Sophie Brones

The Beit Beirut Project: Heritage Practices and the Barakat Building

Keywords: researchers, historians, political scientists and anthropologists

The so-called Barakat building, the ruined yellow building at the corner of Damascus Street and Independence Avenue in the Achrafieh quarter in Beirut, has been dressed, since March 2008, with huge posters. The first poster announced the project of a Museum for the Memory of Beirut (mathaf li dhâkirat Bayrût) but has since then been replaced in May 2010 by another, featuring the Beit Beirut [the house of Beirut] project, which is planned to take place in 2013. Both posters represent stages of this long and tempestuous making of new cultural equipment for Beirut city. The future museum and urban cultural centre will be dedicated to urban memories and history from the nineteenth century. 1 This project paves the way for a new field of investigation in the anthropology of heritage and collecting practices. This paper examines the making of this museum and some of the questions raised by the actual project The museum's shape, contents, purpose and symbolic features relate Beit Beirut to 'society museums', such as Quebec's 'Musée de la civilisation' or Berlin's 'Wall Museum' and represents a new challenge for Lebanon. Like other countries in the Middle East, Lebanon has built, since the second half of the nineteenth century, archaeological museums (the AUB Museum opened in 1868) and, later on, since the beginning of the twentieth century, museums of Islamic and Modern art, which have also been developed in the whole Arab world, as Sonja Mejcher-Atassi and John Pedro Schwartz remark in the introduction of this book. But the challenge of this project is about the way Beit Beirut will feature the Beirutis' 'own lives', as one of its main aims is to express local collective memories 1

and stories and to build part of the museum discourses on the various interpretations of the public sphere. I will, thus, examine the strategies employed to repair -or not -the reality of changing and fragmented Lebanese memories. In particular, I will outline the public appropriation of this private building that was at the beginning kind of ordinary heritage building. Actually, both meanings of the word 'heritage' -inheritance within a family as well as the social construction of what is usually called 'national heritage' -are useful for understanding about this specific case different forms of appropriating the past as well as the underlying conflicts about the city's identity. In the early years of 1990, after having inherited the building in which the museum will take place, the Barakat family wished to convert it into an economic capital project. In addition, the public appropriation -through the battle for its preservation and its expropriation by the Municipality of Beirut -reveals a specific time and context in the collective memory at work in Lebanon and in Beirut's heritage practices. Sustained by Beirut's Municipality and by local heritage associations, this project benefited from a conjunction of interests and a favourable political context after the assassination of ex-Prime Minister Rafic Hariri whichrefreshed, in a certain way, memories of the Lebanese civil war.

The museum building's process constitutes a site for the negotiation of knowledge and ideas between various local and foreign actors. As a case study it allows for the examination and better understanding of the complex and diverse processes of memory and collecting practices in Lebanon, in a distant position from the traditional injunction of the 'duty of memory' or the visible 'amnesia' of political powers that are more often denounced through public spheres when talking about memory. 2 The intensity of emotions and debates which take place around this damaged building reveals how and in what context heritage is thought of and what of the 2 Beirutis' 'own lives' is considered representative or significant by the actors in charge of the project. The analysis of this 'home-made' museum, still in the project phase, aims to focus on collecting as a process that brings together both politics and members of the 'civil society' and expresses an innovative vision of cultural urban heritage, thus reinforcing Beirut's cultural and artistic position within middle-eastern cities. Today, the Barakat building is still in ruins, waiting for the restoration process that should be undertaken before the end of 2012. As with many other damaged structures in Beirut, this stillstanding building will assume a new purpose after restoration. Often, rehabilitations engage commercial activities, such as the restaurants La Centrale in Achrafieh, Walimat Wardé in Hamra, or the L'albergo hotel in the Sodeco area. But rarely do such structures serve cultural purposes, as in the case of the Barakat building. In this chapter, I will outline how this damaged building was transferred from its owners to Beirut's municipality, integrating it into the national heritage. This process is inherently linked to the story of the building's preservation from destruction which revealed the existing tensions between 'heritage preservation activists', the government institutions, and the former owners of the building.

Focus on a Home-Made Museum: From a Private Residence to a Public Institution

The Private Heritage of a Family

The Barakat family, from Beirut's Greek orthodox bourgeoisie, were the original owners of the building. They bought the land on which it stands (plot number 1237) in the early 1920s. The ground and the first floor of the actual building were designed by Youssef Aftimos (1866-1952) and built in 1924. Youssef Aftimos had been the architect of the Municipality of Beirut since 1898. He also designed its building in Wegand Street in 1927, as well as the Grand Theatre in 1929. Moreover, he was behind the construction of the Hamidiyyé Clock (1898) and the Hamidiyyé fountain (1900) that are today located in front of the Grand Serail and in the Sanayeh Garden respectively. His facades introduced Beirut to the 'néo-mauresque' style. In 1932, Fouad Kozah, another famous Lebanese architect, designed the second and third floors of the building. The 'yellow house', as many observers call the building, is divided into two structures; one overlooks Independence Avenue and the other faces Damascus Street. They are connected together by a colonnade that opens up to the sky. Accordingly, one can see the cityscape beyond and across the verandas and openings from each and every room of the inside building. For Mona Hallak, the Lebanese architect who was one of the main actors of the preservation process, the building has a remarkable architectural transparency achieved by an ingenious site plan that opens up the building to both city and sky. It is an aristocratic building with rare and elaborate cement tile patterns enhancing the colourful atmospheres of the rooms: pink, yellow, green and blue walls in sun-washed spaces. 3 Chemaly, who died in 1973. The owner's grandson, the youngest of a seven-children family, got married in the building on 14 April 1975, the day after the official start of the civil war. He also wanted to settle down there, but the location of the building, on what would become the main demarcation line between East and West Beirut, made it one of the first buildings to be attacked by snipers and occupied by Christian militias, in particular the Ahrar of Camille Chamoun. Hence, the family and all the building's inhabitants abandoned their home early in the war. Up until the end of the eighties, the building was used as a defensive position for the eastern part of the city, and had thus been severely damaged during the conflicts, though not in danger of collapsing. Its actual structure and facade bear the traces of the war, bullet holes and shells that often crossed its walls and demolished its stairs and roofs. The inside of the building recalls its various strategic occupations through barricades of bags of sand and reinforced concrete walls that are still intact, indicating fighting strategies against the opposite part of the city. However, this damage does not obscure the original architecture of the building and its past grandeur. At the end of the war, the four heirs of the building entrusted its management to a lawyer who was also a member of the Barakat family. Many investors were interested in buying the land situated at the crossroads of two main axes of the city and close to the 'new downtown' of SOLIDERE, 5 the private real estate company in charge of the development and rebuilding of downtown Beirut since the early nineties. Those investors made proposals to the family seeking to develop the land. In fact, at that time, the family had two alternatives: either to sell the building or to keep the land and destroy the building in order to rebuild a bigger and taller one. Furthermore, along with most owners of ancient properties in downtown Beirut, the Barakat family land had been expropriated by SOLIDERE after 1991. Having 'lost' their goods in downtown Beirut, they intended to benefit from their remaining estates. For this reason, one of the Barakat heirs justified his intention to sell the building and its land for three and a half million dollars with: 'I don't care who buys the house as long as it gets sold. We've already lost our capital in the downtown area; we can't lose anymore.' Rather than sell, the family could also have destroyed the building, of which only 4,500 m 2 were exploited, and rebuild another apartment building in order to gain 13,500 m 2 more, according to the actual building code dating from 1954. At the time, different architects submitted suggestions for several projects. One of them, Jacques Liger-Belair, who was a friend of the family, made plans for three different projects that would have avoided the building's destruction: a luxurious hotel, an office, and a commercial building (souk for goldsmiths). In 1997, the family asked for the demolition of the building. The works started but it -was not long, however, before the 'Beirut's Heritage Preservation Activists' began to fight for its preservation.

Public Appropriation and the Creation of a National Heritage

As is usually the case, the importance of preserving the building came to light only once it was directly threatened by destruction. The various strategies of the owners as well as those of the public powers, undertaken in conjunction with local associations, led to a kind of 'struggle for heritage'. What is very particular and striking in this case is that the building rapidly became a new stake for Beirut's municipality and Governorate. The 'Heritage Preservation Activists' got involved in the preservation process which led to the complete stop of the demolition. Among the small number of heritage preservation associations existing in Beirut, the Association pour la Protection des Sites et des Anciennes Demeures (APSAD) was particularly involved in defending the building's existence. This association had been founded in the sixties by Lady Yvonne Sursock-Cochrane, a member of a Greek orthodox patrician family of the urban high bourgeoisie. In post-war Beirut, the Association developed a large preservation programme in the city concerning the old mansions and buildings threatened by destruction because of the increasing speculation in real estate. In their view, the 'yellow house' was an emblematic case.

A Lebanese architect, Mona Hallak, already a member of the Association, became personally engaged in the case and felt a particular personal interest in this building. She is one of the main figures associated with this building's preservation and one of those more deeply engaged in this struggle, as I learnt when I began my research on the subject in 2006; every person linked to the house's history advised me to meet her. These suggestions were beneficial as she was the one who introduced me to the history of the preservation process through generously showing me all the archives she had collected during her years of struggle. However, it should be noted that other people, in particular intellectuals, architects, artists that, in the Lebanese context, more often argue in favour of architectural preservation and expressions of memory became interested in that building and contributed in their own way to the preservation process. Among them was a French photographer, Sophie Haluk, who studied the house and contributed to the writing of its memory by collecting oral stories from snipers who lived in the building during the civil war.

Nonetheless, Mona Hallak's who was associated with this building through her personal efforts in preserving is still deeply involved in the museum building's process. She grew up in Beirut and was seven years old when the war started. After she graduated from the American University of Beirut she earned a masters degree in Florence in 1995. This stay in Italy may have contributed not only to her sensitivity to architectural and artistic heritage but also to the interest of architectural safeguarding She promotes a particular vision of heritage based on the principle that preserving the past should not only be guided by nostalgia, but should also integrate contemporary creation processes. Although this vision is not shared by all APSAD's members, those who participated in the Barakat's building transformation share Mona Hallak's point of view. Between 1997 and 2003, she organized several public actions around the building (press articles, Internet site, TV coverages, lectures, public tours of the building, etc.). In 2001, in Le Grenier, an abandoned restaurant in the Ayn el-Mreissé quarter of Beirut, she organized an exhibition of all the objects and artefacts she had collected in Doctor Chemaly's apartment and clinic. 6 This exhibition gathered artists and intellectuals. Among the audience were Fouad Kozah, the building's second architect, the writer Elias Khoury, the political scientist and urban designer Mona Harb, the anthropologist Pascale Feghali and the artist Rabih Mroue.

Through the years, and thanks to Hallak's actions, all the 'publicity' around the building, and the awareness of legal authorities and media convinced more and more people about the necessity of preserving the Barakat Building. In a context where the legal framework about historical heritage preservation in Lebanon was under elaboration -as the current laws are those promulgated during the French mandate period in 1932 -the Minister of Culture was inefficient in preserving buildings from destruction. Even though the former Minister Michel Eddé (1992-1996) had decided, since 1996, upon the suspension of the demolition of 1,052 old Beirut houses that had been put under review, the next Minister, Fawzi Hobeiche (1996-1998), removed this decision. Hence, many private properties were then destroyed by their owners as they sold their lands, the actual ratios for land exploitation being much larger than the ones dating from previous times Then, since 2000, as Ghassan Salamé was at the head of the newly reformed Ministry of Culture he -reactivated the discussion about the new legal framework for historical heritage preservation in Beirut. Taking into consideration that no legal framework was yet voted in, the Barakat building's expropriation by Beirut's municipality was the government's last solution to avoid its destruction. In June 2002, Beirut's municipality -whose projects were mostly strangled by internal political conflicts -and in particular its director, Abd

The Museum Project

Although the idea of creating a museum had been present throughout the years of struggle for the building's preservation, the need to convert the place into a 'public interest space', according to the expropriation decree, led Beirut's Municipality to think about establishing a museum. In 2003, Mona Hallak, who had supported this idea since the beginning of her fight, wrote an outline explaining the museum project. 7 It included most of the outlined proposals to defend the preservation by different parties over the past six years. Among these were the Lebanese Ministry of Culture, Beirut's Municipality and Governorate, and the General Direction of Antiquities (GDA). The Italian government, through its embassy in Beirut, also joined the project in proposing the creation of an archaeological museum. In addition, the World Monuments Fund of New York offered to raise funds for the project. has taken place after the war and since 1991. This plan was based on a radical change of the social and physical ancient fabric of the district by erasing more than 80 per cent of its historic architectural landscape. As architects and urban designers, some of the 'Heritage Preservation Activists' had their own ideas about Beirut's reconstruction. Some of them had also been involved in the project as consultants. However, their professional cultures were different from those of the big engineering agencies that worked with SOLIDERE, such as Dar al-Handasah. 11 They would rather work through their own private small agencies, and many of them are engaged in academia, holding PhD studies in Europe, the United States or Lebanon and now teaching in prominent Lebanese universities. The formal aspect of their own projects reveals the legacy of the modern period during which Lebanon had many local and foreign important figures. Aware of the need to safeguard historical architecture, they also promote contemporary creation involving original designs that are not mere copies of ancient or traditional styles. 12 From the side of Beirut's municipality, expropriation was not only the more expensive solution but also the sole one for the preservation of the building. Therefore, this striking decision can be partially explained by the positive influence of Ghassan Salamé, the Minister of Culture of that period, and by the good relations of Mona Hallak with Yacoub Sarraf, Beirut's former governor. Moreover, the decision obviously represented a political opportunity for Beirut's Municipality which had been weakened by the war and had lost control over the city centre, far behind SOLIDERE, in the early years of post-war reconstruction in the nineties. The municipal council, as a forum for personal interests with 23 members chosen according to geographical and confessional criteria, brings together personal political allegiances, strategies and resources. The four municipal councillors from the municipality's offices linked to the Ilede-France region (CRIF) had been assigned to work on the project and liaise with the Paris municipality via the French Cultural Mission in Beirut. However, in fact, the Municipality lacked the necessary skills to carry out single-handedly such an architectural project. I observed during various meetings how difficult the evaluation of the needs of such a project seemed to be. For instance, in 2008, the Municipality 'cleaned' the inside of the ruined building, throwing away some of the original art deco coloured tiles that had been stacked by the demolition people in the upper floors, as well as many documents, objects, furniture, sniper barriers and other elements that could have constituted the main basis of the museum's permanent collections.

Nevertheless, the municipal councillors had shown great motivation in discussions with the scientific committee and in leading the project together with the Mairie de Paris's members who provided technical support: a museum expert of Cultural Affairs Direction, a general coordinator from the General Delegation for International Relations, and a cultural heritage and architecture expert of the architect of the Heritage and Architectural Direction, also a member of a non-governmental association promoting the architectural and cultural heritages of Paris's suburbs. 13 organization of the exhibition spaces. But the general architectural project has been contested at several points by the scientific committee, which were summarized in a five-page report sent to the Beirut's Municipality in July 2011. It highlighted several problems related to the architectural treatment as well as to the general preservation scheme of the building.

Setting Up the Museum's Collections: Discourses and Values (2003-2009) Considering 'objects do not speak by themselves' and that their analysis should be based upon the relations they have with their social context, as the editors say in the introduction to this book, it seems important to focus observations on scenographic and museographic practices as they constitute the shaping and framework of specific ideas and values. Nevertheless, as the collecting practices are still a project and as the museum is still not open to the public, I focused my analysis on discourses and values expressed throughout the various negotiations between the municipal council members, the architect in charge of the project, and the members of the scientific committee.

Most museums are constituted in order to exhibit specific collections. Accordingly, museums serve the purpose of exhibiting pre-existing collections, which, in turn, continue to 'grow older' after the museum's construction. In Beirut, for example, the National Museum was founded in 1927 to exhibit a small archaeological collection that resulted from the excavations of a French officer's mission in Lebanon (1919). Whereas various propositions concerning the future museum's role and function have been made since the Barakat building's expropriation, the problem of collections and that of the restoration of the building have been and still are the two main issues of the project. In her outline in 2003, Mona Hallak summarized all the proposals that had been made during the years of struggle for the building's preservation. Mona Hallak put them together to ensure that the Municipality could find in them ideas for the future museum. She supported the idea of displaying the many artefacts she had collected inside the damaged building since 1997, such as those of Dr Chemaly's apartment which she considered to be testimonies and memories of the period from the forties to the beginning of the seventies, in addition to artefacts from more recent events in Lebanese history related to memories of the war. French actors, alongside Beirut's municipality, supported, in these early stages of the project, the creation of an urban design unit for Beirut's municipal frontiers. Then, since the museum project was publicized, independent actors, such as researchers and artists, also thought about the site and its function. All of their ideas converged around a common theme of reconciliation: the building's situation on the ancient demarcation line of the war could symbolically serve the dialogue between Lebanese communities. Mona Hallak quotes P.

Dellport in her outline:

After six years of public campaigns by heritage preservation activists, the Barakat building will be expropriated by the city of Beirut as its Museum of Memory. The acknowledgment of the whole past needs to be a principle entrenched within the collective consciousness of all communities […] making this recollection of the past visible, accessible and shared to contribute to the process of social reconciliation. 14 The Governor Yacoub Sarraf's discourse was based on the same underlying ideas:

The city of Beirut shall expropriate lot 1237 -Achrafieh -and turn the Barakat Building into a museum, a civic cultural centre focusing on the history of urban development of the City of Beirut, offering people a place for interaction and debate in the heart of their capital […] This unique piece of Levantine architecture with such an avant-garde concept of urban setting, at the intersection of Damascus Road and Independence Avenue, was built by the pioneer architect Youssef Bey Aftimos […]. Having been used heavily by snipers during the war due to its strategic location on the dividing "green line", the preservation of their nests still intact will add to the rehabilitation of this building a great symbolic value: a place for meeting and reconciliation, a space for memory so as not to be swept up by amnesia. This project is a unique opportunity to have a living museum dedicated to our urban history 14 Hallak, A Tribute to Beirut. and collective memory, a witness to the rebirth of pre-war successful endeavours, an effort to which every citizen is invited to contribute. 15 By denouncing obliviousness, these discourses serve those who call for remembrance in the name of the 'duty of memory'. Their authors contribute to the work of memory that has emerged in the past few years, particularly in public spheres of contestation, artistic milieus and around the heritage preservation activists. 16

What Should a Museum of Memory Be?

The previous ideas of an archaeological museum did not last long as the scientific committee, together with the Beirut Municipality, decided that the museum -and its collections -would be based on the existing structures, their history and stories. From that point of view, the use of the word 'museum' represented one of the problems the participants in the project had to deal with.

For most of them, it seemed difficult to retain the use of this term in the context of an experiment: making a 'museum' without a pre-existing collection of objects of rich value. For that reason, during the first meetings of the scientific committee with the Municipality, some asked about changing the word 'museum' and proposed calling the future site bayt al-madîna [the house of the city]. But the word museum had been used in the expropriation decree and the participants in the project had to deal with it. As generally understood, the term museum refers to a place where ancient artefacts (or artefacts that are no more in use), artworks or everyday objects, are exhibited. Beirut has several museums: two archaeological museums (the National Museum and the archaeological museum of the American University of Beirut), a fine arts museum (the Sursock Museum), and private ones, such as the Robert Mouawad Museum (ex Henri Pharaon collection). These examples gave the frame for the museum's conceptions for some of the project's members whereas some others were more aware of alternative forms of museums such as society museums or ecomuseums.

Which and Whose Memory?

In a contested social and urban space, the museum can be considered as an answer to a social claim. The word memory (dhâkira), which since 2008 has been in use by Beirut's Municipality on the poster covering the Barakat building's façade, constitutes another issue of the project. In the post-war years, debate about justice and reconciliation had partly been masked by the city centre's reconstruction under the direction of SOLIDERE, the private real estate company founded by the former Prime Minister Rafic Hariri. This project faced a large public debate about social, economic, political and symbolic issues, and started the demolition, in 1992, of almost 80 per cent of the previous architectural buildings of the zone. Jad Tabet -a Lebanese architect who since the early nineties became personally and particularly involved in the challenges against SOLIDERE -said that the Beit Beirut project reflected the failure of 'heritage preservation activists' and heritage associations in protecting the architectural heritage of the city, in which the lack of support from the government was a notable influence. 17 His underlying idea was other preservation processes could have succeeded for many other buildings than the Barakat building. He added that in his opinion, SOLIDERE is generally considered today as an example for heritage preservation even though it had destroyed the main part of Beirut's ancient heritage during the reconstruction process. He referred to tourist maps and publicity produced about the few archaeological sites that were converted to public spaces, the restoration of a limited number of monuments in downtown Beirut and the coherence of the urban fabric and landscape in this zone.

At the beginning of the discussions in 2008, the participants' conception of the 'object' of memory seemed to limit its scope to the Lebanese civil war period (1975-1990) whose traces are visible everywhere in and outside the building. Without consensual agreement on the country's recent history, the history of the war period represents a very complex issue. The Taëf agreement that marked the end of the civil war in 1989 remained silent about the war and its victims. It was followed in 1991 by an amnesty law which Paul Ricoeur interprets as an institutional form of forgetfulness 18 as it omitted to pass judgement on political leaders for the war crimes committed by their militias, favouring instead their conversion into politics. 19 In such a context, where justice has not played its role, healing seems impossible whereas collective memories are submitted to political leadership and community divisions.

As discussed during various meetings and expressed in the reports, the war period will be documented in the museum's interpretation as one of various episodes of Beirut's history. It will be emphasized through the material damage left inside and outside the building as well as through artefacts, such as the sniper's barriers and other traces of the militias' occupations of the building. The general idea is to highlight the war period as the building itself lived it, with evocations and reminiscences that the site, the building and the preserved damage will provoke.

It had been decided that the main purpose of the museum will be Beirut's social and urban history and memories from the nineteenth to the twenty-first centuries, the civil war being no more than a part of the story. A part of the building will feature a permanent exhibition on the previous themes (first and second floors) and another part (third floor) will deal with temporary exhibitions concerning subjects such as everyday life in Beirut, trades, housing and living spaces, etc.

Collecting Memories

Furthermore, thought of as a place for debate and moving cultural purposes, the project is necessarily leading to the invention of new forms of collecting practices. Going through the building's stories is the first step for the permanent collections of the museum. The building 18 Paul Ricoeur, La mémoire, l'histoire, l'oubli (Paris, 2000): 588, cité dans Aida Kanafani-Zahar, Liban, la guerre et la mémoire, (Rennes, 2011): 37. appears as both a container and content for the museum. Thus, the 'yellow house' becomes part of the museum collections. The basis of discussing memories should be the artefacts collected by Mona Hallak in the building since 1997. In Dr Chemaly's apartment, the boxes containing spices, the dental cabinet, dental chair, his objects, instruments and papers (letters, visiting cards, pictures, cinema flyers…) allow the reconstruction of the familial and urban history of that period. 20 Different stages of the building's history, such as its conception, its extensions, its destruction and reuse by militias during the war, are yet another story that the public shall hear.

The avant-garde architecture of the building itself illustrates Beirut's architectural heritage of the mandate period, along with the transformations it brought about, including the passage from stone to concrete, as shown in the building between the first and second floors. The biography of the master architect, Youssef Aftimos, is also linked to the history of the city during the Ottoman period and the French mandate period which only few history books refer to. All these elements that are contained by the building itself are proposed as primary material for the 'memory' collections. Discussions during 2010 concluded that these collections would be completed by various investigations led by specialists assigned by the scientific committee members on different subjects. The themes will generate the collecting of many different objects such as pictures, films, sounds of the city and everyday life objects from homes, works and public spaces. The museum also plans to go beyond its material frontiers by organizing events in other places of the city so as to compensate for the partitioning of the quarters in the city. Furthermore, all parties agreed that the building should serve not only as a museum but also as a centre for debate, research and knowledge on Beirut's architectural heritage. For all these reasons, the building is meant to express a plural and contemporary local identity. Regarding that programme, one ought to enquire about the main methodological issues for collecting. It, therefore, can be understood as an upgrading process: the way the museum upgrades objects that are or were already valued (in a positive or negative meaning) by their original owners. The process of collecting converts the value of objects into a monumental logic, which is understood in the terms of a remembrance project. In this particular case, as an ongoing process, special attention should be paid to the context of material and immaterial objects that will be collected. For example, collecting campaigns launched by the MuCEM (European and Mediterranean Civilizations Museum) of Marseille are made by social anthropologists in an ethnographic way, combining collecting of the objects with memories, stories, atmospheres and uses in which they participate, paying attention to the relations between objects and their users as well as the social context they belong to, and documenting them by videos, photographs and interviews. 21 As for the importance of the object's original contexts, the oral story's subjective visions and the archive's production contexts, will this museum boast about calling itself an ethnographic museum? It may be so as it will exhibit objects from Beirut social practices that will partly be collected by anthropologists. More than exhibiting culture as in traditional folklore museums, the museum intends to assume the description of 'Lebanese lives' through cultural practices and productions.

However, the main issue this project faces is, in my opinion, the way it integrates the socalled 'cultural heritage'. As Sonja Mejcher-Atassi and John Pedro Schwartz say in this book's introduction, 'we must also bear in mind that remembering can itself be a form of forgetting, and collecting, a form of discarding.' As a response to 'achieving closure on the past' that goes with monuments, museums, historical sites and cultural heritage objects, the authors cite the anti-monument and the anti-museum experiences, such as those of the Berlin Jewish Museum in which empty space calls for remembrance and subjective interpretations of the past in a nondirective way. In the same way, the will of Beit Beirut to talk about itself as a 'living entity' and about heritage and political processes that made it a museum and urban cultural centre aims to avoid this enclosure of cultural heritage that makes, once the museum is created, an immobile and static object remaining outside the movement of life.

As demonstrated by the plurality of practices and discourses, heritage has become the focus of debates, collective involvement and reactions from many different actors in the local scene. The destiny of this building is also very particular, as it represents a rare example of the success of both Beirut's heritage preservation activists and its owners who wanted to sell their land, two sides that are generally opposed by their visions about transmitting heritage. Thus, it demonstrates the possible role of the Lebanese government in safeguarding parts of Beirut's architectural heritage. The various strategies outlined above reveal that the government, via the Municipality of Beirut, partly, but officially, can assume the responsibility for some of the country's collective memories that the 'yellow house' symbolizes on many levels. By exhibiting urban memories, as well as memories of war and division, the museum should provide a new context for examining historic events. This 'home-made' museum questions the main issues around the contemporary 'creation' of museums in a post-colonial context as well as the central role of memory in the definition of current artistic trends in Beirut. According to Pierre Nora, the institution of the museum is produced by societies in which memory is in decline and societies that try to stay close to their past because they can no longer choose their destiny. 22 But the Beit Beirut case study also allows an examination of how memory, specifically that of the war, has been used by many local different groups. It shows how public appropriation of the project by the various parties involved in it expresses the will to talk about the past as well as to invent new ways of considering the changing landscape of the city. It may give a renewed discourse about the war, contrasting with the general tendency of erasing its traces, as SOLIDERE has done in downtown Beirut. Will the integration of the war into a new cultural place in the city mean, in a certain way, assuming it as a part of national history? If yes, the museum could therefore answer one of the main functions of what Daniel Fabre considers a capital city: a place where the 'expectation of a collective destiny' would be possible. 23 The main reason for that would be the way this museum renews its relationship to history by referring to collective memories, which have, until now, remained outside historical and political local discourses.

Figure 6

 6 Figure 6.1 The Barakat Building façade on Independence Avenue, Beirut, 2011.

Figure 6 . 2

 62 Figure 6.2 Cement tiles remaining intact in the fourth floor of the building, 2011.

Figure 6 . 3

 63 Figure 6.3 Sand stone fortifications in the first floor of the building, 2011.

  al-Menhem al-Aris, and the Governor of Beirut (mohafez), Yacoub Sarraf, allowed the transformation of the 'yellow house' into a 'museum'. Having purchased the lot for three million dollars, the municipality paid the owners three years later, two days before the 2006 summer war. 6 The installation was part of the Ayloul festival (8-12 September 2001) and the film The Grenier Presentation was run during the exhibition. It is today part of Mona Hallak's archives.

The

  French part included the Institut d'Amenagement et d'Urbanisme de la Region Ilede-France (IAURIF), the Association Internationale des Maires Francophones (AIMF), and the Paris Municipality. In September 2006, Bertrand Delanoé, the mayor of Paris, came to Lebanon for a meeting with the Commission des Relations avec l'Ile-de-France (CRIF) in Beirut's municipality, in which four members of the municipal council participated. Ralf Eid, who was one of the participants, invited Delanoé to visit the yellow house even though it was not in the mayor's programme. 8 According to the municipal councillor, Delanoé was seduced by the architectural and emotional values of the building and offered to provide technical support to the municipality for the conception of the future museum. In March 2008, after two years of standby because of the political crisis in the country after the 2006 summer war, the project was given a new momentum by the Cultural Service of the French Embassy in Beirut (SCAC) which liaises with Paris's municipality experts. A group of Lebanese and French specialists was constituted around the contemporary studies department of the French research institute (IFPO).

7

  Hallak, A Tribute toBeirut. 8 Interview with RalfEid, Beirut, 2009. This group became, a few months later in 2009, the 'scientific committee' for the future museum. 9 It includes some of the actors that took part in the struggle for the preservation of the building between 1997 and 2003, such as Mona Hallak and another architect and member of APSAD, Habib Debs, as well as architects, urban designers and archaeologists from various Lebanese universities: the American University of Beirut (George Arbid), the Lebanese University (Mosbah Rajab, Yasmine Makaroun) and the Lebanese Academia of Fine Arts (Serge Yazigi). The other participants included anthropologists and historians specializing either in Beirut's urban and social fabric or in heritage restoration problems (Franck Mermier, the former director of contemporary studies in IFPO, Carla Eddé, historian and responsible of the History Department in St Joseph University, and myself), as well as Carla Mardini, specialist of museum issues and Lynn Maalouf, journalist, activist, member of the Beirut office of the International Center for Transitional Justice and vice-chair of the administration council of Act for the Dissapeard). Zeina Arida, director of the Arab Image Foundation also joined the committee in 2010. -10The current involvement of these actors in the project can be explained in light of their professional cultures as well as their personal trajectories and engagements. Both collective and individual strategies take place in the local context of preserving heritage in Beirut. In many ways, they illustrate the tensions which exist between the official, but nevertheless inefficient public powers and the non-governmental associations in which those persons are engaged. Some of the Lebanese members of the scientific committee got involved in heritage associations in reaction to SOLIDERE's master plan for Beirut's downtown reconstruction that 9 I have participated in the meetings of the scientific committee since 2008 as an associated researcher of the French Institute in Beirut (IFPO). I am grateful to all its members, and I want to thank, in particular, Franck Mermier, Martine Herlem, Mona Hallak and Habib Debs for their help during my research. I also thank Noha Sadek and Mona Hallak for their rereading of this paper. Although I am associated with the scientific committee's debates, the interpretations given in this paper are all mine. 10 www.fai.org.lb.

11

  Eric Verdeil, Une ville et ses urbanistes: Beyrouth en reconstruction, thèse de géographie (Université de Paris I, 2002). 12 Ibid.

  In 2010, after the 2009 municipal elections, M. Rachid Achkar and M. Nadim Abu Rizk replaced them at the head of the project for the Municipality. Several meetings that brought together the main actors of the project took place in Beirut between 2008 and 2011. The Paris municipality had a specific role in providing an administrative framework for the project in response to the cahier des charges established by Beirut's Municipality which selected in 2009 Youssef Haïdar's agency among four architectural agencies and projects, although the scientific committee had required an international competition for the project. Youssef Haïdar had experience in the renovation and creation of museums in Lebanon, such as the Archaeological Museum of AUB and the Soap Museum in Saïda, South Lebanon. Decisions concerning organizing the collections of the museum have been elaborated by the scientific committee members together with the Paris Municipality members in 2008 and 2009. They guided the architect's plans of the interior spaces and the 13 La Maison de banlieue et de l'architecture: www.maisondebanlieue.asso.fr.

20

  Some of these objects were shown at the Unesco Palace in Beirut in an exhibition organized by the National Heritage Foundation (21-30 May 2008).

  23'L'anticipation d'un destin collectif' was Daniel Fabre's formula in the introduction of the public forum Capitales et patrimoine au XXIe siècle, Québec, LavalUniversity (5-7 Nov. 2009).

Walter Singh-Bartlett, 'Of Heritage, Money, and the Want of Political Will', The Daily Star, (11/1/1999).

SOLIDERE: Société Libanaise de Développement et de Reconstruction.

Round table Mémoires de ville inBeirut's French Cultural Centre, 28 May 2009.

Aida Kanafani-Zahar, Liban, la guerre et la mémoire,(Rennes, 2011) : 38.

www.mucem.org/

Pierre Nora, Les lieux de mémoire(Paris, 1984).

however, refer to a collective research in which I took part, led between 2007 and 2010 by the Institut français du Proche

Verdeil, Eric, Une ville et ses urbanistes: Beyrouth en reconstruction, thèse de géographie, université de Paris I (Paris, 2002).


Camille Maumet

Pierre Maurel

Jean-Christophe Ferré

Christian Barillot

An A Contrario Approach for the Detection of Patient-Specific Brain Perfusion Abnormalities with Arterial Spin Labelling

Keywords: Arterial Spin Labelling, Brain tumour, Hypo-perfusion, Hyper-perfusion, a contrario, General Linear Model, searchlight approach

An a contrario approach for the detection of patient-specific brain perfusion abnormalities with arterial spin labelling

Introduction

Arterial Spin Labelling (ASL), a Magnetic Resonance Imaging (MRI) technique introduced in the early 1990's [START_REF] Detre | Perfusion imaging[END_REF], provides a measure of the level of perfusion as a quantitative index: the cerebral blood flow (CBF). Contrary to standard perfusion imaging, including Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in nuclear medicine or Dynamic Susceptibility weighted Contrast (DSC) in MRI, ASL is completely non-invasive and does not require the injection of an exogenous contrast agent. The ASL sequence however suffers from a low SNR, which is still a serious obstacle for its use in clinical practice.

Since the introduction of ASL, and despite its low SNR, a large number of studies have demonstrated its usefulness in identifying patterns of abnormal perfusion at the group level, for example [START_REF] Pinkham | Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI[END_REF]. While group statistical analyses are of tremendous importance in order to understand the general mechanisms underlying a pathology, there is today an increasing interest towards patient-specific analyses [START_REF] Viviani | Non-normality and transformations of random fields, with an application to voxel-based morphometry[END_REF][START_REF] Klöppel | Diagnostic neuroimaging across diseases[END_REF][START_REF] Scarpazza | When the single matters more than the group: Very high false positive rates in single case Voxel Based Morphometry[END_REF]) that aim to draw conclusions at the level of a single individual. Inference at the patient level is highly desirable in order to perform a diagnosis or provide a personalised treatment. On top of this, some pathologies are intrinsically not well-suited to perform group voxel-wise analyses. It is for instance the case of brain tumours [START_REF] Warmuth | Quantification of Blood Flow in Brain Tumors: Comparison of Arterial Spin Labeling and Dynamic Susceptibility-weighted Contrast-enhanced MR Imaging[END_REF][START_REF] Chawla | Arterial spin-labeling and MR spectroscopy in the differentiation of gliomas[END_REF][START_REF] Weber | Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors[END_REF][START_REF] Sugahara | Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrastenhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue[END_REF], stroke [START_REF] Huck | Arterial spin labeling at 3.0 Tesla in subacute ischemia: comparison to dynamic susceptibility perfusion[END_REF][START_REF] Ferré | Improving quality of arterial spin labeling MR imaging at 3 tesla with a 32-channel coil and parallel imaging[END_REF][START_REF] Wheeler | Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2[END_REF], or some types of epilepsy [START_REF] Colliot | Segmentation of focal cortical dysplasia lesions on MRI using level set evolution[END_REF][START_REF] Pendse | Interictal arterial spin-labeling MRI perfusion in intractable epilepsy[END_REF], that exhibit a different pattern of spatial abnormalities for each patient. In all of these pathologies, measuring the level of perfusion, as an indicator of the well-being of the tissues, has been demonstrated to be a useful information for diagnosis in clinical practice (see for example [START_REF] Warmuth | Quantification of Blood Flow in Brain Tumors: Comparison of Arterial Spin Labeling and Dynamic Susceptibility-weighted Contrast-enhanced MR Imaging[END_REF] for brain tumours, [START_REF] Wheeler | Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2[END_REF] in stroke and [START_REF] Pendse | Interictal arterial spin-labeling MRI perfusion in intractable epilepsy[END_REF][START_REF] Boscolo Galazzo | Patient-specific detection of cerebral blood flow alterations as assessed by arterial spin labeling in drug-resistant epileptic patients[END_REF] for epilepsy).

Very few ASL studies focused on voxelwise quantitative perfusion abnormality detections at the individual level. The identification of individual patterns of hypo-and hyper-perfusions in patients with ASL mainly relies on visual analysis [START_REF] Zaharchuk | Comparison of arterial spin labeling and bolus perfusion-weighted imaging for detecting mismatch in acute stroke[END_REF][START_REF] Chen | Arterial spin-labeling in routine clinical practice: a preliminary experience of 200 cases and correlation with MRI and clinical findings[END_REF]. In [START_REF] Petr | Template-based approach for detecting motor task activation-related hyperperfusion in pulsed asl data[END_REF], a template-based analysis was presented in order to detect individual activation patterns in functional ASL data. Interestingly, they also applied their method to a pathological case in order to detect a hypo-perfusion co-located with a dysplasia in an epileptic patient. The most widespread approach to compute statistical analyses in neuroimaging is the massively univariate General Linear Model (GLM). This versatile model can be used in patient-specific analyses to compare a group of healthy controls to a patient. In [START_REF] Maumet | Patient-specific detection of perfusion abnormalities combining within-subject and between-subject variances in Arterial Spin Labeling[END_REF], we showed that using a heteroscedastic GLM should be favored (over the homoscedastic approach) in ASL studies studying single patients. Recently this method was also applied in epileptic patients [START_REF] Boscolo Galazzo | Patient-specific detection of cerebral blood flow alterations as assessed by arterial spin labeling in drug-resistant epileptic patients[END_REF].

In neuroimaging, Gaussian smoothing is typically applied on pre-processed data before computing the GLM to compensate for small misregistrations, to reduce the effect of potential outliers and to insure that the residuals follows a Gaussian random field [START_REF] Poldrack | Handbook of functional MRI data analysis[END_REF]. While smoothing has demonstrated its usefulness, its use can be problematic in some brain pathologies (such as brain tumors) where the co-localisation of hypo and hyper-perfusions is common. As an example, ring-enhanced lesions present a pattern of abnormal perfusion in which is a central (hypo-perfused) necrosis is surrounded by an (hyper-perfused) enhanced ring. One can easily picture how Gaussian smoothing in this context can be detrimental as it mixes hypo-and hyper-perfusions, possibly cancelling out the observable effects.

As opposed to the massively univariate GLM, a major trend is the use of machine learning methods (cf. [START_REF] Klöppel | Diagnostic neuroimaging across diseases[END_REF][START_REF] Poldrack | Handbook of functional MRI data analysis[END_REF] for a review or [START_REF] Paloyelis | A Spatiotemporal Profile of In Vivo Cerebral Blood Flow Changes Following Intranasal Oxytocin in Humans[END_REF] for an example in ASL). These multivariate approaches are able to combine the voxel-wise information and can therefore achieve a greater sensitivity. While there have been recent effort to extend the use of machine learning approaches to identify departure from a group [START_REF] Miranda | Patient classification as an outlier detection problem: an application of the One-Class Support Vector Machine[END_REF], the large majority of machine learning approaches found in the literature have been developed to tackle a two-(or more) class separation problems. In our context, where each individual presents a different pattern of abnormalities those approaches are ill-suited. Machine learning approaches are also more computationally intensive. Another alternative, lying in between the massively univariate and the fully multivariate methods, is the searchlight approach [START_REF] Kriegeskorte | Information-based functional brain mapping[END_REF]. This locally multivariate procedure focuses on multivariate patterns found in a spherical neighbourhood around each voxel. At its inception, two multivariate metrics were considered: a Euclidean distance and a Mahalanobis distance (taking into account the spatial autocorrelation of the noise) [START_REF] Kriegeskorte | Information-based functional brain mapping[END_REF]Kriegeskorte and Bandettini, 2007b). These locally multivariate metrics achieved a greater sensitivity than the massively univariate GLM in functional MRI studies [START_REF] Kriegeskorte | Information-based functional brain mapping[END_REF].

However, those approaches do not provide a direct interpretation of the detections as hypo-or hyper-perfusions. To determine whether a detection at a given voxel corresponds to a hypo-or hyper-perfusion, those approaches usually rely on the sign observed in the voxel-wise map (Kriegeskorte and Bandettini, 2007a). Recently, this approach was used in combination with machine learning classifiers (for example, see [START_REF] Uddin | Multivariate searchlight classification of structural magnetic resonance imaging in children and adolescents with autism[END_REF] but training a classifier at each location can be very computationally intensive [START_REF] Poldrack | Handbook of functional MRI data analysis[END_REF].

The a contrario approach is a recent statistical framework [START_REF] Desolneux | A grouping principle and four applications[END_REF] which comes from the computer vision community. This approach proceeds by counting the number of elements observed in a local excursion set defined around each voxel. We therefore propose to extend the searchlight procedure to the a contrario multivariate metric. In a contrario, the locally multivariate probability estimation is typically performed by assuming a white noise [START_REF] Desolneux | A grouping principle and four applications[END_REF][START_REF] Aguerrebere | A-contrario localization of epileptogenic zones in SPECT images[END_REF].

However, spatial autocorrelation of the residuals is a well-known phenomenon in MRI, see for example (Wang et al., 2003b) for ASL, and cannot be disregarded. To ensure the validity of the a contrario approach for MRI, we therefore updated the probability estimation to model noise spatial dependency.

In this paper, we propose a new locally multivariate approach, based on an a contrario metric, for the detection of patient-specific brain perfusion abnormalities with ASL. For validation purposes, the proposed a contrario method is compared to the GLM by means of Receiver-Operating-Characteristic (ROC) analyses. Quantitative validation is performed on a dataset of 25 patients diagnosed with brain tumours and 61 healthy volunteers.

We previously investigated the ability to detect hypo-and hyper-perfusions using an a contrario approach in two conference papers (Maumet et al., 2012a,b). On the methodological side, we present here a new variant of our model, which takes into account the spatial autocorrelation of the noise. Furthermore, a larger database is studied, a novel quantitative validation is provided, and a comprehensive quantitative comparison with the GLM is performed.

In section 2, we first introduce the theory and in particular the principles of a contrario analyses. Then, we present the experiments and the datasets under study. The results are presented in section 3. Section 4 gives a discussion and section 5 concludes.

Material and Methods

Theory

This section presents the methods developed in order to detect areas of abnormal perfusion in a patient map by comparison to a group of control subjects. In 2.1.1, we review the standard massively univariate General Linear Model (GLM). In 2.1.2, we describe the proposed locally multivariate a contrario approach.

The massively univariate General Linear Model

The General Linear Model used to detect patterns of abnormal perfusion in a patient by comparison to a group of subjects can be defined as a hierarchical model with two levels: subject and group. As suggested in [START_REF] Maumet | Patient-specific detection of perfusion abnormalities combining within-subject and between-subject variances in Arterial Spin Labeling[END_REF], we use a heteroscedastic model considering two distinct sources of variance: inter-subject and intra-subject. The level of perfusion in the patient map at voxel v is therefore compared to the level of perfusion in the control group with the following t-statistic:

t (v ) = β(n,v) - 1 n-1 s=1 w (s,v ) n-1 s=1 w (s,v ) β(s,v) σ2 G(v ) + σ2 (n,v) + 1 n-1 s=1 w (s,v ) (1)
with

w -1 (s,v ) = σ2 G(v ) + σ2 (s,v )
, where β(s,v) is the estimated perfusion for subject s at voxel v, σ2 G(v ) is the estimated inter-subject variance, σ2 (s,v ) the estimated intra-subject variance (over the ASL repetitions) for subject s and index n denotes the patient of interest.

Under the null hypothesis H 0 that the perfusion value in the patient map is equal to the control group mean, the t-statistic t (v ) follows a Student distribution T n-1 with n -1 degrees of freedoms. The probability under the null hypothesis, π GLM (v ) , of being in presence of such a high level of perfusion at voxel v of the patient map is therefore estimated by:

π GLM (v ) = Pr(T n-1 ≥ t (v ) ). (2)
Hypo-perfusions can respectively be studied with Pr(T n-1 ≤ t (v ) ). Valid detections are then obtained by thresholding the probability map using a correction for multiple testing.

2.1.2. The a contrario approach: a locally multivariate procedure

The a contrario approach [START_REF] Desolneux | A grouping principle and four applications[END_REF]) is a locally multivariate procedure which uses the size of a local excursion set as statistic. As illustrated in fig. 1, the a contrario probability estimation is usually based on a two-step procedure. First, massively univariate voxel-wise probabilities are computed under a so-called "background model".

Second, locally multivariate probabilities are estimated assuming a given type of local noise (usually white).

J v J v J v M J v M Jv M xv v ppre 1 J v M x v Pr(x v ) v p pre J v M x v Pr(x v ) v p pre J v M x v Pr(x v ) v p pre J v M x v Pr(x v ) v p pre J v M x v Pr(x v ) L r v p pre J v M x v Pr(x v ) L r v p pre J v M x v Pr(x v ) L r l r v p pre 1
Figure 1: Overview of the a contrario approach: the a contrario statistic is computed in two steps:

1. Voxel-wise probabilities are estimated under a selected background model, 2. Region-based probabilities are calculated, those typically correspond to the voxel count of a local excursion set in pre-defined regions of interest. Finally, 3. Inference is performed using an appropriate correction for multiple comparisons. The GLM makes inference directly on the voxel-wise probabilities.

In the first step, a model of the background is defined at the voxel level. This model can represent the background noise or be learned from a control population. Let J (v )

be the random variable representing the value observed at the voxel v of the image of interest. Under the background model M, depending on the set of parameters γ, we have:

J (v ) ∼ M(γ (v ) ). (3)
Given x (v ) , the value observed at voxel v, each voxel of the image can be associated with a (univariate) probability under the background model:

Pr(J (v ) ≥ x (v) ), where J (v ) ∼ M(γ (v ) ) (4)
Rousseau et al. first noticed that the term "background model" commonly employed in the a contrario literature could be well considered as a null hypothesis in standard hypothesis testing [START_REF] Rousseau | An a contrario approach for change detection in 3D multimodal images: application to multiple sclerosis in MRI[END_REF]. So that the standard massively univariate GLM (based on unsmoothed data) can in fact be used to produce the input voxel-wise probability map of the a contrario analysis leading to:

Pr(J (v ) ≥ x (v) ) = π GLM (v ) . (5)
In the second step, in order to estimate locally multivariate probabilities, we then need:

1. A partition of the image into sub-regions;

2. A model to estimate the locally multivariate probability in a given region of interest from the univariate voxel-based probabilities.

Partition of the image into sub-regions. Given an a priori shape of the structures to be detected the regions can be selected accordingly. For instance, in the first a contrario application, which aimed at detecting alignments, segments of variable sizes were chosen as regions of analysis [START_REF] Desolneux | A grouping principle and four applications[END_REF]. In our case, the shape of the expected detections is unknown and, as it has been proposed in a contrario [START_REF] Rousseau | An a contrario approach for change detection in 3D multimodal images: application to multiple sclerosis in MRI[END_REF][START_REF] Aguerrebere | A-contrario localization of epileptogenic zones in SPECT images[END_REF] and with the searchlight procedure [START_REF] Kriegeskorte | Information-based functional brain mapping[END_REF], the sub-regions are defined as spheres centred at each voxel.

From univariate voxel-based probabilities to a locally multivariate statistic. The computation of a locally multivariate statistic involves the notion of "rare events". By definition, a rare event occurs at voxel v if the univariate probability (under the null hypothesis) to observe such value, or a more extreme, is smaller than a pre-defined threshold p PRE . The initial voxel-wise probability map is thus thresholded to produce a binary map :

K (v ) =      1, if π GLM (v ) ≤ p PRE , 0, otherwise. with K (v ) ∼ Bern(p PRE ) (6)
where Bern(p PRE ) is a Bernoulli distribution with probability p PRE .

Then, the random variable describing the number of rare events in a region r, L (r ) , is determined by:

L (r ) = v∈r K (v ) (7)
which is equal to the cardinal of the excursion set (parametrised by p PRE ) observed in each region.

The T-statistic used in the massively univariate GLM, is therefore replaced by a locally multivariate statistic in the a contrario approach: the number of rare events L (r ) .

In order to be able to make inference using the a contrario approach, we must determine the distribution of the statistic L (r ) under the null hypothesis.

The original a contrario approach assumes spatial independence of the residuals [START_REF] Desolneux | A grouping principle and four applications[END_REF][START_REF] Aguerrebere | A-contrario localization of epileptogenic zones in SPECT images[END_REF], i.e. the probability under the background model (or equivalently under the null hypothesis) to observe a rare event at a given voxel is independent of the probability to observe a rare event at any other voxel in the image, and in particular in its neighbourhood. However, the presence of spatial autocorrelation of the noise has been well described in the MRI literature, see for example [START_REF] Chumbley | False discovery rate revisited: FDR and topological inference using Gaussian random fields[END_REF] for fMRI or (Wang et al., 2003b) for ASL, and cannot be disregarded.

We draw the attention of the reader that, under the a contrario approach, as for any hypothesis testing procedure, assumptions are made on the distribution of the error but not on the signal itself. Hence, the a contrario approaches makes no assumption on the spatial coherency of the (normal or abnormal) perfusion signal. In line with recent developments in the a contrario approach [START_REF] Myaskouvskey | Beyond Independence: An Extension of the A Contrario Decision Procedure[END_REF], we propose to rely on a multivariate Gaussian distribution in order to estimate the probability of observing a given number of rare events per sphere, as developed hereafter.

Let's first notice, that the probability of observing l (r ) or more rare events can be calculated as a sum of probabilities:

Pr(L (r ) ≥ l (r ) ) = e i=l (r ) Pr(L (r ) = i) (8)
Then, given C (i) (r ) the set of combinations of i elements among r, we have:

Pr(L (r ) = i) = S∈C (i) (r ) Pr K (v) = 1, ∀v ∈ S and K (v) = 0, ∀v ∈ S (9)
The problem now lies in the calculation of the joint probability to observe a given combination of "rare"/"not rare" voxels in the region of interest. Also, by definition of the term "rare event" we have:

Pr K (v) = 1, ∀v ∈ S and K (v) = 0, ∀v ∈ S = Pr π (v ) ≤ p PRE , ∀v ∈ S and π (v ) > p PRE , ∀v ∈ S = Pr T n-1(v ) ≥ Φ -1 Tn-1 (p PRE ), ∀v ∈ S and T n-1(v ) < Φ -1 Tn-1 (p PRE ), ∀v ∈ S , (10)
where Φ -1 Tν in the inverse cumulative function of a Student distribution with ν degrees of freedom, outlining that the joint probability can be estimated from a Student's t random field. As previously proposed in the neuroimaging literature regarding the use of random field theory for multiple testing correction [START_REF] Kiebel | Robust smoothness estimation in statistical parametric maps using standardized residuals from the general linear model[END_REF][START_REF] Zhang | Cluster mass inference via random field theory[END_REF], we focus on the Gaussianised t random field:

z (v ) = Φ -1 (Φ Tn-1 (t (v ) ))
where Φ -1 is the inverse cumulative function of a standard Normal distribution, and on the corresponding multivariate Gaussian random variable Z (v ) .

Then we approximate:

Pr T (v ) ≥ Φ -1 Tn-1 (p PRE ), ∀v ∈ S and T (v ) < Φ -1 Tn-1 (p PRE ), ∀v ∈ S ≈ Pr Z (v ) ≥ Φ -1 (p PRE ), ∀v ∈ S and Z (v ) < Φ -1 (p PRE ), ∀v ∈ S . (11)
As a Gaussian random field, Z (v ) is also representable by a multivariate Gaussian distribution, we have:

     Z (1) . . . Z (e)      ∼ N e (      0 . . . 0      ,         1 σ 2 (1,2) . . . σ 2 (1,e) σ 2 (1,2) . . . . . . σ 2 (1,e) . . . 1         ). ( 12
)
where N e is a multivariate Gaussian distribution of dimension e and σ 2 (i,j) = cov(Z (i) , Z (j) ). The problem now lies in the estimation of the covariance between each pair of voxel σ 2 (i,j) , i = j. To this aim, we use the great amount of work developed in the context of random field theory. In particular, assuming that Z (v ) can be described as a Gaussian random field with a stationary homogeneous Gaussian correlation function, [START_REF] Worsley | A unified statistical approach for determining significant signals in images of cerebral activation[END_REF] proposed an estimation of the spatial correlation. This estimate corresponds to the full-width-at-half-maximum of a Gaussian kernel that, applied to white noise, would lead to the same amount of autocorrelation. We computed this estimate using SPM8 (Statistical Parametric Mapping 8) on a subset of our subjects and found a fullwidth-at-half-maximum approximately equal to 1.5 voxels (in each direction). This value is in line with previous estimates obtained in ASL data (Wang et al., 2003a). Given this estimate of the autocorrelation, σ 2 (i,j) is easily computed (cf. for example [START_REF] Rasmussen | Covariance Functions, in: Gaussian Processes for Machine Learning[END_REF] p.84).

The locally multivariate region-based probability of the a contrario approach, π * (r ) , can therefore be calculated as the sum of joint probabilities in a multivariate Gaussian distribution:

π * (r ) = Pr(L (r ) ≥ l (r ) ) = e i=l (r ) Pr(L (r ) = i)
where Pr(L (r

) = i) = S∈C (i) (r ) Pr Z (v ) ≥ Φ -1 (p PRE ), ∀v ∈ S and Z (v ) < Φ -1 (p PRE ), ∀v ∈ S . (13)
In practice, the probabilities (Pr(L (r ) = i)) 0≤i≤e are computed once at the beginning of the analysis. In the context of this paper, the probability associated to each region r is assigned to its centre voxel v to produce a voxel-wise probability map:

π * CONT (v ) = π * (r ) . (14)
The standard a contrario approach assuming independence of the residuals can be seen as a special case where σ (i,j) = 0 ∀(i, j) ∈ {1 . . . e} 2 , i = j.

Experiments

Simulated data analysis

Simulations were used to study the detections under different level of signal-to-noise ratio (SNR) and for signal of different sizes. Two concentric spheres of opposite signal were generated to mimic ring-enhancing lesions (typically observed in brain lesions). The inner sphere represented a hypo-perfused necrosed area and the outer sphere the ringenhancement. A Gaussian noise was added to the signal image so that the SNR was set

Real data analysis

25 patients diagnosed with brain tumours and 61 healthy volunteers were involved in this study. One control subject and four patients were excluded because of strong borderzone sign [START_REF] Zaharchuk | Arterial spin-label imaging in patients with normal bolus perfusion-weighted MR imaging findings: pilot identification of the borderzone sign[END_REF]. The final dataset therefore included 21 patients (13 males, 8 females, age: 55.2 ± 14.1 years) and 60 healthy volunteers (28 males, 32 females, age: 29.4 ± 7.6 years).

We studied seven smoothing kernels for the GLM (with full-width-at-half-maximum w ∈ {0, 2, 4, 6, 8, 10, 12} mm 3 ) and nine parameter sets for the a contrario approach (the pre-defined p-value p PRE ∈ {0.01, 0.005, 0.001} and the sphere radius rd ∈ {1, 2, 3} voxel(s)). Area under the curve were estimated for false positive rates ranging from 0 to 10%, as this is the area of interest in detection analysis [START_REF] Skudlarski | ROC analysis of statistical methods used in functional MRI: individual subjects[END_REF].

Experiment 1: Group ROC curves

In order to combine the data of all the patients included in this analysis, we computed an average ROC curve (across subjects). Given N hyper , the number of subjects presenting at least one hyper-perfusion, the group true positive rate was then estimated by:

TPR G(punc ) = 1 N hyper N hyper s=1 TPR (s,punc ) (15)
On the other hand, the group false positive rate was estimated across all subjects by:

FPR G(punc ) = 1 N N s=1 FPR (s,punc ) (16)
2.2.4. Experiment 2: Individual ROC curves Best parameters. For each subject, the parameter set (pair (p PRE , rd) in a contrario or w in GLM) leading to the highest area under the ROC was identified and used to plot the corresponding "best" ROC curve.

Best parameter set across all subjects. As statistical analyses are usually performed using a single set of parameters across all subjects (and not adjusting for the best parameter set independently for each subject as performed in the previous paragraph), we also compared the a contrario and GLM methods across all subjects for each parameter set.

Ground truth

Based on clinical knowledge, as in [START_REF] Maumet | Patient-specific detection of perfusion abnormalities combining within-subject and between-subject variances in Arterial Spin Labeling[END_REF], we used a semi-automatic procedure that took advantage of the complementary anatomical (T1w-Gd, T2w FLAIR)

and perfusion (DSC) information to get an estimation of the ground truth. The next subsections will briefly describe this procedure.

Due to its low SNR, ASL is not very well suited to measure low level of perfusion [START_REF] Wintermark | Comparative overview of brain perfusion imaging techniques[END_REF]. That is why we focused on hyper-perfusions for sensitivity estimation. Hypo-perfusions were nevertheless retained for specificity calculation. Fig. 3 displays an example of ground truth for a representative subject. Hyper-perfusions. In order to get an estimation of the positives (hyper-perfusions), we implemented a method inspired by the hotspot technique [START_REF] Noguchi | Perfusion imaging of brain tumors using arterial spin-labeling: correlation with histopathologic vascular density[END_REF] commonly used in clinical practice. First, the affected tissue (tumour and oedema) was segmented using a semi-automated method based on the T2w and T1w-Gd images and visually inspected by an expert neuro-radiologist. Second, we compared the segmented regions to their contralateral counterparts in the DSC CBF map. Voxels overtaking the upper decile were identified as potential hyper-perfusions. Each potential perfusion abnormality was then visually inspected by an expert neuro-radiologist and manually corrected if needed. Special care was taken in order to avoid inclusion of hyper-perfusions related to the presence of arteries. Out of the 17 patients who underwent a DSC sequence, 9 presented hyper-perfusions.

Areas of normal perfusion. According to clinical knowledge, in the absence of metastasis, the perfusion abnormalities should be confined to the affected tissue (tumour and oedema) identifiable on T1w-Gd and T2w. Therefore, the non-affected tissue (brain voxels not segmented as part of the tumour or oedema) was considered as an area of normal perfusion (ground truth negatives). Here, all the 21 patients were included, including patient for who the DSC images were not available.

Computation of the ROC curves. For a given subject and a given method, a point of the ROC curve is obtained as described hereafter. First, the probability map is thresholded with an uncorrected p-value p unc to outline the detections. Then, the true positive rate, TPR (s,punc ) , and false positive rates, FPR (s,punc ) , are computed by comparing the detections to the ground truth defined in section 2.2.5. This operation is iterated with uncorrected p-values ranging from 0 to 1 in order to draw the complete ROC curve.

Here, it is worth noting that, since a cumulative probability distribution is, by definition, a monotonically increasing function, the true positive rates and false positive rates can equivalently be calculated by thresholding the statistic map instead of the probability map. The a contrario ROC curve can therefore be computed by thresholding the map of rare event counts and is thus independent of the method selected to compute the region-based probabilities. For ease of calculation, the ROC curves were estimated using the standard a contrario approach. [START_REF] Ashburner | Unified segmentation[END_REF]. A subject-specific anatomical brain mask was created, excluding voxels with less than 50% of brain tissue in subsequent statistical analyses. A six-parameter rigid-body registration of the ASL volumes was carried out in order to reduce undesired effects due to subject motion. Pair-wise subtraction of the control and labelled scans was then computed. Rigid coregistration onto the whole brain anatomical map was then performed based on normalised mutual information. A standard kinetic model [START_REF] Buxton | A general kinetic model for quantitative perfusion imaging with arterial spin labeling[END_REF] was then applied in order to get ASL CBF, according to the following:

f = 6000 × λ ∆M 2 M 0 α TI wd exp -(TI +idx sl * TI sl )/T1 b ( 17
)
where f is the CBF map in mL.100g -1 .min -1 , M 0 the acquired M 0 map, λ the blood/tissue water partition coefficient, α measures the labelling efficiency, ∆M is the perfusion-weighted map, TI = 1.7 s the inversion time [START_REF] Ferré | Improving quality of arterial spin labeling MR imaging at 3 tesla with a 32-channel coil and parallel imaging[END_REF], idx sl the slice index (0 for the first slice), TI sl = 0.045 s the readout time for one slice, TI wd = 0.7 s the temporal width of the bolus, T1 b the T1 of blood. According to [START_REF] Wang | Regional reproducibility of pulsed arterial spin labeling perfusion imaging at 3T[END_REF], we assumed: λ = 0.9 mL.g -1 , T1 b = 1.5 s and α = 0.95. The 6000 factor allows the conversion from mL.g -1 .s -1 to mL.100g -1 .min -1 which is the standard unit for CBF.

We bring the attention of the reader to the fact that, contrary to what is usually done in ASL pre-processing, ∆M represents the set of perfusion-weighted maps (one volume per repetition) instead of a single perfusion-weighted map obtained by averaging across the repetitions. This is necessary in order to allow for the measurement of the within-subject variance.

Spatial normalization parameters estimated during the segmentation step were then applied to the T1 and ASL CBF map in order to normalize the subjects into the ICBM-452 T1 template space [START_REF] Mazziotta | A four-dimensional probabilistic atlas of the human brain[END_REF]. This registration algorithm was selected since it gives good results even in the presence of large anatomical lesions [START_REF] Crinion | Spatial normalization of lesioned brains: performance evaluation and impact on fMRI analyses[END_REF]. Normalisation in intensity was then applied to each ASL CBF map in order to reduce the inter-subject variability [START_REF] Aslan | On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow[END_REF]. The normalisation parameter was calculated as the average CBF in grey matter similarly to [START_REF] Petr | Template-based approach for detecting motor task activation-related hyperperfusion in pulsed asl data[END_REF].

Dynamic Susceptibility weighted Contrast imaging. The DSC images were processed using MR manufacturer software by manually choosing an arterial input function to calculate: CBF, cerebral blood volume and mean transit time maps. The method is based on a deconvolution algorithm as described in [START_REF] Ostergaard | High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis[END_REF]. Similarly to ASL, DSC CBF maps were co-registered on anatomical maps and spatially normalized.

Results

Simulations

Figure 4 plots the area under the ROC curve (AUC) obtained on the detections of hyper-perfusions and hyper-perfusions for the GLM and the a contrario approach on simulated lesions.

With the GLM, we observe an opposite effects of smoothing on the detection of hypo-perfusions versus hyper-perfusions. While smoothing is beneficial to detect hyperperfusions when the necrosis radius is greater than 2 voxels, for hyper-perfusions, on the other hand, smoothing only helps with a radius of 2. This illustrates the fact that with a Gaussian smoothing the signal can be cancelled by neighboring voxels if they hold signal of opposite sign.

With the a contrario approach, a good level of detection can be reached at the same time for hypo-and hyper-perfusions. As the SNR increase, the a contrario detections get closer to the ground truth with any set of parameters studied.

Real data

In 3.2.1, the ROC curves corresponding to each individual patient are computed and compared. Then, in 3.2.2, the average ROC curve over the group is computed for each method. Finally, a qualitative comparison is presented in 3.2.3.

Individual ROC curves

Best parameters. In fig. 5, it is clearly visible that the proposed a contrario approach outperforms the GLM for all subjects. A paired two-sample t-test comparing the a contrario and the GLM with the best parameter set for each subject outlines a significant difference (p = 0.008). Furthermore the best parameter set found for each subject was less variable for the a contrario approach (the best set was (rd = 3; p PRE = 0.001) for 6 subjects, (rd = 2; p PRE = 0.001) for 2 subjects and (rd = 2; p PRE = 0.005) for the remaining subject) than for the GLM (the best set was w = 4 mm 3 for 2 subjects, w = 6 mm 3 for 1 subject, w = 8 mm 3 for 2 subjects and w = 12 mm 3 for 4 subjects).

Best parameter set across all subjects. Table 1 presents the area under the ROC curves (average over the 9 patients) for the a contrario approach and the GLM. The best area under the curve is obtained for the a contrario approach with p PRE = 0.001 and rd = 3 and for the GLM with w = 6 mm 3 . A paired two-sample t-test between the best configurations outlines the superiority of the a contrario approach (p = 0.004). This is in line with the higher variability of the best parameter set for the GLM outlined in the previous section. Figure 5: Best ROC curves for false positive rates ranging between 0% and 10%, for the massively univariate GLM (red) and the proposed a contrario approach (blue) in nine patients. Overall, the a contrario approach outperforms the GLM.

Group ROC curves

Fig. 6 plots the resulting average ROC curve for each parameter set for the a contrario approach and the GLM. The corresponding area under the curves are summarized in table 2. The results are very close to the one obtained on the set of 9 subjects in the previous section, outlining the fact the false positive rate at a given uncorrected p-value is not varying much across subjects. As before, the a contrario approach outperforms the GLM.

Table 1: Area under the ROC curve, averaged over the 9 subjects presenting hyper-perfusions, for false positive rates ranging between 0% and 10%, with the a contrario approach (with a sphere radius rd ∈ {1, 2, 3} voxel(s) and a pre-defined p-value p ∈ {0.01, 0.005, 0.001}) and the GLM (smoothed with a Gaussian kernel of full-width-at-half-maximum w ∈ {0, 2, 4, 6, 8, 10, 12} mm 3 ). The proposed a contrario approach outperforms all tested configurations of the GLM. and 10%, with the GLM (smoothed with a Gaussian kernel of full-width-at-half-maximum w ∈ {0, 2, 4, 6, 8, 10, 12} mm 3 ) and the a contrario approach (with a sphere radius rd ∈ {1, 2, 3} voxel(s) and a pre-defined p-value pPRE ∈ {0.01, 0.005, 0.001})

Qualitative comparison

In order to illustrate the advantage of the a contrario approach over the GLM, we chose 2 representative subjects and compared the methods at fixed false positive rate and true positive rate. To this aim, we selected the uncorrected p-values that would lead to a pre-specified false positive rate (or true positive rate) from the ROC analysis. We Table 2: Area under the average ROC curve (based on 21 subjects), for false positive rates ranging between 0% and 10%, with the a contrario approach (with a sphere radius rd ∈ {1, 2, 3} voxel(s) and a pre-defined p-value p ∈ {0.01, 0.005, 0.001}) and the GLM (smoothed with a Gaussian kernel of fullwidth-at-half-maximum w ∈ {0, 2, 4, 6, 8, 10, 12} mm 3 ). The proposed a contrario approach outperforms the GLM. Fig. 7 presents the detections obtained with both methods on the 2 selected patients.

The first subject, which presents a small hyper-perfusion, is studied at a true positive rate of 50% and the second at a false positive rate of 5%.

Patient 15 suffers from a gliosarcoma in the left hemisphere near the parahippocampal region. The lesion displays a small hyper-perfusion in its dorsal part, small hypoperfusions are seen in the surrounding oedema. At a true positive rate of 50%, the GLM displays a larger number of false positives than the a contrario approach.

Patient 7 presents a meningioma of both occipital lobes characterized by a large hyper-perfusion. At a false positive rate of 5%, most of the hyper-perfusion was properly detected by both methods. The a contrario approach is however more sensitive as it detects a larger proportion of the hyper-perfusion.

These 2 cases illustrate the reduced sensitivity of the GLM by comparison to the a contrario approach at the same specificity level.

Discussion

Quantitative assessment of the detections and comparison between detection methods are challenging tasks. This is mainly because, like in many other medical imaging problems, the ground truth is not clearly stated. We chose to evaluate this framework 0 on patients diagnosed with tumour pathology because perfusion abnormalities have been widely studied in this context [START_REF] Chalela | Magnetic resonance perfusion imaging in acute ischemic stroke using continuous arterial spin labeling[END_REF][START_REF] Sugahara | Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrastenhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue[END_REF][START_REF] Warmuth | Quantification of Blood Flow in Brain Tumors: Comparison of Arterial Spin Labeling and Dynamic Susceptibility-weighted Contrast-enhanced MR Imaging[END_REF][START_REF] Weber | Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors[END_REF][START_REF] Chawla | Arterial spin-labeling and MR spectroscopy in the differentiation of gliomas[END_REF]. Also, as perfusion is useful clinical information, DSC is part of the clinical routine for these patients.

-The normalisation in intensity used in this paper is not optimal and can lead to the detection of pseudo-decreases or pseudo-increases (for a related discussion cf. [START_REF] Buchert | Adjusted scaling of FDG positron emission tomography images for statistical evaluation in patients with suspected Alzheimer's disease[END_REF]). In theory, based on a Q2TIPS ASL sequence [START_REF] Wong | Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II)[END_REF] one should be able to derive quantitative CBF values and avoid intensity normalisation. However, in the context of this analysis, we observed a large variability in global CBF signal both in the control and patient groups that could not be explained by age or gender.

To compensate for those large variations across subjects, using an intensity normalisation scheme appeared to be a requirement. We hypothesize that the large variations we observed could be explained by an imperfect timing of our sequence. Recent literature (e.g. [START_REF] Villien | Per-subject characterization of bolus width in pulsed arterial spin labeling using bolus turbo sampling[END_REF], [START_REF] Alsop | Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia[END_REF]) recommends using a shorter bolus width than the one we typically used in this experiment. If our saturation pulses were indeed too late, it would mean than only pseudo-quantitative values could be derived from the acquisition hence calling for a normalisation in intensity. The a contrario approach can be applied in presence or absence of a normalisation procedure. When working on truly quantitative metrics, intensity normalisation can be avoided.

Subjects in our patient group were significantly older than the control subjects which is clearly not ideal as age is known to impact both CBF [START_REF] Biagi | Age dependence of cerebral perfusion assessed by magnetic resonance continuous arterial spin labeling[END_REF] and grey matter/white matter structure leading to different observed level of perfusion. While the use of a normalisation scheme lessened the effect of change in global of perfusion, this is not enough to compensate for age-related variations. For more precise detections an age-matched template would be needed. Nevertheless the results observed here are valid and we expect that using an age-matched template would improve the detections.

Calculation of CBF using singular value decomposition on DSC can lead to under or over-estimation of the CBF if the arrival times are not the same in the arterial input function and in the tissue. This is a known drawback of SVD methods and might have biased our estimation of the CBF based on DSC. But, as the ground truth detections were not determined based on a thresholding on absolute values but rather using a rel-0 ative comparison of left and right hemisphere and then manually updated by a clinician if needed, we do not expect this to be too much of a concern.

-The a contrario approach demonstrated a clear improvement over the GLM which is the most widely adopted method to analyse functional MRI data. Compared to other multivariate approaches, such as machine learning techniques, the a contrario approach has the advantage of remaining very simple and providing results in the same manner as a standard GLM analysis. Compared to a classic searchlight approach using Mahalanobis distance, the a contrario approaches has the possibility to intrinsically differentiate hypo-from hyper-perfusions which is critical in the context of brain tumours.

While a comprehensive comparison with those techniques was beyond the scope of this paper, an interesting extension of this experiment could perform a direct comparison of the a contrario approach to machine learning (in particular one-class implementation as in [START_REF] Miranda | Patient classification as an outlier detection problem: an application of the One-Class Support Vector Machine[END_REF]) and searchlight procedures.

In our experiments on real data, the best performance for the a contrario approach were reached for a sphere radius of rd = 3 voxels and a threshold of p PRE = 0.001. This parameter set was found to be best for 6 subjects out of 9 among all tested configurations.

It would be interesting to further investigate how this extends to other analysis and in particular if even smaller p PRE leads to more accurate results.

In this paper, region-based probabilities were computed by computing the joint probability of a multivariate normal distribution. While these can be easily pre-computed to reduce the computational time at execution, they can nevertheless be very computationally intensive to compute for a sphere radius greater than 2 or 3 voxels. Using a non-parametric approach, such as permutation-based or sign-flipping technique [START_REF] Winkler | Permutation inference for the general linear model[END_REF] might be an interesting alternative.

Conclusion

We have presented a locally multivariate procedure using a a contrario metric for the detection of patient-specific perfusion abnormalities in ASL. Using ROC curves, we outlined that this locally multivariate procedure outperforms the massively univariate GLM, commonly employed in neuroimaging. 1

Furthermore, we introduced a non-independent version of this a contrario procedure in order to deal with the spatial autocorrelation of the noise observed in MRI.

We assessed our approach in the context of brain tumours since perfusion patterns have been widely studied in this clinical context. This allowed us to get an estimate of the ground truth and perform a quantitative validation. Our approach is however suitable to a broader range of applications and we plan in the future to study pathologies presenting more subtle patterns of abnormal perfusion.

Ground

Figure 2 :

 2 Figure 2: Simulated lesions. a) Ground truth hypo-perfusion (blue) and hyper-perfusion (red) for a necrosis radius of n ∈ {2, 4, 6} voxels. b) Examples of simulated images for SNR ∈ {0.5, 1, 2} and n = 4 voxels.

Figure 3 :

 3 Figure 3: Ground truth for a representative subject. From left to right: T1-Gd, DSC CBF, groundtruth hyper-perfusions (i.e. ground truth positives) in red and ground-truth area of normal perfusion (i.e. ground truth negatives) in green overlaid on the T1-Gd.

2. 3 .

 3 Data acquisition and pre-processing 2.3.1. Data acquisition Data acquisition was performed on a 3T Siemens Verio MR scanner with a 32-channel head-coil. Patients were scanned in the context of clinical practice. The imaging protocol included a 3D T1-weighted anatomical sequence (T1w) (TR: 1900 ms, TE: 2.27 ms, FOV: 256 mm × 256 mm × 176 mm, flip angle: 9 • , resolution: 1 mm × 1 mm × 1 mm), a PICORE Q2TIPS sequence (Wong et al., 1998) with crusher gradients (TR: 3000 ms, TE: 18 ms, FOV: 192 mm × 192 mm, flip angle: 90 • , resolution: 3 mm × 3 mm, slice thickness: 7 mm, inter-slice gap: 0.7 mm, TI: 1700 ms, TI wd : 700 ms, 60 repetitions (35 subjects) or 30 repetitions (25 subjects), mSENSE parallel imaging with accelerating factor of 2). In addition to these sequences, the patients also underwent a 3D T1w post gadolinium (T1w-Gd) sequence (TR: 1900 ms, TE: 2.27 ms, flip angle: 9 • , FOV: 250 mm × 250 mm ×176 mm, resolution: 1 mm × 1 mm × 1 mm) and a 2D T2w FLAIR sequence (TR: 9000 ms, TE: 90 ms, FOV: 220 mm × 199.4 mm, flip angle: 150

Figure 4 :

 4 Figure 4: Area under the ROC curves (AUC) for the proposed a contrario approach (first row) and the massively univariate GLM (second row) in the detection of hyper-perfusions (first column) and hypo-perfusions (second column) on simulated data (necrosis radius n ∈ {2, 4, 6} voxels and SN R ∈ {0.5, 1, 2}).

  01 p = 0.005 p = 0.001 p = 0.01 p = 0.005 p = 0.001 p = 0.01 p = 0.005 p = 0.001

Figure 6 :

 6 Figure 6: Average ROC curve (based on 21 subjects), for false positive rates ranging between 0%

  01 p = 0.005 p = 0.001 p = 0.01 p = 0.005 p = 0.001 p = 0.01 p = 0.005 p = 0best set of parameters identified for each subject (from section 3.2.1).

Figure 7 :

 7 Figure7: Perfusion abnormalities detections in 2 patients with the GLM and the a contrario approach using the best parameter set for each method. From left to right: ground truth hyper-perfusions (red) and hypo-perfusions (blue) overlaid on the T1w-Gd map; GLM, hyper-perfusions (red to yellow) and hypo-perfusions (dark to light blue); a contrario detections hyper-perfusions (red to yellow) and hypoperfusions (dark to light blue). For the a contrario and GLM detections, minus logarithm of the p-values is displayed.

Acknowledgements

This work has been supported by Région Bretagne, Neurinfo Core Facilities and by the Wellcome Trust.