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Fluorescence Spectroscopy Measurements in Ultrasonic Navigated Resection of Malignant Brain Tumors
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. (MINT)
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. (MINT)ORCID iD: 0000-0002-0555-8877
Department of Physics, Lund University.
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. (MINT)ORCID iD: 0000-0002-0012-7867
2011 (English)In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 43, no 1, 8-14 p.Article in journal (Refereed) Published
Abstract [en]

Background and Objective: Glioblastoma multiforme is a highly malignant primary brain tumor. It has no border but at best a marginal zone, however, invisible to the surgeon. An optical touch pointer (OTP) enabling differentiation of healthy and tumor tissue by means of fiber-optic fluorescence spectroscopy has been developed. In combination with an ultrasonic navigation system, the OTP may be used for demarcation of resectable tumor tissue. The aim of the study was to evaluate the clinical performance of OTP during surgery of malignant brain tumors. 

Study Design/Materials and Methods: Nine patients were operated on with the standard surgical procedure, including white light microscopy and navigation. A total of 5 mg/kg bodyweight of 5-amino-levulin acid was orally administrated before surgery. The OTP was calibrated into the ultrasound-based navigation system and measurements were performed in tumor core and along the tumor border. The ratio between the protoporphyrin IX fluorescence at 635 nm and the autofluorescence was used for quantifications of data. Biopsies (n =20), ultrasound images (n = 30), and visual inspection (n =180) were compared to the fluorescence ratio. 

Results/Conclusion : Healthy and tumor tissue could be identified and differentiated with the OTP(P < 0.001). The fluorescence ratio in average was 0 outside the tumor and low in the gliotic edema zone around the tumor. It increased in the marginal zone and was highest in the solid tumor tissue. In the necrotic tissue, in the center of the tumor, the ratio in average was 0. The OTP can be used in combination with ultrasound-based navigation and may help to determine whether to resect otherwise not identifiable tissue.

Place, publisher, year, edition, pages
2011. Vol. 43, no 1, 8-14 p.
Keyword [en]
5-amino-levulin acid (5-ALA);fluorescence-guided resection (FGR);glioblastoma multiforme;optical touch pointer (OTP);protoporphyrin IX (PpIX) fluorescence;ultrasound navigation
National Category
Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:liu:diva-64689DOI: 10.1002/lsm.21022ISI: 000286440300002OAI: oai:DiVA.org:liu-64689DiVA: diva2:393931
Available from: 2011-02-01 Created: 2011-02-01 Last updated: 2017-12-11Bibliographically 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. 77 p.
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: 2017-08-21Bibliographically approved

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Richter, Johan C.O.Haj-Hosseini, NedaWårdell, Karin

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