Characterization of Thyroid Cancer in Mouse Models Using High-Frequency Quantitative Ultrasound Techniques

Abstract

Currently, the evaluation of thyroid cancer relies on the use of fine needle aspiration biopsy as non-invasive imaging methods do not provide sufficient levels of accuracy for the diagnosis of this disease. In this study, the potential of quantitative ultrasound methods for characterizing thyroid tissues was studied using a rodent model ex vivo. A high-frequency ultrasonic scanning system (40 MHz) was used to scan thyroids extracted from mice that had spontaneously developed thyroid lesions (cancerous or benign). Three sets of mice were acquired having different predispositions to developing thyroid anomalies (a C-cell adenoma, a papillary thyroid carcinoma (PTC), and a follicular variant papillary thyroid carcinoma (FV-PTC)). A fourth set of mice did not develop thyroid anomalies (normal mice) and were used as controls. The backscatter coefficient was estimated from excised thyroid lobes for the different mice. From the backscatter coefficient versus frequency (25 to 45 MHz), the effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated. From the envelope of the backscattered signal, the homodyned K distribution was used to estimate the k parameter (ratio of coherent to incoherent signal energy) and the μ parameter (number of scatterers per resolution cell). Statistically significant differences were observed between the malignant thyroids and the normal thyroids based on the ESD, EAC and μ parameters. The mean values of the ESDs were 18.0 ± 0.92, 15.9 ± 0.81, and 21.5 ± 1.80 µm for the PTC, FV-PTC and the normal thyroids, respectively. The mean values of the EACs were 59.4 ± 1.74, 62.7 ± 1.61, and 52.9 ± 3.42 dB (mm−3) for the PTC, FV-PTC and the normal thyroids, respectively. The mean values of the μ parameters were 2.55 ± 0.37, 2.59 ± 0.43, and 1.56 ± 0.99 for the PTC, FV-PTC and the normal thyroids, respectively. Statistically significant differences were observed between the malignant thyroids and the C-cell adenomas based on the ESD and EAC parameters with estimated values for the ESD of 21.3 ± 1.50 µm and EAC of 54.7 ± 2.24 dB (mm−3) for the C-cell adenomas. These results suggest that high frequency quantitative ultrasound may enhance the ability to detect and classify diseased thyroid tissues.

Ultrasonic attenuation imaging in a rodent thyroid cancer model

“…The estimated mean values are consistent with values obtained previously by an insertion loss method which obtained a mean attenuation value of the sample of 1.19 ± 0.26 dB/cm-MHz [4] in mice thyroids. These values are also consistent with reports of attenuation in human thyroids [11].…”

“…In previous studies, the FV-PTC and PTC groups in mouse models were identified using ESD and EAC [4,10]. However, these estimators could not differentiate the C-cell adenomas from the normal thyroids.…”

“…However, in a study of quantitative ultrasound to differentiate thyroid cancer from normal and benign thyroid hyperplasias in mouse models, no parameter was able to differentiate the benign C-cell adenomas from the normal thyroids [4].…”

Review of Quantitative Ultrasound: Envelope Statistics and Backscatter Coefficient Imaging and Contributions to Diagnostic Ultrasound

“…A high-frequency single-element ultrasonic scanning system was used to scan thyroids extracted from mice that had spontaneously developed thyroid lesions (cancerous or benign) [89]. Four sets of mice were acquired having different predispositions to developing thyroid anomalies.…”

H-scan analysis of thyroid lesions

“…Certain chemical and molecular changes in the nucleus and cell morphology are seen in papillary thyroid carcinoma variants, and these changes have been characterized by scattering properties. [12][13][14] In a population-based study by Smith-Bindman et al, 15 microcalcifications were associated with 38.2% of malignant nodules and 5.4% of benign nodules. Models for classifying microcalcifications as elastic scatterers under ultrasound have been studied previously.…”