Samer Sheikh Ismael Nicolas Turmel
email: nicolasturmel@yahoo.fr

Camille Chesnel

Audrey Charlanes

Claire Hentzen

Frederique Le Breton

Gérard Amarenco

Use of a specific questionnaire and perineal electromyography to assess neuropathic pain after radical retropubic prostatectomy

Keywords: Prostatectomy, neuropathic pain, specific questionnaire, perineal electromyography

Background: Prostate cancer is the most frequent cancer in men and radical retropubic prostatectomy (RRP) is one of the first line treatment. However, RRP have some side effects and can lead to chronic perineal pain. The objective of the study was to determine in patients suffering from perineal pain after RRP the possibility of a neurogenic damage by means of a specific questionnaire dedicated to track down neuropathic pain.

Methods: Forty patients were explored by a specific and validated questionnaire, the Neuropathic Pain Symptom Inventory (NPSI). Patients were divided into two groups: Group A with an NSPI score ≥ 4 was considered as suffering from neuropathic pain and Group B was considered as a control group without neuropathic pain (NSPI score < 4). All patients had a perineal electrophysiological testing to confirm the possibility of a neurogenic damage.

Results: Group A was composed by 13 men and group B by 27 men, mean age 72.45 years and mean duration of pain 2.7 years. In Group A, the most frequent symptoms were burning sensation, electrical shock and numbness.

Location of the pain was global perineal area (8/13), anus (10/13), , penis(5/13) and glans penis (2/13).

Electromyography (EMG) findings confirmed the presence of denervation and neurogenic damages compared with controls (p < 0.001).

Conclusion: One third of the patients consulting for chronic pain following RRP had probably a neuropathic lesion leading to a chronic perineal pain as suggested by an NSPI score ≥ 4 and EMG alterations.

Introduction

Prostate cancer is the most frequent cancer in men, with more than 240 000 patients newly diagnosed per year in the United States alone [START_REF] Siegel | Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths[END_REF]. In these patients, retropubic radical prostatectomy (RRP) is the most common technique for removing the prostate gland. Morbidity related to this procedure is quite low [START_REF] Kirschner-Hermanns | Quality of life following radical prostatectomy[END_REF], however longlasting pain is not generally reported after RRP. Pelvic and perineal pain persisting more than 3 months after surgery has been yet described [START_REF] Sall | Pelvic pain following radical retropubic prostatectomy: a prospective study[END_REF], with a serious impact on patient's quality of life. It could be speculated that some, or a part, the persistent pain occurring after RRP could be secondary to a neurogenic damage due to the surgical procedure. Indeed, alterations of peripheral nervous system following RRP are well known (4-7) and such neurogenic lesions (beside other consequences of neurogenic damage urinary incontinence, erectile dysfunction) can lead to neuropathic pain. The aim of the study is to determine in patients underwent RRP and suffering from perineal pain the possibility of a neurogenic damage by means of a specific questionnaire dedicated to track down neuropathic pain, and then, to confirm neurogenic damage by a perineal electromyographic (EMG) testing.

Patients and Methods

Forty patients admitted for perineal pain following RRP for prostate cancer were enrolled in the study. Pain was at least persistent for 6 months postoperatively. They were all well informed about the project and gave their written consent to participate. We have obtained the agreement of local ethics commitee. (ID-RCB: 2015-A00125-44). The patients had no neurological disorders and none had been treated by radiotherapy.

All the patients were referred to the Neuro-urology Department for EMG examination to track down a neurologic cause related to their chronic pain, especially a pudendal nerve lesion. They underwent a full clinical examination. Perineal skin sensation, anal and bulbo-cavernosus reflexes, voluntary contraction and tone of the anal sphincter were examined in lithotomy position. For all patients, urinary incontinence was evaluated by a specific questionnaire (Urinary Symptom Profile , USP) and erectile dysfunction by the International Index of Erectile Function (IIEF-5).

EMG recordings were performed in all the patients.To demonstrate neurogenic changes, an EMG needle electrode was inserted in the following perineal muscles: urethral sphincter, bulbocavernosus muscle and finally external anal sphincter. Sacral reflex (bulbocavernosus reflex) was elicited by means of stimulations of the dorsal nerve with a record of the motor potentials by means of a needle electrode inserted into the bulbocavernosus muscle. Measurements of right and left latencies were performed at the onset of the motor responses (normal latency < 44 ms).Cortical evoked responses following repetitive stimulation of the pudendal nerve were recorded (normal latency < 44 ms).Finally, terminal motor latencies of the pudendal nerve following intrarectal stimulations were recorded at the onset of motor potential of anal sphincter (normal latency < 3.5 ms).Lesion of peripheral nervous system was defined as neuropathic changes in EMG examination (increased rate of motor unit potentials ≥20/s presence of spontaneous fibrillation and/or positive sharp waves) with at least alteration of sacral latencies and/or pudendal nerve terminal motor latencies and/or cortical evoked potentials.

All the patients fulfilled a specific questionnaire, the Neuropathic Pain Symptom Inventory (NPSI). The NPSI is a validated questionnaire (8) which allows to speculate a neurogenic cause of a chronic pain in case of a total score ≥ 4. (Supplement file). This cutoff has been used to determine two groups of patients. The first group (Group A) included patients with NSPI score ≥ 4 defining patients with neuropathic pain. The second group (Group B) included patients without neuropathic pain and so, with NSPI score < 4. All the results of EMG findings were analyzed with a Fisher test and a p value less than 0.05 was considered as significant. All statistical analyses were performed with the R-studio version 3.3.1

Results

The age of the 40 patients was 72.45 ±7.45 years (mean ±SD) and the duration of the chronic pain was 2.7 ± 2.2 years (mean ±SD). They also had associated erectile dysfunction (n= 38/40) and urinary incontinence (n=9/40). There were no statistical differences between the two groups. Thirteen patients were classified in Group A (NSPI score ≥ 4) and considered as having neuropathic pain. Twenty-seven patients were classified in Group B (NSPI score <4) and considered as without neuropathic pain.

The most frequent symptoms in Group A were burning sensation (10/13 vs 9/27 in Group B), electrical shock (10/13), numbness (10/13) and paresthesia (10/13). Location of the pain was global perineal area (8/13), anus (10/13), penis (5/13), glans penis (2/13), and scrotum (6/13).

EMG findings:

In group A, EMG findings confirmed the presence of a significant denervation in perineal muscles (13/13 vs 3/27 in Group B) (p < 0.001). Sacral latencies were delayed in 3/13 and pudendal nerve terminal latencies in 8/13 (vs 2/27 in Group B). Cortical evoked responses were altered in 2/13 patients in the neuropathic group and 2/27 in the non-neuropathic group (Table 1).

Discussion

This study is the first, to our knowledge, to demonstrate clinically a neurogenic cause of perineal pain following RRP. Moreover, this neurogenic lesion is confirmed by specific neurogenic alterations of EMG testing. In this study, one third of patients consulting for chronic pain following RRP had a neurogenic lesion leading to a chronic perineal pain as suggested by an NSPI score ≥ 4 and EMG alterations.

The first limit of our study is that we could not obtain the overall data on surgical technique of prostatectomy for all included patients, but the primary outcome of our study was to assess neuropathic pain and neurogenic alterations in patients who underwent a radical prostatectomy (RP) regardless of the surgical technique that has been used. Chronic pain following RRP is rarely reported [START_REF] Sall | Pelvic pain following radical retropubic prostatectomy: a prospective study[END_REF][START_REF] Gerbershagen | Preoperative pain as a risk factor for chronic post-surgical pain -six month follow-up after radical prostatectomy[END_REF][START_REF] Gerbershagen | Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer[END_REF][START_REF] Sandblom | Pain and health-related quality of life in a geographically defined population of men with prostate cancer[END_REF]. Indeed, most of the studies are related to evaluation and therapeutic strategies of the immediate pain occurring just after the surgery [START_REF] Joshi | Optimal pain management for radical prostatectomy surgery: what is the evidence?[END_REF].Few studies are devoted to the long-term post RRP painful syndrome [START_REF] Gerbershagen | Preoperative pain as a risk factor for chronic post-surgical pain -six month follow-up after radical prostatectomy[END_REF][START_REF] Gerbershagen | Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer[END_REF]. However, this complication may seriously affect the quality of life of these patients [START_REF] Paice | Management of chronic pain in survivors of adult cancers: American society of clinical oncology clinical practice guideline[END_REF]. Mirzapour et al. [START_REF] Mirzapour | Stool behaviour and local pain after radical perineal and retroperitoneal prostatectomy[END_REF] have reported local pain after 12 months following RRP in 28% of patients and 29% after perineal RP. In the same study, 6 months after RRP or perineal RP, one third of the patients complained of their pain in sitting position. These data support firstly the hypothesis that the pain does not depend on the surgical procedures and secondly that the pain is possibly due to a neurogenic cause since it increases in sitting position suggesting a compression of the pudendal nerve against the ischial tuberosity in this position. Data on local postoperative pain after RRP are available in a systematic review conducted by Ficarra et al [START_REF] Ficarra | Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies[END_REF] in 2009 reporting nine studies. Seven studies compared pain after RRP or laparoscopic radical prostatectomy (LRP) and the most used tool was a validated 10-point visual analogic scale (VAS). All these data concerned acute postoperative pain.

The NSPI has been used to evaluate the type of pain in our 40 patients and suggest a neurogenic cause to this chronic neuropathic pain, if the score was ≥ 4. EMG was done to assess if these patients had also neurogenic damages and to support the data found allowed by NSPI questionnaire. In 2012 Yiou et al [START_REF] Yiou | Neurophysiological testing to assess penile sensory nerve damage after radical prostatectomy[END_REF] assessed the penile cold and vibratory sensory thresholds to reflect the cavernous nerve damage after RP and found that some surgical techniques had better results. Indeed, penile sensory threshold for warm and cold sensation increased after Non-Nerve Sparing Radical Prosatectomy (NNSRP) but not after Nerve Sparing Radical Prostatectomy (NSRP). Vibratory threshold only increased after transperineal NNSRP. With the same neurophysiological evaluation, Lefaucheur et al [START_REF] Lefaucheur | Assessment of penile small nerve fiber damage after transurethral resection of the prostate by measurement of penile thermal sensation[END_REF] in 2000 demonstrated that the warm, cold and vibratory threshold was significantly increased after trans urethral resection of the prostate (TURP) and supported the hypothesis of neurogenic damage (penile small nerve fiber) as the primary cause of post-operative erectile dysfunction. Thus, all these studies support the hypothesis of a neurogenic damage following RRP. Since then, it can be speculated that these neurogenic lesions can lead not only to urinary incontinence and/or impotence, but also to a neuropathic pain since acute or chronic nerve lesions can determine chronic neurogenic pain syndrome.

Nevertheless, even if changes and neurologic damages could be part of the explanations of a neuropathic pain, other causes could be discussed.

Gerbershagen et al [START_REF] Gerbershagen | Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer[END_REF] in 2009 have evaluated the preoperative pain status and its influence on the occurrence of chronic post-surgical pain (CPSP). Mental and physical health regarding CPSP development were analyzed.

From 72 patients evaluated after RP, 12 had CPSP and all the patients suffered from preoperative pain (p=0,003). In this study only one patient suffered from chronic pain at the 6 months follow-up. A systematic review conducted in 2015 by Boogaard et al [START_REF] Boogaard | Predictors of Persistent Neuropathic Pain--A Systematic Review[END_REF] assessed pain and tried to find predictive factors. The main factors leading to post-surgical pain were psychological distress, pain at day 2 (VAS >3) or a higher body mass index. In 2012, the European Association of Urology [START_REF] Bader | Prostate cancer pain management: EAU guidelines on pain management[END_REF] proposed guidelines on prostate cancer pain management. Pain can be precisely caused by the cancer (77%) or by cancer treatment (19%). Furthermore, the overall incidence of chronic pain in prostate cancer patients was found about 30% to 50% [START_REF] Bader | Prostate cancer pain management: EAU guidelines on pain management[END_REF].

Another key point is the clinical evaluation of cancer pain. VAS usually used to quantify chronic pain is not only inadequate in term of diagnosis, but also imperfect for a complete evaluation since pains that impact the psychological, mental and physical health status are not strictly taken into account with this tool. The use of a specific questionnaire as the McGill Pain Questionnaire [START_REF] Melzack | The McGill Pain Questionnaire: major properties and scoring methods[END_REF][START_REF] Deschamps | Assessment of adult cancer pain: shortcomings of current methods[END_REF] seems to be better to evaluate such chronic pain. Furthermore, the interest of a specific questionnaire as the NPSI ( 8) is major, since it can give strong arguments for a neurogenic pain. It characterizes with great accuracy the neurogenic etiology using specific words as "burning" or "electrical shock" or "numbness", all words largely reported by patients suffering from neuropathic pain [START_REF] Dobratz | Word choices of advanced cancer patients: frequency of nociceptive and neuropathic pain[END_REF]. The knowledge of such an etiology, e.g. neuropathic pain, is important in terms of therapeutic strategies [START_REF] Joshi | Optimal pain management for radical prostatectomy surgery: what is the evidence?[END_REF].

Conclusion

A neurogenic cause of perineal pain following RRP is possible. This can be clinically confirmed by using a specific questionnaire like NSPI and eventually by perineal EMG.The knowledge of such an etiology can be taken into account in adjusting the therapeutic strategies.

Table1.

  Results of EMG testing and clinical complications on a population of 40 men who underwent RRP. NPSI , Neuropathic Pain Symptom Inventory (a neurogenic cause of a chronic pain is speculated in case of a total score ≥ 4).

Compliance with Ethical Standards:

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Conflicts of interests: zzzzzzzThe authors declare no conflict of interest.

Supplement file. NSPI questionnaire


Laurent Bertoletti

Judith Catella-Chatron

Adel Merah

Elodie De Magalhaes

Nathalie Moulin

Sandrine Accassat

Cécile Duvillard

Patrick Mismetti

Laurent Pr

Bertoletti

Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients

Keywords: Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients Chronic thromboembolic pulmonary hypertension, pulmonary embolism, cancer, epidemiology

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

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) arise from one or multiple endothelialized pulmonary thrombi that do not resolve after pulmonary embolism (PE).

CTEPH leads to chronic obstruction of the pulmonary artery tree, increased pulmonary vascular resistance, pulmonary hypertension (PH) and progressive right heart failure [START_REF] Lang | Update on Chronic Thromboembolic Pulmonary Hypertension[END_REF].

Untreated CTEPH has a very poor prognosis [START_REF] Riedel | Longterm Follow-up of Patients with Pulmonary Thromboembolism[END_REF].

CTEPH diagnosis is a major clinical challenge because -if diagnosed-patients may be discussed for several treatments options. Pulmonary endarterectomy can potentially cure patients with CTEPH [START_REF] Lang | Factors associated with diagnosis and operability of chronic thromboembolic pulmonary hypertension[END_REF]. Pulmonary balloon angioplasty is becoming a more and more efficient option [START_REF] Moriarty | Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension[END_REF]. Beside these mechanical treatments, Riociguat has demonstrated its positive effect on exercise capacity [START_REF] Ghofrani | Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension[END_REF]. Clinical symptoms and signs are non-specific or absent in early CTEPH, with signs of right heart failure only becoming evident in advanced disease. The mean diagnostic delay was 14 months in the European CTEPH registry [START_REF] Pepke-Zaba | Chronic Thromboembolic Pulmonary Hypertension (CTEPH)[END_REF] between the first symptoms and the diagnosis. Because of its low frequency after PE [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF], diagnostic evaluation for CTEPH is not recommended for all PE survivors, but is suggested in case of clinical suspicion, for example in case of persistent dyspnea [START_REF] Konstantinides | ESC Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) * Endorsed by the European Respiratory Society[END_REF][START_REF] Galiè | ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endor[END_REF]. In case of clinical suspicion, the combination of a high or intermediate echocardiographic probability of PH with the presence of perfusion defects on V/Q lung scan defined CTEPH as "likely", and may prompt the referral of the patients in a PH center [START_REF] Galiè | ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endor[END_REF]. This clinical challenge is upgrated in cancer patients. Venous thromboembolism (VTE) is a common complication of cancer and its therapy [START_REF] Timp | Epidemiology of cancerassociated venous thrombosis[END_REF][START_REF] Ay | Cancer-associated venous thromboembolism : Burden , mechanisms , and management[END_REF]. Approximately 20 % of all VTE cases are related to cancer [START_REF] Timp | Epidemiology of cancerassociated venous thrombosis[END_REF] and cancer patients with VTE have a three-fold higher risk of recurrent VTE compared to patients without cancer [START_REF] Prandoni | Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis[END_REF][START_REF] Hutten | Incidence of Recurrent Thromboembolic and Bleeding Complications Among Patients With Venous Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis[END_REF]. Cancer symptoms may hide CTEPH symptoms or CTEPH symptoms may be interpreted as cancer symptoms.

A recent meta analyse estimates incidence of CTEPH of 3.21% (95% CI 2.0-4.4) after PE, considering only survivors patients, alive after an initial treatment period of 6 months [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF].

Moreover, recurrent VTE was associated with a higher CTEPH incidence than after first PE (Odd Ratio 3.2, 95% CI 1.7-5.9) [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF]. Whereas in survivors patients without major comorbidities, incidence was estimated at 2.78% (95% CI 1.5-4.1) [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF], incidence of CTEPH after PE in patients with active cancer is currently unknown.

We aimed to assess the suspicion of CTEPH, after PE in patients with active cancer.

Methods

We conducted a post hoc analysis of consecutive patients with acute PE, prospectively included in the monocentric registry of Saint Etienne.

Registry design, patients and data collection

Consecutive patients with symptomatic acute PE and active cancer were included in our registry. PE was confirmed with high probability ventilation/perfusion (V/Q) scan, intermediate V/Q with proximal deep venous thrombosis or positive contrast-enhanced, pulmonary embolism-protocol, helical chest computerized tomography. Active cancer was defined according to ISTH definition [START_REF] Kearon | Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH[END_REF]. Patients participating in a therapeutic clinical trial with a blind medication were excluded. All patients provided oral or written consent according to the requirements of the Ethics Committee of the hospital. The participating physicians ensured that eligible patients were consecutively enrolled.

Study variables

The parameters routinely recorded in the registry are: patient baseline characteristics; clinical status including any coexisting or underlying condition (like cancer); laboratory data; treatment received upon VTE diagnosis (drugs, doses and duration); outcome during the course of anticoagulant therapy (mainly recurrent symptomatic VTE, major bleeding, CTEPH clinical suspicion and death).

Among the patients in whom CTEPH was clinically suspected, patients were defined as "CTEPH likely" according to the definition of the European Respiratory Society (ERS) guidelines, with an accelerated tricuspid regurgitation more than 2.8 m/sec on TTE and at least 1-2 segmental or larger sized defects on pulmonary perfusion scan, after more than 3 months of therapeutic anticoagulation [START_REF] Konstantinides | ESC Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) * Endorsed by the European Respiratory Society[END_REF][START_REF] Galiè | ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endor[END_REF].

Treatment and follow up

Patients were managed according to the clinical practice of each clinician; therefore, there was no standardization of choice of drug treatment, dose or duration. Patients were followed-up for at least three months in the outpatient clinic of Saint Etienne. First visit was usually performed between 3 and 6 months after the diagnosis then following visits were provided every 6 or 12 months according the profile of each patient. During each visit, any signs or symptoms suggesting CTEPH complications were prospectively noted (dyspnea, weakness, fatigue, chest pain, palpitations, right heart failure signs, syncope, hemoptysis, cyanosis). During the follow-up, clinicians were free to suspect (or not) CTEPH, if patients presented with persistent dyspnea, and free to program (or not) transthoracic echocardiogram to assess for pulmonary hypertension, and pulmonary perfusion scan to assess for perfusion defects, in order to classify the patients as "CTEPH likely" or "unlikely".

Study design and outcomes

All patients recruited in our registry with active cancer were considered in our analysis. Our primary aim was to estimate the frequency of patients reported as "CTEPH-likely"during the follow-up.

Statistical analysis

Analyses were performed on all patients included in our registry between January 2008 and December 2016, with active cancer. Quantitative variables were presented as the number of case, mean (±standard deviation). Data were processed and analyzed using R package version 3.4.318 [START_REF]R: a Language and Environment for Statistical Computing[END_REF].

Results

Between January 2008 and December 2016, 129 patients with PE and active cancer were included among the 711 patients with PE (18.1%). Baseline patients characteristics are reported in Table 1. Of these, 68 patients (53 %) were male. The mean age was 72 years old with 77 patients (60%) above 70 years old. Initial pulmonary embolism presented with dyspnea for 99 patients (77%). Three patients (2.3%) presented with systemic hypotension.

Among the 24 patients with TTE performed at PE diagnosis, 8 patients (6.2%) had systolic Pulmonary Arterial Pressure over 50 mmHg. Main risk factors of venous thromboembolism (VTE) were history of VTE for 33 patients (26%) and recent surgery for 18 patients (14%). Cancer patient's characteristics are reported in Table 2. Main cancer site were colorectal (19.8%), breast (17%), prostate (16.5%), blood (9%), lung (8.5%). Cancer were metastatic for 41 patients (32%). Cancer treatments include chemotherapy (35%), radiotherapy (12%) and hormonal therapy (13%). Initially, 91% of patients were treated with low molecular weight heparin (LMWH), 7% of patients with unfractionned heparin and 2% of patients with direct oral anticoagulants (DOACS). As a long term therapy (after 6 months), 66% of patients were treated with LMWH, 26% of patients with vitamin K antagonist and 8% patients with DOACS. The median follow up was 190 days (± 240). The overall survival was 91.5 % at the end of follow-up.

During the follow-up, 2 patients (1.5%) were clinically suspected of CTEPH (none of them were those with elevated sPAP at baseline). One patient was classified as "CTEPH-likely", corresponding to an incidence of 0.75% (95% CI 0.0-2.2). This patient was a woman with a locally advanced ovarian cancer. CTEPH was suspected 6 months after PE diagnosis because of persistent dyspnea. TTE and lung scan were favorable to "CTEPH likely". No right heart catheterism (RHC) was performed to confirm CTEPH. The patient received conventional therapy consisting diuretics, oxygen on top of anticoagulant therapy. The patient is still alive 3 years after PE diagnosis.

Discussion

In 129 cancer patients prospectively followed after acute pulmonary embolism, a clinical suspicion of CTEPH was raised in 1.5% and the incidence of "CTEPH likely" (as defined by Europeans guidelines) was 0.75% (95% CI 0.0-2.2).

Compared to data recently aggregated in a meta-analysis [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF], our incidence of "CTEPH likely" patients was near to the incidence of CTEPH after PE in all comers (0.56%), but lower than the incidence found in patient survivors 6 months after PE (3.21%) [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF]. Of note, we included all patients with PE in the setting with active cancer, the median follow up was 6 months, and the survival rate was 91.5% at the end of the follow-up.

We know that cancer patients are at higher risk of venous thrombo embolism. As previously reported, almost 20% of our PE occurred in cancer patients [START_REF] Timp | Epidemiology of cancerassociated venous thrombosis[END_REF] and 3.8% allow to discover cancer in the following year [START_REF] Delluc | Real-world incidence of cancer following a first unprovoked venous thrombosis: Results from the EPIGETBO study[END_REF]. Moreover, this patients have a three-fold higher risk of recurrent VTE compared to those without cancer [START_REF] Prandoni | Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis[END_REF][START_REF] Hutten | Incidence of Recurrent Thromboembolic and Bleeding Complications Among Patients With Venous Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis[END_REF]. Recurrent VTE is associated with a higher CTEPH incidence than after first PE (Odd Ratio 3.2, 95% CI 1.7-5.9) [START_REF] Ende-Verhaar | Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature[END_REF]. Considering that, we expected an higher rate of CTEPH likely patients that thus we found. In a bicentric study of 146 patients followed for CTEPH incidence after acute PE, 17 were suffering from cancer [START_REF] Guérin | Prevalence Of Chronic Thromboembolic Pulmonary Hypertension After Acute Pulmonary Embolism : A Prospective Multicenter Study[END_REF], and only one was diagnosed for CTEPH, after a median time of 26 months of follow-up. Joined with our 129 patients, it seems that CTEPH is not frequently diagnosed after PE in patients with active cancer.

No previous study specifically assessed the incidence of CTEPH suspicion in cancer patients.

Our low incidence may be explained by the non-specificity of the CTEPH clinical signs, like exercise intolerance, fatigue or low grade of dyspnea. Moreover, clinical suspicion of CTEPH may be decreased because symptoms being related to cancer or cancer treatment. Finally, it is possible that doctors may decide to not conduct any other investigation, because of the cancer status, despite overt clinical symptoms.

Our study has several limits. We conducted a monocentric study with an a posteriori analysis but our patients were included consecutively and prospectively. Only 24 TTE were performed at baseline, but none of the 8 patients with pulmonary hypertension at baseline were suspected of CTEPH during the follow-up. Our study population is small, considering the importance of cancer-associated thrombosis, but this is the first to point out the particularities of CTEPH suspicion in cancer patients. Our median follow up is limited to 6 months which may affect the rate of CTEPH suspicion especially since the survival of cancer patients is in constant progress and more and more concerns are currently raised on cardiovascular long-term complications [START_REF] Mery | Atrial fibrillation in cancer patients: Hindsight, insight and foresight[END_REF]. Also, the number of patients include give no sufficient power to assess the risk according the type of cancer or the treatment. Of note, no right heart catheterism was done in the patient suspected of CTEPH.

Conclusion

The frequency of screening for CTEPH seems negligible in cancer patients after PE.

Concomitant cancer may affect the clinical suspicion of CTEPH. CTEPH diagnosis and dedicated therapy may improve the prognosis of some cancer patients with PE. Better individualization of PE patients with cancer at good prognosis is needed.

Table legend :Table 1 .

 legend1 Baseline patients characteristics. PE, Pulmonary Embolism; VTE, Venous Thrombo Embolism; CTPA, CT pulmonary angiogram;

	Patients, N Pancreas	129 1 (0.8%)
	Clinical characteristics Peritoneum	2 (1.6%)
	Male gender ENT (pharynx/larynx + tong)	68 (52.7%) 2 (1.6%)
	Mean age (years ± SD) Others (unknown, sarcome, thyroid)	72.0 ±12.9 3 (2.3%)
	Age > 70yr Metastasis	77 (59.7%) 41 (31.8%)
	Body weight (mean kg ± SD) Cancer treatment	73.6 ± 18.3
	BMI ≤ 18 kg/m² Radiotherapy	6 (4.7%) 15 (11.6%)
	BMI > 30 kg/m² Chemotherapy	20 (15.5%) 45 (34.9%)
	Acute PE index Hormonal therapy	17 (13.2%)
	Syncope (continued)	13 (10.1%)
	Dyspnea	99 (76.7%)
	Fever	15 (11.6%)
	Temperature less than 36°C	2 (1.6%)
	SBP < 100 mmHg	3 (2.3%)
	Heart Rate > 110 bpm	8 (6.2%)
	Sat O2 levels < 90% (Blood gases) n=38	9 (7.0%)
	Inverted T wave (ECG)	18 (14.0%)
	Right Branch Block ( ECG)	11 (8.5%)
	Central Thrombi (CTPA) n=23	1
	PA main branches thrombi (CTPA) n=23	3
	Segmental thrombi (CTPA) n=34	27
	PAP levels > 50 mmHg (TTE baseline) n=24	8
	Risk factors for PE
	Surgery < 2 months	18 (14.0%)
	Immobilization ≥ 4 days	4 (3.1%)
	Estrogen use	16 (12.4%)
	Varicose veines	17 (13.2%)
	Prior VTE	33 (25.6%)
	Underlying diseases
	Atrial fibrillation	4 (3.1%)
	Systemic arterial hypertension	57 (44.2%)
	Diabetes mellitus	14 (10.9%)
	Thyroid diseases	6 (4.7%)
	Depression	5 (3.9%)
	Use of psychotropic drugs	12 (9.3%)
	Use of antiplatelets drugs	28 (21.7%)
	Use of anticoagulants drugs	4 (3.1%)
	Follow-up (mean days)	260.1 ± 240.0
	Follow-up (median days±SD)	190.0 ± 240.0
	Cancer site
	Colorectal	25 (19.4%)
	Breast	24 (18.6%)
	Prostate	19 (14.7%)
	Hematological	12 (9.3%)
	Lung	11 (8.5%)
	Kidney	6 (4.7%)
	Uterus	6 (4.7%)
	Skin	5 (3.9%)
	Stomach	5 (3.9%)
	Ovary	4 (3.1%)
	Bladder	4 (3.1%)


Anne-Laure Fauchille
email: anne-laure.fauchille@ec-nantes.fr

Stephen Hedan

Valéry Valle

Dimitri Pret

Justo Cabrera

Philippe Cosenza

EFFECT OF MICROSTRUCTURE ON HYDRIC STRAIN IN CLAY ROCK: A QUANTITATIVE COMPARISON

Keywords: Hydric loading, strain, Tournemire clay rock, microstructure, phase area fraction, Digital Image Correlation

This paper presents a new method able to compare quantitatively strains and microstructure of a clay material. This method was applied to a Tournemire clay rock sample subjected to cyclic hydric loading in laboratory conditions. Local strains of a centimeter-size Tournemire clay rock sample were quantified by digital image correlation (DIC) on a field of view of 5.5 x 4.1 mm² at the resolution of 2 µm.pixel -1 , at a temperature of 22°C and between 98 and 33% of relative humidity. At the end of the hydric loading, at dry state, the microstructure of the same field of view was mapped by an extended mosaic of scanning electron microscopy images at the resolution of 0.625 µm.pixel -1 and superimposed to the reference images used for DIC. Two microstructural parameters: the mean area and the area fraction of rigid clasts and clay matrix, were quantified by image analysis to be directly superimposed to local strain values. Speckle artefacts partly due to polished surfaces of clasts were filtered in the comparison between strains and microstructure. Strains concentrated in parts of the clay matrix, and at the interface between matrix and several quartz clasts which showed a slight detachment from the matrix. Constant clay and clast area fractions and sizes corresponded to very variable strain values at the microstructure scale. The relationship between strain values, mineral size and area fractions was not linear.

Micro-mechanisms of deformation were therefore very complex at the scale of the experiment. On a very large field of view, very different microstructure behaviors were averaged which avoided any simple relationship between microstructure and strains.

Heterogeneous water distribution and non-local microstructural control factors were suspected.

Introduction

Clay rocks are interesting underground media for high-level radioactive waste repositories in several industrial countries around the world. The storage capabilities are mainly due to a very low intrinsic permeability and thermo-hydro-mechanical and chemical properties of clays which form radiation-proof and fluid-proof barriers for wastes over the next centuries.

The optimization of the long term safety of this type of repository is strongly related to the understanding of deformation mechanisms of the host material at the basin scale, but also in the excavation damaged zone (EDZ) around galleries at the repository scale [START_REF] Cabrera | Projet Tournemire : Synthèse des Résultats des Programmes de Recherche[END_REF][START_REF] Matray | Desaturation and structure relationships around drifts excavated in the well-compacted Tournemire's argillite (Aveyron, France)[END_REF][START_REF] Möri | Mont Terri Project: cyclic deformations in the Opalinus Clay[END_REF]. The initiation and extension of EDZ are governed by a high variability of parameters such as the mineralogy, the anisotropy, the initial stress field, the existence of preexisting fractures and weak joints, the repository's geometry and the hydric state of galleries [START_REF] Bossard | Geological and hydraulic characterisation of the excavation disturbed zone in the Opalinus Clay of the Mont Terri Rock Laboratory[END_REF](Bossard et al., , 2017;;[START_REF] Tsang | Geohydromechanical processes in the Excavation Damaged Zone in crystalline rock, rock salt, and indurated and plastic clays -In the context of radioactive waste disposal[END_REF][START_REF] Blüming | The Excavation-Damaged Zone in clay formations -Time-dependent behaviour and influence on performance assessment[END_REF]Hédan et al., 2014Hédan et al., , 2018)). During both digging and operational phases, clay rocks are subjected to various stimulations such as mechanical damages, temperature and humidity variations, fluid flow, swelling and shrinkage, which can be monotonic or cyclic over months to years. Understanding of the deformation mechanisms of EDZ is therefore a critical issue to minimize the risk assessment of underground nuclear waste storage in argillaceous formations.

Clay rocks are heterogeneous and multiscale materials. The macroscopic deformation is generally controlled by microscopic effects at smaller scales, mainly due to their sedimentary pattern and geological history. The quantitative response of clay rocks to loadings representative of EDZ events is currently poorly understood, especially for hydric loadings. Despite of challenging works performed by [START_REF] Wang | Microscale experimental investigation of the swelling anisotropy of the Callovo-Oxfordian argillaceous rock[END_REF][START_REF] Wang | Irreversible deformation and damage in argillaceous rocks induced by wetting and drying[END_REF] in which heterogeneous strain fields of Callovo-Oxfordian clay rocks from the Paris basin were acquired by digital image correlation and compared with the microstructure under environmental electronic microscopy, the current literature conclusions regarding the link between strains and microstructure are mostly qualitative and focus on very limited areas.

This study provides a first experimental investigation of the quantitative effects of a hydric loading on strains and microstructure of clay rock, on a millimeter size field of view in high resolution. A case study is presented on a Tournemire clay rock sample, from the Underground Research Laboratory (URL) of Tournemire in Aveyron, France.

Clay rocks are composed of clasts, mainly quartz, carbonates, feldspars and sulfur oxides, surrounded by a matrix composed of clay minerals more or less orientated. At the microscale, strains of Callovo-Oxfordian clay rocks subjected to hydric processes have been qualitatively linked to high area fractions of clay matrix and limited area fractions of rigid silica and carbonates, [START_REF] Montes-H | Structural modifications of Callovo-Oxfordian argillite under hydration/dehydration conditions[END_REF][START_REF] Yang | Dependence of elastic properties of argillaceous rocks on moisture content investigated with optical full-field strain measurement techniques[END_REF][START_REF] Wang | Micromechanical experimental investigation and modelling of strain and damage of argillaceous rocks under combined hydric and mechanical loads[END_REF]. This paper provides a quantitative comparison between strains and local area fractions and sizes of clasts and clay matrix at the microstructure scale, during a hydric loading representative of accelerated humidity conditions of the URL galleries. The objectives of this paper are to present (a) a method which allows the quantitative comparison between microstructure and strains, and (b) an application on Tournemire clay rock.

Material and Methods

Tournemire clay rock

The sample used in this study comes from the Upper Toarcian formation from the Tournemire (URL) of the Institute for Radioprotection and Nuclear Safety (IRSN) in Aveyron, France. The sample comes from the borehole FD90 (depth of 4.20-4.40 m) in the 1997 East Gallery (Fauchille et al., 2016a). The Tournemire URL was excavated in a sedimentary basin composed of sub-horizontal consolidated argillaceous Toarcian and marly Domerian layers, located on the southern border of the French Massif Central [START_REF] Bonin | Deep Geological Disposal in Argillaceous Formations: Studies at the Tournemire Test Site[END_REF][START_REF] Cabrera | Projet Tournemire : Synthèse des Résultats des Programmes de Recherche[END_REF][START_REF] Constantin | Tectonique et fracturation associée dans le bassin des Causses (Aveyron, France): le cas du secteur de Tournemire (Aveyron, France)[END_REF]. The mineralogical composition of the argillaceous rocks from the upper Toarcian layers is mainly 40 wt% clay minerals, illite (5-15 wt%), illite/smectite mixed-layer minerals (5-10 wt%), chlorite (1-5 wt%) and kaolinite (15-20 wt%), 10-20 wt% of quartz grains, 10-40 wt% of carbonates (mainly calcite), and 2-7 wt% of pyrite [START_REF] Bonin | Deep Geological Disposal in Argillaceous Formations: Studies at the Tournemire Test Site[END_REF][START_REF] De Windt | Hydrochemistry in an Indurated Argillaceous Formation (Tournemire Tunnel Site, France)[END_REF][START_REF] Cabrera | Projet Tournemire : Synthèse des Résultats des Programmes de Recherche[END_REF].

Methods

Hydric loading

A cubic clay rock sample of 20x20x20 mm 3 was subjected to a desaturation-saturationdesaturation cycle in a waterproof box at controlled relative humidity (RH) and temperature (T). The sample was initially carefully polished with carbide and diamond products, and saturated at RH=98% with a saline solution of CuSO4, 5H2O and at T=22°C (temperature sensor Testo 175 H1 allowing recording RH at ±2% and T at±0.3°C) for two months. It was then desaturated at RH=33% at the same temperature with a saline solution of MgCl2, then resaturated at 98% and desaturated again at RH=33% (Figure 1a). After the cyclic loading, the sample was subjected to a last desaturation at very low RH (3-5%) with a container of P2O5 placed inside the box. During the hydric process, the sample was placed on a precision balance Adam PGW 753E (precision±0.002 g). The weight of the sample at RH=3-5% was taken as reference for the dry state of the sample, to calculate the mean water content along the process. The water content of the sample is therefore underestimated in comparison with water content values around 5% found in the literature and determined after ovendrying for 48 hours at 105°C [START_REF] Cabrera | Projet Tournemire : Synthèse des Résultats des Programmes de Recherche[END_REF]. Two sample's faces were filmed by optical cameras of 5 Mp (2560x1980 pixels) equipped by a telecentric lens (Figure 2). A first view was composed of an entire sample's face and was filmed at a resolution of 10 µm.pixel -1 . A second view of 5.5 x 4.1 mm² from a part of another face was captured in time at the resolution of 2.2 µm.pixel -1, . Beddings planes are in the vertical direction for the first view, and in the horizontal direction for the second view (Figure 2). This paper focuses on the methodology and results linked to the second view only (Figure 2). A spot light of 400 W was placed next to the waterproof box. It was switched on 2 sec before the image capture and switched off afterwards. Images were taken every 30 seconds to 30 minutes during 55 days, depending on the experiment steps. Images were analyzed by Digital Image Correlation (DIC) in order to calculate hydric strains.

The time steps of the loading were defined as a function of stabilized mean water content and strains (Figure 1b,c). The drop of relative humidity after the saturation phase is due to an accidental slight opening of the box containing the setup. As a consequence only desaturation phases are analyzed in the manuscript. Oscillating mean water contents were due to little cycles of temperature during night and working time though (Figure 1b).

After the completed hydric process, the microstructure of the sample was characterized by a mosaic of back scattered electron images under SEM in order to superimpose microstructure and strains calculated by DIC (Figure 2). The main advantage of the desaturation at RH= 5% explained above is to desiccate smoothly the sample before being analyzed under SEM. Observation under SEM requires the sample desaturation to acquire high quality imaging and avoid any damage of both the machine and the sample. Additional details of the experimental setup are available in Fauchille et al., (2016a).

Digital image correlation (DIC)

DIC is an optical full field measurement method, used on a vast range of materials (metallic alloys, glasses, fluids, geomaterials…) and for many industrial and research applications including geomechanics [START_REF] Sutton | Determination of displacements using an improved digital image correlation method[END_REF][START_REF] Bruck | Digital image correlation using Newton-Raphson method of partial differential correction[END_REF][START_REF] Desrues | Localization of the deformation in tests on sand sample[END_REF][START_REF] Valès | Modes de déformation et d'endommagement de roches argileuses profondes sous sollicitations hydro-mécaniques[END_REF][START_REF] Bornert | Multiscale full-field strain measurements for micromechanical investigation of the hydromechanical behaviour of clayey rocks[END_REF]. It is a non-invasive and a non-destructive method which allows the evaluation of the displacement full-field of a 2D surface. It is performed from the quantitative comparison of image partitions called subsets, from a reference image to a deformed image. The comparison of subsets is based on the comparison of grey levels (8 bit) between an initial image and a final one, modified by a specific kinematical transformation. The optical images of the sample during the hydric process were analyzed by an improved DIC method called H k DIC and developed by [START_REF] Valle | Digital Image Correlation Development for the Study of Materials Including Multiple Crossing Cracks[END_REF]. The software used was X-Correl. This method allows the displacement calculation in the presence of single and or crossed cracks in subsets. It can give accurately the displacements near a crack, without knowing the crack distribution or position. In this study, displacements were calculated in subsets from 32 to 64 pixels, which correspond to 70.4 to 140.8 µm, respectively. Strains were calculated by displacement derivation for steps of 2 pixels (Hédan et al., 2014;Fauchille et al., 2016a). In this study, results are presented for main strains ε and ε (Equations 1,2).

ε , = ε , + ε , 2 + ε , sin 2
(1)

ε , = ε , + ε , 2 - ε , sin 2 with θ = , , , (2)
ε , , ε , and ε , are calculated by displacement derivation on neighbour subsets. Strain fields were determined with an increment of 1 pixel between two subsets.

The sample's speckle is natural and no additional painting was used. An image of the speckle is available in the Supplementary Material part of this paper (Appendix 1). Surface roughness and visible polished clasts within the clay matrix are the only markers on the sample's surface. The standard deviation of grey levels was calculated in all subsets of the analyzed images (Equation 3), in order to control the speckle evolution during the hydric loading.

, = ! 1 # + 1 ² % % & ', ( ) * +, * -& , ---------² ) * ., * (3)
# is the size of the subset (here 32 to 64 pixels), & ', ( is the grey level function for the coordinates ', ( , and & , --------is the mean grey level on the subset for the coordinates , .

Due to the fact that the microstructure of the sample was characterized at a dry state and the presence of cracks at the beginning of the test (Fauchille et al., 2016a), the reference images for DIC were chosen at the end of desiccation steps at t0-1 and t0-2 (Figure1a). At t0-1 and t0-2, hydric cracks are closed and the sample is partially desaturated. These steps are therefore used as hydric-stable reference steps. The deformed images were chosen at the beginning of the test at t1 with open cracks and partial saturation and at the beginning of the second desaturation at t2. This configuration allows an optimized comparison between the highest desiccation strains (Figure 1b) and microstructure.

Out-of-plane tests of digital image correlation were performed in the validation phase of the experimental setup. The results revealed that a displacement of the sample of -0.2 mm to +0.2 mm towards to away from the camera did not disturb the measurements of local displacements [START_REF] Fauchille | Déterminismes microstructuraux et minéralogiques de la fissuration hydrique dans les argilites de Tournemire : apports couples de la pétrographie quantitative et de la correlation d'images numériques[END_REF]. In other words, a shrinkage or swelling of the sample of ±1% in the out-of-plane direction of the surface observed is not noticeable with the optical configuration chosen. The subsets of 32×32 pixels to 64×64 pixels always contain claymatrix and clasts. In this configuration, the DIC code cannot distinguish any difference between small displacement of individual clasts and local strains.

Characterization of Microstructure by a mosaic of images under a scanning electron microscope (SEM)

At the end of the second desiccation, the sample was placed into a desiccator at RH=5%.

Then at tSEM (Figure 1b) a surface of 7.1 mm x 5.5 mm including the surface of 5.5 x 4.1 mm² previously filmed by the camera was scanned under SEM, by a mosaic of 153 backscattered electron (BSE) images of 1024x768 pixels at a resolution of 0.625 µm/pixel. Note here that the sample's deformation between t0-2 and tSEM was considered negligible due to the shrinkage curve of clay materials. In other words, the sample's water content between t0-2 and tSEM was below the so-called shrinkage limit of Tournemire clay rock [START_REF] Boisson | In situ and laboratory investigations of fluid flow through an argillaceous formation at different scales of space and time, Tournemire tunnel, southern France[END_REF]. Images were overlapping in area of 11% in the horizontal direction and 14% in the vertical direction to have an excellent correspondence from an image to the following in both directions. The electron beam drift was taken into account to assemble correctly all images [START_REF] Fauchille | Déterminismes microstructuraux et minéralogiques de la fissuration hydrique dans les argilites de Tournemire : apports couples de la pétrographie quantitative et de la correlation d'images numériques[END_REF]. The image acquisition was performed on SEM JEOL 5600 LV equipped by Brukher Esprit software. The acquisition parameters were a voltage of 15 kV, a magnitude x200, and a working distance of 16.3 mm. BSE images are composed of 256 different grey levels (8bits), in which each grey level represents a mean atomic number and a local mean mineralogical composition. The image acquisition was performed with an optimized BSE contrast with a well-defined histogram of grey levels to facilitate the further phase segmentation. At the resolution of 0.625 µm.pixel -1 , this mode allows a well distinction of clay matrix and micrometer-scale clasts (Appendix 2). The clay matrix is defined at the mescoscopic scale as the homogeneous ground mass of the clay rock, mainly composed of fine clay minerals and clasts smaller than 0.625 µm.

Quantitative characterization of microstructure

Phase segmentation

The mineralogical phases were segmented on the reconstructed mosaic of BSE images by the in-house software MicroPhaseMap (Prêt et al., 2010a,b), according to the histogram of 8 bit grey levels and the variance filter. The clay matrix, clasts composed of quartz, carbonates and heavy minerals, and macropores were considered (Appendix 3). Note here that the clay matrix included small clasts smaller than 0.625 µm because it depends on the scale and the resolution of the study.

Quantitative parameters

From the segmented mosaic of BSE images, quantitative parameters were calculated to describe the microstructure. The area, length ratio and orientation of each type of clast were calculated by ImageJ software and in-house codes [START_REF] Fauchille | Variability in spatial distribution of mineral phases in the Lower Bowland Shale, UK, from the mm-to μm-scale: Quantitative characterization and modelling[END_REF]. The area of a clast corresponds to the total number of its pixels. In the same subsets than those previously used for DIC, the area fraction 0 * (Equation 4) is calculated:

0 * , = 1 # + 1 ² % % 1 2,3 3, ) * 3, * 2, ) * 2, * (4)
1 2,3 is the indicator function and equal to 0 or 1 (1 when the pixel 4, 5 corresponds to the segmented phase and 0 else). # is the size of the subset.

The area fraction of a chosen phase p in a square subset of # × # pixels is the ratio of pixels which correspond to the chosen phase by the total number of pixels in the subset. It is thus included between 0 and 1 (or 0 and 100%). 0 * was calculated with the pixels of mineral phases included in the subsets (grey part in Figure 3a).

Each clast is characterized by a fixed area. The mean area of clasts 6 ̅ * (Equation 5) which characterizes every subset (x,y) was calculated by taking into account all clasts totally and partially included in the subset (grey part in Figure 3b).

6 ̅ * , = 1 8 ; % 6 .

.,: ;

.,

'& 8 ; ; 1 6 ̅ * , = 0 '& 8 ; = 0 (5)
8 ; is the number of clasts in the subset centered in (x;y). 6 . is the area of the clast i (carbonate, quartz or heavy minerals) in the subset centered in (x;y).

The mean area of clasts is the ratio of the sum of areas of the clasts present in the subset by the total number of clasts in the same subset.

The comparison between strains and microstructure was also tested with other microstructure configurations (for example by choosing the clasts only with a center included in the subset), but the two configurations in Figure 3 were considered more representative of the local microstructure. The comparison of strain values with 6 ̅ * and 0 * requires an excellent superimposition between the optical image at t0-2 used for DIC (Figure 1b), and the mosaic of SEM images. To quantify the error of superimposition between these images, the distances between the center of 4 markers (well-visible clasts and macropores)

were measured on both images with Deftac software. The mean error of clast position is in the order of 2.3 µm, that is to say that a clast localized on the reference optical image can be in theory at a distance of ± 2.3 µm around on the SEM images.

2D Mapping

The 2D mapping of area fractions and mean area involves the calculation of the values of area fractions and clast's area on each subset's coordinates. This method brings an extended view of local heterogeneities and multiscale interfaces of the microstructural parameters calculated [START_REF] Fauchille | Relationships between desiccation cracking behavior and microstructure of the Tournemire clay rock by coupling DIC and SEM methods[END_REF][START_REF] Fauchille | Variability in spatial distribution of mineral phases in the Lower Bowland Shale, UK, from the mm-to μm-scale: Quantitative characterization and modelling[END_REF]. The maps of area fractions and mineral's mean area have the same dimensions than the strain fields calculated by DIC. The hydric strain values are therefore superimposed one by one to a value of mineral area fraction and clast mean area. Note here that the comparison between microstructure and strains in the subsets can be performed in larger subsets and therefore may depend on the subset size. However for much larger subsets, strains, area fractions and mean areas tend towards mean values of the entire map. For small subsets, the distribution of phase area fraction tends towards a bimodal distribution due to the segmentation of 100% of clay matrix or 100% of clasts. The comparison between strains and microstructure is therefore presented for the same subset size.

Results

Heterogeneous strain fields at the microstructure scale

Hydric strains were highly variable in space during the hydric process. An example of the main strain fields at t1 compared to t0-1 is represented in Figure 4, for a subset of 32 pixels.

Three main hydric cracks (indicated by black arrows in Figure 4a) separated by around one millimeter distance were detected, especially on ε field (Figure 4 a,b).

Discontinuous concentrations of high strains > 0.05 or < -0.05 of ε and ε , respectively, were locally detected by blue to purple and yellow to red colors (Figure 4 c,d). These high strains were separated by more homogeneous zones in which strains are close to zero, represented in green color. Strain values were very heterogeneous, but the spatial distribution of strain values was also heterogeneous among the sample's surface. Aside from the three main cracks, several areas were high strain-richer than others in which the deformation was more diffused. For example, the red zones 1 and 2 in Figure 4a contained heterogeneous strains including high, low and homogeneous strains, respectively. The results were similar for the desaturation between t2 and t0-2 but the three main cracks showed a much limited aperture.

3.2.Variability of microstructure at the mm scale

The distribution of the clast area fraction (Pclasts) was calculated for three sizes of subsets: 32x32, 48x48 and 64x64 pixels (Figure 5a). The area fractions were calculated with a step of 1 pixel, which caused the smoothing of the distributions but did not change the maximum of the curves. For the three subset's sizes, the distribution of area fractions showed a range of variable values included in [0.02 ; 0.9], which corresponded to 2% to 90% of clasts. There was therefore no subset which contained 100% of clays or 100% of clasts. For subset sizes between 32 to 64 pixels, the clast fraction distributions are the highest at 0.18 to 0.22 (red peaks in Figure 5a), so subsets which contain around 20% of clasts and 80% of clay matrix were the most common on the sample's surface. The three peaks were closer to 0 than 1, so the sample'surface contained more clay-rich than clastrich subsets, for any subset size. The location of Pclast values shown in Figure 5a was represented in a 2D map for a subset of 32 pixels in Figure 5b. As strains have been previously presented, the microstructural parameters of Pclast and Aclast were very heterogeneously distributed among the sample's surface. Several areas showed very low concentrations of clasts (P<0.2) whereas localized areas were characterized by area fractions higher than 0.5. The area fractions higher than 0.5 corresponded qualitatively to zones which are rich in large clasts (Figure 5c). It was particularly visible for clasts larger than 1500 pixels, which is equivalent to a mean diameter of 44 pixels in case of circular grains. High concentrations of large clasts were often surrounded by abrupt concentrations of small clasts, probably due to the fact that large grains were taken into account in different subsets in 6 ̅ 32 calculation (Figure 3b). Large clast-rich zones were consequently more localized and discontinuous on the map, contrary to the area fractions previously mapped.

Relationship between microstructure and speckle

The strain field of ε2 was superimposed to the microstructure in Figure 6. Results were similar for ε1. The superimposition of ε to the microstructure showed that the strain concentrations were both present in the clay matrix, at the interface between clasts and clay matrix, and crossed individual or aggregates of large quartz and carbonates (Figure 6 b,c).

Qualitatively, strains smaller than 0.05 represented in green color were located on the clay matrix with limited size clasts (Figure 6c). Nevertheless, large and round clasts of carbonates and quartz located in Figure 6b were partly characterized by surprising strains higher than 0.05 (blue to purple color in Figure 6c) for the humidity and temperature conditions of the experiment. On the whole strain fields at t1 and t2, high strains values of ε and ε did not correspond to clay matrix-rich areas only and low strains to quartz and carbonate-rich areas. The relationship between strain and microstructure seemed to be more complex than expected. The speckle evolution was then investigated to explain the presence of abnormal high strains on rigid particles, usually inert to water during this type of hydric loading (Figure 7). Figure 7a is an extract of the optical images during the hydric loading,

showing how the speckle on the sample's surface changes in time. The surface showed particular changes of local contrast, on areas smaller than the subset's size. Homogeneous brightness drifts were taken into account in the DIC code in the minimization of the correlation coefficient, but not the local contrast. The 2D maps of the standard deviation of grey levels σsk in subsets of 32 pixels were calculated at t1 and t2. The map of σsk at t2

(which represents the grey level variations between t0-2 and t2) is shown in Figure 7b (Equation 3). This map demonstrates that the speckle changes was located in diffuse areas for σsk between 0 and 0.02 and in specific areas for σsk higher than 0.02, heterogeneously distributed on the surface. The location of those areas was sometimes correlated to zones already characterized by a high area fraction or by a high mean area of carbonates and quartz (Figure 5 b,c). However, plenty of zones presenting a standard deviation of grey levels higher than 0.02 did not show any correlated strain value. The speckle changes' map was then superimposed to the microstructure (Figure 7c to e). High variations of speckle were qualitatively correlated to the presence of relatively large and round clasts but very elongated carbonates did not show any particular strain concentrations (Figures 7e,6c).

Figures 6c and 7f have highlighted that high strains and important speckle changes corresponded to large clasts (carbonate, quartz, pyrite) which did not show any deformation evidence on the SEM images. Lower but significant values of σsk were both characterized by quartz grains surrounded by a local roughness, porous clay matrix aggregates due to sample's shrinkage (red circles). Destroyed clay matrix in microaggregates and microcracks were also detected. However the porous matrix aggregates did not always correspond to significant strain or speckle changes, which leaves the possibility that those aggregates formed during and or after the hydric loading. σsk was then directly compared to the mean area of clasts (Figure 8a). Figure 8a has revealed that a constant area of clasts was related to very different speckle changes. However the standard deviation of grey levels slightly increased from 0.01 to 0.015 with increasing clast sizes. According to the optical images (Figure 7a), polished areas of large clasts might correspond to smoother and blurrier surfaces on the optical images, with a lower local contrast. Consequently the local changes of speckle and strains were partly explained by two effects:

(i) several large clasts had a well plane surface due to the initial polishing which avoided DIC to determine accurately local displacements and strains, which increased the error of strain values (ii) the clasts of quartz were subjected to a slight rotation and detachment caused by the clay matrix shrinkage on their boundaries. It was not observed on carbonate because their texture was more cemented and tortuous contrary to quartz which were individual and rounder grains [START_REF] Fauchille | Déterminismes microstructuraux et minéralogiques de la fissuration hydrique dans les argilites de Tournemire : apports couples de la pétrographie quantitative et de la correlation d'images numériques[END_REF]. The effect of (i) on speckle and strain was significantly higher than (ii).

Figure 8b represents the distribution of σsk values for the two desaturation steps. For the second desaturation, the number of subsets characterized by a σsk > 0.0185 (which corresponds to the crossing point of the two plots in Figure 8b) was 1.44 times higher than for the first one. The speckles changes were quantitatively more important during the second desaturation. The subsets with a σsk > 0.02 were then filtered and not considered in the comparison of strains and microstructure. 0.02 corresponded to the slope change after the peak of normalized frequency. These remaining pixels represented 86.6% of the total number of pixels.

Another possibility to interpret high strains in clast-supported regions was that larger voids filed by water at the end of saturation in those regions were drained before the isolated matrix pores, due to their size. In this case there was a time interval between the desiccation of the matrix around those pores and other locations, due to local porosity heterogeneities.

Those pores might have lead to larger strains between rigid clasts and matrix during moistening and eventually resulted in some strain reversal during desiccation. This interpretation is supported by Philip et al., (2017) who have seen that clast-rich regions could hold open larger pores in Opalinus Clay, potentially being filled with water earlier than the surrounding matrix pores.

Quantitative comparison between strains and microstructure

The quantitative comparison of filtered strain values and microstructural parameters was shown for the first desaturation between t0-1 and t1 in Figure 9 a,b. Results were similar for the second desaturation but the first one was considered the most representative due to a better speckle conservation. For subsets of 32 pixels, the areas fractions Pclast bellow 0.25 corresponded to a high variability of strain values, from -0.025 to 0.075. Strain variability decreased with increasing Pclasts. The relationship between strain and P was not linear.

Comparisons with different subsets sizes for strains and microstructure were tested but the results were similar and no linear tendency was highlighted. An example was given for subsets of 64 pixels (Figure 9b). The subset size did not control the link between microstructure and strain, at the scale of the study. Quartz and carbonate area fractions were separately compared to strains (Figure 9c). Area fractions above 0.1 were associated to decreasing strains and low area fractions, which represented higher area fractions of clay matrix. Quartz and carbonate area fractions bellow 0.1 were associated to very variable strain values. Neither local quartz or carbonate concentration only controled the deformation of the sample. Large clasts corresponded to low strain (Figure 9d) but subsets composed of lots of small clasts presented many values of possible strains. The absence of direct correlation between these two microstructural parameters could be explained by the fact that a same phase fraction corresponded to many arrangements and sizes of clasts (Figure 9 b,e). For example a same area fraction of clays and clasts could correspond to a homogeneous concentration of small clasts in the subset, or to an aggregate of few large clasts surrounded by clays.

Discussion

A comparison between strains and microstructure on a representative area

A range of representative elementary areas (REA) of phase area fraction and clast size has been determined on the same multi millimeter-size surface on Tournemire clay rock, by different methods such as the counting box and the dispersion methods [START_REF] Fauchille | Déterminismes microstructuraux et minéralogiques de la fissuration hydrique dans les argilites de Tournemire : apports couples de la pétrographie quantitative et de la correlation d'images numériques[END_REF][START_REF] Cosenza | Statistical representative elementary area of shale inferred by micromechanics[END_REF]. Microstructural and mechanical (bulk and shear moduli) REA of Tournemire clay rock have been estimated at 345 to 696 µm and 687 to 1772 µm, respectively, for relative errors of 5 to 10% [START_REF] Cosenza | Statistical representative elementary area of shale inferred by micromechanics[END_REF]. Mechanical REA are then two times greater than microstructural REA, but their values support the fact that the comparison between strains and microstructure of this study is representative of the mesoscopic scale of Tournemire clay rock. Other studies demonstrated that for Mont-Terri and Posidonia clay rocks, surfaces larger than 140 x 140 to 250 x 250 µm² (depending on the facies) are representative of mineral area fractions in high resolution [START_REF] Klaver | BIB-SEM study of the pore space morphology in early mature Posidonia Shale from the Hils area, Germany[END_REF][START_REF] Houben | A comparative study of representative 2D microstructures in Shaly and Sandy facies of Opalinus Clay (Mont Terri, Switzerland) inferred form BIB-SEM and MIP methods[END_REF]. At a similar scale and resolution, representative elementary surfaces of Bowland Shale were quantified in the range of a few millimeters depending on the relative error of the phase fraction determined [START_REF] Fauchille | Variability in spatial distribution of mineral phases in the Lower Bowland Shale, UK, from the mm-to μm-scale: Quantitative characterization and modelling[END_REF]. The quantitative superimposition of strains and microstructure was only possible on a multi millimeter surface, due the well-known heterogeneous texture of such rock. The surface filmed in this study was significantly larger than the microstructural and mechanical REAs. The most representative surface of microstructure as possible of the two microstructural parameters was taken into account.

4.2.Complex micro-mechanisms of deformation at the microstructure scale

The results revealed the complexity of micro-mechanisms of clay rock deformation during a hydric loading, at the microstructure scale. Hydric strains were very heterogeneously distributed, as previous works also demonstrated [START_REF] Yang | Dependence of elastic properties of argillaceous rocks on moisture content investigated with optical full-field strain measurement techniques[END_REF][START_REF] Wang | Microscale experimental investigation of the swelling anisotropy of the Callovo-Oxfordian argillaceous rock[END_REF][START_REF] Wang | Irreversible deformation and damage in argillaceous rocks induced by wetting and drying[END_REF]. The local clay and clast area fractions did not control the local strains determined by DIC at the scale investigated, neither the clast size, contrary to other studies on Callovo-Oxfordian argillaceous rock in which hydric strains intensity and location were qualitatively linked to the local mineralogy [START_REF] Yang | Dependence of elastic properties of argillaceous rocks on moisture content investigated with optical full-field strain measurement techniques[END_REF][START_REF] Wang | Micromechanical experimental investigation and modelling of strain and damage of argillaceous rocks under combined hydric and mechanical loads[END_REF][START_REF] Wang | Microscale experimental investigation of the swelling anisotropy of the Callovo-Oxfordian argillaceous rock[END_REF]. If speckle changes unlinked to deformation are removed, strains concentrated in the clay matrix and at interfaces between clasts and clays. However the entire matrix showed a heterogeneous behavior with often no local deformation, which suggests other control factors than local clay, quartz or carbonate area fractions and, larger and/or lower scaledependent factors. This interpretation could be supported by the fact REA of microstructure and REA of bulk and shear moduli are different [START_REF] Cosenza | Statistical representative elementary area of shale inferred by micromechanics[END_REF]. Moreover the surface investigated here contains multi modal heterogeneities which may control very different responses of the material and avoids any simple quantitative relationship between strains and microstructure. The results previously shown and the existing literature therefore highlighted that there was no simple link between the local strains and the microstructure. Rather than looking for local factors which control the local strain values, the identification of non-local microstructural factors could be an interesting aspect to focus on, by using for example multi scale imaging techniques with variable resolutions.

Among all types of clasts, only isolated quartz tilted and detached from the surface.

Excluding possible polishing artefacts, clasts had then various responses due to their shape, tortuosity and contacts which facilitated or not their ability to slip and move along clay particles which are deforming. As Bauer-Plaindoux et al., (1998) interpreted on clay rocks subjected to hydro mechanical tests and as [START_REF] Tran | Rôle de la microstructure des sols argileux dans les processus de retraitgonflement: de l'échelle de l'éprouvette à l'échelle de la chambre environnementale[END_REF] observed on natural and removed clay soils; carbonates can form strong bridges against deformation as well.

At the clay particle scale, [START_REF] Ferrage | Investigation of smectite hydration properties by modeling experimental X-ray diffraction patterns: part I. Montmorillonite hydration properties[END_REF] demonstrated that the hydration mechanisms of swelling clay particles (montmorillonite) were heterogeneous during hydration partly due to the nature of cation available. In addition, [START_REF] Menaceur | The status of water in swelling shales: an insight from the water retention properties of the Callovo-Oxfordian claystone[END_REF] demonstrated that drying clay rock caused a reduction of pore diameter which corresponds to a decreasing thickness of clay platelets. At a larger scale, desiccation-induced shrinkages parallel and perpendicular to beddings were related to different connectivities of pore volumes filled by water [START_REF] Ghorbani | Effects of desiccation on the elastic wave velocities of clay-rocks[END_REF]. The removal of water is enhanced in the direction parallel to bedding, due to a higher pore connectivity. In this study, heterogeneous hydric strains parallel to the bedding revealed that those strains might be also driven by a heterogeneous repartition of water and pore connectivity (heterogeneous connectivity of pore throat surface). Heterogeneous water transfers within the microstructure are strongly suspected.

The desiccation process caused a deterioration of the material with clay matrix aggregation, microcracks and quartz tilt, which joined the interpretation of Gasc-Barbier and Tessier (2007), and [START_REF] Ghorbani | Effects of desiccation on the elastic wave velocities of clay-rocks[END_REF]. The hydric crack network following the strain concentration of the same sample, was partly controlled by the spatial distribution of a range of microstructural parameters: the area fraction, the mean area, the orientation, the length ratio and the number of particles [START_REF] Fauchille | Relationships between desiccation cracking behavior and microstructure of the Tournemire clay rock by coupling DIC and SEM methods[END_REF]. Only the combination of all parameters controled the crack location but none of those was a significant control factor independently from the others. The local hydric crack aperture was also partly controlled by the presence of interfaces of clay-rich and clay-poor zones around the cracks (Fauchille et al., 2016b) even if the relationships are not well understood yet. At much higher temperatures and for lower resolutions, hydric strains of Tournemire clay rock were concentrated in a periodic pattern influenced by the orientation of bedding planes and at the interface between the matrix and a multi millimeter carbonate aggregate (Hédan et al., 2012). During heating, tortuous hydric strains of Kimmeridge clay rock were also heterogeneously distributed and preferentially located at interfaces between clays and nonclay phases and in organic matter [START_REF] Figueroa Pilz | Synchrotron tomographic quantification of strain and fracture during simulated thermal maturation of an organic-rich shale, UK Kimmeridge Clay[END_REF]. The literature highlights then vast types and scales of microstructural interfaces, from the interfaces between individual particles to interfaces of clay-rich and clay-poor areas, until the centimeter scale. Among those scales, the microstructure has different capabilities to deform on either side of those interfaces. The quantification and the location of multi scale interfaces of clay rich and clay poor areas could be thus an interesting aspect to investigate on the same mosaic of SEM images, to improve the understanding of the variability of microstructural scale dependent factors on the local strains.

Limitations of DIC at the microstructure scale

The scale of the study corresponds to a limitation scale for DIC. Indeed, a well-polished surface allowed the accurate segmentation of minerals but smooth surfaces of clasts were not good markers for the DIC speckle. [START_REF] Bornert | Multiscale full-field strain measurements for micromechanical investigation of the hydromechanical behaviour of clayey rocks[END_REF][START_REF] Wang | Micromechanical experimental investigation and modelling of strain and damage of argillaceous rocks under combined hydric and mechanical loads[END_REF] and [START_REF] Yang | Dependence of elastic properties of argillaceous rocks on moisture content investigated with optical full-field strain measurement techniques[END_REF] used surface roughness as a natural speckle but this configuration only allowed a qualitative comparison between strains and microstructure because clasts cannot be clear enough on the images. 2D and 3D higher resolution imaging techniques such as SEM equipped with a field emission gun, transmission electronic microscopes, focused ion beam SEM, X-ray nano-tomography and scanning transmission electron microscopy, have been used to demonstrate that going down the scales doesn't allow the separation of clay matrix and heterogeneities which are smaller and smaller deep inside the material [START_REF] Ma | Novel 3D centimetre-to nano-scale quantification of an organic-rich mudstone: The Carboniferous Bowland Shale, Northern England[END_REF][START_REF] Ma | Correlative multi-scale imaging of shales: a review and future perspectives[END_REF][START_REF] Ma | Hierarchical integration of porosity in shales[END_REF][START_REF] Keller | On the application of focused ion beam nanotomography in characterizing the 3D pore space geometry of Opalinus clay[END_REF][START_REF] Keller | Characterization of multi-scale microstructural features in Opalinus Clay[END_REF]. Due to multi-scale heterogeneities in clay rock, the quality of the DIC speckle formed by the arrangement of mineral phases will be always very heterogeneous. One part of the subsets will contain a significant variance of grey levels which allows their accurate tracking from one image to another (typically where smaller particles are). The other part will be composed of much larger particles represented by homogeneous grey levels, for those any accurate tracking will be possible. Increasing the subset size rather the image resolution is not the solution to calculate the local strain because the strains cannot be separated for the clay matrix than the non-clay phases. Similar speckle problems than those met in this study, will therefore happen in higher resolution.

Consequently there is a sort of scale limit between a "continuous" media allowing a good quality speckle for which the comparison between microstructure and strains is reasonable, and a "discontinuous" media composed of well-defined particles for which the comparison is only local and qualitative, or should be characterized by other methods than DIC.

Scaling effects on hydric strains

Desiccation of clay rocks induced volumetric shrinkage associated to water flows [START_REF] Gasc-Barbier | Conception d'un essai triaxial à succion contrôlée[END_REF]Fauchille et al., 2016a). This phenomenon does not happen for other sedimentary rocks such as sandstones or limestones in which clay fraction is very limited or absent. Macroscopic desiccation-driven hardening described by a mean density rise, is associated to the water content of the clay matrix. Qualitative comparisons on Callovo-Oxfordian clay rock revealed that a higher hardening is associated to a higher clay content [START_REF] Ghorbani | Effects of desiccation on the elastic wave velocities of clay-rocks[END_REF]. During triaxial tests, hydro-mechanical clay properties can be more or less expressed due to the geometrical arrangement of clays and clasts of carbonates [START_REF] Bauer-Plaindoux | Propriétés mécaniques des roches argileuses carbonatées: importance de la relation calcite-argile[END_REF]. Based on the results and the literature, three laboratory scales are suggested:

• At the macroscopic scale, the deformation is partly driven by the mean ability of clays to expand or shrink. This ability is partly controlled by the mean texture.

Heterogeneous thermo hydro mechanical behaviours of clayrock are often explained by heterogeneous arrangements of minerals at smaller scales, such as centimeter-scale clasts embedded in carbonate cement for example, beddings, laminae and macroscopic fractures.

• At the mesoscopic scale, the deformation is driven by very heterogeneous features such as interfaces of phase fractions and properties, in the clay matrix and at clast's boundaries. These features are too different to extract a simple linear trend between one single parameter such as clay area or volume fraction, and the local strain value.

Note here that for these two scales, the presence of preexisting fractures due to the geological history of the material or formed during sample extraction and preparation, may generate preferential pathways for water transfer into the matrix during saturation and desaturation. These preferential pathways for water could be linked to strain heterogeneities during hydroloadings.

• At the clay particle scale, the deformation is also driven by a range of multiple factors such as the pore distribution and connectivity, the clay anisotropy and the nature of cations present in interlayers. The clay particle scale can also be separated in three different scales, from the scale of clay layers, clay aggregates, and mixtures of clay aggregates and very thin clasts with the same size than aggregates [START_REF] Cosenza | Statistical representative elementary area of shale inferred by micromechanics[END_REF].

The hydric deformation has therefore scale-dependent controlling factors.

With DIC, the different scales can be compared to identify the role of microscopic heterogeneities on the strains at the mesoscopic scale, and the role of mesoscopic heterogeneities on the macroscopic scale. However the strains calculated will be always dependent on the speckle. Such a comparison has been done by Fauchille et al., (2016) for three different scales and the results revealed the overestimation of volumetric strains at the largest scale investigated due to the presence of desiccation fractures detectable on the sample surface at two lower scales. The different scales of clay rock cited above are each very different from the others and contain specific heterogeneities, which may require "model" materials (such as consolidated and saturated mixtures of sand and clays) with controlled phase fractions and locations of heterogeneities, to increase the probability to extract quantitative relationships between strains and microstructure.

A synthesis of main results and points addressed in the discussion are shown in Table 1.

Conclusion and Perspectives

A new method was presented to improve the understanding of Tournemire clay rock response to a hydric loading at variable relative humidities and a constant temperature, in within the porous network are suspected and will be further investigated.

List of Figures

  the laboratory. The method aimed to compare quantitatively hydric strains determined by digital image correlation on a sample's surface, and microstructure determined by a 2D mosaic of scanning electron microscopy images, on a high resolution multi millimeter field of view. It has been applied on a representative surface of the mineral area fraction and mineral size. Main results revealed that clay matrix and clasts show a very heterogeneous strain distribution during desiccation. The strain values were not quantitatively and linearly driven by the local area fraction of mineral phases at the study scale, which slightly changes the previous suggestions of quantitative links between clay phase and deformation in clay rock at this scale. Non local microstructural controls and heterogeneous water removals

Figure 1 :

 1 Figure 1: (a) Hydro-loading of relative humidity; (b) Mean water content of the sample as a function of time and (c) Main strains as a function of time, during the whole hydric loading. .............................................................................................................................................. 32 Figure 2: Experimental method to compare strains and microstructure quantitatively. ....... 33 Figure 3 : (a) the internal area of clasts and clays is considered to calculate >?, (b) the entire surface of clasts is taken into account to calculate @?. ............................................. 33

  Figure 1: (a) Hydro-loading of relative humidity; (b) Mean water content of the sample as a function of time and (c) Main strains as a function of time, during the whole hydric loading. .............................................................................................................................................. 32 Figure 2: Experimental method to compare strains and microstructure quantitatively. ....... 33 Figure 3 : (a) the internal area of clasts and clays is considered to calculate >?, (b) the entire surface of clasts is taken into account to calculate @?. ............................................. 33

Figure 2 :

 2 Figure 2: Experimental method to compare strains and microstructure quantitatively.

Figure 3 :

 3 Figure 3 : (a) the internal area of clasts and clays is considered to calculate > ? , (b) the entire surface of clasts is taken into account to calculate @ D ? .

Figure 4 :Figure 5 :

 45 Figure 4: (a) Strain field of A B , (b) high magnification view of (a), (c) strain field of A C and (d) high magnification view of (c), for a subset of 32 pixels and the step t0-1 to t1. Ellipsoid red area 1 contains heterogeneous strains and red area 2 homogeneous strains.

Figure 6 :

 6 Figure 6 : Example of superimposition of strain to microstructure between t0-2 and t2: (a) Extract of A C strain field, (b) segmentation of minerals from the mosaic, (c) superimposition of (a) to (b).

Figure 7 :

 7 Figure 7: (a) Variation of speckle on optical images during hydric loading, (b) Map of the standard deviation σsk of speckle between t0-2 and t2; (c) view of (b); (d) microstructure corresponding to (b); (e) superimposition of σsk and microstructure and (f) BSE -SEM images of clasts corresponded to (e).

Figure 8 :

 8 Figure 8: (a) Standard deviation of grey levels σsk vs the mean area of clasts between t0-2 and t2, (b) distribution of the normalized frequency of σsk for the time steps t0-1 to t1 and t0-2 to t2.

Acknowledgments

The authors would like to express their acknowledgment to the NEEDS-MIPOR program (Nucléaire, Energie, Environnement, Déchets, Société-MIlieux POReux) and to the French Institute for Nuclear Safety and Radioprotection (IRSN) for supporting and funding this work.

Representativeness of the comparison between strains and microstructure

Microstructural REA : REA1 = 345-696 µm* Mechanical REA : REA2 = 687-1772 µm* Surface investigated S = 4,1 x 5 mm²

S II REA2 I REA1

Complex hydromechanisms of clay rock deformation during deformation

Main results

Possible interpretations Recommandations

(1) No linear correlation between strains and clay/clast area fraction.

(2) No linear correlation between strains and clast size.

(3) Strains of clast-rich regions are wrong due to a low local contrast and an evoluting speckle.

Strains could be controled by a combination of microstructural factors.

Heterogeneous porosity and water repartition could control local strains.

DIC might not be the best tool to determine strains at the mesoscopic scale when the surface is wellpolished.

Use model clay materials with controled microstructure to compare quantitatively local strains and microstructural parameters.