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Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies

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Abstract

Objectives

We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using R2’ and quantitative susceptibility mapping (QSM).

Materials and methods

Intra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing C6 glioblastoma were imaged using a 3 T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images.

Results

The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for R2’, and 0.1 ± 0.02 ppm for magnetic susceptibility) were significantly higher than those treated with the controls (55 ± 18 (FAC), 45 ± 15 (ALA) s-1 for R2’, p < 0.05, and 0.03 ± 0.03 (FAC), 0.02 ± 0.02 (ALA) ppm for magnetic susceptibility, p < 0.05).

Discussion

Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R2’ or QSM.

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Acknowledgements

The authors thank with grateful appreciation for the assistance and financial support provided by Tehran University of Medical Sciences (TUMS) Tehran, Iran and the support of the National Institute for Medical Research Development (NIMAD). The authors as well thank the staffs in the National Brain Mapping Lab (NBML), Tehran, Iran, for providing MRI services for us. This study was part of the Ph.D. Thesis of Anita Ebrahimpour.

Funding

The research leading to these results received funding from Tehran University of Medical Sciences (TUMS) Tehran, Iran (Grant Number: 36881) and National Institute for Medical Research Development (NIMAD, Grant Number: 977114).

Author information

Authors and Affiliations

  1. Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Anita Ebrahimpour & Nader Riyahi Alam

  2. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Tirgar

  3. Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Behnam Hajipour-Verdom & Parviz Abdolmaleki

  4. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Ardeshir Abbasi

  5. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mahmoudreza Hadjighassem & Saereh Hosseindoost

  6. Department of Neurosurgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Amir Hossein Javadi

  7. Department of Radiology, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Hassan Hashemi

  8. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Abbas Rahimi Foroushani

  9. Concordia University, PERFORM Center, Montreal, QC, Canada

    Nader Riyahi Alam

  10. Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Khoobi

  11. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Khoobi

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  1. Anita Ebrahimpour
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  2. Fatemeh Tirgar
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  3. Behnam Hajipour-Verdom
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  4. Ardeshir Abbasi
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  5. Mahmoudreza Hadjighassem
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  8. Seyed Amir Hossein Javadi
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  11. Nader Riyahi Alam
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Contributions

AE performed the acquisition and quantitative analysis of MRI images, interpretation of data, and drafting the work as the principal author. FT created the rat GBM model. BH-V performed MTT assays. AA conducted Prussian blue staining. MH revised the manuscript critically for in vivo section. PA revised the manuscript critically for in vitro section. SH performed fluorescence imaging. SAHJ and HH revised the manuscript critically for important intellectual content. ARF analyzed the results statistically. NRA contributed to the design of the work for QSM and R2* analysis and approved the final version to be published. MK designed the main conception of this work and approved the final version to be published.

Corresponding authors

Correspondence to Nader Riyahi Alam or Mehdi Khoobi.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

All procedures involving animals were ethically approved by the local ethics committee of the National Institute for Medical Research Development (NIMAD, ethical code: IR.NIMAD.REC.1397.424).

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Ebrahimpour, A., Tirgar, F., Hajipour-Verdom, B. et al. Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies. Magn Reson Mater Phy 35, 3–15 (2022). https://doi.org/10.1007/s10334-021-00978-1

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  • DOI: https://doi.org/10.1007/s10334-021-00978-1

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