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

血管和灌注分形结构的诊断意义是众所周知的，但与放射成像的研究很少。该项目将分形分析应用于慢性心肌缺血的动态CT灌注（CTP）成像，通过量化心肌灌注模式的变化来区分狭窄、大血管和微血管缺血的病理生理。微血管缺血具有重要的临床意义，因为它不能通过侵入性冠状动脉造影治疗，但通常需要侵入性检查。微血管水平的血管舒张受损可由多种可能的潜在病理生理机制触发。这些可能导致心肌明显缺血。微血管灌注模式的改变，根据该项目的总体假设，不同于大血管缺血，因为血管规模在每种情况下都受到影响。这个项目的结果能够证实我们的假设。因此，分形分析也可以用于提高大血管缺血的诊断，特别是在特异性方面。最后，分形分析在单一诊断模式下可靠地识别微血管缺血，即使存在中度狭窄。与Kakuya Kitagawa（日本）合作，我们吸引了第一位DFG墨卡托放射学研究员。他协调的前瞻性多中心研究为建立分形分析提供了宝贵的数据。此外，他的临床和科学专业知识对项目的成功做出了重大贡献。我们的方法在欧洲和美国获得了专利，并在整个项目中确定了肿瘤和炎症的进一步应用。基于我们的研究结果，我们提出了第二个资助期，以前瞻性地在临床上实施分形分析并测试其病理生理局限性。前者将由Aaron So（加拿大）的墨卡托奖学金实现：在他领导的CTP前瞻性多中心研究中，分形分析将被前瞻性地整合，其临床潜力将通过有创参考标准得到验证。与北川教授合作，我们将挑战分形分析在临床上困难的病理生理，如心房颤动或血液透析患者的缺血。最后，我们将在常规CT血管造影中应用分形分析进行心肌表征：我们有理由相信分形分析可以从心肌中提取与主要心血管不良事件（MACE）发生相关的预后信息。多中心DISCHARGE研究（n=1808）将作为数据基础。

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.