Assessment of Mechanical Properties of Tissue in Breast Cancer-Related Lymphedema Using Ultrasound Elastography

Breast cancer-related lymphedema is a consequence of a malfunctioning lymphatic drainage system resulting from surgery or some other form of treatment. In the initial stages, minor and reversible increases in the fluid volume of the arm are evident. As the stages progress over time, the underlying pathophysiology dramatically changes with an irreversible increase in arm volume most likely due to a chronic local inflammation leading to adipose tissue hypertrophy and fibrosis. Clinicians have subjective ways to stage the degree and severity such as the pitting test which entails manually comparing the elasticity of the affected and unaffected arms. Several imaging modalities can be used but ultrasound appears to be the most preferred because it is affordable, safe, and portable. Unfortunately, ultrasonography is not typically used for staging lymphedema, because the appearance of the affected and unaffected arms is similar in B-mode ultrasound images. However, novel ultrasound techniques have emerged, such as elastography, which may be able to identify changes in mechanical properties of the tissue related to detection and staging of lymphedema. This paper presents a novel technique to compare the mechanical properties of the affected and unaffected arms using quasi-static ultrasound elastography to provide an objective alternative to the current subjective assessment. Elastography is based on time delay estimation (TDE) from ultrasound images to infer displacement and mechanical properties of the tissue. We further introduce a novel method for TDE by incorporating higher order derivatives of the ultrasound data into a cost function and propose a novel optimization approach to efficiently minimize the cost function. This method works reliably with our challenging patient data. We collected radio frequency ultrasound data from both arms of seven patients with stage 2 lymphedema, at six different locations in each arm. The ratio of strain in skin, subcutaneous fat, and skeletal muscle divided by strain in the standoff gel pad was calculated in the unaffected and affected arms. The p -values using a Wilcoxon sign-rank test for the skin, subcutaneous fat, and skeletal muscle were 1.24\times 10^{-5} , 1.77\times 10^{-8} , and