Lorentzian-Corrected Apparent Exchange-Dependent Relaxation (LAREX) Ω-Plot Analysis—An Adaptation for qCEST in a Multi-Pool System: Comprehensive In Silico, In Situ, and In Vivo Studies

International Journal of Molecular Sciences, vol. 23, pp. 6920

Abstract

Based on in silico, in situ, and in vivo studies, this study aims to develop a new method for the quantitative chemical exchange saturation transfer (qCEST) technique considering multi-pool systems. To this end, we extended the state-of-the-art apparent exchange-dependent relaxation (AREX) method with a Lorentzian correction (LAREX). We then validated this new method with in situ and in vivo experiments on human intervertebral discs (IVDs) using the Kendall-Tau correlation coefficient. In the in silico experiments, we observed significant deviations of the AREX method as a function of the underlying exchange rate (kba) and fractional concentration (fb) compared to the ground truth due to the influence of other exchange pools. In comparison to AREX, the LAREX-based Ω-plot approach yielded a substantial improvement. In the subsequent in situ and in vivo experiments on human IVDs, no correlation to the histological reference standard or Pfirrmann classification could be found for the fb (in situ: τ = −0.17 p = 0.51; in vivo: τ = 0.13 p = 0.30) and kba (in situ: τ = 0.042 p = 0.87; in vivo: τ = −0.26 p = 0.04) of Glycosaminoglycan (GAG) with AREX. In contrast, the influence of interfering pools could be corrected by LAREX, and a moderate to strong correlation was observed for the fractional concentration of GAG for both in situ (τ = −0.71 p = 0.005) and in vivo (τ = −0.49 p < 0.001) experiments. The study presented here is the first to introduce a new qCEST method that enables qCEST imaging in systems with multiple proton pools.

Authors 13

1. Karl Ludger Radke

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

2. Lena Marie Wilms corresponding

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

3. Miriam Frenken

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

4. Julia Stabinska

   Johns Hopkins University · Johns Hopkins Medicine · Kennedy Krieger Institute

   Affiliation as printed

   Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

   F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA

5. Marek Knet

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

6. Benedikt Kamp

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

7. Thomas Andreas Thiel

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

8. Timm Joachim Filler

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Anatomy I, Heinrich-Heine-University, D-40225 Dusseldorf, Germany

9. Sven Nebelung Aachen Department of Diagnostic and Interventional Radiology

   Universitätsklinikum Aachen · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

   Department of Diagnostic and Interventional Radiology, University Hospital Aachen, D-52074 Aachen, Germany

10. Gerald Antoch

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

11. Daniel Benjamin Abrar

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

12. Hans‐Jörg Wittsack

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany

13. Anja Müller‐Lutz

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Dusseldorf, Germany