Fanny Dégeilh

Jessica Lacombe-Barrios

Carola Tuerk

Catherine Lebel

Véronique Daneault

Ramy El-Jalbout

Jocelyn Gravel

Sylvain Deschênes

Josée Dubois

Chantale Lapierre

Isabelle Gagnon

Mathieu Dehaes

Thuy Mai Luu

Miriam H Beauchamp
email: miriam.beauchamp@umontreal.ca

Behavioral-play familiarization for non-sedated magnetic resonance imaging in young children with mild traumatic brain injury

Keywords: magnetic resonance imaging, sedation, familiarization, early childhood, concussion, brain injury

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Behavioral-play familiarization for non-sedated magnetic resonance imaging in young children with mild traumatic brain injury

Introduction

Traumatic brain injury (TBI) is highly prevalent in children younger than six years old [START_REF] Thurman | The epidemiology of traumatic brain injury in children and youths: A review of research since 1990[END_REF][START_REF] Koepsell | Incidence and descriptive epidemiologic features of traumatic brain injury in King County, Washington[END_REF], in whom, even mild insult to the brain, such as concussion or mild TBI (mTBI)characterized by transient neurological symptoms such as headache, alteration of consciousness, amnesia, or nausea following a violent blow or jolt to the head or body [START_REF] Zemek | Prognosticators of persistent symptoms following pediatric concussion: a systematic review[END_REF] -, has the potential to disturb brain structure or function and affect cognitive, emotional, behavioral, and social functioning [START_REF] Séguin | in press) What about the little ones? Systematic review of cognitive and behavioral outcomes following early TBI[END_REF]. Due to the challenges of collecting neuroimaging data in children five years and younger, toddlers and preschoolers are typically excluded from research efforts to document brain changes after TBI [START_REF] King | A systematic review of cross-sectional differences and longitudinal changes to the morphometry of the brain following paediatric traumatic brain injury[END_REF].

Magnetic resonance imaging (MRI) is highly sensitive to motion which induces blurring and ghosting in the images, thus requiring children to stay still in the scanner for prolonged acquisition periods. In clinical settings, computed tomography (CT) is commonly used for children with TBI for detection of skull fractures and subarachnoid hemorrhage. It can be performed quickly with less need for immobilization than MRI; however, it is a source of ionizing radiation and has low sensitivity to subtle brain lesions following mTBI [START_REF] Beauchamp | Detecting traumatic brain lesions in children: CT versus MRI versus susceptibility weighted imaging (SWI)[END_REF][START_REF] Shenton | A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury[END_REF].

Alternatively, MRI protocols are sometimes prescribed for clinical purposes, but sedation is generally used in young children to facilitate high-quality and efficient image acquisition.

Though necessary in some cases and settings, sedation can be associated with risk of adverse side effects such as seizures and apnea, or mild cognitive or brain disruption (i.e., neurotoxicity and neurodegenerative changes) [START_REF] Lindberg | Feasibility and accuracy of fast MRI versus CT for traumatic brain injury in young children[END_REF][START_REF] Andropoulos | Effect of Anesthesia on the Developing Brain: Infant and Fetus[END_REF]. It is thus not an optimal procedure in young children in addition to being prohibited ethically for research purposes.

Subtle brain lesions or changes following mTBI cannot be adequately visualized on CT or conventional MRI [START_REF] Beauchamp | Detecting traumatic brain lesions in children: CT versus MRI versus susceptibility weighted imaging (SWI)[END_REF][START_REF] Shenton | A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury[END_REF]. In contrast, advanced MRI techniques (e.g., surface-based morphometry, susceptibility-weighted imaging [SWI], diffusion-weighted imaging [DWI]) are highly sensitive for detecting subtle changes in brain structure following pediatric mTBI in school-age children and adolescents. Using these techniques in children 6-17 years old, studies have documented the presence of brain lesions, reduced global and regional brain volumes and cortical thickness, as well as altered white mater microstructure months, even years, following mTBI [START_REF] King | A systematic review of cross-sectional differences and longitudinal changes to the morphometry of the brain following paediatric traumatic brain injury[END_REF][START_REF] Lindsey | Longitudinal Neuroimaging in Pediatric Traumatic Brain Injury: Current State and Consideration of Factors That Influence Recovery[END_REF][START_REF] Dennis | Diffusion MRI in pediatric brain injury[END_REF]. However, putative brain alterations following early mTBI remain unexplored.

A recent study tested the feasibility of fast MRI (i.e., abbreviated, motion-tolerant sequences) without sedation in young children (<6 years old) with TBI of all severities [START_REF] Lindberg | Feasibility and accuracy of fast MRI versus CT for traumatic brain injury in young children[END_REF].

The approach was successful for obtaining MRI data in six minutes without the need for anesthesia or sedation. However, the utility of the procedure was constrained due to the limited sensitivity of fast MRI to detect subtle brain insult, which is more typical of milder injuries, the detection of which is necessary for fully appreciating the consequences of mTBI on the developing brain. In addition, fast MRI sequences are not suited for quantitative MRI analysis.

Children younger than 5 years are the most difficult to scan without sedation [START_REF] Barkovich | Pediatric neuro MRI: tricks to minimize sedation[END_REF][START_REF] Copeland | Infant and Child MRI: A Review of Scanning Procedures[END_REF].

While they are gradually more able to cooperate over this period, reduced daytime sleep complicates scanning during natural sleep, an approach often used successfully in neonates and infants. In typically developing children (TDC) of this age, a brief behavioral familiarization (i.e., introduction of the MRI procedure to the child by play) provides an effective alternative to sedation for acquiring awake MRI in a time-and resource-efficient manner [START_REF] Barkovich | Pediatric neuro MRI: tricks to minimize sedation[END_REF][START_REF] Copeland | Infant and Child MRI: A Review of Scanning Procedures[END_REF]. This procedure is associated with success rates of at least 63% in children younger than six years [START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF][START_REF] Vannest | Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children[END_REF][START_REF] De Bie | Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans[END_REF], against 54% when melatonin is used to induce sleep in children under five years [START_REF] Johnson | The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination[END_REF]. In clinic, using preparation procedures and distraction (e.g., video) during MRI acquisition in children younger than 7 years significantly reduces the frequency of sedation by 34.6% [START_REF] Khan | A program to decrease the need for pediatric sedation for CT and MRI[END_REF]. However, no study to date has applied a behavioralplay approach for acquiring MRI in the context of early mTBI research. TBI-related symptoms and consequences may make it harder for children to lay still in the scanner, and the MRI environment may induce heightened stress and anxiety. For example, mTBI sustained in early childhood has been associated with increased internalizing and externalizing behavior problems [START_REF] Gagner | Behavioral consequences of mild traumatic brain injury in preschoolers[END_REF][START_REF] Li | The effect of pediatric traumatic brain injury on behavioral outcomes: a systematic review[END_REF], as well as anxiety symptoms occurring in the context of post concussive symptoms [START_REF] Dupont | Report of early childhood traumatic injury observations & symptoms: Preliminary validation of an observational measure of postconcussive symptoms[END_REF]. The present study aimed to compare the effectiveness of a behavioral-play familiarization for acquiring non-sedated research MRI between preschool children (3-5 years) with mTBI and their typically developing peers, and to identify factors associated with successful acquisition.

Materials and Methods

The current data were collected as part of a pilot study (DOLFIN Project) prior to a longitudinal cohortstudy (KOALA) on the impact of early mTBI on child development) [START_REF] Beauchamp | Kids' Outcomes and Long-term Abilities (KOALA): Protocol for a prospective, longitudinal cohort study of mild traumatic brain injury in children 6 months to 6 years of age[END_REF].

The studies were approved by the local human research ethics committee and conducted in agreement with the Helsinki declaration. All families provided written informed consent for participation.

Participants

Children with mTBI were recruited at two pediatric emergency departments (CHU Stainte-Justine and Montreal Children's Hospital, Montreal, Canada). TDC were recruited from the general population via pamphlets distributed in local daycares and early childhood care centers.

Inclusion criteria for all children were as follows: and (d) one or more of the following signs or symptoms: palpable skull fracture; headache(s); altered mental status (including agitation, somnolence, slow response, repetitive questioning, confusion); excessive irritability (more than usual) or 'not acting normally' (according to parents); loss of consciousness (any).

Non-sedated neuroimaging protocol

One to three months post-injury (or post-recruitment for the control group; minimum time interval = 15 days), children participated in a 15-minute familiarization adapted from Thieba et al. [START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF] and immediately underwent a non-sedated MRI protocol. Non-sedated MRI acquisition. MRI data were acquired on a 3T scanner (Discovery MR750, GE Healthcare Systems, Milwaukee, WI) using a 32 Channel matrix head while children watched a movie. MRI sequences included a BRAVO T1-weighted anatomic MRI (T1-w), quantitative susceptibility mapping (QSM), 30 directions DWI, SWI, T2-weighted anatomic MRI (not for 4 participants) and resting-state functional MRI (rs-fMRI; not for 1 participant) for a total duration of 35 minutes (see [omitted for review] for complete sequence parameters). The rs-fMRI sequence occurred while the participants continued to watch the movie, as in previous work [START_REF] Long | The brain's functional connectome in young children with prenatal alcohol exposure[END_REF].

Measures

Sociodemographic. Child sex assigned at birth (i.e., male or female), handedness, ethnicity, birth characteristics, developmental and medical history, as well as parental education, income and family characteristics were documented.

MRI acquisition success and full completion. MRI acquisition was considered successful

when the child entered the scanner and completed the two first sequences (T1-w and QSM) corresponding to approximately 15 minutes of MRI acquisition, was set a priori as the MRI acquisition success criterion for two reasons. First, it aligns with the length of previous protocols in neuroimaging studies on typically developing young children [START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF][START_REF] Vannest | Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children[END_REF][START_REF] Dean | Modeling healthy male white matter and myelin development: 3 through 60 months of age[END_REF][START_REF] Dai | Longitudinal associations between white matter maturation and cognitive development across early childhood[END_REF].

Second, the QSM sequence is of particular interest in the context of mTBI. Susceptibility imaging, included in QSM, is sensitive for detecting and quantifying microbleeds following mTBI [START_REF] Levin | Diagnosis, prognosis, and clinical management of mild traumatic brain injury[END_REF][START_REF] Liu | Diffuse axonal injury after traumatic cerebral microbleeds: an evaluation of imaging techniques[END_REF], and possibly more effective than diffusion imaging in the sub-acute phase of mTBI. Indeed, diffusion imaging shows lower sensitivity to detect subtle brain changes in the acute phase (i.e., in the days post-injury) than in the chronic phase (i.e., after 6 months postinjury) of mTBI [START_REF] Studerus-Germann | Central nervous system microbleeds in the acute phase are associated with structural integrity by DTI one year after mild traumatic brain injury: A longitudinal study[END_REF].

The MRI acquisition was considered fully completed when all the sequences from the MRI protocol were completed.

MRI data quality assessment.

Visual quality check. A team member with 10 years expertise in pediatric neuroimaging (FD) visually inspected each image for motion artefacts (e.g., ringing, blurring) and image quality, and were rated as 'usable' versus 'unusable'.

Quantitative quality check. In addition to the visual inspection, structural, DWI and rs-fMRI sequence quality was estimated quantitatively as follow:

1) Structural MRI quality was estimated quantitatively using the CAT-12 toolbox (version: CAT12.6-rc1 [r1429]) part of SPM12 (version: 7487) based on noise, inhomogeneities and image resolution [START_REF] Whitfield-Gabrieli | Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks[END_REF].

2) DWI quantitative quality check was performed based on the outlier report provided by the Eddy tool [START_REF] Andersson | An integrated approach to correction for offresonance effects and subject movement in diffusion MR imaging[END_REF][START_REF] Andersson | Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images[END_REF] part of FSL (version: 5.0.11) [START_REF] Smith | Advances in functional and structural MR image analysis and implementation as FSL[END_REF]. The images were rated on a six-point Likert scale as follows: 0=unusable, > 6 volumes (out of 35) with > 10 slices (out of 54) of signal dropout detected; 1=poor, 1-5 volumes with > 10 slices of signal dropout detected; 2=fair, > 1 volume with [START_REF] King | A systematic review of cross-sectional differences and longitudinal changes to the morphometry of the brain following paediatric traumatic brain injury[END_REF][START_REF] Beauchamp | Detecting traumatic brain lesions in children: CT versus MRI versus susceptibility weighted imaging (SWI)[END_REF][START_REF] Shenton | A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury[END_REF][START_REF] Lindberg | Feasibility and accuracy of fast MRI versus CT for traumatic brain injury in young children[END_REF][START_REF] Andropoulos | Effect of Anesthesia on the Developing Brain: Infant and Fetus[END_REF][START_REF] Lindsey | Longitudinal Neuroimaging in Pediatric Traumatic Brain Injury: Current State and Consideration of Factors That Influence Recovery[END_REF] slices of signal dropout detected; 3=good, [START_REF] Vannest | Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children[END_REF][START_REF] De Bie | Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans[END_REF][START_REF] Johnson | The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination[END_REF][START_REF] Khan | A program to decrease the need for pediatric sedation for CT and MRI[END_REF][START_REF] Gagner | Behavioral consequences of mild traumatic brain injury in preschoolers[END_REF][START_REF] Li | The effect of pediatric traumatic brain injury on behavioral outcomes: a systematic review[END_REF] slices of signal dropout detected in total; 4=very good, [START_REF] Dennis | Diffusion MRI in pediatric brain injury[END_REF][START_REF] Barkovich | Pediatric neuro MRI: tricks to minimize sedation[END_REF][START_REF] Copeland | Infant and Child MRI: A Review of Scanning Procedures[END_REF][START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF][START_REF] Vannest | Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children[END_REF] slices of signal dropout detected in total; 5=excellent, [START_REF] Thurman | The epidemiology of traumatic brain injury in children and youths: A review of research since 1990[END_REF][START_REF] Koepsell | Incidence and descriptive epidemiologic features of traumatic brain injury in King County, Washington[END_REF][START_REF] Zemek | Prognosticators of persistent symptoms following pediatric concussion: a systematic review[END_REF][START_REF] Séguin | in press) What about the little ones? Systematic review of cognitive and behavioral outcomes following early TBI[END_REF][START_REF] King | A systematic review of cross-sectional differences and longitudinal changes to the morphometry of the brain following paediatric traumatic brain injury[END_REF][START_REF] Beauchamp | Detecting traumatic brain lesions in children: CT versus MRI versus susceptibility weighted imaging (SWI)[END_REF][START_REF] Shenton | A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury[END_REF][START_REF] Lindberg | Feasibility and accuracy of fast MRI versus CT for traumatic brain injury in young children[END_REF][START_REF] Andropoulos | Effect of Anesthesia on the Developing Brain: Infant and Fetus[END_REF][START_REF] Lindsey | Longitudinal Neuroimaging in Pediatric Traumatic Brain Injury: Current State and Consideration of Factors That Influence Recovery[END_REF] slices of signal dropout detected in total.

3) Rs-fMRI images were visually inspected for motion artefacts and image quality and were first rated as usable versus unusable (by FD). Then, rs-fMRI image quality was quantitatively assessed using the FSL (version: 5.0.11) motion outliers tool [33] to detect outlier volumes based on root mean square intensity difference to the reference volume. The threshold was defined as the 75 th percentile + 1.5 times the InterQuartile Range.

Parent, child, and research MRI qualitative reports.

The Parent MRI Report is an in-house 6-item parent-report questionnaire designed to document parent knowledge about the MRI before participating in the study, their opinion about the usefulness of the information provided, their child's level of concern about the MRI, and their projection concerning the likelihood that their child will successfully complete the MRI protocol. The questionnaire was given to parents before the familiarization, upon arriving in the MRI waiting room.

Parents were asked to assess these aspects using a 5-point Likert scale (1=Not at all, 5=Very much) before the MRI acquisition while the research assistant set up the material for the familiarization.

The Child MRI Report is an in-house 8-item questionnaire designed to document the child's overall enjoyment and experience of the familiarization and MRI acquisition. It was administered by the research assistant to the participant after the MRI. The items include general questions about the procedure (e.g., Did you like the book?) as well as technical aspects of the MRI experience (e.g., Did you see the video well?). Answers were provided either by yes/no format or a 5-point smiley face Likert scale.

On their Research Team MRI Report, the research assistant and the MRI technician respectively assess the child's and parent's level of concern regarding the MRI acquisition and predict the likelihood of the child completing all MRI sequences.

Statistical analysis

Analyses were run in SPSS (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp).

MRI acquisition success and full completion.

Group differences in the rate of success and full completion of the MRI protocol were tested using Fisher's exact test.

Child experience.

Children's answers to the Child MRI questionnaire were compared between the mTBI and TDC groups using Fisher's exact test (categorial data) and t-test (continuous data).

MRI acquisition success prediction.

The role of the following variables on the MRI acquisition success rate (coded as 0=fail, 1=success) was tested using univariate logistic regressions: likelihood of completeness predicted by the research assistant, the MRI technician, and the parent (Do you think the child will get to the end of the MRI protocol? ; I think my child will be able to complete the MRI.). These predictors were selected to examine whether parent, research staff and MRI technologist observations could provide insights into whether the child is ready to complete the MRI. In addition, variables known to influence child MRI performance [START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF][START_REF] Johnson | Developmental Factors That Predict Head Movement During Resting-State Functional Magnetic Resonance Imaging in 3-7-Year-Old Stuttering and Non-stuttering Children[END_REF] were also chosen as predictors of success including: parent and child concern about the MRI (Are you worried about the MRI? ; Is your child worried about the MRI?), child age and sex, as well as parental education, and parental knowledge of MRI. Considering the sample size and the absence of significant differences between mTBI and TDC in terms of MRI success rate (see results), full MRI protocol completeness, or child experience, the prediction analyses were conducted on the entire sample.

Results

Participants

MRI acquisition success and full completion

Of the 37 children who completed the familiarization, 5 TDC and 2 mTBI refused to undergo MRI scanning. In addition, 1 TDC asked to stop the MRI protocol during the first sequence.

Fifteen TDC (63%, mean age at MRI = 62.3 ± 9.8 months) and 10 mTBI (77%, mean age at MRI = 62.2 ± 8.9 months) completed the two first sequences, thereby reaching the MRI acquisition success criterion (Figure 1,Table1). There was no significant difference in the rate of MRI acquisition success between TDC and mTBI (p=.48; 95% CI [-0.36 14.08]; Cramer's V=.15). Within the mTBI group, there was no significant association between time post-injury and MRI acquisition success rate (p=.33; 95% CI [-0.31 0.73]).

Thirteen TDC (54%, mean age at MRI = 61.7 ± 10.5 months) and 5 mTBI (38%, mean age at MRI = 66.6 ± 5.5 months) completed the full MRI protocol, staying between 30 and 41 minutes in the scanner (Figure 1, Table 1). There was no significant difference in the rate of children who fully completed the MRI protocol between TDC and mTBI (p=.49; 95% CI [0.10 2.53]; Cramer's V=.15). Within the mTBI group, there was no significant association between time post-injury and the rate of children who fully completed the MRI protocol (p=.69; 95% CI [-0.63 0.46]).

Among the 5 mTBI and 2 TDC who met the MRI acquisition success criterion, but who did not complete the full MRI protocol, none explicitly asked to end the acquisition because of fear or discomfort. All children asked to stop the acquisition because they were getting restless or bored or simply stated that they did not want to continue. Note that for three of these participants, technical issues involving the audio-visual equipment or the MRI console occurred before or during the MRI acquisition that prolonged the duration of the exam.

Mean MRI duration was 24.22 ± 14.76 minutes (range = 0-41 minutes). There was no significant group difference in the overall MRI duration between mTBI (M = 25.54 ± 14.00) and TDC (M = 23.50 ± 15.40; p = .70; 95% CI [-12.29 8.22]).

MRI data quality

The images acquired were of high quality: 92% (TDC) and 92% (mTBI) of total images acquired were rated as 'usable' after visual inspection (Table 2). Usable image rates ranged from 75% (T2-w sequence, TDC) to 100% (T1-w and rs-fMRI, both groups). Image quality remained stable throughout the entire protocol.

Structural MRI. T1-w images were acquired in 18 TDC (75%) and 11 mTBI (85%; Table 1).

The images were of high quality, as reflected by visual inspection (Table 2) and quantitative quality (Table 3) rates: 100% of the images were rated as "usable" based on visual inspection, and as "good to excellent" using a quantitative indicator of quality (CAT12 percentage rating points, range=80-92%).

Diffusion-weighted imaging. DWI was acquired on 15 TDC (62%) and 10 mTBI (77%; Table 1). The images were of high quality (Table 2), as reflected by visual inspection and quantitative quality rates: 93% (TDC) and 100% (mTBI) of the images were rated as 'usable' after visual inspection. In both groups, the images were of high quality with 60% of the images rated as 'good to excellent' quality based on the outlier report provided by the Eddy tool.

Rs-fMRI.

Rs-fMRI was acquired on 12 TDC (50%) and six mTBI (43%; Table 1). Rs-fMRI data for two participants were lost due to a technical problem during data transfer. All the images (100%) were rated as 'usable' after visual inspection (Table 2). The images were of high quality with fewer than 13% (TDC) and 10% (mTBI) of volumes revealing excessive motion artifacts (outliers). Removing these volumes would provide at least 13 minutes of resting-state data without motion artifacts.

Child experience

All children were attentive and compliant during the MRI familiarization and 36 (97%) reported that they enjoyed the procedure. The only child that did not like it explained afterwards that he did not enjoy stories in general and that it was not something specific about the MRI familiarization. Among the 19 TDC and the 11 mTBI who agreed to proceed with the MRI acquisition, 13 (68%) TDC and 9 (82%) mTBI liked the experience 'a lot' or 'very much', and 11 (58%) TDC and 8 (73%) mTBI indicated that they would be willing to do an MRI again (Table 3). No significant differences were found between the two groups (Table 3).

Success prediction. MRI success was significantly predicted by the research assistant

Discussion

The present study aimed to evaluate the effectiveness of a brief behavioral-play familiarization for acquiring non-sedated MRI in young children with mTBI, as well as to evaluate factors associated with non-sedated MRI acquisition success. Almost all children (97%) reported that they enjoyed the behavioral-play familiarization and most were willing to do an MRI again. In addition, the 15-minute behavioral-play familiarization developed for this study allowed us to acquire high-quality MRI with excellent success rates without the need for sedation. The majority of children (77% and 63% of 3-to-5-year-old children with and without mTBI) completed at least the two first sequences corresponding to about 15 minutes of acquisition (success threshold). About half of the children (38% mTBI and 54% TDC) stayed in the scanner between 30 and 41 minutes and completed the full MRI protocol.

Success and full completeness rates were similar between children with and without mTBI, suggesting that factors associated with mTBI do not impact the success of the acquisition. This success rate (i.e., 63-77%) is consistent with that previously reported in TDC of the same age using a similar procedure for acquiring non-sedated awake MRI (ranging from 63 to 88%) [START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF][START_REF] Vannest | Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children[END_REF][START_REF] De Bie | Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans[END_REF], or during natural sleep in children aged 0-to-4 years (ranging from 66 to 96%) [START_REF] Almli | The NIH MRI study of normal brain development (Objective-2): Newborns, infants, toddlers, and preschoolers[END_REF]. It was substantially higher than that obtained by using melatonin during MRI acquisition in children under five years (54%) [START_REF] Johnson | The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination[END_REF].

Beyond the excellent acquisition success rate, this familiarization facilitated the acquisition of high quality structural and functional brain images with low motion artifacts.

More than 70% of the T1-w images were rated as 'excellent' according to quantitative quality criteria, 60% of the diffusion images rated as 'good to excellent' quality based on the outlier report and excessive motion artifacts were reported in fewer than 13% of rs-fMRI volumes.

Less than 4% (1/29 structural MRI, 1/25 DWI and 0/18 rs-fMRI) of acquired images were rated as unusable.

Interestingly, parent concern about the MRI was negatively associated with MRI success, but their knowledge about the MRI and level of education were not. Information about the MRI were communicated to the parent via a pamphlet and by phone during the recruitment and appointment scheduling, and again in person before the MRI protocol.

Although the study team was attentive to parents' questions and concerns, it is possible that this result reflects an intrinsic anxiety or stress trait of the parent, rather than a state specific to the MRI. Further investigations are needed to better understand whether intrinsic parent factors (e.g., anxiety, stress level) or mental state are associated with child MRI success.

Child age, but not sex, was associated with MRI success. Older children were more likely to succeed the MRI protocol. Age-specific familiarization steps or adaptations in the procedure may be needed. As the MRI acquisition was conducted on a clinical scanner with restricted and specific timeslots for research MRI, it was not always possible to adapt the MRI appointment to the child's rhythm and daily routine (e.g., naps, snack times). Also, young children are likely to be more sensitive to any issues that extend the time they have to wait for the MRI and technical delays may wear out their patience.

Research assistants and MRI technicians accurately predicted the success of the MRI acquisition. It might be expected that the parent, who knows the child best, would be the one better able to predict how their child will react. However, the MRI protocol is an unfamiliar situation for both the parent and the child, compared to an MRI technician or research assistant who accompany large numbers of children in the scanner and therefore might be able to quickly and accurately see signs that the child will succeed or not. Further investigation is needed to understand which child and parent comments or behaviors suggested to the team that the child would or would not succeed. This knowledge could eventually be shared with the parent during the familiarization to decrease their own concern.

Finally, time post-injury was not associated with success or full protocol completion.

Since almost all children underwent MRI scanning after the acute post-injury period (around one month), symptoms directly resulting from the mTBI may have already subsided and not affected MRI success or quality. In future studies, the procedure should be applied in the acute phase post-injury to investigate whether acute post-concussive symptoms [START_REF] Dupont | Report of Early Childhood Traumatic Injury Observations & Symptoms: Preliminary Validation of an Observational Measure of Postconcussive Symptoms[END_REF] A little -N (%) 0 (0) 0 (0)

Between a little and a lot -N (%) 1 ( 9) 2 (11)

A lot -N (%) 3 ( 27

  (a) aged 36 to 71 months old at recruitment; (b) sufficient mastery of English or French to complete questionnaires (parents) or to understand the MRI familiarization (child); and (c) no MRI contraindications. The following exclusion criteria were applied to all participants: (a) any diagnosed congenital, neurological (other than the mTBI associated with inclusion in this study), developmental, psychiatric, or metabolic disorder; (b) less than 36 weeks of gestation; and (c) prior TBI (other than the mTBI associated with inclusion in this study) serious enough to warrant a visit to the ED of any hospital. The following additional exclusion criteria were applied to mTBI group: (a) hypoxia, hypotension, or shock during or following the injury; (b) administration of sedative medication; (c) surgical intervention following the injury; (d) nonaccidental/intentional injury. Diagnostic criteria for the mTBI group were: (a) ED presentation within 48 hours post-injury to one of the two recruitment sites, (b) documented, non-intentional, traumatic event (e.g. hit, fall, motor vehicle accident) resulting in a nonpenetrating injury, (c) age-appropriate Glasgow coma scale (GCS) score between 13 and 15,

MRI familiarization.

  Parents were provided with detailed information on MRI procedures via a pamphlet which included answers to the most frequently asked questions by children regarding the MRI. Parents and children were also provided two samples of MRI sounds prior to their appointment. The familiarization was provided just before the MRI acquisition by a trained research assistant using customized material as follows: (a) ask the child to choose a TV show/movie to watch during the image acquisition; (b) introduce the child to a puppet (also the main character of the cartoon story) and to a toy MRI; (c) read the puppet's cartoon story which incorporates the MRI procedures step-by-step. While reading the book, invite the child to interact with the puppet and the toy MRI. At the moments indicated in the story, introduce the child to the hospital gown worn during MRI acquisition and to the MRI sounds using headphones similar to the ones used in the MRI; (d) once the story completed, show pictures of children positioned in the MRI scanner and ask the child if they have any questions or concerns. Following this preparation, children were invited to wear the hospital gown. The pediatric MRI technician then welcomed them and made the child comfortable in the MRI. As per usual hospital procedures, the MRI technician showed the equipment to the child and explained what it was used for. During the acquisition, children were allowed to bring the puppet, a plush toy (if MRI-compatible) or a blanket with them. When present in the MRI room, the parent was provided earplugs and could either stay near their child touching their legs during the acquisition or stay seated near the door.

(

  logistic regression coefficient ()=1.39, p=.005, odds ratio (exp())=4.02, 95% CI [1.51 10.67]) and the MRI technician (=0.74, p=.02, exp()=2.10, 95% CI [1.12 3.94]), but not by the parent (=0.59, p=.10, exp()=1.81, 95% CI [0.90 3.64]). Parental concern significantly decreased the chance of success, with 0.21 times less chance of success per point of concern (=-1.56, p=.02, exp()=0.21, 95% CI [0.05 0.82]), but this was not the case for child concern about the MRI procedure (=-0.35, p=.34, exp(B)=0.70, 95% CI [0.35 1.44]). Older children were more likely to succeed the MRI protocol, with 3.11 times more chance of success per year of age (=0.73, p=.007, exp(B)=3.11, 95% CI [1.36 7.08]). Child sex was not associated with MRI success (=-0.58, p=.42, exp(B)=0.56, 95% CI [0.14 2.26]). Parental education and knowledge about the MRI were not significantly associated with MRI success (education: =0.02, p=.96, exp(B)=1.02, 95% CI [0.55 1.89]; knowledge: =0.14, p=.63, exp(B)=1.15, 95% CI [0.65 2.05]).

  affect

  children's ability to undergo MRI scanning.The following limitations need to be considered in interpreting the study results. First, given the study design and objectives, we cannot draw conclusions regarding the utility of the familiarization procedure compared to standard MRI acquisition with no behavioral preparation. Previous work has addressed this question in other groups of children[START_REF] Barkovich | Pediatric neuro MRI: tricks to minimize sedation[END_REF][START_REF] Copeland | Infant and Child MRI: A Review of Scanning Procedures[END_REF][START_REF] Thieba | Factors Associated With Successful MRI Scanning in Unsedated Young Children[END_REF][START_REF] Vannest | Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children[END_REF][START_REF] De Bie | Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans[END_REF],and future studies could document the efficacy of the familiarization compared to other forms of preparation in mTBI specifically. Second, our sample size was modest and larger studies are needed to further investigate the full range of mTBI-related factors that could impact MRI success and quality, such as post-concussive symptoms, time since injury, behavior problems, or parental concerns and anxiety. Future studies should document in more detail both qualitative signs of stress or anxiety as well as quantitative rates of perceived stress or anxiety. Based on the acquisition of good quality MRI images such as presented here, future work in larger samples should aim to investigate brain structure and functional outcomes following early mTBI.In conclusion, the present findings indicate that a brief behavioral-play familiarization allows acquisition of high-quality, non-sedated MRI in young children with mTBI with success rates comparable to those of non-injured peers. Such familiarization does not require a mock scanner (often expensive and unwieldy), nor highly specialized training or background knowledge. It is therefore easily applicable to different environments in both research and clinical settings and could possibly be extended to other pediatric clinical populations to acquire non-sedated MRI.

Figure 1 .

 1 Figure 1. Percentage of children completing each MRI sequence. Abbreviations: DWI,

Table 4 :

 4 Child experience -Comparisons between mild traumatric brain injury (mTBI) and typically developing children (TDC) groups

Table 1 :

 1 Number and percentage of children completing each MRI sequence. Abbreviations: DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; mTBI: mild traumatic brain injury; QSM, quantitative susceptibility mapping; SWI, susceptibilityweighted imaging; T1-w, T1-weighted anatomic MRI; T2-w, T2-weighted anatomic MRI. * Not included in the protocol of the 4 first participants. ** Not included in the protocol of the first participant.

		mTBI	TDC	Total
	Familiarization -n (%)	13 (100) 24 (100) 37 (100)
	No MRI -n (%)	2 (15)	5 (21)	7 (19)
	T1-w -n (%)	11 (85)	18 (75)	29 (78)
	QSM -n (%) Success	10 (77)	15 (63)	25 (68)
	DWI -n (%)	10 (77)	15 (63)	25 (68)
	SWI -n (%)	6 (46)	14 (58)	20 (54)
	T2-w -n (%)	7 (54)	12 (60)* 19 (57)*
	Rs-fMRI -n (%)	6 (46)	12 (52)** 18 (50)**
	Full MRI protocol -n (%)	5 (38)	13 (54)	18 (49)

Table 2 :

 2 Number and percentage of images rated "usable" based on visual inspection of each Abbreviations: DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; mTBI: mild traumatic brain injury; QSM, quantitative susceptibility mapping; SWI, susceptibilityweighted imaging; T1-w, T1-weighted anatomic MRI; T2-w, T2-weighted anatomic MRI.

	MRI sequence
		mTBI	TDC	Total
	T1-w -usable/collected (%)	11/11 (100) 18/18 (100)	29/29 (100)
	QSM -usable/collected (%)	9/10 (90)	14/15 (93)	23/25 (92)
	DWI -usable/collected (%)	10/10 (100)	14/15 (93)	24/25 (96)
	SWI -usable/collected (%)	5/6 (83)	12/14 (86)	17/20 (85)
	T2-w -usable/collected (%)	6/7 (86)	9/12 (75)	15/19 (79)
	Rs-fMRI -usable/collected (%)	6/6 (100) 12/12 (100)	18/18 (100)
	Total -usable/collected (%)	47/50 (94)	79/86 (92) 126/136 (93)

Acknowledgments

We would like to thank the Ste-Justine Hospital radiology team and MRI technologists, in particular Robert Trusilo, for their advice and support throughout the project. We also thank Hongfu Sun (University of Queensland) for her help processing the QSM data.

Funding

This project was funded by grants from the Ste-Justine Hospital Foundation (Défi Trauma) and the Canadian Institutes of Health Research to MHB. CT received a doctoral scholarship (261327) from the Fonds de recherche du Québec-Nature et technologies (FRQNT). FD received a postdoctoral scholarship (35982) from the Fonds de recherche du Québec-Santé (FRQS). MD and TML received salary awards from the FRQS.

Data Availability

Due to the nature of this research, participants of this study did not agree for their data to be shared publicly; therefore, supporting data are not available.

Declarations

Conflicts of interest None. 0.07 (0.39; 0.18) -0.003 (0.84; 0.66) Abbreviations: DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; mTBI: mild traumatic brain injury; QSM, quantitative susceptibility mapping; SWI, susceptibilityweighted imaging; T1-w, T1-weighted anatomic MRI; T2-w, T2-weighted anatomic MRI.

Online Supplementary Material

Parent MRI Report

Please fill out the questionnaire below in order to give us your opinion about the different steps of our study. Please use the scale (1 to 5) to answer the following questions.

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What was your knowledge about the MRI before participating in the study? 1 2 3 4 5 2.

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Did you talk about the MRI with your child before today? 1 2 3 4 5 4.

Are you worried about the MRI? 1 2 3 4 5 5.

Is your child worried about the MRI? 1 2 3 4 5 6.

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Child MRI Report

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Did you like the video? (Video chosen: _________________________________) 1 2 3 4 5 6.

Did you see the video well? No Yes 7.

Did you hear the video well? No Yes 8.

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Research Team MRI Report

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L Rolland

A Mainguy

S Boissier

Ki Zerbo

A Tardivel

M Sébillotte

M Cailleaux

S Patrat-Delon

M Revest

P Tattevin
email: pierre.tattevin@chu-rennes.fr.

M Ki Zerbo

A pilot project of expert nurses for the follow-up of complex intravenous antimicrobial treatment

Keywords: Antimicrobial resistance, Competency building, Nurses, Outpatient parenteral antimicrobial treatment, Task delegation

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The emergence of antimicrobial resistance (AMR) is one of the major challenges for human health, according to the World Health Organization [START_REF]Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis[END_REF]. Antimicrobial stewardship (AMS) has proven effective to optimize antibiotic use [START_REF] Davey | Interventions to improve antibiotic prescribing practices for hospital inpatients[END_REF] and to fight against AMR, but it requires funding and commitment from governments, the hospital administration, health care workers, patients, and the general population. Among health care workers, nurses may play a pivotal role, as they are at the frontline of patient care [START_REF] Zhu | Critical roles of nurses in rational use of antimicrobial agents through multidisciplinary collaboration[END_REF][START_REF] Hendy | Effect of educational intervention on nurses' perception and practice of antimicrobial stewardship programs[END_REF][START_REF] Weier | An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams[END_REF]. However, their role has been neglected in most AMS programs thus far [START_REF] Ierano | Opportunities for nurse involvement in surgical antimicrobial stewardship strategies: A qualitative study[END_REF][START_REF] Weier | An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams[END_REF].

During the years 2018 and 2019, we performed a 60-hour training on AMS dedicated to nurses who committed to specializing in this area, which led to the certification of 'expert nurses in antibiotics'. Within a pilot project funded by the French ministry of health, three of these expert nurses were appointed in 2020 to develop an hospital-based program under the supervision of two infectious diseases physicians, including: i) on-site nurse consultations for the follow-up of outpatient parenteral antimicrobial treatment (OPAT); ii) hotline on OPAT issues for nurses working in other hospitals in the area; iii) peer training on OPAT. We aimed to report the activities undertaken, the achievements, and the challenges met during the first year of this pilot project.

Methods

The Rennes University Hospital is an 1,800-bed tertiary care center in western France (population catchment area, 1 million inhabitants). This hospital coordinates a network of nine public hospitals. The grant awarded by the expert nurses was 100,000 euros, which covers the salary of one full-time nurse for two years, with a monthly supplement of 100 euros as compared to regular nurses' salary in France, to reward their personal commitment to the development of this expertise. The project's terms of references stated that their activities should contribute to better use of antibiotics within the whole hospital network. The continuation of their financial support will depend on a follow-up report including an overview of the main achievements after one year.

The programme started with the opening of dedicated nurse consultations (five half-days per week) in the outpatient department of the infectious diseases ward, under the supervision of an infectious disease physician, who would see the patient at the request of the nurse whenever she thought it necessary, according to a protocol validated by infectious diseases physicians, expert nurses, and the institution. The selection of patients eligible for a follow-up by OPAT-expert nurses was based on predefined criteria (Figure 1). The first consultation with the expert nurse took place after hospital discharge (to home or to another hospital). However, nurses were informed in advance and could collect information from medical charts before meeting the patient. The medical physician who referred the patient to expert nurses' follow-up could be contacted if need be. The list of investigations that could be prescribed by nurses was predefined in the protocol, including additional investigations potentially required in case of common adverse events (e.g., stool testing for Clostridioides difficile in case of severe or persistent diarrhea during antibacterial treatment). All patients had consultations with an infectious disease physician at least at the beginning, and at the end of the OPAT programme.

The one-year report included two main parts. First, an analytical report of consultations performed by expert nurses, with patients' characteristics, infection(s) targeted (sites, pathogens), antibacterial treatment (dose, duration, infusion mode), and outcomes, including adverse events (tolerability, treatment failure, unplanned hospital admission, death). Data were prospectively collected on a standardized questionnaire by the expert nurses (supplementary Table ). Second, we performed an audit of patients and infectious disease physicians. This audit was performed after one year using an online questionnaire with a representative sample of patients and their physicians. Qualitative data are reported as numbers (%), quantitative data as medians [interquartile range]. Due to the exploratory design and limited sample size, no statistical test was performed. This study was approved by the Rennes University Hospital institutional review board.

Results

Between December 1, 2020 and December 31, 2021, 121 patients were managed by one of the three OPAT-expert nurses, for a total number of 621 consultations (mean, 5.3 nurse consultations per patient). Three patients were excluded (lost to follow-up). Twenty-two selected patients fulfilled the questionnaire: 21 (95%) stated that they greatly appreciated the opportunity to be followed by expert nurses during their OPAT. Direct patients-nurses interaction, nurses' professionalism, and the opportunity to receive regular follow-up by an expert health care worker while being at home were the three most appreciated items. Ten selected physicians in charge of patients enrolled in this program fulfilled the questionnaire, with 100% rate of satisfaction: they particularly appreciated that the nurses requested their intervention appropriately (at the right time, when necessary), and that the implementation of nurses' consultations could save time for them, so that they could spend more time on their other duties.

Discussion

We report on the first year of an innovative project aimed to increase the participation of nurses for better use of antibiotics. The main findings of this one-year follow-up are that, at a moderate cost, expert nurses could be increasingly involved in the follow-up of OPAT, with multiple secondary benefits, including: i) patients' safety and satisfaction; ii) decreased workload for physicians in charge, while preserving quality of care. Recent years have demonstrated that shortage of medical physicians is a major issue worldwide, affecting highincome as well as low-and middle-income countries. This has promoted effort to transfer part of medical activities to other health care workers, which has been repeatedly successful [START_REF] Rout | Guidelines for the hospital role of the clinical nurse in antimicrobial stewardship: A scoping review[END_REF][START_REF] Schmid | Interprofessional Collaboration between ICU Physicians, Staff Nurses, and Hospital Pharmacists Optimizes Antimicrobial Treatment and Improves Quality of Care and Economic Outcome[END_REF][START_REF] Sakaguchi | The roles of bedside nurses in Japan in antimicrobial stewardship[END_REF]. This transfer of competency should only be implemented with a rigorous plan, including selection and training of health care workers who will take over the activity, with a clear definition of their tasks, a well-defined roadmap, and regular evaluation of outcomes [START_REF] Essilini | Community pharmacists' views on their current role and future opportunities for antibiotic stewardship: a French qualitative study[END_REF]. In parallel, effort to increase the number and competencies of nurses is of utmost importance, as shortage of staff affects nurses as well as many other health care worker categories. The transfer of activities from medical physicians to nurses should come with an ambitious programme to increase the number of nurses, and to develop their skills to endorse additional activities, such as OPAT follow-up.

In France as in many other countries, nurses cannot prescribe antibiotics. This may be one of the reasons why their participation in AMS programs have been limited so far, despite them being primary actors of patient care, especially in hospital settings [START_REF] Ierano | Opportunities for nurse involvement in surgical antimicrobial stewardship strategies: A qualitative study[END_REF]. Their potential role in the fight against AMR should be reinforced, and may include patient education, as well as empowerment to be more involved in the follow-up of patients during complex antibacterial treatments [START_REF] Klemmer | Description of nurse practitioner functioning as most responsible provider in an intravenous therapy clinic[END_REF]. We hope that this report of our pilot project will encourage colleagues from other sites to engage in more innovative projects.

This one-year report of a pilot project has limitations. First, as it was developed in a university hospital, our findings and the lessons learnt cannot potentially be generalized to other sites. Second, as a pilot project, it only included a limited number of patients, and could only audit a limited number of physicians. Third, the programme was started in 2020 while the COVID-19 pandemic had a dramatic impact on hospitals worldwide. We collectively decided to start the programme despite this dreadful situation, but it may have been easier

(and results may have been more convincing) to postpone the launch after the COVID-19.

However, the fight against AMR is a public health issue, which should not be postponed. Our project of expert nurses for the follow-up of complex intravenous antimicrobial treatment is essential, as it increases participation of a major category of health care workers. We advocate that their skills (in terms of patient education, quality of care, and commitment) will be an asset in the fight against AMR. e-mail : pierre.tattevin@chu-rennes.fr

Contribution of authors

Laetitia Rolland, Anne Mainguy and Sophie Boissier contributed to the project design, followed-up the patients, collected data, and critically reviewed the manuscript.

Figure 1 .

 1 Figure 1. Enrolment of patients and follow-up

2 1

 2 data are presented as medians [interquartile range], qualitative data as numbers (%) A pilot project of expert nurses for the follow-up of complex intravenous antimicrobial treatment L Rolland 1 , A Mainguy 1 , S Boissier 1 , M Ki Zerbo 1 , A Tardivel 1 , M Sébillotte 1 , M Cailleaux 1 , S Patrat-Delon 1 , M Revest 1,2 , P Tattevin 1,Infectious diseases and intensive care unit, Pontchaillou University Hospital, Rennes, France 2 INSERM U1230, IFR140, Rennes 1 University, Rennes, France. Corresponding author: Pr Pierre Tattevin, M.D., Ph.D. Infectious diseases and intensive care unit, CHU de Rennes, Univ Rennes, INSERM U1230, IFR140, F-35033, Rennes, France.

Table 1

 1 ) or obstruction (n=7), with an estimated incidence of 2.2 local infections and 0.8 catheter obstructions per 1,000 catheter-days. No bacteremia or vascular thrombosis was reported. Eleven patients (9%) required unplanned hospital admissions during follow-up, due to adverse events of OPAT in four cases. Three patients experienced treatment failure that required another course of antibacterial treatment, and no patient died.

	Most patients (n=106, 90%) received their intravenous antibacterial treatment through a
	peripherally-inserted central catheter (PICC). The main infections targeted were bone and
	joint (n=76, 64%) and cardiovascular (n=16, 14%) infections, due to Gram-positive (n=74, 63%),
	or Gram-negative (n=13, 11%) bacteria. The median duration of management by expert nurses

details the characteristics of the 118 patients enrolled: median age was 66.5 years [52-75], and maleto-female ratio was 2.5. By the time of the first nurse consultation, most patients (n=98, 83%) had returned home, while others were either in a rehabilitation center (n=13), in another hospital (n=6), or a long-term care facility (n=1). was 29 days

. Early removal of PICC line was necessary in 21 cases (16 patients), after a median duration of 26 days post-catheter insertion [13-39], mostly due to suspected infection (n=11

Table 1 .

 1 Characteristics of patients followed up during expert nurse consultations

	Characteristics of patients	Total population	Ambulatory care
		n=118 (100 %)	n=98 (83%)
	Age, years	66.5 [52-75]	64 [51-73]
	Male-to-female sex ratio	2.5	2.7
	Infection characteristics
	-Bone and joint infections	76 (64%)	62 (63%)
	-Infective endocarditis	16 (14%)	11 (11%)
	-Abdominal or urinary trat infections	6 (5%)	6 (6%)
	-Skin and soft tissue infections	3 (3%)	3 (3%)
	-Neurological infections	4 (3%)	4 (4%)
	-Vascular infections	4 (3%)	3 (3%)
	-Other	9 (8%)	9 (9%)
	Microbiological characteristics
	-Gram-positive bacteria	74 (63%)	55 (55%)
	Staphylococcus aureus	16 (14%)	9 (9%)
	Coagulase-negative staphylococci	13 (11%)	10 (10%)
	(CoNS)
	Streptococcus sp.	19 (16%)	14 (15%)
	Enterococcus sp.	9 (8%)	8 (8%)
	Other	17 (%)	14 (15%)
	-Gram-negative bacteria	13 (11%)	13 (13%)
	Enterobacteriaceae	5 (4%)	5 (5%)
	Pseudomonas aeruginosa	6 (5%)	6 (6%)
	Other	2 (2%)	2 (2%)
	-polymicrobial	24 (20%)	23 (24%)
	-other	4 (3%)	4 (3%)
	Type of vascular access
	-peripherally-inserted central catheter	106 (90%)	89 (90%)
	-midline catheter	7 (6%)	5 (5%)
	-tunneled catheter	1	1
	-subcutaneous venous access device	1	1
	-peripheral venous catheter	1	0
	Vascular access complications, n	Not available	16 (16%)
	-bacteremia		0
	-vascular thrombosis		0
	-hospitalization		1
	-catheter obstruction		4
	-local infection		11
	-mechanical complication		5
	Outcome at the end of nurse follow-up		-
	-death	0
	-relapse	3 (3%)
	-cure or remission	115 (97%)
	Expert nurse follow-up
	-duration, days	29 [22-57]
	-consultations, n	621
	on-site	488 (79%)

Muriel Ki Zerbo and Anne Tardivel contributed to the project design, research for fundings, and critically reviewed the manuscript.

Marine Sébillotte and Marine Cailleaux contributed to patients' follow-up, study analysis, and critically reviewed the manuscript.

Solène Patrat-Delon and Matthieu Revest coordinated the project, wrote the first draft of the study design, obtained the funding, contributed to patients' follow-up, performed the analysis, and critically reviewed the manuscript.

Pierre Tattevin participated in the project design, patients' follow-up, the analysis, and wrote the first draft of the manuscript.

Funding. This project was funded by a grant from the Direction Générale de l'Offre de Soins (DGOS/GHT/2019/194) Acknowledgements. We would like to thank the patients who participated in the study, the health care workers who contributed to the project, our hospital administration for their support, and the health regional agency.

This work has been presented at the XXII Journées Nationales d'Infectiologie (JNI Bordeaux,

France, 2022), and has been awarded the 'Prix du Meilleur Poster Infirmier'. Keywords. Nurses; outpatient parenteral antimicrobial treatment; antimicrobial resistance; competency building; task delegation

Conflicts of Interest. All authors, none.

Highlights

 Nurses can be precious allies in the fight against antimicrobial resistance.

 In a pilot project, three expert nurses were trained for complex antimicrobial treatment follow-up.

 At one year, they performed 621 consultations, mostly (64%) for bone and joint infections.

 No severe adverse event related to the programme was reported.

 Patients, infectious diseases physicians, and expert nurses reported high-level of satisfaction.

ABSTRACT

Objective. To report a pilot project of expert nurses for outpatient parenteral antimicrobial treatment (OPAT) follow-up.

Methods. Three nurses with specific training on antibiotics started a state-funded programme including: i) consultations for OPAT follow-up; ii) hotline for satellite hospitals; iii) peer training. Patients' data were prospectively collected. A representative sample of patients and physicians was interviewed to learn about their opinion on the project.

Results.

From December 2020 to December 2021, 118 patients (median age 66.5 years [52-75], male-to-female ratio 2.5) were enrolled, for a total of 621 consultations. Patients were mostly on OPAT for bone and joint infections (n=76, 64%) and cardiovascular infections (n=16, 14%), for a median duration of 29 days . Eleven patients (9%) required unplanned hospital admissions, and three experienced treatment failure. Most patients (21/22) and physicians in charge (10/10) reported a high level of satisfaction.

Conclusions. Nurses may be important actors for OPAT follow-up.


Jordan Letessier

Aïmen E Gheribi

Jean-Mathieu Vanson
email: jean-mathieu.vanson@cea.fr

Christelle Duguay

Fabrice Rigollet

Jérôme Vicente

Jean-Laurent Gardarein
email: jean-laurent.gardarein@univ-amu.fr

Influence of particle properties on the thermal conductivity of an alumina packed bed α-Al2O3

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

b

effusivité effective, W.K -1 .m -2 .s 1/2 Cp chaleur spécifique, J.K -

Introduction

Lors d'un accident de perte de réfrigérant primaire (APRP) dans les centrales nucléaires à eau pressurisée, le combustible nucléaire peut se fragmenter et se relocaliser dans sa gaine, et les propriétés thermiques de l'ensemble s'en trouvent dégradées. Afin de comprendre les mécanismes de transferts de chaleur dans ces milieux, on a recours à l'utilisation de matériaux modèles, car les mesures en milieu nucléarisé sont très coûteuses. L'alumine fait partie des matériaux modèles couramment utilisés pour simuler le dioxyde d'uranium. D'une manière générale, l'étude des propriétés thermiques des céramiques comme l'alumine est très largement abordée dans la littérature. En effet, leur propriétés mécaniques et thermiques sont intéressantes, ils sont à la fois résistants à la chaleur, et isolants thermiquement. Leur utilisation est donc très appropriée dans le domaine des matériaux réfractaires, ou dans le stockage d'énergie thermique à haute température. Dans notre contexte, nous nous intéressons particulièrement, à l'étude de la conductivité thermique de lits de poudres d'alumine dans l'air à pression ambiante. Différentes publications traitent de l'étude des propriétés thermiques de l'alumine solide sous différentes formes, solide compact, solide poreux et ultraporeux [START_REF] Francl | Thermal conductivity: IX, experimental investigation of effect of porosity on thermal conductivity[END_REF]- [START_REF] Smith | Thermal conductivity of porous materials[END_REF], mais les études de l'alumine sous forme de poudres sont presque inexistantes ou très peu détaillées [START_REF] Laubitz | Thermal conductivity of powders[END_REF]- [START_REF] Van Norman | Using atomic layer deposited tungsten to increase thermal conductivity of a packed bed[END_REF]. Notre étude vise à observer l'influence de deux paramètres sur la conductivité thermique effective d'un lit de poudre d'alumine α-Al2O3. D'une part, nous étudierons l'influence de la taille des grains sur la conductivité thermique effective du milieu, et d'autre part l'influence de la forme des grains, avec des grains de formes sphériques pleins puis des grains de forme sphérique, et creux. Les différences entre ces deux formes de grains sont observées grâce à une mesure au micro-tomographe à rayons X (μ-tomo X) et au microscope à balayage électronique (MEB). Les mesures de notre étude étant faites à température ambiante, et la taille des pores des poudres utilisées étant suffisamment petite, nous négligerons les transferts thermiques par rayonnement et par convection. Nous considérerons uniquement les transferts thermiques par conduction dans les phases solide et gazeuse. Un modèle de conductivité thermique pour les poudres a été développé, et est présenté. Les résultats sont confrontés aux mesures de conductivités effectives réalisées avec un banc expérimental de type « plan chaud ».

Procédures expérimentales

Estimation de la conductivité thermique effective

Les mesures des propriétés thermophysiques des échantillons de poudres d'alumine sont réalisées à l'aide d'un dispositif expérimental, développé par le laboratoire IUSTI, qui repose sur la méthode du plan chaud avec mesure de température sur les deux faces de l'échantillon [START_REF] Maillet | Analysis of the estimation error in a parsimonious temperature-temperature characterization technique[END_REF] (Figure 1). La méthode est transitoire, un flux de chaleur est imposé en face avant de l'échantillon pendant un certain temps (typiquement 2 min) et les mesures sont enregistrées pendant environ 10 minutes. Le plan chaud est alimenté par un générateur de courant continu, avec une tension d'environ 20 V et un courant d'environ 0,7 A. Afin de s'affranchir de la forme temporelle exacte de ce flux entrant en face avant, nous y mesurons la température au cours du temps, conséquence de ce flux imposé et des échanges conductifs qui ont lieu majoritairement vers l'échantillon. C'est cette évolution de température enregistrée en face avant qui servira d'excitation en entrée du modèle [START_REF] Slavin | Theoretical model for the thermal conductivity of a packed bed of solid spheroids in the presence of a static gas, with no adjustable parameters except at low pressure and temperature[END_REF]. L'utilisation de graisse thermique entre le plan où se trouvent les thermocouples et les semelles, permet de limiter la résistance thermique de contact. Un isolant fibreux est disposé tout autour du dispositif pour favoriser un transfert 1D entre les deux faces. Les 3 thermogrammes mesurés en face avant et arrière permettent de s'assurer de l'uniformité des températures sur chaque face. Une fois cette vérification établie, c'est le thermogramme mesuré par le thermocouple central qui est injecté dans le modèle. L'écart type du bruit de mesure est environ égal à 0,01°C pour un échauffement de 2 °C. Nous modélisons le lit de poudre comme un milieu homogène posé sur un milieu semi-infini en face arrière. En utilisant le formalisme des quadripôles thermiques [START_REF] Maillet | Analysis of the estimation error in a parsimonious temperature-temperature characterization technique[END_REF] pour relier, dans l'espace de Laplace, les échauffements et les flux entre la face avant (𝜃 ̅ (0, 𝑝 𝐿𝑝 ), 𝜑 ̅(0, 𝑝 𝐿𝑝 )) et la face arrière (𝜃 ̅ (𝑒 + 2𝑠, 𝑝 𝐿𝑝 ), 𝜑 ̅(𝑒 + 2𝑠, 𝑝 𝐿𝑝 )), l'équation du modèle thermique du problème peut s'écrire :

( 𝜃 ̅ (0,𝑝 𝐿𝑝 ) 𝜑 ̅ (0,𝑝 𝐿𝑝 ) ) = 𝐵𝐶𝐵 ( 𝜃 ̅ (𝑒+2𝑒 𝑠 ,𝑝 𝐿𝑝 ) 𝜑 ̅ (𝑒+2𝑒 𝑠 ,𝑝 𝐿𝑝 )
)

(1)

𝐵 = ( 1 0 𝑥 4 𝑝 𝐿𝑝 1 ) , avec 𝑥 4 = 𝜌 𝑠 𝐶 𝑝,𝑠 𝑒 𝑠 (2) 𝐶 = ( cosh ( √ 𝑥 1 𝑝 𝐿𝑝 ) sinh ( √ 𝑥 1 𝑝 𝐿𝑝 ) 𝑥 2√ 𝑝 𝐿𝑝 𝑥 2√ 𝑝 𝐿𝑝 sinh ( √ 𝑥 1 𝑝 𝐿𝑝 ) cosh ( √ 𝑥 1 𝑝 𝐿𝑝 ) ) , avec 𝑥 1 = 𝑒 2 𝛼 , 𝑥 2 = 𝑏 (3)
En développant l'équation (1) et en l'appliquant pour un échauffement de Laplace unitaire en face avant 𝜃 ̅ (0, 𝑝) = 1, l'échauffement de Laplace obtenu en face arrière 𝜃 ̅ (𝑒 + 2𝑒 𝑠 , 𝑝 𝐿𝑝 ) correspond à la transmittance du système :

𝜃 ̅ (𝑒 + 2𝑒 𝑠 , 𝑝 𝐿𝑝 ) = [cosh( √ 𝑥 1 𝑝 𝐿𝑝 ) + ( 𝑥 4 𝑥 2 √ 𝑝 𝐿𝑝 + 𝑥 3 𝑥 2 ) sinh( √ 𝑥 1 𝑝 𝐿𝑝 )] -1 (5)
𝜃 𝑚𝑜𝑑 (𝑒 + 2𝑒 𝑠 , 𝑡) = 𝓛 -1 {𝜃 ̅ (𝑒 + 2𝑒 𝑠 , 𝑝 𝐿𝑝 )} ⨂ 𝜃 𝑚𝑒𝑠 (0, 𝑡)

Sa transformée inverse de Laplace (effectuée avec l'algorithme de De Hoog [START_REF] De Hoog | An improved method for numerical inversion of Laplace transforms[END_REF]) fournit alors la réponse impulsionnelle modélisée du système en échauffement, en fonction du temps. L'échauffement modélisé en face arrière en fonction du temps 𝜃 𝑚𝑜𝑑 (𝑒 + 2𝑒 𝑠 , 𝑡), est alors Pour chaque paramètre estimé, une incertitude est calculée, elle correspond à l'addition de l'erreur due au bruit de mesure et à l'erreur due à la propagation des incertitudes des paramètres fixes supposés connus, qui est estimée à 10%. On constate que l'incertitude globale pour un paramètre correspond essentiellement à la propagation des incertitudes des paramètres fixes.

Mesure par micro tomographie à rayons X

Des mesures au micro tomographe à rayons X (Figure 2) ont été effectuées dans le but d'observer les différences géométriques et structurales, entre deux échantillons. Les deux échantillons sont positionnés l'un sur l'autre dans un tube de 3,3 cm de diamètre et sont séparés par une feuille de papier. L'image 3D après traitement est recadrée pour chaque échantillon sur une volume élémentaire représentatif égale à 500 × 500 × 500 voxels, pour une largeur de voxel égale à 1,5 m. La Figure 3 est un exemple d'une image tomographique obtenue dans une coupe de l'échantillon r1.

Modèle de conduction

L'écart de conductivité thermique, à porosités égales entre un milieu poreux connecté comme une mousse et non connecté comme un lit de poudre, peut varier d'un ou plusieurs ordres de grandeur. Les caractéristiques microstructurales, sont donc des éléments importants à prendre en compte. Par exemple, le ratio entre la conductivité thermique d'une mousse d'alumine [START_REF] Sciamanna | Mechanical properties and thermal conductivity of porous alumina ceramics obtained from particle stabilized foams[END_REF] et nos mesures sur une poudre, est d'au moins 25. Afin d'expliquer cet écart, nous avons développé un modèle qui prend en compte les propriétés de la poudre à une échelle microscopique (la conductivité thermique du monocristal), mésoscopique (par la porosité intragranulaire) et macroscopique (porosité inter-granulaire). Contrairement aux modèles habituels de conductivités thermiques dans les milieux poreux, qui sont souvent déduits de la description des transferts thermiques sur une géométrie très simplifiée de la microstructure, ou qui se basent sur la théorie des milieux effectifs donnant des résultats parfois à plusieurs ordres de grandeur de la mesure, notre modèle repose sur la théorie de la percolation [START_REF] Gheribi | Evidence of second order transition induced by the porosity in the thermal conductivity of sintered metals[END_REF], [START_REF] Gheribi | Experimental study of the thermal conductivity of sintered tungsten: Evidence of a critical behaviour with porosity[END_REF]. L'expression de la conductivité effective écrite avec notre modèle est la suivante :

λ 𝑒,𝑚𝑜𝑑 = λ 𝑐𝑟 × 𝑔(𝑑 𝑐𝑟 ) × (1 -𝑝 𝑎 ) ⏟ λ 𝑔 × (1 -𝑝 𝑟 ) × 𝑓 𝑐 (𝑝 𝑐 , 𝑝 𝑟 ) + 𝑝 × λ 𝑎𝑖𝑟 (7)
e,mod, cr, g, air, représentent respectivement la conductivité thermique effective du lit de poudre, du monocristal, du grain et de l'air. dcr correspond à la taille caractéristique d'un monocristal composant le grain. p, pa, pr, pc, sont respectivement la porosité effective, intragranulaire, inter-granulaire et critique. La porosité critique est la porosité à partir de laquelle la connectivité des grains s'effondre, il s'agit du seuil de percolation thermique. Dans le cas de nos échantillons et de leur microstructure nous avons choisi de bloquer ce paramètre à pc = 0,16. Cette valeur correspond au seuil de percolation pour un arrangement de sphères en cubique centrée, avec la prise en compte des premiers et seconds voisins [START_REF] Jerauld | Percolation and conduction on the 3D Voronoi and regular networks: a second case study in topological disorder[END_REF]. Les facteurs (1 -𝑝 𝑎 ) et (1 -𝑝 𝑟 ) correspondent à la pondération du transfert thermique passant par la phase solide. La relation qui relie la porosité effective p à pa et pr est la suivante :

(1 -𝑝) = (1 -𝑝 𝑎 )(1 -𝑝 𝑟 ) (8)
La fonction fc, nous donne le facteur de réduction de la conductivité thermique dans la phase solide et provient directement de la théorie de la percolation. La conductivité du cristal pure d'α-alumine est considérée comme étant égale à cr = 36,6 W/(mK) à 293 K. Cette valeur est purement théorique [START_REF] Gheribi | Application of the CALPHAD method to predict the thermal conductivity in dielectric and semiconductor crystals[END_REF]. Pour avoir la conductivité d'un grain de poudre, il faut connaitre la taille des monocristaux qui composent les grains. En effet, plus la taille de ces cristaux est petite, plus il y a des joints entre ces cristaux, cela augmente la résistance thermique et diminue la conductivité globale d'un grain de poudre. La fonction g nous permet de calculer la réduction de la conductivité pour la phase solide d'un grain en fonction de la taille des monocristaux [START_REF] Gheribi | Effect of Grain Boundaries on the Lattice Thermal Transport Properties of Insulating Materials: A Predictive Model[END_REF]. Dans le cas de l'α-alumine cette fonction s'écrit :

𝑔(𝑑 𝑐𝑟 ) = 1 -𝑐 tan -1 (1/𝑐) , avec 𝑐 = √8,05 × 10 -9 /𝑑 𝑐𝑟 (9)
L'équation du modèle [START_REF] Van Norman | Using atomic layer deposited tungsten to increase thermal conductivity of a packed bed[END_REF] peut-être raffinée selon l'échantillon étudié en modifiant les paramètres microstructuraux, pour prendre en compte par exemple la distribution de taille des pores, ou des grains. De plus, notre modèle est écrit pour l'étude d'une poudre pure, dans le cas d'une poudre hétérogène, il conviendrait de rajouter un terme pour la composition des phases de type EMT, par exemple. En se servant d'un modèle classique comme celui de Aivazov et Domashnev, on arrive à prédire environ 93% de la dégradation de la conductivité thermique de notre échantillon comparée à la valeur de conductivité du cristal pur λ 𝑐𝑟 [START_REF] Aivazov | Influence of porosity on the conductivity of hot-pressed titanium-nitride specimens[END_REF], [START_REF] Rhee | Porosity-Thermal conductivity correlations for ceramic materials[END_REF]. Avec notre modèle nous arrivons à prévoir 99,7% de la dégradation, ce qui est nettement meilleur.

Aivazov et Domashnev

Notre modèle

Expression des modèles λ 𝐴𝐷 = 1 -𝑝 1 -8𝑝 2 λ 𝑐𝑟 λ 𝑒,𝑚𝑜𝑑 [START_REF] Van Norman | Using atomic layer deposited tungsten to increase thermal conductivity of a packed bed[END_REF] Prédiction de la dégradation de la conductivité thermique (λ 𝑐𝑟 -λ 𝑚𝑜𝑑 )/(λ 𝑐𝑟 -λ 𝑚𝑒𝑠 ) ~93% ~99,7%

Conclusion

L'étude de la conductivité thermique de poudres d'alumine nous a permis de relever des paramètres microscopiques, mésoscopiques et macroscopiques importants pour le transfert de chaleur dans les milieux poreux non connectés. La conductivité d'un grain d'une poudre ne peut pas être approximée par celle du cristal pur. Les cristaux qui composent les grains ont des joints entre eux qui ajoutent de la résistance thermique, la conductivité globale du grain diminue alors lorsque leur nombre augmente. La porosité intra-granulaire est un paramètre mésoscopique qui réduit la conduction effective d'un grain. Les paramètres les plus impactant sont l'arrangement des grains entre eux et la porosité inter-granulaire. Ce sont ces paramètres, qui selon la théorie de la percolation, réduisent la conductivité thermique totale du milieu. En effet, si la porosité inter-granulaire dépasse le seuil de percolation, on a un effondrement de la conductivité thermique effective du milieu. Avec la connaissance de la porosité inter-granulaire de deux échantillons de poudres d'alumine, nous avons réussi à prédire 99,7% de la dégradation de la conductivité thermique comparée au cristal pur.

Figure 1 :

 1 Figure 1 : Schéma du dispositif expérimental La matrice B représente une semelle de cuivre. Son épaisseur faible et sa conductivité importante, permettent de la modéliser par une couche purement capacitive. La matrice C quant à elle, représente le lit de poudre comme un matériau homogène équivalent d'épaisseur 𝑒, de diffusivité 𝛼 et d'effusivité 𝑏. La condition limite sur le bloc de PVC, supposé semi-infini (temps caractéristique de diffusion 𝑡 𝑑𝑖𝑓𝑓,𝑃𝑉𝐶 ≈ 10 4 s pour un temps de mesure d'environ 800 s), permet de relier le flux et l'échauffement en face arrière par : 𝜑 ̅(𝑒 + 2𝑒 𝑠 , 𝑝 𝐿𝑝 ) = 𝑥 3 √ 𝑝 𝐿𝑝 𝜃 ̅ (𝑒 + 2𝑒 𝑠 , 𝑝 𝐿𝑝 ) , avec 𝑥 3 = 𝑏 𝑃𝑉𝐶 (4)

  Plan chaud (180mm x 120 mm) Semelles de cuivre (épaisseur 1 mm) Isolant (époxy, fibre de verre) Support PVC (Épaisseur 10cm, supposé semi-infini) Isolant fibreux Thermocouples type K (Ø = 0,25 mm) Echantillon de poudre d'alumine (épaisseur du lit 10 mm)

Figure 2 :

 2 Figure 2 : Photo du canon du tomographe, du tube contenant l'alumine, du porte échantillon

Figure 3 :

 3 Figure 3 : Image tomographique d'une coupe de l'échantillon r1 (0,75mm de côté), avant (à gauche) et après (à droite) le traitement de séparation de la phase solide et de la phase fluide.

Figure 1 :

 1 Figure 1 : Conductivités thermiques mesurées et prédites par notre modèle en fonction de la taille moyenne des grains, les valeurs à côté des losanges correspondent aux valeurs de porosités intergranulaires utilisées pour le calcul du modèle

Figure 5 :

 5 Figure 5 : Images MEB de deux grains appartenant aux deux types de poudres étudiées, pour les correspondances des indices c5, r1 voir tableau 2

  calculé par convolution temporelle (notée ⨂) entre cette réponse impulsionnelle et le thermogramme mesuré en face avant. Dans l'équation[START_REF] Laubitz | Thermal conductivity of powders[END_REF], on peut voir que la transmittance modèle du système ne dépend que de 4 paramètres : x1 et x2 sont respectivement le temps diffusif apparent et l'effusivité équivalente du lit de particules, x3 est l'effusivité du bloc de PVC et x4 est la capacitance surfacique d'une semelle de cuivre. Voici un ordre de grandeur pour les valeurs de ces paramètres, 𝑥 1 ≈ 500 s, 𝑥 2 ≈ 400 Jm -2 K -1 s -1/2 , 𝑥 3 ≈ 518 Jm -2 K -1 s -1/2 , 𝑥 4 ≈ 3400 J K -1 m -2 . Une étude de sensibilité montre que la capacitance surfacique des semelles x4 est un paramètre peu sensible du modèle, il sera donc fixé à sa valeur nominale. De plus, l'effusivité du porte-échantillon arrière en PVC a été mesurée par ailleurs, elle sera donc également fixée. Il reste donc seulement les deux paramètres x1 et x2 à estimer. La résolution du problème par méthode inverse consiste à minimiser l'écart entre les échauffements mesurés 𝜃 𝑚𝑒𝑠 (𝑒 + 2𝑒 𝑠 , 𝑡) et modélisés 𝜃 𝑚𝑜𝑑 (𝑒 + 2𝑒 𝑠 , 𝑡) en face arrière, en ajustant x1 et x2. Pour minimiser cet écart, nous utilisons l'algorithme de Gauss-Newton. Les valeurs de x1 et x2 obtenues après minimisation, nous donnent 𝛼 et b, nous en déduisons la conductivité équivalente du lit 𝜆 = 𝑥 2 √

	𝑒 2 𝑥 1	= 𝑏√𝛼.

Influence de la taille des grains

  Afin d'observer l'influence de la taille des grains, nous avons étudié 5 échantillons de poudres (Tableau 2), dont la taille médiane varie entre 1,35 μm et 65,8 μm. Ces échantillons proviennent du même fournisseur et sont issus du même procédé de fabrication. La porosité effective est un paramètre qui influe significativement sur la conductivité thermique effective d'un lit de poudre. Pour les échantillons c2, c3, c4, c5, elle est fixe et environ égale à 66%. Nous considérons aussi le diamètre des cristaux qui composent les grains, fixe et égal à 0,1 μm (estimation faite au MEB). Les mesures des diamètres médians d50, sont réalisées avec un granulomètre laser en voie humide. Le paramètre d50 correspond à la valeur médiane de la distribution des tailles de grains pondérées en volume. La masse m est mesurée avec une balance avant d'insérer l'échantillon dans l'enceinte. La porosité effective du lit p, est calculée comme suit :Les mesures de conductivité thermique nous montrent (Figure4) que pour une diminution de taille de grains médian de 65,8 à 4,93 μm, la conductivité thermique est divisée par 2,5. Il semblerait donc que la conductivité thermique d'un même type de poudre décroisse avec la taille médiane des grains. En réalité, c'est l'incertitude sur la valeur de la porosité intergranulaire qui explique cette différence. La Figure4, compare les mesures aux valeurs prédites par notre modèle. La porosité inter-granulaire est une donnée que nous avons mesurée au microtomographe pour les deux échantillons c5 et r1 de la Figure4. Les losanges bleus et magentas

	Tableau 1 : Comparaison des capacités prédictives de la dégradation de la conductivité thermique
		entre notre modèle et celui de Aivazov et Domashnev
	4. Résultats
	4.1. 𝑝 = 1 -	𝜌 𝜌 𝑐𝑟	avec 𝜌 = 𝑚/𝑉 la densité effective de l'échantillon	(10)
		n° Diamètre médian	Diamètre	Porosité effective	Porosité inter-	Epaisseur du
			des grains de	des cristaux : dcr	p	granulaire	lit : e
			poudre : d50
			μm		μm	%	%	mm
	Grain sphérique creux	c1 1,35 c2 4,93		83,4 64,5	non mesurée 10,0±0,5 non mesurée
		c3 23,3	0,1	66,1	non mesurée
		c4 44,8	0,1	66	non mesurée
		c5 65,8	0,1	66,6	40,5%
	Grain sphérique plein r1 56,4	0,1	70	37%	10,0±0,5
				Tableau 2 : Propriétés des lits de poudres

correspondent aux valeur prédites par notre modèle en connaissant la porosité pr. En connaissant cette donnée microstructurale, nous expliquons l'écart entre r1 et c5 mais aussi pour tous les autres points. Dans le cas de r1 et c5, le modèle donne des valeurs très proches de la barre d'erreur de la mesure. La Figure

4

montre la grande sensibilité de notre modèle, et de la conductivité thermique d'une poudre, à la porosité inter-granulaire. Nous pouvons ajouter que le choix des paramètres fixés dans l'élaboration du modèle (par exemple pc) est discutable et ajustable en fonction de la configuration du cas étudié.