Subharmonic-Aided Pressure Estimation for Monitoring Interstitial Fluid Pressure in Tumors: Calibration and Treatment with Paclitaxel in Breast Cancer Xenografts

Abstract

Interstitial fluid pressure (IFP) in rats with breast cancer xenografts was non-invasively estimated using subharmonic-aided pressure estimation (SHAPE) versus an invasive pressure monitor. Moreover, monitoring of IFP changes after chemotherapy was assessed. Eighty-nine rats (calibration n = 25, treatment n = 64) were injected with 5 × 10⁶ breast cancer cells (MDA-MB-231). Radiofrequency signals were acquired (39 rats successfully imaged) with a Sonix RP scanner (BK Ultrasound, Richmond, BC, Canada) using a linear array (L9-4, transmit/receive: 8/4 MHz) after administration of Definity (Lantheus Medical Imaging, North Billerica, MA, USA; 180 μL/kg) and compared with readings from an invasive pressure monitor (Stryker, Berkshire, UK). An inverse linear relationship was established between tumor IFP and SHAPE (y = -1.06x + 28.27, r = -0.69, p = 0.01) in the calibration group. Use of this relationship in the treatment group resulted in r = 0.74 (p < 0.05) between measured (pressure monitor) and SHAPE-estimated IFP (average error: 6.24 mmHg). No significant before/after differences were observed with respect to paclitaxel treatment (5 mg/kg, Mayne Pharma, Paramus, NJ, USA) with either method (p ≥ 0.15).

Keywords: Breast cancer xenografts; Contrast agents; Interstitial fluid pressure; Microbubbles; Subharmonic-aided pressure estimation; Ultrasound.