Fractal analysis of perfusion imaging in synovitis: a novel imaging biomarker for grading inflammatory activity based on assessing angiogenesis
- PMID: 35149603
- PMCID: PMC8845323
- DOI: 10.1136/rmdopen-2021-002078
Fractal analysis of perfusion imaging in synovitis: a novel imaging biomarker for grading inflammatory activity based on assessing angiogenesis
Abstract
Objectives: The mutual and intertwined dependence of inflammation and angiogenesis in synovitis is widely acknowledged. However, no clinically established tool for objective and quantitative assessment of angiogenesis is routinely available. This study establishes fractal analysis as a novel method to quantitatively assess inflammatory activity based on angiogenesis in synovitis.
Methods: First, we established a pathophysiological framework for synovitis including fractal analysis of software perfusion phantoms, which allowed to derive explainability with a known and controllable reference standard for vascular structure. Second, we acquired MRI datasets of patients with suspected rheumatoid arthritis of the hand, and three imaging experts independently assessed synovitis analogue to Rheumatoid Arthritis MRI Scoring (RAMRIS) criteria. Finally, we performed fractal analysis of dynamic first-pass perfusion MRI in vivo to evaluate angiogenesis in relation to inflammatory activity with RAMRIS as reference standard.
Results: Fractal dimension (FD) achieved highly significant discriminability for different degrees of inflammatory activity (p<0.01) in software phantoms with known ground-truth of angiogenic structure. FD indicated increasingly chaotic perfusion patterns with increasing grades of inflammatory activity (Spearman's ρ=0.94, p<0.001). In 36 clinical patients, fractal analysis quantitatively and objectively discriminated individual RAMRIS scores (p≤0.05). Area under the receiver-operating curve was 0.84 (95% CI 0.7 to 0.89) for fractal analysis when considering RAMRIS as ground-truth. Fractal analysis additionally identified angiogenesis in cases where RAMRIS underestimated inflammatory activity.
Conclusions: Based on angiogenesis and perfusion pathophysiology, fractal analysis non-invasively enables comprehensive, objective and quantitative characterisation of inflammatory angiogenesis with subjective and qualitative RAMRIS as reference standard. Further studies are required to establish the clinical value of fractal analysis for diagnosis, prognostication and therapy monitoring in inflammatory arthritis.
Keywords: Magnetic Resonance Imaging; arthritis; synovitis.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Conflict of interest statement
Competing interests: FM holds a US 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 Marc Dewey. FM receives grant support from the German Research Foundation (DFG, grant number Ml 2272/1-1 (392304398)), which covers 50% of his position. FP has received research grants from Lilly, Novartis and UCB. FP received speaker and consultancy fees from AbbVie, AMGEN, Bristol-Myers Squibb, Hexal, Janssen, MSD, Novartis, Pfizer, Roche und UCB. K-GAH has received lecture fees from AbbVie, MSD, Novartis, and Pfizer. 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 Florian Michallek. MD receives grant support from the German Research Foundation for this project (DFG, grant number 392304398). MD has received grant support from the FP7 Program of the European Commission for the randomised multicentre DISCHARGE trial (603266-2, HEALTH-2012.2.4.-2). He also received grant support from German Research Foundation (DFG) in the Heisenberg Programme (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. MD 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. TD has received personal fees from MSD, Novartis and Canon MS.
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