MIDOS: a novel stochastic model towards a treatment planning system for microsphere dosimetry in liver tumors.

PURPOSE: Transarterial radioembolization (TARE) procedures treat liver tumors by injecting radioactive microspheres into the hepatic artery. Currently, there is a critical need to optimize TARE towards a personalized dosimetry approach. To this aim, we present a novel microsphere dosimetry (MIDOS) stochastic model to estimate the activity delivered to the tumor(s), normal liver, and lung. METHODS: MIDOS incorporates adult male/female liver computational phantoms with the hepatic arterial, hepatic portal venous, and hepatic venous vascular trees. Tumors can be placed in both models at user discretion. The perfusion of microspheres follows cluster patterns, and a Markov chain approach was applied to microsphere navigation, with the terminal location of microspheres determined to be in either normal hepatic parenchyma, hepatic tumor, or lung. A tumor uptake model was implemented to determine if microspheres get lodged in the tumor, and a probability was included in determining the shunt of microspheres to the lung. A sensitivity analysis of the model parameters was performed, and radiation segmentectomy/lobectomy procedures were simulated over a wide range of activity perfused. Then, the impact of using different microspheres, i.e., SIR-Sphere®, TheraSphere®, and QuiremSphere®, on the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), and mean absorbed dose was analyzed. RESULTS: Highly vascularized tumors translated into increased TNR. Treatment results (TNR and LSF) were significantly more variable for microspheres with high particle load. In our scenarios with 1.5 GBq perfusion, TNR was maximum for TheraSphere® at calibration time in segmentectomy/lobar technique, for SIR-Sphere® at 1-3 days post-calibration, and regarding QuiremSphere® at 3 days post-calibration. CONCLUSION: This novel approach is a decisive step towards developing a personalized dosimetry framework for TARE. MIDOS assists in making clinical decisions in TARE treatment planning by assessing various delivery parameters and simulating different tumor uptakes. MIDOS offers evaluation of treatment outcomes, such as TNR and LSF, and quantitative scenario-specific decisions.

A stochastic model of blood flow to calculate blood dose during radiotherapy.

Purpose. Lymphopenia is a common side effect in patients treated with radiotherapy, potentially caused by direct cell killing of circulating lymphocytes in the blood. To investigate this hypothesis, a method to assess dose to circulating lymphocytes is needed.Methods. A stochastic model to simulate systemic blood flow in the human body was developed based on a previously designed compartment model. Blood dose was obtained by superimposing the spatiotemporal distribution of blood particles with a time-varying dose rate field, and used as a surrogate for dose to circulating lymphocytes. We discuss relevant theory on compartmental modeling and how to combine it with models of explicit organ vasculature.Results. A general workflow was established which can be used for any anatomical site. Stochastic compartments can be replaced by explicit models of organ vasculatures for improved spatial resolution, and tumor compartments can be dynamically assigned. Generating a patient-specific blood flow distribution takes about one minute, fast enough to investigate the effect of varying treatment parameters such as the dose rate. Furthermore, the anatomical structures contributing most to the overall blood dose can be identified, which could potentially be used for lymphocyte-sparing treatment planning.Conclusion. The ability to report the blood dose distribution during radiotherapy is imperative to test and act upon the current paradigm that radiation-induced lymphopenia is caused by direct cell killing of lymphocytes in the blood. We have built a general model that can do so for various treatment sites. The presented framework is publicly available athttp://github.com/mghro/hedos.

Intra-brain vascular models within the ICRP mesh-type adult reference phantoms for applications to internal dosimetry.

Objective. Phantoms of the International Commission on Radiological Protection provide a framework for standardized dosimetry. The modeling of internal blood vessels-essential to tracking circulating blood cells exposed during external beam radiotherapy and to account for radiopharmaceutical decays while still in blood circulation-is, however, limited to the major inter-organ arteries and veins. Intra-organ blood is accounted for only through the assignment of a homogeneous mixture of parenchyma and blood [single-region (SR) organs]. Our goal was to develop explicit dual-region (DR) models of intra-organ blood vasculature of the adult male brain (AMB) and adult female brain (AFB).Approach. A total of 4000 vessels were created amongst 26 vascular trees. The AMB and AFB models were then tetrahedralized for coupling to the PHITS radiation transport code. Absorbed fractions were computed for monoenergetic alpha particles, electrons, positrons, and photons for both decay sites within the blood vessels and for tissues outside these vessels. RadionuclideS-values were computed for 22 and 10 radionuclides commonly employed in radiopharmaceutical therapy and nuclear medicine diagnostic imaging, respectively.Main results. For radionuclide decays, values ofS(brain tissue ← brain blood) assessed in the traditional manner (SR) were higher than those computed using our DR models by factors of 1.92, 1.49, and 1.57 for therapeutic alpha-emitters, beta-emitters, and Auger electron-emitters, respectively in the AFB and by factors of 1.65, 1.37, and 1.42 for these same radionuclide categories in the AMB. Corresponding ratios of SR and DR values ofS(brain tissue ← brain blood) were 1.34 (AFB) and 1.26 (AMB) for four SPECT radionuclides, and were 1.32 (AFB) and 1.24 (AMB) for six common PET radionuclides.Significance. The methodology employed in this study can be explored in other organs of the body for proper accounting of blood self-dose for that fraction of the radiopharmaceutical still in general circulation.

A mesh-based model of liver vasculature: implications for improved radiation dosimetry to liver parenchyma for radiopharmaceuticals.

PURPOSE: To develop a model of the internal vasculature of the adult liver and demonstrate its application to the differentiation of radiopharmaceutical decay sites within liver parenchyma from those within organ blood. METHOD: Computer-generated models of hepatic arterial (HA), hepatic venous (HV), and hepatic portal venous (HPV) vascular trees were algorithmically created within individual lobes of the ICRP adult female and male livers (AFL/AML). For each iteration of the algorithm, pressure, blood flow, and vessel radii within each tree were updated as each new vessel was created and connected to a viable bifurcation site. The vascular networks created inside the AFL/AML were then tetrahedralized for coupling to the PHITS radiation transport code. Specific absorbed fractions (SAF) were computed for monoenergetic alpha particles, electrons, positrons, and photons. Dual-region liver models of the AFL/AML were proposed, and particle-specific SAF values were computed assuming radionuclide decays in blood within two locations: (1) sites within explicitly modeled hepatic vessels, and (2) sites within the hepatic blood pool residing outside these vessels to include the capillaries and blood sinuses. S values for 22 and 10 radionuclides commonly used in radiopharmaceutical therapy and imaging, respectively, were computed using the dual-region liver models and compared to those obtained in the existing single-region liver model. RESULTS: Liver models with virtual vasculatures of ~ 6000 non-intersecting straight cylinders representing the HA, HPV, and HV circulations were created for the ICRP reference. For alpha emitters and for beta and auger-electron emitters, S values using the single-region models were approximately 11% (AML) to 14% (AFL) and 11% (AML) to 13% (AFL) higher than the S values obtained using the dual-region models, respectively. CONCLUSIONS: The methodology employed in this study has shown improvements in organ parenchymal dosimetry through explicit consideration of blood self-dose for alpha particles (all energies) and for electrons at energies below ~ 100 keV.