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Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors
Published on: March 29, 2019
In vivo magnetic resonance imaging of treatment-induced apoptosis
Xiaoyu Jiang1,2, Eliot T McKinley3, Jingping Xie1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, 37232, USA.
Abstract:
Imaging apoptosis could provide an early and specific means to monitor tumor responses to treatment. To date, despite numerous attempts to develop molecular imaging approaches, there is still no widely-accepted and reliable method for in vivo imaging of apoptosis. We hypothesized that the distinct cellular morphologic changes associated with treatment-induced apoptosis, such as cell shrinkage, cytoplasm condensation, and DNA fragmentation, can be detected by temporal diffusion spectroscopy imaging (TDSI). Cetuximab-induced apoptosis was assessed in vitro and in vivo with cetuximab-sensitive (DiFi) and insensitive (HCT-116) human colorectal cancer cell lines by TDSI. TDSI findings were complemented by flow cytometry and immunohistochemistry. Cell cycle analysis and flow cytometry detected apoptotic cell shrinkage in cetuximab-treated DiFi cells, and significant apoptosis was confirmed by histology. TDSI-derived parameters quantified key morphological changes including cell size decreases during apoptosis in responsive tumors that occurred earlier than gross tumor volume regression. TDSI provides a unique measurement of apoptosis by identifying cellular characteristics, particularly cell shrinkage. The method will assist in understanding the underlying biology of solid tumors and predict tumor response to therapies. TDSI is free of any exogenous agent or radiation, and hence is very suitable to be incorporated into clinical applications.
Insights
Temporal diffusion spectroscopy imaging (TDSI) detects cell shrinkage during apoptosis, offering a novel, non-invasive method for monitoring tumor treatment response. This technique shows promise for early prediction of therapy effectiveness in cancer.
Area of Science:
- Oncology
- Medical Imaging
- Biophysics
Background:
- Accurate in vivo imaging of apoptosis is crucial for monitoring cancer treatment efficacy.
- Current molecular imaging methods for apoptosis lack widespread clinical acceptance and reliability.
- Cellular morphologic changes during apoptosis present a potential target for novel imaging techniques.
Purpose of the Study:
- To investigate the utility of temporal diffusion spectroscopy imaging (TDSI) for detecting and quantifying apoptosis.
- To assess TDSI's ability to identify cellular shrinkage, a key feature of apoptosis.
- To evaluate TDSI as a non-invasive method for monitoring tumor response to cetuximab treatment.
Main Methods:
- TDSI was employed to assess apoptosis in cetuximab-sensitive (DiFi) and insensitive (HCT-116) colorectal cancer cell lines in vitro and in vivo.
- TDSI findings were correlated with flow cytometry, cell cycle analysis, and immunohistochemistry.
- Morphological changes, specifically cell shrinkage, were quantified using TDSI parameters.
Main Results:
- TDSI successfully detected and quantified cell shrinkage associated with cetuximab-induced apoptosis in responsive cancer cells.
- Apoptotic cell shrinkage was observed in DiFi cells, confirmed by flow cytometry and histology.
- TDSI identified early cellular changes, including cell size reduction, preceding macroscopic tumor regression.
Conclusions:
- TDSI provides a unique, non-invasive measurement of apoptosis by detecting characteristic cellular changes like shrinkage.
- This imaging modality can aid in understanding tumor biology and predicting treatment response.
- TDSI's lack of exogenous agents or radiation makes it suitable for clinical integration.
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