Histology-Based Microscale Human Spleen Model for Radiopharmaceutical Therapy Dosimetry
Abstract
Purpose
For radiopharmaceuticals emitting high linear energy transfer (LET) particles, such as alpha particles, the spleen can receive substantial localized doses due to its reticuloendothelial function. To capture dose heterogeneity, this study aims to develop three-dimensional (3D) mesh-based microscale spleen models for humans, based on the reticulin-stained histology, to enable precise tissue-level dosimetry for radiopharmaceutical applications.
Methods
The microscale human spleen models were developed by segmenting the reticulin-stained human spleen histology slides. Seven regions of interest (ROIs), including four with large blood vessels, were imaged from the histology sections using a Zeiss Axiophot microscope. Among the splenic structures, white pulp (germinal, mantle, marginal zones), trabeculae, and vessels were manually segmented twice by independent observers to reduce segmentation uncertainties arising from human errors. Red pulp sinusoids were segmented based on the intensity thresholding approach. White pulp, trabeculae, and sinusoids were converted to 3D surface meshes using 3D Slicer software, which were then refined to remove defects using Rhinoceros 3D software. To consider the histology-induced blood shrinkage, the mesh models were enlarged to in vivo conditions based on a shrinkage factor, which was derived by measuring the mean diameter of the red blood cells from the images and comparing it with the literature values.
Results
Seven microscale human spleen models were generated in polygonal-mesh format based on histology images. The models capture realistic anatomy of red and white pulp, trabeculae, and blood vessels. These models are watertight, with no intersections or defects. These high-fidelity meshes are ready for Monte Carlo-based dosimetry, enabling tissue-level dose calculations for radiopharmaceutical applications, including high-LET particle therapies.
Conclusion
This study developed seven mesh-based microscale human spleen models that capture the precise splenic tissue anatomy with an approximate volume of 1.2 mm3. These models will be used to produce radionuclide S values for use in radiopharmaceutical dosimetry.