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Local Pathways Towards De-escalation of Libya's Conflict

Invitation Only Research Event

28 January 2020 - 3:00pm to 4:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Usama Otman Essed, Libya Center for Strategic & Future Studies
Chair: Tim Eaton, Middle East and North Africa Programme, Chatham House

A shaky truce remains broadly in place among rival Libyan forces fighting for control of Tripoli. However, a durable ceasefire to bring an end to the current bout of conflict, which was initiated by Khalifa Haftar’s Libyan Arab Armed Forces’ (LAAF) offensive on the capital in April 2019, has not been reached. In recent weeks attention has focused on talks hosted in Moscow and Berlin, with the former aimed at agreeing a ceasefire and the latter seeking to reach agreement among international actors to bring an end to external military support for Libyan warring actors, and to craft a way forward for future intra-Libyan talks. Yet, there has been little emphasis on Libyan actors – beyond Haftar and prime minister Fayez al-Serraj – in this process.
 
This roundtable will bring together experts and policymakers to discuss means of de-escalating the conflict and seeking a lasting resolution through the development of interconnected intra-Libyan social and security negotiation tracks. Mr Usama Otman Essed of the Libya Center for Strategic and Future Studies (LCSFS) will present his research group’s ideas on these issues and discuss their ongoing efforts to promote dialogue among social and security actors.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Prospects for Reforming Libya’s Economic Governance: Ways Forward

Invitation Only Research Event

6 February 2020 - 10:30am to 12:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Jason Pack, Non-Resident Fellow, Middle East Institute
Tim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham House
Chair: Elham Saudi, Director, Lawyers for Justice Libya

There is a broad consensus that Libya’s rentier, patronage-based system of governance is a driver, and not only a symptom, of Libya’s continuing conflict. The dysfunction of Libya’s economic system of governance has been exacerbated by the governance split that has prevailed since 2014 whereby rival administrations of state institutions have emerged. Despite these challenges, a system of economic interdependence, whereby forces aligned with Field Marshal Haftar control much of the oil and gas infrastructure and the UN-backed Government of National Accord controls the means of financial distribution, has largely prevailed. Yet, at the time of writing, this is under threat: a damaging oil blockade is being implemented by forces aligned with Haftar and those state institutions that do function on a national basis are finding it increasingly difficult to avoid being dragged into the conflict.

This roundtable will bring together analysts and policymakers to discuss these dynamics and look at possible remedies. Jason Pack, non-resident fellow at the Middle East Institute, will present the findings of his latest paper on the issue which recommends the formation of 'a Libyan-requested and Libyan-led International Financial Commission vested with the requisite authorities to completely restructure the economy.' Tim Eaton, who has been leading Chatham House’s work on Libya’s conflict economy, supporting UNSMIL’s efforts in this field, will act as respondent.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule




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Conflict and the Water Crisis in Iraq

Invitation Only Research Event

9 March 2020 - 9:00am to 10:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Azzam Alwash, Founder & CEO, Nature Iraq
Peter Schwartzstein, Independent Journalist; Non-Resident Fellow, Centre for Climate Security
Discussant: Dr Jehan Baban, Founder & President, The Iraqi Environment and Health Society-UK
Chair: Dr Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Department, Chatham House

Water is a critical issue for Iraq’s future stability and prosperity. Only a few decades ago, the country was one of the most fertile in the region, with two major rivers flowing through it. Today, national and transboundary pollution, mismanagement, and debilitating cycles of conflict have contributed to a situation where only half of current water needs are being met, and where an 80% reduction in the flow of water down the Tigris and Euphrates rivers has led to the loss of millions of acres of formerly productive land and the displacement of rural communities.

Water scarcity can be a driver of violence and conflict. Tribal conflicts over water sources have erupted sporadically in the south and the contamination of municipal water which led to the hospitalization of some 118,000 citizens was a trigger for the large-scale protests in Basra in late 2018. Without concerted action by national and local governments, companies and international agencies, the situation will only worsen as higher temperatures and reduced rainfall drive rural-to-urban migration and increase the risk of drought, food insecurity and water-related diseases.

At this roundtable, part of the Chatham House Iraq Initiative, experts will discuss the domestic, regional and international factors that continue to exacerbate the water crisis in Iraq, and propose solutions, including technical innovation, public sector capacity-building and greater international cooperation, that might contribute to effective state-building, build resilience to the effects of climate change and reduce the risk of further conflict.

Event attributes

Chatham House Rule

Georgia Cooke

Project Manager, Middle East and North Africa Programme
+44 (0)20 7957 5740




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Lebanon Is Paying the Cost of Its Dysfunctional Politics

26 February 2020

Nadim Shehadi

Associate Fellow, Middle East and North Africa Programme
A series of fights to political stalemate have led its economy to the brink and cut it off from its natural economic partners in the Gulf.

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Protests against economic conditions and government inaction turned violent in January. Photo: Getty Images.

To understand Lebanon’s financial collapse, look to its politics.

The country has been deeply damaged by an increasingly dysfunctional political system. A series of compromises have alienated it from its main markets in the Gulf and strangled its economy; anyone that has glanced at fluctuations in Lebanese bank deposits over the last 10 years can see the correlation.

Imagine if Boris Johnson or Donald Trump were obliged to form joint governments with Jeremy Corbyn or Bernie Sanders. The result would be paralysis and lack of accountability as each party pulls the country in opposite directions and blames the other for the state of limbo. This has been the state of affairs in Lebanon since the Doha agreement of 2008. 

That agreement followed an 18-month siege that paralyzed Beirut and an attack on the city by Hezbollah’s ‘black shirts’. The Doha formula imposed governments of national unity between Prime Minister Saad Hariri’s pro-Saudi camp and Hezbollah’s pro-Iran camp and their respective internal allies.

The pattern was set: each period of subsequent paralysis was followed by further compromise as the tug of war pulled the country away from its principal economic partners, the Arab Gulf states, with the regional balance of power tilting towards Hezbollah. 

It was not supposed to be like this. The Baabda Declaration in June 2012, reached after a process of national dialogue, was meant to secure Lebanon’s neutrality in regional conflicts, with both sides promising to hold back on external alliances and coexist despite difference over major regional issues like the war in Syria, the standoff between the US and Iran or relations with Israel or the Gulf states.

This has worn away. The Baabda declaration itself became a sham when Hezbollah inserted itself into the war in Syria in support of the Assad regime and overtly got involved in Iraq and Yemen as an Iranian proxy. This was followed by Saudi opposition to concessions by Hariri that led to the election of General Michel Aoun, an ally of Hezbollah, as president in October 2016; again, after a political paralysis that lasted 29 months with no active government and no head of state.  

The Saudis were also furious when President Aoun’s son-in-law, Foreign Minister Gebran Bassil, abstained from condemning the burning of the Saudi embassy in Tehran at an Arab League meeting in Cairo in January 2016, citing the need to preserve national unity.

Fearing that he was simply providing Hezbollah with protection in the guise of compromise, the Saudis pressured Hariri to resign in November 2017 during a trip to Riyadh, but he later challenged that by retracting on his resignation when back in Beirut. Lebanon was caught between two sides, and as the regional conflict intensified from tension to open confrontation, neutrality was no longer an option.

Gulf connections

An estimated 350,000 Lebanese expats live and work in Saudi Arabia, the UAE, Qatar and Kuwait. These countries are also the main clients for Lebanese contractors, consultants and advertising companies, some of which have offices there. The domestic tourism industry relies heavily on Arab Gulf visitors and they are a principal source of foreign investments especially in the real estate sector.

Lebanon also enjoyed a certain degree of political and economic protection from the US and the Gulf, and Hezbollah benefited indirectly from that protection, as it also shielded it to a certain degree from sanctions.

The deterioration of relations meant that the country was cut off by its Gulf partners. This was manifested in travel bans for Gulf Cooperation Council (GCC) nationals to Lebanon and a decrease in investments and bank deposits, as well as a decrease in remittances from Lebanese expats, partly because of economic crisis in the Gulf countries themselves.

Saudi Arabia withdrew $4 billion of aid to the Lebanese army and internal security forces, and no aid or deposits were forthcoming as the economic and financial situation deteriorated. 

The costs to the Lebanese economy include the opportunity cost created by the annual threat of war with Israel, after which trips are cancelled and projects postponed. Hezbollah also controls a section of Beirut port where it pays no duty or taxes. Add to that the economic fallout from the war in Syria, such as the impact on exports, the inflow of refugees and the cost of Hezbollah’s involvement.

The burden of these political factors is difficult to estimate but it constitutes the ransom that the Lebanese economy bears as a cost of the compromise. This is not to absolve Lebanese politicians from corruption or bankers of mismanagement but to add that political factors cannot be ignored.

The cumulative cost and economic impact of being cut off from its main economic partner eventually bankrupted the country. The fiscal and financial aspects, with Lebanon’s inability to service its debt, are but a reflection of these political factors. In the long run, the key to avoiding complete collapse is to restore relations with the GCC and free Lebanon from that very costly grip.




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Expanding Sino–Maghreb Relations: Morocco and Tunisia

26 February 2020

Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia.

Yahia H. Zoubir

Senior Professor of International Studies, KEDGE Business School, France and Visiting Fellow, Brookings Doha Center

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Chinese President Xi Jinping and King Mohammed VI of Morocco wave during a welcoming ceremony outside the Great Hall of the People in Beijing on 11 May 2016. Photo: Getty Images.

Summary

  • China’s presence in the Maghreb has increased in recent years, raising concerns among Western powers. China has focused on bilateral relations with these countries while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF). However, this engagement has limited strategic value compared to relations China has with Saudi Arabia or the United Arab Emirates.
  • Since the launch of the Belt and Road Initiative (BRI) in 2013, China has shown greater interest in the Maghreb as an entry point to European and African markets. China has pursued commercial relations over political influence in the region. Morocco and Tunisia are still dependent on France, their former colonial power, and the European Union, which exert great political, economic, security and cultural influence over the two countries.
  • The Maghreb countries’ economic relations with China have grown exponentially, with Algeria forming the closest relationship. However, Morocco and Tunisia are keen to attract China’s investment and involvement in major construction and infrastructure projects to boost industrial and economic development. While China’s investments in Morocco and Tunisia remain at a low level, trade relations with both countries have grown steadily. Politically, China’s policy of noninterference in domestic affairs appeals to Maghreb states, which resent Western interference.
  • China’s influence in the Maghreb remains minimal. Its soft power push has struggled to promote advantages of strong relations with China beyond economics. Furthermore, Morocco and Tunisia’s populations have generally scant knowledge about China’s politics and culture. China has tried to address this lack of familiarity through the establishment of Confucius Institutes and other cultural activities. However, language and cultural barriers still impede the development of close relations, compared to those China has with other countries in Africa.




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POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests

Invitation Only Research Event

18 March 2020 - 9:00am to 10:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham House
Emaddedin Badi, Non-Resident Scholar, Middle East Institute
Tim Eaton, Senior Research Fellow, MENA Programme Chatham House
Valerie Stocker, Independent Researcher

Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country,  armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.

In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.

This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Georgia Cooke

Project Manager, Middle East and North Africa Programme
+44 (0)20 7957 5740




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The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests

17 March 2020

This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics.

Tim Eaton

Senior Research Fellow, Middle East and North Africa Programme

Abdul Rahman Alageli

Associate Fellow, Middle East and North Africa Programme

Emadeddin Badi

Policy Leader Fellow, School of Transnational Governance, European University Institute

Mohamed Eljarh

Co-founder and CEO, Libya Outlook

Valerie Stocker

Researcher

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Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien

Summary

  • Libya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.
  • In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.
  • The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.
  • Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.
  • Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:
  • Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for    the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.
  • In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.
  • In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.
  • To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:
  • Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.
  • In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.
  • In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.
  • Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.
  • In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive.




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Webinar: How is the MENA Region Dealing with the COVID-19 Outbreak?

Research Event

2 April 2020 - 12:30pm to 1:30pm

Event participants

Omar Dewachi, Associate Professor of Medical Anthropology, Department of Anthropology, Rutgers University
Tin Hinane El Kadi, Associate Fellow, MENA Programme, Chatham House
Moderator: Sanam Vakil, Deputy Head & Senior Research Fellow, MENA Programme, Chatham House

At this webinar, part of the Chatham House MENA Programme Online Event Series, experts will explore how the coronavirus pandemic is impacting the economy, state-society relations and healthcare throughout the Middle East and North Africa. How are governments handling this crisis and what measures have they put in place to stop the spread of the virus? Why are some governments withholding information about the number of cases? What has the response from the public been so far? How is this affecting the region and how does it compare to the global picture?

The event will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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COVID-19 Impact on Refugees is Also Political

31 March 2020

Dr Lina Khatib

Director, Middle East and North Africa Programme
The spread of coronavirus in the Levant puts Syrian as well as other refugees and internally displaced people at particular risk because of the policies and practices of the authorities.

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The word Corona written in the sand on the beach in Lebanon's southern city of Saida. amid the spread of coronavirus in the country. Photo by MAHMOUD ZAYYAT/AFP via Getty Images.

As Lebanon strains to contain COVID-19, it is not clear which governmental public health policies apply to refugees. The government announced free testing for coronavirus in the public Rafiq Hariri University Hospital in Beirut but has not mentioned if refugees are eligible.

Lebanon’s coronavirus containment strategy is based on self-reporting and, given incidents of forced deportation and harassment of Syrian refugees from both the authorities and local communities, it is certainly less likely refugees would present themselves to the health authorities for fear of deportation.

Despite agreeing a Lebanon Crisis Response Plan with the UN for refugees, different ministries were left to implement it without coordination, just as Lebanese politicians from all sides started trying to rally popular support for ridding Lebanon from refugees - in particular from Syria, who Lebanese leaders say are causing a strain on the country’s already weak infrastructure.

This finger pointing is coupled with the leaders’ own complete disregard for the rampant corruption and lack of accountability within Lebanon’s political class, which contribute to the weakening of the country’s infrastructure.

For refugees who do find themselves back in Syria, there are different challenges according to which area they are in. In the north-east, the WHO and international NGOs (INGOs) negotiate with both Kurdish authorities as well as the government - each presenting its own hurdles.

Kurdish authorities in northeast Syria have closed the Semalka border with Iraqi Kurdistan, posing a serious dilemma for INGOs offering services in north-east Syria but concerned about their staff safety whose movement is now curtailed.

The government of Syria has stipulated all emergency response must go through its ministries. But this limits what the WHO can do in the country and gives Syrian authorities the ability to block ‘cross-line aid’ which goes from government-controlled to non-government areas.

Despite reports that doctors raised the alarm about suspected cases well before patient zero was confirmed, the government appears to be either covering up the actual extent of the spread of COVID-19 or failing to respond. Some limited testing kits have arrived but testing has barely started.

The WHO’s Syria plan is divided into three regions (north-west, north-east, and areas under government control). But concerns remain as to how workable such a decentralized plan is because of the government’s practices. In January, the UN Security Council did not renew the cross-border response resolution for the Yaroubiye border crossing between Syria and Iraq that the WHO was using to send medical supplies into north-east Syria.

Syrian authorities do not permit recently authorized ‘cross-line’ responders to engage with non-government authorities in areas outside regime control. This essentially voids the authorization to work cross-line as it is practically impossible to implement programs. The WHO has sought approval from the Syrian Ministry of Foreign Affairs to move medical supplies by land to north-east Syria.

While promising facilitation, the Ministry’s reply comes with conditions of seeking detailed approval for every shipment. When Eastern Ghouta was under siege, similar conditions led to certain supplies being removed from UN/ICRC convoys to Eastern Ghouta, and there is no guarantee this will not happen again.

Due to lack of capacity in north-east Syria, coronavirus tests conducted by the WHO there must be processed through the Central Public Health Laboratory in Damascus. Samples are transported twice a week from Qamishli to Damascus but no results were ever received from Damascus for those tests.

While the WHO is able to coordinate access to north-west Syria with the Turkish authorities, the prospective coronavirus testing capacity in the Idlib region is low – despite claims that thousands of kits are arriving, a lack of resource on the ground means potentially only 20 tests per day could be done in an area inhabited by an estimated three million people.

Following the recently announced ceasefire in the area, many internally displaced people are returning from the Turkish border to their homes in the north-west, but such mass movement increases the risk of coronavirus spreading. People also continue to move between Syria, Iraq, Turkey and Lebanon, posing a challenge to the WHO’s COVID-19 response in the Levant, as the WHO has distinct response plans for each country in the region and it is difficult to coordinate across these plans.

Challenges face refugees even if they head towards Europe due to the potential for conflation between migration control and coronavirus outbreak control. Aurelie Ponthieu, Coordinator for Forced Migration at Médecins Sans Frontières (MSF) says there is a risk some countries could use COVID-19 to impose draconian measures towards asylum seekers.

The crisis has also put a halt to search and rescue operations in the Mediterranean because European countries are not allowing boats carrying migrants to disembark under the pretext of limiting the spread of coronavirus. And for migrants who already made it - such as in Greece - they are now being put in collective quarantines in asylum centers, often with poor medical facilities.

Ponthieu also reports that migrants being quarantined on overcrowded navy ships docked in Greek ports, making social distancing impossible. And she is concerned the Greek authorities are imposing a curfew on asylum seekers but not on the local population.

UNHCR is stressing that people’s right of asylum must not be overruled by concerns about the spread of coronavirus, while local and international NGOs across the Levant are trying to coordinate their advocacy on lifting restrictions on freedom of movement for humanitarian workers and on other policies and practices by authorities in the region which are adversely affecting refugee and other vulnerable communities.

The international community must not lose sight of the impact of the crisis on refugees and migrants. It is not enough simply to supply humanitarian and medical assistance without paying attention to the policies and practices of the different authorities who have direct control over the fate of vulnerable communities.

The author would like to thank Aurelie Ponthieu and the two INGO field workers who all agreed to be interviewed to inform this analysis piece.




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Webinar: OPEC, Falling Oil Prices and COVID-19

Corporate Members Event Webinar

7 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Julian Lee, Oil Strategist, Bloomberg LP London
Dr John Sfakianakis, Associate Fellow, Middle East and North Africa Programme, Chatham House; Chief Economist and Head of Research, Gulf Research Center
Professor Paul Stevens, Distinguished Fellow, Energy, Environment and Resources Programme, Chatham House
Emily Stromquist, Director, Castlereagh Associates
Chair: Dr Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

In early March, global oil prices fell sharply, hitting lows of under $30 a barrel. Two factors explain this collapse: firstly the decrease in global demand for oil as a result of the COVID-19 pandemic and, secondly, the breakdown in OPEC-Russian relations and the subsequent Saudi-Russian price war which has seen both countries move to flood the market with cheap oil.
 
Against this backdrop, the panellists will reflect on the challenges currently facing OPEC as well as the oil industry as a whole. How are OPEC countries affected by the ever-evolving Covid-19 pandemic? What are the underlying causes behind the Saudi-Russian price war? Is the conflict likely to be resolved soon? And what are the implications of these challenges for the oil industry?

This event is part of a fortnightly series of 'Business in Focus' webinars reflecting on the impact of COVID-19 on areas of particular professional interest for our corporate members and giving circles.

Not a corporate member? Find out more.




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Webinar: Can the Justice and Development Party Still Absorb Popular Anger in Morocco?

Webinar Research Event

8 April 2020 - 1:00pm to 2:00pm

Event participants

Mohammed Masbah, Director, Moroccan Institute for Policy Analysis; Associate Fellow, MENA Programme, Chatham House
Moderator: Lina Khatib, Director, MENA Programme, Chatham House

Ever since independence, the Moroccan monarchy has used political parties to legitimize the country’s authoritarian political process and structure, and to absorb social and political anger. The palace puts successive governments and other elected institutions, such as local and regional councils, at the frontline of public blame, and replaces them once they fail this function.

In a recent article, MENA Programme Associate Fellow, Mohammed Masbah, examines how the Moroccan monarchy has used this strategy with the ruling Justice and Development Party (PJD) so that the palace remains the centre of political power, while the PJD – and other political parties before it– takes responsibility for coping with the mounting socio-economic crisis.

In this webinar, part of the Chatham House project on The Future of the State in the Middle East and North Africa, the article’s author will discuss the risks this approach presents for the long-term stability of Morocco and what reforms are needed to increase citizens’ dwindling confidence in the political process.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful.




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Can Morocco Effectively Handle the COVID-19 Crisis?

6 April 2020

Dr Mohammed Masbah

Associate Fellow, Middle East and North Africa Programme

Anna Jacobs

Senior Research Assistant, Brookings Doha Center
The Moroccan government is capitalizing on a burst of unity, social solidarity and public support in the face of a crisis. However, if it fails to effectively mitigate the public health and economic impacts of the COVID-19 pandemic, this spirit of solidarity and cooperation will not last long.

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A general view of empty stores during curfew as a precaution against the new type of coronavirus (COVID-19) in Rabat, Morocco on 1 April 2020. Photo by Jalal Morchidi/Anadolu Agency via Getty Images.

In Morocco, the COVID-19 pandemic has increased public trust in government, but people still have doubts about the effectiveness of the healthcare system. According to a recent study conducted by the Moroccan Institute for Policy Analysis (MIPA), the majority of Moroccans surveyed are generally satisfied with the measures taken by the government to battle the coronavirus. However, the same survey also shows that Moroccans do not have confidence in the healthcare sector’s ability to respond to this pandemic.

The positive perceptions of the government’s response can be explained by the swift and strict measures enacted. King Mohammed VI held a high-level meeting with the prime minister, the minister of health, and top security officials on 17 March and a few days later, on 20 March, the Moroccan government declared a state of health emergency and began to implement aggressive measures to contain the virus.

This has included closing airports, schools, mosques, cafés and shops – with the exception of food markets – preventing large gatherings, as well as strict guidelines to ensure social distancing. As of 2 April, nearly 5000 people have been arrested for violating the state of health emergency.

In order to address urgent medical needs and to mitigate the economic impact of the pandemic, the King ordered the creation of an emergency fund, raising more than 32.7 billion Moroccan Dirhams ($3.2 billion). The Ministry of Finance will begin to make cash transfers to vulnerable citizens, and especially those who have lost their jobs. However, the stipulations surrounding these cash transfers will be decided in the coming weeks.

Updates about the virus are communicated daily by the Ministry of Health, despite growing criticism of its communication strategy. As of 4 April, Moroccan authorities have confirmed 883 cases and 58 deaths.

Call for national unity

In times like these, there is a call for unity in the face of a national and global crisis, and opposition groups such as Adl wal Ihssan and Rif activists have expressed their support for government measures and have encouraged people to follow the new guidelines and restrictions. However, despite calls to release political prisoners, Moroccan authorities have not indicated that they will do so. This is a missed opportunity vis-à-vis the opposition because it could have served as a way to further strengthen national unity during the crisis.

These are all promising signs and point to what is likely to be a short-term burst in unity and institutional trust. However, the institutional weaknesses in governance and the healthcare system have not disappeared, which is why this increase in institutional trust should be taken with a grain of salt.

Public trust issues

This pandemic poses tremendous challenges for governments across the globe, and this holds especially true for states in the Middle East and North Africa region, where citizens do not approve of government performance and do not trust key state institutions. The 2019 Arab Barometer survey found that Moroccans do not trust most of the country’s political institutions (notably the parliament and the Council of Ministers) and the level of satisfaction with the government’s performance remains extremely low.

On the public health front, as shown in two of MIPA’s recent surveys, trust in the healthcare system is also very low. Around three-quarters of those surveyed do not trust Moroccan hospitals, highlighting the acute structural problems in the healthcare system. In fact, there is a stark divide between private and public healthcare, as well as a huge gap in access to healthcare facilities between urban and rural areas. Most of the country’s hospitals and doctors are located in major urban areas and the only three laboratories with capabilities for COVID-19 testing are located in Rabat and Casablanca, but even there, testing capacity is very limited.

Similar to other countries, there could be a major shortage of doctors and medical equipment throughout Morocco. So far, the Ministry of Finance has said that 2 billion dirhams of the emergency fund will go towards purchasing medical equipment such as beds, ventilators, tests, prevention kits and radiology equipment, but the timeline remains unclear.

A vulnerable economy

There is significant concern about the medium- and long-term economic impact of the virus. Two of the country’s key economic sectors have already been hit hard: agriculture and tourism. The agricultural sector was already struggling due to the impact of drought, while the coronavirus pandemic is likely to impact Morocco’s tourism industry not just this year, but well into 2021. In terms of government response, the emergency fund is a strong start, but questions surrounding the management of these funds have already been raised.

The most vulnerable parts of the population have been affected by the economic crisis because of the country’s bulging informal sector – in which most people work - and a very weak private sector. In fact, two-thirds of the workforce are not covered by a pension plan, almost half of the working population does not currently benefit from medical coverage and there is no social care system for vulnerable parts of the population. As of 1 April, more than 700,000 workers have lost their jobs.

Moving forward?

Even if public perceptions of the government’s response are positive at the moment, this is most likely a short-term surge that should not be taken for granted. Despite the efforts made by the government, Morocco’s health system is not equipped to handle this crisis. Even with the new measures that have been implemented, if the spread of the virus gets out of control, more funds, more doctors, and more equipment will be needed. Given the structural weaknesses of the healthcare system, this will be an uphill battle.

Moreover, even if the government manages to mitigate the public health impact, the economic consequences will be dire—especially in the tourism industry—and will severely hurt those workers in the informal sector who are living without a safety net. In Morocco, this category represents most of the working population.

This crisis highlights that the Moroccan government must urgently tackle its large portfolio of unfinished reforms, notably in healthcare, the economy, and labour rights. So far, the government is capitalizing on the spirit of unity, social solidarity and public support. The future trajectory of the pandemic and the effectiveness of governance will determine if this spirit of solidarity will last. If the government fails to effectively mitigate the public health and economic impacts of this pandemic, this solidarity and cooperation will not last long.




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COVID 19: Assessing Vulnerabilities and Impacts on Iraq

7 April 2020

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Dr Mac Skelton

Director, Institute of Regional and International Studies (IRIS), American University of Iraq, Sulaimani; Visiting Fellow, Middle East Centre, London School of Economics

Dr Abdulameer Mohsin Hussein

President of the Iraq Medical Association
Following 17 years of conflict and fragile state-society relations, the war-torn country is particularly vulnerable to the pandemic.

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Disinfecting shops in Baghdad's Bayaa neighbourhood as a preventive measure against the spread of COVID-19. Photo by AHMAD AL-RUBAYE/AFP via Getty Images.

Iraq is a country already in turmoil, suffering fallout from the major military escalation between the US and Iran, mass protests calling for an end to the post-2003 political system, and a violent government crackdown killing more than 600 and wounding almost 30,000 - all presided over by a fragmented political elite unable to agree upon a new prime minister following Adil abd al-Mehdi’s resignation back in November.

COVID-19 introduces yet another threat to the fragile political order, as the virus exposes Iraq’s ineffective public health system dismantled through decades of conflict, corruption and poor governance.

Iraqi doctors are making every effort to prepare for the worst-case scenario, but they do so with huge structural challenges. The Ministry of Health lacks enough ICU beds, human resources, ventilators, and personal protective equipment (PPE). Bogged down in bureaucracy, the ministry is struggling to process procurements of equipment and medications, and some doctors have made purchases themselves.

But individual efforts can only go so far as many Iraqi doctors are concerned the official numbers of confirmed COVID-19 cases do not reflect the complexity of the situation on the ground.

The ministry relies predominately upon patients self-presenting at designated public hospitals and has only just begun community-based testing in areas of suspected clusters. Reliance on self-presentation requires a level of trust between citizens and state institutions, which is at a historic low. This gap in trust – 17 years in the making – puts Iraq’s COVID-19 response particularly at risk.

Iraq’s myriad vulnerabilities

Certain social and political factors leave Iraq uniquely exposed to the coronavirus. The country’s vulnerability is tied directly to its social, religious and economic interconnections with Iran, an epicenter of the pandemic.

Exchanges between Iran and Iraq are concentrated in two regions, with strong cross-border links between Iraqi and Iranian Kurds in the north-east, and Iraqi and Iranian Shia pilgrims in the south. Cross-border circulation of religious pilgrims is particularly concerning, as they can result in mass ritual gatherings.

The high number of confirmed cases in the southern and northern peripheries of the country puts a spotlight on Iraq's failure in managing healthcare. The post-2003 government has failed to either rebuild a robust centralized healthcare system, or to pave the way for a federalized model.

Caught in an ambiguous middle between a centralized and federalized model, coordination across provinces and hospitals during the coronavirus crisis has neither reflected strong management from Baghdad nor robust ownership at the governorate level.

This problem is part of a wider challenge of managing centre-periphery relations and federalism, which since 2003 has not worked effectively. Baghdad has provided all 18 provinces with instructions on testing and treatment, but only a handful have enough resources to put them into practice. Advanced testing capacity is limited to the five provinces with WHO-approved centers, with the remaining 13 sending swabs to Baghdad.

But the greatest challenge to Iraq’s COVID-19 response is the dramatic deterioration of state-society relations. Studies reveal a profound societal distrust of Iraq’s public healthcare institutions, due to corruption and militarization of medical institutions. Numerous videos have recently circulated of families refusing to turn over sick members - particularly women - to medical teams visiting households with confirmed or suspected cases.

As medical anthropologist Omar Dewachi notes, the ‘moral economy of quarantine’ in Iraq is heavily shaped by a history of war and its impact on the relationship between people and the state. Although local and international media often interpret this reluctance to undergo quarantine as a matter of social or tribal norms, distrusting the state leads many families to refuse quarantine because they believe it resembles a form of arrest.

The management of coronavirus relies upon an overt convergence between medical institutions and security forces as the federal police collaborate with the Ministry of Health to impose curfews and enforce quarantine. This means that, troublingly, the same security establishment which violently cracked down on protesters and civil society activists is now the teeth behind Iraq’s COVID-19 response.

Without trust between society and the political class, civil society organizations and protest movements have directed their organizational structure towards awareness-raising across Iraq. Key religious authorities such as Grand Ayatollah Sistani have called for compliance to the curfew and mobilized charitable institutions.

However, such efforts will not be enough to make up for the lack of governance at the level of the state. In the short-term, Iraq’s medical professionals and institutions are in dire need of technical and financial support. In the long-term, COVID-19 is a lesson that Iraq’s once robust public healthcare system needs serious investment and reform.

COVID-19 may prove to be another catalyst challenging the ‘muddle through’ logic of the Iraqi political elite. International actors have largely been complicit in this logic, directing aid and technical support towards security forces and political allies in the interest of short-term stability, and neglecting institutions which Iraqis rely on for health, education, and well-being.

The response to the crisis requires cooperation and buy-in of a population neglected by 17 years of failed governance. This is a seminal event that may push the country to the brink, exposing and stirring underlying tensions in state-society relations.

This analysis was produced as part of the Iraq Initiative.




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COVID-19 and the Iranian Shadows of War

8 April 2020

Dr Sanam Vakil

Deputy Director and Senior Research Fellow, Middle East and North Africa Programme
Coronavirus has plunged Iran into the country’s biggest crisis since its war with Iraq. More than 30 years later, the lingering effects of the war are shaping Iran’s reaction to the pandemic.

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Spraying disinfectant at Tajrish bazaar in Tehran, Iran, during the coronavirus pandemic in March 2020. Photo by Majid Saeedi/Getty Images.

In the face of the COVID-19 pandemic, many global leaders have invoked war analogies – from the Pearl Harbor attack to the collective spirit on display during the Second World War – to highlight past lessons learned or rally their populations.

For Iran’s leadership, more recent war analogies hold resonance and help explain the ideological and political conundrum limiting an effective COVID-19 response. While the Islamic Republic has weathered a multitude of challenges, COVID-19 is putting unprecedented strain on Iran’s already fragile, heavily-sanctioned economy and further exposing domestic political fissures amid ongoing international tensions.

Iran has been identified as the regional epicentre of the pandemic with a steadily rising number of deaths, including several of the country’s political and military elite. Yet the Iranian government has not evoked the collective memory of the war as an opportunity for national resistance and mobilization.

Sluggish and poorly managed

This is unsurprising, because thus far the Iranian government’s response to COVID-19 has been sluggish and poorly managed. After an initial slow response, Iran then attempted to downplay the impact of the virus, covering up the number of cases and deaths and blaming the United States, before implementing a poorly coordinated action plan marred by government infighting.

For the Iranian leadership, the Iran-Iraq war has been the single most influential and defining period – it has impacted its political ideology, domestic and security policies and international relations. More than half a million Iranians died, and a paranoid worldview and sense of isolation was cemented among many elite leaders such as Supreme Leader Ali Khamenei.

The war created a valiant culture of leadership from Qassem Soleimani to presidents Mahmoud Ahmadinejad and Hashemi Rafsanjani and, over time, has resulted in the development of Iran’s asymmetrical defense capabilities.

The war enabled a dark purge of political opponents and the gradual birth of Iran’s reformist faction, all while the ethos of sacrifice and martyrdom was linked to the collective notions of resistance.

These would be carried forward in other resistance campaigns both regional and economic. Most defining was Ayatollah Khomeini’s infamous 1988 decision to ‘drink the poisoned chalice’ and end the long war. Three decades later, Iran continues to contend with those outcomes.

To acknowledge that the COVID-19 crisis could have equally profound consequences would add further pressure to the Islamic Republic at a time of incomparable vulnerability. Even before this crisis, the Iranian government linked sanctions to economic warfare, making future negotiations conditional on sanctions relief.

Iranian hardliners used the opportunity to promote Iran’s subsistence-based resistance economy designed to insulate Iran’s economy from external shocks such as sanctions. While both groups recognize the economic urgency, their contending strategies help explain the muddled government response and the ongoing ideological competition between the political elites.

Rouhani has argued that a full lockdown of the Iranian economy is impossible because it is already under significant strain from sanctions - the Iranian economy experienced a 9.5% contraction in 2019 and is expected to worsen in the coming year.

That said, through Iran’s New Year holidays the government did take action to slow the spread of the virus, discouraging travel and shutting schools, pilgrimage sites and cancelling Friday prayers. Finally, on 4 April, after receiving permission from Khamenei to do so, Rouhani withdrew $1 billion from Iran’s National Development Fund and is distributing the money through loans and credits to 23 million households.

Aid from a number of Iran’s parastatal agencies was also announced. Conversely, in his annual New Year’s speech the supreme leader securitized the crisis by laying blame on the United States for spreading the virus as a form of biological terrorism. Iran’s army chief of staff Major General Bagheri was tasked with building hospitals and the Islamic Revolution Guard Corps given authority to clear the streets.

The recent expulsion of Médecins Sans Frontières from Iran highlights the mix of paranoia and resistance culture still on display. US sanctions on Iran have significantly weakened Iran’s economy and limited Tehran’s ability to purchase much needed medical supplies and equipment. Unable to access its foreign reserves due to sanctions, the Rouhani government has applied for a $5 billion loan from the IMF.

European countries alongside a number of US members of congress have appealed to the Trump administration to ease sanctions on humanitarian grounds. While Washington continues to pursue its steadfast approach, referring to Iran’s campaign as a ‘sanctions relief scam’, Germany, France, and the UK have offered $5 million in aid and launched INSTEX – a trading mechanism designed to circumvent sanctions to allow non-sanctioned humanitarian trade.

The impact of coronavirus on Iranian society remains to be seen. But the impact of sanctions has placed heavy economic and psychological burden on the people. Feeling abandoned by the Iranian state and the United States could produce a mix of contradictory nationalistic and independent impulses.

The social contract – already fragile amid protests and government repression – reveals declining trust. Without national mobilization and calls for unity reminiscent of the war period, Iranians have stepped in, highlighting the continued resilience of civil society. Support for the medical establishment has been celebrated throughout the country and on social media. Charities, the private sector - through one initiative known as Campaign Nafas (Breathe) - and diaspora groups have initiated fundraising drives and assistance measures.

Iran’s relations with the international community, and specifically the United States, remain an unresolved consequence of the war. The 2015 Iranian nuclear agreement was the closest Tehran and Washington came to resolving decades of tensions, containment and sanctions.

COVID-19 has further heightened the trajectory of tensions between Tehran and Washington suggesting that any new deal, while necessary, is not on the cards. Tit-for-tat military exchanges have been on the rise in Iraq and Yemen while American and Iranian leaders issue threats and warnings of potential escalation.

Abdullah Nasseri, an advisor to Iran’s reformists, recently stated that in order to manage the coronavirus crisis, the Iranian government needed to make a decision akin to the 1988 United Nations resolution 598 that ended war hostilities. Ayatollah Khomeini famously commented on that ceasefire, stating: ‘Happy are those who have departed through martyrdom. Unhappy am I that I still survive.… Taking this decision is more deadly than drinking from a poisoned chalice. I submitted myself to Allah's will and took this drink for His satisfaction’. 

While a similar compromise today might appear deadly to the political establishment, it is clear that a paradigm shift away from the shadows of Iran’s last war is urgently needed to manage the challenges stemming from COVID-19.




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Webinar: Will COVID-19 Mark the Endgame for Iraq's Muhasasa Ta'ifia?

Research Event

30 April 2020 - 2:00pm to 3:00pm

Event participants

Ahmed Tabaqchali, Chief Investment Officer, Asia Frontier Capital Iraq Fund; Adjunct Assistant Professor, American University of Iraq Sulaimani
Moderator: Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Control of oil rents underpins Iraq’s post-2003 political order. This political order, known as Muhasasa Ta’ifia (ethno-sectarian apportionment), features an elite bargain inclusive of all major ethnic and sect-based political groups. It has enabled the state's continuity and apparent stability through multiple crises, including the 2008 financial crisis, the 2014 oil crisis, and the war with ISIS.

In a recent article, Ahmed Tabaqchali examines how the crash in oil rents, brought about by COVID-19’s disruption of the world economy, exposes the structural inconsistencies and inherent contradictions of the Muhasasa Tai’fia system. The article argues that the current Iraqi political elite is ill-equipped to resolve the multi-faceted challenge facing the country because of its increasing fragmentation and the erosion of its legitimacy, advanced institutional decay and fundamentally different oil dynamics.

In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, the article’s author will discuss the deficiencies of the Muhasasa Ta’ifia system and will offer his insight into the future of this governance model in the context of a worsening economic crisis resulting from the COVID-19 pandemic and existing demographic pressures.
 
You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.
 

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change?

29 April 2020

Dr Georges Fahmi

Associate Fellow, Middle East and North Africa Programme
The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do.

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An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images.

COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.

Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.

However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has  created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.

In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.

Exposes economic vulnerability

Economic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.

Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.

The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.

Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.

On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.

Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.

This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. 

But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.

The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism.




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Nuclear Tensions Must Not Be Sidelined During Coronavirus

1 May 2020

Ana Alecsandru

Research Assistant, International Security Programme
Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime.

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Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images.

Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.

With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.

It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.

Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.

Continuing distrust

But with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.

Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.

While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.

If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.

Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.

For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.

This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.

However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.

Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.

France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.

COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.

As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.

While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.

But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic.




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COVID-19 Crisis – Business as Usual for Gaza?

6 May 2020

Mohammed Abdalfatah

Asfari Foundation Academy Fellow
The COVID-19 pandemic has brought unprecedented challenges, economic collapse and strict lockdowns in many parts of the world. For the people of Gaza, this reality is nothing new.

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Palestinians light fireworks above the rubble during the Muslim holy month of Ramadan amid concerns about the spread of the coronavirus disease (COVID-19), in Gaza City , 30 April 2020. Photo by Majdi Fathi/NurPhoto via Getty Images.

In August 2012, when the UN released its report Gaza in 2020: A liveable place?, they could not have imagined what the world would look like in 2020: cities under lockdown, restrictions on movement, border closures, widespread unemployment, economic collapse, fear and anxiety and, above all, uncertainty about what the future holds.

For Gaza’s population of 2 million people this reality is nothing new. The conditions that the rest of the world are currently experiencing as a result of the COVID-19 pandemic is similar to the tight blockade Gaza has been living under ever since Hamas took over in 2007. Israel has imposed severe restrictions on the movement of people and goods, youth unemployment has reached 60 per cent, and over 80 per cent of Gaza’s population are now dependent on international aid.

The people of Gaza are having to face the COVID-19 crisis already at a disadvantage, with poor infrastructure, limited resources and a shortage of the most basic services, such as water and power supply. It also has a fragile health system, with hospitals lacking essential medical supplies and equipment, as well as the capacity to deal with the outbreak as there are only 84 ICU beds and ventilators available.

 

Meanwhile, intra-Palestinian divisions have persisted and were evident in the initial reaction to the pandemic. When President Mahmoud Abbas announced a state of emergency, it took two days for the Hamas-led government in Gaza to follow suit and shut down schools and universities. They later made a separate emergency appeal to address the crisis and prepare for a COVID-19 response in Gaza. This lack of coordination is typical of the way the Palestinian Authority and Hamas approach crisis situations.

After the initial uncoordinated response, Hamas, as the de-facto ruler of Gaza, has asserted its ability to control Gaza’s borders by putting in place quarantine measures for everyone who enters the strip, whether through the Erez checkpoint with Israel or the Rafah border with Egypt. They have also assigned 21 hospitals, hotels, and schools as compulsory quarantine centres for all arrivals from abroad, who have to stay in quarantine for 21 days. In comparison, there are 20 quarantine centres in the West Bank.  These strict measures have prevented the spread of the virus in the community and confined it to the quarantine centres, with only 20 confirmed cases of COVID-19 as of 6 May. Gaza’s de-facto authorities have also been able to monitor markets and prices to ensure the availability of essential goods.

Faced with a major crisis, Al-Qassam Brigades – the armed wing of Hamas – have tried to play the role of a national army by participating in efforts to fight the pandemic. They have relatively good logistical capacity and have contributed to the construction of two quarantine facilities with a total capacity of 1,000 units to prepare for more arrivals into Gaza. At the local level, municipalities have been disinfecting public spaces and facilities in addition to disseminating information about the virus and related preventative and protective measures. Other precautionary measures put in place include closing the weekly open markets, and restricting social gatherings like weddings and funerals.

Despite COVID-19, it’s business as usual when it comes to international dealings with Gaza. The key parties in the conflict – Israel, Hamas and the Palestinian Authority – along with the main external actors – Egypt, the United Nations and Qatar – have continued to stick to their policies aimed at keeping the security situation under control and preventing further escalation. Although Israel has allowed entry of pharmaceutical supplies and medical equipment into Gaza during the pandemic, it has kept its restrictions on the movement of goods and people in place, while keeping a close eye on the development of the COVID-19 outbreak in Gaza – a major outbreak here would be a nightmare scenario for Israel.

Meanwhile, Qatar has continued to address the humanitarian and economic needs of Gaza in an attempt to ease the pressure and prevent further escalation. It has pledged $150 million over the next six months to help families in Gaza from poorer backgrounds. Gaza has also been discussed by the Middle East Quartet, as Nickolay Mladenov, the UN special coordinator for the Middle East Peace Process, expressed his concern about the risk of a disease outbreak in Gaza during a call with the members of the Quartet.

Amid the pandemic, threats are still being exchanged between Israel and Hamas. The Israeli defence minister, Naftali Bennett, requested that in return for providing humanitarian aid to Gaza, Hamas agrees to return the remains of two Israeli soldiers killed in the 2014 war. While openly rejecting Bennett's statement, the leader of Hamas in Gaza, Yahya Sinwar, has offered to move forward with a prisoner swap deal if Israel agrees to release elderly prisoners and detainees in addition to detained women and children. Though dealing with its own COVID-19 outbreak, Egypt has started to mediate between the two parties in an attempt to stabilize the situation and reach a prisoner swap deal.

In the wake of this pandemic, lessons should be learned and policies should be examined, by all parties. Firstly, Israel should re-evaluate its security measures towards Gaza by easing restrictions on movement and trade which would have a positive impact on living conditions for Gaza’s population. The current measures have proven to be unsustainable and have contributed to the endless cycle of violence. Secondly, the intra-Palestinian division should end, to save Palestinians from contradictory policies and insufficient capacity on both sides. In fact, all previous attempts have failed to end this self-destructive division and this is due to the absence of political will on both sides. Elections seem to be the only viable path towards unity. Finally, efforts by the international community should go beyond stabilizing the security situation and ongoing crisis inside Gaza, where disruption of normal life is the norm.

While the world has reacted to this pandemic with a whole host of new policies and emergency measures, it has remained business as usual when dealing with Gaza. Should COVID-19 spread in Gaza, its people – who have already paid the price of a continuous blockade and intra-Palestinian division for 13 years – will pay a heavy price yet again. However, this time it is not a crisis that they alone will have to face.




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Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors

Sodium–glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-3H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations.




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The National Oncology PET Registry (NOPR): A monumental effort by a few leaders




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Rapid Brain Nicotine Uptake from Electronic Cigarettes

This study sought to determine brain nicotine kinetics from the use of increasingly popular electronic cigarettes (E-cigs). Methods: Brain uptake of nicotine following inhalation from E-cigs was directly assessed in 17 E-cig users (8 females), using 11C-nicotine and positron emission tomography. The brain nicotine kinetics parameters from E-cigs were compared with those from smoking combustible cigarettes (C-cigs). Results: After inhalation of a single puff of E-cig vapor, brain nicotine concentration rose quickly (mean T1/2 27 sec) with a peak amplitude 25% higher in females than males, resembling previous observations with C-cigs. Nonetheless, brain nicotine accumulation from E-cigs was smaller than that from C-cigs in both males and females (24% and 32%, respectively). Conclusion: E-cigs can deliver nicotine rapidly to the brain. Therefore, to the extent that rapid brain uptake promotes smoking reward, e-cigarettes might maintain a degree of nicotine dependence and also serve as non-combustible substitutes for cigarettes.




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Head-to-head comparison of 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors: a prospective study

Purpose: 68Ga-DOTA-JR11 is an antagonist for somatostatin receptor used in neuroendocrine imaging. The purpose of this study is to compare 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: Patients with histologically-proven, metastatic and/or unresectable, well-differentiated neuroendocrine tumors were prospectively recruited in this study. They received an intravenous injection of 68Ga-DOTATATE (4.0 ± 1.3 mCi) on the first day and 68Ga-DOTA-JR11 (4.0 ± 1.4 mCi) on the second day. Whole-body PET/CT scans were performed at 40 to 60 minutes after injection on the same scanner. Physiologic uptake of normal organs, lesion numbers, and lesion uptake were compared. Results: Twenty-nine patients were prospectively enrolled in the study. The SUVmax of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow were significantly lower on 68Ga-DOTA-JR11 than on 68Ga-DOTATATE PET/CT (P<0.001). 68Ga-DOTA-JR11 detected significantly more liver lesions (539 vs. 356, P = 0.002), but fewer bone lesions (156 vs. 374, P = 0.031, Figure 3) than 68Ga-DOTATATE. The tumor-to-background ratio of liver lesions was significantly higher on 68Ga-DOTA-JR11 (7.6 ± 5.1 vs. 3.4 ± 2.0, P<0.001). 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT showed comparable results for primary tumors and lymph node metastases based on either patient-based or lesion-based comparison. Conclusion: 68Ga-DOTA-JR11 performs better in the detection ability and TBR of liver metastases. However, 68Ga-DOTATATE outperforms 68Ga-DOTA-JR11 in the detection of bone metastases. The differential affinity of different metastatic sites provides key information for patient selection in imaging and peptide receptor radionuclide therapy.




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Tau PET imaging with 18F-PI-2620 in patients with Alzheimer's disease and healthy controls: a first-in-human study

18F-PI-2620 is a positron emission tomography (PET) tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer’s disease (AD) and other neurodegenerative disorders. Preclinically, 18F-PI-2620 binds to both, 3R and 4R tau isoforms. The purpose of this first-in-human study was to evaluate the ability of 18F-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess its safety and tolerability of this new tau PET tracer. Methods: Participants with clinical diagnosis of probable AD and healthy controls (HC) underwent dynamic 18F-PI-2620 PET imaging for 180 min. 18F-PI-2620 binding was assessed visually and quantitatively using Distribution Volume Ratios (DVR) estimated from non-invasive tracer kinetics and standardized uptake value ratios (SUVR) measured at different time points post-injection (p.i.) with the cerebellar cortex as the reference region. Time-activity curves and SUVR were assessed in AD and HC, as well as DVR and SUVR correlations and effect size (Cohen’s d) over time. Results: 18F-PI-2620 showed peak brain uptake around 5 min p.i. and fast wash-out in non-target regions. In AD subjects, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and posterior cingulate cortex. DVR and SUVR in these regions were significantly higher in AD compared to HC. Very low background signal was observed in HC. 18F-PI-2620 administration was safe and well tolerated. SUVR time activity curves in most regions and subjects achieved a secular equilibrium after 40 min p.i.. A strong correlation (R2 > 0.93) was found between non-invasive DVR and SUVR for all imaging windows starting >30 min p.i.. Similar effect sizes between AD and HC groups were obtained across the different imaging windows. 18F-PI-2620 uptake in neocortical regions was significantly correlated with the degree of cognitive impairment. Conclusion: Initial clinical data obtained in AD and HC demonstrate the high image quality with excellent signal-to-noise of 18F-PI-2620 PET for imaging tau deposition in AD subjects. Non-invasive quantification using DVR and SUVR for 30 min imaging windows between 30-90 min p.i., e.g. 45-75 min, provides robust and significant discrimination between AD and HC subjects. 18F-PI-2620 uptake in expected regions is highly correlated to neurocognitive performance.




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Combined Visual and Semi-quantitative Evaluation Improves Outcome Prediction by Early Mid-treatment 18F-fluoro-deoxi-glucose Positron Emission Tomography in Diffuse Large B-cell Lymphoma.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immuno-chemotherapy after two cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying two different methods of interpretation: the Deauville visual five-point scale (5-PS) and a change in standardised uptake value by semi-quantitative evaluation. Methods: 145 patients with newly diagnosed DLBCL underwent pre-treatment PET (PET-0) and PET-2 assessment. PET-2 was classified according to both the visual 5-PS and percentage SUV changes (SUV). Receiver operating characteristic (ROC) analysis was performed to compare the accuracy of the two methods for predicting progression-free survival (PFS). Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET–) groups and compared. Results: Both with visual and SUV-based evaluations significant differences were found between the PFS of iPET– and iPET+ patient groups (p<0.001). Visually the best negative (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if Deauville score 4-5 (89% and 59%, respectively). Using the 66% SUV cut-off value, reported previously, NPV and PPV were 80 and 76%, respectively. SUV at 48.9% cut-off point, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). Visual and semi-quantitative SUV<48.9% assessment of each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100% respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL, iPET had good prognostic value interpreted either visually or semi-quantitatively. We determined that the most effective SUV cut-off was at 48.9%, and that when combined with visual 5-PS assessment, a positive PET-2 was highly predictive of treatment failure.




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SUV25 and {micro}PERCIST: Precision Imaging of Response to Therapy in Co-Clinical FDG-PET Imaging of Triple Negative Breast Cancer (TNBC) Patient-Derived Tumor Xenografts (PDX)

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived tumor xenografts (PDX). Inter- and intra-tumor heterogeneity of PDX, however, present several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics of FDG-PET to assess response to combination docetaxel/carboplatin therapy in a co-clinical trial involving triple negative breast cancer (TNBC) PDX. We characterize the reproducibility of SUV metrics to assess response to therapy and optimize a preclinical PERCIST (µPERCIST) paradigm to complement clinical standards. Considerations in this effort included variability in tumor growth rate and tumor size; solid tumor vs. tumor heterogeneity and necrotic phenotype; and optimal selection of tumor slice versus whole tumor. A test-retest protocol was implemented to optimize the reproducibility of FDG-PET SUV thresholds, SUVpeak metrics, and µPERCIST parameters. In assessing response to therapy, FDG-PET imaging was performed at baseline and +4 days following therapy. The reproducibility, accuracy, variability, and performance of imaging metrics to assess response to therapy were determined. We defined an index—"Quantitative Response Assessment Score (QRAS)"—to integrate parameters of prediction and precision, and thus aid in selecting optimal image metrics of response to therapy. Our data suggests that a threshold value of 25% (SUV25) of SUVmax was highly reproducible (<9% variability). Concordance and reproducibility of µPERCIST were maximized at α=0.7 and β=2.8 and exhibited high correlation to SUV25 measures of tumor uptake. QRAS scores favor SUV25 followed by SUVP14 as optimal metrics of response to therapy. Additional studies are warranted to fully characterize the utility of SUV25 and µPERCIST SUVP14 as image metrics of response to therapy across a wide range of therapeutic regiments and PDX models.




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Long term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 (177Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer

Objectives: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies.




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Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors

Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.




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Comparison between 18F-FDG-PET- and CT-based criteria in non-small cell lung cancer (NSCLC) patients treated with Nivolumab

Due to their peculiar mechanism of action, the evaluation of radiological response to immune checkpoint inhibitors (ICI) presents many challenges in solid tumors. We aimed to compare the evaluation of first response to Nivolumab by means of CT-based criteria with respect to fluorodeoxyglucose positron emission tomography (FDG-PET) response criteria in non-small-cell lung cancer (NSCLC) patients. Methods: 72 patients with advanced NSCLC were recruited in a mono-institutional ancillary trial within the expanded access program (EAP; NCT02475382) for Nivolumab. Patients underwent CT scan and FDG-PET at baseline and after 4 cycles (first evaluation). In case of progressive disease (PD), an additional evaluation was performed after two further cycles in order to confirm progression. We evaluated the response to treatment with CT scan by means of response evaluation criteria in solid tumors (RECIST) 1.1 and Immuno-related Response Criteria (IrRC) and with FDG-PET by means of PERCIST and immunotherapy-modified-PERCIST (imPERCIST) criteria. The concordance between CT- and PET-based criteria and the capability of each method to predict overall survival (OS) were evaluated. Results: 48/72 patients were evaluable for first response assessment with both PET- and CT-based criteria. We observed low concordance between CT- and PET-based criteria (Kappa value of 0.346 and 0.355 and Kappa value of 0.128 and 0.198 between PERCIST and imPERCIST versus RECIST and irRC respectively). Looking at OS, IrRC were more reliable to distinguish responders from non-responders. However thanks to the prognostic value of partial metabolic response assessed by both PERCIST and Immuno-PERCIST, PET-based response maintained prognostic significant in patients classified as progressive disease on the basis of irRC. Conclusion: Even though the present study did not support the routine use of FDG-PET in the general population of NSCLC patients treated with ICI, it suggests the added prognostic value of the metabolic response assessment, potentially improving the therapeutic decision-making.




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Label-free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-guided Surgery by Photoacoustic Imaging

Objectives: The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of study is to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma in a very early stage and perform tumor resection by intraoperative photoacoustic image-guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a B16 melanoma hepatic metastasis mouse model (n = 10) was established to study the development of micrometastases in vivo. Next, the hepatic metastasis mice models were imaged by scalable PAI instrument, ultrasound, 9.4 T high-resolution magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), and bioluminescence imaging. Photoacoustic images acquired with optical wavelengths spanning from 680 to 850 nm were spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in the signal-to-background ratios among different modalities were determined with the two-tailed paired t test. The diagnosis results were assessed with histologic examinations. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify tumor boundary. In vivo metastatic melanoma removal in surgery was precisely guided by the portable PAI system. Results: PAI achieved as small as ~400 µm hepatic melanoma detection at a depth up to 7 mm in vivo, which could early detect small melanoma compared with ultrasound and MRI in mouse models. The signal ratio of tumor-to-liver acquired with PAI in micrometastases at 8 days (4.2 ± 0.2, n = 6) and 14 days (9.2 ± 0.4, n = 5) were significantly higher than those obtained with PET/CT (1.8 ± 0.1, n = 5 and 4.5 ± 0.2, n = 5, P <0.001 for both). Functional PAI provided dynamic oxygen saturation changes during tumor growth. The limit of detection was measured to be approximately 219 cells per microliter in vitro. We successfully performed intraoperative photoacoustic image-guided surgery in vivo using the rapid portable PAI system. Conclusion: Our findings offer a rapid and effective tool to noninvasively detect micrometastases and guide intraoperative resection as a complementary clinical imaging application.




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Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC

We performed post-hoc analyses on the utility of pre-therapeutic and early interim 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to four cycles of 1.85 GBq/m²/cycle 90Y-DOTATOC with a maximal kidney biologic effective dose of 37 Gy. All patients underwent a 68Ga-DOTATOC PET/computed tomography (CT) at baseline and seven weeks after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semi-automatically delineated using a customized standardized uptake value (SUV) threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival (PFS) and overall survival (OS) were 13.9 and 22.3 months, respectively. An SUVmean higher than 13.7 (75th percentile (P75)) was associated with better survival (hazard ratio (HR) 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 ml (P75) was associated with worse OS (HR 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with PFS were found. A composite score based on SUVmean and IBI allowed to further stratify patients in three categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (P75) was associated with worse survival (HR 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization.




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Imaging P-glycoprotein Induction at the Blood-Brain Barrier of a Beta-Amyloidosis Mouse Model with 11C-Metoclopramide PET

P-glycoprotein (ABCB1) plays an important role at the blood-brain barrier (BBB) in promoting the clearance of neurotoxic beta-amyloid (Aß) peptides from the brain into the blood. ABCB1 expression and activity were found to be decreased in the brains of Alzheimer disease (AD) patients. Treatment with drugs which induce cerebral ABCB1 activity may be a promising approach to delay the build-up of Aß deposits in the brain by enhancing the clearance of Aß peptides from the brain. The aim of this study was to investigate whether PET with the weak ABCB1 substrate radiotracer 11C-metoclopramide can measure ABCB1 induction at the BBB in a beta-amyloidosis mouse model (APP/PS1-21 mice) and in wild-type mice. Methods: Groups of wild-type and APP/PS1-21 mice aged 50 or 170 days underwent 11C-metoclopramide baseline PET scans or scans after intraperitoneal treatment with the rodent pregnane X receptor (PXR) activator 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN, 25 mg/kg) or its vehicle over 7 days. At the end of the PET scans, brains were harvested for immunohistochemical analysis of ABCB1 and Aß levels. In separate groups of mice, radiolabeled metabolites of 11C-metoclopramide were determined in plasma and brain at 15 min after radiotracer injection. As an outcome parameter of cerebral ABCB1 activity, the elimination slope of radioactivity washout from the brain (kE,brain) was calculated. Results: PCN treatment resulted in an increased clearance of radioactivity from the brain as reflected by significant increases in kE,brain (from +26% to +54% relative to baseline). Immunohistochemical analysis confirmed ABCB1 induction in the brains of PCN-treated APP/PS1-21 mice with a concomitant decrease in Aß levels. There was a significant positive correlation between kE,brain values and ABCB1 levels in the brain. In wild-type mice, a significant age-related decrease in kE,brain values was found. Metabolite analysis showed that the majority of radioactivity in the brain was composed of unmetabolized 11C-metoclopramide in all animal groups. Conclusion: 11C-metoclopramide can measure ABCB1 induction in the mouse brain without the need to consider an arterial input function and may find potential application in AD patients to non-invasively evaluate strategies to enhance the clearance properties of the BBB.




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18F-Fluorodeoxyglucose Positron Emission Tomography / Computed Tomography in Left-Ventricular Assist Device Infection: Initial Results Supporting the Usefulness of Image-Guided Therapy

Background: Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body 18F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained over a period of up to two years. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of cases), subcutaneous driveline path (87%), pump pocket (49%) and outflow tract (58%). Driveline smears revealed staphylococcus or pseudomonas strains as the underlying pathogen in a majority of cases (48 and 34%, respectively). At receiver-operating characteristics analysis, an 18F-FDG standardized uptake value (SUV) >2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend towards lower survival vs infection of 2 or less components (P = 0.089), while involvement of thoracic lymph nodes was significantly associated with adverse outcome (P = 0.001 for nodal SUV above vs below median). Finally, patients that underwent early surgical revision within 3 months after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up when compared to those receiving delayed surgical revision (n = 11; p<0.05). Conclusion: Whole-body 18F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course.




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18F-fluorodexyglucose Position Emission Tomography identifies altered brain metabolism in patients with Cri du Chat syndrome

Cri-Du-Chat Syndrome (CdCs) is a rare genetic disease caused by a deletion in the short arm of chromosome 5 (5p) with a variable clinical spectrum. To date no study in literature has ever investigated the alterations of brain glucose metabolism in these subjects by means of [18F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). The aims of this study were to detect difference in brain FDG metabolism in patients affected by CdCs with different clinical presentations and identify possible "brain metabolic phenotypes" of this syndrome. Methods: 6 patients (age: 5 M and 1 F, age range: 10-27) with CdCs were assessed for presence of cognitive and behavioral symptoms with a battery of neuropsychological tests and then classified as patient with a severe or mild phenotype. Then, patients underwent a brain 18F-FDG PET/CT scan. PET/CT findings were compared to a control group, matched for age and sex, by using statistical parametric mapping (SPM). Association of different clinical phenotypes and 18F-FDG PET/CT findings was investigated. Results: Four patients presented a severe phenotype, whereas 2 patients demonstrated mild phenotype. SPM single subject and group analysis compared to the control cohort revealed a significant hypometabolism in the left temporal lobe (BAs 20, 36 and 38), in the right frontal subcallosal gyrus (BA 34) and caudate body, and in the cerebellar tonsils (p<0.001). Hypermetabolism (P = 0.001) was revealed in the right superior and precentral frontal gyrus (BA 6) in patient group compared to the control cohort. In SPM single subject analysis the hypermetabolic areas were detected only in patients with a severe phenotype. Conclusion: This study revealed different patterns of brain glucose metabolism in patients with severe and mild phenotype compared to control subjects. In particular, the hypermetabolic abnormalities in the brain, evaluated by18F-FDG PET/CT, seem to correlate with the severe phenotype in patients with CdCs.




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Does 2-FDG-PET Accurately Reflect Quantitative In vivo Glucose Utilization?

2-Deoxy-2-[18F]fluoro-D-glucose (2-FDG) with positron emission tomography (2-FDG-PET) is undeniably useful in the clinic, among other uses, to monitor change over time using the 2-FDG standardized uptake values (SUV) metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumption that there is an exact proportionality between glucose metabolism and 2-FDG metabolism, called the lumped constant, LC. This report describes that LC is not constant for a specific tissue and may be variable before and after disease treatment. The purpose of this work is not to deny the clinical value of 2-FDG PET; it is a reminder that when one extends the use of an appropriately qualified imaging method, new observations may arise and further validation would be necessary. Current understanding of glucose-based energetics in vivo is based on the quantification of glucose metabolic rates with 2-FDG PET, a method that permits the non-invasive assessment in various human disorders. However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs) but not for sodium-dependent glucose co-transporters (SGLTs), which have recently been shown to be distributed in multiple human tissues. Thus, the GLUT-mediated in vivo glucose utilization measured by 2-FDG PET would be blinded to the potentially substantial role of functional SGLTs in glucose transport and utilization. Therefore, in these circumstances the 2-FDG LC used to quantify in vivo glucose utilization should not be expected to remain constant. 2-FDG LC variations have been especially significant in tumors, particularly at different stages of cancer development, affecting the accuracy of quantitative glucose measures and potentially limiting the prognostic value of 2-FDG, as well as its accuracy in monitoring treatments. SGLT-mediated glucose transport can be estimated using α-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside (Me-4FDG). Utilizing both 2-FDG and Me-4FDG should provide a more complete picture of glucose utilization via both GLUT and SGLT transporters in health and disease stages. Given the widespread use of 2-FDG PET to infer glucose metabolism, appreciating the potential limitations of 2-FDG as a surrogate for glucose metabolic rate and the potential reasons for variability in LC is relevant. Even when the readout for the 2-FDG PET study is only an SUV parameter, variability in LC is important, particularly if it changes over the course of disease progression (e.g., an evolving tumor).




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Head to head prospective comparison of quantitative lung scintigraphy and segment counting in predicting pulmonary function of lung cancer patients undergoing video-assisted thoracoscopic lobectomy

Prediction of post-operative pulmonary function in lung cancer patients before tumor resection is essential for patient selection for surgery and is conventionally done with a non-imaging segment counting method (SC) or a two-dimensional planar lung perfusion scintigraphy (PS). The purpose of this study was to compare quantitative analysis of PS to single photon emission computed tomography/computed tomography (SPECT/CT) and to estimate the accuracy of SC, PS and SPECT/CT in predicting post-operative pulmonary function in patients undergoing lobectomy. Methods: Seventy-five non-small cell lung cancer (NSCLC) patients planned for lobectomy were prospectively enrolled (68% males, average age 68.1±8 years ). All patients completed pre-operative forced expiratory volume capacity (FEV1), diffusing capacity of the lung for carbon monoxide (DLCO), Tc99m-MAA lung perfusion scintigraphy with PS and SPECT/CT quantification. A subgroup of 60 patients underwent video-assisted thoracoscopic (VATS) lobectomy and measurement of post-operative FEV1 and DLCO. Relative uptake of the lung lobes estimated by PS and SPECT/CT were compared. Predicted post-operative FEV1 and DLCO were derived from SC, PS and SPECT/CT. Prediction results were compared between the different methods and the true post-operative measurements in patients who underwent lobectomy. Results: Relative uptake measurements differed significantly between PS and SPECT/CT in right lung lobes, with a mean difference of -8.2±3.8, 18.0±5.0 and -11.5±6.1 for right upper, middle and lower lobes respectively (p<0.001). The differences between the methods in the left lung lobes were minor with a mean difference of -0.4±4.4 (p>0.05) and -2.0±4.0 (p<0.001) for left upper and lower lobes respectively. No significant difference and strong correlation (R=0.6-0.76, p<0.001) were found between predicted post-operative lung function values according to SC, PS, SPECT/CT and the actual post-operative FEV1 and DLCO. Conclusion: Although lobar quantification parameters differed significantly between PS and SPECT/CT, no significant differences were found between the predicted post-operative lung function results derived from these methods and the actual post-operative results. The additional time and effort of SPECT/CT quantification may not have an added value in patient selection for surgery. SPECT/CT may be advantageous in patients planned for right lobectomies but further research is warranted.




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Evaluation of 11C-NR2B-SMe and its Enantiomers as PET Radioligands for Imaging the NR2B Subunit within the NMDA Receptor Complex in Rats

[S-Methyl-11C](±)-7-methoxy-3-(4-(4-(methylthio)phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol (11C-NR2B-SMe) and its enantiomers were synthesized as candidates for imaging the NR2B subunit within the N-methyl-D-aspartate receptor with positron emission tomography (PET). Methods: Brains were scanned with PET for 90 min after intravenous injection of one of the candidate radioligands into rats. To detect any NR2B specific binding of radioligand in brain, various pre-blocking or displacing agents were evaluated for their impact on the PET brain imaging data. Radiometabolites from brain and other tissues were measured ex vivo and in vitro. Results: Each radioligand gave high early whole brain uptake of radioactivity, followed by a brief fast decline and then a slow final decline. 11C-(S)-NR2B-SMe was studied extensively. Ex vivo measurements showed that radioactivity in rat brain at 30 min after radioligand injection was virtually unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. High-affinity NR2B ligands, Ro-25-6981, ifenprodil, and CO10124, showed increasing preblock of whole brain radioactivity retention with increasing dose (0.01 to 1.25 mg/kg, i.v.). Five 1 antagonists (FTC146, BD1407, F3, F4, and NE100) and four 1 agonists ((+)-pentazocine, (±)-PPCC, PRE-084, (+)-SKF10047) were ineffective preblocking agents, except FTC146 and F4 at high dose. Two potent 1 receptor agonists, TC1 and SA4503, showed dose-dependent preblocking effects in the presence or absence of pharmacological 1 receptor blockade with FTC146. Conclusion: 11C-(S)-NR2B-SMe has adequate NR2B-specific PET signal in rat brain to warrant further evaluation in higher species. TC1 and SA4503 likely have off-target binding to NR2B in vivo.




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Immune checkpoint imaging in oncology - a game changer towards personalized immunotherapy?

Immune checkpoint blockade represents a promising approach in oncology, showing anti-tumor activities in various cancers. However, although being generally far more well-tolerated than classical cytotoxic chemotherapy, this treatment, too, may be accompanied by considerable side effects and not all patients benefit equally. Therefore, careful patient selection and monitoring of the treatment response is mandatory. At present, checkpoint-specific molecular imaging is increasingly investigated as a tool for patient selection and response evaluation. Here, an overview of the current developments in immune checkpoint imaging is provided.




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Will SPECT/CT Cameras soon be able to display Absorbed Doses? Dosimetry from Single Activity Concentration Measurements.




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Tobacco smoking in people is not associated with altered 18 kDa-translocator protein levels: A Positron Emission Tomography study

Rationale: The effects of tobacco smoking on the brain’s immune system are not well elucidated. While nicotine is immunosuppressive, other constituents in tobacco smoke have inflammatory effects. Positron Emission Tomography (PET) imaging of the 18-kDa translocator protein (TSPO) provide a biomarker for microglia, the brain’s primary immunocompetent cells. This work compared brain TSPO levels in 20 tobacco smokers (abstinent for at least 2 hours) and 20 nonsmokers using a fully quantitative modeling approach for the first time. Methods: [11C]PBR28 PET scans were acquired with arterial blood sampling to estimate the metabolite-corrected input function. [11C]PBR28 volumes of distribution (VT) were estimated throughout the brain with multilinear analysis. Results: Statistical analyses revealed no evidence for significant differences in regional [11C]PBR28 VT between smokers and non-smokers (whole-brain Cohen’s d=0.09) despite adequate power to detect medium effect sizes. Conclusion: These findings inform previous PET studies reporting lower TSPO radiotracer concentrations in brain (measured as standardized uptake value, SUV) of tobacco smokers compared to nonsmokers by demonstrating the importance of accounting for radiotracer concentrations in plasma. These findings suggest that compared to nonsmokers, smokers have comparable TSPO levels in brain. Additional work with other biomarkers is needed to fully characterize effects of tobacco smoking on the brain’s immune system.




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Data-driven motion detection and event-by-event correction for brain PET: Comparison with Vicra

Head motion degrades image quality and causes erroneous parameter estimates in tracer kinetic modeling in brain PET studies. Existing motion correction methods include frame-based image-registration (FIR) and correction using real-time hardware-based motion tracking (HMT) information. However, FIR cannot correct for motion within one predefined scan period while HMT is not readily available in the clinic since it typically requires attaching a tracking device to the patient. In this study, we propose a motion correction framework with a data-driven algorithm, i.e., using the PET raw data itself, to address these limitations. Methods: We propose a data-driven algorithm, Centroid of Distribution (COD), to detect head motion. In COD, the central coordinates of the line of response (LOR) of all events are averaged over 1-sec intervals to generate a COD trace. A point-to-point change in the COD trace in one direction that exceeded a user-defined threshold was defined as a time point of head motion, which was followed by manually adding additional motion time points. All the frames defined by such time points were reconstructed without attenuation correction and rigidly registered to a reference frame. The resulting transformation matrices were then used to perform the final motion compensated reconstruction. We applied the new COD framework to 23 human dynamic datasets, all containing large head motions, with 18F-FDG (N = 13) and 11C-UCB-J (N = 10), and compared its performance with FIR and with HMT using the Vicra, which can be considered as the "gold standard". Results: The COD method yielded 1.0±3.2% (mean ± standard deviation across all subjects and 12 grey matter regions) SUV difference for 18F-FDG (3.7±5.4% for 11C-UCB-J) compared to HMT while no motion correction (NMC) and FIR yielded -15.7±12.2% (-20.5±15.8%) and -4.7±6.9% (-6.2±11.0%), respectively. For 18F-FDG dynamic studies, COD yielded differences of 3.6±10.9% in Ki value as compared to HMT, while NMC and FIR yielded -18.0±39.2% and -2.6±19.8%, respectively. For 11C-UCB-J, COD yielded 3.7±5.2% differences in VT compared to HMT, while NMC and FIR yielded -20.0±12.5% and -5.3±9.4%, respectively. Conclusion: The proposed COD-based data-driven motion correction method outperformed FIR and achieved comparable or even better performance as compared to the Vicra HMT method in both static and dynamic studies.




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Clinical evaluation of a data-driven respiratory gating algorithm for whole-body positron emission tomography with continuous bed motion

Respiratory gating is the standard to overcome respiration effects degrading image quality in positron emission tomography (PET). Data-driven gating (DDG) using signals derived from PET raw data are promising alternatives to gating approaches requiring additional hardware. However, continuous bed motion (CBM) scans require dedicated DDG approaches for axially-extended PET, compared to DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort, comparing it to hardware-based gating using gated and fully motion-corrected reconstructions. Methods: 56 patients with suspected malignancies in thorax or abdomen underwent whole-body 18F-FDG CBM-PET/CT imaging using DDG and hardware-based respiratory gating (pressure-sensitive belt gating, BG). Correlation analyses were performed on both gating signals. Besides static reconstructions, BG and DDG were used for optimally-gated PET (BG-OG, DDG-OG) and fully motion-corrected PET (elastic motion correction; BG-EMOCO, DDG-EMOCO). Metabolic volumes, SUVmax and SUVmean of lesions were compared amongst the reconstructions. Additionally, the quality of lesion delineation in different PET reconstructions was independently evaluated by three experts. Results: Global correlation coefficients between BG and DDG signals amounted to 0.48±0.11, peaking at 0.89±0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO and DDG-EMOCO compared to static images (P<0.001; median SUVmax: static, 14.3±13.4; BG-EMOCO, 19.8±15.7; DDG-EMOCO, 20.5±15.6; BG-OG, 19.6±17.1; DDG-OG, 18.9±16.6). No significant differences between BG-OG and DDG-OG, and BG-EMOCO and DDG-EMOCO, respectively, were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P<0.001); no significant difference was found comparing BG and DDG (EMOCO, OG, respectively). Conclusion: DDG-based motion-compensation of CBM-PET acquisitions outperforms static reconstructions, delivering qualities comparable to hardware-based approaches. The new algorithm may be a valuable alternative for CBM-PET systems.




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Performance of digital PET compared to high-resolution conventional PET in patients with cancer

Recently introduced PET systems using silicon photomultipliers with digital readout (dPET) have an improved timing and spatial resolution, aiming at a better image quality, over conventional PET (cPET) systems. We prospectively evaluated the performance of a dPET system in patients with cancer, as compared to high-resolution (HR) cPET imaging. Methods: After a single FDG-injection, 66 patients underwent dPET (Vereos, Philips Healthcare) and cPET (Ingenuity TF, Philips Healthcare) imaging in a randomized order. We used HR-reconstructions (2x2x2 mm3 voxels) for both scanners and determined SUVmax, SUVmean, lesion-to-background ratio (LBR), metabolic tumor volume (MTV) and lesion diameter in up to 5 FDG-positive lesions per patient. Furthermore, we counted the number of visible and measurable lesions on each PET scan. Two nuclear medicine specialists blindly determined the Tumor Node Metastasis (TNM) score from both image sets in 30 patients referred for initial staging. For all 66 patients, these specialists separately and blindly evaluated image quality (4-point scale) and determined the scan preference. Results: We included 238 lesions that were visible and measurable on both PET scans. We found 37 additional lesions on dPET in 27 patients (41%), which were unmeasurable (n = 14) or invisible (n = 23) on cPET. SUVmean, SUVmax, LBR and MTV on cPET were 5.2±3.9 (mean±SD), 6.9±5.6, 5.0±3.6 and 2991±13251 mm3, respectively. On dPET SUVmean, SUVmax and LBR increased 24%, 23% and 27%, respectively (p<0.001) while MTV decreased 13% (p<0.001) compared to cPET. Visual analysis showed TNM upstaging with dPET in 13% of the patients (4/30). dPET images also scored higher in image quality (P = 0.003) and were visually preferred in the majority of cases (65%). Conclusion: Digital PET improved the detection of small lesions, upstaged the disease and images were visually preferred as compared to high-resolution conventional PET. More studies are necessary to confirm the superior diagnostic performance of digital PET.




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High Resolution Depth-Encoding PET Detector Module with Prismatoid Light Guide Array

Depth-encoding detectors with single-ended readout provide a practical, cost-effective approach for constructing high resolution and high sensitivity PET scanners. However, the current iteration of such detectors utilizes a uniform glass light guide to achieve depth-encoding, resulting in non-uniform performance throughout the detector array due to suboptimal intercrystal light sharing. We introduce Prism-PET, a single-ended readout PET detector module with a segmented light guide composed of an array of prismatoids that introduces enhanced, deterministic light sharing. Methods: High resolution PET detector modules were fabricated with single-ended readout of polished multicrystal lutetium yttrium orthosilicate (LYSO) scintillator arrays directly coupled 4-to-1 and 9-to-1 to arrays of 3.2 x 3.2 mm2 silicon photomultiplier pixels. Each scintillator array was coupled at the non-readout side to a light guide (one 4-to-1 module with a uniform glass light guide, one 4-to-1 Prism-PET module and one 9-to-1 Prism-PET module) to introduce intercrystal light sharing, which closely mimics the behavior of dual-ended readout with the additional benefit of improved crystal identification. Flood histogram data was acquired using a 3 MBq Na-22 source to characterize crystal identification and energy resolution. Lead collimation was used to acquire data at specific depths to determine depth-of-interaction (DOI) resolution. Results: The flood histogram measurements showed excellent and uniform crystal separation throughout the Prism-PET modules while the uniform glass light guide module had performance degradation at the edges and corners. A DOI resolution of 5.0 mm full width at half maximum (FWHM) and energy resolution of 13% were obtained in the uniform glass light guide module. By comparison, the 4-to-1 coupled Prism-PET module achieved 2.5 mm FWHM DOI resolution and 9% energy resolution. Conclusion: PET scanners based on our Prism-PET modules with segmented prismatoid light guide arrays can achieve high and uniform spatial resolution (9-to-1 coupling with ~ 1 mm crystals), high sensitivity, good energy and timing resolutions (using polished crystals and after applying DOI-correction), and compact size (depth-encoding eliminates parallax error and permits smaller ring-diameter).




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Digital Solid-State SPECT/CT Quantitation of Absolute 177Lu-Radiotracer Concentration: In Vivo/In Vitro Validation

The accuracy of lutetium-177 (177Lu) radiotracer concentration measurements using quantitative clinical software was determined by comparing in vivo results for a digital solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography / x-ray computed tomography) system to in vitro sampling. First, image acquisition parameters were assessed for an International Electrotechnical Commission (IEC) body phantom emulating clinical count rates loaded with a "lung" insert and 6 hot spheres with a 12:1 target-to-background ratio of 177Lu solution. Then, the data of 28 whole-body SPECT/CT scans of 7 patients who underwent 177Lu prostate membrane antigen (177Lu-PSMA) radioligand therapy was retrospectively analyzed. Three users analyzed SPECT/CT images for in vivo urinary bladder radiotracer uptake using quantitative software (Q.Metrix, GE Healthcare). In vitro radiopharmaceutical concentrations were calculated using urine sampling obtained immediately after each scan, scaled to standardized uptake values (SUVs). Any in vivo/in vitro identity relations were determined by linear regression (ideally slope=1, intercept=0), within a 95 % confidence interval (CI). Phantom results demonstrated lower quantitative error for acquisitions using the 113 keV 177Lu energy peak rather than including the 208 keV peak, given that only low-energy collimation was available in this camera configuration. In the clinical study, 24 in vivo/in vitro pairs were eligible for further analysis, having rejected 4 as outliers (via Cook’s distance calculations). All linear regressions (R2 ≥ 0.92, P<0.0001) provided identity in vivo/in vitro relations (95 % CI), with SUV averages from all users giving a slope of 1.03±0.09, an intercept of –0.25±0.64 g/mL, and an average residual difference of 20.4 %. Acquiring with the lower energy 177Lu energy peak, solid-state SPECT/CT imaging provides an accuracy to within ~20 % for in vivo urinary bladder radiotracer concentrations. This non-invasive in vivo quantitation method can potentially improve diagnosis, improve patient management and treatment response assessment, and provide data essential to 177Lu dosimetry.




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Early prostate-specific antigen changes and clinical outcome following 177Lu-PSMA radionuclide treatment in patients with metastatic castration-resistant prostate cancer

Background: Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes following 177Lu-labelled prostate specific membrane antigen (LuPSMA) radionuclide treatment in mCRPC patients. Methods: Men who were treated under a compassionate access program with LuPSMA at our institution and had available PSA values at baseline, at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to three groups based on PSA changes: 1) response: ≥30% decline, 2) progression: ≥25% increase and 3) stable: <30% decline and <25% increase. The co-primary endpoints were overall survival and imaging-based progression-free survival. The secondary end points were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A ≥30% decline in PSA at 6 wk was associated with longer overall survival (median 16.7 mo; 95%CI 14.4–19.0) compared with patients with stable PSA (median: 11.8 mo; 95%CI 8.6–15.1; P = 0.007) and progression (median: 6.5 mo; 95%CI 5.2–7.8; p<0.001). Patients with ≥30% decline in PSA at 6 wk also had a reduced risk of imaging-based progression compared with patients with stable PSA (HR: 0.60; 95%CI 0.38–0.94; P = 0.02), while patients with PSA progression had a higher risk of imaging-based progression compared with those showing stable PSA (HR: 3.18; 95%CI 1.95–5.21; p<0.001). The percentage changes of PSA at 6 wk and 12 wk were highly associated (r=0.90; p<0.001). 29 of 31 (94%) patients who experienced early PSA progression at 6 wk achieved biochemical progression at 12 wk. Overall, only 1 of 36 (3%) patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). Limitations of the study included its retrospective nature and the single center experience. Conclusion: PSA changes at 6 wk after LuPSMA initiation are an early indicator of long-term clinical outcome. Patients progressing by PSA after 6 wk of treatment could benefit from a very early treatment switch decision. PSA flare-up during LuPSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of LuPSMA.




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Prognostic Value of 18F-FDG PET/CT in a Large Cohort of 495 Patients with Advanced Metastatic Neuroendocrine Neoplasms (NEN) Treated with Peptide Receptor Radionuclide Therapy (PRRT)

The objective of this retrospective study was to determine the role of 18F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with 177Lu- and/or 90Y- DOTATOC/DOTATATE PRRT between 2/2002 and 7/2018. All subjects received both 68Ga-DOTATOC/TATE/NOC and 18F-FDG PET/CT prior to treatment and were followed 3-189 months. Kaplan-Meier analysis, log-rank test (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: 199 patients (40.2%) presented with pancreatic NEN, 49 with CUP (cancer of unknown primary), 139 with midgut NEN, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8 and other locations in 42 patients. FDG-PET/CT was positive in 382 (77.2%) patients and 113 (22.8%) were FDG-negative before PRRT, while 100% were 68Ga-DOTATOC/TATE/NOC positive. For all patients, the median PFS and OS, defined from start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive FDG predicted shorter PFS (18.5 mo vs 24.1 mo; P = 0.0015) and OS (53.2 mo vs 83.1 mo; P < 0.001) than negative FDG. Amongst the pancreatic NEN, the median OS was 52.8 mo in FDG positive and 114.3 mo in FDG negative subjects (P = 0.0006). For all patients with positive 18F-FDG uptake, and a ratio of the highest SUVmax on 68Ga-SSTR PET to the most 18F-FDG-avid tumor lesions >2, the median OS was 53.0 mo, compared to 43.4 mo in those patients with a ratio <2 (P = 0.030). For patients with no 18F-FDG uptake (complete "mismatch" imaging pattern), the median OS was 108.3 mo vs 76.9 mo for SUVmax >15.0 and ≤15.0 on 68Ga-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on 18F-FDG PET is an independent prognostic factor in patients with NEN treated with PRRT. Metabolic imaging with 18F-FDG PET/CT compliments the molecular imaging aspect of 68Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative 18F-FDG PET/CT imaging is associated with the most favorable long-term prognosis.




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The optimal imaging window for dysplastic colorectal polyp detection using c-Met targeted fluorescence molecular endoscopy

Rationale: Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met targeted fluorescent peptide, in a population at high-risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multi-diameter single-fiber reflectance, single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13mg/kg) at a one-, two- or three-hour dose-to-imaging interval (N = 3 patients per cohort). Two cohorts were expanded to six patients based on target-to-background ratios (TBR). Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly increased fluorescence in the colorectal lesions compared to surrounding tissue, with a TBR of 1.53, 1.66 and 1.74 respectively (mean intrinsic fluorescence (Q·μfa,x) = 0.035 vs. 0.023mm-1, P<0.0003; 0.034 vs. 0.021mm-1, P<0.0001; 0.033 vs. 0.019mm-1, P<0.0001). Fluorescence correlated to histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a one-to-three hour dose-to-imaging interval. No clinically significant differences were observed between the cohorts, although a one-hour dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies.




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18F-DCFPyL PET/CT in Patients with Subclinical Recurrence of Prostate Cancer: Effect of Lesion Size, Smooth Filter and Partial Volume Correction on Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria

Purpose: To determine the effect of smooth filter and partial volume correction (PVC) method on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on the molecular imaging (mi) PSMA scoring. Materials & Methods: Men with biochemical recurrence of prostate cancer with negative CT and bone scintigraphy were referred for 18F-DCFPyL PET/CT. Examinations were performed on one of 2 PET/CT scanners (GE Discovery 610 or Siemens mCT40). All suspected tumor sites were manually contoured on co-registered CT and PET images, and each was assigned a miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomical CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified "rule of thumb" (RoT) correction factor (CF) was derived for lesions at various sizes (<4mm, 4-7mm, 7-9mm, 9-12mm). This was then applied to the original dataset and miPSMA scores obtained using the RoT CF were compared to those found using the actual corrections. Results: There were 75 men (median age, 69 years; median serum PSA of 3.69 ug/L) with 232 metastatic nodes < 12 mm in diameter (mean lesion volume of 313.5 ± 309.6 mm3). Mean SUVmax before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively (p<0.00001). The mean CF for lesions <4mm (n = 22), 4-7mm (n = 140), 7-9mm (n = 50), 9-12 mm (n = 20) was 4 (range: 2.5-6.4), 2.8 (range: 1.6-4.9), 2.3 (range: 1.6-3.3) and 1.8 (range 1.4-2.4), respectively. Overall miPSMA scores were concordant between the corrected dataset and RoT in 205/232 lesions (88.4%). Conclusion: There is a significant effect of smooth filter and partial volume correction on measured PSMA activity in small nodal metastases, impacting the miPSMA score.




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Benefit of improved performance with state-of-the art digital PET/CT for lesion detection in oncology

Latest digital whole-body PET scanners provide a combination of higher sensitivity and improved spatial and timing resolution. We performed a lesion detectability study on two generations of Siemens Biograph PET/CT scanners, the mCT and Vision, to study the impact of improved physical performance on clinical performance. Our hypothesis is that the improved performance of the Vision will result in improved lesion detectability, allowing shorter imaging times or equivalently, lower injected dose. Methods: Data were acquired with the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network torso phantom combined with a 20-cm diameter cylindrical phantom. Spherical lesions were emulated by acquiring spheres-in-air data, and combining it with the phantom data to generate combined datasets with embedded lesions of known contrast. Two sphere sizes and uptakes were used: 9.89 mm diameter spheres with 6:1 (lung) and 3:1 (cylinder) and 4.95 mm diameter spheres with 9.6:1 (lung) and 4.5:1 (cylinder) local activity concentration uptakes. Standard image reconstruction was performed: ordinary Poisson ordered subsets expectation maximization algorithm with point spread function and time-of-flight modeling and post-reconstruction smoothing with a 5 mm Gaussian filter. The Vision images were also generated without any post-reconstruction smoothing. Generalized scan statistics methodology was used to estimate the area under the localization receiver operating characteristic curve (ALROC). Results: Higher sensitivity and improved TOF performance of Vision leads to reduced contrast in the background noise nodule distribution. Measured lesion contrast is also higher on the Vision due to its improved spatial resolution. Hence, the ALROC values are noticeably higher for the Vision relative to the mCT. Conclusion: Improved overall performance of the Vision provides a factor of 4-6 reduction in imaging time (or injected dose) over the mCT when using the ALROC metric for lesions >9.89 mm in diameter. Smaller lesions are barely detected in the mCT, leading to even higher ALROC gains with the Vision. Improved spatial resolution of the Vision also leads to a higher measured contrast that is closer to the real uptake, implying improved quantification. Post-reconstruction smoothing, however, reduces this improvement in measured contrast, thereby reducing the ALROC values for small, high uptake lesions.




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A Prospective, Comparative Study of Planar and Single-photon Emission Computed Tomography Ventilation/Perfusion Imaging for Chronic Thromboembolic Pulmonary Hypertension

Objectives: The study compared the diagnostic performance of Planar Ventilation/perfusion (V/Q) and V/Q Single-photon computed tomography (SPECT), and determined whether combining perfusion scanning with low-dose computed tomography (Q-LDCT) may be equally effective in a prospective study of patients with chronic thromboembolic pulmonary hypertension (CTEPH) patients. Background: V/Q scanning is recommended for excluding CTEPH during the diagnosis of pulmonary hypertension (PH). However, Planar V/Q and V/Q SPECT techniques have yet to be compared in patients with CTEPH. Methods: Patients with suspected PH were eligible for the study. PH attributable to left heart disease or lung disease was excluded, and patients whose PH was confirmed by right heart catheterization and who completed Planar V/Q, V/Q-SPECT, Q-LDCT, and pulmonary angiography were included. V/Q images were interpreted and patients were diagnosed as instructed by the 2009 EANM guidelines, and pulmonary angiography analyses were used as a reference standard. Results: A total of 208 patients completed the study, including 69 with CTEPH confirmed by pulmonary angiography. Planar V/Q, V/Q-SPECT, and Q-LDCT were all highly effective for diagnosing CTEPH, with no significant differences in sensitivity or specificity observed among the three techniques (Planar V/Q [sensitivity/specificity]: 94.20%/92.81%; V/Q-SPECT: 97.10%/91.37%, Q-LCDT: 95.65%/90.65%). However, V/Q-SPECT was significantly more sensitive (V/Q-SPECT: 79.21%; Planar V/Q: 75.84%, P = 0.012; Q-LDCT: 74.91%, p<0.001), and Planar V/Q was significantly more specific (Planar V/Q: 54.14%; V/Q-SPECT 46.05%, p<0.001; Q-LDCT: 46.05%, P = 0.001) than the other two techniques for identifying perfusion defects in individual lung segments. Conclusion: Both Planar V/Q and V/Q-SPECT were highly effective for diagnosing CTEPH, and Q-LDCT may be a reliable alternative method for patients who are unsuitable for ventilation imaging.