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Combination of Hand-Held Probe and Microscopy for Fluorescence Guided Surgery in the Brain Tumor Marginal Zone
Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. (MINT)
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. (MINT)ORCID iD: 0000-0002-0555-8877
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. (MINT)ORCID iD: 0000-0002-0012-7867
2017 (English)In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, Vol. 18, p. 185-192Article in journal (Refereed) Published
Abstract [en]

Background

Visualization of the tumor is crucial for differentiating malignant tissue from healthy brain during surgery, especially in the tumor marginal zone. The aim of the study was to introduce a fluorescence spectroscopy-based hand-held probe (HHF-probe) for tumor identification in combination with the fluorescence guided resection surgical microscope (FGR-microscope), and evaluate them in terms of diagnostic performance and practical aspects of fluorescence detection.

Material and Methods

Eighteen operations were performed on 16 patients with suspected high-grade glioma. The HHF-probe and the FGR-microscope were used for detection of protoporphyrin (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) and evaluated against histopathological analysis and visual grading done through the FGR-microscope by the surgeon. A ratio of PpIX fluorescence intensity to the autofluorescence intensity (fluorescence ratio) was used to quantify the spectra detected by the probe.

Results

Fluorescence ratio medians (range 0 – 40) measured by the probe were related to the intensity of the fluorescence in the FGR-microscope, categorized as “none” (0.3, n = 131), “weak” (1.6, n = 34) and “strong” (5.4, n = 28). Of 131 “none” points in the FGR-microscope, 88 (67%) exhibited fluorescence with the HHF-probe. For the tumor marginal zone, the area under the receiver operator characteristics (ROC) curve was 0.49 for the FGR-microscope and 0.65 for the HHF-probe.

Conclusions

The probe was integrated in the established routine of tumor resection using the FGR-microscope. The HHF-probe was superior to the FGR-microscope in sensitivity; it detected tumor remnants after debulking under the FGR-microscope. The combination of the HHF-probe and the FGR-microscope was beneficial especially in the tumor marginal zone.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2017. Vol. 18, p. 185-192
Keywords [en]
High-grade glioma, Fluorescence guided resection (FGR), 5-Aminolaevulinic acid (5-ALA), Fluorescence spectroscopy, Protoporphyrin (PpIX)
National Category
Medical Engineering
Identifiers
URN: urn:nbn:se:liu:diva-134849DOI: 10.1016/j.pdpdt.2017.01.188ISI: 000404315000028PubMedID: 28223144OAI: oai:DiVA.org:liu-134849DiVA, id: diva2:1079583
Note

Funding agencies: Swedish Governmental Agency for Innovation Systems (Vinnova); Swedish Foundation for Strategic Research (SSF); Swedish Research Council (VR) [311-2006-7661, 523-2013-2735]; NovaMedTech; Swedish Childhood Cancer Foundation [MT 2013-0043]; ALF Grants Region

Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-05-07Bibliographically approved
In thesis
1. Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe
Open this publication in new window or tab >>Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malignant gliomas grow infiltrative in the brain and can therefore not be completely removed by neurosurgical means. However, for an optimized oncological treatment it has proven useful to resect as much as possible of tumor. The identification of the tumor in the marginal zone is difficult but crucial. Studies have shown that visualization of the specific enhancement of 5-aminolevulinic acid(5-ALA) in the tumor can help to maximize the resection. The Department of Biomedical Engineering, Linköping University, has developed an optical hand-held probe (HHP) to identify tumor tissue with a high sensitivity by means of fluorescence spectroscopy.

The technical design and the optical properties of the probe were gradually developed in a standard neurosurgical setting during resection of malignant gliomas. The device could easily be implemented in the operating room, meeting all requirements in terms of sterile handling and without interference of any kind with other equipment. The integration of the device in a navigation system and its use in combination with a blue light surgical microscope were simple. Measurements in 27 operations during resection of malignant gliomas were compared to results from biopsies from the same tumor locations. The equipment was tested as a stand-alone device (n = 180), integrated in a navigation system or in combination with the blue light microscope (n = 190). A ratiocal culated from the measurements enabled objective and comparable values for different tissue types, in correspondence with the findings from the histopathological examinations and in accordance with the navigation system as well as with the surgical microscope.The marginal zone was explored and tumor fluorescence could be identified beyond the fluorescence as seen through the microscope. A higher sensitivity of the HHP was confirmed; the specificity was lower.

The combined use of the HHP with a navigation system and with asurgical microscope was beneficial.

Abstract [sv]

Maligna hjärntumörer växer infiltrerande i hjärnan och kan därförinte helt avlägsnas genom kirurgiska operationer. För en optimerad behandling har det emellertid visat sig vara av värde att avlägsna såmycket som möjligt av tumörvävnaden. Identifiering av tumören i gränszonen är mycket svårt, men avgörande. Studier har visat att visualisering av den specifika laddningen av 5-aminolevulinsyra (5-ALA) i tumören kan bidra till att maximera resektionen. Institutionen för Medicinsk Teknik (IMT) på Linköpings universitet,har utvecklat en liten handhållen optisk prob (HHP) för att identifiera tumörvävnad med hög känslighet med hjälp avfluorescens-spektroskopi.

Den tekniska konstruktionen och de optiska egenskaperna hos proben utvecklades stegvis genom testning i flera neurokirurgiska operationer för resektion av maligna gliom. Utrustningen uppfyllde alla krav när det gällde steril hantering i operationssalen och kunde användas utan störningar av något slag med annan operationsutrustning. Integreringen i ett navigerings-system och användningen i kombination med ett kirurgiskt mikroskop för fluorescens-styrd kirurgi var oproblematiska. Mätningar under 27 operationer vid resektion av maligna gliom jämfördes med resultat från biopsier från samma tumörtagningsställen. Utrustningen testades såväl som en fristående enhet (n = 180) och som integrerad i ett navigationssystem eller i kombination med mikroskopet (n =190). En särskild kvot beräknad ur mätningarna möjliggjorde objektiva och jämförbara värden för olika vävnader, i överensstämmelse med resultaten från de vävnadspatologiska undersökningarna och i överensstämmelse med navigationssystemet såväl som med det kirurgiska mikroskopet.

Tumörernas gränszon undersöktes och tumörfluorescens kunde identifieras bortom fluorescensen som mikroskopet visade. En högre känslighet hos HHP bekräftades; specificiteten var lägre. Den kombinerade användningen av HHP med ett navigationssystem och med ett kirurgiskt mikroskop visade sig vara fördelaktig.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. p. 77
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1581
National Category
Surgery Neurosciences Medical Laboratory and Measurements Technologies Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-139793 (URN)10.3384/diss.diva-139793 (DOI)978-91-7685-475-4 (ISBN)
Public defence
2017-09-01, Hugo Theorell, ingång 7, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2018-01-13Bibliographically approved

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