Steve Raoul Noumegni
email: stevenoumegni91@yahoo.com

Clément Hoffmann

Divi Cornec

Simon Gestin

; Luc Bressollette

Sandrine Jousse-Joulin

Steve Raoul

Temporal arteries ultrasound to diagnose giant cell arteritis: a practical guide

Keywords: Ultrasound, Temporal arteries, Giant cell arteritis, Doppler

The diagnostic modalities of giant cell arteritis (GCA) have evolved significantly in recent years. Between the different diagnostic tools developed, Doppler ultrasound of temporal arteries with a sensitivity and specificity reaching 69% and 82% respectively, is now recognized to have strong skills and therefore, takes a place of choice in the diagnostic strategies of GCA. Moreover, with the increasing development of new ultrasound technologies, the accuracy of Doppler ultrasound in GCA seems to be constantly improving.

In this article, we describe in details the scanning technique to perform while realizing Doppler ultrasound of temporal arteries to assess GCA, as well as the diagnostic performances of this tool according to current literature.

Introduction

Giant cell arteritis (GCA) is a systemic vasculitis which correspond to a segmental and focal panarteritis (inflammation reaching the entire wall of the arteries) of large and mediumsized arteries [START_REF] Koster | Giant Cell Arteritis: Pathogenic Mechanisms and New Potential Therapeutic Targets[END_REF]. It can affect all vessels of the body, but preferably the external carotid branches (e.g., temporal and occipital arteries 35-90%), the ophthalmic arteries (12-70%), the subclavian arteries (42-46%), the axillary arteries (17.5%-48%), and the thoracic aorta (20-85%). [START_REF] Koster | Giant Cell Arteritis: Pathogenic Mechanisms and New Potential Therapeutic Targets[END_REF][START_REF] Prieto-González | Large Vessel Involvement in Biopsy-Proven Giant Cell Arteritis: Prospective Study in 40 Newly Diagnosed Patients Using CT Angiography[END_REF][START_REF] Agard | Aortic Involvement in Recent-Onset Giant Cell (Temporal) Arteritis: A Case-Control Prospective Study Using Helical Aortic Computed Tomodensitometric Scan[END_REF][START_REF] Czihal | Sonographic and Clinical Pattern of Extracranial and Cranial Giant Cell Arteritis[END_REF][START_REF] Kermani | Arterial Lesions in Giant Cell Arteritis: A Longitudinal Study[END_REF]).

The diagnosis is based on a rigorous clinical and paraclinical approach; confirmation of the diagnosis always justifies the introduction of high dose oral corticosteroid therapy.

However, a strong clinical suspicion especially if severity signs exist, in particular transient amaurosis or blindness, requires the initiation as soon as possible of corticosteroid therapy before the completion of additional examinations tool to confirm the diagnosis [START_REF] Ninan | Giant Cell Arteritis: Beyond Temporal Artery Biopsy and Steroids[END_REF]Winkler and True 2018;[START_REF] Sait | The 2016 Revised ACR Criteria for Diagnosis of Giant Cell Arteritis -Our Case Series: Can This Avoid Unnecessary Temporal Artery Biopsies?[END_REF][START_REF] Hunder | The American College of Rheumatology 1990 Criteria for the Classification of Giant Cell Arteritis[END_REF]). In cases of high clinical probability, the initiation of corticosteroid therapy should not be delayed by paraclinical investigations; however, a well-organized clinical approach should be implement and the realization if necessary of additional examinations (Doppler ultrasound of the temporal arteries, position-emission tomography-PET, magnetic resonance imaging-MRI, computed tomography angiography-CTA) which are considered sufficient to make the diagnosis and clearly eliminate the differential diagnosis [START_REF] Baig | Giant Cell Arteritis: Early Diagnosis Is Key[END_REF][START_REF] Luqmani | The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): A Diagnostic Accuracy and Cost-Effectiveness Study[END_REF][START_REF] Schmidt | Ultrasound in the Diagnosis and Management of Giant Cell Arteritis[END_REF].

Many studies comparing Doppler ultrasound (DU) to temporal arteries biopsy (TAB), reported a sensitivity of around 54-77%, which is not far from TAB sensitivity (39-77%), and is almost better (95.4%) according to some studies [START_REF] Romera-Villegas | The Role of Color Duplex Sonography in the Diagnosis of Giant Cell Arteritis[END_REF][START_REF] Luqmani | The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): A Diagnostic Accuracy and Cost-Effectiveness Study[END_REF][START_REF] Davies | The Role of Temporal Artery Biopsies in Giant Cell Arteritis[END_REF]; moreover, TAB can give false-negative results in up to 60% of cases, due to delay in performing the test after initiation of treatment, sampling errors or the segmented nature of the abnormalities [START_REF] Davies | The Role of Temporal Artery Biopsies in Giant Cell Arteritis[END_REF]. Some of these authors therefore recommend to consider DU as an alternative to temporal artery biopsy [START_REF] Romera-Villegas | The Role of Color Duplex Sonography in the Diagnosis of Giant Cell Arteritis[END_REF]; and the 2018 European League against Rheumatism (EULAR) recommendations even suggest the use of Doppler ultrasound in the first line of the diagnostic process of GCA [START_REF] Ehlers | EULAR Recommendations for a Core Data Set to Support Observational Research and Clinical Care in Giant Cell Arteritis[END_REF].

Despite the fact that DU of temporal arteries require the expertise of a well-trained operators, many physicians of variables medical specialties use to perform DU of temporal arteries depending on their clinical practice without a clearly defined protocol. The lack of standardization of temporal arteries' DU scanning technique, particularly in vascular medicine community lead us to give in this article the diagnostic performances of this test and propose a detailed scanning procedure.

Methods

A comprehensive literature search was performed in Medline/PubMed, EMBASE and Cochrane databases search to identify potentially eligible studies using a combination of the following medical subject headings (MeSH): ultrasound, temporal arteries, giant cell arteritis, doppler. After this, we screened the reference lists of eligible articles with as main objective, to identify articles including metanalysis or most recent articles on accuracies of doppler ultrasound in the diagnosis of GCA. Search results were compiled using the citation management software Zotero version 5.0.77. This review started in December 2019 and ended in February 2020. We therefore, carried out an extensive narrative and critical literature review on diagnosis performances of DU to diagnose GCA and after giving a detail description of the scanning technique. All relevant papers were consulted independently of design and year of publication; we therefore found and consulted 6 articles from Cochrane library (5 of them available in EMBASE) and 18 from PubMed/Medline.

Generality on GCA

Giant cell arteritis, is a systemic vasculitis affecting large and medium-sized arteries that can be both cranial (10-46% of patients) and extra-cranial (54%-87%) ; among the cranial arteries, the most affected are the temporal arteries [START_REF] Koster | Giant Cell Arteritis: Pathogenic Mechanisms and New Potential Therapeutic Targets[END_REF][START_REF] Czihal | Sonographic and Clinical Pattern of Extracranial and Cranial Giant Cell Arteritis[END_REF][START_REF] Nesher | Low-Dose Aspirin and Prevention of Cranial Ischemic Complications in Giant Cell Arteritis[END_REF][START_REF] Kermani | Arterial Lesions in Giant Cell Arteritis: A Longitudinal Study[END_REF].

Patients with GCA may have visual disturbances, including blindness or transient amaurosis, which should be considered as severity signs, and should lead to the urgent initiation of corticosteroid therapy initially intravenous with 1 to 3 bolus of Methylprednisolone (240 to 1000 mg / day), followed by oral corticosteroid therapy at a daily dose of 0.7 to 1 mg / kg) [START_REF] Soriano | Visual Loss and Other Cranial Ischaemic Complications in Giant Cell Arteritis[END_REF]. Patients may also have headache or neck pain, jaw claudication, abnormal sensitivity of the temples to palpation and arthromyalgia as seen in isolated rhizomelic pseudo-polyarthritis [START_REF] Sait | The 2016 Revised ACR Criteria for Diagnosis of Giant Cell Arteritis -Our Case Series: Can This Avoid Unnecessary Temporal Artery Biopsies?[END_REF]. Finally, GCA affected patients present in almost all cases (80-93%), a with a biological inflammatory syndrome that consists of an increase in the level of C-reactive protein (CRP) (sensitivity of 86.9-100%), and/or an increase in erythrocyte sedimentation rate (ESR) (sensitivity of 76 -92 %). (Waller and Jawad 2017; [START_REF] Kermani | Utility of Erythrocyte Sedimentation Rate and C-Reactive Protein for the Diagnosis of Giant Cell Arteritis[END_REF][START_REF] Levy | How Common Is Inflammatory Marker-Negative Disease in Giant Cell Arteritis?[END_REF]. Despite the regularity of clinical and biological signs in patients with GCA, the diversity of potential differential diagnoses requires a rigorous diagnostic approach; the ACR (American College of Rheumatology) criteria originally defined in 1990 with a sensitivity of 93.5% and a specificity of 91.2%, were established to facilitate this process [START_REF] Hunder | The American College of Rheumatology 1990 Criteria for the Classification of Giant Cell Arteritis[END_REF]). They include (with a diagnosis threshold of 3/5 criteria), age of 50 years or older, new-onset headache, temporal artery abnormality (tenderness to palpation or decreased pulsation, unrelated to atherosclerosis of cervical arteries), elevated erythrocyte sedimentation rate ESR ≥ 50 mm/h, and abnormal TAB [START_REF] Hunder | The American College of Rheumatology 1990 Criteria for the Classification of Giant Cell Arteritis[END_REF]). It should be noted that these criteria include the histology of the temporal arteries and therefore the need to carry out a TAB; which in some cases, would remain useful up to 4 weeks after the initiation of corticosteroid therapy [START_REF] Sait | The 2016 Revised ACR Criteria for Diagnosis of Giant Cell Arteritis -Our Case Series: Can This Avoid Unnecessary Temporal Artery Biopsies?[END_REF][START_REF] Ray-Chaudhuri | Effect of Prior Steroid Treatment on Temporal Artery Biopsy Findings in Giant Cell Arteritis[END_REF].

A positive TAB usually finds a segmental and focal panarteritis with or without a multinuclear giant cell granuloma [START_REF] Stacy | Subtleties in the Histopathology of Giant Cell Arteritis[END_REF]. There is a fibrous thickening of the intima, destruction of the internal elastic lamina with histiocytic reaction on contact, destruction of the smooth muscle cells of the media with a polymorphic inflammatory infiltrate predominantly of mononuclear cells (lymphocytes, hystiocytes, plasma cells) which can extend to all three parietal tunics of vessel wall [START_REF] Stacy | Subtleties in the Histopathology of Giant Cell Arteritis[END_REF]. Blood cloth are also present in some cases, and unlike seen in other vasculitis, fibrinoid necrosis is rare [START_REF] Stacy | Subtleties in the Histopathology of Giant Cell Arteritis[END_REF][START_REF] Lee | Clinical Course and Management of a Consecutive Series of Patients with 'Healed Temporal Arteritis[END_REF]. In addition, it should be noted that GCA can interest the intra or extra-adventitious vessels (vasa vasorum) and histologically give an infiltrate of pericapillary mononuclear inflammatory cells with absence of fibrinoid necrosis; what makes the difference with necrotizing vasculitis like granulomatosis with polyangiitis [START_REF] Esteban | Small-Vessel Vasculitis Surrounding a Spared Temporal Artery: Clinical and Pathological Findings in a Series of Twenty-Eight Patients[END_REF].

According to the literature, given the invasiveness of TAB and the limits of its sensitivity, which is around 77% [START_REF] Rubenstein | Sensitivity of Temporal Artery Biopsy in the Diagnosis of Giant Cell Arteritis: A Systematic Literature Review and Meta-Analysis[END_REF], studies have been carried out to determine whether a different approach could be used to assess GCA. This is how several modalities such as PET-scanning, MRI and especially Doppler ultrasound (DU), have been studied and are more and more often used in clinical practice [START_REF] Davies | The Role of Temporal Artery Biopsies in Giant Cell Arteritis[END_REF].

Overview of temporal arteries anatomy

The superficial temporal artery (STA) which participates in the vascularization of the parotid gland and the lateral part of the face and scalp, is the smaller of the two terminal branches of the external carotid artery, the maxillary artery being the most important; it arises in the parotid gland and goes upwards, in the same orientation as the external carotid [START_REF] Pinar | Anatomy of the Superficial Temporal Artery and Its Branches: Its Importance for Surgery[END_REF]. Shortly after its origin and before it leaves the parotid, the superficial temporal artery gives a first collateral, the transverse facial artery; then, it continues upward before leaving the parotid accompanied by the superficial temporal vein and the auriculotemporal nerve issuing from the mandibular nerve [START_REF] Nakajima | The Arterial Anatomy of the Temporal Region and the Vascular Basis of Various Temporal Flaps[END_REF][START_REF] Doscher | Superficial Temporal Artery and Vein as Recipient Vessels for Scalp and Facial Reconstruction: Radiographic Support for Underused Vessels[END_REF].

The STA further passes in front of the tragus and behind the temporomandibular joint, crosses the zygomatic arch and becomes subcutaneous; it is at this level that we can have the pre-tragic pulse while the palpation of the temporal pulse takes place a little higher on the path of the artery [START_REF] Nakajima | The Arterial Anatomy of the Temporal Region and the Vascular Basis of Various Temporal Flaps[END_REF]. At the level of the upper edge of the zygomatic process, STA gives two important collaterals: the middle temporal and zygomatico-orbital (or zygomatico-malar) arteries. The middle temporal artery which provides vascularization of the temporal muscle, crosses the fascia and anastomoses with the anterior and posterior deep temporal arteries originating from the maxillary artery [START_REF] Pinar | Anatomy of the Superficial Temporal Artery and Its Branches: Its Importance for Surgery[END_REF][START_REF] Stock | Anatomy of the Superficial Temporal Artery[END_REF]. Between 3 and 5 cm above the zygomatic arch, the superficial temporal artery divides into two terminal branches: a frontal anterior branch and a posterior parietal branch (Figure 1) [START_REF] Cobb | Superficial Temporal Artery: The 'C' Shape Half-Buttonhole Configuration as It Courses over the Zygomatic Arch[END_REF].

It is important to mention that many anatomic variations exist. A recent meta-analysis reported that the frontal and parietal branches of the STA are present in 97.6% and 96.4% of the cases, respectively and that in3.1% of the cases, there were no bifurcation [START_REF] Koziej | The Superficial Temporal Artery: A Meta-Analysis of Its Prevalence and Morphology[END_REF]. When it exist, The STA bifurcation point is located above the zygomatic arch in 79.1%, below the zygomatic arch in 6.7%, and on the zygomatic arch in 11.1% of the cases [START_REF] Koziej | The Superficial Temporal Artery: A Meta-Analysis of Its Prevalence and Morphology[END_REF]).

Setting to be used for Doppler ultrasound of temporal arteries

Modern high-frequency ultrasound probes provide excellent resolution of 0.1 mm, particularly in anatomical areas that localize within 1 cm below the skin surface; therefore, DU is particularly valuable for examining the common superficial temporal arteries, as well as their frontal and parietal branches [START_REF] Schmidt | Ultrasound in the Diagnosis and Management of Giant Cell Arteritis[END_REF].

According to the 2018 recommendations of the EULAR on the use of ultrasound technique to assess GCA, probes with a frequency greater than or equal to 15 Mhz in 2 dimensions (2D) and frequencies between 7 and 12 Mhz in Doppler mode should be used for the study of temporal arteries [START_REF] Ehlers | EULAR Recommendations for a Core Data Set to Support Observational Research and Clinical Care in Giant Cell Arteritis[END_REF]. For the study of extra-cranial supra-aortic trunks, probes of frequency between 7 and 15 Mhz in 2D and of frequency between 4 and 8 Mhz in Doppler mode should be used [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF][START_REF] Ehlers | EULAR Recommendations for a Core Data Set to Support Observational Research and Clinical Care in Giant Cell Arteritis[END_REF]. Probes with frequencies >20 MHz are increasingly available, and such probes may allow a better visualization of temporal arteries wall and intima-media complex [START_REF] Schmidt | Ultrasound in the Diagnosis and Management of Giant Cell Arteritis[END_REF]. A study is ongoing in our unit to compare a 18 MHz probe with a 22 MHz probe in the diagnostic of giant cell arteritis with final diagnosis retained by the physician as gold standard; results are expected to be publish very soon (registered as clinical trial under number: 29BRC19.0275).

The gain and the dynamic range must allow the differentiation of the vascular wall from the lumen of the vessel. The pulse repetition frequency (PRF) should be set between 2 and 3.5 kHz depending on the on the velocity of the flow and the depth. The angle between sound waves and artery should be ≤60° [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF]. A PRF too high and a gain too low can give a false Halo sign at the level of irregular thickened area, as seen in case of arteriosclerosis; this can be avoid after choosing a adapted PRF by gradually increase the gain until the appearance of a overfilling of the vessel, and then decrease the gain just below that point.

The use of power mode is interesting for the study of very superficial arteries; as it generally allows to better fill the lumen of the vessel. Indeed, this mode does not depend on angle between sound waves and artery and has a higher sensitivity for flow detection. The use of Color Doppler mode and power mode is then possible but the EULAR recommendations clearly suggest to prefer Color Doppler mode [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF]). Many other Doppler modes which may enhance the quality of ultrasound images particularly for very small vessel, have been recently developed, these modes include the wide-band mode, the B-flow mode and the color velocity imaging (CVI) mode; but event if there are few data in the literature on the application of these modes in temporal arteries assessment, these data remain insufficient to support the added value of these modes in the diagnosis of GCA [START_REF] Tegeler | Color Velocity Imaging: Introduction to a New Ultrasound Technology[END_REF][START_REF] Volpe | B-Flow Ultrasound in a Case of Giant Cell Arteritis[END_REF][START_REF] Monti | The Proposed Role of Ultrasound in the Management of Giant Cell Arteritis in Routine Clinical Practice[END_REF].

Scanning technique of temporal arteries ultrasound

When performing DU of the temporal arteries, patients should be lying supine or semiseated, they can also be lying laterally. Whether supine or lateral, in our experience, the examiner is seated or standing at the right of the patient; who respectively present its right and then left temporal area or vice versa for the analysis of the homolateral artery. It is important to note that this varies by center and also depend on operator habits. In our center, we usually use an "Toshiba Canon Aplio i800" brand ultrasound machine with a linear probe with greyscale frequency of 18 MHz; the gain and PRF (2-3 kHz) are set to allow a clearly differentiation of the vessel.

We usually start by locating the common trunk of the temporal artery examined in transverse section by placing the ultrasound probe at the level of the tragus perpendicular to the supposed axis of the artery (Figure 2); with the probe indicator directed to the front. A first global scan using B Mode and Color Doppler is then carried out with the aim of identifying the potential easily detectable abnormalities and locating the arterial bifurcation as well as the frontal and parietal branches.

We then continue the examination by resuming more slowly with maximum attention a scan in transverse then in longitudinal section of the temporal artery, its parietal and frontal branches; followed each time by a firm compression of the artery to identify a possible compression sign (Figure 3). Compression is performed systematically in our practice whether or not there is a Halo sign. The longitudinal section scan is not always carried out when no abnormality is identified in transverse section, especially at the level of frontal and parietal branches. Sometimes we can use power mode (Figure 4) when the artery has a significant atheromatous infiltration so as not to wrongly conclude that there is an occlusion.

Table 1 gives a summary of procedure to perform temporal arteries ultrasound.

Positive ultrasound sign in GCA Halo sign

Halo sign is described as a hypo or iso-echogenic dark aspect of the vessel walls, which is more often regular and circumferential in transverse view (Figure 5) [START_REF] Habib | Color Duplex Ultrasonography of Temporal Arteries: Role in Diagnosis and Follow-up of Suspected Cases of Temporal Arteritis[END_REF]). This sign is just a translation of the thickening of vessel wall due to inflammation and some authors even consider it as a pathognomonic sign of GCA on ultrasound (van der [START_REF] Geest | Novel Ultrasonographic Halo Score for Giant Cell Arteritis: Assessment of Diagnostic Accuracy and Association with Ocular Ischaemia[END_REF][START_REF] Arida | The Diagnostic Value of Ultrasonography-Derived Edema of the Temporal Artery Wall in Giant Cell Arteritis: A Second Meta-Analysis[END_REF].

According to the literature, in patients with a strong clinical suspicion of GCA, the sensitivity and specificity of Halo sign are respectively 77% and 96%, with a specificity reaching 100% in case of bilateral sign [START_REF] Duftner | Imaging in Diagnosis, Outcome Prediction and Monitoring of Large Vessel Vasculitis: A Systematic Literature Review and Meta-Analysis Informing the EULAR Recommendations[END_REF]. These characteristics may be improved by the compression of the arteries studied by the ultrasound probe; which may thus rise the sensitivity between of 77 to 79% and lead to a specificity of 100% (M. [START_REF] Aschwanden | Temporal Artery Compression Sign--a Novel Ultrasound Finding for the Diagnosis of Giant Cell Arteritis[END_REF]2015). A study by Nesher G et all carried out on 69 patients suspected with GCA in 2002, found that the Halo sign in 24 of 69 patients and GCA was diagnosed in 12 of them, giving a positive predictive value of only 50%. While no Halo was detected in 45 cases of which only 2 had GCA, resulting in a high negative predictive value of 96% [START_REF] Nesher | The Predictive Value of the Halo Sign in Color Doppler Ultrasonography of the Temporal Arteries for Diagnosing Giant Cell Arteritis[END_REF]. Another study reported a higher positive predictive value up to 96.6% especially in case of bilateral Halo sign [START_REF] Aranda-Valera | Diagnostic Validity of Doppler Ultrasound in Giant Cell Arteritis[END_REF].

A recent study described a Halo score which allows to quantify the extent of vascular inflammation in GCA; with extensive vascular inflammation on ultrasound providing a strong diagnostic confirmation and association with ocular ischaemia (van der [START_REF] Geest | Novel Ultrasonographic Halo Score for Giant Cell Arteritis: Assessment of Diagnostic Accuracy and Association with Ocular Ischaemia[END_REF].

This score encompassed both the number of Halos (number of temporal arteries segments and axillary arteries with Halo sign, and the maximum halo thickness in each vascular region); it varies between 0 and 48 with a value of 10 or above defining a high Halo score that may help to firmly diagnose GCA in a substantial portion of patients (21%), with a high specificity (>95%) (van der [START_REF] Geest | Novel Ultrasonographic Halo Score for Giant Cell Arteritis: Assessment of Diagnostic Accuracy and Association with Ocular Ischaemia[END_REF].

Compression sign

A positive compression sign is defined as visibility of the vessel wall upon transducerimposed compression of the artery (Figure 3) ; this sign has been described by Aschwanden et al, and has diagnostic properties similar to the Halo sign for ACG research (M. [START_REF] Aschwanden | Temporal Artery Compression Sign--a Novel Ultrasound Finding for the Diagnosis of Giant Cell Arteritis[END_REF]). In fact, in a prospective study on 80 subjects suspected of having GCA, the authors highlighted Halo sign and compression sign in 34 of the 43 subjects finally diagnosed with GCA, resulting in a sensitivity of 79 % and a specificity of 100 % for both the Halo and the compression sign (M. [START_REF] Aschwanden | Temporal Artery Compression Sign--a Novel Ultrasound Finding for the Diagnosis of Giant Cell Arteritis[END_REF]. Moreover, the compression sign is a simple and robust sonographic marker with excellent inter-observer agreement; this has been shown by Aschwanden et all in a study where two physicians examined 60 consecutive patients with suspicion of GCA and found identical results in 59 of the 60 patients, giving a strong inter-observer agreement of 0.92 (M. [START_REF] Aschwanden | The Ultrasound Compression Sign to Diagnose Temporal Giant Cell Arteritis Shows an Excellent Interobserver Agreement[END_REF].

Finally, due to the fact that both Halo and compression signs are translation of vessel wall inflammation, the compression sign can be considered as a mirror of Halo sign which can help to reduce the risk of misdiagnosis due to an inappropriate color gain or PRF setting.

Others signs

In addition to the Halo sign and the compression sign, several studies have reported other ultrasound abnormalities that may be encountered in the GCA; theses abnormalities include stenosis, occlusions, modification of the intima-media thickness and sometimes aneurysm [START_REF] Ehlers | EULAR Recommendations for a Core Data Set to Support Observational Research and Clinical Care in Giant Cell Arteritis[END_REF][START_REF] Schäfer | Ultrasound Cut-off Values for Intima-Media Thickness of Temporal, Facial and Axillary Arteries in Giant Cell Arteritis[END_REF]. Stenosis are diagnosed on color and pulsed Doppler flow analysis; they are characterized by an acceleration of the circulatory flow (Figure 6), a spectral dispersion and modifications of downstream and upstream flows. As in other inflammatory diseases, stenosis in GCA are usually long, regular, threadlike, and symmetric; they can be confused with atheromatous stenosis which are often shorter, irregular, calcified and asymmetric (Figure 6) [START_REF] Gülcü | Long-Term Follow-Up of Endovascular Repair in the Management of Arterial Stenosis Caused by Takayasu's Arteritis[END_REF]. Despite the frequent rate of these abnormalities, it is important to note that neither stenosis, nor occlusions which are recognized by an absence of Doppler flow, has proven sufficient diagnostic value for GCA [START_REF] Begarin | Performance diagnostique d'un nouveau critère échographique dans la maladie de Horton : épaisseur intima media temporale/épaisseur intima media carotidienne[END_REF].

Accuracy and reliability of temporal arteries Doppler ultrasound in GCA diagnosis

In a meta-analysis made by [START_REF] Karassa | Meta-Analysis: Test Performance of Ultrasonography for Giant-Cell Arteritis[END_REF] including 23 studies and 2036 patients suspected with GCA, the weighted sensitivity and specificity of a positive DU based on the halo sign was 69% and 82%, respectively, compared with biopsy, and 55% and 94% respectively, compared with ACR criteria (2005). Several other literature review with or without meta-analysis were carried out since with the aim of determining the diagnostic performance of DU in the diagnosis of GCA; thus in 2010, Arida et al reported a sensitivity and specificity of 68% and 91% respectively with ACR criteria as gold standard (2010). Ball et al also in 2010, reported a sensitivity and specificity of 75% and 83%, respectively, with TAB as a reference test. Two more recent meta-analysis where made in 2018 and 2019; the first by Duftner et al in 2018, including 8 studies and 605 patients with the final diagnosis retained by the clinician as a reference test reported a sensitivity and specificity of 77% and 96% respectively (2010; 2018) ; the second made by Rinagel et al including 25 studies and 1062 patients with TAB as reference test reported a sensitivity of 68% and a specificity of 81% [START_REF] Rinagel | Diagnostic Performance of Temporal Artery Ultrasound for the Diagnosis of Giant Cell Arteritis: A Systematic Review and Meta-Analysis of the Literature[END_REF]). These different reviews reporting a sensitivity varying between 69 and 77% and a specificity varying between 82 and 96%, suggest that DU could be a good alternative to TAB in many patients; moreover, DU may be more sensitive than temporal artery biopsy because the last evaluates only a limited anatomical region in a systemic disease [START_REF] Schmidt | Ultrasound in the Diagnosis and Management of Giant Cell Arteritis[END_REF]. Moreover, even if the values reported were inferior to those widely described in literature, Luqmani et al found a better sensitivity of ultrasound (54%, 95% CI: 48% to 60%) compared to biopsy (39%, 95% CI: 33% to 46%) in a study carried out in 2016, including 381 patients suspected with GCA (2016). Table 2 gives a summary of the studies presented above.

Despite the fact that DU of the temporal arteries is highly operator dependent, requiring to develop and maintain expertise in the technique, the 2018 EULAR recommendations propose the use of DU of temporal arteries associated or not to DU of axillary arteries in the first line of the diagnostic process of GCA, with a condition, that this exam should be immediately accessible, so as not to delay treatment if required (Dejaco et al. 14 2018). The advantages of DU over other imaging techniques in GCA are based on its availability, safety, tolerability and its high resolution of 0.1 mm [START_REF] Schmidt | Ultrasound in the Diagnosis and Management of Giant Cell Arteritis[END_REF]. EULAR also suggest that in the case of a strong pre-test probability, a positive DU may be sufficient to make the diagnosis of GCA, without performing TAB [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF] ; for example, in patients with a high clinical suspicion of GCA (>50%), in case of jaw claudication, visual symptoms, new-onset headache, and elevated CRP and ESR, a positive ultrasound would result in a post-test probability of at least 95%, and a negative ultrasound decreases the probability to 20%, hence, GCA is still the possible diagnosis and further investigations are necessary [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF][START_REF] Griner | Selection and Interpretation of Diagnostic Tests and Procedures. Principles and Applications[END_REF]. Conversely, considering a pretest probability of 5% and a positive ultrasound result, the post-test probability would increase only up to 50% and in case of a negative ultrasound, however, the post-test probability is just around 1.3%; thus in case of low diagnostic suspicion of GCA, a normal DU makes the diagnosis very unlikely [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF][START_REF] Griner | Selection and Interpretation of Diagnostic Tests and Procedures. Principles and Applications[END_REF].

A recent review by Brkic et al on the clinical applicability of ultrasound in systemic vasculitis reaching the large vessels highlighted several benefits of temporal arteries DU in patients with suspected GCA, including the significant reduction in the prevalence of blindness by its early realization and the initiation of corticosteroid therapy when necessary [START_REF] Brkic | Clinical Applicability of Ultrasound in Systemic Large Vessel Vasculitides[END_REF]). The early realization of DU, especially within the 24 hours after the admission may be highly benefit in term of complications' prevention and, this is why the fast-track approach described in 2016 and which decreases to up to 88% the risk of blindness compared with the conventional standard of care, is promoted [START_REF] Diamantopoulos | The Fast-Track Ultrasound Clinic for Early Diagnosis of Giant Cell Arteritis Significantly Reduces Permanent Visual Impairment: Towards a More Effective Strategy to Improve Clinical Outcome in Giant Cell Arteritis?[END_REF]).

However, regarding the limits of this diagnostic tool, notably related to the fact that it is highly operator dependent despite the good intra-reader and inter inter-reader reliabilities, the authors propose an algorithm integrating a clinical score of probability of the GCA [START_REF] Brkic | Clinical Applicability of Ultrasound in Systemic Large Vessel Vasculitides[END_REF][START_REF] Laskou | A Probability Score to Aid the Diagnosis of Suspected Giant Cell Arteritis[END_REF][START_REF] Schäfer | Assessing Vasculitis in Giant Cell Arteritis by Ultrasound: Results of OMERACT Patient-Based Reliability Exercises[END_REF]. This score which details can be found in article Laskou et al [START_REF] Laskou | A Probability Score to Aid the Diagnosis of Suspected Giant Cell Arteritis[END_REF], includes age, gender, duration of symptoms, CRP value, symptoms (headache, polymyalgic symptoms, ischaemic symptoms of jaw claudication or visual disturbance, constitutional symptoms as fever of unknown origin, night sweats, unintentional weight loss), signs (visual disturbances, temporal arteries abnormalities, extracranial arteries abnormalities, cranial nerve palsy) and possible alternative diagnosis (infection, cancer, systemic rheumatic diseases, head and neck pathology, or other) [START_REF] Laskou | A Probability Score to Aid the Diagnosis of Suspected Giant Cell Arteritis[END_REF]; out of a possible maximum score of 32, a value of 9 or below defines low probability of GCA and a value of 10 or above defines high probability of GCA with a sensitivity of 95.7%, a specificity 86.7%, and 88.4% of correctly classified cases considering the diagnosis ascertained after 6 months follow up as gold standard [START_REF] Laskou | A Probability Score to Aid the Diagnosis of Suspected Giant Cell Arteritis[END_REF].

Place of other imaging tools for the diagnosis of GCA

In addition to DU, several other imaging tools have been studied in recent years in the diagnosis of giant cell arteritis. CTA and MRI are used for the diagnosis of extra-cranial forms of GCA; they are mainly interesting in the detection of large vessels involvement [START_REF] Prieto-González | Large Vessel Involvement in Biopsy-Proven Giant Cell Arteritis: Prospective Study in 40 Newly Diagnosed Patients Using CT Angiography[END_REF]. CTA can be used to detect temporal arteries abnormalities (blurring of the vessel wall and enhancement of the perivascular soft tissues) with a sensitivity of 71.4%, and a specificity of 85.7% for diagnosis of GCA considering TAB as gold standard [START_REF] Conway | Diagnostic Utility of Computed Tomographic Angiography in Giant-Cell Arteritis[END_REF]. MRI in patients with GCA allows study of the inflammatory arterial wall taking contrast in T1 weighted image , when edema is visible in T2 weighted image [START_REF] Siemonsen | 3T MRI Reveals Extra-and Intracranial Involvement in Giant Cell Arteritis[END_REF] ; its sensitivity and specificity are respectively around 88.9 and 91.7 with ACR criteria as gold standard and they are around 100% and 80% respectively when considering TAB as gold standard [START_REF] Bley | Assessment of the Cranial Involvement Pattern of Giant Cell Arteritis with 3t Magnetic Resonance Imaging[END_REF]. Note that the high resolution 3 Teslas MRI allows analysis of the cephalic arteries (intra and extra-cranial) in addition to the arteries of the large vessels [START_REF] Siemonsen | 3T MRI Reveals Extra-and Intracranial Involvement in Giant Cell Arteritis[END_REF]. The PET can identify vasculitis lesions' in the whole body, brain metabolism interfering with interpretation; this tool has a sensitivity of 66.7% and a specificity of 100% with a positive predictive value which may be higher than the CTA in GCA [START_REF] Lariviere | Positron Emission Tomography and Computed Tomography Angiography for the Diagnosis of Giant Cell Arteritis: A Real-Life Prospective Study[END_REF].

Place of Doppler ultrasound for follow-up of patients with GCA

According to the use of ultrasound in follow up of patient with GCA, studies reported the disappearance of the Halo sign in temporal arteries in the majority of patients after 2 to 4 weeks of corticosteroid therapy (69% at 2 weeks and 100% at 4 weeks) ; which seem to be consistent with the period of potentially positive TAB after initiation of corticosteroid therapy [START_REF] Habib | Color Duplex Ultrasonography of Temporal Arteries: Role in Diagnosis and Follow-up of Suspected Cases of Temporal Arteritis[END_REF][START_REF] Karahaliou | Colour Duplex Sonography of Temporal Arteries before Decision for Biopsy: A Prospective Study in 55 Patients with Suspected Giant Cell Arteritis[END_REF][START_REF] Ray-Chaudhuri | Effect of Prior Steroid Treatment on Temporal Artery Biopsy Findings in Giant Cell Arteritis[END_REF]. Note that the time to disappearance of the Halo sign can varies widely between 2 days and several months after initiation of corticosteroid therapy at the levels of extra-cranial arteries in general [START_REF] Santoro | Temporal Ultrasonography Findings in Temporal Arteritis: Early Disappearance of Halo Sign after Only 2 Days of Steroid Treatment[END_REF]Markus Aschwanden et al. 2010). Therefore, the examination of these vessels might be of potential value for monitoring purposes; however, none of these studies addressed whether DU was helpful for the assessment of relapse [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF]. The EULAR therefore recommend that DU and/or MRI, and or CTA may be used in patients with GCA for long-term monitoring of structural damage, particularly to detect stenosis, occlusion, dilatation and/or aneurysms; with the frequency of screening as well as the imaging method applied defined on an individual basis [START_REF] Dejaco | EULAR Recommendations for the Use of Imaging in Large Vessel Vasculitis in Clinical Practice[END_REF].

Conclusion

Ultrasound of temporal arteries has emerged in recent year and is now one of the first line diagnosis tools for giant cell arteritis. Despite the fact that it has good inter-observer and intra-observer variability, the particularity of this imaging exam is that it is highly operator dependent, and thus can lead to non-neglected rate of false negative or false positive cases if it is not performed in an appropriate manner. Moreover, the early realization of this exam can considerably decrease the risk of severe complications; this highlight once again the necessity of efficient acquisition and interpretation of images, which can be obtained only by harmonization and standardization of scanning techniques widely among physician.

Step

Patient installation supine, semi-seated or in lateral decubitus

Step

Setting verification

Step Location of common trunk of the temporal artery in transverse section by placing the ultrasound probe at the level of the tragus perpendicular to the axis of the artery

Step

Global transverse scanning to identify using B Mode and Color Doppler easily detectable abnormalities and locating the arterial bifurcation

Step Slow scan in transverse and longitudinal section of common trunk, frontal and parietal branches to identify potentially existing Halo sign

Step Slow scan in transverse section with segmental compression to identify potentially existing compression sign.

Step Slow scan in transverse section with power mode if there is a significant atheromatous infiltration

  Physicians ofEdinburgh. 2017; 47 (3): 303. Winkler A, and True D. "Giant Cell Arteritis: 2018 Review." Missouri Medicine 2018; 115 (5): 468-70.

Figure 1 :

 1 Figure 1: superficial temporal arteries, from the book "gray anatomy of human body".

Figure 2 :Figure 3 :

 23 Figure 2: position of the ultrasound probe at the beginning of examination of a right

Figure 4 :

 4 Figure 4: common normal left temporal artery examined by Doppler mode (A) and

Figure 5 :

 5 Figure 5: Halo sign on a left common temporal artery on Doppler mode (A) and power

Figure 6 :

 6 Figure 6: Normal flow in a right tortuous common temporal artery on Doppler mode

Table 1 : procedure to perform temporal arteries ultrasound

 1

Table 2 : overview of DU sensitivity and specificity based on halo sign for GCA.

 2

	Authors, years	Sensitivity (gold standard)	standard) Specificity (gold	patients Number of	Type of study
	Karassa et al, 2005	69% (TAB)	82% (TAB)	2036	Meta-analysis (23 studies)
		55% (ACR)	94% (ACR)
	Arida et al,2010	68% (ACR)	91% (ACR)	575	Meta-analysis (8 studies)
	Ball et al, 2010	75% (TAB)	83% (TAB)	998	Meta-analysis (17 studies)
	Luqmani et al, 2016	54% (TAB)	81% (TAB)	381	Cross-sectional study
	Duftner et al, 2018	77% (clinician final diagnosis)	96% (clinician final diagnosis)	605	Meta-analysis (8 studies)
	Rinagel et al, 2019	68% (TAB)	81% (TAB)	1062	Meta-analysis (25 studies)

-ACR: American College of Rheumatology criteria -TAB: Temporal Artery Biopsy

Declarations

Competing interests: The authors declare that they have no competing interests.