Projektbeschreibung
Software zur Nutzung neuer MRT-Marker für Hirn-Scans mit Standard-Magnetresonanztomografen
Kleine Gefäßerkrankungen des Gehirns (Small Vessel Disease, SVD) sind signifikante strukturelle und funktionelle Störungen der zerebralen Mikrozirkulation, was vor allem im Alter das Risiko für Schlaganfall und Hirnblutung erhöht. Diese Mikroangiopathien sind auch eine der Hauptursachen für kognitive Störungen und Demenz. Das Krankheitsgeschehen in vivo über Gehirn-Scans nachzuverfolgen, ist allerdings noch schwierig, auch sind weder präventive Arzneimittel noch Heilungsmöglichkeiten verfügbar. So entwickelte das Projekt SELMA Techniken, um kleine Gefäße mit leistungsstarken 7-Tesla-Magnetresonanztomografen (7T-MRT) sichtbar werden zu lassen. Ziel ist, die 7T-MRT-Pulssequenzen über automatisierte Analysetools auf gängige 3T-MRT-Scanner zu übertragen, um das Einsatzspektrum zu erweitern und robuste Biomarker für wirksame Behandlungen von Erkrankungen der kleinen Blutgefäße zu entwickeln.
Ziel
Problem:
Cerebral small vessel disease (SVD) is a hallmark of serious brain diseases such as acute stroke and dementia. It has a major impact on society, since it affects quality of life of many ageing individuals, and increasingly challenges the healthcare resources. Current image-based biomarkers do not reflect SVD itself, but rather macroscopic, irreversible brain damage, secondary to the abnormalities of the small vessels. This greatly hampers development of new drugs as clinical trials lack effective biomarkers directly reflecting SVD.
Solution:
The SmallVesselMRI ERC project (337333), yielded 7T MRI methods with the potential to offer a paradigm shift in SVD research. We have developed new MRI measures that, for the first time, allow non-invasive assessment of the condition of the small vessels themselves, including blood flow velocity pulsation in small perforating vessels, which informs on vessel stiffness. The current proof-of-concept project ‘trial-ready Small vEsseL MRI MArkers (SELMA) aims to make these novel promising vascular parameters ready for use in phase II/III clinical trials. Our ambition is to bridge the gap between high end imaging research platforms and widespread clinical MRI, in order to enable drug-target engagement studies in clinical trials for newly developed drugs.
SELMA will:
1) Port the small-vessel 7T MRI pulse sequences to clinically ubiquitous 3T MRI scanners. 2) Develop a software tool that can provide robust, automated data analysis. 3) Determine the reproducibility of the SELMA biomarkers in a group of 35 healthy individuals with scan-rescan experiments. 4) Provide clinical proof of concept by a pilot study in 15 patients with SVD, measuring the vascular parameters before and after administration of a pharmaceutical agent. Using results of our proof of concept study, we will develop a business plan to approach the pharmaceutical industry to change the paradigm in drug development for SVD treatment.
Wissenschaftliches Gebiet
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencescomputer and information sciencesdata science
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesbasic medicineneurologydementia
- medical and health sciencesbasic medicineneurologystroke
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-POC - Proof of Concept GrantGastgebende Einrichtung
3584 CX Utrecht
Niederlande