WORK PACKAGE 7

Quantification of imaging biomarkers

Fifteen INMiND partner institutions from eleven countries (Belgium, Denmark, Finland, France, Germany, Hungary, Italy, Spain, Sweden, The Netherlands, United Kingdom) are involved in the research activities of this work package. Leader of this work package is Adriaan LAMMERTSMA, head of the Department of Radiology & Nuclear Medicine & PET at the VU University Medical Center Amsterdam (The Netherlands).

The main objectives of this work package are:

To develop methods enabling quantification of studies performed in WP5/6/8/9. This is important, as

  • in vivo uptake of a ligand depends on several physiological processes (e.g. delivery, perfusion, extraction, binding to a receptor, non-specific binding, etc.);

  • only binding to a receptor associated with neuroinflammation is relevant and this requires a kinetic model to extract the binding information from imaging data;

  •  quantification is essential for assessment of disease progression and modification by therapy.

WP7 Related papers


Epub ahead of print

Ugga L, Romeo V, Tedeschi E, Brunetti A, Quarantelli M. Superparamagnetic iron oxide nanocolloids in MRI studies of neuroinflammation. J Neurosci Methods. 2018 Jun 18. pii: S0165-0270(18)30181-X; epub ahead of print.
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Yu K, Saam Youshani A, Wilkinson FL, O’Leary C, Cook P, Liao A, Mosses D, Waugh C, Shorrock H, Pathmanaban O, Macdonald A, Kamaly-Asl I, Roncaroli F, Bigger BW. A non-myeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma. Neuropathol Appl Neurobiol. 2018 Apr 20; epub ahead of print.
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2018

Veronese M, Reis Marques T, Bloomfield PS, Rizzo G, Singh N, Jones D, Agushi E, Mosses D, Bertoldo A, Howes O, Roncaroli F, Turkheimer FE. Kinetic modelling of [11C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis. J Cereb Blood Flow Metab. 2018;38(7):1227-1242.
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Wimberley C, Lavisse S, Brulon V, Peyronneau MA, Leroy C, Bodini B, Remy P, Stankoff B, Buvat I, Bottlaender M. Impact of endothelial TSPO on the quantification of 18F-DPA71. J Nucl Med. 2018;59(2):307-314.
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2017

Beliveau V, Ganz M, Feng L, Ozenne B, Højgaard L, Fisher PM, Svarer C, Greve DN, Knudsen GM. A high-resolution in vivo atlas of the human brain's serotonin system. J Neurosci. 2017;37(1):120-128.
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Collste K, Plavén-Sigray P, Fatouros-Bergman H, Victorsson P, Schain M, Forsberg A, Amini N, Aeinehband S; Karolinska Schizophrenia Project (KaSP) consortium., Erhardt S, Halldin C, Flyckt L, Farde L, Cervenka S. Lower levels of the glial cell marker TSPO in drug-naïve first episode psychosis patients as measured using PET and [11C]PBR28. Mol Psychiatry. 2017;22(6):850-856.
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Feng L, Jensen P, Thomsen G, Dyssegaard A, Svarer C, Knudsen LV, Møller K, Thomsen C, Mikkelsen JD, Guilloteau D, Knudsen GM, Pinborg LH. The Variability of Translocator Protein Signal in Brain and Blood of Genotyped Healthy Humans using in vivo [123I]CLINDE-SPECT imaging – a test-retest study.  J Nucl Med. 2017 Jun;58(6):989-995.
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Forsberg A, Cervenka S, Jonsson Fagerlund M, Rasmussen LS, Zetterberg H, Erlandsson Harris H, Stridh P, Christensson E, Granström A, Schening A, Dymmel K, Knave N, Terrando N, Maze M, Borg J, Varrone A, Halldin C, Blennow K, Farde L, Eriksson LI. The immune response of the human brain to abdominal surgery. Ann Neurol. 2017;81(4):572-582.
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Ganz M, Feng L, Hansen HD, Beliveau V, Svarer C, Knudsen GM, Greve DN. Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands. J Cereb Blood Flow Metab. 2017;37(9):3243-3252.
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Golla SS, Timmers T, Ossenkoppele R, Groot C, Verfaillie S, Scheltens P, van der Flier WM, Schwarte L, Mintun MA, Devous M, Schuit RC, Windhorst AD, Lammertsma AA, Boellaard R, van Berckel BN, Yaqub M. Quantification of Tau Load Using [18F]AV1451 PET. Mol Imaging Biol. 2017;19(6):963-971.
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Golla SSV, Lubberink M, van Berckel BNM, Lammertsma AA, Boellaard R. Partial volume correction of brain PET studies using iterative deconvolution in combination with HYPR denois. EJNMMI Res. 2017;7(1):36.
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Van der Aart J, van der Doef TF, Horstman P, Schuit RC, van Lingen A, Windhorst AD, van Berckel BNM, Lammertsma AA. Human Dosimetry of the NMDA Receptor Ligand [11C]GMOM. J Nucl Med. 2017;58(8):1330-1333.
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Willekens SM, Van Weehaeghe D, Van Damme P, Van Laere K. Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks. Eur J Nucl Med Mol Imaging. 2017;44(3):533-547.
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Willekens SM, Van Weehaeghe D, Van Damme P, Van Laere K. Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks. Eur J Nucl Med Mol Imaging. 2017;44(3):533-547.
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2016

Ahmad R, Postnov A, Bormans G, Versijpt J, Vandenbulcke M, Van Laere K. Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2016;43(12):2219-2227.
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Collste K, Forsberg A, Varrone A, Amini N, Aeinehband S, Yakushev I, Halldin C, Farde L, Cervenka S. Test-retest reproducibility of [11C]PBR28 binding to TSPO in healthy control subjects. Eur J Nucl Med Mol Imaging. 2015 Aug 22; epub ahead of print.
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Feng L, Svarer C, Madsen K, Ziebell M, Dyssegaard A, Ettrup A, Hansen HD, Lehel S, Yndgaard S, Paulson OB, Knudsen GM, Pinborg LH. Design of infusion schemes for neuroreceptor imaging: application to [11C]Flumazenil-PET steady-state study. Biomed Res Int. 2016;2016:9132840.
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Golla SS, Boellaard R, Oikonen V, Hoffmann A, van Berckel BN, Windhorst AD, Virta J, Te Beek ET, Groeneveld GJ, Haaparanta-Solin M, Luoto P, Savisto N, Solin O, Valencia R, Thiele A, Eriksson J, Schuit RC, Lammertsma AA, Rinne J. Parametric binding images of the TSPO ligand [18F]DPA-714. J Nucl Med. 2016;57(10):1543-1547.
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Greve DN, Salat DH, Bowen SL, Izquierdo-Garcia D, Schultz AP, Catana C, Becker JA, Svarer C, Knudsen G, Sperling RA, Johnson KA. Different partial volume correction methods lead to different conclusions: an 18F-FDG PET study of aging. Neuroimage. 2016 Feb 23;132:334-343.
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Holmes SE, Hinz R, Drake RJ, Gregory CJ, Conen S, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS. In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study. Mol Psychiatry. 2016;21(12):1672-1679.
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Jonasson M, Wall A, Chiotis K, Saint-Aubert L, Wilking H, Sprycha M, Borg B, Thibblin A, Eriksson JP, Sörensen J, Antoni G, Nordberg A, Lubberink M. Tracer kinetic analysis of (S)-18F-THK5117 as a PET tracer for assessing tau pathology. J Nucl Med. 2016 Apr;57(4):574-81.
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Kanegawa N, Collste K, Forsberg A, Schain M, Arakawa R, Jucaite A, Lekander M, Olgart Höglund C, Kosek E, Lampa J, Halldin C, Farde L, Varrone A, Cervenka S. In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects. Brain Behav Immun. 2016;54:149-57.
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Ory D, Postnov A, Koole M, Celen S, de Laat B, Verbruggen A, Van Laere K, Bormans G, Casteels C. Quantification of TSPO overexpression in a rat model of local neuroinflammation induced by intracerebral injection of LPS by the use of [18F]DPA-714 PET. Eur J Nucl Med Mol Imaging. 2016 Jan;43(1):163-72.
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Rodriguez-Vieitez E, Carter SF, Chiotis K, Saint-Aubert L, Leuzy A, Schöll M, Almkvist O, Wall A, Långström B, Nordberg A. Comparison of Early-Phase 11C-Deuterium-L-Deprenyl and 11C-PiB PET for Assessing Brain Perfusion in Alzheimer's Disease. J Nucl Med. 2016 Jul;57(7):1071-7.
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Thomas C, Vercouillie J, Doméné A, Tauber C, Kassiou M, Guilloteau D, Destrieux C, Sérrière S,  Chalon S. Detection of neuroinflammation in a rat model of subarachnoid hemorrhage  using [18F]DPA-714 PET imaging. Mol Imaging. 2016 ;15. pii: 1536012116639189.
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Van der Doef TF, Golla SS, Klein PJ, Oropeza-Seguias GM, Schuit RC, Metaxas A, Jobse E, Schwarte LA, Windhorst AD, Lammertsma AA, van Berckel BN, Boellaard R. Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man. J Cereb Blood Flow Metab. 2016 Jun;36(6):1111-21.
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Van der Doef TF, de Witte LD, Sutterland AL, Jobse E, Yaqub M, Boellaard R, de Haan L, Eriksson J, Lammertsma AA, Kahn RS, van Berckel BN. In vivo (R)[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ Schizophr. 2016;2:16031.
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2015

Farde L. Spotlight: TSPO binding may also represent ‘resting’ microglia. Clin Transl Imaging. 2015;3(6):491-492.
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Golla SS, Boellaard R, Oikonen V, Hoffmann A, van Berckel BN, Windhorst AD, Virta J, Haaparanta-Solin M, Luoto P, Savisto N, Solin O, Valencia R, Thiele A, Eriksson J, Schuit RC, Lammertsma AA, Rinne JO. Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer’s disease patients. J Cereb Blood Flow Metab. 2015;35(5):766-72.
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Golla SS, Klein PJ, Bakker J, Schuit RC, Christiaans JA, van Geest L, Kooijman EJ, Oropeza-Seguias GM, Langermans JA, Leysen JE, Boellaard R, Windhorst AD, van Berckel BN, Metaxas A. Preclinical evaluation of [18F]PK-209, a new PET ligand for imaging the ion-channel site of NMDA receptors. Nucl Med Biol. 2015;42(2):205-12.
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Hinz R, Boellaard R. Challenges of quantification of TSPO in the human brain. Clinical and Translational Imaging. 2015;3(6):403-416.
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Quarantelli M. MR/MRS in neuroinflammation: Methodology and applications. Clin Transl Imaging. 2015;3:475-489.
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Sérrière S, Tauber C , Vercouillie J, Mothès C, Pruckner C, Guilloteau D, Kassiou M, Doméné A, Garreau L, Page G, Chalon S. Amyloid load and translocator protein 18 kDa in APPswePS1-dE9 mice: a longitudinal study. Neurobiol Aging. 2015;36(4):1639-52.
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Varrone A, Oikonen, V, Forsberg A, Joutsa J, Takano A, Solin O, Haaparanta-Solin M, Nag S, Nakao R, Al-Tawil N, Wells LA, Rabiner EA, Valencia R, Schultze-Mosgau M, Thiele A, Vollmer S, Dyrks T, Lehman L, Heinrich T, Hoffmann A, Nordberg A, Halldin C, Rinne JO. Positron emission tomography imaging of the 18-kDa Translocator Protein (TSPO) with [18F]FEMPA in Alzheimer's disease patients and control subjects. Eur J Nucl Med Mol Imaging. 2015;42(3):438-46.
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Zbib H, Mouysset S, Stute S, Girault JM, Charara J, Chalon S, Galineau L, Buvat I, Tauber C. Unsupervised spectral clustering for segmentation of dynamic PET images. IEEE Trans. Nucl. Sci. 2015;62(3):840-850.
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2014

Feng L, Svarer C, Thomsen G, de Nijs R, Larsen VA, Jensen P, Adamsen D, Dyssegaard A, Fischer W, Meden P, Krieger D, Møller K, Knudsen GM, Pinborg LH. In vivo quantification of cerebral translocator protein binding in humans using 6-chloro-2-(4'-123I-Iodophenyl)-3-/N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT. J Nucl Med. 2014;55(12):1966-72.
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Jaouen V, Gonzalez P, Stute S, Guilloteau D, Chalon S, Buvat I and Tauber C. Variational segmentation of vector-valued images with gradient vector flow. IEEE Trans Image Process. 2014;23(11):4773-85.
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Rissanen E, Tuisku J, Luoto P, Arponen E, Johansson J, Oikonen V, Parkkola R, Airas L, Rinne JO. Automated reference region extraction and population-based input function for brain [(11)C]TMSX PET image analyses. J Cereb Blood Flow Metab. 2015;35(1):157-65.
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Salvatore E, Tedeschi E, Mollica C,  Vicidomini C, Varrone A, Coda ARD, Brunetti A, Salvatore M, De Michele G, FIlla A, Pappatà S. Supratentorial and infratentorial damage in spinocerebellar ataxia 2: A diffusion-weighted MRI study. Mov Disord. 2014;29(6):780-6.
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Sérrière S, Tauber C, Vercouillie J, Guilloteau D, Deloye JB, Garreau L, Galineau L, Chalon S. In vivo PET quantification of the dopamine transporter in rat brain with [¹⁸F]LBT-999. Nucl Med Biol. 2014;41(1):106-13.
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2013

Boutin H, Prenant C, Maroy R, Galea J, Greenhalgh AD, Smigova A, Cawthorne C, Julyan P, Wilkinson SM, Banister SD, Brown G, Herholz K, Kassiou M, Rothwell NJ. [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. PLoS One. 2013;8(2):e56441.
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Casteels C, Vunckx K, Aelvoet SA, Baekelandt V, Bormans G, Van Laere K, Koole M. Construction and evaluation of quantitative small-animal PET probabilistic atlases for [¹⁸F]FDG and [¹⁸F]FECT functional mapping of the mouse brain. PLoS One. 2013;8(6):e65286.
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Mouysset S, Zbib H, Stute S, Girault JM, Charara J, Noailles J, Chalon S, Buvat I, Tauber C. Segmentation of dynamic PET images with kinetic spectral clustering. Phys Med Biol. 2013;58(19):6931-44.
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2012

Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B, Boisgard R. Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [¹⁸F]DPA-714. J Neurosci. 2012;32(17):5728-36.
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Bandi P, Zsoter N, Koncz P, Babos M, Hobor S, Mathé D, Papp L. Automated material map generation from MRI scout pairs for preclinical PET attenuation correction. Conf Proc IEEE Eng Med Biol Soc. 2012;2012:5351-4.
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Corcia P, Tauber C, Vercoullie J, Arlicot N, Prunier C, Praline J, Nicolas G, Venel Y, Hommet C, Baulieu JL, Cottier JP, Roussel C, Kassiou M, Guilloteau D, Ribeiro MJ. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941.
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Jacobs AH, Tavitian B; INMiND consortium. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab. 2012;32(7):1393-415.
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Yaqub M, van Berckel BN, Schuitemaker A, Hinz R, Turkheimer FE, Tomasi G, Lammertsma AA, Boellaard R. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies. J Cereb Blood Flow Metab. 2012;32(8):1600-8.
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