DCE-MRI detected vascular permeability changes in the rat spinal cord do not explain shorter latency times for paresis after carbon ions relative to photons

  • Alina L. Bendinger
    Correspondence
    Corresponding author at: German Cancer Research Center (DKFZ), Dept. of Medical Physics in Radiation Oncology (E040), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
    Affiliations
    Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany
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  • Thomas Welzel
    Affiliations
    Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany

    Dept. of Radiation Oncology and Radiotherapy, University Hospital of Heidelberg, Heidelberg, Germany
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  • Lifi Huang
    Affiliations
    Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany

    Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany
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  • Inna Babushkina
    Affiliations
    Core Facility Small Animal Imaging Center, German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Peter Peschke
    Affiliations
    Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Dept. of Radiation Oncology and Radiotherapy, University Hospital of Heidelberg, Heidelberg, Germany
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  • Jürgen Debus
    Affiliations
    Dept. of Radiation Oncology and Radiotherapy, University Hospital of Heidelberg, Heidelberg, Germany

    Clinical Cooperation Unit Radiation Therapy, German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Christin Glowa
    Affiliations
    Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany

    Dept. of Radiation Oncology and Radiotherapy, University Hospital of Heidelberg, Heidelberg, Germany
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  • Christian P. Karger
    Affiliations
    Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany
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  • Maria Saager
    Affiliations
    Dept. of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany
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Published:October 08, 2021DOI:https://doi.org/10.1016/j.radonc.2021.09.035

      Highlights

      • DCE-MRI alterations precede radiation-induced myelopathy in the rat spinal cord.
      • Increased vascular permeability was found for both photons and carbon ions.
      • Vascular permeability increased earlier and was more pronounced for photons.
      • This indicates radiation-specific molecular mechanisms in the myelopathy development.

      Abstract

      Background and purpose

      Radiation-induced myelopathy, an irreversible complication occurring after a long symptom-free latency time, is preceded by a fixed sequence of magnetic resonance- (MR-) visible morphological alterations. Vascular degradation is assumed the main reason for radiation-induced myelopathy. We used dynamic contrast-enhanced (DCE-) MRI to identify different vascular changes after photon and carbon ion irradiation, which precede or coincide with morphological changes.

      Materials and methods

      The cervical spinal cord of rats was irradiated with iso-effective photon or carbon (12C-)ion doses. Afterwards, animals underwent frequent DCE-MR imaging until they developed symptomatic radiation-induced myelopathy (paresis II). Measurements were performed at certain time points: 1 month, 2 months, 3 months, 4 months, and 6 months after irradiation, and when animals showed morphological (such as edema/syrinx/contrast agent (CA) accumulation) or neurological alterations (such as, paresis I, and paresis II). DCE-MRI data was analyzed using the extended Toft’s model.

      Results

      Fit quality improved with gradual disintegration of the blood spinal cord barrier (BSCB) towards paresis II. Vascular permeability increased three months after photon irradiation, and rapidly escalated after animals showed MR-visible morphological changes until paresis II. After 12C-ion irradiation, vascular permeability increased when animals showed morphological alterations and increased further until animals had paresis II. The volume transfer constant and the plasma volume showed no significant changes.

      Conclusion

      Only after photon irradiation, DCE-MRI provides a temporal advantage in detecting early physiological signs in radiation-induced myelopathy compared to morphological MRI. As a generally lower level of vascular permeability after 12C-ions led to an earlier development of paresis as compared to photons, we conclude that other mechanisms dominate the development of paresis II.

      Keywords

      Abbreviations:

      12C-ions (carbon ions), AIF (arterial input function), BAT (bolus arrival time), BSCB (blood spinal cord barrier), CA (contrast agent), CSF (cerebrospinal fluid), DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging), EBA (endothelial barrier antigen), ETM (extended Toft’s model), Gd-DTPA (Gadopentetic acid), H&E (hemalaun/eosin), LET (linear energy transfer), MITK (medical imaging interaction toolkit), MRI (magnetic resonance imaging), PFA (paraformaldehyde), RBE (relative biological effectiveness), ROI (region of interest), SOBP (spread-out Bragg peak), TURBO-FLASH (turbo fast low angle shot)
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