Beamlet based direct aperture optimization for MERT using a photon MLC

PURPOSE A beamlet based direct aperture optimization (DAO) for modulated electron radiotherapy (MERT) using photon multileaf collimator (pMLC) shaped electron fields is developed and investigated. METHODS The Swiss Monte Carlo Plan (SMCP) allows the calculation of dose distributions for pMLC shaped electron beams. SMCP is interfaced with the Eclipse TPS (Varian Medical Systems, Palo Alto, CA) which can thus be included into the inverse treatment planning process for MERT. This process starts with the import of a CT-scan into Eclipse, the contouring of the target and the organs at risk (OARs), and the choice of the initial electron beam directions. For each electron beam, the number of apertures, their energy, and initial shape are defined. Furthermore, the DAO requires dose-volume constraints for the structures contoured. In order to carry out the DAO efficiently, the initial electron beams are divided into a grid of beamlets. For each of those, the dose distribution is precalculated using a modified electron beam model, resulting in a dose list for each beamlet and energy. Then the DAO is carried out, leading to a set of optimal apertures and corresponding weights. These optimal apertures are now converted into pMLC shaped segments and the dose calculation for each segment is performed. For these dose distributions, a weight optimization process is launched in order to minimize the differences between the dose distribution using the optimal apertures and the pMLC segments. Finally, a deliverable dose distribution for the MERT plan is obtained and loaded back into Eclipse for evaluation. For an idealized water phantom geometry, a MERT treatment plan is created and compared to the plan obtained using a previously developed forward planning strategy. Further, MERT treatment plans for three clinical situations (breast, chest wall, and parotid metastasis of a squamous cell skin carcinoma) are created using the developed inverse planning strategy. The MERT plans are compared to clinical standard treatment plans using photon beams and the differences between the optimal and the deliverable dose distributions are determined. RESULTS For the idealized water phantom geometry, the inversely optimized MERT plan is able to obtain the same PTV coverage, but with an improved OAR sparing compared to the forwardly optimized plan. Regarding the right-sided breast case, the MERT plan is able to reduce the lung volume receiving more than 30% of the prescribed dose and the mean lung dose compared to the standard plan. However, the standard plan leads to a better homogeneity within the CTV. The results for the left-sided thorax wall are similar but also the dose to the heart is reduced comparing MERT to the standard treatment plan. For the parotid case, MERT leads to lower doses for almost all OARs but to a less homogeneous dose distribution for the PTV when compared to a standard plan. For all cases, the weight optimization successfully minimized the differences between the optimal and the deliverable dose distribution. CONCLUSIONS A beamlet based DAO using multiple beam angles is implemented and successfully tested for an idealized water phantom geometry and clinical situations.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Numerical solution of optimal control problems with constant control delays

We investigate a class of optimal control problems that exhibit constant exogenously given delays in the control in the equation of motion of the differential states. Therefore, we formulate an exemplary optimal control problem with one stock and one control variable and review some analytic properties of an optimal solution. However, analytical considerations are quite limited in case of delayed optimal control problems. In order to overcome these limits, we reformulate the problem and apply direct numerical methods to calculate approximate solutions that give a better understanding of this class of optimization problems. In particular, we present two possibilities to reformulate the delayed optimal control problem into an instantaneous optimal control problem and show how these can be solved numerically with a stateof- the-art direct method by applying Bock’s direct multiple shooting algorithm. We further demonstrate the strength of our approach by two economic examples.

Combinations of dexmedetomidine and alfaxalone with butorphanol in cats: application of an innovative stepwise optimisation method to identify optimal clinical doses for intramuscular anaesthesia

OBJECTIVES The aim of this study was to optimise dexmedetomidine and alfaxalone dosing, for intramuscular administration with butorphanol, to perform minor surgeries in cats. METHODS Initially, cats were assigned to one of five groups, each composed of six animals and receiving, in addition to 0.3 mg/kg butorphanol intramuscularly, one of the following: (A) 0.005 mg/kg dexmedetomidine, 2 mg/kg alfaxalone; (B) 0.008 mg/kg dexmedetomidine, 1.5 mg/kg alfaxalone; (C) 0.012 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; (D) 0.005 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; and (E) 0.012 mg/kg dexmedetomidine, 2 mg/kg alfaxalone. Thereafter, a modified 'direct search' method, conducted in a stepwise manner, was used to optimise drug dosing. The quality of anaesthesia was evaluated on the basis of composite scores (one for anaesthesia and one for recovery), visual analogue scales and the propofol requirement to suppress spontaneous movements. The medians or means of these variables were used to rank the treatments; 'unsatisfactory' and 'promising' combinations were identified to calculate, through the equation first described by Berenbaum in 1990, new dexmedetomidine and alfaxalone doses to be tested in the next step. At each step, five combinations (one new plus the best previous four) were tested. RESULTS None of the tested combinations resulted in adverse effects. Four steps and 120 animals were necessary to identify the optimal drug combination (0.014 mg/kg dexmedetomidine, 2.5 mg/kg alfaxalone and 0.3 mg/kg butorphanol). CONCLUSIONS AND RELEVANCE The investigated drug mixture, at the doses found with the optimisation method, is suitable for cats undergoing minor clinical procedures.

SOMS: SurrOgate MultiStart algorithm for use with nonlinear programming for global optimization

SOMS is a general surrogate-based multistart algorithm, which is used in combination with any local optimizer to find global optima for computationally expensive functions with multiple local minima. SOMS differs from previous multistart methods in that a surrogate approximation is used by the multistart algorithm to help reduce the number of function evaluations necessary to identify the most promising points from which to start each nonlinear programming local search. SOMS’s numerical results are compared with four well-known methods, namely, Multi-Level Single Linkage (MLSL), MATLAB’s MultiStart, MATLAB’s GlobalSearch, and GLOBAL. In addition, we propose a class of wavy test functions that mimic the wavy nature of objective functions arising in many black-box simulations. Extensive comparisons of algorithms on the wavy testfunctions and on earlier standard global-optimization test functions are done for a total of 19 different test problems. The numerical results indicate that SOMS performs favorably in comparison to alternative methods and does especially well on wavy functions when the number of function evaluations allowed is limited.

Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data. MSforID'

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their Setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Search for direct chargino production in anomaly-mediated supersymmetry breaking models based on a disappearing-track signature in pp collisions at sqrts=7 TeV with the ATLAS detector

A search for direct chargino production in anomaly-mediated supersymmetry breaking scenarios is performed in p p collisions at root s = 7 TeV using 4.7 fb(-1) of data collected with the ATLAS experiment at the LHC. In these models, the lightest chargino is predicted to have a lifetime long enough to be detected in the tracking detectors of collider experiments. This analysis explores such models by searching for chargino decays that result in tracks with few associated hits in the outer region of the tracking system. The transverse-momentum spectrum of candidate tracks is found to be consistent with the expectation from the Standard Model background processes and constraints on chargino properties are obtained.

Search for direct slepton and gaugino production in final states with two leptons and missing transverse momentum with the ATLAS detector in pp collisions at sqrts=7 TeV

A search for the electroweak pair production of charged sleptons and weak gauginos decaying into final states with two leptons is performed using 4.7 fb(-1) of proton-proton collision data at root s = 7 TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excesses are observed with respect to the prediction from Standard Model processes. In the scenario of direct slepton production, if the sleptons decay directly into the lightest neutralino, left-handed slepton masses between 85 and 195 GeV are excluded at 95% confidence level for a 20 GeV neutralino. Chargino masses between 110 and 340 GeV are excluded in the scenario of direct production of wino-like chargino pairs decaying into the lightest neutralino via an intermediate on-shell charged slepton for a 10 GeV neutralino. The results are also interpreted in the framework of the phenomenological minimal supersymmetric Standard Model.

Search for direct third-generation squark pair production in final states with missing transverse momentum and two b-jets in sqrts = 8 TeV pp collisions with the ATLAS detector

The results of a search for pair production of supersymmetric partners of the Standard Model third-generation quarks are reported. This search uses 20.1 fb(-1) of pp collisions at root s = 8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The lightest bottom and top squarks ((b) over tilde (1) and (t) over tilde (1) respectively) are searched for in a final state with large missing transverse momentum and two jets identified as originating from b-quarks. No excess of events above the expected level of Standard Model background is found. The results are used to set upper limits on the visible cross section for processes beyond the Standard Model. Exclusion limits at the 95% confidence level on the masses of the third-generation squarks are derived in phenomenological supersymmetric R-parity-conserving models in which either the bottom or the top squark is the lightest squark. The (b) over tilde (1) is assumed to decay via (b) over tilde (1) -> b (chi) over tilde (0)(1) and the (t) over tilde (1) via (t) over tilde (1) b (chi) over tilde (+/-)(1), with undetectable products of the subsequent decay of the (chi) over tilde (+/-)(1) due to the small mass splitting between the (chi) over tilde (+/-)(1) and the (chi) over tilde (0)(1)

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at √s=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton-proton collision data at s√=8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t~→tχ~01 or t~→bχ~±1→bW(∗)χ~01, where χ~01 (χ~±1) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t~→tχ~01. For a branching fraction of 100%, top squark masses in the range 270-645 GeV are excluded for χ~01 masses below 30 GeV. For a branching fraction of 50% to either t~→tχ~01 or t~→bχ~±1, and assuming the χ~±1 mass to be twice the χ~01 mass, top squark masses in the range 250-550 GeV are excluded for χ~01 masses below 60 GeV.

Search for direct production of charginos, neutralinos and sleptons in final states with two leptons and missing transverse momentum in pp collisions at √s = 8 TeV with the ATLAS detector

Searches for the electroweak production of charginos, neutralinos and sleptons in final states characterized by the presence of two leptons (electrons and muons) and missing transverse momentum are performed using 20.3 fb−1 of proton-proton collision data at ps = 8TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excess beyond Standard Model expectations is observed. Limits are set on the masses of the lightest chargino, next-to-lightest neutralino and sleptons for different lightest-neutralino mass hypotheses in simplified models. Results are also interpreted in various scenarios of the phenomenological Minimal Supersymmetric Standard Model.

Search for direct top squark pair production in events with a Z boson, b-jets and missing transverse momentum in √s=8 TeV pp collisions with the ATLAS detector

A search is presented for direct top squark pair production using events with at least two leptons including a same-flavour opposite-sign pair with invariant mass consistent with the Z boson mass, jets tagged as originating from b-quarks and missing transverse momentum. The analysis is performed with proton–proton collision data at √ s = 8 TeV collected with the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of 20.3 fb−1. No excess beyond the Standard Model expectation is observed. Interpretations of the results are provided in models based on the direct pair production of the heavier top squark state (˜t2) followed by the decay to the lighter top squark state (˜t1) via ˜t2 → Z ˜t1, and for ˜t1 pair production in natural gaugemediated supersymmetry breaking scenarios where the neutralino (˜χ 01 ) is the next-to-lightest supersymmetric particle and decays producing a Z boson and a gravitino ( ˜G ) via the ˜χ 01→ Z ˜G process.