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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01422

Attenuation correction approaches for serotonin transporter quantification with PET/MRI

 Lucas Rischka1, Gregor Gryglewski1,  Neydher Berroteran-Infante2,  Ivo Rausch3, Gregory M. James1,  Manfred Klöbl1, Helen Sigurdardottir1, Markus Hartenbach2,  Andreas Hahn1, Wolfgang Wadsak2, 4,  Markus Mitterhauser2, 5,  Thomas Beyer3, Siegfried Kasper1, Daniela Prayer6,  Marcus Hacker2 and  Rupert Lanzenberger1*
  • 1Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria
  • 2Division of Nuclear Medicine, Department of Biomedical Imaging and Image guided Therapy, Medical University of Vienna, Austria
  • 3Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
  • 4Center for Biomarker Research in Medicine (CBmed), Austria
  • 5Ludwig Boltzmann Institut Angewandte Diagnostik, Austria
  • 6Division of Neuroradiology and Musculoskeletal Radiology, University Clinic for Radiology and Nuclear Medicine, Medical University of Vienna, Austria

Background
Several MR-based attenuation correction (AC) approaches were developed to conquer the challenging AC in hybrid PET/MR imaging. These AC methods are commonly evaluated on standardized uptake values or tissue concentration. However, in neurotransmitter system studies absolute quantification is more favorable due to its accuracy. Therefore, our aim was to investigate the accuracy of segmentation- and atlas-based MR AC approaches on serotonin transporter (SERT) distribution volumes and occupancy after a drug challenge.
Methods
18 healthy subjects (7 male) underwent two [11C]DASB PET/MRI measurements in a double-blinded, placebo controlled, cross-over design. After 70 min the selective serotonin reuptake inhibitor (SSRI) citalopram or a placebo was infused. The parameters total and specific volume of distribution (VT, VS=BPP) and occupancy were quantified. All subjects underwent a low-dose CT scan as reference AC method. Besides the standard AC approaches DIXON and UTE, a T1-weighted structural image was recorded to estimate a pseudo-CT based on an MR/CT database (pseudoCT). Another evaluated AC approach superimposed a bone model on AC DIXON. Lastly, an approach optimizing the segmentation of UTE images was analyzed (RESOLUTE). PET emission data were reconstructed with all 6 AC methods. The accuracy of the AC approaches was evaluated on a region of interest-basis for the parameters VT, BPP and occupancy with respect to the results of AC CT.
Results
Variations for VT and BPP were found with all AC methods with bias ranging from -15% to 17%. The smallest relative errors for all regions were found with AC pseudoCT (<|5%|). Although the bias between BPP SSRI and BPP placebo varied markedly with AC DIXON (<|12%|) and AC UTE (<|9%|), a high correlation to AC CT was obtained (r²~1). The relative difference of the occupancy for all tested AC methods was small for SERT high binding regions (<|4%|).
Conclusion
The high correlation might offer a rescaling from the biased parameters VT and BPP to the true values. Overall, the pseudoCT approach yielded smallest errors and the best agreement with AC CT. For SERT occupancy, all AC methods showed little bias in high binding regions, indicating that errors may cancel out in longitudinal assessments.

Keywords: PET/MRI, Serotonin transporter (5HTT), [11C] DASB, Occupancy, attenuation correction (AC), absolute quantification

Received: 03 May 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Rischka, Gryglewski, Berroteran-Infante, Rausch, James, Klöbl, Sigurdardottir, Hartenbach, Hahn, Wadsak, Mitterhauser, Beyer, Kasper, Prayer, Hacker and Lanzenberger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Rupert Lanzenberger, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria, rupert.lanzenberger@meduniwien.ac.at