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

Brokinkel, Benjamin; Kröger, Sabrina; Senner, Volker; Jeibmann, Astrid; Kärst, Uwe; Stummer, Walter

doi:10.1007/s00701-018-3488-x

Cited by 9 publications

(9 citation statements)

References 14 publications

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“…Most importantly, sensitivity and specificity rates were inconsistent between studies, although remaining high with an overall sensitivity of 92–98% and specificity of 95%. No correlation between fluorescent intensity and WHO grade or histological subtype became apparent and fluorescence was often heterogenic [7–23, 33, 34]. These findings are similar to our own experience.…”

Section: Resultssupporting

confidence: 88%

“…Most publications report cases or case series evaluating fluorescence status (intensity, homogeneity) in intracranial meningioma [7–23]. In a recent review [33] and meta-analysis [34], it appeared difficult to draw conclusions regarding the role of 5-ALA in meningioma surgery due to the experimental nature of 5-ALA-guided meningioma surgery.…”

Section: Resultsmentioning

confidence: 99%

“…Unaffected dura mater did not fluoresce in 17 cases (57%) [7–9, 12, 20]. Additionally, six affected dural tails (20%) did not fluoresce [20, 23]. Lastly, Brokinkel et al [23] showed PpIX formation of a non-fluorescent-invaded tail, using mass spectrometry.…”

Section: Resultsmentioning

confidence: 99%

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The application of fluorescence techniques in meningioma surgery—a review

et al. 2018

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Surgical resections of meningiomas, the most common intracranial tumor in adults, can only be curative if radical resection is achieved. Potentially, the extent of resection could be improved, especially in complex and/or high-grade meningiomas by fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA), indocyanine green (ICG), or fluorescein. This review aims to summarize and evaluate these fluorescence-guided meningioma surgery techniques. PubMed and Embase were searched for relevant articles. Additionally, we checked reference lists for further studies. Forty-eight articles were included in the final analysis. 5-ALA fluoresced with varying sensitivity and selectivity in meningiomas and in invaded bone and dura mater. Although ICG was mainly applied for video angiography, one report shows tumor fluorescence 18–28 h post-ICG injection. Lastly, the use of fluorescein could aid in the identification of tumor remnants; however, detection of dural tail is highly questionable. Fluorescence-guided meningioma surgery should be a reliable, highly specific, and sensitive technique. Despite numerous studies reporting the use of fluorescent dyes, currently, there is no evidence that these tools improve the radical resection rate and long-term recurrence-free outcome in meningioma surgery without neurological deficits. Evidence regarding the effectiveness and increased safety of resection after the application of these fluorophores is currently lacking. Future research should focus on the development of a meningioma-targeted, highly sensitive, and specific fluorophore.Electronic supplementary materialThe online version of this article (10.1007/s10143-018-01062-4) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

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The application of fluorescence techniques in meningioma surgery—a review

et al. 2018

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“…Hence, molecular and elemental MSI was introduced as a complementary technique to examine the potential chances and boundaries of fluorescence diagnosis. Within the molecular MSI domain, MALDI MS was demonstrated to have a high applicability, even of FGS for meningioma, since it accomplishes the investigation of intact molecules by soft ionization [98].…”

Section: Tof Ms Applications To Biomarkers Of Human Glioblastomamentioning

confidence: 99%

Mass Spectrometry for Cancer Biomarkers

Albulescu¹,

Petrescu²,

Sârbu³

et al. 2019

Proteomics Technologies and Applications

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Cancer is considered as the second cause of morbidity and also mortality, after cardiovascular diseases. Despite the immense progress in efficacious biomarkers made in the present time, there are very few of them that can timely detect cancers or that can predict treatment outcomes or stratify patients according to their response to the treatment. Among other modern instruments involved in the research of this disease, proteomics emerged strongly, since it analyzes the "molecular effectors." Although it has some setbacks (like the lack of amplification of the signal), it is however one of the best means of investigating the presence and causes and predicting the evolution patterns of the disease. This chapter describes briefly pre-analytical (pre-MS steps), the main concepts, and the MS equipment used for such applications, followed by the presentation of several proteomic applications in melanoma, glioblastoma, pancreatic cancer, and colon cancer.

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“…In the field of molecular MSI, matrix-assisted laser desorption–ionization (MALDI) MS has been established as the most frequently used technique, allowing the analysis of intact molecules by soft ionization. Recently, Brokinkel et al presented the complementary use of fluorescence microscopy and MALDI-MSI to investigate the applicability of FGS for meningioma . For elemental mapping with low limits of detection and the possibility of obtaining quantitative data, coupling laser ablation with inductively coupled plasma (LA-ICP) MS has evolved into an important imaging technique.…”

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confidence: 99%

Complementary Molecular and Elemental Mass-Spectrometric Imaging of Human Brain Tumors Resected by Fluorescence-Guided Surgery

et al. 2018

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Fluorescence-guided surgery (FGS) has been established as a powerful technique for glioblastoma resection. After oral application of the prodrug 5-aminolevulinic acid (5-ALA), protoporphyrin IX (PpIX) is formed as an intermediate of the heme-biosynthesis cascade and accumulates within the tumor. By intraoperative fluorescence microscopy, the specific PpIX fluorescence can be used to differentiate the tumor from healthy brain tissue. To investigate possible limitations of fluorescence diagnosis, the complementary use of molecular and elemental mass-spectrometry imaging (MSI) is presented. Matrix-assisted laser-desorption-ionization mass spectrometry (MALDI-MS) is used to examine the distribution of PpIX and heme b in human brain tumors. MALDI-MS/MS imaging is performed to validate MS data and improve the signal-to-noise ratio (S/N). Comparing the imaging results with histological evaluation, increased PpIX accumulation in areas of high tumor-cell density is observed. Heme b accumulation are only found in areas of blood vessels and hemorrhage, confirming the hampered transformation from PpIX to heme b in glioblastoma tissue. Investigation of non-neoplastic brain tissue and glioblastoma resected without external 5-ALA administration as control samples with true-negative fluorescence verified the absence of PpIX accumulation. Analysis of necrotic tumor tissue and gliosarcoma, one rare type of glioma appearing nonfluorescent during FGS, as case examples with false-negative-fluorescence diagnosis, revealed the absence of significant amounts of PpIX, indicating an impairment of PpIX formation. Molecular analysis is complemented by quantitative laser ablation-inductively coupled plasma (LA-ICP) MSI correlating heme b and Fe distribution. Mathematical pixel-by-pixel correlation of molecular and elemental data revealed a positive correlation with heteroscedasticity for the spatially resolved heme b signal intensities and Fe concentrations.

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

Abstract: 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.

Cited by 9 publications

References 14 publications

The application of fluorescence techniques in meningioma surgery—a review

The application of fluorescence techniques in meningioma surgery—a review

Mass Spectrometry for Cancer Biomarkers

Complementary Molecular and Elemental Mass-Spectrometric Imaging of Human Brain Tumors Resected by Fluorescence-Guided Surgery

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