Coupling biomechanics to a cellular level model: An approach to patient-specific image driven multi-scale and multi-physics tumor simulation

Modeling of tumor growth has been performed according to various approaches addressing different biocomplexity levels and spatiotemporal scales. Mathematical treatments range from partial differential equation based diffusion models to rule-based cellular level simulators, aiming at both improving our quantitative understanding of the underlying biological processes and, in the mid- and long term, constructing reliable multi-scale predictive platforms to support patient-individualized treatment planning and optimization. The aim of this paper is to establish a multi-scale and multi-physics approach to tumor modeling taking into account both the cellular and the macroscopic mechanical level. Therefore, an already developed biomodel of clinical tumor growth and response to treatment is self-consistently coupled with a biomechanical model. Results are presented for the free growth case of the imageable component of an initially point-like glioblastoma multiforme tumor. The composite model leads to significant tumor shape corrections that are achieved through the utilization of environmental pressure information and the application of biomechanical principles. Using the ratio of smallest to largest moment of inertia of the tumor material to quantify the effect of our coupled approach, we have found a tumor shape correction of 20\% by coupling biomechanics to the cellular simulator as compared to a cellular simulation without preferred growth directions. We conclude that the integration of the two models provides additional morphological insight into realistic tumor growth behavior. Therefore, it might be used for the development of an advanced oncosimulator focusing on tumor types for which morphology plays an important role in surgical and/or radio-therapeutic treatment planning.

IMRT credentialing for prospective trials using institutional virtual phantoms: results of a joint European Organization for the Research and Treatment of Cancer and Radiological Physics Center project.

BACKGROUND AND PURPOSE Intensity-modulated radiotherapy (IMRT) credentialing for a EORTC study was performed using an anthropomorphic head phantom from the Radiological Physics Center (RPC; RPC(PH)). Institutions were retrospectively requested to irradiate their institutional phantom (INST(PH)) using the same treatment plan in the framework of a Virtual Phantom Project (VPP) for IMRT credentialing. MATERIALS AND METHODS CT data set of the institutional phantom and measured 2D dose matrices were requested from centers and sent to a dedicated secure EORTC uploader. Data from the RPC(PH) and INST(PH) were thereafter centrally analyzed and inter-compared by the QA team using commercially available software (RIT; ver.5.2; Colorado Springs, USA). RESULTS Eighteen institutions participated to the VPP. The measurements of 6 (33%) institutions could not be analyzed centrally. All other centers passed both the VPP and the RPC ±7%/4 mm credentialing criteria. At the 5%/5 mm gamma criteria (90% of pixels passing), 11(92%) as compared to 12 (100%) centers pass the credentialing process with RPC(PH) and INST(PH) (p = 0.29), respectively. The corresponding pass rate for the 3%/3 mm gamma criteria (90% of pixels passing) was 2 (17%) and 9 (75%; p = 0.01), respectively. CONCLUSIONS IMRT dosimetry gamma evaluations in a single plane for a H&N prospective trial using the INST(PH) measurements showed agreement at the gamma index criteria of ±5%/5 mm (90% of pixels passing) for a small number of VPP measurements. Using more stringent, criteria, the RPC(PH) and INST(PH) comparison showed disagreement. More data is warranted and urgently required within the framework of prospective studies.

Accelerator and detector physics at the Bern medical cyclotron and its beam transport line.

The cyclotron laboratory for radioisotope production and multi-disciplinary research at the Bern University Hospital (Inselspital) is based on an 18-MeV proton accelerator, equipped with a specifically conceived 6-m long external beam line, ending in a separate bunker. This facility allows performing daily positron emission tomography (PET) radioisotope production and research activities running in parallel. Some of the latest developments on accelerator and detector physics are reported. They encompass novel detectors for beam monitoring and studies of low current beams.

Variability of mesospheric water vapor above Bern in relation to the 27-day solar rotation cycle

Many studies investigated solar–terrestrial responses (thermal state, O₃ , OH, H₂O) with emphasis on the tropical upper atmosphere. In this paper the Focus is switched to water vapor in the mesosphere at a mid-latitudinal location. Eight years of water vapor profile measurements above Bern (46.88°N/7.46°E) are investigated to study oscillations with the Focus on periods between 10 and 50 days. Different spectral analyses revealed prominent features in the 27-day oscillation band, which are enhanced in the upper mesosphere (above 0.1 hPa, ∼64 km) during the rising sun spot activity of solar cycle 24. Local as well as zonal mean Aura MLS observations Support these results by showing a similar behavior. The relationship between mesospheric water and the solar Lyman-α flux is studied by comparing thesi-milarity of their temporal oscillations. The H₂O oscillation is negatively correlated to solar Lyman-α oscillation with a correlation coefficient of up to −0.3 to −0.4, and the Phase lag is 6–10 days at 0.04 hPa. The confidence level of the correlation is ≥99%. This finding supports the assumption that the 27-day oscillation in Lyman-α causes a periodical photo dissociation loss in mesospheric water. Wavelet power spectra, cross-wavelet transform and wavelet coherence analysis (WTC)complete our study. More periods of high common wavelet power of H₂O and solar Lyman-α are present when amplitudes of the Lyman-α flux increase. Since this is not a measure of physical correlation a more detailed view on WTC is necessary, where significant (two sigma level)correlations occur intermittently in the 27 and 13-day band with variable Phase lock behavior. Large Lyman-α oscillations appeared after the solar super storm in July 2012 and the H₂O oscillations show a well pronounced anticorrelation. The competition between advective transport and photo dissociation loss of mesospheric water vapor may explain the sometimes variable Phase relationship of mesospheric H₂O and solar Lyman-α oscillations. Generally, the WTC analysis indicates that solar variability causes observable photochemical and dynamical processes in the mid-latitude mesosphere.

Physics potential of a long-baseline neutrino oscillation experiment using a J-PARC neutrino beam and Hyper-Kamiokande

Hyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of HyperKamiokande is the study of CP asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this paper, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis uses the framework and systematic uncertainties derived from the ongoing T2K experiment. With a total exposure of 7.5 MW × 10⁷ s integrated proton beam power (corresponding to 1.56 × 10²² protons on target with a 30 GeV proton beam) to a 2.5-degree off-axis neutrino beam, it is expected that the leptonic CP phase δCP can be determined to better than 19 degrees for all possible values of δCP , and CP violation can be established with a statistical significance of more than 3 σ (5 σ) for 76% (58%) of the δCP parameter space. Using both νe appearance and νµ disappearance data, the expected 1σ uncertainty of sin²θ₂₃ is 0.015(0.006) for sin²θ₂₃ = 0.5(0.45).