WORK PACKAGE 6

In vivo monitoring of NI, ND and endoNSC interactions in animal models and of the effect of M1/M2 conversion modulators in animal models

Twelve INMiND partner institutions from eight countries (Belgium, Finland, France, Germany, Hungary, Italy, Sweden, United Kingdom) are involved in the research activities of this work package. Leader of this work package is Annemie VAN DER LINDEN, head of the Bio-Imaing Lab at the University of Antwerp (Belgium).

The main objectives of this work package are:

Full characterization of NI, ND and endoNSC involvement using in vivo imaging tools (including optimised and validated new tools from WP5) in the same animal model to study:

  • the interaction between NI, ND and endoNSC in different disease models longitudinally;

  • the effect of therapeutics;

  • the effect of molecular modulators of M1/M2 conversion discovered in WP1/2 on NI, ND and endoNSC migration/multiplication.

WP6 Related papers


Epub ahead of print

Belloy ME, Naeyaert M, Abbas A, Shah D, Vanreusel V, van Audekerke J, Keilholz SD, Keliris GA, Van der Linden A, Verhoye M. Dynamic resting state fMRI analysis in mice reveals a set of Quasi-Periodic Patterns and illustrates their relationship with the global signal. Neuroimage. 2018 Feb 15. pii: S1053-8119(18)30075-2; epub ahead of print.
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Takkinen JS, López-Picón FR, Kirjavainen AK, Pihlaja R, Snellman A, Ishizu T, Löyttyniemi E, Solin O, Rinne JO, Haaparanta-Solin M. [18F]FMPEP-d2 PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease. Neurobiol Aging. 2018 May 18;69:199-208; epub ahead of print.
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2018

Beckers L, Ory D, Geric I, Declercq L, Koole M, Kassiou M, Bormans G, Baes M. Increased expression of translocator protein (TSPO) marks pro-inflammatory microglia but does not predict neurodegeneration. Mol Imaging Biol. 2018;20(1):94-102.
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Belloli S, Zanotti L, Murtaj V, Mazzon C, Di Grigoli G, Monterisi C, Masiello V, Iaccarino L, Cappelli A, Poliani PL, Politi LS, Moresco RM. (18)F-VC701-PET and MRI in the in vivo neuroinflammation assessment of a mouse model of multiple sclerosis. J Neuroinflammation. 2018;15(1):33.
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Chaney A, Bauer M, Bochicchio D, Smigova A, Kassiou M, Davies KE, Williams SR, Boutin H. Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe ×PS1Δe9 transgenic mouse model of Alzheimer's disease. J Neurochem. 2018;144(3):318-335.
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Crabbé M, Van der Perren A, Weerasekera A, Himmelreich U, Baekelandt V, Van Laere K, Casteels C. Altered mGluR5 binding potential and glutamine concentration in the 6-OHDA rat model of acute Parkinson’s disease and levodopa-induced dyskinesia. Neurobiol Aging. 2018;61:82-92.
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Foucault-Fruchard L, Tronel C, Bodard S, Gulhan Z, Busson J, Chalon S, Antier D. Involvement of heme oxygenase-1 in neuroprotective effects induced by an alpha 7 nicotinic receptor agonist in a rat model of brain excitotoxicity. Neural Regen Res. 2018;13(4):737-741.
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López-Picón FR, Snellman A, Eskola O, Helin S, Solin O, Haaparanta-Solin M, Rinne JO. Neuroinflammation appears early and then plateaus in a mouse model of Alzheimer's disease shown by PET imaging. J Nucl Med. 2018;59(3):509-515.
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Shah D, Latif Hernandez A, De Strooper B, Saito T, Verhoye M, D’Hooge R, Van der Linden A. Premature defects in spatial reversal learning coincide with hypersynchronous telencephalic BOLD functional connectivity in APPNL-F/NL-F knock-in mice. Sci Rep. 2018;8(1):6264.
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2017

Airas L, Rissanen E, Rinne J. Imaging of microglial activation in MS using PET: Research use and potential future clinical application. Mult Scler. 2017;23(4):496-504.
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Bertoglio D, Verhaeghe J, Santermans E, Amhaoul H, Jonckers E, Wyffels L, Van Der Linden A, Hens N, Staelens S, Dedeurwaerdere S. Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities. Brain Behav Immun. 2017;61:69-79.
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Cerami C, Iaccarino L, Perani D. Molecular imaging of neuroinflammation in neurodegenerative dementias: The role of in vivo PET imaging. Int J Mol Sci. 2017;18(5).
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Gargiulo S, Coda AR, Panico M, Gramanzini M, Moresco RM, Chalon S, Pappatà S. Molecular imaging of neuroinflammation in preclinical rodent models using positron emission tomography. Q J Nucl Med Mol Imaging 2017;61:60-75.
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Keller T, Krzyczmonik A, Forsback S, López Picón FR, Kirjavainen AK, Takkinen J, Rajander J, Cacheux F, Damont A, Dollé F, Rinne JO, Haaparanta-Solin M, Solin O. Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, a Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in healthy Sprague Dawley rats.
Mol Imaging Biol. 2017;19(5):736-745.
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Libbrecht S, Van den Haute C, Malinouskaya L, Gijsbers R, Baekelandt V. Evaluation of WGA-Cre-dependent topological transgene expression in the rodent brain. Brain Struct Funct. 2017;222(2):717-733.
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Pihlaja R, Haaparanta-Solin M, Rinne JO. The anti-inflammatory effects of lipoxygenase and cyclo-oxygenase inhibitors in inflammation-induced human fetal glia cells and the Aβ degradation capacity of human fetal astrocytes in an ex vivo assay. Front Neurosci. 2017;11:299.
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Struys T, Govaerts K, Oosterlinck W, Casteels C, Bronckaers A, Koole M, Van Laere K, Herijgers P, Lambrichts I, Himmelreich U, Dresselaers T. In vivo evidence for long-term vascular remodeling resulting from chronic cerebral hypoperfusion in mice. J Cereb Blood Flow Metab 2017; 37(2): 726-739.
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Takkinen JS, López-Picón FR, Al Majidi R, Eskola O, Krzyczmonik A, Keller T, Löyttyniemi E, Solin O, Rinne JO, Haaparanta-Solin M. Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging.  J Cereb Blood Flow Metab. 2017;37(8):2870-2882.
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Wijasa TS, Sylvester M, Brocke-Ahmadinejad N, Kummer MP, Brosseron F, Gieselmann V, Heneka MT. Proteome profiling of s-nitrosylated synaptosomal proteins by isobaric mass tags. J Neurosci Methods. 2017;291:95-100.
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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

Blockx I, Einstein S, Guns PJ, Van Audekerke J, Guglielmetti C, Zago W, Roose D, Verhoye M, Van der Linden A, Bard F. Monitoring blood-brain barrier integrity following amyloid-beta immunotherapy using Gadolinium-enhanced MRI in a PDAPP mouse model. J Alzheimers Dis. 2016;54(2):723-35.
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Fricke IB, Viel T, Worlitzer MM, Collmann FM, Vrachimis A, Faust A, Wachsmuth L, Faber C, Dollé F, Kuhlmann MT, Schäfers K, Hermann S, Schwamborn JC, Jacobs AH. 6-hydroxydopamine-induced Parkinson’s disease-like degeneration generates acute micro- and astrogliosis in the nigrostriatal system but no Bioluminescence Imaging detectable alteration in adult neurogenesis. Eur J Neurosci. 2016;43(10):1352-65.
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Gargiulo S, Anzilotti S, Coda AR, Gramanzini M, Greco A, Panico M, Vinciguerra A, Zannetti A, Vicidomini C, Dollé F, Pignataro G, Quarantelli M, Annunziato L, Brunetti A, Salvatore M, Pappatà S. Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with 18F-DPA-714 and micro-PET/CT. Eur J Nucl Med Mol Imaging. 2016;43(7):1348-59.
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Guglielmetti C, Le Blon D, Santermans E, Salas-Perdomo A, Daans J, De Vocht N, Shah D, Hoornaert C, Praet J, Peerlings J, Kara F, Bigot C, Mai Z, Goossens H, Hens N, Hendrix S, Verhoye M, Planas AM, Berneman Z, van der Linden A, Ponsaerts P. Interleukin-13 immune gene therapy prevents CNS inflammation and demyelination via alternative activation of microglia and macrophages. Glia. 2016;64(12):2181-2200.
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Guglielmetti C, Veraart J, Roelant E, Mai Z, Daans J, Van Audekerke J, Naeyaert M, Vanhoutte G, Delgado Y Palacios R, Praet J, Fieremans E, Ponsaerts P, Sijbers J, Van der Linden A, Verhoye M. Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination. Neuroimage. 2016;125:363-77.
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Le Blon D, Guglielmetti C, Hoornaert C, Quarta A, Daans J, Dooley D, Lemmens E, Praet J, De Vocht N, Reekmans K, Santermans E, Hens N, Goossens H, Verhoye M, Van der Linden A, Berneman Z1, Hendrix S, Ponsaerts P. Intracerebral transplantation of interleukin 13-producing mesenchymal stem cells limits microgliosis, oligodendrocyte loss and demyelination in the cuprizone mouse model. J Neuroinflammation. 2016;13(1):288.
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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;43(1):163-72.
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Praet J, Bigot C, Orije J, Naeyaert M, Shah D, Mai Z, Guns PJ, Van der Linden A, Verhoye M. Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model. Neuroimage Clin. 2016;12:85-92.
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Shah D, Blockx I, Keliris GA, Kara F, Jonckers E, Verhoye M, Van der Linden A. Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain. Brain Struct Funct. 2016;221(6):3067-79.
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Shah D, Deleye S, Verhoye M, Staelens S, Van der Linden A. Resting-state functional MRI and [18F]-FDG PET demonstrate differences in neuronal activity between commonly used mouse strains. Neuroimage. 2016;125:571-7.
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Shah D, Praet J, Latif Hernandez A, Höfling C, Anckaerts C, Bard F, Morawski M, Detrez JR, Prinsen E, Villa A, De Vos WH, Maggi A, D'Hooge R, Balschun D, Rossner S, Verhoye M, Van der Linden A. Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition. Alzheimers Dement. 2016;12(9):964-76.
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2015

Airas L, Dickens AM, Elo P, Marjamäki P, Johansson J, Eskola O, Jones PA, Trigg W, Solin O, Haaparanta-Solin M, Anthony DC, Rinne J. In vivo PET imaging demonstrates diminished microglial activation after fingolimod treatment in an animal model of multiple sclerosis. J Nucl Med. 2015;56(2):305-10.
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Amhaoul H, Hamaide J, Bertoglio D, Reichel SN, Verhaeghe J, Geerts E, Van Dam D, De Deyn PP, Kumar-Singh S, Katsifis A, Van Der Linden A, Staelens S, Dedeurwaerdere S. Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis. Neurobiol Dis. 2015;82:526-39.
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Di Grigoli G, Monterisi C, Belloli S, Masiello V, Politi LS, Valenti S, Paolino M, Anzini M, Matarrese M, Cappelli A, Moresco RM. Radiosynthesis and preliminary biological evaluation of [18F]VC701, a radioligand for translocator protein. Mol Imaging. 2015;14:1535-3508.
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Farde L. Spotlight: TSPO binding may also represent ‘resting’ microglia. Clin Transl Imaging. 2015;3(6):491-492.
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Jonckers E, Shah D, Hamaide J, Verhoye M, Van der Linden A. The power of using functional fMRI on small rodents to study brain pharmacology and disease. Front Pharmacol. 2015;6:231.
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Praet J, Orije J, Kara F, Guglielmetti C, Santermans E, Daans J, Hens N, Verhoye M, Berneman Z, Ponsaerts P, Van der Linden A. Cuprizone-induced demyelination and demyelination-associated inflammation result in different proton magnetic resonance metabolite spectra. NMR Biomed. 2015;28(4):505-13.
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Praet J, Santermans E, Daans J, Le Blon D, Hoornaert C, Goossens H, Hens N, Van der Linden A, Berneman Z, Ponsaerts P. Early inflammatory responses following cell grafting in the CNS trigger activation of the sub-ventricular zone: a proposed model of sequential cellular events. Cell Transplantation. 2015;24(8):1481-92.
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Rodriguez-Vieitez E, Ni R, Gulyás B, Tóth M, Häggkvist J, Halldin C, Voytenko L, Marutle A, Nordberg A. Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study. Eur J Nucl Med Mol Imaging. 2015;42(7):1119-32.
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Shah D, Blockx I, Guns PJ, De Deyn PP, Van Dam D, Jonckers E, Delgado YPR, Verhoye M, Van der Linden A. Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI. Neuroimage. 2015;109:151-9.
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Van der Perren A, Macchi F, Toelen J, Carlon MS, Maris M, de Loor H, Kuypers DR, Gijsbers R, Van den Haute C, Debyser Z, Baekelandt V. FK506 reduces neuroinflammation and dopaminergic  neurodegeneration in an alpha-synuclein-based rat model for Parkinson's disease. Neurobiol Aging. 2015;36(3):1559-68.
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Van der Perren A, Toelen J, Casteels C, Macchi F, Van Rompuy AS, Sarre S, Casadei N, Nuber S, Himmelreich U, Osorio Garcia MI, Michotte Y, D’Hooge R, Bormans G, Van Laere K, Gijsbers R, Van den Haute C, Debyser Z, Baekelandt V. Longitudinal follow-up and characterization of a robust rat model for Parkinson’s disease based on overexpression of alpha-synuclein with adeno-associated viral vectors. Neurobiol Aging. 2015;36(3):1543-58.
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Verkhratsky A, Marutle A, Rodriguez-Arellano JJ, Nordberg A. Glial asthenia and functional paralysis: a new perspective on neurodegeneration and Alzheimer´s disease. Neuroscientist. 2015;21(5):552-568.
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Waldron AM, Verhaeghe J, Wyffels L, Schmidt M, Langlois X, Van Der Linden A, Stroobants S, Staelens S. Preclinical comparison of the amyloid-β radioligands [11C]Pittsburgh compound B and [18F]florbetaben in aged APPPS1-21 and BRI1-42 mouse models of cerebral amyloidosis. Mol Imaging Biol. 2015;17(5):688-96.
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Zinnhardt B, Viel T, Wachsmuth L, Vrachimis A, Wagner S, Breyholz HJ, Faust A, Hermann S, Kopka K, Faber C, Dollé F, Pappata S, Planas AM, Tavitian B, Schäfers M, Sorokin LM, Kuhlmann MT, Jacobs AH. Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke.  J Cereb Blood Flow Metab. 2015;35(11):1711-21.
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2014

Aelvoet SA, Ibrahimi A, Macchi F, Gijsbers R, Van den Haute C, Debyser Z, Baekelandt V. Non-invasive bioluminescence imaging of alpha-synuclein oligomerization in mouse brain using split firefly luciferase reporters. J Neurosci. 2014;34(49):16518-32.
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Dickens AM, Vainio S, Marjamäki P, Johansson J, Lehtiniemi P, Rokka J, Rinne J, Solin O, Haaparanta-Solin M, Jones PA, Trigg W, Anthony DC, Airas L. Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med. 2014;55(3):466-72.
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Guglielmetti C, Praet J, Rangarajan JR, Vreys R, De Vocht N, Maes F, Verhoye M, Ponsaerts P, Van der Linden A. Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum. Neuroimage. 2014;86:99-110.
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Jonckers E, Delgado y Palacios R, Shah D, Guglielmetti C, Verhoye M, Van Der Linden A. Different anesthesia regimes modulate the functional connectivity outcome in mice. Magn Reson Med. 2014;72(4):1103-12.
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Ooms M, Rietjens R, Rangarajan JR, Vunckx K, Valdeolivas S, Maes F, Himmelreich U, Fernandez-Ruiz J, Bormans G, Van Laere K, Casteels C. Early decrease of type 1 cannabinoid receptor binding and phosphodiesterase 10A activity in vivo in R6/2 Huntington mice. Neurobiol Aging. 2014;35(12):2858-69.
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Praet J, Guglielmetti C, Berneman Z, Van der Linden A, Ponsaerts P. Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis. Neurosci Biobehav Rev. 2014;47:485-505.
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Snellman A, Rokka J, López-Picón F, Eskola O, Salmona M, Forloni G, Scheinin M, Solin O, Rinne JO, Haaparanta-Solin M. In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimer's disease with a high specific activity PET imaging agent [18F]flutemetamol. EJNMMI Research 2014;4:37
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Vandeputte C, Reumers V, Aelvoet SA, Thiry I, De Swaef S, Van Den Haute C, Pascual-Brazo J, Farr TD, Vande Velde G, Hoehn M, Himmelreich U, Van Laere K, Debyser Z, Gijsbers R, Baekelandt V. Bioluminescence imaging of stroke-induced neural stem cell response. Neurobiol Dis. 2014;69:144-55.
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2013

Sekar S, Jonckers E, Verhoye M, Willems R, Veraart J, Van Audekerke J, Couto J, Giugliano M, Wuyts K, Dedeurwaerdere S, Sijbers J, Mackie C, Ver Donck L, Steckler T, Van der Linden A. Subchronic memantine induced concurrent functional disconnectivity and altered ultra-structural tissue integrity in the rodent brain: revealed by multimodal MRI. Psychopharmacology (Berl). 2013;227(3):479-91.
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2012

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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