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Magnetic resonance spectroscopy and imaging on fresh human brain tumor biopsies at microscopic resolution

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Abstract

The metabolic composition and concentration knowledge provided by magnetic resonance spectroscopy (MRS) liquid and high-resolution magic angle spinning spectroscopy (HR-MAS) has a relevant impact in clinical practice during magnetic resonance imaging (MRI) monitoring of human tumors. In addition, the combination of morphological and chemical information by MRI and MRS has been particularly useful for diagnosis and prognosis of tumor evolution. MRI spatial resolution reachable in human beings is limited for safety reasons and the demanding necessary conditions are only applicable on experimental model animals. Nevertheless, MRS and MRI can be performed on human biopsies at high spatial resolution, enough to allow a direct correlation between the chemical information and the histological features observed in such biopsies. Although HR-MAS is nowadays a well-established technique for spectroscopic analysis of tumor biopsies, with this approach just a mean metabolic profile of the whole sample can be obtained and thus the high histological heterogeneity of some important tumors is mostly neglected. The value of metabolic HR-MAS data strongly depends on a wide statistical analysis and usually the microanatomical rationale for the correlation between histology and spectroscopy is lost. We present here a different approach for the combined use of MRI and MRS on fresh human brain tumor biopsies with native contrast. This approach has been designed to achieve high spatial (18 × 18 × 50 μm) and spectral (0.031 μL) resolution in order to obtain as much spatially detailed morphological and metabolical information as possible without any previous treatment that can alter the sample. The preservation of native tissue conditions can provide information that can be translated to in vivo studies and additionally opens the possibility of performing other techniques to obtain complementary information from the same sample.

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Abbreviations

FLASH:

Fast low-angle shot

GBM:

Glioblastoma multiform

H&E:

Hematoxylin and eosin

HR-MAS:

High-resolution magic angle spinning spectroscopy

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

MRM:

Magnetic resonance microscopy

MRS:

Magnetic resonance spectroscopy

NAA:

N-Acetylaspartate

OM:

Optical microscopy

PBS:

Phosphate-buffered saline

PFA:

Para-formaldehyde

PRESS:

Point-resolved spectroscopy

RARE:

Rapid acquisition with relaxation enhancement

VAPOR:

Variable pulse power and optimized relaxation delays

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Acknowledgments

The authors acknowledge the SCSIE-University of Valencia Microscopy Service for the histological preparations. They also acknowledge financial support from the Spanish Government project SAF2007-6547, the Generalitat Valenciana project GVACOMP2009-303, and the E.U.s VI Framework Program via the project “Web accessible MR decision support system for brain tumor diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data” (FP6-2002-LSH 503094).

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Authors and Affiliations

  1. Department of Physical Chemistry, University of Valencia, C/ Dr. Moliner 50, 46100, Burjassot, Valencia, Spain

    M. Carmen Martínez-Bisbal, Beatriz Martínez-Granados, Bernardo Celda & Vicent Esteve

  2. Centre for Molecular Recognition and Technologic Development (IDM), Polytechnic University of Valencia, 46022, València, Valencia, Spain

    M. Carmen Martínez-Bisbal

  3. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Camino de vera, s/n, 46100, Burjassot, Valencia, Spain

    Beatriz Martínez-Granados & Vicent Esteve

  4. Neurosurgery Service, Hospital La Ribera, Ctra. Corbera, km 1, 46600, Alzira, Valencia, Spain

    Vicente Rovira

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  1. M. Carmen Martínez-Bisbal
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  2. Beatriz Martínez-Granados
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  3. Vicente Rovira
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  4. Bernardo Celda
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  5. Vicent Esteve
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Correspondence to Vicent Esteve.

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Martínez-Bisbal, M.C., Martínez-Granados, B., Rovira, V. et al. Magnetic resonance spectroscopy and imaging on fresh human brain tumor biopsies at microscopic resolution. Anal Bioanal Chem 407, 6771–6780 (2015). https://doi.org/10.1007/s00216-015-8847-3

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  • DOI: https://doi.org/10.1007/s00216-015-8847-3

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