E T Berthet
email: elsa.berthet@inrae.fr

A Camarda

E Salvia

B Ozkalp-Poincloux

M Cassotti

RIODD 2023: Change or Collapse? Multidisciplinary analyses, landmarks, and proposals in the face of the need for a rapid and profound change in our ways of producing, consuming, and exchanging

Keywords: Food system transformation, Consumers' transformative capacities, Fixation effect, Innovative design, Developmental psychology

Transforming our food systems to increase their sustainability requires involving all stakeholders, not to mention consumers, in the exploration of innovative solutions. As fixation effects are considered to be one of the main cognitive obstacles to creativity, this ongoing research aims to analyse how consumers' fixation effects on food transition evolve as a function of their age. By combining skills in cognitive psychology and design sciences, we have developed an ad hoc protocol to study fixation effects on food transition. Since 2022, we have been implementing it with more than 700 pupils from primary, middle and high school, as well as adults, in a rural area of western France. As analysis is ongoing, this paper mainly presents the research rationale, the methodology developed and applied as well as preliminary results. Knowledge of fixation effects according to consumers' age and profile will enable us to design tools and methods to stimulate consumers' creativity, and more broadly to increase their capacity to transform their food systems towards sustainability.

Résumé (en français):

Transformer nos systèmes alimentaires pour accroître leur durabilité nécessite d'impliquer toutes les parties prenantes, notamment les consommateurs, dans l'exploration de solutions innovantes. Les effets de fixation étant considérés comme l'un des principaux obstacles cognitifs à la créativité, notre recherche, en cours, vise à analyser l'évolution des effets de fixation des consommateurs sur la transition alimentaire en fonction de leur âge. En combinant des compétences en psychologie cognitive et en sciences du design, nous avons développé un protocole ad hoc. Depuis 2022, nous l'avons déjà mis en oeuvre auprès de plus de 700 élèves de primaire, collège et lycée, ainsi que des adultes, dans une zone rurale de l'ouest de la France. Etant donné que les analyses sont en cours, cet article présente essentiellement la problématique, la méthodologie de recherche, ainsi que des résultats préliminaires. La connaissance que nous aurons de ces effets de fixation nous permettra de concevoir des outils et des méthodes pour stimuler la créativité des consommateurs et, plus largement, augmenter leur capacité à transformer leurs systèmes alimentaires.

Introduction

Involving consumers in food system transformation, a need to bridge parallel literatures

The current and future complex large-scale challenges related to biodiversity collapse, pandemic outbreaks and climate change threaten the sustainability of our societies. Our agricultural and food systems (hereafter food systems) both suffer from, and contribute to, these challenges. Indeed, agriculture is a major contributor to greenhouse gas emissions, while threats posed by climate change directly and indirectly disrupt the production, processing, transport and marketing of food [START_REF] Ericksen | Vulnerability and resilience of food systems. Food security and global environmental change[END_REF]. The COVID-19 pandemic and the current war in Ukraine particularly enlighten the fragility of our food systems [START_REF] Béné | Resilience of local food systems and links to food security-A review of some important concepts in the context of COVID-19 and other shocks[END_REF]. The challenges linking agriculture and food value chains to diets, health and planetary ecosystems can no longer be ignored; the need for fundamental transformation of food systems towards increased resilience is now irrefutable (O 'Brien, 2012[START_REF] Webb | The urgency of food system transformation is now irrefutable[END_REF]. Given the current and future complex large-scale challenges related to climate change and biodiversity collapse, incremental changes are now inadequate [START_REF] Nalau | When is transformation a viable policy alternative[END_REF], and calls are made for societies to implement transformative approaches in order to manage complex problems in a more sustainable way (O 'Brien, 2012[START_REF] Olsson | The concept of the Anthropocene as a game-changer: a new context for social innovation and transformations to sustainability[END_REF][START_REF] Chapin | Earth stewardship: a strategy for social-ecological transformation to reverse planetary degradation[END_REF]). Yet, how to implement such a systemic transformation, and what are the capacities required for this, remain open questions.

This research draws on the notion of transformative capacities, defined in the literature on socioecosystem (SES) resilience as the ability of individuals or organizations to transform a socio-ecosystem, i.e. to fundamentally and definitively change certain elements or aspects of this system [START_REF] Olsson | Building transformative capacity for ecosystem stewardship in social-ecological systems[END_REF][START_REF] Westley | Tipping toward sustainability: emerging pathways of transformation[END_REF]. Yet the distinction between the capacities that allow for adaptation and the capacities that allow for transformation is still not well understood. Based on theoretical understandings of SES transformation, [START_REF] Moore | Navigating emergence and system reflexivity as key transformative capacities[END_REF] deemed two capacities critical for systemic transformation:

(1) the ability to navigate emergence, i.e. to get prepared to uncertainty and surprises, and (2) enhanced system reflexivity, which they link to institutional reflexivity [START_REF] Suddaby | Reflexivity: The role of embedded social position and entrepreneurial social skill in processes of field level change[END_REF], that is, the capacity to see, interrogate, and reimagine the taken-for-granted structures that sustain current systems and peopleplanet relationships. Hence, developing people's transformative capacities involves combining different types of abilities, such as those of innovation, anticipation, adaptation to change and reflexivity [START_REF] Moore | Navigating emergence and system reflexivity as key transformative capacities[END_REF]. Research on food system transformation has traditionally targeted producers, be they farmers, extension services, policy actors and supply chain intermediaries such as agri-food industries, as they are leading contributors to the food system's significant ecological footprint. Nevertheless, the role of consumers has also begun to receive increasing attention from policy makers, practitioners, and academics [START_REF] Ringer | The impact of sustainability information on consumer decision making[END_REF][START_REF] Hatanaka | Beyond consuming ethically? Food citizens, governance, and sustainability[END_REF][START_REF] Tukker | Environmental impacts of products: A detailed review of studies[END_REF], Renting et al., 2012[START_REF] Lamine | Agri-food systems and territorial development: innovations, new dynamics and changing governance mechanisms[END_REF]. Indeed, as underlined by the FAO (2018), "consumers around the world can be a powerful force for change towards more sustainable and equitable food systems". Various concepts have been developed to underline the role of consumers in shaping sustainable production and food systems, such as ethical consumerism, reflexive consumption, prosumption and political consumerism. These concepts advance the idea of "citizen-consumers" who exercise citizenship in the marketplace [START_REF] Hatanaka | Beyond consuming ethically? Food citizens, governance, and sustainability[END_REF], Renting et al., 2012). The underlying assumption is that if consumers make conscientious food choices in the marketplace, this will result in market demands for more sustainable production practices, and ultimately generate change at both producers and potentially all supply-chain levels.

This literature essentially considers consumers as individuals able to choose between existing alternatives proposed by food system producers. Focusing on consumer sovereignty, which can be enhanced by information, choice and alternative retailers, is a dominant perspective in consumer sciences as well as for government, industry and most consumers' organizations [START_REF] Shaw | Consumption as voting: an exploration of consumer empowerment[END_REF][START_REF] Mcgregor | Sustainable consumer empowerment through critical consumer education: a typology of consumer education approaches[END_REF]. This perspective has led to a growth in labels and accompanying communication initiatives such as public service announcements and education campaigns [START_REF] Ringer | The impact of sustainability information on consumer decision making[END_REF]Ringer, 2016, Grunert et al., 2014). Yet, various scholars underline that such information is not sufficient to change food practices: first, concerns include consumer reliance on other actors to guide their decision-making as well as the individualized character of their agency [START_REF] Vermeir | Sustainable food consumption: Exploring the consumer "attitudebehavioral intention" gap[END_REF]. Second, there remains a gap between this type of information provided to the consumers and their understanding of sustainability issues [START_REF] Grunert | Sustainability labels on food products: Consumer motivation, understanding and use[END_REF]. Third, surveys have shown that although 30% to 70% of consumers say they want to buy greener, healthier and more socially responsible products, only 1% to 5% actually do [START_REF] Eckhardt | Why don't consumers consume ethically[END_REF]. The contributing factors that intervene between sustainability preferences and purchasing decision, beyond potential economic constraints, include scepticism about corporate claims regarding product and supplychain sustainability as well as doubt about the impact that an individual consumer can make [START_REF] Ringer | The impact of sustainability information on consumer decision making[END_REF].

Scholars are increasingly calling for forms of engagement by consumers that go beyond "voting with dollars" [START_REF] Hatanaka | Beyond consuming ethically? Food citizens, governance, and sustainability[END_REF]. To that end, there is a need to develop a critically and analytically aware attitude to consumption and to one's action as a consumer in society, also named critical consumer empowerment [START_REF] Mcgregor | Sustainable consumer empowerment through critical consumer education: a typology of consumer education approaches[END_REF]. Giving someone information is helping create the ability to do something, but this is not empowerment. To be empowered entails holding the perception that one has the authority to take action, which make people value their potential and their capacity for self-growth, learning, and taking action [START_REF] Mcgregor | Sustainable consumer empowerment through critical consumer education: a typology of consumer education approaches[END_REF][START_REF] Ziervogel | Moving from adaptive to transformative capacity: Building foundations for inclusive, thriving, and regenerative urban settlements[END_REF]. Further, critical food literacy reflects the dynamic interplay between people and their environment, suggesting that effective engagement with food issues may empower individuals not only to improve their own diets, but also contribute to broader changes in the food system. Empowerment may increase citizens' participation, exploration of solution and decision-making towards transformative action, thus contributing to a more democratic and sustainable food system [START_REF] Bornemann | Empowering people-Democratising the food system? Exploring the democratic potential of food-related empowerment forms[END_REF]. The literature in critical empowerment thus underlines the specificity of the knowledge and skills that consumers need to acquire if they wish to transform their food system. Yet, what such knowledge and skills encompass is still unclear.

Fostering innovative design capacities, a neglected stake of food system transformation To date, while the literatures on transformation capacities and on critical consumer empowerment tackle similar issues, and both underline that the knowledge and skills required to commit stakeholders (e.g., consumers) and enable them to transform their food system remain to be characterized and developed, they remain separated. According to [START_REF] Ziervogel | Moving from adaptive to transformative capacity: Building foundations for inclusive, thriving, and regenerative urban settlements[END_REF] transformative capacity "includes the capacity to imagine, enact, and sustain a transformed world and a way of life that is in balance with the carrying capacity of our Earth". Yet, consumers are rarely considered as food system innovation designers, but rather as innovation end-users. In this line, both literatures put emphasis on the stakes of innovation adoption and dissemination, and mostly neglect the capacities required to generate innovative solutions. However, whether it is a matter of transforming one's food practices or renewing the organisations, institutions and governance of a food system, solutions to develop are not straightforward. Creativity and innovation capacities are needed. There is a need to understand how individuals and collectives may increase their creativity to tackle food and ecological transitions. Innovation processes require both cognitive and organisational specific skills for innovative design, which are studied by both design sciences and cognitive psychology [START_REF] Le Masson | Strategic management of innovation and design[END_REF].

In this research, we aim to study the capacity of consumers to design and implement innovative solutions, either individually or collectively, to change their food practices in the aim of contributing to transform their food system. To that end, we seek to identify the obstacles to consumers' innovative design capacities. Drawing on developmental psychology and design sciences, we focus on cognitive bias called fixation effect (Smith et al., 1995). Fixation effects result from our automaticity in using easily accessible knowledge leads to, which constrain the exploration of solutions to a small number of category of solutions. According to the triadic model of creativity, individuals tend to follow the "path of least resistance" when they have to solve a problem creatively, which strongly constrains the exploration of paths leading to more original solutions [START_REF] Cassotti | Inhibitory control as a core process of creative problem solving and idea generation from childhood to adulthood[END_REF]. Thus, the first ideas that spontaneously come to mind would lead individuals to focus on a limited number of alternatives, while other, more creative solutions would be accessible by mobilizing other, more generative types of reasoning. Recent studies [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF][START_REF] Cassotti | Inhibitory control as a core process of creative problem solving and idea generation from childhood to adulthood[END_REF][START_REF] Camarda | Do we need inhibitory control to be creative? Evidence from a dual-task paradigm[END_REF] argue that the ability to resist the spontaneous activation of design heuristics and privilege other types of reasoning, is critical to support creativity. These studies suggest that the ability to think of something truly new and original requires inhibiting (i.e., block the activation of) spontaneous solutions that come to mind quickly and unconsciously [START_REF] Cassotti | Inhibitory control as a core process of creative problem solving and idea generation from childhood to adulthood[END_REF] as well as a capacity to explore new paths of solutions. Studies in developmental psychology also highlight that the nature of fixation effects during the generation of creative ideas changes with age, education, and expertise [START_REF] Cassotti | Inhibitory control as a core process of creative problem solving and idea generation from childhood to adulthood[END_REF][START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF]. Children, adolescents and adults can have strong differences in their learning abilities, and more specifically in terms of fixation effects, due to different cognitive specificities and developmental trajectories [START_REF] Casey | Imaging the developing brain: what have we learned about cognitive development[END_REF][START_REF] Kleibeuker | Creativity development in adolescence: Insight from behavior, brain, and training studies[END_REF]. For example, inhibition control function develops until late adolescence, and this explains an important part of the difficulty adolescents encounter in generating creative ideas when compared to adults [START_REF] Kleibeuker | Creativity development in adolescence: Insight from behavior, brain, and training studies[END_REF].

To identify individuals' fixation effect, scholars combined tools and methods from cognitive psychology and design sciences: they applied the CK (Concept-Knowledge) design theory (Hatchuel and[START_REF] Hatchuel | A new approach of innovative design: an introduction to C-K theory[END_REF][START_REF] Hatchuel | CK design theory: an advanced formulation[END_REF] formalism to map ideas. The C-K formalism allows to distinguish exploration paths that are based on the spontaneous activation of knowledge (i.e., fixation effects) from exploration paths that rely on the activation of less accessible knowledge (outside fixation effects) [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF].

Once fixation effects are identified, further research has demonstrated that it was possible to develop levers to overcome them and stimulate creativity according to one's personal fixation [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF][START_REF] Ezzat | How minimal executive feedback influences creative idea generation[END_REF]. In fact, these studies have demonstrated that a well-chosen example of solution (i.e., example outside of the path of fixation) can stimulate participants' creativity regardless their age [START_REF] Cassotti | Inhibitory control as a core process of creative problem solving and idea generation from childhood to adulthood[END_REF]. They have also shown that different strategies used by experts can enhance the exploration of creative path of solutions. Thus, using the example as information that "must not be followed" can be a source of stimulation for expansive ideas [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF]. Furthermore, the minimal feedback from an expert that would allow individuals to become aware of their fixation effects would push them to explore new ways of solutions [START_REF] Ezzat | How minimal executive feedback influences creative idea generation[END_REF]. This literature suggests that there exist levers to enhance individuals' creative capacities, hereby enhancing their innovative design capacities and potentially their transformative capacities.

Fixation effects are considered to be one of the main cognitive obstacles to creativity, as they constrain the exploration of ideas to a limited field depending on one's knowledge. The idea we're defending is that if we want to increase consumers' capacity to propose innovative solutions to change their own food consumption practices, and more broadly to upscale food transition, it is useful to identify their fixation effects in this area. The fixation effects on issues related to ecological transition, and more specifically food transition, are to date unknown. To identify them, we mobilize the formalism of C-K theory [START_REF] Hatchuel | CK design theory: an advanced formulation[END_REF], which categorizes ideas in the form of a tree structure and represents the links between knowledge and ideas. In contrast with most consumer studies that target adult consumers, our research is focused on consumers from children to adults, encompassing teenagers, even if they do not necessarily buy their own food. The (non-exclusive) focus on young consumers has several motivations: younger generations are now particularly concerned with eco-anxiety; children and young people have decision power, both directly as consumers and citizens themselves, as future buyers, and indirectly as they influence parents' choices and consumption [START_REF] Benn | Consumer education between 'consumership'and citizenship: experiences from studies of young people[END_REF]. Our research questions are as follows: How do consumers' fixation effects, on the issue of food transition toward sustainability, evolve as a function of their age? Subsequently, how does the ability to propose creative solutions to an ecological problem develops with age? This research offers an opportunity of examining creativity development from the angle of a concrete situation linked to ecology. We hypothesize that the ability to explore in ecological tasks depends on three elements: 1) the ability to explore ideas and to be generative; 2) access to knowledge bases and 3) a critical mind linked to knowledge about food and ecology. The research protocol presented below addresses these three hypotheses.

As the research is on-going, this paper is mainly methodological. We detail in the following part the protocol elaborated to answer this research question and the way we applied it in our study area since 2022. We then give some preliminary results and present some research perspectives.

Presentation of the study area

Our research is conducted in the south of Deux-Sèvres department, Nouvelle-Aquitaine Region, western France. In this rural area, agriculture is a dynamic sector employing 3.9% of the working population and agri-food industry accounts for one in four employees, working in animal husbandry (sheep, cattle and poultry), ready meals, butter and cheese production. Population density is 62 hab./km² (France average population density is 100 hab/km²). This cereal plain has known over the past decades a strong agricultural intensification and specialization, leading to an increasing use of pesticides and a simplification of the landscape due to the removal of hedges, the enlargement of crop fields, the simplification of crop rotations, and the reduction of mixed farming for the benefit of cereal farming. Agricultural intensification poses considerable environmental problems with regard to water quality, health or biodiversity. The food system of this territory has become more and more globalized, as agriculture relies on imported resources (fertilizers, pesticides, seeds, etc.) and about 60% of its production is exported abroad. Conflicts related to water resources are increasing due to chronic water shortage compounded by climate change and to developing projects of water reserves for agricultural use. Our research is more particularly conducted in a Long-Term Social-Ecological Research (LTSER) site, the "Zone Atelier Plaine & Val de Sèvre" (ZAPVS), managed by the CEBC [START_REF] Bretagnolle | Towards sustainable and multifunctional agriculture in farmland landscapes: lessons from the integrative approach of a French LTSER platform[END_REF][START_REF] Berthet | Place-based social-ecological research is crucial for designing collective management of ecosystem services[END_REF]. This research infrastructure is a large (ca. 435 km²) rural territory, covering 40 villages (c.24 municipalities) totalling 34,000 inhabitants (Fig. 1), and encompassing about 400 farms. It is surrounded by Niort (121,200 inhabitants), which is the main employment area, and Melle (3,607 inhabitants). Since 1994, the ZAPVS is an observatory dedicated to understand the SES dynamics in response to changes in agricultural management; it includes the monitoring of land cover, biodiversity, farming practices [START_REF] Bretagnolle | Towards sustainable and multifunctional agriculture in farmland landscapes: lessons from the integrative approach of a French LTSER platform[END_REF] and, since more recently, food consumption practices [START_REF] Berthet | Setting-up place-based and transdisciplinary research to foster agrifood system transformation: Insights from the Aliment'Actions project in western France[END_REF]. Transdisciplinary research programs have been carried out for more than ten years with farmers, cooperatives, NGOs, municipal councils and schools [START_REF] Berthet | Considering agro-ecosystems as ecological funds for collective design: New perspectives for environmental policy[END_REF][START_REF] Bretagnolle | Towards sustainable and multifunctional agriculture in farmland landscapes: lessons from the integrative approach of a French LTSER platform[END_REF][START_REF] Gaba | Social-ecological experiments to foster agroecological transition[END_REF][START_REF] Houte | L'émancipation des habitants pour une gouvernance adaptative de la biodiversité: étude d'un dispositif participatif[END_REF].

The ZAPVS and its adjacent cities Niort and Melle count 36 primary schools (6-10 year-old pupils), 13 middle schools (11-15 year-old pupils), 9 high schools (16-18 year-old pupils), among which 5 general high schools and 4 technical or professional high schools.

Research strategy

In this research project, we are conducting a diagnosis to understand the potential barriers to consumers' transformative capacities, in particular their fixation effects and knowledge gaps regarding food and ecological transition. As we assume that fixation effects and knowledge gaps are not going to be the same for different types of consumers -especially according to their age, we target different types of consumers: children, teenagers and adults.

Since 2022, we have visited 2 general high schools, 1 agricultural high school, 1 middle school and 7 primary schools (see Figure 1). In total, we have met more than 700 pupils and adults (see Table 1).

An ad-hoc protocol to assess fixation effects according to age

By combining skills in cognitive psychology and design sciences, our research team has developed an ad hoc protocol to study fixation effects on food transition. The methodology for such a diagnosis has been applied over the past ten years in various contexts [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF][START_REF] Cassotti | Inhibitory control as a core process of creative problem solving and idea generation from childhood to adulthood[END_REF]. It consists in four successive steps: (i) Formulating the creativity briefs. A creativity brief should have minimal properties, such as being intelligible by a large audience, and being open enough to allow for idea exploration and narrow enough to guide the respondents' exploration.

(ii) Building one "idea referential" per brief, i.e., an arborescence of ideas using the CK theory formalism. The CK formalism allows the researchers to pre-explore a wide range of ideas and organize these ideas that could be proposed by the respondents on an idea referential.

(iii) Conducting the creativity tasks. A creativity task consists in asking individuals to give the highest number of ideas to solve a problem formulated as a creativity brief. After the researchers enounce the creativity brief, the respondents have 10 minutes to write down their responses on a paper sheet. (iv) Using the "idea referential" to position the various responses proposed by the participants. For each creativity brief, we position the ideas proposed by the respondents on the various branches of the idea (CK) referential, and count the number of ideas per branch. The high number of respondents targeted in this study allows for statistical analysis and a robust assessment of the fixation effects.

We have elaborated three creativity briefs to cover contrasted aspects of food system sustainability issues: "How to feed oneself without wasting food?" to tackle food disposal; "How can I ensure that everything I eat comes from my village?" to tackle food supply chains; and "How do I make sure I never run out of water at home?" to broaden the issue of ecological transition. A preliminary step consists in calibrating the creativity briefs in lab conditions to see if respondents are able to generate a minimal number of contrasted responses. For each participant groups, we conducted one creativity task related to food and ecological transition (out of the three mentioned above) and one control creativity task, called the egg task, whose brief is "How to ensure that a hen egg dropped from 10 meters high does not break". C-K modelling of this idea generation task has made it possible to better characterize fixation effects by identifying systematic deviations from a reference model of possible exploration in children and adults [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF], but also engineers and designers [START_REF] Agogué | Resisting classical solutions: The creative mind of industrial designers and engineers[END_REF][START_REF] Ezzat | How minimal executive feedback influences creative idea generation[END_REF]. The egg task was submitted many times to participants of various ages, and all the solutions proposed by the participants could be grouped into 10 meta-categories [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF]. In the studies conducted, it appeared that 80% of the solutions were grouped into just three meta-categories ("slow the fall", "absorb the shock" and "protect the egg"). Since these three meta-categories are very frequent, they are considered to be the result of the fixation bias and are therefore called fixed ideas [START_REF] Agogué | The impact of type of examples on originality: Explaining fixation and stimulation effects[END_REF]. The other ideas, which are rarer but more creative, are called expanding ideas.

We added to this creativity assessment protocol questions related to knowledge on food and ecological issues (2 questionnaires), as well as to lifestyle and ecological behaviour (2 questionnaires). The first knowledge questionnaire aims to assess the capacity of participants to discriminate true and false responses (preconceived ideas); the second is a general QCM. The first lifestyle questionnaire aims to assess daily behaviour with regard to food and nature and the second one deals with eco-friendly practices.

Our aim is to identify, on the one hand, knowledge gaps regarding issues related to food and the environment, and, on the other hand, the relationships that the respondents have with food and nature. The combination of creativity tasks and questionnaires about knowledge and lifestyle is aimed at a better understanding of the relationships between consumers' creativity, knowledge and lifestyle.

The experiment takes place within the classrooms with paper and pencils. Each participant answers the various questions individually, without communicating with others and without looking for information on the Internet. As the interventions are experimental, it is important to ensure good conditions of experimentation. Each intervention is conducted by two experimenters, so that each class can be divided into two groups in order to maintain as much concentration as possible. The first author of the paper has participated to all the interventions led in 2022 and 2023, accompanied by various colleagues. Each experimenter is briefed prior to the intervention and provided with a manual detailing the behaviour required (e.g. do not judge any response; do not help any participant; do not give any example, etc.).

Data is collected anonymously and confidentially. At the end of the experiment, a participant number is given to each child to ensure anonymity. Participation is voluntary. For each minor participant, we send an information letter to the parents prior to the intervention and ask them to sign a parental authorization form for their child's participation. We also collect signed consents from adult participants and adolescents. We do not process data without authorization. The research protocol has been checked ad approved by the research ethic board of Paris University (CER U-Paris) and is conducted in compliance with RGPD.

For each class, the researchers go back to the pupils after conducting some preliminary data analysis, in order to present them with the results. The objectives are to explain our research motivation and project, discuss the results with the respondents, make them exchange with each other about their responses and about the issues at stake, and let them know better about research activities and careers. See Figure 2 for a scheme of data collection, process, analysis and restitution.

Data analysis

Following the data collection, the research team transcribes all responses in Excel sheets. In parallel, the mapping of ideas is built for each brief with the CK methodology. This mapping allows identifying categories and sub-categories of ideas. In parallel, each response given by the respondents is coded and affected to a sub-category and category. Both top-down and bottom-up categorizations of ideas are harmonized. Then the coding is conducted by two researchers independently.

For each creativity task, we analyse several variables as a function of the age of the respondents:

-Fluency, which is the number of ideas generated in ten minutes on a given creativity task -Flexibility, which is the number of categories of ideas explored -Fixation, which is the number of ideas generated in the "fixation" categories (i.e., the ones that are the most explored by the respondents) -Expansion, which is the number of ideas generated in the "expansion" categories (i.e., the ones that are the less explored by the respondents)

These are theoretical representations of system 1, i.e., access to relatively close, easily accessible knowledge bases, and system 2, which requires access to more distant knowledge. We assess if these variables are more similar within a group of age and between groups of ages.

We also compare the fluency and flexibility of the respondents' exploration of ideas on creativity briefs regarding food and ecology on the on hand, and on the control task (egg task) on the other hand. We analyse the potential impact of creativity task order, as well as the correlation between the tasks.

Lastly, we assess the scores obtained for each knowledge and lifestyle questionnaires. We look for relationships between questionnaires on knowledge, on lifestyle, and creativity according to the various categories of ages of the respondents.

Preliminary results

All the data collected has not been processed yet and further data is to be collected over the coming year. This is why the results presented here are preliminary and partial.

As far as the egg task is concerned, the primary school pupils' fixations are mainly at the level of "cushioning the shock" and "using a living device (whether animals or humans) to stop the fall". Middle school pupils have the same fixations as primary school pupils. The fixation effect for high school pupils encompasses in addition to these two meta-categories of ideas the one "slowing down the fall". The fixation effect of adults is even broader as it also encompasses the meta-category "protecting the egg". Our calculation also concludes that flexibility significantly increases with age, which confirms the development of the ability to explore different solutions with age. We do not see significant effect of development on fluency. Yet, interestingly, many ideas proposed by primary school pupils are not feasible; these solutions that are not feasible disappear the older the respondents get. Overall, there are always fewer responses in expansion than in fixation whatever the age. All these results are congruent with those of previous studies on the egg task.

CK mapping on the food and ecology creativity tasks are being built. We obtain more meta-categories and sub-categories of responses than with the egg task, which is not surprising as the food thematic questions asked are broader and more complex than the egg task question. Yet it is important to limit the number of both meta-and sub-categories, and we need to refine the categories iteratively.

With regards to the task of "eating without wasting food", our CK preliminary tree distinguishes first "food waste reduction at the supply-chain level", then "individual consumption behaviour", then "collective action that may influence consumption behaviour". Further, for the branch "individual consumption behaviour", it distinguishes "before eating", "while eating" and "after eating". The fixation of primary school pupils seems to be focused on the branch "individual consumption behaviour" and "while eating" (e.g., asking for less food in the plate), as well as "after eating" (e.g., giving the remaining food to others). For middle and high school pupils, the fixation is quite similar to the one of primary school pupils, but broadened to the idea of "recycling and reusing what they don't eat", for example composting. For adults, the focus is broadened to what happens before consumption: e.g., reducing the quantities of what one buy, favouring food that does not produce waste, etc. in all cases, solutions to be conducted at the individual level are far more taken into consideration than collective solutions or solutions to be explored at the supply-chain level. When calculating average fluency for each creativity task (see Figure 3), we first notice that there are significant differences between classes and tasks. We can also see that there is a correlation between the fluency of the Egg task and the Food waste task, but not between the Egg task and the other ones (Local food and water). The average fluency is always higher for the Egg task than for the Food waste task and it is the same to a lesser extent regarding the Local food task; but it is not the case regarding the Water task for which the respondents gave many ideas (yet we need to collect more answers on this task).

Regarding knowledge questionnaires, primary school pupils have more difficulties to discriminate true and false responses than teenagers (questionnaire 1). General knowledge (questionnaire 2) increases with age but all the scores are quite good as they are above 30 out of 40 for all classes. Finally, our preliminary analysis shows that most respondents declare that they have an eco-friendly behaviour in their daily practices.

Discussion and perspectives

The aim of this communication paper is mainly to present the rationale and methodology of an innovative on-going research project that focuses on how to help consumers develop their creative capacities to enhance their transformative capacities to make food systems more sustainable. To date, fixation effects have mostly been studied on generic tasks (such as the Egg task) in laboratory conditions. Is this research, we test them on new creativity briefs related to ecological transitions, and empirically, in a range of educational establishments, villages and towns. The unsustainable trajectory of our agrifood system requires the implementation of transformative approaches [START_REF] Olsson | The concept of the Anthropocene as a game-changer: a new context for social innovation and transformations to sustainability[END_REF][START_REF] Brien | Is the 1.5 C target possible? Exploring the three spheres of transformation[END_REF]. However, although the idea of transformation has become prominent within the scientific community, there is no clear consensus as to what the concept means in practice. To date, most proposals addressing these issues have remained conceptual, with little work on how to move from the theory to the practice of transformation at the scale of SES. This research project seeks to tackles the complex, multi-actor and dynamic aspects of social-ecological systems, as (i) it is interdisciplinary, combining management and design sciences, psychology and ecology, as well as transdisciplinary as it involves non-academic facilitators and relies on collaborations with local stakeholders. It is embedded in a place-based, long-term and large-scale research infrastructure (ZAPVS), thus allows to follow up the research on the long term.

In the field of sustainability sciences, this research project contributes to better understand practical aspects of SES transformation, what the notion of transformative capacity encompasses, and how this notion may be applied to consumers to contribute to the transformation of their food system. In the field of design sciences, this project provides both operational and conceptual knowledge on how to support collective design processes with actors (i) who are not necessarily initially part of pre-existing organisations, but might generate new forms of collective action through their design process, (ii) who are generally not considered as designers (and do not consider themselves as such either), and (iii) who, for at least part of them, do not necessarily have an interest in contributing to transform the system they are part of.

It is planned to pursue this diagnosis of fixation effects by completing data collection so that the age groups per creativity tasks are balanced as well as data analysis. In particular, we plan to identify fixation effects related to food waste, food supply chains and water management, as a function of age; and subsequently, how the ability to propose creative solutions to such ecological problems develops with age? We will also try to better understand to what extent idea generation on these issues is related to knowledge, ability to discriminate true from false statements a access to knowledge bases and lifestyle.

This diagnostic phase will be followed by the implementation of innovative design workshops in various classes, which will be conducted iteratively over several weeks. The aim of these workshops will be to develop both design capacities and reflexivity of the participants, be they children, teenagers or adults, so that they propose and implement collective projects aiming to transform their food consumption and, further, their food system. It is not the purpose of this paper to develop the methodology and underlying theoretical aspects. Yet, in a nutshell, the workshops are thought to take place over 7 two-hour sessions.

An introductory session will consist in a presentation of the project, the principles and objectives of the method, and the planned schedule; in addition, a pre-test will be carried out in the form of a questionnaire to assess the initial state of the participants' knowledge and ideas. Three sessions will then be devoted to providing knowledge + generating ideas. The aim of these workshops will be to train the participants to 1) identify potential fixation effects by identifying easily accessible knowledge and ideas, 2) inhibit these fixation effects, 3) explore alternative paths by specifying concepts (or ideas) and seeking out new knowledge. At the end of these three sessions, the idea is to move towards the selection of a limited number of ideas to be developed. The two last sessions will be dedicated to reflexivity enhancing and project collective implementation. A post-test will be implemented several months later to assess the impact of this collective design approach.

Figure 1 :

 1 Figure 1: Location of the educational establishments in which the interventions were conducted in 2022-2023. (PS: Primary school; MS: Middle school; HS: High school).

Figure 2 :

 2 Figure 2: Data processing after the interventions in the classrooms.

Figure 3 :

 3 Figure 3: Average fluency according to creativity task for primary, middle and high school.

Table 1 :

 1 Number and levels of pupils involved in this research.

	City/village	Educational establishment	Classes	Number of pupils met
	Niort	P. Guérin general high school	6 classes 2nd	173
	Prahecq	E. Zola middle school	2 classes 5e + 2 classes 4e	86
	Fors	Primary school	1 class CM1-CM2	21
	Thorigné	Primary school	1 class CM1 + 1 class CM2	45
	St-Symphorien	Primary school	1 class CM2	23
	Beauvoir-sur-Niort Primary school	1 class CM1 + 1 class CM1	43
	Melle	J. Desfontaines general high school	4 classes 1e + 2 classes 2nd	171
	Marigny	Primary school	1 class CM1-CM2	24
	Mougon	Primary school	1 class CM1 + 1 class CM2	48
	Beaussais	Primary school	1 class CM1-CM2	23
	Melle	J. Bujault agricultural high school	1 class 2nd et 1 class T	35
	TOTAL		High shool	379
			Middle school	86
			Primary school	227

Acknowledgements

The authors acknowledge funding from the Nouvelle Aquitaine Region (Novland and CapTransfo projects) and French National Research Agency (Enact project -ANR-22-CE03-0010-01). The authors thank all the professors, pupils and parents who accepted to take part in this research. Finally, the authors thank the many colleagues who have contributed to implement this diagnostic of fixation effects, in particular C. Bombard, M. Goinard, A. Cappe de Baillon, E. Rodon and R. Degen.


F Boisson

A Hourlier

V Bekaert

L Thomas

P Marchand

E Santiago

L Cao

D Brasse

Imaging Capabilities of the IRIS and IRIS XL-260 PET/CT Systems for High-Throughput Imaging: a Quantification Cross Validation Study

The concept of imaging several subjects simultaneously is an active preclinical research topic. In the present paper, we assessed the imaging capabilities of two PET/CT systems based on similar detector technology. The IRIS system is a mice/rat imaging system arranged in two rings of eight detectors each, the more recent IRIS XL 260, dedicated to Non-Human Primate (NHP) imaging has a single ring of sixteen detectors. Both systems were equipped with standard animal cells (Minerve) and 3-mice adapters. Our objective is to study which of these systems could be more appropriate to perform quantitative high-throughput imaging on mice. Phantoms and [ 18 F]FDG tumor-bearing mice acquisitions have been conducted in single and high-throughput modes using both the IRIS (up to 3 mice) and the IRIS XL-260 PET/CT (up to 6 mice) systems.

Image Quality Phantom results obtained in high-throughput mode show some slight degradation of the recovery coefficient for rods of 1, 2 and 3 mm in diameter compared to the single-mode results, as one would normally expect. Similarly, we observed a decrease in image uniformity between the single-and the high-throughput modes for both the IRIS PET and the IRIS XL-260 PET systems. We performed [ 18 F]FDG tumorbearing mice PET acquisitions with both systems. In order to estimate the quantification differences in all the studied configurations, we calculate the ratios between the %ID/g values extracted from the PET images and the ex-vivo values. In single mode acquisitions, ratios of 0.94 ± 0.09 and 0.83 ± 0.08 were obtained for the IRIS and the IRIS XL-260 PET systems, respectively. In high-throughput mode, ratios of 0.78 ± 0.12 and 0.73 ± 0.13 were obtained for the IRIS and the IRIS XL-260 PET systems, respectively. The difference in %ID/g between static acquisitions and ex-vivo value is not statistically significant (p-value > 0.1) for both PET systems in single mode, as well as for the IRIS system in highthroughput mode. We noted a slightly higher statistical difference between static acquisitions and ex-vivo values for the IRIS XL-260 system with a p-value of 0.015.

Phantoms and in-vivo studies have made it possible to highlight the capability of the two systems to perform high-throughput acquisitions. Our results suggest that the IRIS system configuration may be the most suitable when aiming for quantitative high-throughput mice imaging. The large transverse field of view of the IRIS XL-260 makes it possible to image a greater number of mice simultaneously, which may be useful in specific cases, such as studies using an expensive radiotracer and/or with a short half-life. However, the IRIS PET/CT offers a full axial coverage of the animals and a higher sensitivity.

I. INTRODUCTION

In preclinical emission tomography imaging, several research groups have recently proposed to image several mice simultaneously mainly to reduce the costs and to increase the throughput. Simultaneous scanning of several animals also ensures injections with the This work involved human subjects or animals in its research. Approval of all ethical and experimental procedures and protocols was granted by the Alsace Regional Ethics Committee for Animal Experimentation under Application APAFIS#15255, and performed in line with the European Institutes of Health Guidelines.

All authors declare that they have no known conflicts of interest in terms of competing financial interests or personal relationships that could have an influence or are relevant to the work reported in this paper.

same specific activity, which may be otherwise subject to significant variations when animals are injected at different times and possibly with tracers from different production batches. However, scanning two (or more) animals comes with some downsides such as an increased attenuation, dead-time and rates of scatter and random events [START_REF] Siepel | Scanning multiple mice in a small-animal PET scanner: influence on image quality[END_REF], [START_REF] Habte | Impact of a multiple mice holder on quantitation of high-throughput MicroPET imaging with and without CT attenuation correction[END_REF]. In addition, it is well known that the performance of a Positron Emission Tomograph (PET) system, in terms of spatial resolution and sensitivity, is optimal at the center of the field of view (FOV) and degrades quickly with increasing distance from the center.

Wolf et al and Aide et al studied the possibility to scan several small rodents using clinical PET associated with a Computed Tomograph (CT) systems [START_REF] Wolf | Imaging tumour-bearing animals using clinical scanners[END_REF], [START_REF] Aide | High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications[END_REF]. Clinical PET scanners have a limited spatial resolution as compared to small-animal PET scanners. However, Aide et al demonstrated the feasibility of scanning multiple animals with a clinical PET scanner using advanced reconstruction algorithms that include a spatially variant spatial resolution model [START_REF] Aide | High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications[END_REF]. Previous studies on simultaneous scanning of multiple animals have also been published using small-animal PET scanners. Siepel et al investigated the effect of scanning four mice simultaneously on image quality [START_REF] Siepel | Scanning multiple mice in a small-animal PET scanner: influence on image quality[END_REF]. The same year, Aide et al first evaluated the feasibility to scan four mice simultaneously using the Inveon PET scanner [START_REF] Aide | High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously[END_REF]. This study assessed spatial resolution and scatter measurements as well as image quality using the Image Quality Phantom (IQP), and tumor bearing mice imaged in groups of four but did not report on the uniformity behavior. A few years later, Habte et al investigated the impact of attenuation correction on quantification when using a multiple-mouse holder for both the Inveon and microPET R4 Siemens scanners [START_REF] Habte | Impact of a multiple mice holder on quantitation of high-throughput MicroPET imaging with and without CT attenuation correction[END_REF]. They reported quantitative differences between singleand multiple-mice mode scans when using CT-based attenuation correction and obtained less that 15% difference between the two acquisition modes in terms of measured mean ROI values extracted from [18F]FDG mice images. In 2016, Reilhac et al assessed the PET signal degradation when scanning two mice simultaneously scanning in the Siemens Inveon small-animal PET scanner [START_REF] Reilhac | Simultaneous scanning of two mice in a smallanimal PET scanner: a simulation-based assessment of the signal degradation[END_REF]. Both simulated and experimental results showed that dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. However, dual-mice imaging strongly reduced the sensitivity to relative signal variations in mean and standard deviation of the measured activity concentrations in several regions of interests when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other.

In parallel with these studies, several research teams have been specifically working on the design of dedicated holders to ensure an optimal and reproducible positioning of several animals in the field of view of the scanners. In 2009, Cheng et al designed a head holder for scanning two rats simultaneously in small animal PET scanners to maintain high sensitivity and to minimize repositioning error between scans [START_REF] Cheng | A rat head holder for simultaneous scanning of two rats in small animal PET scanners: design, construction, feasibility testing and kinetic validation[END_REF]. More recently, Greenwood et al designed a 4-mice hotel for use in a nanoScan PET/CT system (Mediso Medical Imaging Systems) [START_REF] Greenwood | High-Throughput PET/CT Imaging Using a Multiple-Mouse Imaging System[END_REF]. They suggested that [ 18 F]FDG radiotracer uptake in the major organs of healthy mice scanned simultaneously versus those scanned individually produced similar quantitative values, despite the expected biologic variation in radiotracer retention and excretion.

Our objective is to study which scanner could be the most appropriate to perform quantitative high-throughput mice imaging. We assessed the imaging capabilities of two PET/CT systems from the Inviscan company (Inviscan SAS). The first system is dedicated to mice and rat imaging (IRIS PET/CT) and the second is designed for non human primate (NHP) imaging (IRIS XL-260). These two systems are based on similar detector technology. The IRIS PET/CT consists in two rings of eight detectors each. The IRIS XL-260 PET/CT consists in a single ring of sixteen detectors. Phantoms and [ 18 F]FDG tumour-bearing mice acquisitions were conducted in single and high-throughput modes with both the IRIS and the IRIS XL-260 PET/CT systems in order to evaluate the capability of high throughput between the two systems in terms of quantification.

II. MATERIALS AND METHODS

A. Systems Description

The PET component of the IRIS system consists in 16 modules arranged in two octagonal rings. Each module comprises a matrix of 27 × 26 Cerium doped lutetium-yttrium orthosilicate crystals doped with cerium (LYSO:Ce) of 1.6 × 1.6 × 12 mm 3 . The matrix is directly coupled to a Position Sensitive Photo-Multiplier Tube (PSPMT) (Hamamatsu Photonics). A full description of the IRIS system can be found in [START_REF] Belcari | NEMA NU-4 Performance Evaluation of the IRIS PET/CT Preclinical Scanner[END_REF].

We also assessed the high-throughput capability on mice imaging of the new IRIS XL-260 PET, a system dedicated to NHP which has a bore size of 260 mm and a trans-axial Field-of-View of 210 mm. The IRIS XL-260 PET detector ring consists in 16 modules arranged in one single ring. Each detector module comprises a 32 × 32 matrix of 1.54 × 1.54 × 16 mm 3 LYSO:Ce crystals, coupled to a PSPMT (Hamamatsu Photonics). The IRIS XL-260 PET system has an absolute sensitivity of 2.7% for a 250-750 keV energy window measured according to the NEMA procedure [START_REF]NEMA Standards Pub[END_REF]. Note that the IRIS XL-260 PET system's sensitivity is similar to the IRIS XL-220 PET system's as reported in [START_REF] Boisson | Performance evaluation of the IRIS XL-220 PET/CT system, a new camera dedicated to non-human primates[END_REF]. The CT component consists in a microfocus x-ray tube with a power of 80 W and a plat panel CMOS detector. The CT covers a FOV up to 210 mm in the transaxial and 85 mm in the axial directions with a single acquisition.

As the two PET systems show different detector geometry and sensitivity, we have chosen the activity levels placed in the systems' fields of view to obtain similar singles count rate values on both systems to ensure a similar behavior of the readout electronics in high-throughput mode. In addition, phantoms and mice acquisitions were performed at similar locations within the system's FOV.

B. Phantom Studies

IQPs were used to assess the quantification capabilities of the IRIS and IRIS XL-260 PET/CT systems. These IQPs were designed to fit in the multi-mice holders as reported in [START_REF] Greenwood | High-Throughput PET/CT Imaging Using a Multiple-Mouse Imaging System[END_REF]. They are smaller in diameter but show the same features as the IQP described in the NEMA NU-4 recommendations [START_REF]NEMA Standards Pub[END_REF]. They are composed of a main phantom body that contains a fillable cylindric chamber (diameter = 20 mm) and a solid part (20 mm in length) into which five fillable rods with various diameters (1, 2, 3, 4, and 5 mm) have been drilled. A lid attached to the uniform region of the phantom supports two cold-region chambers. These regions are hollow cylinders (15 mm in length and 5.5 mm in inner diameter with 1-mm wall thickness), to be filled with non-radioactive water and air, respectively. The IQP phantoms were filled with 3.7 MBq of [ 18 F]FDG solution each.

PET acquisitions were first performed with only one IQP placed in the central part of the FOV of both systems. Then three to six IQP phantoms were placed in the hotels described in the animal experiments section. The duration of the scans was set to 10 min each. CT acquisitions were performed right after the PET scans. We followed the NEMA NU-4 2008 standard for the analysis of the IQP data to compute the image uniformity and the recovery coefficients (RCs) for each rod. PET data were reconstructed using the iterative 3D OSEM algorithm. The calibration factor was included in the normalization file and applied during the reconstruction process. PET data were fully corrected for attenuation, random coincidences, radioactive decay and dead time. No scatter correction was applied.

C. Animals and Xenographt Model

4T1 cells were cultured in 75 cm 2 culture flasks containing DMEM High Glucose (Gibco), glutamax (Gibco). Medium was supplemented with 10% foetal bovine serum (Life technologies) and 1% of Penicillin-Streptomycin (10,000 U/mL) (Gibco). Cells were grown at 37 • C in a humidified atmosphere containing 5% CO2 and subcultured three times per week. The viability and number of cells were determined with the trypan blue exclusion technique. 24 female BALB/c mice (19.4 ± 0.3 g, 8 weeks old; Charles River) were kept at constant temperature (22 • C) and humidity (40%) with 12h light/dark cycles and were allowed free access to forage and water until 4h before the beginning of each imaging procedure. Animals were housed in individually ventilated cages. A cell suspension of one million 4T1 cells in 50 µL of PBS was injected subcutaneously into the right mammary gland under inhalation anesthesia (1.5-2% of isoflurane). All animal experiments were performed in accordance with European Institutes of Health Guidelines regarding the care and use of animals for experimental procedures and were approved by the Alsace Regional Ethics Committee for Animal Experimentation (approval identification: APAFIS#15255).

D. Animal Experiments

One week post cells injection, the 24 mice underwent an intraperitoneal injection of [ 18 F]FDG. The mean injected activity was 4.28 ± 0.19 MBq. Anesthesia was induced and maintained with 1.5% isoflurane in medical air with a calibrated vaporizer for the entire procedure. Throughout the investigation, mice were kept at a constant temperature of 37 • C.

The cohort of 24 mice was divided into 4 groups of 6, imaged according to different acquisition modes. Figure 1 shows a photograph of the experimental setups using the multiple-animal hotel.

1) Animal Experiments on the IRIS system: Six mice were used to perform high-throughput imaging acquisitions, consisting of 3 mice being imaged simultaneously as shown in Fig 1(A). A rat cell (Equipement veterinaire MINERVE, Estenay, France) was used to maintain the mice temperature and anesthesia. Mice hotels, specifically designed to fit the Minerve rat cell were used to position 3 mice per hotel. The two groups of 3 mice each underwent 60 min of dynamic 3D PET acquisitions starting 15 min after [ 18 F]FDG injection.

The last 6 mice were imaged individually positioned at the center of the FOV. Each mouse underwent two distinct 10 min static PET acquisitions starting 15 min and 65 min after [ 18 F]FDG injection, respectively. 3) PET Reconstruction and Data Analysis: For both PET systems, images were reconstructed using the manufacturer's default settings, consisting in an iterative three-dimensional (3D) orderedsubset expectation maximization OSEM algorithm (8 iterations, 8 subsets) using Monte Carlo based system matrices. The calibration factor was included in the normalization file and applied during the reconstruction process. PET data were fully corrected for attenuation, random coincidences, radioactive decay and dead time. No scatter correction was applied.

PET data analyses were performed using the AMIDE software package [START_REF] Loening | AMIDE: a free software tool for multimodality medical image analysis[END_REF]. Ellipsoids were manually drawn on the tumors, large enough to account for the entire radiotracer uptakes. Inside the volume, a region of interest (ROI) was defined by all the voxels with a value greater than 40% of the maximum activity concentration value. The percentage of injected dose per gram value (%iD/g) was then calculated for all tumors as the average activity concentration calculated inside the ROI divided by the injected activity.

To obtain the tumor quantification ground truth, all 4T1-bearing mice were sacrificed and dissected at the end of scanning procedure. After excision, the tumors were weighed and placed in an automatic gamma counter (Hidex, Turku, Finland) for 1 min. The count obtained was converted to absolute activity using a calibration curve and then corrected for radioactive decay. The results are expressed as a percentage of injected dose per gram of tissue (%ID/g) calculated as the measured organ activity divided by its weight and the injected activity value.

We also calculated the ratios between the %ID/g values extracted from the PET images and the ex-vivo values to estimate the quantification degradation in all the studied acquisition modes. We then compared each variable between the groups using the Mann-Whitney rank test function. Statistical calculation was performed considering a p < 0.05 level of significance. The image uniformity measured for both PET systems in singleand high-throughput modes are presented in Figure 2. The IRIS system presents a slightly better image uniformity compared to the IRIS XL-260 system in high-throughput mode.

III. RESULTS

A. Phantom Studies

Figure 3 illustrates the experimental results reported in Table I obtained using the IQP for the two systems in both single-and highthroughput modes.

B. Animal Experiments

Figure 4 shows the Maximum Intensity Projection (MIP) obtained in high-throughput mode using both PET/CT systems.

The use of the mouse hotel makes it necessary to present a MIP in order to demonstrate that all the tumors are clearly identified in all the animals present in the scanners' field of views in high-throughput mode.

Figure 5 shows the percentage of injected dose per gram measured in the two distinct 10 min static PET acquisitions and the ex-vivo values obtained using the gamma counter for both scanners in single mode acquisitions.

The difference in terms of percentage of injected dose per gram measured in the tumor between the two static acquisitions follows a classic bio-kinetics behavior of [ 18 F]FDG following an intraperitoneal injection. Furthermore, the difference in %ID/g between the last static acquisition (5 minutes before animal sacrifice) and the ex-vivo value is not statistically significant (p-value > 0.05) for both PET systems in single mode.

Figure 6 shows the percentage of injected dose per gram measured in the 60 min of dynamic 3D PET acquisitions starting 15 min after [ 18 F]FDG injection and the ex-vivo values obtained using the gamma counter for both scanners in high-throughput mode acquisitions.

In high-throughput mode, there is a difference between the results obtained with the IRIS and the IRIS XL-260 systems. The difference in %ID/g between the last static acquisition and the ex-vivo value is not statistically significant for the IRIS system. However, there is a significant statistical difference between the last static acquisition and the ex-vivo values for the IRIS XL-260 PET system, with a p-value of 0.015.

In order to estimate the quantification degradation in all the studied configurations, we calculate the ratios between the %ID/g values extracted from the PET images and the ex-vivo values, as presented in Figure 7. Ex-vivo values were considered as the reference.

In single mode acquisitions, ratios of 0.94 ± 0.09 and 0.83 ± 0.08 were obtained for the IRIS and the IRIS XL-260 PET systems, respectively. In high-throughput mode, ratios of 0.78 ± 0.12 and 0.73 ± 0.13 were obtained for the IRIS and the IRIS XL-260 PET systems, respectively.

IV. DISCUSSION

The concept of high-throughput imaging is an active preclinical research topic. Imaging several animals simultaneously makes it possible to meet the statistical expectations of the studies while respecting the principles of the 3Rs in the ethical framework for animal research and the care and well-being of each individual. However, it is essential to study the impact on image quality and quantitative accuracy of scanning several animals simultaneously. In PET, the increased injected dose present in the field of view, the greater attenuation or even the effects of dead time and scatter are all phenomena that can alter the quality of the image and the quantitative precision.

We have assessed the quantification capabilities of two preclinical PET/CT systems from the Inviscan Company when imaging multiple mice simultaneously. The manufacturer currently proposes 2 PET/CT systems, the IRIS PET/CT dedicated to mice and rat imaging and the IRIS XL 260 PET/CT, dedicated to large animal imaging. The two systems are based on similar detector technology but have very different detector configuration.

Most of users who have a requirement for large animal imaging as well as rodents will not be acquiring two dedicated systems, for several reasons, such as lack of space or limited budget. State-of-theart preclinical PET/CT systems usually provide sufficient axial FOV to image the entire mouse. However for rat imaging and primate imaging this is not the case. Rat full body will most of the time be imaged in multiple scan mode. Primate imaging also requires multi scan imaging unless one organ is imaged dynamically. In the case of multi-mice imaging, a rodent dedicated system will always be preferable for practical reasons. However we evaluated whether the IRIS XL 260 PET/CT can perform multi-mice imaging with similar image quality and throughput capability.

Results show a loss in image uniformity between the single-and the high-throughput modes for both the IRIS and the IRIS XL-260 systems. The results are consistent with other similar reported studies. Greenwood et al reported similar degradations in terms of image uniformity and RCs values [START_REF] Greenwood | High-Throughput PET/CT Imaging Using a Multiple-Mouse Imaging System[END_REF]. The IRIS system presents a better image uniformity compared to the IRIS XL-260 system in highthroughput mode, although the loss in uniformity is stronger in IRIS compared to XL-260.

In terms of Recovery coefficients obtained in high-throughput mode, using the single mode as reference, results show recovery coefficients losses (from 0.17 to 0.06 and from 0.16 to 0.02 for the IRIS and the XL-260, respectively) for the smallest rod of the phantom, which go along with the highest standard deviation of the RCs. RC numbers were slightly lower for the IRIS XL-260 than RCs obtained with the IRIS system. Similar losses in RCs were reported in [START_REF] Aide | High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously[END_REF] where RC for the 2mm rod went from 0.7 to 0.47 and the RC for the 1mm rod went from 0.35 to not visible. In [START_REF] Greenwood | High-Throughput PET/CT Imaging Using a Multiple-Mouse Imaging System[END_REF], the authors also reported comparable losses in RCs (RC for 1 mm dropping from 0.25 to 0.06).

Several parameters may explain these results. First of all, the scatter fraction for the IRIS is slightly higher than the one for the XL-260 system. Also, while the mean values in the IQP uniform region are similar for both systems, extracted values corresponding to the rods are lower for the XL-260, despite similar spatial resolutions values. This could be explained by the difference between the two system matrices used to reconstruct the data, but also the convergence of the reconstruction algorithms which could be different as we used the manufacturer's default settings. We also observed an over-estimation of the RCs (RC > 100%) using the IRIS system for the larger rods. Similar over-estimation of RCs were also reported in [START_REF] Aide | High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously[END_REF]. Kim et al recently reported similar results demonstrating the impact of the reconstruction algorithms and parameters but also the use of the maximum value in the rods during the data processing, which can lead to an over-estimation of the RCs compared to the average or peak values, which could limit this phenomenon [START_REF] Kim | Assessment of MicroPET Image Quality Based on Reconstruction Methods and Post-Filtering[END_REF].

Overall, the results seem to indicate that the IRIS system offers a better performance in terms of image uniformity and RCs in both single-and high-throughput mode acquisitions when imaging several mice.

The quantitative assessment was also conducted in single and highthroughput modes on [ 18 F]FDG tumor-bearing mice. Several studies reported reduced quantification accuracies up to 15% when scanning multiple animals simultaneously compared to conventional single animal scanning [START_REF] Habte | Impact of a multiple mice holder on quantitation of high-throughput MicroPET imaging with and without CT attenuation correction[END_REF], [5] - [START_REF] Cheng | A rat head holder for simultaneous scanning of two rats in small animal PET scanners: design, construction, feasibility testing and kinetic validation[END_REF]. We obtained similar results with both the IRIS and the IRIS XL-260 systems. Aide et al reported a 90% mean ratio between PET quantitative data and ex-vivo counting [START_REF] Aide | High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously[END_REF], while we obtained similar ratios in single mode acquisition (0.94 ± 0.09 and 0.83 ± 0.08 for the IRIS and the IRIS XL-260 systems, respectively) and slightly lower ones in high-throughput acquisition mode. The IRIS system presents good performance in terms of quantification, despite the absence of scatter correction, which partly explains the loss in RC and uniformity observed in high-throughput mode. Although it presents a large transverse field of view allowing to image a greater number of animals simultaneously, the loss in RC and uniformity is slightly more important in the case of the IRIS XL-260 system.

Although these two scanners are based on the same detection technology, their geometries give them significantly different performance. The axial coverage and the diameter of the detection ring differ drastically between the two scanners. This leads to significantly lower sensitivity in the case of the NHP scanner (2.7% absolute sensitivity compared to 8% for the IRIS considering an energy window of 250-750 keV, [START_REF] Belcari | NEMA NU-4 Performance Evaluation of the IRIS PET/CT Preclinical Scanner[END_REF]). In addition, the axial coverage of the IRIS system makes it possible to image the entire body of a mouse, unlike the IRIS XL-260 system for which a significant proportion of the activity is found outside the field of view. Despite a shorter axial field of view, the IRIS XL-260 offers the possibility of simultaneously imaging a large number of animals thanks to its wide transverse field of view. In addition, it presents sufficient quantitative performance for studies focusing on a specific organ. The disadvantage of imaging a large number of animals (n≥6) remains to lower the amount of activity injected per animal to ensure a low level of count loss due to detector dead-time. Furthermore, the IRIS XL-260 presents itself as a good alternative in the case of studies using an expensive radiotracer and/or with a short half-life, thus making it possible to ensure that all the animals will be injected with the same specific activity. Finally, this study was based on results extracted from acquisitions performed 15 minutes post-injection. Investigating the quantitative capacities of these systems in the context of compartmental analysis studies of the kinetics of a radiotracer would require a completely different methodological approach, such as the use of catheters and injection pumps. However, Cheng et al have demonstrated that the challenge relating to such studies remains essentially technical because their results showed that the difference in Ki caused by dual scanning as opposed to single scanning was not statistically significant [START_REF] Cheng | A rat head holder for simultaneous scanning of two rats in small animal PET scanners: design, construction, feasibility testing and kinetic validation[END_REF].

V. CONCLUSION

Our objective was to study two commercially available PET/CT systems with different detector ring geometric arrangement and establish if one system in particular is more appropriate to perform quantitative high-throughput mice imaging. The IRIS PET/CT system is dedicated to mice and rat imaging, the IRIS XL 260 is dedicated to NHP imaging. Phantoms and in-vivo studies have made it possible to highlight their capacities to perform high-throughput acquisitions.

The results suggest that the IRIS system configuration provides more accurate quantitative results when aiming for whole-body highthroughput imaging. The large transverse field of view of the IRIS XL-260 makes it possible to image a greater number of mice simultaneously, which may be usefull in specific cases such as studies using an expensive radiotracer and/or with a short half-life. However, it maybe preferable to reduce the number of animals in order to minimize the quantification bias by considering a full axial coverage of the animals while maximizing the sensitivity.

Fig. 1 .

 1 Fig. 1. Photographs of the experimental high-throughput setups using (A) IRIS PET/CT and (B) the IRIS XL-260 systems.

Fig. 2 .

 2 Fig. 2. Image uniformity measured for both PET systems in single-and high-throughput modes.

Fig. 3 .

 3 Fig. 3. (A) Recovery Coefficient values for both systems in single-and highthroughput modes and (B) the corresponding average standard deviation.

Fig. 4 .

 4 Fig. 4. (A) MIP in high-throughput mode obtained with the IRIS system (3 mice) and (B) MIP in high-throughput mode obtained with the IRIS XL260 system (6 mice). Red arrows highlight the 4T1 tumors in all imaged animals.

Fig. 5 .

 5 Fig. 5. Percentage of injected dose per gram measured in the two distinct 10 min static PET acquisitions starting 15 min and 65 min after [ 18 F]FDG injection and the ex-vivo values obtained using the gamma counter. The measured values obtained in single mode using the IRIS PET system are presented in (A) and (B) for the IRIS XL-260 PET system.

Fig. 6 .

 6 Fig. 6. Percentage of injected dose per gram measured in 60 min of dynamic 3D PET acquisitions starting 15 min after [ 18 F]FDG injection. The ex-vivo values obtained using the gamma counter are represented by the red squares. (A) and (B) represent the measured values obtained in high-throughput mode using the IRIS and the IRIS XL-260 PET systems, respectively.

Fig. 7 .

 7 Fig. 7. Ratios between the %ID/g values extracted from the PET images and the ex-vivo values using both PET systems in both single-and high-throughput modes.

TABLE I AVERAGE

 I STANDARD DEVIATIONS OF THE RECOVERY COEFFICIENTS OBTAINED IN BOTH SINGLE ( s ) AND HIGH-THROUGHPUT (

	Rod	5 mm	4 mm	3 mm	2 mm	1 mm
	I s	4.5	5.0	4.9	6.8	10.3
	I h	7.8 ± 0.8	8.2 ± 0.7	9.4 ± 0.9	9.9 ± 1.4	10.8 ± 1.0
	X s	8.4	8.9	10.4	8.6	11.6
	X h	9.8 ± 0.7	9.8 ± 0.7	11.2 ± 1.5	12.2 ± 2.1	16.0 ± 3.4

h ) MODES USING THE IRIS (I ) AND THE IRIS XL-260 (X ).

This article has been accepted for publication in IEEE Transactions on Radiation and Plasma Medical Sciences. This is the author's version which has not been fully edited and content may change prior to final publication. Citation information: DOI 10.1109/TRPMS.2022.3222565 © 2022 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See https://www.ieee.org/publications/rights/index.html for more information.

ACKNOLEDGMENTS

The authors wish to thank the Cyrcé platform and its staff from the Institut Pluridisciplinaire Hubert Curien for their help in performing all the experiments.