Preliminary characterization of an experimental breast cancer cells brain metastasis mouse model by MRI/MRS

  • R. V. Simões
  • A. Martinez-Aranda
  • B. Martín
  • S. Cerdán
  • A. Sierra
  • C. Arús
Research Article



Chemotherapy increases survival in breast cancer patients. Consequently, cerebral metastases have recently become a significant clinical problem, with an incidence of 30–40% among breast carcinoma patients. As this phenomenon cannot be studied longitudinally in humans, models which mimic brain metastasis are needed to investigate its pathogenesis. Such models may later be used in experimental therapeutic approaches.

Material and methods/results

We report a model in which 69% of the animals (9/13 BALB/c nude mice) developed MR-detectable abnormal masses in the brain parenchyma within a 20 to 62-day time window post intra-carotid injection of 435-Br1 human cells. The masses detected in vivo were either single (7 animals) or multiple (2 animals). Longitudinal MR (MRI/MRS) studies and post-mortem histological data were correlated, revealing a total incidence of experimental brain metastases of 85% in the cases studied (11/13 animals). ADC maps perfectly differentiated edema and/or CSF areas from metastasis. Preliminary MRS data also revealed additional features: decrease in N-acetyl aspartate (NAA) was the first MRS-based marker of metastasis growth in the brain (micrometastasis); choline-containing compounds (Cho) rose and creatine (Cr) levels decreased as these lesions evolved, with mobile lipids and lactate also becoming visible. Furthermore, MRS pattern recognition-based analysis suggested that this approach may help to discriminate different growth stages.


This study paves the way for further in vivo studies oriented towards detection of different tumor progression states and for improving treatment efficiency.


Brain metastasis Breast cancer Proton magnetic resonance spectroscopy Magnetic resonance imaging Pattern recognition 



Apparent diffusion coefficient


American Standard Code for Information Interchange


Cerebral blood flow


Cerebral blood volume


Contrast-enhanced T1 MRI




Dulbecco’s Modified Eagle Medium with nutrient mixture F12 Ham


Days post-injection


Diffusion weighted imaging


Fetal bovine serum


Field of view


Green fluorescent protein


Graphical user interface










Line broadening


Hanks’ balanced salt solution


Proton magnetic resonance spectroscopy


Mobile lipids


magnetic resonance imaging


Matrix size


multi-slice multi-echo


Number of averages


Tissue freezing medium


Proliferating cell nuclear antigen


Point resolved spectroscopy


Rapid acquisition by relaxation enhancement




Signal to noise ratio


Specific pathogen free


Total acquisition time


Echo time


Repetition time


Variable pulse power and optimized relaxation delays


MRS peak width at half height


Big delta


Small delta


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Copyright information

© ESMRMB 2008

Authors and Affiliations

  • R. V. Simões
    • 1
    • 2
    • 3
  • A. Martinez-Aranda
    • 4
  • B. Martín
    • 4
  • S. Cerdán
    • 5
  • A. Sierra
    • 4
  • C. Arús
    • 1
    • 2
  1. 1.Grup d’Aplicacions Biomèdiques de la Ressonància Magnètica Nuclear (GABRMN)Universitat Autònoma de BarcelonaCerdanyola del VallèsSpain
  2. 2.Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)Cerdanyola del VallèsSpain
  3. 3.Centro de Neurociências e Biologia Celular de Coimbra (CNC)Universidade de CoimbraCoimbraPortugal
  4. 4.Centre d’Oncologia Molecular, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), CSUBBarcelonaSpain
  5. 5.Departamento de Modelos experimentales de enfermedades humanasInstituto de Investigaciones Biomédicas “Alberto Sols” UAM-CSICMadridSpain

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