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.

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 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.

Weed seed resources for birds in fields with contrasting conventional and genetically modified herbicide-tolerant crops.

The UK Farm Scale Evaluations (FSEs) have shown that the use of broad spectrum herbicides on genetically modified herbicide-tolerant (GMHT) crops can have dramatic effects on weed seed production compared to management of conventional varieties. Here, we use FSE data and information on bird diets to determine how GMHT cropping might change the food resources available to farmland birds. More than 60 fields of each of four crops, spring- and winter-sown oilseed rape, beet and maize, were split, one half being sown with a conventional variety, the other with a GMHT variety. Seed rain from weeds known to be important in the diets of 17 granivorous farmland bird species was measured under the two treatments. In beet and spring oilseed rape, rain of weed seeds important in the diets of 16 bird species was significantly reduced in GMHT compared to conventional halves; for no species did it increase. In winter oilseed rape, rain of weed seeds important in the diets of 10 species was significantly reduced in GMHT halves; for only one species did it increase significantly. By contrast, in maize, rain of weed seeds important in the diets of seven species was significantly greater in GMHT halves; for no species was it reduced. Treatment effects for the total weed seed energy available to each bird species were very similar to those for seed rain alone. Measuring the effects on individual bird species was outside the scope of this study. Despite this, these results suggest that should beet, spring and winter rape crops in the UK be largely replaced by GMHT varieties and managed as in the FSEs, this would markedly reduce important food resources for farmland birds, many of which declined during the last quarter of the twentieth century. By contrast, GMHT maize would be beneficial to farmland birds.