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Translating neuroimaging findings from research into clinical practice

Periodic Report Summary 2 - PSYSCAN (Translating neuroimaging findings from research into clinical practice)

Project Context and Objectives:
The PSYSCAN project is designed to translate findings from neuroimaging research into mainstream clinical practice. The aim of PSYSCAN is to use neuroimaging to facilitate diagnosis at the (pre)symptomatic stage, more accurate patient stratification and better measurement of disease progression of psychotic disorders. This will be achieved through the development of the PSYSCAN tool. A key feature of the tool is that it is designed to stratify patients on the basis of distinctions that influence clinical care, and are thus clinically meaningful. The PSYSCAN tool will build on IXICO and Cambridge Cognition technology deployed in global clinical trials and in healthcare for dementia diagnosis, along with academic state-of-the-art to integrate neuroimaging measures with complementary clinical, cognitive and genetic data, and use novel statistical approaches to help clinicians in the assessment of patients in the early stage of psychosis.
In order to reach these goals, PSYSCAN has assembled a diverse multidisciplinary team of top researchers in psychosis and the ultra-high risk state of psychosis, who have the range of skills required to deliver a program of research that meets all the call’s requirements and have access to / will collect a number of unique samples, described below. By bringing together major clinical academic centres, Small and Medium Enterprises (SMEs) with expertise in the development of assessment tools and neuroimaging processing, an MRI manufacturer, and the pharmaceutical industry, we will ensure that the PSYSCAN tool will have a strong and sustainable impact in this field.
The partners in PSYSCAN represent the nationally funded psychosis / mental health networks in the UK, the Netherlands, Denmark, Spain, Germany, Italy, Ireland, Austria, Switzerland, Israel and Australia, as well as other partners. The original consortium has been expanded to now include, at no extra cost, a larger network of European sites key in psychosis research, as described in the summary of Work Package (WP) 5.

The PSYSCAN concept
The PSYSCAN tool will consist of three different applications:
1. PSYSCAN-Predict will be used in subjects at high risk of psychosis to facilitate prediction of the onset of psychosis and of functional outcome.
2. PSYSCAN-Stratify will be used in patients with first episode psychosis to aid early diagnosis and stratification according to subsequent clinical course and functional outcome.
3. PSYSCAN-Monitor will be used in both high risk and first episode patients to facilitate the measurement of disease progression.
The tool will be validated through large-scale naturalistic studies in these two clinical groups, capitalising on a multi-national network of centres within the consortium.
Figure 1 provides a schematic view of how the PSYSCAN tool will work. Clinical, demographic, and cognitive data from the patient are directly entered by the clinician via a bespoke interface on an iPad. Neuroimaging data acquired from the patient are processed using dedicated software installed at the scanning facility. Both sets of data are transferred to a central database for processing and analysis. A range of plug-in modules can be used, depending on the type of analysis required for each clinical application. Key features include the integration of and neuroimaging (NI) and non- neuroimaging (non-NI) measures, and the use of machine learning methods in conjunction with large reference databases to make predictions that are specific to the patient being assessed. The tool has three main clinical applications. PSYSCAN-Predict facilitates the prediction of the onset of psychosis in people at high risk. PSYSCAN-Stratify helps the clinician make an early diagnosis in patients with first episode psychosis, and stratify them according to their future course. PSYSCAN-Monitor allows the clinician to measure disease progression over time. The results of the analyses are directly fed back to the clinician's iPad in a clear report in 'traffic-light' format.

Project Results:
The PSYSCAN project has two main objectives:

Main objective 1:
To develop and validate a neuroimaging-based tool (PSYSCAN) for early diagnosis, patient stratification and measurement of disease progression in psychotic disorders.
The sub-objectives are:
1. To specify the requirements for the clinical use of NI-tools across Member States in an online survey, to optimize implementation of the tools once developed.
2. To develop three NI-based applications for the tool:
• PSYSCAN-Predict
• PSYSCAN-Stratify
• PSYSCAN-Monitor
3. To validate the PSYSCAN tool for these applications in naturalistic prospective studies of high risk and first episode populations.

Main objective 2:
To promote the translational application of neuroimaging in psychiatry.
The sub-objectives are:
1. To disseminate the results of the PSYSCAN project across European Member States.
2. To commercially exploit and implement the PSYSCAN tool across European Member States, through SME and industrial partners.
3. To provide recommendations for refinement of the PSYSCAN tool for application in other mental disorders, in line with the Europe 2020 agenda and the European Pact for Mental Health.
1.2 Work performed and results achieved so far
PSYSCAN will execute its work through 6 highly interactive and integrated work packages (WPs, see Figure 2). WP1 is dedicated to project management. WP2 will collate existing datasets of NI and non-NI measures that facilitate presymptomatic and early diagnosis, patient stratification, and the measurement of disease progression, and will be used as independent sample to validate the findings from WP5. WP3 will develop new software that can be used to stratify patients on the basis of connectivity and individual patient data, and will form a key part of the PSYSCAN tool. WP4 will produce the tool, using data and software from WP5 and WP3. The tool will be discovered and developed in two large multi-centre naturalistic studies within the consortium in WP5, and will subsequently be validated in the remaining of WP5 as well as with the legacy datasets from WP2. The validated PSYSCAN tool will then be disseminated across the EU in WP6.

Current status of PSYSCAN
Since the last EU reporting period all the systems and procedures to enable the prospective studies have been completed and neuroimaging (NI) and non- neuroimaging (non-NI) data are currently being acquired. The original consortium has been expanded to include (at no extra cost) a larger network of European sites. We are also adding four non-European subcontractor sites. The current PSYSCAN Consortium is depicted in Figure 3. In WP5 a total of 16 sites are now involved in recruitment of First Episode Psychosis patients. All of these sites have ethical committee approval and have had an Initiation Call. WP5 has already recruited a total of 55 participants with First Episode of psychosis in 7 months, which is 13% of the target total. For the recruitment of participants at Clinical High Risk of Psychosis in WP5, a total of 13 sites are involved. All of these sites also have ethical committee approval, and all but three have had an Initiation Call. They have recruited a total of 13 participants at Clinical High Risk of Psychosis, which is 4% of the target total. However, this reflects recruitment from only one site: the others have only just completed the administrative requirements, but are now ready to start. The neuroimaging acquisition sequences in these studies have been standardized in collaboration with WP4 so that data is collected in a similar manner across all sites. The MRI sequences in use include a 3D T1W, FLAIR, DTI, and a resting state fMRI protocol.
Retrospective data from a total of 2195 subjects have been collated by WP 2 from 6 partners, which is 22% of the anticipated total. These include structural MRI, DTI, and fMRI data, as well as non-neuroimaging data, including clinical and cognitive data, from patients with first episode of psychosis, ultra-high risk subjects and controls.
Both the (new) prospective data and the (legacy) retrospective data are transferred to IXICO for storage. Since the last reporting period the online database has been configured and fully developed by IXICO, lead partner for WP4. This uses their data management platform called ‘TrialTracker’, which has been extended with a bespoke Assessments module that is accessible by every site via their dedicated iPads. The interfaces of these iPad are linked to this online database and sites can see/edit data entered on the iPad and submit to the database. WP4 is closely communicating with WP5 to ensure that the user interface on the iPad is user friendly and allows for minor adaptations to be made when needed. WP4 also liaises with WP3 to develop the addition of image analysis algorithms to TrialTracker and setting up the data-analyses pipelines.
WP3 is now fully functioning, with two postdoctoral research workers in place. WP3’s focus is on designing the pre-processing pathways and investigating possible network analysis and machine learning approaches, which are intended to be components of the PSYSCAN tool. Significant progress has been made in outlining the properties of the data-analyses pipelines and volumetric pipeline for structural MRI and DTI images have established. WP3 will further this progress by implementing pipelines for the other imaging modalities and non-imaging measures. They will then identify the most promising brain network biomarkers and test different machine learning approaches. WP4 will consecutively embed the most effective graph theory/machine learning approaches in their pipelines.
WP6 has set up and is currently expanding a database containing contact information of more than 350 stakeholders among psychiatry professionals, professional associations, academic institutions and research bodies, patient organizations and non-governmental organizations involved in the provision of care to patients with psychosis, as well as pharma and medical technology providers. Important developments are disseminated to these stakeholders via a project newsletter (first issue was released in September 2016). WP6 is now also disseminating relevant findings via Twitter @PSYSCANproject and a newly designed project website (
In summary, significant progress has been made in all areas of the project since the last reporting period.

Potential Impact:
PSYSCAN is designed to translate findings from neuroimaging research into mainstream clinical practice. The aim is to improve the diagnosis, clinical differentiation, monitoring and management of psychotic disorders. This is likely to have both socio-economic and societal impacts.
• Develop new imaging technology. Development of a powerful NI tool with three applications designed to address clinically meaningful issues: (i) prediction of onset of mental disorder in the context of a high-risk paradigm (PSYSCAN-predict), (ii) prediction of clinical and functional differentiation across and within traditional diagnostic categories of affective and non-affective psychotic illness in first episode illness (PSYSCAN-diagnosis and clinical differentiation), and (iii) to follow the course of structural brain changes in relation to illness plasticity (illness progression and illness remission) and functional outcomes (work, independent living, relationships) after the first episode (PSYSCAN-monitor).
• Optimise new imaging technology. The impact of existing imaging technology will be maximised through the standardisation of image acquisition and analysis across Europe, and the integration of imaging data with complementary clinical, genetic and cognitive measures.
• Show clinical benefit for patients with psychiatric disorders. Clinical benefits for patients will be extensively assessed by clinical validation of the NI tool and its widespread implementation in clinical practice across Europe on the basis of naturalistic, prospectively followed, cohorts. The tools are designed to allow clinicians to use imaging and non-imaging measures to improve clinical care and thus benefit patients with psychiatric disorders.
• Encourage SME participation & foster innovation in line with Europe2020 agenda and EPMH. SME partners with expertise in image processing and the production of clinical assessment tools will play a central role in the successful development, dissemination and implementation of the tools across Europe. PSYSCAN will particularly benefit young people with mental health problems, and will facilitate early clinical intervention, in line with the Europe2020 agenda and the European Pact for Mental Health (EPMH).
Besides these targeted impacts, PSYSCAN will have a broader impact. Although PSYSCAN has been developed for psychosis, its approach can also be applied to other mental disorders, because the principles and some of the predictors would remain the same.
Figure 4 illustrates the steps that are needed to improve the diagnosis, monitoring and management of psychotic disorders. A multidisciplinary consortium of worldwide experts in psychosis, neuroimaging, data management, and multi-centre clinical trials has been established. Access to an unprecedented collection of neuroimaging, cognitive and clinical data from cohorts of psychosis patients, patients at ultra-high risk of psychosis, and controls, both in terms of quality and quantity, has been ensured. This retrospective data has been collated and stored at IXICO’s servers as part of WP2. Furthermore, prospective data has been acquired as part of WP5 and transferred to the data servers as well. All of this is being accomplished by capitalising on knowledge and experience of existing international research co-operations and cross-border collaborations. A list of 350 stakeholders has been established by WP6, a Twitter account (@PSYSCANproject) has been created and the dedicated website ( has been renewed and made more user friendly. The standardisation of psychiatric assessment across the EU has been accomplished. The development and optimization of imaging technology across EU and the wider PSYSCAN network will ensue from the course of Work Package 5 and will be part of future reports to the EC. Similarly, the clinical benefits for patients will be extensively assessed by clinical validation of the neuroimaging tool and its widespread implementation in clinical practice across Europe on the basis of naturalistic, prospectively followed, cohorts, during the course of WP5. The project has successfully encouraged strong involvement of SME and industry. SME and industry partners with expertise in image processing and the production of clinical assessment tools are playing a central role in the successful development, dissemination and implementation of the tools across Europe. The iPad clinical interfaces have been developed by CamCog and is now in use at 20 sites around the globe with data of 80 subjects captured into the database as part of WP5. IXICO has provided a standardized imaging protocol to all sites across the PSYSCAN consortium, has tested and determined its feasibility at each site, and the protocol has been implemented at all sites.

Public website address:
Twitter: @PSYSCANreport

List of Websites: