Avelumab first-line maintenance in advanced urothelial carcinoma: Complete screening for prognostic and predictive factors using machine learning in the JAVELIN Bladder 100 phase 3 trial.

BACKGROUND: Avelumab first-line (1 L) maintenance is a standard of care for advanced urothelial carcinoma (aUC) based on the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab 1 L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients who were progression free after receiving 1 L platinum-containing chemotherapy. Here, we comprehensively screened JAVELIN Bladder 100 trial datasets to identify prognostic factors that define subpopulations of patients with longer or shorter OS irrespective of treatment, and predictive factors that select patients who could obtain a greater OS benefit from avelumab 1 L maintenance treatment. METHODS: We performed machine learning analyses to screen a large set of baseline covariates, including patient demographics, disease characteristics, laboratory values, molecular biomarkers, and patient-reported outcomes. Covariates were identified from previously reported analyses and established prognostic and predictive markers. Variables selected from random survival forest models were processed further in univariate Cox models with treatment interaction and visually inspected using correlation analysis and Kaplan-Meier curves. Results were summarized in a multivariable Cox model. RESULTS: Prognostic baseline covariates associated with OS included in the final model were assignment to avelumab 1 L maintenance treatment, Eastern Cooperative Oncology Group performance status, site of metastasis, sum of longest target lesion diameters, levels of C-reactive protein and alkaline phosphatase in blood, lymphocyte proportion in intratumoral stroma, tumor mutational burden, and tumor CD8+ T-cell infiltration. Potential predictive factors included site of metastasis, tumor mutation burden, and tumor CD8+ T-cell infiltration. An analysis in patients with PD-L1+ tumors had similar findings to those in the overall population. CONCLUSIONS: Machine learning analyses of data from the JAVELIN Bladder 100 trial identified potential prognostic and predictive factors for avelumab 1 L maintenance treatment in patients with aUC, which warrant further evaluation in other clinical datasets.

Privacy Attitudes toward Mouse-Tracking Paradata Collection.

Survey participants' mouse movements provide a rich, unobtrusive source of paradata, offering insight into the response process beyond the observed answers. However, the use of mouse tracking may require participants' explicit consent for their movements to be recorded and analyzed. Thus, the question arises of how its presence affects the willingness of participants to take part in a survey at all-if prospective respondents are reluctant to complete a survey if additional measures are recorded, collecting paradata may do more harm than good. Previous research has found that other paradata collection modes reduce the willingness to participate, and that this decrease may be influenced by the specific motivation provided to participants for collecting the data. However, the effects of mouse movement collection on survey consent and participation have not been addressed so far. In a vignette experiment, we show that reported willingness to participate in a survey decreased when mouse tracking was part of the overall consent. However, a larger proportion of the sample indicated willingness to both take part and provide mouse-tracking data when these decisions were combined, compared to an independent opt-in to paradata collection, separated from the decision to complete the study. This suggests that survey practitioners may face a trade-off between maximizing their overall participation rate and maximizing the number of participants who also provide mouse-tracking data. Explaining motivations for paradata collection did not have a positive effect and, in some cases, even reduced participants' reported willingness to take part in the survey.

Revisiting the Open Sampling format: Improving risky choices through a novel graphical representation.

When making risky choices, people often fall short of the norm of expected value (EV) maximization. Previous research has shown that presenting options in the Open Sampling (OSa) format, a 10-by-10 matrix of randomly arranged outcomes, can improve choices and reduce decision times. First, the current research aims to replicate and extend the findings on the OSa format. To this end, we compare OSa to the common description-based format as well as further graphical representations, and investigate the resulting accordance with EV maximization and decision time. Second, we study whether people lower (vs. higher) in numeracy, the ability to use probabilistic and mathematical concepts, particularly benefit from a graphical representation of options. We conducted five high-powered studies (total N = 1,575) in which participants chose repeatedly between two risky gambles, using different populations and gamble-problem sets. Overall, we could not find a benefit of the OSa format in terms of EV accordance in any of the five studies. However, three studies also tested a novel variant of the OSa format with grouped outcomes and found that it consistently improved EV accordance compared with all other formats. All graphical formats led to faster decisions without harming decision quality. The effects of presentation format were not moderated by numeracy in three of the four studies that assessed numeracy. In conclusion, our research introduces a new presentation format which consistently improves risky choices and can also be used to communicate risks in applied contexts such as medical decision making.

lab.js: A free, open, online study builder.

Web-based data collection is increasingly popular in both experimental and survey-based research because it is flexible, efficient, and location-independent. While dedicated software for laboratory-based experimentation and online surveys is commonplace, researchers looking to implement experiments in the browser have, heretofore, often had to manually construct their studies' content and logic using code. We introduce lab.js, a free, open-source experiment builder that makes it easy to build studies for both online and in-laboratory data collection. Through its visual interface, stimuli can be designed and combined into a study without programming, though studies' appearance and behavior can be fully customized using HTML, CSS, and JavaScript code if required. Presentation and response times are kept and measured with high accuracy and precision heretofore unmatched in browser-based studies. Experiments constructed with lab.js can be run directly on a local computer and published online with ease, with direct deployment to cloud hosting, export to web servers, and integration with popular data collection platforms. Studies can also be shared in an editable format, archived, re-used and adapted, enabling effortless, transparent replications, and thus facilitating open, cumulative science. The software is provided free of charge under an open-source license; further information, code, and extensive documentation are available from https://lab.js.org/ .

Mouse-tracking reveals cognitive conflict during negative impression formation in women with Borderline Personality Disorder or Social Anxiety Disorder.

Individuals with Borderline Personality Disorder (BPD) or Social Anxiety Disorder (SAD) suffer from substantial interpersonal dysfunction and have difficulties establishing social bonds. A tendency to form negative first impressions of others could contribute to this by way of reducing approach behavior. We tested whether women with BPD or SAD would show negative impression formation compared to healthy women (HCs). We employed the Thin Slices paradigm and showed videos of 52 authentic target participants to 32 women with BPD, 29 women with SAD, and 37 HCs. We asked participants to evaluate whether different positive or negative adjectives described targets and expected BPD raters to provide the most negative ratings, followed by SAD and HC. BPD and SAD raters both agreed with negative adjectives more often than HCs (e.g., 'Yes, the person is greedy'), and BPD raters rejected positive adjectives more often (e.g., 'No, the person is not humble.'). However, BPD and SAD raters did not differ significantly from each other. Additionally, we used the novel process tracing method mouse-tracking to assess the cognitive conflict (via trajectory deviations) raters experienced during decision-making. We hypothesized that HCs would experience more conflict when making unfavorable (versus favorable) evaluations and that this pattern would flip in BPD and SAD. We quantified cognitive conflict via maximum absolute deviations (MADs) of the mouse-trajectories. As hypothesized, HCs showed more conflict when rejecting versus agreeing with positive adjectives. The pattern did not flip in BPD and SAD but was substantially reduced, such that BPD and SAD showed similar levels of conflict when rejecting and agreeing with positive adjectives. Contrary to the hypothesis for BPD and SAD, all three groups experienced substantial conflict when agreeing with negative adjectives. We discuss therapeutic implications of the combined choice and mouse-tracking results.

Negativity on two sides: Individuals with borderline personality disorder form negative first impressions of others and are perceived negatively by them.

Impression formation is vital for social interactions and theorized to be negatively biased in borderline personality disorder (BPD). We assessed 2 sides of impression formation in BPD: BPD individuals as raters who form first impressions and as targets of others' first impressions. We further investigated BPD-Rater × Target interactions. We showed videos of 52 targets (26 BPD, 26 healthy controls [HC], 46% male) to unmedicated women with BPD (n = 32), a clinical control group with social anxiety disorder (SAD; n = 29), and a HC group (n = 37). We hypothesized (a) that BPD raters would evaluate targets more negatively than SAD and HC raters. Indeed, BPD raters evaluated targets as significantly less trustworthy, less approachable, and less similar to themselves than HC raters. Descriptively, rater groups showed a pattern of BPD < SAD < HC, but the differences between SAD and both other rater groups failed to reach statistical significance. We further expected (b) HC raters to evaluate BPD targets more negatively than HC targets, and results supported this hypothesis. Lastly, we hypothesized (c) that BPD raters would perceive BPD targets more positively than HC targets, which was not supported. We discuss how negative first impressions by and of BPD individuals could contribute to loneliness and interpersonal dysfunction and suggest potential interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Design factors in mouse-tracking: What makes a difference?

Investigating cognitive processes by analyzing mouse movements has become a popular method in many psychological disciplines. When creating mouse-tracking experiments, researchers face many design choices-for example, whether participants indicate responses by clicking a button or just by entering the button area. Hitherto, numerous different settings have been employed, but little is known about how these methodological differences affect mouse-tracking data. We systematically investigated the influences of three central design factors, using a classic mouse-tracking paradigm in which participants classified typical and atypical exemplars. In separate experiments, we manipulated the response indication, mouse sensitivity, and starting procedure. The core finding that mouse movements deviate more toward the nonchosen option for atypical exemplars was replicated in all conditions. However, the size of this effect varied. Specifically, it was larger when participants indicated responses via click and when they were instructed to initialize the movement early. Trajectory shapes also differed between setups. For example, a dynamic start led to mostly curved trajectories, responses via click led to a mix of straight and "change-of-mind" trajectories, and responses via touch led to mostly straight trajectories. Moreover, the distribution of curvature indices was classified as bimodal in some setups and as unimodal in others. Because trajectory curvature and shape are frequently used to make inferences about psychological theories, such as differentiating between dynamic and dual-system models, this study shows that the specific design must be carefully considered when drawing theoretical inferences. All methodological designs and analyses were implemented using open-source software and are available from https://osf.io/xdp7a/.

Correction to: Validating mouse-tracking: How design factors influence action dynamics in intertemporal decision making.

The following reference was omitted from this article.

Lost to translation: How design factors of the mouse-tracking procedure impact the inference from action to cognition.

From an embodiment perspective, action and cognition influence each other constantly. This interaction has been utilized in mouse-tracking studies to infer cognitive states from movements, assuming a continuous manifestation of cognitive processing into movement. However, it is mostly unknown how this manifestation is affected by the variety of possible design choices in mouse-tracking paradigms. Here we studied how three design factors impact the manifestation of cognition into movement in a Simon task with mouse tracking. We varied the response selection (i.e., with or without clicking), the ratio between hand and mouse cursor movement, and the location of the response boxes. The results show that all design factors can blur or even prevent the manifestation of cognition into movement, as reflected by a reduction in movement consistency and action dynamics, as well as by the adoption of unsuitable movement strategies. We conclude that deliberate and careful design choices in mouse-tracking experiments are crucial to ensuring a continuous manifestation of cognition in movement. We discuss the importance of developing a standard practice in the design of mouse-tracking experiments.

Low positive affect display mediates the association between borderline personality disorder and negative evaluations at zero acquaintance.

BACKGROUND: Several recent studies have demonstrated that naïve raters tend to evaluate individuals with Borderline Personality Disorder (BPD) negatively at zero-acquaintance (i.e., in a 'first impression' type situation, where the rater has no knowledge of the individual and no prior interactions with them). Specifically, individuals with BPD were evaluated as less trustworthy, likeable, and cooperative than healthy participants (HCs). Based on previous impression formation studies, we hypothesized that the non-verbal cues positive affect display, negative affect display, and eye contact contribute to negative first impressions of those with BPD. METHODS: To address this question, we recruited 101 participants that rated the degree of positive affect display, negative affect display, and eye contact in 52 videos of age-and gender-matched BPD and HC participants. We hypothesized that low positive affect display, high negative affect display, and eye contact would mediate the association between group (BPD vs. HC) and ratings of trustworthiness, likeability, and cooperativeness. RESULTS: Ratings for positive affect display were significantly lower and those for negative affect display significantly higher for BPD versus HC targets, whereas eye contact did not differ significantly between groups. In multiple mediation models, positive affect display significantly mediated the association between group and trustworthiness/likeability, whereas negative affect display only mediated the association between group and likeability. None of the individual cues was a significant mediator of the association between group and cooperation. CONCLUSIONS: We emphasize therapeutic possibilities to improve positive affect display -and thus overall first impressions- to increase the chances of forming social bonds for BPD individuals.

Validating mouse-tracking: How design factors influence action dynamics in intertemporal decision making.

Mouse-tracking is an increasingly popular process-tracing method. It builds on the assumption that the continuity of cognitive processing leaks into the continuity of mouse movements. Because this assumption is the prerequisite for meaningful reverse inference, it is an important question whether the assumed interaction between continuous processing and movement might be influenced by the methodological setup of the measurement. Here we studied the impacts of three commonly occurring methodological variations on the quality of mouse-tracking measures, and hence, on the reported cognitive effects. We used a mouse-tracking version of a classical intertemporal choice task that had previously been used to examine the dynamics of temporal discounting and the date-delay effect (Dshemuchadse, Scherbaum, & Goschke, 2013). The data from this previous study also served as a benchmark condition in our experimental design. Between studies, we varied the starting procedure. Within the new study, we varied the response procedure and the stimulus position. The starting procedure had the strongest influence on common mouse-tracking measures, and therefore on the cognitive effects. The effects of the response procedure and the stimulus position were weaker and less pronounced. The results suggest that the methodological setup crucially influences the interaction between continuous processing and mouse movement. We conclude that the methodological setup is of high importance for the validity of mouse-tracking as a process-tracing method. Finally, we discuss the need for standardized mouse-tracking setups, for which we provide recommendations, and present two promising lines of research toward obtaining an evidence-based gold standard of mouse-tracking.

Negative evaluation of individuals with borderline personality disorder at zero acquaintance.

Previous research suggests that individuals with Borderline Personality Disorder (BPD) tend to evaluate other people as untrustworthy or hostile, which could contribute to the marked interpersonal problems in BPD. In contrast, alterations in first impressions of potential interaction partners of those with BPD remain under-researched and poorly understood. Herein, we focused on how naïve raters evaluate BPD individuals, hypothesizing that raters would tend to evaluate them negatively. To test this hypothesis, we recruited 26 BPD and 26 healthy control participants (46% male) as targets in the 'Thin Slices' paradigm. Targets were video-taped while talking about their personal preferences (e.g. hobbies). Subsequently, these short videos ('Thin Slices') were presented to two rater samples (n = 92 and n = 44), who evaluated targets' likeability, trustworthiness, and cooperative behavior in an economic game. In both studies, raters evaluated BPD targets as less likeable and trustworthy, and in one study also as less cooperative. These findings are contrasted with results from an economic game, in which BPD targets behaved no less cooperatively than controls. We discuss limitations with regard to socioeconomic differences between the target groups and explore how negative evaluations by others may contribute to the interpersonal difficulties in BPD. We suggest that - given future replication with more strictly matched target groups- interventions aimed at improving impression management could be beneficial for BPD patients.

Generalized Processing Tree Models: Jointly Modeling Discrete and Continuous Variables.

Multinomial processing tree models assume that discrete cognitive states determine observed response frequencies. Generalized processing tree (GPT) models extend this conceptual framework to continuous variables such as response times, process-tracing measures, or neurophysiological variables. GPT models assume finite-mixture distributions, with weights determined by a processing tree structure, and continuous components modeled by parameterized distributions such as Gaussians with separate or shared parameters across states. We discuss identifiability, parameter estimation, model testing, a modeling syntax, and the improved precision of GPT estimates. Finally, a GPT version of the feature comparison model of semantic categorization is applied to computer-mouse trajectories.

Is action execution part of the decision-making process? An investigation of the embodied choice hypothesis.

In this study, we aimed to explore whether action execution is an inherent part of the decision-making process. According to the hypothesis of embodied choice, the decision-making process is bidirectional as action dynamics exert their backward influence on decision processes through changing the cost and value of the potential options. This influence takes place as moving toward one option increases the commitment to and, therefore, the likelihood of choosing that option. This commitment effect can be the result of either (a) the continuous act of getting closer to this option or (b) the increased movement cost associated with changing the movement direction to select a different option. To disentangle the potential influence of these two factors, we developed the Guided Movement Task, a choice task designed to bias participant's computer-mouse movements by constraining the allowed movement space by a corridor. Using this task, we created different conditions in which the participants' mouse cursor, after being guided toward one of the options, either had equal or unequal distances to the choice options. By this manipulation, we could test whether the continuous act of getting closer to an option in itself is sufficient to influence people's decisions-a claim of "strong embodiment." In two experiments, we found that the likelihood of choosing an option only increased when the distances between the two options were unequal after the initial movement but not when they were equal. These results disagree with the hypothesis that action execution is an inherent part of the decision-making process. (PsycINFO Database Record

Stuck at the starting line: How the starting procedure influences mouse-tracking data.

Mouse-tracking is an increasingly popular method to trace cognitive processes. As is common for a novel method, the exact methodological procedures employed in an individual study are still relatively idiosyncratic and the effects of different methodological setups on mouse-tracking measures have not been explored so far. Here, we study the impact of one commonly occurring methodological variation, namely whether participants have to initiate their mouse movements to trigger stimulus presentation (dynamic starting condition) or whether the stimulus is presented automatically after a fixed delay and participants can freely decide when to initiate their movements (static starting condition). We compared data from a previous study in which participants performed a mouse-tracking version of a Simon task with a dynamic starting condition to data from a new study that employed a static starting condition in an otherwise identical setup. Results showed reliable Simon effects and Congruency Sequence effects on response time (RT) and discrete trial-level mouse-tracking measures (i.e., average deviation) in both starting conditions. In contrast, within-trial continuous measures (i.e., extracted temporal segments) were weaker and occurred in a more temporally compressed way in the static compared to the dynamic starting condition. This was in line with generally less consistent movements within and across participants in the static compared to the dynamic condition. Our results suggest that studies that use within-trial continuous measures to assess dynamic aspects of mouse movements should apply dynamic starting procedures to enhance the leakage of cognitive processing into the mouse movements.

Mousetrap: An integrated, open-source mouse-tracking package.

Mouse-tracking - the analysis of mouse movements in computerized experiments - is becoming increasingly popular in the cognitive sciences. Mouse movements are taken as an indicator of commitment to or conflict between choice options during the decision process. Using mouse-tracking, researchers have gained insight into the temporal development of cognitive processes across a growing number of psychological domains. In the current article, we present software that offers easy and convenient means of recording and analyzing mouse movements in computerized laboratory experiments. In particular, we introduce and demonstrate the mousetrap plugin that adds mouse-tracking to OpenSesame, a popular general-purpose graphical experiment builder. By integrating with this existing experimental software, mousetrap allows for the creation of mouse-tracking studies through a graphical interface, without requiring programming skills. Thus, researchers can benefit from the core features of a validated software package and the many extensions available for it (e.g., the integration with auxiliary hardware such as eye-tracking, or the support of interactive experiments). In addition, the recorded data can be imported directly into the statistical programming language R using the mousetrap package, which greatly facilitates analysis. Mousetrap is cross-platform, open-source and available free of charge from https://github.com/pascalkieslich/mousetrap-os .

Tumor Infiltration in Enhancing and Non-Enhancing Parts of Glioblastoma: A Correlation with Histopathology.

PURPOSE: To correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1). MATERIALS AND METHODS: In 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as "viable tumor cells", "blood" or "necrotic tissue (with or without cellular component)". Cell counting was done semi-automatically. RESULTS: NE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as "viable tumor tissue" decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2). DISCUSSION: The appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.

No Signal Intensity Increase in the Dentate Nucleus on Unenhanced T1-weighted MR Images after More than 20 Serial Injections of Macrocyclic Gadolinium-based Contrast Agents.

Purpose To determine the effect of more than 20 serial injections of macrocyclic gadolinium-based contrast agents (GBCAs) on the signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance (MR) images. Materials and Methods In this retrospective, institutional review board-approved study, 33 patients who underwent at least 20 consecutive MR imaging examinations (plus an additional MR imaging for reference) with the exclusive use of macrocyclic GBCAs gadoterate meglumine and gadobutrol were analyzed. SI ratio differences were calculated for DN-to-pons and DN-to-middle cerebellar peduncle (MCP) ratios by subtracting the SI ratio at the first MR imaging examination from the SI ratio at the last MR imaging examination. One-sample t tests were used to examine if the SI ratio differences differed from 0, and Bayes factors were calculated to quantify the strength of evidence for each test. Results Patients underwent a mean of 23.03 ± (standard deviation) 4.20 GBCA administrations (mean accumulated dose, 491.21 mL ± 87.04 of a 0.5 M GBCA solution) with an average of 12.09 weeks ± 2.16 between every administration. Both ratio differences did not differ significantly from 0 (DN-to-pons ratio: -0.0032 ± 0.0154, P = .248; DN-to-MCP ratio: -0.0011 ± 0.0093, P = .521), and one-sided Bayes factors provided substantial to strong evidence against an SI ratio increase (Bayes factor for DN-to-pons ratio = 0.09 and that for DN-to-MCP ratio = 0.12). Conclusion The study indicates that 20 or more serial injections of macrocyclic GBCAs administered with on average 3 months between each injection are not associated with an SI increase in the DN. © RSNA, 2016.

Psynteract: A flexible, cross-platform, open framework for interactive experiments.

We introduce a novel platform for interactive studies, that is, any form of study in which participants' experiences depend not only on their own responses, but also on those of other participants who complete the same study in parallel, for example a prisoner's dilemma or an ultimatum game. The software thus especially serves the rapidly growing field of strategic interaction research within psychology and behavioral economics. In contrast to all available software packages, our platform does not handle stimulus display and response collection itself. Instead, we provide a mechanism to extend existing experimental software to incorporate interactive functionality. This approach allows us to draw upon the capabilities already available, such as accuracy of temporal measurement, integration with auxiliary hardware such as eye-trackers or (neuro-)physiological apparatus, and recent advances in experimental software, for example capturing response dynamics through mouse-tracking. Through integration with OpenSesame, an open-source graphical experiment builder, studies can be assembled via a drag-and-drop interface requiring little or no further programming skills. In addition, by using the same communication mechanism across software packages, we also enable interoperability between systems. Our source code, which provides support for all major operating systems and several popular experimental packages, can be freely used and distributed under an open source license. The communication protocols underlying its functionality are also well documented and easily adapted to further platforms. Code and documentation are available at https://github.com/psynteract/ .

Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PURPOSE: Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine. MATERIALS AND METHODS: Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods. RESULTS: The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: -0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: -0.0250 ± 0.0284, P = 0.011). CONCLUSIONS: In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.