Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia
Reactive microgliosis is an important pathological component of neuroinflammation and has been implicated in a wide range of brain diseases including brain tumors, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Mapping reactive microglia in-vivo is often performed w...
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description | Reactive microgliosis is an important pathological component of neuroinflammation and has been implicated in a wide range of brain diseases including brain tumors, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Mapping reactive microglia
in-vivo
is often performed with PET scanning whose resolution, cost, and availability prevent its widespread use. The advent of diffusion compartment imaging (DCI) to probe tissue microstructure
in vivo
holds promise to map reactive microglia using MRI scanners. But this potential has never been demonstrated. In this paper, we performed longitudinal DCI in rats that underwent dorsal root axotomy triggering Wallerian degeneration of axons—a pathological process which reliably activates microglia. After the last DCI at 51 days, rats were sacrificed and histology with Iba-1 immunostaining for microglia was performed. The fraction of extra-axonal restricted diffusion from DCI was found to follow the expected temporal dynamics of reactive microgliosis. Furthermore, a strong and significant correlation between this parameter and histological measurement of microglial density was observed. These findings strongly suggest that extra-axonal restricted diffusion is an
in-vivo
marker of reactive microglia. They pave the way for MRI-based microglial mapping which may be important to characterize the pathogenesis of neurological and psychiatric diseases. |
doi_str_mv | 10.1038/s41598-019-50432-5 |
format | Article |
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in-vivo
is often performed with PET scanning whose resolution, cost, and availability prevent its widespread use. The advent of diffusion compartment imaging (DCI) to probe tissue microstructure
in vivo
holds promise to map reactive microglia using MRI scanners. But this potential has never been demonstrated. In this paper, we performed longitudinal DCI in rats that underwent dorsal root axotomy triggering Wallerian degeneration of axons—a pathological process which reliably activates microglia. After the last DCI at 51 days, rats were sacrificed and histology with Iba-1 immunostaining for microglia was performed. The fraction of extra-axonal restricted diffusion from DCI was found to follow the expected temporal dynamics of reactive microgliosis. Furthermore, a strong and significant correlation between this parameter and histological measurement of microglial density was observed. These findings strongly suggest that extra-axonal restricted diffusion is an
in-vivo
marker of reactive microglia. They pave the way for MRI-based microglial mapping which may be important to characterize the pathogenesis of neurological and psychiatric diseases.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-50432-5</identifier><identifier>PMID: 31554896</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>59 ; 59/57 ; 631/378/1689 ; 692/308/53/2421 ; Alzheimer's disease ; Animals ; Axons ; Axons - pathology ; Axotomy ; Brain cancer ; Brain diseases ; Brain Diseases - pathology ; Brain tumors ; Diffusion ; Dorsal roots ; Female ; Histology ; Humanities and Social Sciences ; Inflammation ; Magnetic resonance imaging ; Magnetic Resonance Imaging - methods ; Mental disorders ; Microglia ; Microglia - pathology ; Movement disorders ; multidisciplinary ; Multiple sclerosis ; Neurodegeneration ; Neurodegenerative diseases ; Neuroimaging ; Parkinson's disease ; Pathogenesis ; Positron emission tomography ; Rats ; Rats, Long-Evans ; Rodents ; Schizophrenia ; Science ; Science (multidisciplinary) ; Spinal cord ; Tumors ; Wallerian Degeneration - pathology</subject><ispartof>Scientific reports, 2019-09, Vol.9 (1), p.13874-10, Article 13874</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-41640429f1a2b72810be7f41b2234aac1279424b24baf4b0fa8eee73c478fdab3</citedby><cites>FETCH-LOGICAL-c474t-41640429f1a2b72810be7f41b2234aac1279424b24baf4b0fa8eee73c478fdab3</cites><orcidid>0000-0002-7659-3880</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761095/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761095/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,41119,42188,51575,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31554896$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taquet, Maxime</creatorcontrib><creatorcontrib>Jankovski, Aleksandar</creatorcontrib><creatorcontrib>Rensonnet, Gaëtan</creatorcontrib><creatorcontrib>Jacobs, Damien</creatorcontrib><creatorcontrib>des Rieux, Anne</creatorcontrib><creatorcontrib>Macq, Benoît</creatorcontrib><creatorcontrib>Warfield, Simon K.</creatorcontrib><creatorcontrib>Scherrer, Benoît</creatorcontrib><title>Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Reactive microgliosis is an important pathological component of neuroinflammation and has been implicated in a wide range of brain diseases including brain tumors, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Mapping reactive microglia
in-vivo
is often performed with PET scanning whose resolution, cost, and availability prevent its widespread use. The advent of diffusion compartment imaging (DCI) to probe tissue microstructure
in vivo
holds promise to map reactive microglia using MRI scanners. But this potential has never been demonstrated. In this paper, we performed longitudinal DCI in rats that underwent dorsal root axotomy triggering Wallerian degeneration of axons—a pathological process which reliably activates microglia. After the last DCI at 51 days, rats were sacrificed and histology with Iba-1 immunostaining for microglia was performed. The fraction of extra-axonal restricted diffusion from DCI was found to follow the expected temporal dynamics of reactive microgliosis. Furthermore, a strong and significant correlation between this parameter and histological measurement of microglial density was observed. These findings strongly suggest that extra-axonal restricted diffusion is an
in-vivo
marker of reactive microglia. They pave the way for MRI-based microglial mapping which may be important to characterize the pathogenesis of neurological and psychiatric diseases.</description><subject>59</subject><subject>59/57</subject><subject>631/378/1689</subject><subject>692/308/53/2421</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Axons</subject><subject>Axons - pathology</subject><subject>Axotomy</subject><subject>Brain cancer</subject><subject>Brain diseases</subject><subject>Brain Diseases - pathology</subject><subject>Brain tumors</subject><subject>Diffusion</subject><subject>Dorsal roots</subject><subject>Female</subject><subject>Histology</subject><subject>Humanities and Social Sciences</subject><subject>Inflammation</subject><subject>Magnetic resonance imaging</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Mental disorders</subject><subject>Microglia</subject><subject>Microglia - pathology</subject><subject>Movement disorders</subject><subject>multidisciplinary</subject><subject>Multiple sclerosis</subject><subject>Neurodegeneration</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Parkinson's disease</subject><subject>Pathogenesis</subject><subject>Positron emission tomography</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Rodents</subject><subject>Schizophrenia</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Spinal cord</subject><subject>Tumors</subject><subject>Wallerian Degeneration - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taquet, Maxime</au><au>Jankovski, Aleksandar</au><au>Rensonnet, Gaëtan</au><au>Jacobs, Damien</au><au>des Rieux, Anne</au><au>Macq, Benoît</au><au>Warfield, Simon K.</au><au>Scherrer, Benoît</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-09-25</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>13874</spage><epage>10</epage><pages>13874-10</pages><artnum>13874</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Reactive microgliosis is an important pathological component of neuroinflammation and has been implicated in a wide range of brain diseases including brain tumors, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Mapping reactive microglia
in-vivo
is often performed with PET scanning whose resolution, cost, and availability prevent its widespread use. The advent of diffusion compartment imaging (DCI) to probe tissue microstructure
in vivo
holds promise to map reactive microglia using MRI scanners. But this potential has never been demonstrated. In this paper, we performed longitudinal DCI in rats that underwent dorsal root axotomy triggering Wallerian degeneration of axons—a pathological process which reliably activates microglia. After the last DCI at 51 days, rats were sacrificed and histology with Iba-1 immunostaining for microglia was performed. The fraction of extra-axonal restricted diffusion from DCI was found to follow the expected temporal dynamics of reactive microgliosis. Furthermore, a strong and significant correlation between this parameter and histological measurement of microglial density was observed. These findings strongly suggest that extra-axonal restricted diffusion is an
in-vivo
marker of reactive microglia. They pave the way for MRI-based microglial mapping which may be important to characterize the pathogenesis of neurological and psychiatric diseases.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31554896</pmid><doi>10.1038/s41598-019-50432-5</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7659-3880</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 59 59/57 631/378/1689 692/308/53/2421 Alzheimer's disease Animals Axons Axons - pathology Axotomy Brain cancer Brain diseases Brain Diseases - pathology Brain tumors Diffusion Dorsal roots Female Histology Humanities and Social Sciences Inflammation Magnetic resonance imaging Magnetic Resonance Imaging - methods Mental disorders Microglia Microglia - pathology Movement disorders multidisciplinary Multiple sclerosis Neurodegeneration Neurodegenerative diseases Neuroimaging Parkinson's disease Pathogenesis Positron emission tomography Rats Rats, Long-Evans Rodents Schizophrenia Science Science (multidisciplinary) Spinal cord Tumors Wallerian Degeneration - pathology |
title | Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia |
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