Dosimetrically coupled multiscale tetrahedral mesh models of human liver vasculature: implications for radiopharmaceutical dosimetry of both organ blood and parenchyma

Abstract

Objective.To develop a computational framework coupling multiscale vascular models of the human liver for improved radiation dosimetry calculations that clearly distinguish the absorbed dose to tissue parenchyma and that to its blood content at all spatial scales. This framework thus addresses limitations of homogeneous blood/tissue organ models in present use in radiopharmaceutical therapy.Approach.High-fidelity tetrahedral mesh models of liver vasculature were constructed at two spatial scales. At the macroscale, detailed hepatic arterial, venous, and portal venous networks were generated within reference adult male and female computational phantoms. At the microscale, a classical hexagonal liver lobule model incorporating sinusoids, bile compartments, and cellular components was developed. A mathematical framework was further developed to couple Monte Carlo radiation transport results across these spatial scales, enabling comprehensive dosimetric calculations for radiation dose to both blood and parenchymal tissues.Main Results.The coupled model system successfully accounted for the entire blood content of the liver, with approximately 31% represented in macroscale vessels (⩾100μm diameter) and 69% within microscale structures. Specific absorbed fractions were computed for monoenergetic photons, electrons, and alpha particles, demonstrating reciprocity between blood-to-parenchyma and parenchyma-to-blood crossfire. ReferenceS-values were computed for 22 therapeutic and 11 diagnostic radionuclides, providing the first comprehensive dataset for blood-specific and parenchyma-specific internal dosimetry calculations in the liver.Significance.This work establishes a novel framework for multi-scale radiation transport calculations in vascularized organs, enabling separate tracking of blood and parenchymal tissue doses. The methodology has immediate applications in improving dose calculations for radiopharmaceutical therapies, Y-90 microsphere radioembolization treatment, and analysis of blood dose during external beam radiotherapy. The approach can be readily adapted for other vascularized organs, representing a significant advancement in radiation dosimetry accuracy for both therapeutic and diagnostic applications by fully and independently accounting for organ activity localized within two tissue compartments-organ blood and organ parenchyma.

Keywords: blood self-dose; computational phantoms; liver vasculature; radiopharmaceutical dosimetry.

Figure 1.

The liver surface of the adult male (left) and adult female (right) MRCP partitioned into the standard eight segments of the Couinaud classification.

Figure 2.

Output from CGAL of transformed cylindrical vessel segments (left) and 2-manifold surface mesh produced via 3D Alpha Wrapping (right). The apparent increase in vessel thickness in the continuous mesh is due to a prescribed offset that is passed to the 3D Alpha Wrapping algorithm and is accounted for by systematically reducing the radii of the input vessel segments by a commensurate thickness.

Figure 3.

Posterior view of the hepatic arterial (A), hepatic venous (B), hepatic portal venous (C), and combined (D) macroscale vascular networks for the adult male.

Figure 4.

Posterior view of the hepatic arterial (A), hepatic venous (B), hepatic portal venous (C), and combined (D) macroscale vascular networks for the adult female.

Figure 5.

Microscale liver lobule model includes hepatic arteries and veins, portal veins, central vein, bile ducts, bile canaliculi, blood sinusoids, space of Disse, and Kupffer cells. (A) Hexagonal lobule model in polygon mesh format. (B) Kupffer cells adhering to the (luminal side of) epithelia of the sinusoid network. (C) Refined rectangular prism lobule model in tetrahedral mesh format (hepatocyte-labeled tetrahedral which fill the empty space in the model are omitted for clarity).

Figure 6.

Overview of multiscale liver vasculature model. Shown, from left to right, are decreasing spatial scales and the associated cell types, radiations, and other objects which are relevant at that scale. Diagrams representing cell types and blood vessels were taken from the NIH BioArt Source.

Figure 7.

Polygon and tetrahedral mesh adult male MRCP with highly detailed liver vasculature. (A) Clipped coronal view of tetrahedralized whole-body phantom. (B) Perspective view of phantom with liver surface hidden to reveal organ vasculature. (C) Clipped axial view of tetrahedralized whole-body phantom.

Figure 8.

Polygon and tetrahedral mesh adult female MRCP with highly detailed liver vasculature. (A) Clipped coronal view of tetrahedralized whole-body phantom. (B) Perspective view of phantom with liver surface hidden to reveal organ vasculature. (C) Clipped axial view of tetrahedralized whole-body phantom.

Figure 9.

Absorbed fractions (left) and specific absorbed fractions (right) for blood and parenchyma sources of monoenergetic alphas, electrons, and photons within the adult male liver vasculature phantoms.

Figure 10.

Absorbed fractions (left) and specific absorbed fractions (right) for blood and parenchyma sources of monoenergetic alphas, electrons, and photons within the adult female liver vasculature phantoms.

Figure 11.

Absorbed fractions to the whole liver for blood and parenchyma sources of monoenergetic alphas, electrons, and photons within the adult male (left column) and adult female (right column) liver vasculature phantoms.

Figure 12.

Specific absorbed fractions for the adult male (left column) and adult female (right column) assuming a multiscale or macroscale-only dosimetry model.