Usability and accuracy of high-resolution detectors for daily quality assurance for robotic radiosurgery

For daily CyberKnife QA a Winston-Lutz-Test (Automated-Quality-Assurance, AQA) is used to determine sub-millimeter deviations in beam delivery accuracy. This test is performed using gafchromic film, an extensive and user-dependent method requiring the use of disposables. We therefore analyzed the usability and accuracy of high-resolution detector arrays. We analyzed a liquid-filled ionization-chamber array (Octavius 1000SRS, PTW, Germany), which has a central resolution of 2.5mm. To test sufficient sensitivity, beam profiles with robot shifts of 0.1mm along the arrays' axes were measured. The detected deviation between the shifted and central profile were compared to the real robot's position. We then compared the results to the SRS-Profiler (SunNuclear, USA) with 4.0mm resolution and to the Nonius (QUART, Germany), a single-line diode detector with 2.8mm resolution. Finally, AQA variance and usability were analyzed performing a number of AQA tests over time, which required the use of specially designed fixtures for each array, and the results were compared to film. Concerning sensitivity, the 1000SRS detected the beam profile shifts with a maximum difference of 0.11mm (mean deviation = 0.03mm) compared to the actual robot shift. The Nonius and SRS-Profiler showed differences of up to 0.15mm and 0.69mm with mean deviation of 0.05mm and 0.18mm, respectively. Analyzing the variation of AQA results over time, the 1000SRS showed a comparable standard deviation to film (0.26mm vs. 0.18mm). The SRS-Profiler and the Nonius showed a standard deviation of 0.16mm and 0.24mm, respectively. The 1000SRS seems to provide equivalent accuracy and sensitivity to the gold standard film when performing daily AQA tests. Compared to other detectors in our study the sensitivity as well as the accuracy of the 1000SRS appears to be superior and more user-friendly. Furthermore, no significant modification of the standard AQA procedure is required when introducing 1000SRS for CyberKnife AQA

High resolution ion chamber array delivery quality assurance for robotic radiosurgery: commissioning and validation

AbstractPurposeHigh precision radiosurgery demands comprehensive delivery-quality-assurance techniques. The use of a liquid-filled ion-chamber-array for robotic-radiosurgery delivery-quality-assurance was investigated and validated using several test scenarios and routine patient plans.Methods and materialPreliminary evaluation consisted of beam profile validation and analysis of source–detector-distance and beam-incidence-angle response dependence. The delivery-quality-assurance analysis is performed in four steps: (1) Array-to-plan registration, (2) Evaluation with standard Gamma-Index criteria (local-dose-difference⩽2%, distance-to-agreement⩽2mm, pass-rate⩾90%), (3) Dose profile alignment and dose distribution shift until maximum pass-rate is found, and (4) Final evaluation with 1mm distance-to-agreement criterion. Test scenarios consisted of intended phantom misalignments, dose miscalibrations, and undelivered Monitor Units. Preliminary method validation was performed on 55 clinical plans in five institutions.ResultsThe 1000SRS profile measurements showed sufficient agreement compared with a microDiamond detector for all collimator sizes. The relative response changes can be up to 2.2% per 10cm source–detector-distance change, but remains within 1% for the clinically relevant source–detector-distance range. Planned and measured dose under different beam-incidence-angles showed deviations below 1% for angles between 0° and 80°. Small-intended errors were detected by 1mm distance-to-agreement criterion while 2mm criteria failed to reveal some of these deviations. All analyzed delivery-quality-assurance clinical patient plans were within our tight tolerance criteria.ConclusionWe demonstrated that a high-resolution liquid-filled ion-chamber-array can be suitable for robotic radiosurgery delivery-quality-assurance and that small errors can be detected with tight distance-to-agreement criterion. Further improvement may come from beam specific correction for incidence angle and source–detector-distance response

Usability and accuracy of high-resolution detectors for daily quality assurance for robotic radiosurgery

For daily CyberKnife QA a Winston-Lutz-Test (Automated-Quality-Assurance, AQA) is used to determine sub-millimeter deviations in beam delivery accuracy. This test is performed using gafchromic film, an extensive and user-dependent method requiring the use of disposables. We therefore analyzed the usability and accuracy of high-resolution detector arrays. We analyzed a liquid-filled ionization-chamber array (Octavius 1000SRS, PTW, Germany), which has a central resolution of 2.5mm. To test sufficient sensitivity, beam profiles with robot shifts of 0.1mm along the arrays' axes were measured. The detected deviation between the shifted and central profile were compared to the real robot's position. We then compared the results to the SRS-Profiler (SunNuclear, USA) with 4.0mm resolution and to the Nonius (QUART, Germany), a single-line diode detector with 2.8mm resolution. Finally, AQA variance and usability were analyzed performing a number of AQA tests over time, which required the use of specially designed fixtures for each array, and the results were compared to film. Concerning sensitivity, the 1000SRS detected the beam profile shifts with a maximum difference of 0.11mm (mean deviation = 0.03mm) compared to the actual robot shift. The Nonius and SRS-Profiler showed differences of up to 0.15mm and 0.69mm with mean deviation of 0.05mm and 0.18mm, respectively. Analyzing the variation of AQA results over time, the 1000SRS showed a comparable standard deviation to film (0.26mm vs. 0.18mm). The SRS-Profiler and the Nonius showed a standard deviation of 0.16mm and 0.24mm, respectively. The 1000SRS seems to provide equivalent accuracy and sensitivity to the gold standard film when performing daily AQA tests. Compared to other detectors in our study the sensitivity as well as the accuracy of the 1000SRS appears to be superior and more user-friendly. Furthermore, no significant modification of the standard AQA procedure is required when introducing 1000SRS for CyberKnife AQA

A modified Camel and Cactus Test detects presymptomatic semantic impairment in genetic frontotemporal dementia within the GENFI cohort

Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = -0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field