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The heart of stroke: Pipes, Perfusion, Parenchyma

Periodic Reporting for period 4 - HEARTOFSTROKE (The heart of stroke: Pipes, Perfusion, Parenchyma)

Reporting period: 2019-09-01 to 2020-02-29

Stroke is the second cause of death and the third cause of disability worldwide. Treatment options for stroke are limited and the underlying causes remain unknown in 40% of patients. In HEARTOFSTROKE I perform in depth investigations of the vasculature (Pipes), blood supply (Perfusion) and brain tissue damage (Parenchyma) to better understand the cause of a stroke in an individual patient. Together, these Pipes, Perfusion and Parenchyma are described in HEARTOFSTROKE as the ‘3Ps’. In HEARTOFSTROKE, I will develop innovative MRI methods to quantify the burden of cerebrovascular disease of the Pipes, Perfusion and Parenchyma (Objective 1-7). The new MRI methods will be applied in patients to explain the presence of smaller and larger infarcts (Objective 8-10). The developed patient specific biomarkers may pave the way for designing preventive and therapeutic strategies aimed at reducing the burden of neurodegenerative diseases.

In conclusion, we developed and showed the clinical use of novel MRI markers that characterize the burden of cerebrovascular disease at the leven of both the vasculature (Pipes), the brain perfusion and the brain parenchyma including small infarcts.
The results of the HEARTOFSTROKE project has moved beyond the state of the art for both the vasculature (Pipes), Perfusion and Parenchyma. The HEARTOFSTROKE results have contributed to a more complete assessment of the burden of cerebrovascular disease. For the vasculature (Pipes) the characterization of the burden of disease on the level of the brain vasculature is now possible with intracranial vessel wall MRI scans developed and criteria for the assessment of vessel wall lesions on these scan with correlations performed with histopathology. For the Perfusion new analysis methods have been developed to extract more hemodynamic information from arterial spin labeling perfusion MRI scans. For the Parenchyma the complete burden of brain tissue infarcts is better extracted from the high resolution 7Tesla, 3Tesla and 1.5Tesla MRI scans based on the characterization, including imaging criteria, for small infarcts of the cerebellum and the deep gray matter.
The MRI imaging results from the clinical translational studies (Objectives 8-10) are fully analysed. From the input of the first clinical studies further improvements of the methods developed under the Objectives 1-7 were performed. As an example for the Pipes (Vasculature; Objective 1-3) MRI vessel wall imaging methods was developed and evaluated in patients for the detection of intracranial vascular calcifications. Furthermore, the regional perfusion heterogeneity of arterial spin labeling perfusion signal was analysed with methods that take into account the normal arterial spin label signal that is expected from a reference group (Objective 4-6); these methods are ready to be applied in clinical practice in patients. For the brain tissue the characterization (Objective 7) of small (micro) infarcts in all deep gray matter structures of the brain was performed. The ‘next generation’ of biomarkers developed in the first years of the HEARTOFSTROKE project (Objective 1-7) was evaluated in the patient studies. By doing so we established in HEARTOFSTROKE the complete burden of brain tissue damage of the cortex (macro and microinfarcts), deep gray matter and cerebellum (smaller and larger infarcts) and white matter lesions will be established and correlated with vascular changes in the next 2 years (Objective 8-10). As an example; In HEARTOFSTROKE I identified a relation both with ageing, hypertension and diabetes and the severity (number) of intracranial arterial vessel wall lesions both in a population with non-symptomatic and symptomatic patients with a either a stroke or transient ischemic attack (TIA). Furthermore, we found an association between the burden of intracranial atherosclerosis on 7T MRI and markers of extracranial atherosclerosis.
Relevance of multi-modal imaging for diagnosing cerebrovascular disease [JCBFM 2018].