Endoscopic fluorescence visualization of 5-ALA photosensitized central nervous system tumors in the neural tissue transparency spectral range
-
Maxim Loshchenov
,
Petr Zelenkov
Abstract
Background:
Fluorescence endoscopy systems for photosensitizer visualization have proved to be powerful tools for highlighting malignant tumor boundaries as well as detecting small, visually non-detectable, residual parts during photodynamic therapy. Most of these devices use excitation wavelengths in the blue visual spectrum range (405 nm) which limits the penetration depth in the tissue.
Objective:
In the study being presented in this article an apparatus and a method were developed for performing endoscopic fluorescence diagnostics of photosensitizer accumulation using excitation light in the red part of visual spectrum, i.e., 635 nm, which allows not only a deeper penetration of light into the tissue but also better scanning abilities and a higher diagnostic quality. Additionally, 635-nm radiation can penetrate thin layers of blood which appear during surgery.
Material and methods:
In order to use 635-nm excitation, a specially designed video endoscopy system was developed. The key feature of the video system is a dual camera video receiver where one sensitive B/W camera receives the fluorescence signal and a color camera receives the real-time image in natural colors during navigation. The software developed for the apparatus allows overlaying of the video output of fluorescence image on top of the conventional color image in real-time. The experimental setup and method were tested on Intralipid-based phantoms with protoporphyrin IX (PpIX) concentrations of 0.5–5 mg/kg, and then on two patients during surgery. The patients were administered 20 mg/kg 5-ALA photosensitizer 3 h before surgery according to standard practice of 5-ALA in neurosurgery.
Results:
The experiments demonstrate that the designed setup is sensitive enough for clear visualization of biological concentrations of PpIX in both phantoms with 0.5 mg/kg PpIX and previously photosensitized tissues of patients.
Conclusion:
Further prospective validation is needed to translate the results to clinical practice.
Zusammenfassung
Hintergrund:
Fluoreszenz-Endoskopie-Systeme für die Photosensibilisator-Visualisierung haben sich als leistungsfähige Werkzeuge für die Sichtbarmachung von Tumorgrenzen sowie die Erkennung kleiner, visuell nicht nachweisbarer Tumorreste während der photodynamischen Therapie erwiesen. Die meisten dieser Geräte nutzen Anregungswellenlängen im blauen sichtbaren Spektralbereich (405 nm), die jedoch die Eindringtiefe im Gewebe begrenzen.
Zielsetzung:
In der vorliegenden Studie wird ein System/Verfahren zur endoskopischen Fluoreszenzdiagnostik der Photosensibilisator-Akkumulation vorgestellt, das Anregungslicht im roten Teil des sichtbaren Spektrums, d.h. 635 nm, nutzt und somit nicht nur ein tieferes Eindringen von Licht im Zielgewebe ermöglicht, sondern auch bessere Scan-Eigenschaften und eine höhere diagnostische Qualität liefert. Die 635-nm-Strahlung kann zudem dünne, während der Operation auftretende Schichten von Blut durchdringen.
Material und Methoden:
Zur Realisierung der 635-nm-Anregung wurde ein spezielles Video-Endoskopie-System entwickelt. Hauptbestandteil dieses Video-Systems ist ein dualer Kamera-Video-Empfänger: eine empfindliche S/W-Kamera empfängt das Fluoreszenz-Signal und eine Farbkamera das Echtzeit-Bild in natürlichen Farben während der Navigation. Die für das Gerät speziell entwickelte Software ermöglicht die Überlagerung des Fluoreszenz-Bildes am Videoausgang mit dem herkömmlichen Farbbild in Echtzeit. Versuchsaufbau und Verfahren wurden zunächst an Intralipid-basierten Phantomen mit Protoporphyrin IX (PpIX)-Konzentrationen von 0,5–5 mg/kg und danach unter klinischen Bedingungen während zweier Operationen getestet. Den beiden Patienten wurden dabei jeweils 20 mg/kg 5-ALA-Photosensibilisator 3 h vor der Operation verabreicht – entsprechend der üblichen Praxis in der Neurochirurgie.
Ergebnisse:
Die Experimente haben gezeigt, dass das entwickelte System empfindlich genug für eine klare Visualisierung von biologischen Konzentrationen von PpIX ist, sowohl in Phantomen mit ≥0,5 mg/kg PpIX als auch in zuvor photosensibilisierten Geweben von Patienten.
Fazit:
Eine weitere prospektive Validierung wird benötigt, um die Ergebnisse in die klinische Praxis zu überführen.
Acknowledgments
This study was partially funded by Moscow Government and SRC NIOPIK. Also this study was partially supported by RFBR, research project #13-04-12066.
References
[1] Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature 2008;452(7187):580–9.10.1038/nature06917Search in Google Scholar PubMed PubMed Central
[2] Valdés PA, Leblond F, Kim A, Harris BT, Wilson BC, Fan X, Tosteson TD, Hartov A, Ji S, Erkmen K, Simmons NE, Paulsen KD, Roberts DW. Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. J Neurosurg 2011;115(1):11–7.10.3171/2011.2.JNS101451Search in Google Scholar PubMed PubMed Central
[3] Utsuki S, Oka H, Sato S, Suzuki S, Shimizu S, Tanaka S, Fujii K. Possibility of using laser spectroscopy for the intraoperative detection of nonfluorescing brain tumors and the boundaries of brain tumor infiltrates. Technical note. J Neurosurg 2006;104(4):618–20.10.3171/jns.2006.104.4.618Search in Google Scholar PubMed
[4] Valdés PA, Leblond F, Jacobs VL, Wilson BC, Paulsen KD, Roberts DW. Quantitative spectrally-resolved intraoperative fluorescence imaging. Sci Rep 2012;2:798. doi: 10.1038/srep00798.10.1038/srep00798Search in Google Scholar PubMed PubMed Central
[5] Matveev BP, Kudashev BV, Bukharkin BV, Stratonnikov AA, Kulenok NV, Loschenov VB. Spectral and imaging fluorescence analysis with ALA-induced protoporphyrin IX with the aim to increase the efficiency of bladder transurethral resections. Proc SPIE 2001;4156:194. doi:10.1117/12.413703.10.1117/12.413703Search in Google Scholar
[6] Moriyama EH, Kim A, Bogaards A, Lilge L, Wilson BC. An intraoperative radiometric fluorescence system for in vivo imaging. In: Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2008), paper BTuC7. http://www.opticsinfobase.org/abstract.cfm?URI=BIOMED-2008-BTuC7 [Accessed on April 15, 2013].Search in Google Scholar
[7] Potapov AA, Usachev DJ, Loshakov VA, Cherekaev VA, Kornienko VN, Pronin IN, Kobiakov GL, Kalinin PL, Gavrilov AG, Stummer W, Golbin DA, Zelenkov PV. First experience in 5-ALA fluorescence-guided and endoscopically assisted microsurgery of brain tumors. Med Laser Appl 2008;23(4):202–8.10.1016/j.mla.2008.07.006Search in Google Scholar
[8] Zawacka-Pankau J, Krachulec J, Grulkowski I, Bielawski KP, Selivanova G. The p53-mediated cytotoxicity of photodynamic therapy of cancer: recent advances. Toxicol Appl Pharmacol 2008;232(3):487–97.10.1016/j.taap.2008.07.012Search in Google Scholar PubMed
[9] Loschenov VB, Stratonnikov AA. Spectra line separation method for sophisticated data analysis of biological tissue optical spectra. Proc SPIE 1994;2081:237. doi:10.1117/12.166834.10.1117/12.166834Search in Google Scholar
[10] Valdés PA, Leblond F, Kim A, Wilson BC, Paulsen KD, Roberts DW. A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery. Opt Lett 2012;37(11):1817–9.10.1364/OL.37.001817Search in Google Scholar PubMed PubMed Central
[11] Valdés PA, Kim A, Brantsch M, Niu C, Moses ZB, Tosteson TD, Wilson BC, Paulsen KD, Roberts DW, Harris BT. δ-aminolevulinic acid-induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy. Neuro Oncol 2011;13(8):846–56.10.1093/neuonc/nor086Search in Google Scholar PubMed PubMed Central
[12] Montcel B, Mahieu-Williame L, Armoiry X, Meyronet D, Guyotat J. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas. Biomed Opt Express 2013;4(4):548–58.10.1364/BOE.4.000548Search in Google Scholar PubMed PubMed Central
[13] Ando T, Kobayashi E, Liao H, Maruyama T, Muragaki Y, Iseki H, Kubo O, Sakuma I. Precise comparison of protoporphyrin IX fluorescence spectra with pathological results for brain tumor tissue identification. Brain Tumor Pathol 2011;28(1):43–51.10.1007/s10014-010-0002-4Search in Google Scholar PubMed
©2014 by Walter de Gruyter Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Laser interstitial thermal therapy (LITT) of the brain – Experiences and new indications
- Magazine section
- Snapshots
- Reviews
- Laser interstitial thermal therapy with and without MRI guidance for treatment of brain neoplasms – A systematic review of the literature
- Laser interstitial thermal therapy for treatment of post-radiosurgery tumor recurrence and radiation necrosis
- MRI-guided laser interstitial thermal therapy of intracranial tumors and epilepsy: State-of-the-art review and a case study from pediatrics
- Original contributions
- Percutaneous selective laser amygdalo-hippocampectomy (SLAH) for treatment of mesial temporal lobe epilepsy within an interventional MRI suite
- Interstitial laser irradiation of cerebral gliomas – neurobiological background, technique and typical results
- Prognostic factors of overall survival after laser interstitial thermal therapy in patients with glioblastoma
- Laser interstitial thermal therapy as a novel treatment modality for brain tumors in the thalamus and basal ganglia
- Preliminary research report
- Endoscopic fluorescence visualization of 5-ALA photosensitized central nervous system tumors in the neural tissue transparency spectral range
- Congress announcements
- 21st Annual Meeting of the Deutsche Gesellschaft für Lasermedizin (DGLM) e.V.
- Congresses 2014/2015
Articles in the same Issue
- Frontmatter
- Editorial
- Laser interstitial thermal therapy (LITT) of the brain – Experiences and new indications
- Magazine section
- Snapshots
- Reviews
- Laser interstitial thermal therapy with and without MRI guidance for treatment of brain neoplasms – A systematic review of the literature
- Laser interstitial thermal therapy for treatment of post-radiosurgery tumor recurrence and radiation necrosis
- MRI-guided laser interstitial thermal therapy of intracranial tumors and epilepsy: State-of-the-art review and a case study from pediatrics
- Original contributions
- Percutaneous selective laser amygdalo-hippocampectomy (SLAH) for treatment of mesial temporal lobe epilepsy within an interventional MRI suite
- Interstitial laser irradiation of cerebral gliomas – neurobiological background, technique and typical results
- Prognostic factors of overall survival after laser interstitial thermal therapy in patients with glioblastoma
- Laser interstitial thermal therapy as a novel treatment modality for brain tumors in the thalamus and basal ganglia
- Preliminary research report
- Endoscopic fluorescence visualization of 5-ALA photosensitized central nervous system tumors in the neural tissue transparency spectral range
- Congress announcements
- 21st Annual Meeting of the Deutsche Gesellschaft für Lasermedizin (DGLM) e.V.
- Congresses 2014/2015
