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Projects / Programmes source: ARIS

Study of the structure and the dynamics of blood clot dissolution: mathematical modeling supported by magnetic resonance experiments

Research activity

Code Science Field Subfield
3.06.00  Medical sciences  Cardiovascular system   

Code Science Field
B140  Biomedical sciences  Clinical physics, radiology, tomography, medical instrumentation 
Keywords
blood clots, pulmonary emboli, thrombolysis, magnetic resonance imaging, light microscopy, mathematical modeling
Evaluation (rules)
source: COBISS
Researchers (7)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  07630  PhD Aleš Blinc  Cardiovascular system  Researcher  2008 - 2011  501 
2.  14574  PhD Mojca Urška Mikac  Physics  Researcher  2008 - 2011  151 
3.  07925  Ana Sepe    Technical associate  2008 - 2010  131 
4.  12056  PhD Igor Serša  Physics  Head  2008 - 2011  473 
5.  08094  PhD Mirza Šabovič  Cardiovascular system  Researcher  2008 - 2011  424 
6.  21359  PhD Gregor Tratar  Cardiovascular system  Researcher  2008 - 2011  99 
7.  28490  PhD Jernej Vidmar  Cardiovascular system  Junior researcher  2008 - 2010  89 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  91,882 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,921 
Abstract
The goal of this project is to investigate by magnetic resonance imaging and light microscopy mechanisms of blood clot thrombolysis and to optimize its parameters. The project will be based on modeling of thrombolytic processes within morphologically most common forms of blood clots in vitro. First, we intend to explain significant differences in lysabilty of morphologically different blood clots by fluorescent confocal microcopy and correlate these results with magnetic resonance imaging. Then we plan to investigate dissolution of non-occlusive blood clots in physiological conditions (pulsatile flow) by various methods of magnetic resonance microscopy. These results will be then supplemented with ex vivo dissolution results of pulmonary emboli acquired in autopsies. Based on these experimental results different mathematical models for clot dissolution will be developed and verified. The models will enable finding optimal conditions for efficient thrombolysis, i.e., concentration of thrombolytic agent as a function the perfusion channel size, the blood flow rate and clot morphology. The method of fluorescent confocal microscopy will serve also as the additional comparative method for analysis of clot perfusion channel during the dissolution. We intend to investigate correlation between the flow rate through the clot and the structure of the clot perfusion channel. We expect that in the fast flow regime the flow channel has rough surface and dissolution products are large and not well chemically degraded, while in the slow flow regime the flow channel has smooth surface and dissolution products are much smaller and better chemically degraded. To verify this hypothesis we will employ biochemical light microscopy analysis of plasma, which will help us determining the size of blood clot desegregation products in thrombolysis.
Significance for science
Thrombolysis as the main recanalization treatment is still in use of treatment of massive pulmonary embolism, in some selected cases in treatment of thrombosis in extremities, and in myocardium infarction where PTA is unavailable or is contraindicated. Even though thrombolytic treatment is losing its importance in clinical practice due to the spread of percutaneous revascularization interventions is its role increasing in treatment of ischemic stroke. Prompt diagnostics of thromboembolic events prior to thrombolytic treatment is of a high importance in clinic due to possible hemorrhage complications that may threaten patient’s life. Until now the method of choice in diagnostics of thromboembolic events was a standard contrast angiography that was often combined with CT, whereas MRI was not used as much, even though it is safe and noninvasive. MRI is a promising method in diagnostics of thromboembolic events because of its high specificity and sensitivity. Those two will become even more important with a new generation of high-resolution and high magnetic field MRI scanners. In this project our aim was to precisely specify diagnostic and prognostic importance of MRI techniques in assessment of lysability of a thromboembolic material prior to thrombolytic treatment and so to expose possible complications and solutions in the use of MRI in diagnostics of thromboembolic events. MRI can characterize structure of the thromboembolic material Furthermore, use of modern MRI techniques showed that MRI can also serve as a prognostic marker for the thrombolysis outcome, which is very relevant in a proper treatment of thromboembolic events and can also indirectly increase patient safety. In addition, we showed experimentally that success of thrombolysis is not just strictly a biochemical process, but is also strongly determined by mechanical influences of blood flow along the clot. This result has more than just a theoretical importance. It also can help planning other revascularization procedures on thromboembolic material more resistant standard thrombolysis procedures.
Significance for the country
Our studies on thrombolysis are conducted in close collaboration with the Clinical Centre Ljubljana, Department of the vascular diseases, which is one among the leading European institutions. Recently, use of thrombolysis worldwide is decreasing due to increasing use of catheter guided removal of thromboembolic material. However, in some fields thrombolytic procedures are still irreplaceable (isehamic stroke and pulmonary embolism). It is assumed that the use of thrombolytic treatment would be even bigger if diagnostics of thromboembolic material would be more specific and accurate. That is why our group is convinced that MRI has may still undiscovered potentials that can help improving diagnostics of thromboembolic material. We were one of the first groups that has showed advantages of MRI in diagnostic characterization of thromboemboli. We have showed that MRI can due to its specificity and selectivity serve as an exceptionally good prognostic marker of the outcome of thrombolysis. The results of our study are clinically relevant as it is expected that high-resolution strong magnetic field clinical magnets, that enable MRI of thromboembolic material, will become widely available. In addition it is unlikely that thrombolysis will be replaced by catheter guided procedures everywhere. In some regions (brain, lungs, …) catheter procedures are too risky so that thrombolysis is the only option. Such scenario is in support of our scientific efforts in exploration MRI diagnostic potentials in thrombolysis. Our current studies were all in vitro and were trying to explain mechanisms of thrombolytic treatment. In future studies on 3T clinical MRI scanners the same methods and approaches could be tested in vivo. These would be of much higher clinical relevance and would put Slovenia among the leading countries in MRI diagnostics in thrombolytic procedures.
Most important scientific results Annual report 2008, 2009, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, 2009, final report, complete report on dLib.si
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