June 2025 - Lisa Körner

English subtitles on Youtube available: click on the gear icon and select “Untertitel” – “English”

Priv.-Doz.in Dr.in Lisa Körner, PhD

MedUni Wien RESEARCHER OF THE MONTH June 2025

The fluorophore 5-aminolevulinic acid, widely used in high-grade glioma (HGG) surgery, is thought to cause selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumor cells. We aimed to improve clinical detection of PpIX via paired use of Stimulated Raman Histology (SRH) and Two-Photon Fluorescence Microscopy (TPFM). Fresh tumor specimens from 115 HGG patients across four centers. We found a weak negative correlation between tissue cellularity and fluorescence intensity of PpIX across all specimens. Further, TPFM images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings show how SRH and TPFM imaging can provide a window into the immune microenvironment of gliomas.

Selected Literature

1. Nasir-Moin M, Wadiura LI, Sacalean V, Juros D, Movahed-Ezazi M, Lock EK, Smith A, Lee M, Weiss H, Müther M, Alber D, Ratna S, Fang C, Suero-Molina E, Hellwig S, Stummer W, Rössler K, Hainfellner JA, Widhalm G, Kiesel B, Reichert D, Mischkulnig M, Jain R, Straehle J, Neidert N, Schnell O, Beck J, Trautman J, Pastore S, Pacione D, Placantonakis D, Oermann EK, Golfinos JG, Hollon TC, Snuderl M, Freudiger CW, Heiland DH, Orringer DA. Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy. Nat Biomed Eng. 2024 Jun;8(6):672-688. doi: 10.1038/s41551-024-01217-3. Epub 2024 Jul 10. PMID: 38987630.
2. Orringer DA, Pandian B, Niknafs YS, Hollon TC, Boyle J, Lewis S, Garrard M, Hervey-Jumper SL, Garton HJL, Maher CO, Heth JA, Sagher O, Wilkinson DA, Snuderl M, Venneti S, Ramkissoon SH, McFadden KA, Fisher-Hubbard A, Lieberman AP, Johnson TD, Xie XS, Trautman JK, Freudiger CW, Camelo-Piragua S. Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy. Nat Biomed Eng. 2017;1:0027. doi: 10.1038/s41551-016-0027. Epub 2017 Feb 6. PMID: 28955599; PMCID: PMC5612414.
3. Hollon T, Jiang C, Chowdury A, Nasir-Moin M, Kondepudi A, Aabedi A, Adapa A, Al-Holou W, Heth J, Sagher O, Lowenstein P, Castro M, Wadiura LI, Widhalm G, Neuschmelting V, Reinecke D, von Spreckelsen N, Berger MS, Hervey-Jumper SL, Golfinos JG, Snuderl M, Camelo-Piragua S, Freudiger C, Lee H, Orringer DA. Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging. Nat Med. 2023 Apr;29(4):828-832. doi: 10.1038/s41591-023-02252-4. Epub 2023 Mar 23. PMID: 36959422; PMCID: PMC10445531.
4. Hadjipanayis CG, Widhalm G, Stummer W. What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas? Neurosurgery. 2015 Nov;77(5):663-73. doi: 10.1227/NEU.0000000000000929. PMID: 26308630; PMCID: PMC4615466.