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Visualizing protoporphyrin IX formation in the dura tail of meningiomas by mass spectrometry imaging

  • Technical Note - Brain Tumors
  • Published:
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Abstract

Background

The advantages of 5-aminolevulinacid (5-ALA)-induced fluorescence-guided surgery in meningiomas are increasingly discussed. In this context, despite detectable tumor tissue in histopathologial analyses, no fluorescence was shown at the dura tail using the standard operating microscope. Thus, 5-ALA metabolism in this surgically important site remains unknown but needs to be elucidated when further evaluating indications of fluorescence-guided surgery in meningiomas.

Method

We here present the spatially resolved identification of protoporphyrin IX (PpIX) in sphenoid ridge meningioma cryosections from a patient who underwent fluorescence-guided microsurgery using molecular imaging analysis by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS).

Results

Despite a strong fluorescence of the main tumor, no fluorescence could be detected at the dura tail using the standard operating microscope (blue-light, 405 nm). However, histopathological analyses clearly showed meningioma tissue. Remarkably, MALDI-MS/MS analysis revealed PpIX formation also at the non-fluorescing dura tail. However, no PpIX was detected in the tumor free dura mater.

Conclusion

MALDI-MS/MS visualized a selective accumulation of PpIX within the tumor tissue including the dura tail. Thus, absence of fluorescence in the dura tail as visualized by the operating microscope is not caused by the lack of PpIX formation.

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References

  1. Brokinkel B, Hess K, Mawrin C (2017) Brain invasion in meningiomas-clinical considerations and impact of neuropathological evaluation: a systematic review. Neuro-Oncology 19:1298–1307

    Article  PubMed  PubMed Central  Google Scholar 

  2. Foster N, Eljamel S (2016) ALA-induced fluorescence image guided surgery of meningiomas: a meta-analyses. Photodiagn Photodyn Ther 15:73–78. https://doi.org/10.1016/j.pdpdt.2016.05.006

    Article  Google Scholar 

  3. Greer T, Sturm R, Li L (2011) Mass spectrometry imaging for drugs and metabolites. J Proteome 74:2617–2631

    Article  CAS  Google Scholar 

  4. Hagiya Y, Fukuhara H, Matsumoto K, Endo Y, Nakajima M, Tanaka T, Okura I, Kurabayashi A, Furihata M, Inoue K, Shuin T, Ogura S (2013) Expression levels of PEPT1 and ABCG2 play key roles in 5-aminolevulinic acid (ALA)-induced tumor-specific protoporphyrin IX (PpIX) accumulation in bladder cancer. Photodiagn Photodyn Ther 10:288–295

    Article  CAS  Google Scholar 

  5. Hefti M, Holenstein F, Albert I, Looser H, Luginbuehl V (2011) Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity. Photochem Photobiol 87:235–241

    Article  PubMed  CAS  Google Scholar 

  6. Knipps J, Beseoglu K, Kamp M, Fischer I, Felsberg J, Neumann LM, Steiger HJ, Cornelius JF (2017) Fluorescence behaviour and dural infiltration of meningioma analyzed by 5-ALA based fluorescence: operating microscope versus mini-spectrometer. World Neurosurg. https://doi.org/10.1016/j.wneu.2017.08.140

  7. Millesi M, Kiesel B, Mischkulnig M, Martinez-Moreno M, Wohrer A, Wolfsberger S, Knosp E, Widhalm G (2016) Analysis of the surgical benefits of 5-ALA-induced fluorescence in intracranial meningiomas: experience in 204 meningiomas. J Neurosurg 125:1408–1419

    Article  PubMed  CAS  Google Scholar 

  8. Motekallemi A, Jeltema HR, Metzemaekers JD, van Dam GM, Crane LM, Groen RJ (2015) The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review. Neurosurg Rev 38:619–628

    Article  PubMed  PubMed Central  Google Scholar 

  9. Peyre M, Clermont-Taranchon E, Stemmer-Rachamimov A, Kalamarides M (2013) Miniaturized handheld confocal microscopy identifies focal brain invasion in a mouse model of aggressive meningioma. Brain Pathol 23:371–377

    Article  PubMed  Google Scholar 

  10. Sanai N, Snyder LA, Honea NJ, Coons SW, Eschbacher JM, Smith KA, Spetzler RF (2011) Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas. J Neurosurg 115:740–748

    Article  PubMed  CAS  Google Scholar 

  11. Sun N, Walch A (2013) Qualitative and quantitative mass spectrometry imaging of drugs and metabolites in tissue at therapeutic levels. Histochem Cell Biol 140:93–104. https://doi.org/10.1007/s00418-013-1127-4

    Article  PubMed  CAS  Google Scholar 

  12. Teng L, Nakada M, Zhao SG, Endo Y, Furuyama N, Nambu E, Pyko IV, Hayashi Y, Hamada JI (2011) Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy. Br J Cancer 104:798–807

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Yang X, Palasuberniam P, Kraus D, Chen B (2015) Aminolevulinic acid-based tumor detection and therapy: molecular mechanisms and strategies for enhancement. Int J Mol Sci 16:25865–25880

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Zhao SG, Chen XF, Wang LG, Yang G, Han DY, Teng L, Yang MC, Wang DY, Shi C, Liu YH, Zheng BJ, Shi CB, Gao X, Rainov NG (2013) Increased expression of ABCB6 enhances protoporphyrin IX accumulation and photodynamic effect in human glioma. Ann Surg Oncol 20:4379–4388

    Article  PubMed  Google Scholar 

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Correspondence to Benjamin Brokinkel.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Data collection and scientific use was approved by the local ethics committee (Münster 2007-420-f-S). Informed consent was obtained from the participant included in the study.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria, educational grants, participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

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Brokinkel, B., Kröger, S., Senner, V. et al. Visualizing protoporphyrin IX formation in the dura tail of meningiomas by mass spectrometry imaging. Acta Neurochir 160, 1433–1437 (2018). https://doi.org/10.1007/s00701-018-3488-x

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  • DOI: https://doi.org/10.1007/s00701-018-3488-x

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