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

Abstract

Purpose

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.

Conclusions

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

Keywords

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

Abbreviations

ADC

Apparent diffusion coefficient

ASCII

American Standard Code for Information Interchange

CBF

Cerebral blood flow

CBV

Cerebral blood volume

CE-T1 MRI

Contrast-enhanced T1 MRI

DAB

Diaminobenzidine

DMEM/F12

Dulbecco’s Modified Eagle Medium with nutrient mixture F12 Ham

d_PI

Days post-injection

DWI

Diffusion weighted imaging

FBS

Fetal bovine serum

FOV

Field of view

GFP

Green fluorescent protein

GUI

Graphical user interface

H&E

Hematoxylin–eosin

IHC

Immunohistochemistry

ic

Intracarotid

ip

Intraperitoneal

LB

Line broadening

HBSS

Hanks’ balanced salt solution

1H MRS

Proton magnetic resonance spectroscopy

ML

Mobile lipids

MRI

magnetic resonance imaging

MTX

Matrix size

MSME

multi-slice multi-echo

NEX

Number of averages

OCT

Tissue freezing medium

PCNA

Proliferating cell nuclear antigen

PRESS

Point resolved spectroscopy

RARE

Rapid acquisition by relaxation enhancement

sc

Subcutaneous

SNR

Signal to noise ratio

SPF

Specific pathogen free

TAT

Total acquisition time

TE

Echo time

TR

Repetition time

VAPOR

Variable pulse power and optimized relaxation delays

Δν1/2

MRS peak width at half height

Δ

Big delta

δ

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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