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Imaging of Murine Brain Tumors Using a 1.5 Tesla Clinical MRI System

Published online by Cambridge University Press:  02 December 2014

Wouter R. van Furth ,
Suzanne Laughlin ,
Michael D. Taylor ,
Bodour Salhia ,
Todd Mainprize ,
Mark Henkelman ,
Michael D. Cusimano ,
Cameron Ackerley  and
James T. Rutka
Wouter R. van Furth
Affiliation:
Arthur & Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada
Suzanne Laughlin
Affiliation:
Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Department of Medical Imaging, Toronto, Ontario, Canada
Michael D. Taylor
Affiliation:
Arthur & Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada
Bodour Salhia
Affiliation:
Arthur & Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada
Todd Mainprize
Affiliation:
Arthur & Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada
Mark Henkelman
Affiliation:
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Michael D. Cusimano
Affiliation:
Division of Neurosurgery, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
Cameron Ackerley
Affiliation:
Arthur & Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada
James T. Rutka
Affiliation:
Arthur & Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada
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Abstract

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Background:

In this study, we investigated the feasibility of using a 1.5 Tesla (T) clinical magnetic resonance imaging (MRI) system for in vivo assessment of three histopathologically different brain tumor models in mice.

Methods:

We selected mouse models in which tumor growth was observed in different intracranial compartments: Patched+/- heterozygous knock-out mice for tumor growth in the cerebellum (n = 5); U87 MG human astrocytoma cells xenografted to the frontal lobe of athymic mice (n =15); and F5 (n = 15) or IOMM-Lee (n = 15) human malignant meningioma cells xenotransplanted to the athymic mouse skull base or convexity. Mice were imaged using a small receiver surface coil and a clinical 1.5 T MRI system. T1- and fast spin echo T2-weighted image sequences were obtained in all animals. Gadolinium was injected via tail vein to better delineate the intracranial tumors. Twenty mice were followed by serial MRI to study tumor growth over time. In these mice, images were typically performed after tumor implantation, and at two week intervals. Mice were euthanized following their last imaging procedure, and their tumors were examined by histopathology. The histopathological preparations were then compared to the last MR images to correlate the imaging features with the pathology.

Results:

Magnetic resonance imaging delineated the tumors in the cerebellum, frontal lobes and skull base in all mouse models. The detection of intracranial tumors was enhanced with prior administration of gadolinium, and the limit of resolution of brain tumors in the mice was 1-2 mm3. Sequential images performed at different time intervals showed progressive tumor growth in all animals. The MR images of tumor size and location correlated accurately with the results of the histopathological analysis.

Conclusion:

Magnetic resonance imaging of murine brain tumors in different intracranial compartments is feasible with a 1.5 T clinical MR system and a specially designed surface coil. Tumors as small as 1-2 mm3 can be detected with good image resolution. Mice harbouring nascent brain tumors can be followed sequentially by serial MR imaging. This may allow for a noninvasive means by which tumor growth can be measured, and novel therapies tested without resorting to sacrifice of the mice.

Résumé:

RÉSUMÉ: Introduction:

Nous avons évalué la possibilité d’utiliser un système d’imagerie par résonance magnétique (IRM) 1.5 Tesla (T) utilisé en clinique pour l’étude in vivo de trois modèles différents au point de vue histopathologique de tumeurs cérébrales chez la souris.

Méthodes:

Nous avons choisi des modèles présentant une tumeur dans différents compartiments intracrâniens: des souris knock-out hétérozygotes Patched+/- pour les tumeurs du cervelet (n = 5); des cellules d’astrocytome humain U87 MG xénotransplantées dans le lobe frontal de souris athymiques (n = 15); et des cellules de méningiome malin humain F5 (n = 15) ou IOMM Lee (n = 15) xénotransplantées à la base du crâne ou à la convexité de souris athymiques. Une petite sonde de surface et un système IRM 1.5 T utilisé en clinique ont été utilisés et on a obtenu des séquences pondérées T1 et écho de spin T2 chez tous les animaux. Du gadolinium a été injecté par la veine de la queue pour mieux faire ressortir les tumeurs intracrâniennes. Vingt souris ont été suivies par IRM sérié pour suivre la croissance tumorale. Chez ces souris, les images ont été obtenues après l’implantation de la tumeur et aux deux semaines par la suite. Les souris ont été sacrifiées après la dernière séance d’imagerie et les tumeurs ont été examinées en histopathologie. Les préparations histopathologiques ont ensuite été comparées aux dernières images obtenues par RM pour établir des corrélations entre l’imagerie et la pathologie.

Résultats:

L’IRM a mis en évidence les tumeurs dans le cervelet, les lobes frontaux et à la base du crâne chez tous les modèles de souris. La détection des tumeurs intracrâniennes était rehaussée par l’administration préalable de gadolinium et la limite de résolution des tumeurs cérébrales chez les souris était de 1-2 mm3. Des images séquentielles obtenues à différents intervalles ont montré une croissance progressive de la tumeur chez tous les animaux. Les images de la taille et de la localisation de la tumeur obtenues par RM correspondaient exactement aux résultats de l’analyse histopathologique.

Conclusion:

Il est possible d’utiliser un système de RM 1.5 T utilisé en clinique et une sonde spécialement conçue pour l’IRM de tumeurs cérébrales dans différents compartiments intracrâniens chez la souris. Avec une bonne résolution, on peut détecter des tumeurs de 1 ou 2 mm3. On peut suivre des souris porteuses de tumeurs cérébrales naissantes par l’IRM en série. Cette méthode permet de suivre la croissance tumorale de façon non effractive et de tester de nouveaux traitements sans devoir sacrifier les souris.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 30 , Issue 4 , November 2003 , pp. 326 - 332
Copyright
Copyright © The Canadian Journal of Neurological 2003

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