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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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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 |
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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 |
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