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Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release
Published on: June 12, 2021
Quantitative ultrasound for the monitoring of novel microbubble and ultrasound radiosensitization
Justin Lee1, Raffi Karshafian, Naum Papanicolau
1Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, and University of Toronto, Toronto, Ontario, Canada.
Abstract:
There is a need for cancer imaging to provide "real-time" information about the metabolic and cellular responses of tumours. Quantitative ultrasound techniques have recently been demonstrated to be a potential method of assessing tumour response at the cellular level. Anti-cancer treatments administered to xenograft-bearing mice consisted of radiotherapy and a novel antivascular therapy utilizing encapsulated microbubble agents in the presence of ultrasound. Radiation dose and microbubble concentrations were varied and the treatment modalities were given in combination to assess the possible enhancement of tumour cell death. Quantitative methods were used to non-invasively assess responses. Results demonstrated statistically significant changes in backscatter parameters (midband fit, spectral intercept) in tumours treated with high doses of radiotherapy or a high concentration of microbubbles. Combined treatments demonstrated further increases in ultrasound parameters. Histopathologic assessment was used and tumour cell death was found to correlate with increases in ultrasound parameters.
Insights
Quantitative ultrasound imaging offers real-time assessment of cancer treatment response. This study shows ultrasound parameters correlate with tumor cell death, aiding in evaluating therapies like radiotherapy and microbubble-based treatments.
Area of Science:
- Oncology
- Medical Imaging
- Biophysics
Background:
- Cancer imaging needs real-time metabolic and cellular response assessment.
- Quantitative ultrasound (QUS) shows potential for non-invasive cellular-level tumor response evaluation.
- Current methods lack real-time feedback on treatment efficacy.
Purpose of the Study:
- To evaluate the efficacy of quantitative ultrasound techniques for assessing tumor response to anti-cancer treatments.
- To investigate the correlation between ultrasound backscatter parameters and tumor cell death.
- To explore the combined effects of radiotherapy and microbubble-based antivascular therapy.
Main Methods:
- Xenograft-bearing mice models were used.
- Treatments included varied doses of radiotherapy and microbubble concentrations, both individually and in combination.
- Quantitative ultrasound parameters (midband fit, spectral intercept) were measured non-invasively.
- Histopathologic analysis was performed to assess tumor cell death.
Main Results:
- Statistically significant changes in QUS backscatter parameters were observed with high-dose radiotherapy or high microbubble concentrations.
- Combined treatment modalities showed enhanced increases in ultrasound parameters.
- Increased ultrasound parameters strongly correlated with increased tumor cell death.
Conclusions:
- Quantitative ultrasound is a promising non-invasive tool for real-time monitoring of tumor response to combined therapies.
- QUS parameters can serve as biomarkers for treatment-induced tumor cell death.
- This technique could optimize cancer treatment strategies by providing rapid feedback on efficacy.

