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Updated: May 9, 2026
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Published on: November 10, 2023
Low-frequency quantitative ultrasound imaging of cell death in vivo
Ali Sadeghi-Naini1, Naum Papanicolau, Omar Falou
1Imaging Research-Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.
Purpose:
Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.
Methods:
Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.
Results:
Ultrasound-based spectroscopic biomarkers indicated significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r2=0.71, 0.82; p<0.001).
Conclusions:
In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency, in addition to high-frequency ultrasound, can detect tissue changes associated with cell death in vivo in response to cancer treatments.
Insights
Quantitative ultrasound can detect early tumor response to cancer therapies by identifying cell death. This imaging technique shows promise for monitoring treatment effectiveness in preclinical models.
Area of Science:
- Biomedical Engineering
- Medical Imaging
- Oncology
Background:
- Current clinical imaging lacks rapid tumor response assessment post-treatment.
- Early detection of treatment efficacy is crucial for optimizing cancer therapy.
Purpose of the Study:
- To demonstrate ultrasound's efficacy in quantitatively detecting early tumor response to cancer therapies.
- To evaluate ultrasound at clinically relevant frequencies for in vivo tissue change detection.
Main Methods:
- Utilized conventional and high-frequency ultrasound (4-28 MHz) on xenograft tumors.
- Applied quantitative spectroscopic and signal envelope statistical analyses.
- Investigated responses to chemotherapy, radiation, and microbubble therapy.
Main Results:
- Ultrasound spectroscopic biomarkers (midband fit, spectral slope, 0-MHz intercept) showed significant cell-death associated changes.
- Biomarker changes correlated well with histological findings of cell death (r2=0.71, 0.82).
- High-frequency ultrasound and signal envelope analysis provided confirmatory results.
Conclusions:
- Quantitative ultrasound at clinically relevant frequencies can detect in vivo tissue changes related to cancer treatment-induced cell death.
- This preclinical study establishes a foundation for using ultrasound as a rapid tumor response assessment tool.
- Findings support the potential of ultrasound for real-time monitoring of therapeutic effectiveness.
