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Glioblastoma: Validation and Comparison Between Primary Tumor and Its Murine Model



Juni 2015

Letztes Update:


Indikation (Clinical Trials):


Erwachsene (18+)


Andreas Hottinger

Ecole Polytechnique Fédérale de Lausanne


Andreas F Hottinger, MD-PhD
Study Chair
CHUV Lausanne University Hospital


(1 von 1)

CHUV, University Hospital Lausanne
1066 Lausanne
SwitzerlandRekrutierend» Google-Maps
Andreas F Hottinger, MD, PhD
Phone: +41 21 314 0168

Laurence Benoit
Phone: +41 21 314 0168
» Ansprechpartner anzeigen


Detailed Description:

The presented project will focus on the evaluation of a multimodal approach comparing human

GBM to paired samples of orthotopic xenografts using high resolution MRI and MRS and

multidimensional molecular profiling.

20 patients with a high probability for newly diagnosed GBM based on MRI-scan ( 3 Tesla (3T)

MRI, T1, T2, T1 gadolinium, DWI & MRI Spectroscopy) will be identified in the CHUV prior to

undergoing neurosurgical resection. Patients will undergo extensive experimental radiological

examination using specific MRI sequences on the 7 Tesla (7T) MRI to identify specific

metabolic pathways (see below, section on imaging). Thereafter patients will undergo maximal

safe neurosurgical resection of their tumors. The portion of the tumor that is not used for

diagnostic purposes will be collected immediately for further use (see below, section on

molecular evaluations). Following resection, patients will undergo standard of care treatment

[usually combined radio-chemotherapy, or will be offered participation in a clinical trial.

The clinical parameters will be collected, including histopathological features and the

evolution and growth pattern of the residual tumor (if present), or the development of

recurrences will thereafter be compared to the parameters and evolution of the xenograft


At high magnet field strength (7T), high signal-to-noise ratio and increased spectral

dispersion allow more reliable measurement of a large number of metabolites using Magnetic

Resonance Spectroscopy in comparison to clinical available field strengths (3T and below). In

addition, the authors have developed a full sensitivity short-echo-time single voxel

spectroscopy (SVS) sequence "semi-adiabatic SPECIAL"(2) which was implemented, validated at

7T and allows the quantification of 15 metabolites with high precision including

N-acetylaspartate(NAA), glutamine(Gln), glutamate(Glu), myo-inositol(Ins),

phosphorylethanolamine(PE), total choline(tCho), creatine, phosphocreatine,

N-acetylaspartylglutamate(NAAG), lactate(Lac), glutathione(GSH), aspartate (Asp),

taurine(Tau), scyllo-inositol and γ-aminobutyric acid(GABA). This localization technique was

further extended to a MR Spectroscopic Imaging (MRSI) technique at 7T, which allows mapping

of the spatial distributions of cerebral metabolites. Furthermore, glycine is a possible

marker for tumor malignancy and its detection in vivo has been established in our previous

study using TE=30ms with SPECIAL sequence at 7T. Therefore, in this study the aforementioned

techniques will be used to obtain the neurochemical information and its spatial distribution

in the glioblastoma of the patients. These data will be further compared with the

neurochemical information obtained in the orthotopic xenografts in the mouse brain derived

from the respective glioblastoma patient.

All MRS measurements of glioblastoma patients will be performed on a 7T MR scanner with a CP

Transmit / 32 channel receive array head coil. Based on the high resolution T1-weighted

images obtained using the MP2RAGE sequence, Volume of Interest (VOI) for spectroscopy will be

placed according to the location of the glioblastoma. Total acquisition time of MRS will be

within 30 min. In vivo MRS spectra will be post-processed and metabolite concentrations will

be quantified to create metabolite maps.

Molecular and functional investigations of paired samples of primary glioblastoma and

respective orthotopic xenografts in the mouse

The aim of the present study is to determine the molecular, histopathological, and functional

properties, including growth patterns such as invasiveness, of the original GBM and the

respective derived orthotopic xenografts in the mouse, and link them to imaging/ metabolism

parameters obtained by high resolution MRI.

GBM samples from patients collected at surgery will be divided into 2 parts, (i) snap frozen

for molecular analyses, and (ii) cultivated under stem cell conditions for subsequent

stereotactic transplantation into male immune-compromised mice and establishment of sphere



Inclusion Criteria:

- High level of suspicion of glioblastoma

- Planned neurosurgical resection

- Adequate bone marrow function

- Adequate liver and kidney function

Exclusion Criteria:

- inability to undergo MRI

- inability to undergo neurosurgical resection


Primary outcome:

1. GBM metabolites using high resolution spectroscopy (Time Frame - 2 years):
High resolution spectroscopy metabolite analysis of GBM

2. Next generation sequencing of GBM tumor tissue (Time Frame - 2 years):
Molecular comparison of primary GBM tumor and paired orthotropic xenograft

Geprüfte Regime

  • 7 Tesla MRI, no contrast agent:
    Patients with newly diagnosed glioblastoma undergo a 7Tesla MRI


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