Real-Time Detection of Breast Cancer-Related Lymphedema with Shear-Wave Elastography: The Holder-Optimized Elastography Method

BackgroundBreast cancer-related lymphedema (BCRL) is a common complication following breast cancer treatment. While lymphoscintigraphy is considered the diagnostic gold standard, it is unsuitable for routine periodic monitoring or assessment of treatment efficacy. Shear wave elastography (SWE) offers a possible alternative, but traditional modes of operation limit its potential. Proposed SolutionsThe Holder-Optimized Elastography (HOE) method is introduced to eliminate pressure issues introduced by manual operation of ultrasound probes by stabilizing them above the cutis. MethodsThe HOE method was used to acquire ARFI images of high-velocity areas (HVAs, with shear wave velocity greater than 7 m/s) in limbs with and without BCRL (as confirmed and characterized by lymphoscintigraphy) in two cohorts of 15 and 125 patients. ResultsThe HOE method enabled ARFI elastography to directly and consistently visualize the effects caused by both obstructed lymphatic vessels and intraluminal lymphatic fluid as HVAs, whereas traditional hand-held methods did not. Inter-limb differences in HVA burden showed moderate diagnostic performance for detecting BCRL and grading obstruction with modest sensitivity. However, there was systematic underestimation of both early and confluent advanced lesions. ConclusionHOE-based HVA imaging has potential for rapid and non-invasive monitoring of lymphedema course and treatment response and may serve as a useful adjunct to existing diagnostic tools for BCRL. However, further technical refinements and quantitative analytic methods will be required to fully exploit the richer SWV information provided by HOE and to enhance the diagnostic utility of HVAs. Summary StatementThe Holder-Optimized Elastography method ("HOE" method) increases the diagnostic capability of ARFI elastography for breast cancer-related lymphedema, allowing for the non-invasive detection of some lymphatic obstructions but not all. Key ResultsThe Holder-Optimized Elastography (HOE) method revealed the effects caused by fluid-filled lymphatic vessels as "High-Velocity Areas" (HVAs), which are difficult to detect by conventional methods. HVA counts for detecting lymphedema (any obstruction vs. no obstruction) showed high specificity (0.86-1.00) but low sensitivity (0.57-0.67). Conversely, HVA counts for staging lymphedema (i.e. total vs. partial obstruction) showed high sensitivity (up to 1.00) but low specificity (0.48-0.66). The inter-limb difference of HVAs counted in whole-limb scans between affected and unaffected limbs (aka, the "Global Mean Difference") provided the most balanced diagnostic performance (sensitivity 0.67-0.79, specificity 0.88-0.89).