Quantitative ultrasound imaging of therapy response in bladder cancer in vivo

William T. Tran1,2, Lakshmanan Sannachi1,3, Naum Papanicolau1,4, Hadi Tadayyon1,3, Azza Al Mahrouki1, Ahmed El Kaffas1, Alborz Gorjizadeh1, Justin Lee1,5, Gregory J. Czarnota1,3,5

1Sunnybrook Health Sciences Centre, Department of Radiation Oncology, Toronto Canada

2Sheffield Hallam University, Centre for Health and Social Care Research, Sheffield UK

3University of Toronto, Department of Medical Biophysics, Toronto Canada

4Ryerson University, Department of Computer Science, Toronto Canada

5University of Toronto, Department of Radiation Oncology, Toronto Canada

Correspondence to:

Gregory Jan Czarnota, email: gregory.czarnota@sunnybrook.ca

Keywords: quantitative ultrasound, ultrasound, vascular disrupting agents, radiation therapy

Received: January 14, 2016     Accepted: April 08, 2016     Published: April 18, 2016


Background and Aims: Quantitative 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.

Methods: Tumor-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 Conclusions: There 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.

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