title: Quantitative imaging by pixel-based contrast-enhanced ultrasound reveals a linear relationship between synovial vascular perfusion and the recruitment of pathogenic IL-17A-F+IL-23+CD161+CD4+T helper cells in psoriatic arthritis joints.
abstract: To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study. Gray scale CEUS evaluation was performed on the same joint immediately after joint aspiration, by automatic assessment perfusion data, using a new quantification approach of pixel-based analysis and the gamma-variate model. The set of perfusional parameters considered by the time intensity curve includes the maximum value (peak) of the signal intensity curve, the blood volume index or area under the curve, (BVI, AUC) and the contrast mean transit time (MTT). The direct ex vivo analysis of the frequencies of SF IL17A-F+CD161+IL23+CD4+T cells subsets were quantified by fluorescence-activated cell sorter (FACS). In cross-sectional analyses, when tested for multiple comparison setting, a false discovery rate at 10%, a common pattern of correlations between CEUS Peak, AUC (BVI) and MTT parameters with the IL17A-F+IL23+- IL17A-F+CD161+- and IL17A-F+CD161+IL23+CD4+T cells subsets, as well as lack of correlation between both peak and AUC values and both CD4+T and CD4+IL23+T cells, was observed. The pixel-based CEUS assessment is a truly measure synovial inflammation, as a useful tool to develop quantitative imaging biomarker for monitoring target therapeutics in PsA.
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. ugo.fiocco@unipd.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Fiocco
authors.affiliation: Section of Radiology, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Stramare
authors.affiliation: Haematology and Clinical Immunology Branch, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Martini
authors.affiliation: Section of Radiology, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Coran
authors.affiliation: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, via S. Pansini 5, 80131, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caso
authors.affiliation: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, via S. Pansini 5, 80131, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Costa
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Felicetti
authors.affiliation: Department of Information Engineering, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Rizzo
authors.affiliation: Department of Information Engineering, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Tonietto
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Scanu
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Oliviero
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Bernd
authors.initials: B
authors.lastname: Raffeiner
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Maristella
authors.initials: M
authors.lastname: Vezzù
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences - Section of Anatomy Pathology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunardi
authors.affiliation: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, via S. Pansini 5, 80131, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Scarpa
authors.affiliation: Department of Medicine, Unit of Ultrasonography in Internal Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Sacerdoti
authors.affiliation: Section of Radiology, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Rubaltelli
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
authors.affiliation: Department of Information Engineering, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Grisan
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015535:Arthritis, Psoriatic / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002469:Cell Separation; D003287:Contrast Media / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D007596:Joints / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D010477:Perfusion; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D003287:Contrast Media; C508717:IL17A protein, human; C508840:IL23A protein, human; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D055651:NK Cell Lectin-Like Receptor Subfamily B
keywords: Imaging ultrasound; Interleukin-17; Psoriatic arthritis; Quantitative imaging; T cells