Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence‐guided neurosurgery: An ex vivo feasibility study
Open accessAbstract
Achieving a maximal safe extent of resection during brain tumor surgery is the goal for improved patient prognosis. Fluorescence‐guided neurosurgery using 5‐aminolevulinic acid (5‐ALA) induced protoporphyrin IX has thereby become a valuable tool enabling a high frequency of complete resections and a prolonged progression‐free survival in glioblastoma patients. We present a widefield fluorescence lifetime imaging device with 250 mm working distance, working under similar conditions such as surgical microscopes based on a time‐of‐flight dual tap CMOS camera. In contrast to intensity‐based fluorescence imaging, our method is invariant to light scattering and absorption while being sensitive to the molecular composition of the tissue. We evaluate the feasibility of lifetime imaging of protoporphyrin IX using our system to analyze brain tumor phantoms and fresh 5‐ALA‐labeled human tissue samples. The results demonstrate the potential of our lifetime sensing device to go beyond the limitation of current intensity‐based fluorescence‐guided neurosurgery.
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Current PpIX visualization with wide-field surgical microscopy is highly sensitive for revealing the tumor core for bulky tumor resection, but not good for tumor visualization at the tumor margin due to low tumor cell density and surgical cavities because of the tissue hindrance to light penetration.
“As mentioned above, current PpIX visualization with wide-field surgical microscopy is highly sensitive for revealing the tumor core for bulky tumor resection, but not good for tumor visualization at the tumor margin due to low tumor cell density and surgical cavities because of the tissue hindrance to light penetration.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [79]
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- Authors
- Erkkilä, M. T., Bauer, B., Hecker‐Denschlag, N., Madera Medina, M. J., Leitgeb, R. A., Unterhuber, A., Gesperger, J., Roetzer, T., Hauger, C., Drexler, W., Widhalm, G., & Andreana, M.
- Affiliations
- Carl Zeiss (Germany) (DE)
- Advanced Development Microsurgery, Carl Zeiss Meditec AG Oberkochen Germany
- Medical University of Vienna (AT)
- Vienna General Hospital (AT)
- Institute of Neurology General Hospital and Medical University of Vienna Vienna Austria
- Corresponding author
- Erkkilä, Mikael T.
- ORCID
- Venue
- Journal of Biophotonics
- Publisher
- Wiley
- Published
- 2019-02-20
- Volume
- 12
- Issue
- 6
- Pages
- e201800378-e201800378
- ISSN
- 1864-063X (ISSN-L)
- 1864-0648
- PMC
- PMC7065606
- OpenAlex
- W2909013976
- Cited by
- 39
- References
- 27
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 9
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biophotonics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Carl Zeiss Meditec AG
- H2020 Marie Skłodowska-Curie Actions (721766)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- fluorescence lifetime imaging, protoporphyrin IX, 5-aminolevulinic acid, glioblastoma, brain tumor resection, wide-field imaging
- MeSH terms
- Brain, Feasibility Studies, Humans, Protoporphyrins, Phantoms, Imaging, Neurosurgical Procedures, Surgery, Computer-Assisted, Optical Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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