Although the knowledge about Sudden Cardiac Death (SCD) and its risk factors and treatment is continuously growing, it still remains the most likely reason of mortality in western countries. In general, the short timespan between witnessed symptoms and sudden death caused by cardiovascular disease is about one hour or, if no symptoms are observed, 24 hours. The preliminary occurring Sudden Cardiac Arrest (SCA) bases in approximately 70% of all SCD cases on Coronary Heart Diseases (CHD) provoking Myocardial Infarctions (MI) by atherosclerotic plaque on myocardial relevant arteries. Consequently, the restricted blood flow reduces the oxygen density triggering the mechanism of fibrotic scarring, in which connective tissue replaces the functional muscle tissue. This unexcitable collagenous scar tissue alters the myocardial conductivity. Untreated, arrhythmias, in particular ventricular fibrillation (VF), can be initiated being responsible for 50% of total SCD3,4. During VF ventricular muscles twitches randomly rather than contracting ending up with an interrupted pump activity. Recent developments show that the correction of cardiac conductivity by using Catheter Ablation (CA) can decrease the risk of VF and, consequently, SCD. An Electrophysiology Study (EPS) offers the electric potential map of the myocardium and indicates abnormal electrical circuits interrupting the propagation of electrical impulses. These causative fibrotic areas are terminated through heating induced by catheter-based electrodes with alternating current in the radiofrequency range. Low resolution aggravates a precise differentiation between affected and physiological myocardial tissue. In addition, applied to muscle tissue CA has also the ability to cause fibrotic scarring explaining the relation between unprecise guidance of CA and a higher probability of recurrences. Promising imaging modalities to increase the therapeutic success are advanced techniques such as Second Harmonic Generation (SHG) microscopy and Optical Coherence Tomography (OCT) for more sensitive diagnostics. SHG imaging can reveal density and individual fibril morphology of collagen. Classification into different stages of fibrillogenesis can be performed allowing allocation of examined cardiac tissue into non-infarcted, pharmacological treated and untreated. In contrast, OCT provides real-time three-dimensional imaging of tissue morphology. Switching from structural to spectroscopic investigation, Raman excitation offers the unique molecular fingerprint and, therefore, the conclusive evidence of molecular changes in point-scan acquisition. Accordingly, combining OCT, SHG microscopy and Raman spectroscopy in one setup with a shared sample arm and a common objective facilitates to benefit from the individual advantages of each modality.
Sudden cardiac death being the most likely reason of mortality in western countries is associated with preliminary occurring myocardial infarctions causing variations in structure, texture, metabolism and molecular composition. Common therapy methods lacking sufficient resolution for precise differentiation between fibrotic and physiological cardiac tissue. Novel multimodal diagnostic approaches are required and explored with our developed ultrahigh-resolution multimodal optical imaging platform including optical coherence tomography, multiphoton microscopy and line scan Raman spectroscopy in a label-free manner at cellular resolution. Co-registration of all modalities and integrated multiparametric analysis and radiomics provide complementary morphological, metabolic and molecular contrast for unprecedented cardiac tissue classification.
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