Correlation of Preclinical In Vivo Imaging Modalities and Immunohistochemistry for Tumor Hypoxia and Vasculature

Background/Aim: Tumors exhibit impaired blood flow and hypoxic areas, which can reduce the effectiveness of treatments. Characterizing these tumor features can inform treatment decisions, including the use of vasculature modulation therapies. Imaging provides insight into these characteristics, with techniques varying between clinical and preclinical settings. Materials and Methods: To investigate changes in different tumor regions over time, R2*values from blood oxygen-level dependent MRI (BOLD-MRI), blood flow from power Doppler ultrasound, and oxygen saturation from photoacoustic ultrasound were analyzed and compared to CD31+ and pimonidazole tissue staining. To aid in preclinical translation, the fluorescence of a hypoxia probe was also compared to ultrasound techniques. Results: The imaging techniques detected tumor heterogeneity and an overall decrease in blood flow and oxygen levels over time. The analysis found varying correlations between regions, indicating an indirect relationship between imaging outcomes, which is influenced by external factors. Regional analysis allowed for more accurate results, as areas less affected by various factors were examined separately from highly impacted regions, aiding in their identification. Conclusion: Examining tumor regions with multiple imaging techniques allowed for better understanding and identification of modality-specific limitations, as certain techniques may incorrectly suggest that tumors are more vascularized and less hypoxic than they are.