This project addresses the need for reliable, highly sensitive means of detecting metastases to lymph nodes (LNs) and distinguishing them from primary lymphomas and LNs affected by benign conditions. This capability will allow improved staging and treatment of disease. Accordingly, we seek to validate existing encouraging results obtained in prior studies using quantitative-ultrasound (QUS) methods to detect metastases in LNs by applying and evaluating these promising methods using a clinical scanner to acquire ultrasonic echo-signal data from patients undergoing medically required ultrasonically guided fine-needle aspirations (FNAs) of suspicious LNs. This project includes a broad range of disease types from a large and diverse patient population. Validation efforts will develop, deploy, and validate an application for QUS-based detection and characterization of LNs implemented in a clinical scanner. Successful validation will establish a foundation for incorporation of QUS-based methods for LN evaluation into clinical ultrasonic scanners. Such instruments will be able to evaluate suspicious LNs intra-operatively in the operating room or pre-operatively in the examination room. The collaborating researchers will synergize capabilities in the following general ways: Weill Cornell Medicine will provide project oversight and coordination and will apply, refine, and test QUS and classification methods; General Electric Research will provide ultrasound instrumentation and will develop and validate the QUS application for the scanner; Stony Brook Medicine will recruit patients and acquire ultrasonic and cytopathological data from patients undergoing fine-needle-aspiration biopsies of their LNs.