Cargando…

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combinat...

Descripción completa

Detalles Bibliográficos
Autores principales: Holmes, Holly E., Powell, Nick M., Ma, Da, Ismail, Ozama, Harrison, Ian F., Wells, Jack A., Colgan, Niall, O'Callaghan, James M., Johnson, Ross A., Murray, Tracey K., Ahmed, Zeshan, Heggenes, Morten, Fisher, Alice, Cardoso, M. Jorge, Modat, Marc, O'Neill, Michael J., Collins, Emily C., Fisher, Elizabeth M. C., Ourselin, Sébastien, Lythgoe, Mark F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374887/
https://www.ncbi.nlm.nih.gov/pubmed/28408879
http://dx.doi.org/10.3389/fninf.2017.00020
_version_ 1782518971051802624
author Holmes, Holly E.
Powell, Nick M.
Ma, Da
Ismail, Ozama
Harrison, Ian F.
Wells, Jack A.
Colgan, Niall
O'Callaghan, James M.
Johnson, Ross A.
Murray, Tracey K.
Ahmed, Zeshan
Heggenes, Morten
Fisher, Alice
Cardoso, M. Jorge
Modat, Marc
O'Neill, Michael J.
Collins, Emily C.
Fisher, Elizabeth M. C.
Ourselin, Sébastien
Lythgoe, Mark F.
author_facet Holmes, Holly E.
Powell, Nick M.
Ma, Da
Ismail, Ozama
Harrison, Ian F.
Wells, Jack A.
Colgan, Niall
O'Callaghan, James M.
Johnson, Ross A.
Murray, Tracey K.
Ahmed, Zeshan
Heggenes, Morten
Fisher, Alice
Cardoso, M. Jorge
Modat, Marc
O'Neill, Michael J.
Collins, Emily C.
Fisher, Elizabeth M. C.
Ourselin, Sébastien
Lythgoe, Mark F.
author_sort Holmes, Holly E.
collection PubMed
description With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.
format Online
Article
Text
id pubmed-5374887
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-53748872017-04-13 Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy Holmes, Holly E. Powell, Nick M. Ma, Da Ismail, Ozama Harrison, Ian F. Wells, Jack A. Colgan, Niall O'Callaghan, James M. Johnson, Ross A. Murray, Tracey K. Ahmed, Zeshan Heggenes, Morten Fisher, Alice Cardoso, M. Jorge Modat, Marc O'Neill, Michael J. Collins, Emily C. Fisher, Elizabeth M. C. Ourselin, Sébastien Lythgoe, Mark F. Front Neuroinform Neuroscience With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes. Frontiers Media S.A. 2017-03-31 /pmc/articles/PMC5374887/ /pubmed/28408879 http://dx.doi.org/10.3389/fninf.2017.00020 Text en Copyright © 2017 Holmes, Powell, Ma, Ismail, Harrison, Wells, Colgan, O'Callaghan, Johnson, Murray, Ahmed, Heggenes, Fisher, Cardoso, Modat, O'Neill, Collins, Fisher, Ourselin and Lythgoe. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Holmes, Holly E.
Powell, Nick M.
Ma, Da
Ismail, Ozama
Harrison, Ian F.
Wells, Jack A.
Colgan, Niall
O'Callaghan, James M.
Johnson, Ross A.
Murray, Tracey K.
Ahmed, Zeshan
Heggenes, Morten
Fisher, Alice
Cardoso, M. Jorge
Modat, Marc
O'Neill, Michael J.
Collins, Emily C.
Fisher, Elizabeth M. C.
Ourselin, Sébastien
Lythgoe, Mark F.
Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy
title Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy
title_full Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy
title_fullStr Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy
title_full_unstemmed Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy
title_short Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy
title_sort comparison of in vivo and ex vivo mri for the detection of structural abnormalities in a mouse model of tauopathy
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374887/
https://www.ncbi.nlm.nih.gov/pubmed/28408879
http://dx.doi.org/10.3389/fninf.2017.00020
work_keys_str_mv AT holmeshollye comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT powellnickm comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT mada comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT ismailozama comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT harrisonianf comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT wellsjacka comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT colganniall comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT ocallaghanjamesm comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT johnsonrossa comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT murraytraceyk comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT ahmedzeshan comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT heggenesmorten comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT fisheralice comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT cardosomjorge comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT modatmarc comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT oneillmichaelj comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT collinsemilyc comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT fisherelizabethmc comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT ourselinsebastien comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy
AT lythgoemarkf comparisonofinvivoandexvivomriforthedetectionofstructuralabnormalitiesinamousemodeloftauopathy