A Dorsal Skinfold Window Chamber Tumor Mouse Model for Combined Intravital Microscopy and Magnetic Resonance Imaging in Translational Cancer Research
April 12th, 2024
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.
Overview
This study presents a dorsal window chamber mouse model that integrates intravital microscopy with MRI for enhanced imaging capabilities. The approach aims to improve the clinical translation of findings from preclinical studies by correlating high-resolution imaging with clinically relevant modalities.
Key Study Components
Area of Science
- Neuroscience
- Imaging Techniques
- Oncology
Background
- Intravital microscopy provides high-resolution images but has limited tissue penetration.
- MRI offers greater depth penetration but lacks spatial resolution.
- Combining these modalities can enhance understanding of tumor microenvironments.
- Perfusion-sensitive imaging methods reveal microvasculature's role in tumor response.
Purpose of Study
- To correlate intravital microscopy with MRI for better clinical translation.
- To explore how microvasculature impacts tumor response to therapies.
- To utilize advanced imaging techniques for longitudinal studies.
Methods Used
- Dorsal window chamber mouse model for intravital imaging.
- Magnetic resonance imaging for depth penetration.
- Optical coherence tomography for biophotonics imaging.
- AI image analysis for identifying predictive biomarkers.
Main Results
- Successful integration of intravital microscopy with MRI.
- Revealed insights into tumor microvasculature and treatment response.
- Demonstrated the utility of 3D printing in custom tool manufacturing.
- AI analysis facilitated the identification of novel biomarkers.
Conclusions
- The combined imaging approach enhances the understanding of tumor biology.
- It may streamline the translation of preclinical findings to clinical applications.
- Future studies can build on this model to explore other therapeutic strategies.
Frequently Asked Questions
Executive Industry Relevance
Bridging the micro-to-macro imaging gap is critical for translating preclinical tumor biology insights into clinically actionable biomarkers and therapeutic strategies. The dorsal skinfold window chamber model enables direct spatial correlation between high-resolution intravital microscopy and clinically relevant MRI, supporting predictive confidence in translational oncology. This integrated imaging approach enhances portfolio decision-making by validating preclinical findings against modalities used in patient care.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables mechanistic de-risking by visualizing tumor microvasculature response to therapy at cellular and tissue scales.
- Supports functional target validation through longitudinal monitoring of microenvironmental changes post-treatment.
- Facilitates predictive biomarker identification by correlating microscopic and macroscopic imaging outputs.
Screening & Assay Development
- Prepares validated in vivo models for quantitative imaging-based screening of therapeutic interventions.
- Standardizes imaging outputs across modalities, improving reproducibility and assay comparability.
- Enables scalable, multimodal imaging workflows for robust compound evaluation in oncology pipelines.
Translational & Preclinical Research
- Aligns preclinical imaging findings with clinical MRI, enhancing disease relevance and translational continuity.
- Supports risk-adjusted advancement by providing direct evidence of treatment response in a disease-relevant system.
- Improves predictive confidence for biomarker-driven patient stratification strategies.
Pipeline & Workflow Integration
This model integrates seamlessly from early discovery through preclinical validation, enabling direct comparison of imaging biomarkers across the translational continuum.
- Discovery Biology: Facilitates hypothesis testing on tumor microenvironment dynamics and therapy response.
- Screening: Provides reproducible, quantitative imaging endpoints for compound and modality evaluation.
- Analytics: Delivers co-registered, multi-scale imaging data for robust statistical analysis and biomarker discovery.
- Translational Research: Bridges preclinical and clinical imaging, supporting biomarker alignment and validation.
- Enterprise Reuse: Establishes a reusable platform for multimodal imaging studies across oncology programs.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in tumor response studies.
- Operational Value: Standardizes imaging protocols and enables scalable, longitudinal studies.
- Strategic Value: Informs go/no-go decisions and reduces late-stage biological risk through translational imaging validation.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of oncology assets.
Implementation Considerations
- Requires expertise in both preclinical imaging and clinical MRI modalities.
- Demands access to advanced imaging instrumentation and 3D printing for custom tool fabrication.
- Necessitates cross-team standardization of imaging protocols and data analysis workflows.
- Adaptation may be needed for different tumor models or therapeutic modalities.
- Co-registration accuracy and longitudinal study design are critical for robust translational outputs.
Biopharma FAQs
Chapters in this video
0:00
Introduction
2:50
Tumor Cells Inoculation in Mice Through Precise Landmarking and Injection Techniques
4:57
Window Chamber Surgery in Tumor Cell Injected Mice for Tumor Growth Visualization and Imaging
6:59
Integrative Imaging Techniques for Tumor Analysis in Mice
