Construction of Histology-Based Three-Dimensional Minipig Renal Cortex Model for Preclinical Dosimetry
Abstract
Purpose
In the preclinical phase of radiopharmaceutical development, minipigs are frequently used to evaluate radiation-induced toxicity prior to human translation. Among normal organs, the kidney is a critical dose-limiting organ due to its roles in filtration, excretion, and reabsorption of radiopharmaceuticals. For alpha-emitting radiopharmaceuticals, microscale tissue structures are required for accurate dose estimation given the short range of alpha particles. This study aimed to develop a three-dimensional microscale model of the minipig renal cortex based on histology images for preclinical dosimetry.
Methods
A total of 200 serially-sectioned H&E-stained histological images of the renal cortex were obtained from a 6-month-old female minipig, with 5 µm thickness and 2.74 µm pixel size. Images were aligned using landmark-based rigid registration. Glomeruli and Bowman’s capsules were segmented with 3D Slicer’s grow-from-seeds algorithm and manual refinement. Segmented structures were converted to 3D surface meshes, with defects (e.g., holes) corrected using Blender. Custom Python code was used to construct proximal and distal convoluted tubules, filling the remaining space within a 1 × 1 × 1 mm³ volume based on morphometric parameters measured from the images.
Results
A 1 x 1 x 1 mm3 3D renal cortex model of the female minipig was developed in polygonal-mesh format. The model represents key microscale renal structures, including glomeruli, bowman’s capsules, and proximal and distal convoluted tubules, providing a realistic anatomical representation of the minipig renal cortex. The model was converted into tetrahedral-mesh format and implemented in PHITS Monte Carlo radiation transport code. Electron and alpha specific absorbed fractions (SAFs) were calculated to support preclinical dosimetric evaluations.
Conclusion
A histology-based 3D microscale renal cortex model of the minipig was successfully developed and applied to Monte Carlo radiation transport simulations. This model provides a robust anatomical and computational foundation for tissue-level dosimetry in preclinical studies and supports improved animal-to-human dose translation.