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Increased measurement capabilities for neurodegenerative diseases

Image showing young woman patient ready to undergo magnetic resonance imaging in a modern hospital laboratory
Young woman patient is ready to undergo magnetic resonance imaging in a modern hospital laboratory

EMPIR project develops SI-traceable methods to support earlier diagnosis of neurodegenerative diseases

Neurodegenerative diseases (NDDs) are a growing threat in an ageing population and an increasing burden on Europe’s healthcare system. Completed EMPIR project ‘Metrology and innovation for early diagnosis and accurate stratification of patients with neurodegenerative diseases’ (NeuroMET2, 18HLT09) developed measurement methods to assist earlier diagnosis of NDDs and the development of targeted therapies.

Development of cognitive assessment app

The project partners developed a novel metrologically validated method for more accurate cognitive assessment and memory testing of NDD patients - the NeuroMET Memory Metric (NMM) – and an app to deliver this method in a clinical setting. The development of the NMM and its associated app was facilitated by the project’s patient cohort. The cohort consisted of 129 participants from the Charité hospital in Berlin who were assessed longitudinally over the course of 6 years under both this project and the preceding ‘Innovative measurements for improved diagnosis and management of neurodegenerative diseases’ (NeuroMET, 15HLT04) project. The patient cohort is the first of its kind to be metrologically characterised and thus provides a powerful resource for future NDD research. The app was tested by clinicians at Charité during the project and, in November 2022, a webinar was held to inform clinicians about the app and its uses. Patients and their families were also kept informed of progress throughout the course of the project via a series of engagement events.

Collaboration with industrial and clinical contacts

The projects partners maintained close relationships with industrial and clinical partners to ensure that new developments were translated effectively into the clinical setting.

This was particularly evident in the field of Magnetic resonance imaging (MRI) and spectroscopy (MRS). These techniques are often used for diagnosing NDDs, and therefore improved protocols and references could aid earlier diagnosis. In routine healthcare settings, MRI scans are usually performed with 3T MRI machines, which are less expensive and more commonly available than research-grade 7T MRI machines which give more detailed imaging and lower measurement uncertainty, but a much greater cost. The project developed new reference sequences based on 7T MRI/MRS data which were then translated to 3T. This means that the measurements performed at 3T in a routine clinical setting are traceable to a higher order 7T reference. This novel approach was transferred to clinicians at Greifswald University Medicine in Germany via a series of visits, secondments, and a webinar. The transfer was supported by Siemens, a leading manufacturer of MRI machines in Europe. This protocol yields improved results on 3T MRI machines and facilitates earlier diagnosis of NDDs.

New reference method procedures for NDD biomarkers

Additionally, the project developed three SI-traceable methods for detection of NDD protein biomarkers at clinically relevant levels by mass spectrometry. The proteins of interest were neurofilament light protein, p-tau, and α-synuclein. The α-synuclein reference method, previously developed in the NeuroMET project, was validated during this project and used for comparison with orthogonal techniques, including a clinical MS method and a real-time quaking-induced conversion (RT-QuIC) assay. The candidate higher order reference methods for neurofilament light protein and p-tau will be further developed and validated in the current European Metrology Partnership project ‘Standardisation of measurements of neurodegenerative disease biomarkers’ (22HLT07, NEuroBioStand).

The project coordinator Will Webster (LGC) comments on the success of the project

“The 18HLT09 NeuroMET2 and 15HLT04 NeuroMET projects are excellent examples of multidisciplinary collaborations between European metrology institutes and the industrial and clinical communities to address the significant societal challenge posed by NDDs. The methods and measurement systems developed under these projects will aid both early diagnosis of NDDs, and monitoring of disease progression by more accurate patient stratification”

This EMPIR project is co-funded by the European Union's Horizon 2020 research and innovation programme and the EMPIR Participating States.


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