Thibaut ; Faller

PhD Aurélien J Trotier

MS Alice F Rousseau

PhD Jean-Michel Franconi

PhD Sylvain Miraux

PhD Emeline J Ribot
email: ribot@rmsb.u-bordeaux.fr

Thibaut ; Faller

MS Thibaut L Faller

Multi-Slice MP2RAGE sequence for fast T1 mapping at 7T

Keywords: MP2RAGE, 2D Multi-slice, T1 mapping, mouse, Thermometry, 7T MP2RAGE, 2D Multi-slice, T1 mapping, mouse, Thermometry, 7T Magnetic Resonance in Medicine

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

Introduction

The Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence was initially developed for 3D acquisitions [START_REF] Marques | MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1mapping at high field[END_REF]. It has been used for brain T 1 mapping in humans (1-3) and small-animals [START_REF] Trotier | Compressed-Sensing MP2RAGE sequence: Application to the detection of brain metastases in mice at 7T[END_REF][START_REF] Driencourt | T1 mapping of the mouse brain following fractionated manganese administration using MP2RAGE[END_REF], at 3T and 7T. Its combination with Compressed Sensing [START_REF] Trotier | Compressed-Sensing MP2RAGE sequence: Application to the detection of brain metastases in mice at 7T[END_REF] or Echo Planar (EPI) encoding has enabled faster acquisitions for instance whole human brain mapping in approximately 3 min [START_REF] Van Der Zwaag | Distortion-matched T1 maps and unbiased T1-weighted images as anatomical reference for high-resolution fMRI[END_REF]. In parallel, its implementation with radial encoding has been used for mouse abdominal T 1 maps, with high robustness to motion and to acceleration using under-sampling [START_REF] Faller | Radial MP2RAGE sequence for rapid 3D T1 mapping of mouse abdomen: application to hepatic metastases[END_REF]. Nevertheless, because of its 3D encoding, the acquisition time is still too long for routine use.

To date, 2D encoding remains the reference method for fast and ultra-fast imaging. It has also regained interest since the development of Simultaneous Multi-Slice technique [START_REF] Barth | Simultaneous multislice (SMS) imaging techniques[END_REF].

For parametric T 1 mapping, sequences based on the Look-Locker scheme [START_REF] Ehses | IR TrueFISP with a golden-ratio-based radial readout: fast quantification of T1, T2, and proton density[END_REF] or fingerprinting [START_REF] Jiang | MR fingerprinting using fast imaging with steady state precession (FISP) with spiral readout[END_REF] have been employed. However, long acquisition times or high computational requirements, especially in signal post-processing, are needed. One of the fastest and most widely used T 1 mapping method is the Variable Flip Angle (VFA) [START_REF] Deoni | Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state[END_REF][START_REF] Cheng | Rapid high-resolutionT1 mapping by variable flip angles: Accurate and precise measurements in the presence of radiofrequency field inhomogeneity[END_REF].

The latter requires at least 2 images at different nutation angles. Also, a steady state needs to be reached before data acquisition. Multiple angles may also have to be employed to measure a wide range of T 1 . Finally, this approach is very sensitive to the nutation angle [START_REF] Svedin | Technical Note: The effect of 2D excitation profile on T1 measurement accuracy using the variable flip angle method with an average flip angle assumption[END_REF], thus preventing fast and robust 2D T1 mapping.

In regard to these different approaches, there is still a need for developing a fast and robust T 1 mapping method that can be applied to multiple areas of the body, and for numerous purposes, like diagnosis and monitoring of lesions or guiding interventional procedures. Indeed, quantitative T 1 values can be used in numerous pathologies as a diagnostic or prognostic tool [START_REF] Weidensteiner | Tumour T1 changes in vivo are highly predictive of response to chemotherapy and reflect the number of viable tumour cells -a preclinical MR study in mice[END_REF][START_REF] Ravoori | Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model. Kanthou C[END_REF][START_REF] Chow | Measurement of liver T1 and T2 relaxation times in an experimental mouse model of liver fibrosis[END_REF]. It can also be useful in interventional MRI, as a surrogate to PRF thermometry either in lipid [START_REF] Todd | Hybrid proton resonance frequency/T1 technique for simultaneous temperature monitoring in adipose and aqueous tissues[END_REF][START_REF] Todd | In vivo evaluation of multi-echo hybrid PRF/T1 approach for temperature monitoring during breast MR-guided focused ultrasound surgery treatments[END_REF] or bone [START_REF] Han | Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI[END_REF] or in areas affected by respiration which can induce large changes in the phase [START_REF] Svedin | Respiration artifact correction in three-dimensional proton resonance frequency MR thermometry using phase navigators[END_REF].

Thus, the goal of this study is to develop a 2D MP2RAGE sequence to rapidly acquire T 1 maps with fast reconstruction. To further improve the pulse sequence efficiency, the multiple dead times within the chronogram were used for the acquisition of multiple 2D slices, leading to 6 T 1 maps achieved in 9s. The current study evaluates the versatility of a new 2D Multi-Slice MP2RAGE (MS-MP2RAGE) sequence, in two different contexts (i) as a

Methods

MRI system

Experiments were performed on a 7T Bruker BioSpec system equipped with a gradient coil of 660 mT m 1 maximum strength and 110 s rise time. A transmit volume resonator operating in quadrature mode (75.4 mm inner diameter, 70 mm active length), and a receive proton phased array (RAPID Biomedical GmbH -4 elements of 30 mm long around an elliptic cylinder housing: 19 × 25.5 mm) were used.

For temperature monitoring experiments, the volume resonator was used in transmit and receive mode. T 1 maps were reconstructed using MATLAB (Mathworks, Natick, MA) with gpuNUFFT (21) on a workstation containing two Xeon E5-2620 v4 processors (2.10 GHz, 8 cores, INTEL Santa Clara, California) with 32 GB RAM and a Quadro M5000 Graphic Processing Unit (GPU) card (8 GB RAM, NVIDIA, Santa Clara, California).

2D Multi-Slice radial MP2RAGE sequence development

The MS-MP2RAGE sequence was developed with a golden-angle radial encoding scheme.

As for the 3D Cartesian (1) and radial (7) MP2RAGE sequences, the selective inversion pulse was followed by two gradient echo blocks (GRE1 and GRE2) acquired at two different inversion times (TI 1 and TI 2 , respectively). The sequence repetition time was referred to as MP2RAGE TR .

In order to measure T 1 values between 500 and 2500 ms, TI 1 -TI 2 -MP2RAGE TR parameters were set at 1000-3000-9000 ms. The reception bandwidth was set at 100 kHz (781 Hz/pixel) to get a TR of 5 ms within each GRE block. To avoid signal contamination from the successive echoes, gradient spoilers were applied during the last millisecond. Thus, the GRE blocks -containing 128 echoes -lasted 640 ms. As selective pulses were used, the delays present in the MP2RAGE sequence could be used to acquire five other slices (Figure 1). Slices were interleaved to prevent inversion slabs overlap.

Overall, the delay between an inversion and the corresponding GRE1 was sufficient to acquire a GRE block from another slice. Also, the delay between GRE1 and GRE2 was long enough to acquire two GRE blocks from other slices. More precisely, the GRE1 blocks of Slices 3 and 5 were acquired between the GRE1 and GRE2 of Slice 1. The corresponding inversions were performed directly before the GRE1 of Slices 1 and 3, respectively. As a consequence, the GRE2 blocks of Slices 3 and 5 were acquired after the GRE2 of Slice 1.

A dead time of 4.5 s remained after the GRE2 of Slice 5 for magnetization recovery. Thus, another set of three intricate slices (Slices 2, 4 and 6) was acquired during this delay. To reduce acquisition time, the inversion of Slice 2 was performed before the GRE2 of Slice 5.

As a result, the MS-MP2RAGE sequence enables to simultaneously acquire T 1 maps of 6 slices within 9 seconds. A set of six T 1 maps was reconstructed in less than 2 seconds.

Phantom imaging

To measure the performance of the MS-MP2RAGE sequence, T 1 maps were acquired on five tubes with increasing T 1 values, on five different days, at room temperature (25±2°C). Also, the 3D radial MP2RAGE (7) was performed on these phantoms, using the following parameters: Inversion pulse: 10-ms adiabatic hyperbolic secant applied on 150% of the imaging slab; TI 1 -TI 2 -MP2RAGE TR = 1000/3000/9000ms; 0.25ms-hermite pulse; 1 = 2 =7°; TR=5ms; 128 repetitions; FOV = (25 mm) 3 , matrix = (128) 3 , resolution = (195 m) 3 .

F o r P e e r R e v i e w 6
The MS-MP2RAGE acquisitions were performed using the following parameters: FOV = (25 mm) 2 , matrix = (128) 2 , resolution = (195 m) 2 , 1mm slice thickness.

The same excitation pulse was used in both GRE blocks ( 1 = 2 = 7°, 21.6 kHz transmission bandwidth). Three different excitation pulse shapes were tested: 3 lobes cardinal sine (sinc3), Hermitian and Gaussian. The transmission bandwidth being constant, the pulse durations were 0.64, 0.25 and 0.13 ms, respectively. The corresponding frequential excitation profiles are shown in Supporting Information Figure S1a. Because low flip angles were used, the different excitation profiles had only low influence on the signal -thus on the T 1 measurements (Supporting Information Figure S1b).

Slab-selective inversions were performed using a 10-ms adiabatic hyperbolic secant pulse. Because long MP2RAGE TR were used, the steady-state magnetization (directly before an inversion) and the equilibrium magnetization were similar (less than 1% difference). Therefore, for each MP2RAGE TR , the lookup table specifically developed for radial encoding ((7); Supporting Information S1c) was used to measure T 1 (no dummy scan was used).

Inversion and slice gap influences

To study the effect of the selective inversion on T 1 accuracy, the sequence was performed with a single slice. Different inversion slabs covering 100, 125, 150, 175, 200 and 1000 % of the imaging slice thickness were used in combination with the three excitation pulses (sinc3, Hermitian and Gaussian) within the GRE blocks.

The influence of the gap separating the six slices was studied by increasing it from 0 to 25, 50 and 100% of the imaging slice thickness (ie 0, 0.25, 0.5 and 1 mm, respectively for a 1mm imaging slice).

MR thermometry using the MS-MP2RAGE sequence

Three tubes containing agarose gels (1% in saline) with gadoteridol at 75, 135 and 300 µM were prepared. To regulate their temperature inside the MRI scanner, the tubes were placed in a home-made 3D-printed water circulation system: the system temperature was controlled using circulating water, the water being heated in a bath placed outside of the magnet room. An optical thermic probe (Luxtron 812, LumaSense The temperature was recorded as the tubes were heated from 10 to 60°C. During this time, 600 repetitions of the MS-MP2RAGE sequence were performed. The sequence parameters were: inversion slab coverage of 150%, sinc3 excitation pulse, in-plane spatial resolution (312µm) 2 , FOV = (30mm) 2 , matrix = 96 2 , slice thickness = 3mm, 50% inter-slice gap = 1.5mm. An axial orientation was used to measure the T 1 of the three tubes simultaneously. The acquisition lasted 1 h 30 min. This experiment was independently performed four times.

The 3D radial MP2RAGE [START_REF] Faller | Radial MP2RAGE sequence for rapid 3D T1 mapping of mouse abdomen: application to hepatic metastases[END_REF] was also performed at 10°C and 44°C, using the following parameters: Inversion pulse: 10-ms adiabatic hyperbolic secant applied on 1000% of the imaging slab; TI 1 -TI 2 -MP2RAGE TR = 1000/3000/9000ms; 1ms-sinc10H pulse; 1 = 2 =7°; TR=5ms; 128 repetitions; FOV = (25 mm) 3 , matrix = (128) 3 , resolution = (195 m) 3 .

As a linear increase of T 1 with temperature was observed, the T 1 could be approximated as T 1 = T 1 0 +AT, where both the slope A and the T 1 extrapolated at 0°C (T 1 0 ) are empirical constants, while is the temperature in Celcius. Both constants (T 1 0 and A) were 𝑇 determined by linear regression and averaged over three experiments.

For the two tubes with the highest gadolinium (Gd) concentrations, all measurements (from 10 to 60°C) were taken into account. However, for the third tube (75 µM), the T 1 above 40°C became too long to be measured with the current MP2RAGE parameters (>2500ms). Therefore, in this case, only the measurements acquired between 10 and 40 °C were used.

The accuracy and precision of the temperature measurements were evaluated on each of the three tubes:

-To evaluate accuracy, temperature deviations were calculated: the difference between the temperature estimations (based on MS-MP2RAGE T 1 maps) and reference temperatures (from the probe) were measured for the 600 repetitions.

The temperature bias was estimated as the mean over the 600 deviation values.

To determine the uncertainty, the corresponding standard deviation was calculated. To evaluate the ability to monitor temperature in adipose tissues, the same experiment was conducted three times on three identical tubes filled with olive oil.

In vivo imaging

The brain and abdomen of C57/Bl6 female mice (8 weeks old, Charles River, Labresle, France) were scanned using the MS-MP2RAGE sequence. Three mice were used for each body region. Similar parameters as for temperature imaging were used, except for the slice thickness, which was set at 1.5 mm, and the 50% inter-slice gap set at 0.75mm. 200 repetitions were applied continuously, for a total exam time of 30 min.

The IR sequence previously described for phantom imaging was also applied on the brain of three other healthy mice. The same parameters were used, except: 25 TI from 10 ms to 11900 ms, TR = 12 s, scan time = 2h.

The experimental procedures were approved by the Animal Care and Use Institutional ethics committee of Bordeaux, France (approval no. APAFiS 2629-2015110618597936).

Data analysis

To obtain reference T 1 values and inversion efficiencies (named "eff") from the IR sequence, the signal of each of the five Gd-containing tubes was fitted using the equation [START_REF] Barral | A robust methodology for in vivo T 1 mapping[END_REF]:

y = abs(M0 x (1-(1+eff) x exp(-x/T1)))
Eq [START_REF] Marques | MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1mapping at high field[END_REF].

A reference T 1 value was calculated as the mean T The influence of the inversion selectivity and the excitation pulse profile were assessed on single slice MP2RAGE measurements. For each of the five tubes, the differences between the T 1 values obtained with the MP2RAGE and IR sequences were calculated.

These differences were averaged over the five experiments and expressed as a percentage of the corresponding reference T 1 value of each tube. Finally, all these relative T 1 differences were averaged over the five tubes and the corresponding standard deviation was calculated.

The influence of the gap between imaging slices was measured for the tube with the longest T 1 (ie 75 µM). The T 1 of each slice was independently averaged over five experiments. The mean T 1 and corresponding standard deviation were calculated over the six slices.

To measure the precision and accuracy of the sequence after optimization of the parameters, the mean T 1 over the six slices was calculated and averaged over five experiments. The corresponding standard deviation and relative difference with the reference T 1 (obtained with the IR sequence) and with the 3D radial MP2RAGE were calculated. In addition, to assess the T 1 variation between slices (named Slice STDEV in Table 1), the standard deviation of the T 1 measured in the six slices were averaged over five experiments.

To measure T 1 of the mouse brain cortex and mi-brain with the IR sequence, the signals were fitted using a mono or a bi-exponential equation:

y = abs(M 0,L x (1+eff) x exp(-x/T 1,L )+M 0,S x (1+eff) x exp(-x/T 1,S ))
Eq [START_REF] Marques | New Developments and Applications of the MP2RAGE Sequence -Focusing the Contrast and High Spatial Resolution R1 Mapping Yacoub E, editor[END_REF],

where L and S stand for "Long T 1 " and "Short T 1 " components, and eff stands for inversion efficiency.

To quantify the stability of the

Results

Impact of the spatial selectivity of the inversion pulse on the T 1 measurements

When increasing the inversion slab coverage, the T 1 values tend to reach a plateau (Figure 2a). When a sinc3 pulse is used, this plateau is reached as soon as the inversion slab covered 150% of the excitation slice thickness. However, with the other pulses (Hermitian and Gaussian), a minimum thickness of 175% or >200% was necessary to reach the reference T 1 value, respectively. Therefore, the combination of a sinc3 excitation pulse and a 150% inversion slab was used for the MS-MP2RAGE experiments thereafter.

Impact of the excitation slice gap on the T 1 measurements

Figure 2b) shows the influence of the gap between the 6 imaging slices on the T 1 measurements (with 150% inversion slab). Even though slice acquisitions were interlaced, the T 1 values were affected when the slices were adjacent (0%-gap): the T 1 values were under-estimated by up to 10% and a high T 1 standard deviation was measured over the six slices. Increasing the gap to half the width of the imaging slice (50%-gap) allowed to obtain similar T 1 measurements on all the 6 slices. T 1 measurements obtained with a 100%-gap were similar to those with a 50%-gap. In order to maintain fine characterization of the sample of interest, a 50%-gap was set for the following experiments.

Measurement accuracy

A wide range of T 1 values (800 to 2000 ms) was assessed using the MS-MP2RAGE sequence with the parameters optimized above (150% selective inversion, sinc3 excitation pulses, 50% inter-slice-gap), the 3D radial MP2RAGE and the standard IR sequence (Table 1). The comparison between the sequences shows T 1 differences below 5%.

MR thermometry using T 1 measurement

F o r P e e r R e v i e w 11
The fast acquisition strategy developed here enabled to apply the MS-MP2RAGE sequence for MR thermometry. The T 1 maps acquired every 9 s enabled to observe a linear increase of the T 1 with temperature for the three Gd concentrations tested (Figure 3).

The 3D radial MP2RAGE sequence applied at two temperatures (10°C and 44°C) demonstrated less than 5% differences in T 1 values compared to the ones obtained with the MS-MP2RAGE sequence. This implies a minimum effect of Diffusion in our set up.

For the 75, 135 and 300 µM tubes, the corresponding slopes (A) were measured at 39±2, 27±1 and 21±3 ms °C-1 , respectively. The corresponding T 1 interpolated at 0°C ( ) were 𝑇 0 1 estimated at 780±20, 410±40 and 290±60 ms, respectively.

From these empirical constants (A and T 1 0 ), temperatures from 10 to 60 °C were predicted based on the T 1 values measured with the MS-MP2RAGE sequence (Figure 4). For the tube containing 75 µM of Gd, T 1 got too long (above 2500ms) to be measured with the current parameters at high temperatures.

Temperature biases of 1.7±0.5, 0.0±1.0 and 3.0±0.9 °C with corresponding precisions of ±0.5, ±1.0 and ±0.7°C were measured for the 75, 135 and 300µM tubes, respectively.

Globally, a T 1 TDC of 2.2±0.2 %/°C was measured at 30°C on the three tubes.

In tubes filled with olive oil, T 1 values from 300 to 600 ms were measured over the 10 to 60°C elevation (data not shown). A mean slope of 2.4±0.9 ms.°C -1 was measured (ie 26% uncertainty on the slope); the mean T 1 0 was 427±7 ms.

In vivo measurement

Using the IR sequence, a short T 1 component (T 1,S 95ms) could be measured using a biexponential fit (Supporting Information Table S1). This component can generate up to 5%-underestimations of T 1,L when fitting the data with a mono-exponential equation.

Also, the data enabled to measure the inversion efficiency (eff) on the mouse brain at 93% ± 3%. Consequently, this value was used into the MP2RAGE signal equations. The corresponding T 1 measurements obtained with the MS-MP2RAGE sequence lengthened by 5% and 4.3% in the cortex and mid-brain, respectively. The MS-MP2RAGE sequence was then applied on mice. In the brain (Figure 5a, upper row), T 1 standard deviations of 8 ms were measured along a 30-min acquisition (ie 200 repetitions) corresponding to a COV of less than 1% (Figure 5b).

The sequence was then used for mouse abdominal imaging while free breathing (Figure 5a, lower row). Due to the radial encoding, respiratory motion did not result in obvious in-plane motion artifacts. Due to the large reception bandwidth used here, no chemical shift was observed. The standard deviation measured in a ROI drawn inside the liver was 60 ms corresponding to a COV of 6%, over 200 repetitions. Similar standard deviations were observed on a second slice in the liver, yet the mean T 1 was slightly different between the two slices (921±57 and 890±60 ms, respectively, Figure 5b). Over a 30-min acquisition, low T 1 standard deviation was measured in the back muscle (15 ms, i.e. COV= 1%).

Discussion

This paper demonstrates the possibility to obtain accurate T 1 maps with a 2D implementation of the radial MP2RAGE sequence [START_REF] Marques | MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1mapping at high field[END_REF][START_REF] Faller | Radial MP2RAGE sequence for rapid 3D T1 mapping of mouse abdomen: application to hepatic metastases[END_REF]. The main advantages of the current approach rely on its broad applicability, rapid acquisition scheme, and its simplicity in image reconstruction. In comparison, VFA methods require 3D implementations [START_REF] Svedin | Technical Note: The effect of 2D excitation profile on T1 measurement accuracy using the variable flip angle method with an average flip angle assumption[END_REF] and are less robust to B 1 than the MP2RAGE sequence. Look-Locker and Fingerprinting sequences demand high computational requirements for generating the T1 maps. Compared to 3D MP2RAGE approaches (4,6), the 2D encoding scheme drastically reduced the scan time of the MP2RAGE sequence, while maintaining accurate T 1 measurements. To further accelerate, using selective pulses, the dead times of the MP2RAGE sequence were used to acquire multiple slices. This resulted in a compact and fast T 1 mapping sequence, with the possibility to acquire 6 slices in 9 seconds. Despite this encoding strategy, the Specific Absorption Rate (SAR) of this sequence was estimated at < 0.5W/kg, which is well below the recommended values. Thus, translating this sequence into a routine protocol in clinics is feasible. Yet, 2D imaging has also some specific requirements. To prevent parasite signal from spins outside the inversion slabespecially when using Hermitian and Gaussian pulses -the inversion selectivity needed to be adapted, which in turn conditioned the size of the inter-slice gap. A way of reducing this gap would be to improve pulse selectivity while maintaining a short TR. Apodization function [START_REF] Park | A New Tailored Sinc Pulse and Its Use for Multiband Pulse Design[END_REF] or Variable-Rate Selective Excitation (VERSE) [START_REF] Conolly | Variable-rate selective excitation[END_REF][START_REF] Lee | Time-optimal design for multidimensional and parallel transmit variable-rate selective excitation[END_REF]) could be used. values measured with the MS-MP2RAGE sequence had to be corrected for the inversion efficiency, leading to values within the range found in the existing literature [START_REF] Trotier | Compressed-Sensing MP2RAGE sequence: Application to the detection of brain metastases in mice at 7T[END_REF][START_REF] Castets | In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence[END_REF][START_REF] Guilfoyle | Quantitative measurements of proton spin-lattice (T1) and spin-spin (T2) relaxation times in the mouse brain at 7.0 T[END_REF][START_REF] Pohmann | Contrast at high field: Relaxation times, magnetization transfer and phase in the rat brain at 16.4 T[END_REF][START_REF] Gao | Preclinical MR fingerprinting (MRF) at 7 T: effective quantitative imaging for rodent disease models[END_REF].

This study highlights the potential of this sequence to be used during longitudinal studies.

Still, Magnetization Transfer effect [START_REF] Rioux | Biexponential longitudinal relaxation in white matter: Characterization and impact on T1 mapping with IR-FSE and MP2RAGE[END_REF] and T2 decay during the long inversion pulse [START_REF] Norris | An analysis of the effects of short T2 values on the hyperbolic-secant pulse[END_REF][START_REF] Kellman | Adiabatic inversion pulses for myocardial T1 mapping[END_REF] might explain the remaining <15% T 1 differences with a IR sequence.

Nevertheless, in the liver, after correction of the inversion efficiency, the mean T 1 values measured with the MS-MP2RAGE sequence were in agreement with those found in the literature [START_REF] Faller | Radial MP2RAGE sequence for rapid 3D T1 mapping of mouse abdomen: application to hepatic metastases[END_REF][START_REF] Chow | Measurement of liver T1 and T2 relaxation times in an experimental mouse model of liver fibrosis[END_REF]. Variability in T 1 standard deviations can be due to respiration motion, which could prevent a perfect overlap between inversion slabs and imaging slices.

Another source of T 1 errors might come from motion between the acquisitions of the GRE1 and GRE2 blocks of the same slice, which may be corrected through the deletion of motion-corrupted projections identified by a self-gating method [START_REF] Winter | Self-navigation under non-steady-state conditions: Cardiac and respiratory self-gating of inversion recovery snapshot FLASH acquisitions in mice[END_REF]. Another solution would be to perform 9-seconds apnea, which can be easily implemented on humans.

Another way to improve the robustness to motion, is to use less-selective inversions , that would require increasing the inter-slice gap. To counteract this decrease in spatial resolution in the slice direction, a solution would be to increase the gap to 100%, and acquire missing slices in a second set of six slices within another MS-MP2RAGE TR (thus 12 adjacent slices could be acquired in 18 s). In that case, one set of six slices should be acquired in a sequential mode (rather than interlaced), which will not affect the T 1 values of the next slice set. The compatibility of the sequential mode with 100%-gap is illustrated in Supporting Information Table S2.

Application to thermometry

One application of the fast T 1 mapping obtained with the MS-MP2RAGE sequence is temperature monitoring. At 7T, there is a lack of literature concerning tissue T 1 variations with temperature. Nevertheless, the slopes obtained in our study are close to those obtained in the literature at 3T in breast aqueous tissues [START_REF] Svedin | Simultaneous proton resonance frequency shift thermometry and T 1 measurements using a single reference variable flip angle T 1 method[END_REF] or in fat [START_REF] Todd | Hybrid proton resonance frequency/T1 technique for simultaneous temperature monitoring in adipose and aqueous tissues[END_REF][START_REF] Kuroda | Temperature dependence of relaxation times in proton components of fatty acids[END_REF]. According to our data, a precision of ±1°C was feasible in aqueous tissues that were not corrupted 14 by motion. Yet, a low temperature accuracy was observed that could be due to lack of accuracy and precision when determining empirical constants (A and T 1 0 ) from the small sample size, as well as difficulties to replicate the phantoms and variations in the probe location within the 3 mm imaging slice.

Using the current MS-MP2RAGE parameters, a wide range of T 1 values were measured.

This is an advantage compared to VFA-based thermometry, which requires specific flip angles to accurately measure a small range of T 1 values. A minor drawback with our current sequence was that T 1 longer than 2500 ms could not be measured. In the perspective of translating the sequence into a temperature monitoring protocol, this might not be a limiting factor. Indeed, at 3T, from the empirical constants (A and T 1 0 ) determined from Birkl et al [START_REF] Birkl | Temperature-induced changes of magnetic resonance relaxation times in the human brain: A postmortem study[END_REF] on the brain cortex -which has one of the longest T 1 values in the brain (1) -a T 1 of approximately 2000 ms was simulated at 60 °C. Still, if there is a need for measuring >2500ms T 1 values, the sequence parameters could be adapted. TI 1 , TI 2 and MP2RAGE TR could be lengthened while affecting the temporal resolution or the flip angle could be increased (Supporting Information Figure S1c) which in that case might require B 1 correction.

One advantage of T 1 mapping versus PRF methods is the possibility to measure temperature variations in adipose tissues, or bones using a UTE encoding scheme [START_REF] Han | Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI[END_REF][START_REF] Du | Qualitative and quantitative ultrashort-TE MRI of cortical bone[END_REF].

In oil, the T 1 measured in the current study at 20°C is close to the value measured in sequence was low compared to the one measured at 3T by Todd et al [START_REF] Todd | Hybrid proton resonance frequency/T1 technique for simultaneous temperature monitoring in adipose and aqueous tissues[END_REF]; the large slope variation could be explained by the proximity of the T 1 value of oil from the lower bound of the MP2RAGE lookup table. To circumvent this issue, the TI 1 could be reduced to 800 ms. This would imply reducing the number of projections per GRE to 100, which could be compensated using either k-Space Weighted Image Contrast (KWIC) [START_REF] Song | k-space weighted image contrast (KWIC) for contrast manipulation in projection reconstruction MRI[END_REF] or Compressed Sensing (CS) [START_REF] Trotier | Compressed-Sensing MP2RAGE sequence: Application to the detection of brain metastases in mice at 7T[END_REF][START_REF] Block | Undersampled radial MRI with multiple coils. Iterative image reconstruction using a total variation constraint[END_REF][START_REF] Levine | 3D Cartesian MRI with compressed sensing and variable view sharing using complementary poisson-disc sampling[END_REF]. Still, if fat is the tissue of interest, TI 2 and MP2RAGE TR could also be reduced to 2400 and 7000 ms, respectively, which would improve the temporal resolution. Thus, T 1 values could be measured between 400 and 2000 ms rather than between 500 and 2500 ms, as in the current study.

Limitations for thermometry applications

As already demonstrated, T 1 mapping cannot be used to measure absolute temperature, due to tissue-dependent T 1 -Temperature evolutions. To further develop the MS-MP2RAGE sequence as a temperature monitoring protocol, calibration studies can be performed to characterize the T 1 -Temperature dependence of the tissue of interest. PRF information might also be necessary. Several publications have already developed MR sequences in order to simultaneously obtain PRF and T 1 measurements [START_REF] Todd | Hybrid proton resonance frequency/T1 technique for simultaneous temperature monitoring in adipose and aqueous tissues[END_REF][START_REF] Todd | In vivo evaluation of multi-echo hybrid PRF/T1 approach for temperature monitoring during breast MR-guided focused ultrasound surgery treatments[END_REF][START_REF] Svedin | Simultaneous proton resonance frequency shift thermometry and T 1 measurements using a single reference variable flip angle T 1 method[END_REF][START_REF] Hey | Simultaneous T1 measurements and proton resonance frequency shift based thermometry using variable flip angles[END_REF][START_REF] Bos | Simultaneous monitoring of temperature and T1: Methods and preliminary results of application to drug delivery using thermosensitive liposomes[END_REF][START_REF] Diakite | Irreversible change in the T1 temperature dependence with thermal dose using the proton resonance frequency-T1 technique[END_REF].

Due to a radial encoding similar to the one implemented here and the use of a KWIC filter, 3D PRF and T 1 maps were obtained extremely rapidly [START_REF] Zhang | A variable flip angle golden-angle-ordered 3D stac -of-radial MRI technique for simultaneous proton resonant frequency shift and T 1 -based thermometry[END_REF]. Nevertheless, the implementation and the process for image reconstruction could be difficult to operate in routine. To obtain both information with the MS-MP2RAGE sequence, the TE of the GRE can be lengthened to get closer to the optimal condition TE=T 2 *. Nevertheless, a longer TE would generate a longer echo train than the current sequence, which would either limit the use of the Multi-Slice acquisition developed here, or decrease the spatial resolution of the T 1 maps due to the reduction in the number of echoes per train.

Perspectives

In MR thermometry, fast acquisitions have to be coupled to fast image reconstruction.

Here, a set of 6 slices was reconstructed in less than 2 seconds. To further accelerate this reconstruction, one of our future directions is to implement the open-source Gadgetron software [START_REF] Hansen | Gadgetron: An open source framework for medical image[END_REF]47) to dynamically modify the sequence parameters along with the temperature elevation.

Another perspective would be to use acceleration methods to acquire more slices in a single MP2RAGE TR . For instance, the GRE length could be shortened using undersampling; KWIC [START_REF] Song | k-space weighted image contrast (KWIC) for contrast manipulation in projection reconstruction MRI[END_REF] or CS [START_REF] Trotier | Compressed-Sensing MP2RAGE sequence: Application to the detection of brain metastases in mice at 7T[END_REF][START_REF] Block | Undersampled radial MRI with multiple coils. Iterative image reconstruction using a total variation constraint[END_REF][START_REF] Levine | 3D Cartesian MRI with compressed sensing and variable view sharing using complementary poisson-disc sampling[END_REF] could then be used to reduce aliasing artifacts.

Parallel imaging would also enable simultaneous multi-slice acquisition (48,49), thus extending applications of the MS-MP2RAGE sequence to whole-body T1 mapping.

It would also be possible to replace the radial encoding scheme by a Cartesian one to get better resolution in the absence of motion, or to implement an Ultra-short Echo Time (UTE) encoding to measure T 1 in short T2* environments.

Conclusion

The MS-MP2RAGE sequence has shown to be an efficient method to rapidly acquire 2D T 1

maps, which has a potential for 'on-the-fly' reconstruction. Depending on the application, the pulse sequence could be combined with different encoding schemes and acceleration methods. µM Gd (T 1 =1852 ms measured by IR, dashed line), as a function of the gap between each slice. The gap was increased from 0% to 25%, 50% and 100%. For each slice, the mean T 1 over the five experiments is represented by a dot. For each gap, the mean T 1 (cross) and the corresponding error bar over all six slices are shown. The 1-mm slices were acquired with an interlaced scheme, using an inversion slab set at 150% and a sinc3 excitation pulse.

F

Figure captions

  on phantoms for MR thermometry and (ii) for in vivo fast T 1 mapping of mouse brain and abdomen.

  The tubes were prepared with saline and gadoteridol (ProHance®, Bracco imaging) concentrated at[START_REF] Zhang | A variable flip angle golden-angle-ordered 3D stac -of-radial MRI technique for simultaneous proton resonant frequency shift and T 1 -based thermometry[END_REF] 75, 100, 135, and 215 µM to obtain T 1 values from 800 to 2000 ms. The reference T 1 values and inversion efficiencies were determined via a gold standard Inversion-Recovery (IR) sequence: Inversion pulse: 10-ms adiabatic hyperbolic secant applied on 1250% of the imaging slice thickness; 120 TI from 100 to 12000ms (100ms increment), TE = 10 ms, TR = 15 s, FOV = 25 × 18 mm 2 , matrix = 128 × 64, resolution= 195 × 281 m 2 , 1 slice, thickness=2 mm, RARE Factor= 4; scan time h.

7 Technologies

 7 Inc., Santa Clara, USA) was inserted into a fourth tube containing only agarose gel.

8 -

 8 To evaluate the precision, the differences between two successive temperature deviations were computed. The standard deviation over the 599 differences was then calculated.The T 1 Temperature Dependence Coefficient (TDC) of each tube was determined by dividing the mean slope by the corresponding T 1 value measured at 30°C as already performed by Kuroda et al.[START_REF] Kuroda | Temperature dependence of relaxation times in proton components of fatty acids[END_REF].

  T 1 measurements obtained with the MS-MP2RAGE sequence run continuously for 30-min, Regions of Interest (ROI) were drawn in the liver (in two different slices), in the back muscle, in the midbrain and brain cortex. The mean T 1 of each of these ROI was displayed as a function of exam time. The temporal coefficient COV) was calculated by dividing the temporal standard deviation of T 1 during the 30-min scan by its mean.

13 Application

 13 for fast in vivo mappingFast T 1 mapping of the whole mouse brain with the MS-MP2RAGE sequence showed the ability to measure T 1 values with low variations along time (less than 1%). The in vivo T 1

  hypodermis (fat) by Barral et al at the same temperature at 7T (38) -despite a difference in sample characteristics. The T 1 -Temperature slope measured with the MS-MP2RAGE

Figure 1 :

 1 Figure 1: Chronogram of the 2D MS-MP2RAGE sequence. In this implementation, the usual MP2RAGE delays -namely TI 1 , TI 2 and MP2RAGE TR -are respectively set to 1000, 3000 and 9000 ms. GRE blocks of 640 ms were set. Other delays are shown on the chronogram of Slice 3. The interleaving of the six slices is shown.

Figure 2 :

 2 Figure 2: Impact of the inversion selectivity and inter-slice gap on the T 1 measurements. a) Relative T 1 difference (in percent) between MS-MP2RAGE and IR measurements using Gaussian (grey), Hermitian (hatch) or Cardinal sine (black) excitation pulses as a function of the inversion slab coverage (expressed in percentage of the 1-mm excitation slice thickness). b) T 1 measurements on six different slices located on the tube containing 75

Figure 3 :

 3 Figure 3: T 1 measurements while heating. a) Three representative axial T 1 maps (top) of agarose gels containing Gd at 75 (green), 135 (red) and 300 (blue) µM acquired at three temperatures (10°C, 25°C and 40°C). The tube encircled in gray contains the temperature probe. b) Graph showing the T 1 measured in the three corresponding Gd-containing tubes as a function of the temperature measured with the probe. For each tube, the linear equation of T 1 dependence on temperature is calculated using linear regression.

21 Figure 4 :

 214 Figure 4: Temperature monitoring. The mean slopes and intercept (A and T 1 0 ) were calculated over three experiments, and used to estimate temperature warming during an independent experiment. The temperatures were estimated within the three Gdcontaining tubes 75 (green), 135 (red) and 300 (blue) µM in the slice at the location of the probe (black solid line). The circulating water was first warmed to 60°C for 50 minutes, then to 80°C for 40 minutes, explaining the inflexion around 50 minutes.

Figure 5 :

 5 Figure 5: T 1 evolution in vivo over 30 minutes. a) Six axial T 1 maps of the brain (first row) and six coronal T 1 maps of the abdomen (second row) were acquired with 1-mm slice thickness, spaced by 0.5 mm. Each six slices set was acquired in 9 s, while free breathing. b) T 1 evolution in mouse back muscle (blue), in two slices containing the liver (red full and dashed lines), in the mouse midbrain (black dashed line) and brain cortex (black full line) are shown.

  Chronogram of the 2D MS-MP2RAGE sequence. In this implementation, the usual MP2RAGE delays -namely TI1, TI2 and MP2RAGETR -are respectively set to 1000, 3000 and 9000 ms. GRE blocks of 640 ms were set. Other delays are shown on the chronogram of Slice 3. The interleaving of the six slices is shown. 521x285mm (300 x 300 DPI) Impact of the inversion selectivity and inter-slice gap on the T1 measurements. a) Relative T1 difference (in percent) between MS-MP2RAGE and IR measurements using Gaussian (grey), Hermitian (hatch) or Cardinal sine (black) excitation pulses as a function of the inversion slab coverage (expressed in percentage of the 1mm excitation slice thickness). b) T1 measurements on six different slices located on the tube containing 75 µM Gd (T1=1852 ms measured by IR, dashed line), as a function of the gap between each slice. The gap was increased from 0% to 25%, 50% and 100%. For each slice, the mean T1 over the five experiments is represented by a dot. For each gap, the mean T1 (cross) and the corresponding error bar over all six slices are shown. The 1-mm slices were acquired with an interlaced scheme, using an inversion slab set at 150% and a sinc3 excitation pulse. 588x222mm (300 x 300 DPI) heating. a) Three representative axial T1 maps (top) of agarose gels containing Gd at 75 (green), 135 (red) and 300 (blue) µM acquired at three temperatures (10°C, 25°C and 40°C). The tube encircled in gray contains the temperature probe. b) Graph showing the T1 measured in the three corresponding Gd-containing tubes as a function of the temperature measured with the probe. For each tube, the linear equation of T1 dependence on temperature is calculated using linear regression. 465x405mm (300 x 300 DPI) Temperature monitoring. The mean slopes and intercept (A and T10) were calculated over three experiments, and used to estimate temperature warming during an independent experiment. The temperatures were estimated within the three Gd-containing tubes 75 (green), 135 (red) and 300 (blue) µM in the slice at the location of the probe (black solid line). The circulating water was first warmed to 60°C for 50 minutes, then to 80°C for 40 minutes, explaining the inflexion around 50 minutes. 330x279mm (300 x 300 DPI) vivo over 30 minutes. a) Six axial T1 maps of the brain (first row) and six coronal T1 maps of the abdomen (second row) were acquired with 1-mm slice thickness, spaced by 0.5 mm. Each six slices set was acquired in 9 s, while free breathing. b) T1 evolution in mouse back muscle (blue), in two slices containing the liver (red full and dashed lines), in the mouse midbrain (black dashed line) and brain cortex (black full line) are shown. 1463x1393mm (30 x 30 DPI) Page 49 of 49 Magnetic Resonance in Medicine Magnetic Resonance in Medicine

TableTable 1 :

 1 In vitro T 1 measurements obtained with the MS-MP2RAGE (sinc3 pulse, 150%

	selective inversion, 50% gap), the IR and the 3D radial MP2RAGE sequences. The
	differences (expressed in percentage of the corresponding T1 value) between the MS-
	MP2RAGE and the IR sequences and between the MS-MP2RAGE and the 3D radial
	MP2RAGE sequences are shown.
	[Gd] / µM	45	75	100	135	215
	reference IR T 1 / ms	885±8.7 1058±29 1335±25 1568±89 1853±47
	MS-MP2RAGE T 1 / ms	891±21	1060±28	1340±27	1542±103	1851±32
	(± Slice STDEV / ms)	(±4.0)	(±6.9)	(±5.7)	(±8.4)	(±9.9)
	MS-MP2RAGE vs IR / %	0.65	0.15	0.47	-1.6	-0.12
	3D MP2RAGE T 1 / ms	931±28 1111±37 1384±25 1600±116 1903±39
	MS-MP2RAGE vs 3D	4.6	4.8	3.2	3.7	2.9
	MP2RAGE / %

Acknowledgment

This study was achieved within the context of the Laboratory of Excellence TRAIL ANR-10-LABX-57. The authors thank Dr N. Koonjoo for English editing.

Supporting Information captions

The hypothesis of an ideal slice profile to compute the lookup table would lead to T 1 overestimations, depending on the T 1 . Still, as low flip-angles are usually used (<7°), this overestimation is quite low: for Hermitian and sinc3 pulses, an overestimation of less than 2% is evaluated when T 1 is shorter than 2500ms. It is slightly less than doubled when using a Gaussian pulse, which has a lower Time-Bandwidth Product (2.74 against 5.4 and 6.21 for the sinc3 and Hermitian, respectively). c) Simulation of lookup tables computed with different flip angles (blue: 1°, red: 4°, yellow: 7°, purple: 10°, green: 13°). S1: Mouse brain T 1 measurements using the IR sequence and two different fit equations (mono-or bi-exponential). The inversion efficiencies (eff), the short and long T1 component (T 1,S and T 1,L , respectively), and the ratio M 0,S /M 0,L are shown for two brain regions (cortex and mid-brain).

Supporting Information Table

Supporting Information Table S2: T 1 measurements using the MS-MP2RAGE in a sequential mode (with 100%-gap) and the IR sequence on the 75 µM Gd-containing tube.


T Gineste

M Belhaj

G Teyssedre

J Puech

Investigation of the electron emission properties of Silver: from exposed to ambient atmosphere Ag surface to ion-cleaned Ag surface

Electron emission properties of materials are highly dependent to the surface and the first nanometres subsurface. Technical materials, i.e used within applications are ordinarily exposed to atmosphere, which interacts with the surface. The contamination layer building up at the surface of materials and/or oxidation layer affects dramatically the electron emission proprieties. In this paper, starting from 99.99% pure silver sample, exposed 4 years to ambient atmosphere, we monitored the variations of the electron emission properties and the surface composition during step by step ion etching procedure.

INTRODUCTION / SECTION TITLE

When a solid is hit by incident electrons, the energy transfer can result in the emission of secondary electrons (SE) and backscattered electrons (BSE). Electron emission (EE) is a physical phenomenon involved in several scientific and technical fields such as micro-analysis [START_REF] Seiler | Secondary electron emission in the scanning electron microscope[END_REF], particle accelerator [START_REF] Ohmi | Beam-Photoelectron Interactions in Positron Storage Rings[END_REF][3] space technology (spacecraft charging [START_REF] Balcon | Secondary Electron Emission on Space Materials: Evaluation of the Total Secondary Electron Yield From Surface Potential Measurements[END_REF], hall effect thrusters [START_REF] Dunaevsky | Secondary electron emission from dielectric materials of a Hall thruster with segmented electrodes[END_REF]), nuclear Physics [START_REF] Gunn | Evidence for strong secondary electron emission in the tokamak scrape-off layer[END_REF]. Electron emission is also at the origin of multipactor effect that can occur in several radiofrequency (rf) devices operating under vacuum (waveguides, circulators). Multipactor effect can be defined as the generation of an electron cloud by resonance between electron emission and rf field [START_REF] Sombrin | Le claquage hyperfréquences et l'effet multipactor dans les satellites[END_REF]. The consequences of this adverse effect are a power limitations and additional constraints in the design of rf components. The estimate of its onset threshold is highly needed. In many situations, the threshold could be estimated from simulations [START_REF] Buyanova | Influence of secondary emission yield on the saturation properties of multipactor discharges between two parallel metal plates[END_REF]. In the framework of a multi-laboratory project [START_REF] Puech | Synthesis of the results of the EVEREST project[END_REF], it was clearly established that all tested multipactor models and simulation software are extremely sensitive to the electron emission properties of the material components. Therefore, to improve the modelling of this effect and prevent occurrence, it is necessary to determine accurately some properties of the emitted electrons such as (i) the secondary electron emission yield (SEY), (ii) the electron backscattered yield (BSEY) and (iii) the energy distribution N(E). These properties are ordinarily extracted from measurements performed on materials of high purity evaporated [START_REF] Bronshtein | VTORICHNAYA ELEKTRONNAYA EMISSIYA[END_REF] or ion cleaned [START_REF] Assa'd Et | Backscattering coefficients for low energy electrons[END_REF] under ultra-high vacuum conditions (UHV). However, the materials used in rf devices are usually exposed days and months to ambient atmosphere. Thus, their surface properties are extremely different from that of the bulk. Since the emitted secondary electrons have a low energy (a few eV) and are generated in the first few nanometers in depth; obviously, the tabulated EE properties of pure materials are far from being representative of technical materials. For instance, the maximum of the electron emission yield (EEY) of pure aluminium is lower than 1 [START_REF] Bronshtein | VTORICHNAYA ELEKTRONNAYA EMISSIYA[END_REF], while that of technical aluminium is higher than 3 [START_REF] Baglin | The secondary electron yield of technical materials and its variation with surface treatments[END_REF]. The aim of this work is to study experimentally the electron emission of exposed to atmosphere silver and to establish the relation between the EE properties and the surface composition. Technical Ag surface (exposed to atmosphere) is supposed to be composed by Ag 2 S [START_REF] Russ | Characteristics of Contacts Contaminated With Silver Sulfide Film[END_REF] and other deposited compounds, like water and hydrocarbons [START_REF] Amodio | Atmospheric Deposition: Sampling Procedures, Analytical Methods, and Main Recent Findings from the Scientific Literature[END_REF]. A special experimental protocol was developed to extract relevant quantities. The electron emission yield (EEY) is investigated from very low incidence energy (some eV) to 2000eV. A step by step Argon ion etching was performed in situ. The surface composition is monitored by Auger electron spectroscopy (AES) during cleaning process. The EEY was measured at each step. An overall drop of the EEY was observed during the ion cleaning process. The maximum of the EEY decreases from 2.26 to 1.67 and the first crossover energy increases from 18 eV to 130 eV during the ion cleaning process. The effect of the ion-cleaning on the EEY tends to be suppressed after venting of the vacuum chamber. The EEY variations were linked to the surface composition.

EXPERIMENTAL

The experimental setup

The principle of the experimental protocol is represented in figure 1. EEY measurements, AES and electron emission spectra were recorded before and after each erosion step. Similar protocol has been used by Contini et al [START_REF] Contini | Auger electron spectroscopy study of the interface between bulk aluminum and bulk aluminum oxide[END_REF] to study electron emission loss spectra of aluminium at only three etching steps All measurements were performed in the CELESTE facility at ONERA. This facility is entirely dedicated and designed to the study of electron emission. A dry turbomolecular pump associated with an oil-free primary pump allows the system to be maintained at a vacuum level down to 5×10 -9 mbar. The tank is grounded. The sample holder allows the variation of the electron incidence angle from 0° (normal incidence angle) to 60°. An ELG-2 electron gun from Kimball Instrument was used. The electron beam was pulsed during EEY measurements to limit the surface conditioning effect [START_REF] Baglin | The secondary electron yield of technical materials and its variation with surface treatments[END_REF] and was continuous during spectra acquisition. The Tectra ion gun used has an energy range from 50eV to 5000eV. Argon gas is injected though a microleak valve and atoms are excited by microwaves generated by a microwave magnetron with a 2.45GHz frequency. The Omicron hemispherical electron analyzer can record spectra from 2 to 2000eV with an accuracy of 0.5meV. The sample was negatively biased to -9V during EEY and AES measurements to avoid experimental noise in the very first eV of the emission spectrum in the AES case and to avoid low energy secondary electrons to be recollected by the sample. It should be noticed that due to the -9V sample biasing, all the AES spectra are shifted by 9eV to high energies. Prior to measurements, the tank was baked to 180°C for 16 hours.

Sample

The sample was Ag (Ag00470/31) of high purity (99.99%) provided by Goodfellow Company. It was exposed for more than 4 years to ambient atmosphere. It has a square shape of 32×20 mm 2 area and a 0.5 mm thickness. Roughness measurements performed on the sample using a Zygo interferometer prior to the experiments revealed an average roughness of 160 nm. The sample has been washed by ethanol before mounting in the measurement system, where it was outgassed in UHV for 10 days before the first measurement. It was also heated to 100°C for 4 hours during the UHV exposure.

Erosion parameter

The sample was etched with Argon ions in 14 steps. Short ion irradiations durations were chosen for the first steps to avoid a too fast composition evolution. The irradiation duration of each step was progressively increased, starting with 30s for the first one until 30min for the last step. The same parameters (Ar ions energy of 1 keV, 3,5µAcm -2 , normal incidence) for each erosion step were applied; only the erosion duration of each step was varied. The ion current, measured using a Faraday cup was adjusted to 3.5μA/cm². The results presented in this paper are focused on (a) the as received sample (before erosion), (b) the sample at an intermediate state corresponding to an erosion time of 62.5 min and (c) the sample considered as completely cleaned after 132 min of erosion (final state). The final state is considered reached when both the AES spectrum, due to contaminants and EEY have reached a steady state.The thickness of the removed layer was estimated considering the etching rate (atom/ion) found in literature [START_REF] Behrisch | Sputtering by Particle Bombardment: Experiments and Computer Calculations from Threshold to MeV Energies[END_REF][17], Two majors hypothesis were used to estimate removed thickness as a function of the etching time: 1. The measured ion current is not totally representative of the incident Ar flux, neutral Ar may also impact the sample surface and therefore lead to underestimate of removed thickness. 2. The etching rate considered is that of pure silver.

This hypothesis is partially incorrect, especially for the first etching steps when the major portion of ejected atoms are contaminants and not silver. This may lead to uncertainty in the removed thickness estimation because the etching rate of contamination layer is unknown.

RESULTS

Surface composition

The AES microanalysis technique was used to monitor the surface and near surface chemical composition (few nanometers in depth). After each erosion step, several AES peaks (as Ag, C, O, S) were recorded under 2 keV electron excitation with an incident angle of 57° with respect to normal incidence. No Auger peak characteristic of sulphur was observed during the entire protocol which is in contradiction with previous reports [START_REF] Russ | Characteristics of Contacts Contaminated With Silver Sulfide Film[END_REF]. The evolution of Ag peak (transition MNN), C peak (transition KLL) and O peak (transition KLL) at the three main steps are represented in figures 2, 3 and 4. Each curve has been vertically shifted for sake of clarity. The evolution of the surface composition could be described according to the following four main evolutions. i.

On the 'as received' sample, the silver peak is weak as represented in figure 2. This feature implies that the mean thickness of the contamination layer is comparable to the mean Auger electrons escape depth (few nm). This is supported by the large carbon contamination peak detected on the silver surface around 265eV. A weak oxygen peak is also observed. ii.

After the first three etching step corresponding to 1.5 min of erosion, oxygen is totally eliminated. This oxygen was presumably contained in thin deposited water layer on the sample as it was already reported by Baglin on several metals [START_REF] Baglin | The secondary electron yield of technical materials and its variation with surface treatments[END_REF]. The C and Ag Auger peaks remain unchanged. iii.

At the intermediate state, the C peak was broadened to the higher energies range. This broadening implies that a chemical valance shift occurred during the cleaning process. Indeed, the carbon compounds are most probably fragmented by ion bombardment resulting in a statistical increase of the number of different chemical bound. The increase of the Ag peak is due to the partial removing of the contamination. iv.

At

Electron emission yields at initial and final state of cleaning process

The experimental method used for EEY measurements is described in [START_REF] Gineste | A novel experimental setup for the measurement electron backscattering yield[END_REF]. The EEY, function of the energy of primary electrons of Ag sample exposed to atmosphere and cleaned sample (after final erosion step) are plotted on figure 6. Ec 1 at normal incidence increases from 18eV for as-received sample to 130eV for cleaned sample. The shape of the EEY curve also changes. A huge variation of the energy corresponding to the maximum of the EEY, EEY max was observed. EEYmax shifts from 300eV for the as received sample to 700eV for the cleaned one. EEY measurements of air-exposed and cleaned Ag are compared on figure 6 to that measured for pure Ag (evaporated under UHV) at normal incidence as reported by Bruining et al. [START_REF] Bruining | Secondary electron emission: Part I. Secondary electron emission of metals[END_REF] and by Brönstein et al. [START_REF] Bronshtein | VTORICHNAYA ELEKTRONNAYA EMISSIYA[END_REF].

Evolution of electron emission yield during the cleaning process

Complete EEY measurements have only been performed at the initial state and at the final state. Nevertheless, the EEY was measured at two particular incident energies during the 14 steps of the Ar etching.

In order to provide an overview of the cleaning protocol effects, figure 7 shows the evolution of EEY as a function of the experiment time at incident energy of 300 eV and after each erosion step. The estimated erosion depth is also displayed for each etching step.

The eroded thickness is supposed to be directly proportional to the etching duration.

i. At initial state, EEY is about 2.27 at 300eV incident energy. The first erosion step leads to a substantial EEY decrease of about 30%. This critical evolution could be linked to the water layer removal that starts during this first etching step [START_REF] Baglin | The secondary electron yield of technical materials and its variation with surface treatments[END_REF]. This assumption is supported by the rapid decrease of the peak O KLL. ii. After the first erosion steps (experimental times 0 to 100h), the EEY continuously increases even if the ion sources as well as the electron gun is switched off. To explain the last results two reasons can be advocated. The first one is that the irradiation could increase the kinetic of the contamination deposition [START_REF] Al-Ajlony | Electron irradiationenhanced water and hydrocarbon adsorption in EUV lithography devices[END_REF]. The second possible reason is that the broken and excited hydrocarbons molecules by the Ar bombardment are relaxed and recombined slowly between two etching steps. iii. From the second etching step until erosion depth estimated to 21.8nm. The EEY measured after each step is still deceasing. For an experimental time between 240h and 300h, the EEY is at minimum, being less than that of the cleaned Ag and of the contaminated Ag. An interface effect between silver and hydrocarbons contaminants seems to lower EEY and broken the linearity of the EEY evolutions from contaminated sample values to cleaned Ag EEY values. Indeed, the escape probability of low secondary electrons is highly affected by the chemical bonding of the native surface. According to the nature of the surface terminations, an upwards surface band bending may occurs resulting in a decreases in secondary electron emission through the creation of a surface barrier [START_REF] Stacey | The effect of temperature on the secondary electron emission yield from single crystal and polycrystalline diamond surfaces[END_REF] [22] iv. After the tenth step and an estimated removed thickness of about 42nm (302h experimental time), contamination appears as fully eliminated and the EEY is considered as characteristic of pure silver. This feature is supported by Auger electron analysis, as seen on figure 5. Once pure Ag is reached, EEY is quite stable.

Evolution of electron emission yield after exposition to ambient atmosphere.

After the cleaning procedure of the sample, the sample was exposed to air twice. It was exposed for 15 min, then reintroduced into the UHV chamber and exposed again to air for 24h hours. Two measurements have been performed (at 760h and 810h). The EEY converges to initial values due to the rapid deposition of a new contamination layer as indicate the C Auger peak increase after 15min atmosphere exposition step (N°15 in figure 5).

OUTCOMES

We have investigated in details the step by step evolution of the EEY from as received silver sample (exposed for 4 years to ambient atmosphere) to a sample considered as pure Ag. Important evolutions of the EEY curve shape are observed during the cleaning process under Ar ions bombardment. An overall decrease of the yield was observed and in particular the first crossover energy shifts from 18 eV (as received sample) to 130 eV (pure sample). This huge difference could have an impact on space applications and particularly on multipacting in wave guides. When the sample is exposed to ambient atmosphere after the cleaning process, the sample recovers progressively its initial state properties in a relatively short time. This last observation may explain the fact that the EEY measured by different groups on many technical silver or silver plate samples over years are extremely stable [START_REF] Puech | Synthesis of the results of the EVEREST project[END_REF]. The contamination layer built within a few days after sample processing plays the role of quite stable "passivation layer" whose surface electronic properties screen those of the silver. The presented results highlight the fact that the use of tabulated electron emission data measured or modelled very often on pure and clean materials for fundamental investigations purpose, must be used with great caution in context of applications (such as rf devices exposed to atmosphere).

Fig. 1 .

 1 Fig. 1. Schematic representation of experimental setup CELESTE 2.2. Sample

  the final state, C peak was drastically decreased. A weak peak is still detected due to a possible implantation of carbon during ion etching and/or possible diffusion during cleaning process from the surface to the volume. At this stage, most of contaminants have been removed resulting in stable and high intensity Ag peak. During all the cleaning process, no energy shift of the Ag peak was observed. This observation supports the fact that studied silver does not present any visible chemical bonding with any other species. Intensities of Ag, C and O Auger peaks are plotted on figure 5 at every step of the protocol. Intensities are deduced from highness of Auger peak derivative. C and O are plotted following the main Y axis end Ag peak following the secondary Y axis.

Fig. 2 .

 2 Fig. 2. Auger peak of Ag (biased-9V). As received, Intermediate and Cleaned Ag correspond to cumulated ion erosion times of 0, 62.5 and 132 min.

Fig. 3 .Fig. 4 .Fig. 5 .

 345 Fig. 3. Auger peak of carbon on Ag (biased -9V).. As received, Intermediate and Cleaned Ag correspond to cumulated ion erosion times of 0, 62.5 and 132 min

Fig. 6 .

 6 Fig. 6. Comparison of EEY of Air exposed and cleaned Ag to pure Ag data from the literature

Fig. 7 .

 7 Fig. 7. Evolution of EEY at 300 eV as a function of experiment time. Diamonds symbols represent the Arcleaning steps. Indexes correspond to the estimated erosion depth (in nm)