) for improving breast imaging-reporting and data system (BI-RADS) scoring accuracy, especially in high-risk or borderline breast diseases. The primary purpose is to characterize breast tumors based on their dielectric properties. Early detection of high-risk lesions and increasing the accuracy of tumor sampling and pathological diagnosis are secondary objectives of the study. METHODS: The tumor detection probe (TDP) was first applied to the mouse model for electrical safety evaluations by electrical current measurement. Then it was utilized for characterization of 138 human palpable breast lesions that were to undergo core needle biopsy (CNB), vacuum-assisted biopsy (VAB), or fine needle aspiration (FNA) on the surgeon's requests. Impedance phase slope (IPS) in frequency ranges of 100- 500 kHz and impedance magnitude in f = 1 kHz were extracted as the classification parameters. Consistency of radiological and pathological declarations for the excisional recommendation was then compared with the IPS values. RESULTS: Considering pathological results as the gold standard, meaningful correlations between IPS and pathophysiological status of lesions recommended for excision (such as atypical ductal hyperplasia, papillary lesions, complex sclerosing adenosis, and fibroadenoma) were observed (p < 0.0001). These pathophysiological properties may include cell size, membrane permeability, packing density, adenosis, cytoplasm structure, etc. Benign breast lesions showed IPS values greater than 0, while high-risk proliferative, precancerous, or cancerous lesions had negative IPS values. Statistical analysis showed 95% sensitivity with area under the curve (AUC) equal to 0.92. CONCLUSION: Borderline breast diseases and high-risk lesions that should be excised according to standard guidelines can be diagnosed with TDP before any sampling process. It is an important outcome for high-risk lesions that are radiologically underestimated to BI-RADS3, specifically in younger patients with dense breast masses that present challenges in mammographic and sonographic evaluations. Also, the lowest IPS value detects the most pathologic portions of the tumor for increasing sampling accuracy in large tumors. SIGNIFICANCE: Precise detection of high-risk breast masses, which may be declared BI-RADS3 instead of BI-RADS4a.

Distinguishment of populated metastatic cancer cells from primary ones based on their invasion to endothelial barrier by biosensor arrays fabricated on nanoroughened poly(methyl methacrylate).

Determining the migratory and invasive capacity of cancer cells as well as clarifying the underlying mechanisms are most relevant for developing biosensors in cancer diagnosis, prognosis, drug development and treatment. Intravasation of metastatic cells into blood stream initiated by their invasion to vascular layer would be a significant characteristic of metastasis. Many types of biochemical and bioelectrical sensors were developed for early detection of metastasis. The simplicity of the setup, the ease of the readout, detection of the trace of rare metastatic cells and the feasibility to perform the assay with standard laboratory equipment are some of the challenges limiting the usability of the sensors in tracing the metastasis. Here we describe a biosensor based on recently reported metastatic diagnosis assay; Metas-Chip, with the assistance of nanoroughened Poly-methyl methacrylate (PMMA) layer to diagnose populated metastatic breast cells from primary cancerous ones. Retraction and detachment of Human Umbilical Vein Endothelial Cells (HUVECs) invaded by metastatic cells as a recently found phenomena is the mechanism of the action. A population of HUVECs would be detached from the gold microelectrodes, patterned on nanoroughened surface, which would lead to large changes in impedance. Here, applying biocompatible and patternable nanoroughened surface instead of using adhesive layers which might produce electrical noises resulted in great sensitivity and detectivity of the sensor. Apart from the tight interaction between endothelial cells and nanocontacts of the electrodes, using low concentration (10%) of tumor cells in this invasion assay, might enhance its application in clinical trials.