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Abstract: FR-PO694

Determining Individual Glomerular Proteinuria and Periglomerular Infiltration in a Cleared Murine Kidney by 3D Fast-Marching Algorithm

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Kurts, Christian, University Clinic of Bonn, Bon, Germany
  • Böhner, Alexander Marc Christian, University Clinic of Bonn, Bon, Germany
  • Böhner, Karin Agnes Maria, University Clinic of Bonn, Bon, Germany
  • Braehler, Sebastian, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Attenberger, Ulrike, University Clinic of Bonn, Bon, Germany
  • Rumpf, Martin, Rheinische Friedrich-Wilhelms-Universitat Mathematisch-Naturwissenschaftliche Fakultat, Bonn, Nordrhein-Westfalen, Germany
  • Effland, Alexander, Rheinische Friedrich-Wilhelms-Universitat Mathematisch-Naturwissenschaftliche Fakultat, Bonn, Nordrhein-Westfalen, Germany
Background

Research in organs with a complex architecture like the kidney benefits from 3D image analysis. However, limited resolution and imperfections of real-world 3D image material often preclude algorithmic image analysis. We here present a methodical framework to overcome these obstacles.

Methods

We optimized our optical tissue clearing protocol to preserve fluorescence signals for light-sheet-fluorescence-microscopy and compensated attenuation effects using adjustable 3D correction fields. Next, we adapted the Fast-Marching algorithm (FMA) to conduct backtracking in 3D environments. Furthermore, we designed a local concentration measure termed Volumetric impact factor (VIF) to quantify extractable objects in 3D microenvironments.

Results

We applied this framework to cleared kidneys of mice with nephrotoxic nephritis, a model for human crescentic glomerulonephritis. Our framework generated a list of anatomical and functional parameters of each individual glomerulus of a murine kidney. Using FMA, we determined and visualized the individual proteinuria (Figure 1). Using VIF, we quantified the individual periglomerular dendritic cell infiltration in nephritic kidneys. By correlating these parameters, we disprove the intuitional assumption that the most infiltrated glomeruli are the most proteinuric. Instead, the glomerular density predicted proteinuria.

Conclusion

Our framework allows multiparameter image analysis and advanced 3D analysis of all nephrons of a murine kidney and facilitates understanding of renal immunopathology.

Visual verification of the FMA as a slice-by-slice reduction. Glomeruli in green and intratubular albumin deposits in orange. Shortest intratubular path between protein deposit and causative glomerulus is in purple.

Funding

  • Government Support – Non-U.S.