Radiation dose estimates based on Monte Carlo simulation for spiral breast computed tomography imaging in a large cohort of patients.

BACKGROUND: Spiral breast computed tomography (BCT) equipped with a photon-counting detector (PCD) is a new radiological modality allowing for the compression-free acquisition of high-resolution 3-D datasets of the breast. Optimized dose exposu04170/re setups according to breast size were previously proposed but could not effectively be applied in a clinical environment due to ambiguity in measuring breast size. PURPOSE: This study aims to report the standard radiation dose values in a large cohort of patients examined with BCT, and to provide a mathematical model to estimate radiation dose based on morphological features of the breast. METHODS: This retrospective study was conducted on 1657 BCT examinations acquired between 2018 and 2021 from 829 participants (57 ± 10 years, all female). Applying a dedicated breast tissue segmentation algorithm and Monte Carlo (MC) simulation, mean absorbed dose (MAD), mean glandular dose (MGD), mean skin dose (MSD), maximum glandular dose (maxGD), and maximum skin dose (maxSD) were calculated and related to morphological features such as breast volume, effective diameter, breast length, skin volume, and glandularity. Effective dose (ED) was calculated by applying the corresponding beam and tissue weighting factors, 1 Sv/Gy and 0.12 per breast. Relevant morphological features predicting dose values were identified based on the Spearman's rank correlation coefficient. Exponential or bi-exponential models predicting the dose values as a function of morphological features were fitted by using a non-linear least squares (LS) method. The models were validated by assessing R2 and residual standard error (RSE). RESULTS: The most relevant morphological features for radiation dose estimation were the breast volume (correlation coefficient: -0.8), diameter (-0.7), and length (-0.6). The glandularity presented a weak-positive correlation (0.4) with MGD and maxGD due to the inhomogeneous distribution of the glandularity and absorbed dose in the 3-D breast volume. The standard MGDs were calculated to be 7.3 ± 0.7, 6.5 ± 0.3, and 5.9 ± 0.3 mGy, MADs to 7.6 ± 0.8, 6.8 ± 0.3, and 6.2 ± 0.3 mGy, maxSDs to 19.9 ± 1.6, 19.5 ± 0.5, and 18.9 ± 0.5 mGy, and EDs to 0.88 ± 0.08, 0.78 ± 0.04, and 0.72 ± 0.04 mSv for small, medium, and large breasts with average breast lengths of 5.9 ± 1.6, 8.7 ± 1.3, and 12.2 ± 2.0 cm, respectively. The estimated glandularity - 23.1 ± 16.9, 12.5 ± 11.4, and 6.9 ± 7.3% from small to large breasts. The mathematical models were able to estimate the MAD, MGD, MSD, and maxSD as a function of each morphological feature with only upto 0.5 mGy RSE. CONCLUSION: We presented the typical morphological features and standard dose values according to the breast size acquired from a large patient cohort. We established radiation dose estimation models allowing accurate estimation of dose values including MGD with an acceptable RSE based on each of the easily measured morphological features of the breast. Clinicians could use the breast length to operate as a dosimetric alert of the scanner prior to a BCT scan. Radiation exposure for BCT was lower than diagnostic mammography (MG) and cone-beam breast CT (BCT).

A hidden Markov model for lymphatic tumor progression in the head and neck.

Currently, elective clinical target volume (CTV-N) definition for head and neck squamous cell carcinoma (HNSCC) is mostly based on the prevalence of nodal involvement for a given tumor location. In this work, we propose a probabilistic model for lymphatic metastatic spread that can quantify the risk of microscopic involvement in lymph node levels (LNL) given the location of macroscopic metastases and T-category. This may allow for further personalized CTV-N definition based on an individual patient's state of disease. We model the patient's state of metastatic lymphatic progression as a collection of hidden binary random variables that indicate the involvement of LNLs. In addition, each LNL is associated with observed binary random variables that indicate whether macroscopic metastases are detected. A hidden Markov model (HMM) is used to compute the probabilities of transitions between states over time. The underlying graph of the HMM represents the anatomy of the lymphatic drainage system. Learning of the transition probabilities is done via Markov chain Monte Carlo sampling and is based on a dataset of HNSCC patients in whom involvement of individual LNLs was reported. The model is demonstrated for ipsilateral metastatic spread in oropharyngeal HNSCC patients. We demonstrate the model's capability to quantify the risk of microscopic involvement in levels III and IV, depending on whether macroscopic metastases are observed in the upstream levels II and III, and depending on T-category. In conclusion, the statistical model of lymphatic progression may inform future, more personalized, guidelines on which LNL to include in the elective CTV. However, larger multi-institutional datasets for model parameter learning are required for that.

Accounting for Range Uncertainties in the Optimization of Combined Proton-Photon Treatments Via Stochastic Optimization.

PURPOSE: Proton treatment slots are a limited resource. Combined proton-photon treatments, in which most fractions are delivered with photons and only a few with protons, may represent a practical solution to optimize the allocation of proton resources over the patient population. We demonstrate how a limited number of proton fractions can be optimally used in multimodality treatments and address the issue of the robustness of combined treatments against proton range uncertainties. METHODS AND MATERIALS: Combined proton-photon treatments are planned by simultaneously optimizing intensity modulated radiation therapy and proton therapy plans while accounting for the fractionation effect through the biologically effective dose model. The method was investigated for different tumor sites (a spinal metastasis, a sacral chordoma, and an atypical meningioma) in which organs at risk (OARs) were located within or near the tumor. Stochastic optimization was applied to mitigate range uncertainties. RESULTS: In optimal combinations, proton and photon fractions deliver similar doses to OARs overlaying the target volume to protect these dose-limiting normal tissues through fractionation. Meanwhile, parts of the tumor are hypofractionated with protons. Thus, the total dose delivered with photons is reduced compared with simple combinations in which each modality delivers the prescribed dose per fraction to the target volume. The benefit of optimal combinations persists when range errors are accounted for via stochastic optimization. CONCLUSIONS: Limited proton resources are optimally used in combined treatments if parts of the tumor are hypofractionated with protons and near-uniform fractionation is maintained in serial OARs. Proton range uncertainties can be efficiently accounted for through stochastic optimization and are not an obstacle for clinical application.

Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer.

PURPOSE: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. METHODS AND MATERIALS: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. RESULTS: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. CONCLUSION: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.

MRI Based Bayesian Personalization of a Tumor Growth Model.

The mathematical modeling of brain tumor growth has been the topic of numerous research studies. Most of this work focuses on the reaction-diffusion model, which suggests that the diffusion coefficient and the proliferation rate can be related to clinically relevant information. However, estimating the parameters of the reaction-diffusion model is difficult because of the lack of identifiability of the parameters, the uncertainty in the tumor segmentations, and the model approximation, which cannot perfectly capture the complex dynamics of the tumor evolution. Our approach aims at analyzing the uncertainty in the patient specific parameters of a tumor growth model, by sampling from the posterior probability of the parameters knowing the magnetic resonance images of a given patient. The estimation of the posterior probability is based on: 1) a highly parallelized implementation of the reaction-diffusion equation using the Lattice Boltzmann Method (LBM), and 2) a high acceptance rate Monte Carlo technique called Gaussian Process Hamiltonian Monte Carlo (GPHMC). We compare this personalization approach with two commonly used methods based on the spherical asymptotic analysis of the reaction-diffusion model, and on a derivative-free optimization algorithm. We demonstrate the performance of the method on synthetic data, and on seven patients with a glioblastoma, the most aggressive primary brain tumor. This Bayesian personalization produces more informative results. In particular, it provides samples from the regions of interest and highlights the presence of several modes for some patients. In contrast, previous approaches based on optimization strategies fail to reveal the presence of different modes, and correlation between parameters.