Katzdobler, Sabrina, Nitschmann, Alexander, Barthel, Henryk, Bischof, Gerard, Beyer, Leonie, Marek, Ken, Song, Mengmeng, Wagemann, Olivia, Palleis, Carla, Weidinger, Endy, Nack, Anne, Fietzek, Urban, Kurz, Carolin, Haeckert, Jan, Stapf, Theresa, Ferschmann, Christian, Scheifele, Maximilian, Eckenweber, Florian, Biechele, Gloria, Franzmeier, Nicolai, Dewenter, Anna, Schoenecker, Sonja, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael ORCID: 0000-0002-2683-9432, Schildan, Andreas, Patt, Marianne, Stephens, Andrew W., van Eimeren, Thilo, Neumaier, Bernd, Drzezga, Alexander, Danek, Adrian ORCID: 0000-0001-8857-5383, Classen, Joseph, Buerger, Katharina, Janowitz, Daniel, Rauchmann, Boris-Stephan ORCID: 0000-0003-4547-6240, Stoecklein, Sophia, Perneczky, Robert, Schoeberl, Florian, Zwergal, Andreas, Hoeglinger, Gunter U., Bartenstein, Peter, Villemagne, Victor, Seibyl, John, Sabri, Osama, Levin, Johannes ORCID: 0000-0001-5092-4306 and Brendel, Matthias . Additive value of [F-18]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome. Eur. J. Nucl. Med. Mol. Imaging. NEW YORK: SPRINGER. ISSN 1619-7089

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Abstract

Purpose Early after [F-18]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [F-18]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [F-18]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. Methods Seventy-eight patients with 4RTs (71 +/- 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 +/- 12 years, 35 female) and twelve age-matched controls (69 +/- 8 years, 8 female) underwent dynamic (0-60 min) [F-18] PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value - 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). Results Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R = - 0.431; p = 0.0005). Conclusion [F-18]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Katzdobler, SabrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitschmann, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barthel, HenrykUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bischof, GerardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marek, KenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Song, MengmengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagemann, OliviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palleis, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weidinger, EndyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nack, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fietzek, UrbanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurz, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haeckert, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stapf, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferschmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheifele, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckenweber, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biechele, GloriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franzmeier, NicolaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dewenter, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoenecker, SonjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saur, DorotheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeter, Matthias L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rumpf, Jost-JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rullmann, MichaelUNSPECIFIEDorcid.org/0000-0002-2683-9432UNSPECIFIED
Schildan, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patt, MarianneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stephens, Andrew W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Eimeren, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumaier, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danek, AdrianUNSPECIFIEDorcid.org/0000-0001-8857-5383UNSPECIFIED
Classen, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janowitz, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rauchmann, Boris-StephanUNSPECIFIEDorcid.org/0000-0003-4547-6240UNSPECIFIED
Stoecklein, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perneczky, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoeberl, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zwergal, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeglinger, Gunter U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenstein, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villemagne, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seibyl, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabri, OsamaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, JohannesUNSPECIFIEDorcid.org/0000-0001-5092-4306UNSPECIFIED
Brendel, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-695343
DOI: 10.1007/s00259-022-05964-w
Journal or Publication Title: Eur. J. Nucl. Med. Mol. Imaging
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1619-7089
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DIAGNOSIS; PET; BIOMARKERSMultiple languages
Radiology, Nuclear Medicine & Medical ImagingMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69534

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