Super-Resolution Ultrasound Imaging for Monitoring the Therapeutic Efficacy of a Vascular Disrupting Agent in an
Kenneth Hoyt1,2
1Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
Objective:
Evaluate the use of super-resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular-disrupting agent (VDA).
Methods:
A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA-MB-231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein. Following baseline ultrasound imaging, VDA drug (combretastatin A4 phosphate, CA4P, Sigma Aldrich) or control saline was injected via the placed catheter. After 4 or 24 hours, repeat ultrasound imaging along the same tumor cross-section occurred. Direct intratumoral pressure measurements were obtained using a calibrated sensor. All raw ultrasound data were saved for offline processing and SRUS image reconstruction using custom MATLAB software (MathWorks Inc). From a region encompassing the tumor space and the entire postprocessed ultrasound image sequence, time MB count (TMC) curves were generated in addition to traditional SRUS maps reflecting MB enumeration at each pixel location. Peak enhancement (PE) and wash-in rate (WIR) were extracted from these TMC curves. At termination, intratumoral microvessel density (MVD) was quantified using tomato lectin labeling of patent blood vessels.
Results:
SRUS images exhibited a clear difference between control and treated tumors. While there was no difference in any group parameters at baseline (0 hour, P > .09), both SRUS-derived PE and WIR measurements in tumors treated with VDA exhibited significant decreases by 4 (P = .03 and P = .05, respectively) and 24 hours (P = .02 and P = .01, respectively), but not in control group tumors (P > .22). Similarly, SRUS derived microvascular maps were not different at baseline (P = .81), but measures of vessel density were lower in treated tumors at both 4 and 24 hours (P < .04). An inverse relationship between intratumoral pressure and both PE and WIR parameters were found in control tumors (R2 > .09, P < .03).
Conclusion:
SRUS imaging is a new modality for assessing tumor response to treatment using a VDA.
Insights
Super-resolution ultrasound (SRUS) imaging effectively detects early tumor response to vascular-disrupting agent (VDA) treatment. This novel imaging modality shows significant decreases in microvascular parameters in treated tumors, indicating treatment efficacy.
Area of Science:
- Medical Imaging
- Oncology
- Pharmacology
Background:
- Early detection of tumor response to treatment is crucial for effective cancer therapy.
- Vascular-disrupting agents (VDAs) target tumor vasculature, but their efficacy requires sensitive monitoring.
- Super-resolution ultrasound (SRUS) imaging offers potential for high-resolution visualization of microvasculature.
Purpose of the Study:
- To evaluate the utility of SRUS imaging for early assessment of tumor response to VDA treatment.
- To compare SRUS-derived microvascular parameters with traditional measures of tumor vascularity.
Main Methods:
- Human breast cancer xenografts (MDA-MB-231) were established in athymic mice.
- Ultrasound imaging with microbubble contrast was performed before and after VDA (CA4P) or saline injection.
- SRUS image reconstruction and analysis of microvascular parameters (Peak Enhancement, Wash-in Rate, vessel density) were conducted.
Main Results:
- SRUS imaging revealed significant decreases in Peak Enhancement and Wash-in Rate in VDA-treated tumors at 4 and 24 hours post-injection (P < .05).
- SRUS-derived microvascular maps showed reduced vessel density in treated tumors compared to controls (P < .04).
- No significant changes in microvascular parameters were observed in control group tumors.
Conclusions:
- Super-resolution ultrasound (SRUS) imaging is a promising new modality for the early assessment of tumor response to vascular-disrupting agent (VDA) therapy.
- SRUS can accurately quantify changes in tumor microvasculature, providing valuable insights into treatment efficacy.
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