Three-dimensional quantitative ultrasound for detecting lymph node metastases.

PURPOSE: Detection of metastases in lymph nodes (LNs) is critical for cancer management. Conventional histological methods may miss metastatic foci. To date, no practical means of evaluating the entire LN volume exists. The aim of this study was to develop fast, reliable, operator-independent, high-frequency, quantitative ultrasound (QUS) methods for evaluating LNs over their entire volume to effectively detect LN metastases. METHODS: We scanned freshly excised LNs at 26 MHz and digitally acquired echo-signal data over the entire three-dimensional (3D) volume. A total of 146 LNs of colorectal, 26 LNs of gastric, and 118 LNs of breast cancer patients were enrolled. We step-sectioned LNs at 50-µm intervals and later compared them with 13 QUS estimates associated with tissue microstructure. Linear-discriminant analysis classified LNs as metastatic or nonmetastatic, and we computed areas (Az) under receiver-operator characteristic curves to assess classification performance. The QUS estimates and cancer probability values derived from discriminant analysis were depicted in 3D images for comparison with 3D histology. RESULTS: Of 146 LNs of colorectal cancer patients, 23 were metastatic; Az = 0.952 ± 0.021 (95% confidence interval [CI]: 0.911-0.993); sensitivity = 91.3% (specificity = 87.0%); and sensitivity = 100% (specificity = 67.5%). Of 26 LNs of gastric cancer patients, five were metastatic; Az = 0.962 ± 0.039 (95% CI: 0.807-1.000); sensitivity = 100% (specificity = 95.3%). A total of 17 of 118 LNs of breast cancer patients were metastatic; Az = 0.833 ± 0.047 (95% CI: 0.741-0.926); sensitivity = 88.2% (specificity = 62.5%); sensitivity = 100% (specificity = 50.5%). 3D cancer probability images showed good correlation with 3D histology. CONCLUSIONS: These results suggest that operator- and system-independent QUS methods allow reliable entire-volume LN evaluation for detecting metastases. 3D cancer probability images can help pathologists identify metastatic foci that could be missed using conventional methods.

Entire-volume serial histological examination for detection of micrometastases in lymph nodes of colorectal cancers.

The purpose of this study was to accurately detect lymph-node micrometastases, i.e., metastatic cancer foci that have a size between 2.0 and 0.2 mm, in nodes excised from colorectal cancer (CRC) patients, and to determine how frequently micrometastases might be missed when standard histological examination procedures are used. A total of 311 lymph nodes were removed and examined from 90 patients with Stage I to IV CRC. The number of slices of histology sections ranged from 6 to 75 per node (average = 25.5; SD = 11.1), which provided a total of 7,943 slices. Lymph nodes were examined in their entire volume at every 50-µm and 100-µm intervals for nodes smaller and larger than 5 mm respectively. The total number of thin sections examined in each node and the number of thin sections where metastatic foci were present were counted. The number of thin sections with metastatic foci and the total number of slices was determined for each node. In addition, the presence or absence of metastatic foci in the "central" slice was determined. Micrometastases were found in 12/311 (3.9%) of all lymph nodes. In the 12 lymph nodes with micrometastases, the rate of metastatic slices over all slices was 39.4% (range = 6.3 to 81.3%; SD = 25.8%) In the central slice of each node, micrometastases were present only in 6 of 12 lymph nodes (50%); accordingly, they were not present in the central slice for half the micrometastatic nodes. These 6 nodes represented 1.9% of the 311 nodes and 11.1% of the 54 metastatic nodes. This study suggests that a significant fraction of micrometastases can be missed by traditional singleslice sectioning; half of the micrometastases would have been overlooked in our data set of 311 nodes.