Exploration of Fractal Analysis for Characterisation and Quantification of Myocardial Ischaemia on Multi-Modality Perfusion Imaging

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Diagnostic implications of the fractal structure of the vasculature and perfusion are well known but have been poorly studied with radiological imaging. The funded project applied fractal analysis to dynamic CT perfusion (CTP) imaging in chronic myocardial ischaemia to differentiate a stenotic, macrovascular from a microvascular pathophysiology of ischaemia based by quantifying changes in the myocardial perfusion pattern. Microvascular ischaemia is of clinical importance because it cannot be treated by invasive coronary angiography but often requires invasive testing. Impaired vasodilation at the microvascular level can be triggered by a variety of possible underlying pathophysiological mechanisms. These might lead to manifest ischaemia of the myocardium. Microvascular changes in the perfusion pattern, which, according to the overarching hypothesis of the project, differ from those seen in macrovascular ischaemia because of the vascular scale affected in each case. The results of this project were able to confirm our hypothesis. Thus, fractal analysis can also be used to improve the diagnosis of macrovascular ischaemia, especially regarding specificity. Finally, fractal analysis reliably identified microvascular ischaemia in a single diagnostic modality even in the presence of moderate stenoses. With Kakuya Kitagawa (Japan), we were able to attract the first DFG Mercator Fellow in radiology. A prospective multicenter study coordinated by him provided valuable data for establishing fractal analysis. In addition, his clinical and scientific expertise contributed significantly to the success of the project. Our method is subject to a patent issued in Europe and the USA and further applications in neoplasia and inflammation were identified throughout the project. Based on our results, we propose a second funding period to prospectively implement fractal analysis clinically and to test its pathophysiological limits. The former will be achieved by a Mercator Fellowship with Aaron So (Canada): In a prospective, multicenter study on CTP led by him, fractal analysis will be prospectively integrated, and its clinical potential will be validated with an invasive reference standard. In cooperation with Prof. Kitagawa, we will challenge fractal analysis in clinically difficult pathophysiologies such as ischaemia in patients with atrial fibrillation or hemodialysis. Finally, we will apply fractal analysis for myocardial characterisation in routine CT angiography: We have reason to believe that fractal analysis can extract prognostic information from the myocardium, which correlate with the occurrence of major adverse cardiovascular events (MACE). The multicenter DISCHARGE study (n=1808) will serve as the data basis.