Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy

Abstract

Abstract : Neoadjuvant chemotherapy is currently the standard of care for locally advanced breast cancer (LABC). Monitoring tumor response is advantageous for patients. This project aims at establishing noninvasive monitoring of neoadjuvant chemotherapy in the breast using subharmonic aided pressure estimation (SHAPE) to estimate the interstitial fluid pressure (IFP) in LABC. In vitro experiments with the ultrasound contrast agent Definity have showed an inverse linear relationship between the change in subharmonic amplitude and hydrostatic pressure (r2=0.63-0.95, p0.01) over the pressure range associated with breast tumors (0 50 mmHg). In vivo proof of concept for SHAPE as a noninvasive monitor of IFP (r2=0.67-0.96, p0.01) has been provided based on a swine model. The work on in vivo SHAPE measurements of IFP was selected for the final of the American Institute of Ultrasound in Medicine (AIUM) 2011 Young Investigator Award (for VG Halldorsdottir) and was awarded FIRST place out of 90 abstracts submitted for this competition. In total, 97 female, nude rats were implanted with MDA-MB-231 cells and 51 animals were successfully studied with SHI and SHAPE 21, 24 or 28 days after tumor inoculation. However, the comparisons between SHAPE and Stryker IFP measurements have yet to be completed. The SHI images of tumor vascularity were compared to immunohistochemical markers of angiogenesis (CD31, COX-2 and VEGF). The strongest correlation determined by linear regression in this breast cancer model was between SHI and percent area stained with VEGF (r=0.53).