TY - JOUR
T1 - Fractal analysis of 4D dynamic myocardial stress-CT perfusion imaging differentiates micro- and macrovascular ischemia in a multi-center proof-of-concept study
AU - Michallek, Florian
AU - Nakamura, Satoshi
AU - Ota, Hideki
AU - Ogawa, Ryo
AU - Shizuka, Takehito
AU - Nakashima, Hitoshi
AU - Wang, Yi Ning
AU - Ito, Tatsuro
AU - Sakuma, Hajime
AU - Dewey, Marc
AU - Kitagawa, Kakuya
N1 - Funding Information:
The study protocol is published in the UMIN-Clinical Trial Registry under the registration number UMIN000016353, has received institutional review board approval (Clinical Research Ethics Review Committee of Mie University Hospital), and complied with the Declaration of Helsinki. Written informed consent from all participants has been obtained. The AMPLIFiED study was funded by Bayer Japan. Florian Michallek: FM holds a United States patent (USPTO: 10,991,109, Patent 2021) on fractal analysis of perfusion imaging and has filed a patent application on the same topic at the European Patent Office (PCT/EP2016/071551), each together with MD. FM receives grant support from the German Research Foundation (DFG, grant number Ml 2272/1-1 [392304398]), which covers 50% of his position. Marc Dewey: MD holds a United States patent (USPTO: 10,991,109, Patent 2021) on fractal analysis of perfusion imaging and has filed a patent application on the same topic at the European Patent Office (PCT/EP2016/071551), each together with FM. MD receives grant support from the German Research Foundation for this project (DFG, grant number DE 1361/18-1 [392304398]). MD has received grant support from the FP7 Program of the European Commission for the randomized multicenter DISCHARGE trial (603266-2, HEALTH-2012.2.4.-2). He also received grant support from German Research Foundation (DFG) in the Heisenberg Program (DE 1361/14-1), graduate program on quantitative biomedical imaging (BIOQIC, GRK 2260/1), the Priority Programme Radiomics for the investigation of coronary plaque and coronary flow (DE 1361/19-1 [428222922] and 20-1 [428223139] in SPP 2177/1). He also received funding from the Berlin University Alliance (GC_SC_PC 27) and from the Digital Health Accelerator of the Berlin Institute of Health. MD is European Society of Radiology (ESR) Research Chair (2019–2022) and the opinions expressed in this article are the author’s own and do not represent the view of ESR. Per the guiding principles of ESR, the work as Research Chair is on a voluntary basis and only remuneration of travel expenses occurs. Prof. Dewey is also the editor of Cardiac CT, published by Springer Nature, and offers hands-on courses on CT imaging ( www.ct-kurs.de ). Institutional master research agreements exist with Siemens, General Electric, Philips, and Canon. The terms of these arrangements are managed by the legal department of Charité – Universitätsmedizin Berlin. Hajime Sakuma: HS has received support from Daiichi Sankyo Co. Ltd, Fuji Pharma Co. Ltd., FUJIFILM RI Pharma Co. Ltd., Eisai Co. Ltd. Kakuya Kitagawa: KK has received support from Siemens Japan. SN, HO, RO, TS, HN, YW and TI do not declare competing interests relevant to this manuscript.
Funding Information:
FM and MD are grateful for the funding received from the German Research Foundation for this project (DFG, project number 392304398, grants Ml 2272/1-1 and DE 1361/18-1, https://gepris.dfg.de/gepris/projekt/392304398 ). Open Access funding enabled and organized by Projekt DEAL.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Fractal analysis of dynamic, four-dimensional computed tomography myocardial perfusion (4D-CTP) imaging might have potential for noninvasive differentiation of microvascular ischemia and macrovascular coronary artery disease (CAD) using fractal dimension (FD) as quantitative parameter for perfusion complexity. This multi-center proof-of-concept study included 30 rigorously characterized patients from the AMPLIFiED trial with nonoverlapping and confirmed microvascular ischemia (nmicro = 10), macrovascular CAD (nmacro = 10), or normal myocardial perfusion (nnormal = 10) with invasive coronary angiography and fractional flow reserve (FFR) measurements as reference standard. Perfusion complexity was comparatively high in normal perfusion (FDnormal = 4.49, interquartile range [IQR]:4.46–4.53), moderately reduced in microvascular ischemia (FDmicro = 4.37, IQR:4.36–4.37), and strongly reduced in macrovascular CAD (FDmacro = 4.26, IQR:4.24–4.27), which allowed to differentiate both ischemia types, p < 0.001. Fractal analysis agreed excellently with perfusion state (κ = 0.96, AUC = 0.98), whereas myocardial blood flow (MBF) showed moderate agreement (κ = 0.77, AUC = 0.78). For detecting CAD patients, fractal analysis outperformed MBF estimation with sensitivity and specificity of 100% and 85% versus 100% and 25%, p = 0.02. In conclusion, fractal analysis of 4D-CTP allows to differentiate microvascular from macrovascular ischemia and improves detection of hemodynamically significant CAD in comparison to MBF estimation.
AB - Fractal analysis of dynamic, four-dimensional computed tomography myocardial perfusion (4D-CTP) imaging might have potential for noninvasive differentiation of microvascular ischemia and macrovascular coronary artery disease (CAD) using fractal dimension (FD) as quantitative parameter for perfusion complexity. This multi-center proof-of-concept study included 30 rigorously characterized patients from the AMPLIFiED trial with nonoverlapping and confirmed microvascular ischemia (nmicro = 10), macrovascular CAD (nmacro = 10), or normal myocardial perfusion (nnormal = 10) with invasive coronary angiography and fractional flow reserve (FFR) measurements as reference standard. Perfusion complexity was comparatively high in normal perfusion (FDnormal = 4.49, interquartile range [IQR]:4.46–4.53), moderately reduced in microvascular ischemia (FDmicro = 4.37, IQR:4.36–4.37), and strongly reduced in macrovascular CAD (FDmacro = 4.26, IQR:4.24–4.27), which allowed to differentiate both ischemia types, p < 0.001. Fractal analysis agreed excellently with perfusion state (κ = 0.96, AUC = 0.98), whereas myocardial blood flow (MBF) showed moderate agreement (κ = 0.77, AUC = 0.78). For detecting CAD patients, fractal analysis outperformed MBF estimation with sensitivity and specificity of 100% and 85% versus 100% and 25%, p = 0.02. In conclusion, fractal analysis of 4D-CTP allows to differentiate microvascular from macrovascular ischemia and improves detection of hemodynamically significant CAD in comparison to MBF estimation.
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U2 - 10.1038/s41598-022-09144-6
DO - 10.1038/s41598-022-09144-6
M3 - Article
C2 - 35332236
AN - SCOPUS:85127020302
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 5085
ER -