Quantitative ultrasound imaging of therapy response in bladder cancer in vivo

Abstract

Background and AimsQuantitative ultrasound (QUS) was investigated to monitor bladder cancer treatment response in vivo and to evaluate tumor cell death from combined treatments using ultrasound-stimulated microbubbles and radiation therapy.MethodsTumor-bearing mice (n=45), with bladder cancer xenografts (HT- 1376) were exposed to 9 treatment conditions consisting of variable concentrations of ultrasound-stimulated Definity microbubbles [nil, low (1%), high (3%)], combined with single fractionated doses of radiation (0 Gy, 2 Gy, 8 Gy). High frequency (25 MHz) ultrasound was used to collect the raw radiofrequency (RF) data of the backscatter signal from tumors prior to, and 24 hours after treatment in order to obtain QUS parameters. The calculated QUS spectral parameters included the mid-band fit (MBF), and 0-MHz intercept (SI) using a linear regression analysis of the normalized power spectrum.Results and ConclusionsThere were maximal increases in QUS parameters following treatments with high concentration microbubbles combined with 8 Gy radiation: (ΔMBF = +6.41 ± 1.40 (±SD) dBr and SI= + 7.01 ± 1.20 (±SD) dBr. Histological data revealed increased cell death, and a reduction in nuclear size with treatments, which was mirrored by changes in quantitative ultrasound parameters. QUS demonstrated markers to detect treatment effects in bladder tumors in vivo.

Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide metabolism

“…It has been previously demonstrated that exposure of tumour vasculature to ultrasound-stimulated microbubbles can enhance effects of radiation significantly. In that work, in vivo experiments in which ultrasound-stimulated microbubble and radiation treatments were conducted demonstrated a synergy dependent on blood vessel disruption [ 2 , 6 , 8 , 9 , 12 – 13 ]. Previous data indicated that tumour cell death is secondary to vascular disruption resulting from endothelial cell death.…”

Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer

“…33,34 Some studies showed that when acoustic cavitation is combined with radiation or chemotherapy, enhanced therapeutic effects are observed. 35 For example, when treating in vivo 45 cases of bladder cancer in mice, Tran et al 36 showed additive antitumour and antivascular effects when ultrasound microbubbles were combined with radiation, thus opening up a wide spectrum of possibilities for future treatment of human cancer. Moreover, cavitation mechanism can indirectly cause the formation of a lithotripsy shockwaves that seems to present broad potential for non-thermal biologic effect in treating tumour, even if limited experiences reports that lithotripsy associated with cavitation phaenomenon may increase the development of distance metastasis.…”

Quantitative Ultrasound Spectroscopy for Differentiation of Hepatocellular Carcinoma from At-Risk and Normal Liver Parenchyma

“…QUS parameters have been demonstrated to be sensitive to subtle microstructural characteristics and alterations occurring in tissue due to biological responses and tissue morphology resulting from disease or treatment. These have been previously demonstrated in preclinical studies (14,27,(28)(29)(30) and in a clinical setting including patients with prostate cancer [disease detection (31), and extent of the disease (17)], as well as colorectal, gastric, and breast cancer patients to detect lymph node metastases (12,32). Furthermore, QUS can be used in clinic to evaluate cancer treatment response and help clinicians adapt cancer therapies and exchange ineffective treatment therapies at an early stage (12,25,26,33).…”