Projects / Programmes
Optimization of MRI techniques for assessment of thrombolytic treatment outcome
| Code |
Science |
Field |
Subfield |
| 3.06.00 |
Medical sciences |
Cardiovascular system |
|
| Code |
Science |
Field |
| B530 |
Biomedical sciences |
Cardiovascular system |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
blood clots; acute ischemic stroke; thrombolysis; thrombectomy; MRI; microscopy
Researchers (14)
Organisations (3)
Abstract
Acute ischemic stroke is one of the leading causes of death in the western world. Early treatment of the stroke is usually based on recanalization approaches, namely, administration of thrombolytic agents and/or mechanical removal of blood clots. Microscopically, blood clots are composed of platelets and red blood cells (RBCs) interspersed within the fibrin network. A fibrin network by itself is a permeable porous structure; however, its permeability may be strongly influenced by the presence of platelets as well as of fibrin cross-linking which could considerably thicken the network. Entrapped RBCs in the clots reduce pore sizes within the network and therefore also reduce the permeability of the clots. Furthermore, distribution and proportion of the entrapped blood cells in the clots (RBCs and platelets) influence mechanical properties of the clots as well. Therefore, overall susceptibility of clots to thrombolytic treatment (thrombolysis or mechanical thrombectomy) is strongly influenced by clot permeability and their mechanical properties. An accurate assessment of the clot structure and composition could be helpful in treatment planning and prognosis of recanalization.
Magnetic resonance imaging (MRI) is a sensitive tool for diagnosing ischemic stroke based on detecting water mobility in different tissue compartments. The detection is enabled by the diffusion-weighted imaging (DWI) followed by a calculation of the apparent diffusion constant (ADC) map or by transversal NMR relaxation time (T2) mapping, which is sensitive to changes of the surface-to-volume ratio in the tissue that result in different surface-induced NMR relaxations. Differences in water mobility and NMR relaxation parameters between RBC-rich and platelet-rich regions were already found as an efficient discriminating factor for characterization of venous thrombi and assessment of their lytic outcome.
The aim of the research project is to optimize magnetic resonance imaging methods for easier management of stroke treatment by predicting an outcome of the thrombolytic treatment first and second by predicting possible complications during mechanical thrombectomy is cases where thrombolysis fails. In the first part of the project cerebral blood clots retrieved during mechanical thrombectomy procedures will be MRI scanned on a high-spatial resolution MRI scanner by different imaging (3D spin-echo or gradient echo) and different mapping (ADC, T2, T1, MT) methods. The same samples will be also analyzed by histology/Immunohistology for different blood clot components (RBC content, platelet involvement, density of the fibrin fiber network). MR-measured clot parameters will be then statistically analyzed for possible correlations with the corresponding histologically-determined parameters and also with the treatment procedure parameters (success of thrombolysis, thrombectomy procedure time, number of thrombectomy device passes). Possible correlation with the later will help developing prediction models for thrombolysis/thrombectomy outcome based on MR data. In the second part of the project we will aim to explain causes for stroke treatment outcomes by analyzing possible abnormalities of cerebral blood clots from stroke patients using advanced optical microscopy methods (confocal microscopy and high-resolution two photon STED). As the methods require tissue florescence which fibrin fibers do not have artificial fibrin-labeled blood clots from blood of the patients will be done and analyzed as well. In the third part of the project we will focus on in vivo MR imaging of blood clots. The imaging will be performed on patients having arteriovenous (AV) fistulas with formed blood clots. The AV fistula MR imaging will enable testing various imaging protocols in terms of their resolution, contrast and SNR and thus enabling optimizing parameters for MR imaging of blood clots in vivo.
Significance for science
The results of MRI and optical microscopy studies on cerebral blood clots ex vivo will help us to better understand thrombolysis of the clots and possible complications in mechanical thrombectomy. The results of the histological analysis of cerebral blood clots will be compared and the comparison statistically evaluated by the results of MR imaging of the same samples. On the basis of this comparison, criteria for determining the relevant components of blood clots from MR maps of different MR parameters (ADC; T1, T2, MT) will be deduced. A possible correlation between the measured MR parameters and the success of the thrombolytic/thrombectomic intervention will be checked, and based on these results models for predicting the outcome of the stroke treatment will be developed. In patients with occlusion in the AV fistula, the optimization of techniques for MR imaging of blood clots in vivo will be performed, and an appropriate MR imaging protocol will be developed. Using advanced methods of optical microscopy, such as confocal microscopy and dual-photon ultra-resolution STED microscopy, the structure of cerebral blood clots and of artificial blood clots from the blood of patients with the addition of a fibrin-labelling dye will be studied. We will check whether there is a link between any specific features of these clots and the stroke patient treatment outcome.
Significance for the country
The results of MRI and optical microscopy studies on cerebral blood clots ex vivo will help us to better understand thrombolysis of the clots and possible complications in mechanical thrombectomy. The results of the histological analysis of cerebral blood clots will be compared and the comparison statistically evaluated by the results of MR imaging of the same samples. On the basis of this comparison, criteria for determining the relevant components of blood clots from MR maps of different MR parameters (ADC; T1, T2, MT) will be deduced. A possible correlation between the measured MR parameters and the success of the thrombolytic/thrombectomic intervention will be checked, and based on these results models for predicting the outcome of the stroke treatment will be developed. In patients with occlusion in the AV fistula, the optimization of techniques for MR imaging of blood clots in vivo will be performed, and an appropriate MR imaging protocol will be developed. Using advanced methods of optical microscopy, such as confocal microscopy and dual-photon ultra-resolution STED microscopy, the structure of cerebral blood clots and of artificial blood clots from the blood of patients with the addition of a fibrin-labelling dye will be studied. We will check whether there is a link between any specific features of these clots and the stroke patient treatment outcome.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
