Determining individual glomerular proteinuria and periglomerular infiltration in a cleared murine kidney by a...

Area of Science:

• Biomedical Imaging
• Renal Pathology
• Computational Biology

Background:

• Three-dimensional (3D) imaging is crucial in research and medicine.
• Real-world 3D image limitations hinder algorithmic analysis.
• Analyzing functional and spatial relationships in organs like the kidney requires advanced methods.

Purpose of the Study:

• To develop a framework for 3D imaging and analysis of functional and spatial relations.
• To enable precise quantification of parameters in experimental nephritis.
• To investigate correlations between proteinuria and immune cell infiltration in glomeruli.

Main Methods:

• Optimized optical tissue-clearing protocols for fluorescence preservation.
• Developed adjustable 3D correction fields to compensate for attenuation.
• Adapted the fast marching algorithm for 3D backtracking and object concentration analysis.

Main Results:

• Quantified individual proteinuria and immune cell infiltration in glomeruli of a glomerulonephritis mouse model.
• Found no direct correlation between glomeruli inflammation and proteinuria.
• Discovered a positive correlation between spatial density of adjacent glomeruli and proteinuria.

Conclusions:

• The location of kidney biopsies may influence observed glomerular damage severity due to clustered proteinuric glomeruli.
• The developed algorithmic pipeline can analyze various parameters in organs with functional subunits.
• The framework is adaptable to other imaging modalities and organs.