18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression

Trine P Ludvigsen; Sune F Pedersen; Andreas Vegge; Rasmus S Ripa; Helle H Johannesen; Adam E Hansen; Johan Löfgren; Camilla Schumacher-Petersen; Rikke K. Kirk; Henrik D Pedersen; Berit Ø Christoffersen; Mathilde Ørbæk; Julie L Forman; Thomas L Klausen; Lisbeth H Olsen; Andreas Kjaer

doi:10.1016/j.atherosclerosis.2019.04.209

¹⁸F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression

Trine P Ludvigsen, Sune F Pedersen, Andreas Vegge, Rasmus S Ripa, Helle H Johannesen, Adam E Hansen, Johan Löfgren, Camilla Schumacher-Petersen, Rikke K. Kirk, Henrik D Pedersen, Berit Ø Christoffersen, Mathilde Ørbæk, Julie L Forman, Thomas L Klausen, Lisbeth H Olsen, Andreas Kjaer

5 Citations (Scopus)

Abstract

Background and aims: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis. Methods: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, ¹⁸ F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression. Results: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBR _Max (95% confidence interval) CI _TBRMax : 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CI _TBRMax : -5.94;-0.07). No difference was observed between DNO and Control (CI _TBRMax : −2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρ _s = 0.58; MMP9, ρ _s = 0.46; SPP1, ρ _s = 0.44 and CTSK, ρ _s = 0.49; (p ≤ 0.01 for all). Conclusions: In a model of atherosclerosis, ¹⁸ F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.

Original language	English
Journal	Atherosclerosis
Volume	285
Pages (from-to)	55-63
Number of pages	9
ISSN	0021-9150
DOIs	https://doi.org/10.1016/j.atherosclerosis.2019.04.209
Publication status	Published - Jun 2019

Access to Document

10.1016/j.atherosclerosis.2019.04.209

Cite this

Ludvigsen, T. P., Pedersen, S. F., Vegge, A., Ripa, R. S., Johannesen, H. H., Hansen, A. E., Löfgren, J., Schumacher-Petersen, C., Kirk, R. K., Pedersen, H. D., Christoffersen, B. Ø., Ørbæk, M., Forman, J. L., Klausen, T. L., Olsen, L. H., & Kjaer, A. (2019). ¹⁸F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression. Atherosclerosis, 285, 55-63. https://doi.org/10.1016/j.atherosclerosis.2019.04.209

Ludvigsen, TP, Pedersen, SF, Vegge, A, Ripa, RS, Johannesen, HH, Hansen, AE, Löfgren, J, Schumacher-Petersen, C, Kirk, RK, Pedersen, HD, Christoffersen, BØ, Ørbæk, M, Forman, JL, Klausen, TL, Olsen, LH & Kjaer, A 2019, '¹⁸F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression', Atherosclerosis, vol. 285, pp. 55-63. https://doi.org/10.1016/j.atherosclerosis.2019.04.209

@article{8863dea6a4394438bf98e888469a1f67,

title = "18F-FDG PET/MR-imaging in a G{\"o}ttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression",

abstract = " Background and aims: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis. Methods: G{\"o}ttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18 F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression. Results: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBR Max (95% confidence interval) CI TBRMax : 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CI TBRMax : -5.94;-0.07). No difference was observed between DNO and Control (CI TBRMax : −2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρ s = 0.58; MMP9, ρ s = 0.46; SPP1, ρ s = 0.44 and CTSK, ρ s = 0.49; (p ≤ 0.01 for all). Conclusions: In a model of atherosclerosis, 18 F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation. ",

author = "Ludvigsen, {Trine P} and Pedersen, {Sune F} and Andreas Vegge and Ripa, {Rasmus S} and Johannesen, {Helle H} and Hansen, {Adam E} and Johan L{\"o}fgren and Camilla Schumacher-Petersen and Kirk, {Rikke K.} and Pedersen, {Henrik D} and Christoffersen, {Berit {\O}} and Mathilde {\O}rb{\ae}k and Forman, {Julie L} and Klausen, {Thomas L} and Olsen, {Lisbeth H} and Andreas Kjaer",

note = "Copyright {\textcopyright} 2019. Published by Elsevier B.V.",

year = "2019",

month = jun,

doi = "10.1016/j.atherosclerosis.2019.04.209",

language = "English",

volume = "285",

pages = "55--63",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - 18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis

T2 - Correlations with histology and quantitative gene expression

AU - Ludvigsen, Trine P

AU - Pedersen, Sune F

AU - Vegge, Andreas

AU - Ripa, Rasmus S

AU - Johannesen, Helle H

AU - Hansen, Adam E

AU - Löfgren, Johan

AU - Schumacher-Petersen, Camilla

AU - Kirk, Rikke K.

AU - Pedersen, Henrik D

AU - Christoffersen, Berit Ø

AU - Ørbæk, Mathilde

AU - Forman, Julie L

AU - Klausen, Thomas L

AU - Olsen, Lisbeth H

AU - Kjaer, Andreas

PY - 2019/6

Y1 - 2019/6

N2 - Background and aims: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis. Methods: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18 F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression. Results: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBR Max (95% confidence interval) CI TBRMax : 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CI TBRMax : -5.94;-0.07). No difference was observed between DNO and Control (CI TBRMax : −2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρ s = 0.58; MMP9, ρ s = 0.46; SPP1, ρ s = 0.44 and CTSK, ρ s = 0.49; (p ≤ 0.01 for all). Conclusions: In a model of atherosclerosis, 18 F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.

AB - Background and aims: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis. Methods: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18 F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression. Results: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBR Max (95% confidence interval) CI TBRMax : 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CI TBRMax : -5.94;-0.07). No difference was observed between DNO and Control (CI TBRMax : −2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρ s = 0.58; MMP9, ρ s = 0.46; SPP1, ρ s = 0.44 and CTSK, ρ s = 0.49; (p ≤ 0.01 for all). Conclusions: In a model of atherosclerosis, 18 F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.

U2 - 10.1016/j.atherosclerosis.2019.04.209

DO - 10.1016/j.atherosclerosis.2019.04.209

M3 - Journal article

C2 - 31004968

SN - 0021-9150

VL - 285

SP - 55

EP - 63

JO - Atherosclerosis

JF - Atherosclerosis

ER -

18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression

Abstract

Access to Document

Fingerprint

Cite this

¹⁸F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression