In vivo assessment of prostate cancer response using quantitative ultrasound characterization of ultrasonic scattering properties

Deepa Sharma,Anoja Giles,Martin Stanisz,Mateusz Faltyn,Laurentius Oscar Osapoetra,Gregory J Czarnota

doi:10.1186/s12885-021-08706-7

Abstract

BackgroundThe study here investigated quantitative ultrasound (QUS) parameters to assess tumour response to ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) treatment in vivo. Mice bearing prostate cancer xenografts were exposed to various treatment conditions including 1% (v/v) Definity microbubbles stimulated at ultrasound pressures 246 kPa and 570 kPa and HT duration of 0, 10, 40, and 50 min. Ultrasound radiofrequency (RF) data were collected using an ultrasound transducer with a central frequency of 25 MHz. QUS parameters based on form factor models were used as potential biomarkers of cell death in prostate cancer xenografts.ResultsThe average acoustic concentration (AAC) parameter from spherical gaussian and the fluid-filled spherical models were the most efficient imaging biomarker of cell death. Statistical significant increases of AAC were found in the combined treatment groups: 246 kPa + 40 min, 246 kPa + 50 min, and 570 kPa + 50 min, in comparison with control tumours (0 kPa + 0 min). Changes in AAC correlates strongly (r2 = 0.62) with cell death fraction quantified from the histopathological analysis.ConclusionScattering property estimates from spherical gaussian and fluid-filled spherical models are useful imaging biomarkers for assessing tumour response to treatment. Our observation of changes in AAC from high ultrasound frequencies was consistent with previous findings where parameters related to the backscatter intensity (AAC) increased with cell death.

Highlights

Treatment response monitoring is crucial in the management of cancer progression
This study demonstrates the potential of quantitative ultrasound (QUS) spectroscopy for the non-invasive evaluation of tumour response to cancer treatment
The middle row depicts tumour section treated with 246 kPa and HT (0, 10, 40, and 50 min) and the bottom row shows stained tumour cross-sections upon exposure of 570 kPa and HT (0, 10, 40, and 50 min)

Summary

Introduction

Treatment response monitoring is crucial in the management of cancer progression. Depending on the severity of cancer and its type, a treatment plan can be adjusted if needed. One of the most commonly performed tests to diagnose and examine treatment response is biopsy. This involves invasive procedures to access tissue or collect cell samples [1] and is associated with inherent risks. Several non-invasive alternatives to biopsy for response monitoring have been developed and studied, one of which includes a quantitative ultrasound (QUS) spectroscopy. The study here investigated quantitative ultrasound (QUS) parameters to assess tumour response to ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) treatment in vivo. Mice bearing prostate cancer xenografts were exposed to various treatment conditions including 1% (v/v) Definity microbubbles stimulated at ultrasound pressures 246 kPa and 570 kPa and HT duration of 0, 10, 40, and 50 min. QUS parameters based on form factor models were used as potential biomarkers of cell death in prostate cancer xenografts

Methods

Results

Conclusion