Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions.

Area of Science:

• Biomedical imaging
• Molecular pathology
• Infectious disease research

Background:

• Traditional tissue analysis requires prior knowledge of targets or destructive processing for discovery.
• Existing methods limit the ability to study molecular distribution and discover new disease markers simultaneously.
• A gap exists in analyzing intact tissue architecture alongside comprehensive molecular discovery.

Purpose of the Study:

• To develop a multimodality imaging platform for discovery-based molecular histology.
• To overcome limitations of current tissue analysis techniques.
• To enable unbiased, spatial analysis of molecular changes in disease models.

Main Methods:

• Development of a novel multimodality imaging platform.
• Application of the platform to a mouse model of *Staphylococcus aureus* infection.
• Label-free, discovery-based molecular profiling of intact tissues.

Main Results:

• Identified infection-associated alterations in protein and elemental distribution in mouse tissues.
• Demonstrated unbiased, 3D analysis of disease-induced molecular architecture changes.
• Revealed molecular heterogeneity at the host-pathogen interface.

Conclusions:

• The developed platform facilitates discovery-based molecular histology without sacrificing tissue architecture.
• Enables culture-free diagnosis of infection via imaging-based analyte detection.
• Provides new insights into the molecular basis of host-pathogen interactions in disseminated infections.