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JoVE Journal
Cancer Research
A Dorsal Skinfold Window Chamber Tumor Mouse Model for Combined Intravital Microscopy and Magneti...
A Dorsal Skinfold Window Chamber Tumor Mouse Model for Combined Intravital Microscopy and Magneti...
JoVE Journal
Cancer Research
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JoVE Journal Cancer Research
A Dorsal Skinfold Window Chamber Tumor Mouse Model for Combined Intravital Microscopy and Magnetic Resonance Imaging in Translational Cancer Research

A Dorsal Skinfold Window Chamber Tumor Mouse Model for Combined Intravital Microscopy and Magnetic Resonance Imaging in Translational Cancer Research

Full Text
2,131 Views
10:25 min
April 12, 2024

DOI: 10.3791/66383-v

W. Jeffrey Zabel*1, Nader Allam*1, Hector Alejandro Contreras Sanchez1, Warren Foltz2,3, Costel Flueraru4, Edward Taylor2,3, Alex Vitkin1,2,3

1Department of Medical Biophysics,University of Toronto, 2Radiation Medicine Program,Princess Margaret Cancer Centre, 3Department of Radiation Oncology,University of Toronto, 4Advanced Electronic and Photonics Research Center,National Research Council of Canada

Translation of Intravital microscopy findings is challenged by its shallow depth penetration into tissue. Here we describe a dorsal window chamber mouse model that enables co-registration of intravital microscopy and clinically applicable imaging modalities (e.g., CT, MRI) for direct spatial correlation, potentially streamlining clinical translation of intravital microscopy findings.

Preclinical intravital imaging has very high resolution, but limited depth penetration in the tissue, which makes it very good for preclinical imaging studies. On the other hand, MRI is much more clinically applicable and has a higher depth penetration, but very low spatial resolution. The goal of this study is to correlate these two modalities with each other in order to better translate our findings from preclinical intravital microscopy into the clinic via magnetic resonance imaging.

Perfusion-sensitive imaging methods in MRI and biophotonics, including our optical coherence tomography and geography system, are revealing how the microvasculature impacts tumor response to hypofractionated radiotherapy. 3D printing is also aiding through cost-effective custom tool manufacturing, facilitating longitudinal studies. Finally, AI image analysis is facilitating the identification of novel radiotherapy predictive biomarkers.

We've made several findings concerning the tumor response to hypofractionated radiotherapy, including more recently, the temporal kinetics of both radiobiologically significant and abstracted AI-derived tissue response metrics. Additionally, we have demonstrated the promise for multimodal imaging being performed more accurately, correlating both MRI, macroscopic and optical coherence tomography, microscopic, angiography-derived metrics. By extending the effective length of longitudinal studies, we may better identify predictive biomarkers for long-term tumor treatment response.

Additionally, by improving robustness of co-registration between macroscopic clinically available imaging modalities and microscopic preclinical imaging modalities, we may enhance the translatability of our findings from benchtop to bedside. During a stereotactic body radiation therapy, high doses of radiation are delivering a reduced number of fractions. One potential radiobiological target associated with increased cell death in SVRT is the tumor microvasculature.

By combining high-resolution optical angiography and MRI, we want to enable functional MRI microvascular imaging for patient-specific SVRT treatment planning and improved outcomes.

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Dorsal Skinfold Window ChamberTumor Mouse ModelIntravital MicroscopyMagnetic Resonance ImagingTranslational Cancer ResearchPreclinical ImagingMRI CorrelationPerfusion-sensitive ImagingBiophotonicsOptical Coherence TomographyRadiotherapy Biomarkers3D PrintingLongitudinal StudiesCo-registrationStereotactic Body Radiation TherapyTumor Microvasculature

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