From pixels to pathophysiology - imaging immunity in cerebro- and cardiovascular disease

Abstract

This thesis, consisting of six experimental chapters, shows the advantages of using high-field MRI and PET imaging together with targeted contrast agents and tracers for understanding pathophysiology and monitoring disease progression. We employed various translational imaging techniques in experimental animal models to elucidate the functioning of the immune system in cerebro- and cardiovascular diseases, predominantly focusing on ischemic stroke and myocardial infarction. The first part focuses on multimodal imaging of immune processes after acute, subacute and chronic myocardial infarction and stroke. The second part focuses on proof-of-concept studies with a novel radiotracer and a nanoparticle platform which can be applied for theranostic (i.e. therapeutic and diagnostic) purposes. For the second part, well-established disease models for ischemic heart disease, atherosclerosis and heart allograft transplantation were applied to demonstrate the efficiency of the radiotracer and the nanobiologic platform. The experiments detailed in this thesis represent a modest step forward in identifying imaging methods and targets of interest for understanding pathophysiology of stroke and myocardial infarction. Examples, such as evaluating the metabolic activity of a stroke lesion, mapping myeloid cell trafficking after an ischemic event, or assessing vascular integrity of the bone marrow, showcase the potential for imaging biomarkers. While individually these biomarkers may not bring in drastic changes in treatment paradigms, their true potential lies in integration. When combined with acute treatment, laboratory tests, functional assessments, and immunomodulatory interventions, these imaging biomarkers may consolidate into a comprehensive and individually relevant tool for guiding treatment decisions and influencing recovery strategies.