Three-dimensional high-frequency spectral and envelope quantification of excised human lymph nodes

Quantitative imaging methods using high-frequency ultrasound (HFU, >;20 MHz) offer a means of characterizing biological tissue at the microscopic level. In this study, three-dimensional (3D) quantitative-ultrasound (QUS) methods were developed to detect metastases in freshly-dissected lymph nodes of cancer patients. 3D ultrasound radio-frequency data were acquired using a 26-MHz center-frequency transducer, and each node was inked prior to tissue fixation to recover orientation after sectioning for 3D histological evaluation. Backscattered echo signals were processed using 3D cylindrical regions-of-interest (ROIs) to yield eight QUS estimates associated with tissue microstructure. The first four QUS estimates (i.e., effective scatterer size, acoustic concentration, intercept, and slope) were estimated from a normalized backscattered spectrum, and the other four QUS estimates were obtained by parameterizing the envelope statistics of the ROIs using Nakagami and homodyned-K models. These QUS methods were applied to 145 lymph nodes from 95 colorectal and gastric cancer patients. The ability of these eight QUS estimates to classify lymph nodes and detect cancer was evaluated using ROC curves. An area under the ROC curve of 0.971 with specificity and sensitivity of 91% (using a leave-one-out procedure) were obtained by combining effective scatterer size and one envelope parameter based on the homodyned-K distribution. Therefore, these advanced 3D QUS methods potentially can be valuable for detecting small metastatic foci in dissected lymph nodes.