Optical touch pointer for fluorescence guided glioblastoma resection using 5‐aminolevulinic acid

Abstract

Background and Objective: Total tumor resection in patients with glioblastoma multiforme (GBM) is difficult to achieve due to the tumor's infiltrative way of growing and morphological similarity to the surrounding functioning brain tissue. The diagnosis is usually subjectively performed using a surgical microscope. The objective of this study was to develop and evaluate a hand-held optical touch pointer using a fluorescence spectroscopy system to quantitatively distinguish healthy from malignant brain tissue intraoperatively. Study Design/Materials and Methods:A fluorescence spectroscopy system with pulsed modulation was designed considering optimum energy delivery to the tissue, minimal photobleaching of PpIX and omission of the ambient light background in the operating room (OR). 5-aminolevulinic acid (5-ALA) of 5 mg/kg body weight was given to the patients with a presumed glioblastoma multiforme prior to surgery. During the surgery a laser pulse at 405 nm was delivered to the tissue. PpIX in glioblastoma tumor cells assigned with peaks at 635 nm and 704 nm was detected using a fiber optical probe.Results/Conclusion: By using the pulsed fluorescence spectroscopy, PpIX fluorescence is quantitatively detected in the glioblastoma multiforme. An effective suppression of low power lamp background from the recorded spectra in addition to a significant reduction of high power surgical lights is achieved.

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

“…The system was designed and adapted for neurosurgical applications as we have described in a previous publication [9]. The probe consisted of a central fiber connected to the excitation light (λ = 405 nm) and several surrounding fibers connected to a 2048 element charge coupled device (CCD) based spectrometer (EPP 2000, StellarNet, Inc., Tampa, FL, USA) with maximum 8192 photon counts expressed in arbitrary units (a.u.).…”

“…The tumor resection using the microscope is based on removing the sites with strong fluorescence and leaving the weak fluorescence sites both of which are based on the visual observation of the surgeon. Fiber-optic probe based spectroscopy is an alternative to the surgical microscope for detecting fluorescence objectively [8][9][10][11][12]. The probe is beneficial when the microscope fails to show any fluorescence specifically at the end of tumor removal for examining the resection cavity.…”

“…The aim of the present study was to investigate the clinical relevant implications of applying a four times lower ALA dose (5 mg/kg) than the recommended for the microscope and to compare the fluorescence signal intensities and the diagnostic performance for each dose. The studies were performed using a fluorescence spectroscopy system and a handheld fiber optic probe described previously [9]. …”

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

“…Additionally, a broad and characteristic emission spectrum is induced, allowing the extraction of valuable spectral information. [46,47] Moreover, the use of a 405 nm light source also leads to the excitation of tissue autofluorescence, which could be used as an additional parameter for tissue discrimination [48][49][50] or serve as reference for the normalization of PpIX signals [27].…”

“…[22][23][24] A tumor-related deficient blood brain barrier and an altered activity level of several enzymes including ferrochelatase, which catalyzes the conversion of PpIX to heme, are central reasons for this phenomenon. [25] Tumor recognition with 5-ALA-induced PpIX is already effectively used for fluorescence-guided resection of malignant gliomas using surgical microscopes [22,23,26] or fiber optical probes [27,28]. It leads to a significantly increased complete resection rate of these diffusely growing tumors and to a significantly enhanced progression-free survival rate after 6 months, translating into a progression-free survival prolongation of 1.5 months as compared to conventional white light resection.…”