Brain tumor needle biopsies are performed to retrieve tissue samples for neuropathological analysis. Although preoperative images guide the procedure, there are risks of hemorrhage and sampling of non-tumor tissue. This study aimed to develop and evaluate a method for frameless one-insertion needle biopsies with in situ optical guidance and present a processing pipeline for combined postoperative analysis of optical, MRI, and neuropathological data. An optical system for quantified feedback on tissue microcirculation, gray-whiteness, and the presence of a tumor (protoporphyrin IX (PpIX) accumulation) with a one-insertion optical probe was integrated into a needle biopsy kit that was used for frameless neuronavigation. In Python, a pipeline for signal processing, image registration, and coordinate transformation was set up. The Euclidian distances between the pre- and postoperative coordinates were calculated. The proposed workflow was evaluated on static references, a phantom, and three patients with suspected high-grade gliomas. In total, six biopsy samples that overlapped with the region of the highest PpIX peak without increased microcirculation were taken. The samples were confirmed as being tumorous and postoperative imaging was used to define the biopsy locations. A 2.5 ± 1.2 mm difference between the pre- and postoperative coordinates was found. Optical guidance in frameless brain tumor biopsies could offer benefits such as quantified in situ indication of high-grade tumor tissue and indications of increased blood flow along the needle trajectory before the tissue is removed. Additionally, postoperative visualization enables the combined analysis of MRI, optical, and neuropathological data.

BACKGROUND: Stereotactic neurosurgical brain biopsies are afflicted with risks of inconclusive results and hemorrhage. Such complications can necessitate repeated trajectories and prolong surgical time.

OBJECTIVE: To develop and introduce a 1-insertion stereotactic biopsy kit with direct intraoperative optical feedback and to evaluate its applicability in 3 clinical cases.

METHODS: An in-house forward-looking probe with optical fibers was designed to fit the outer cannula of a side-cutting biopsy kit. A small aperture was made at the tip of the outer cannula and the edges aligned with the optical probe inside. Stereotactic biopsies were performed using the Leksell Stereotactic System. Optical signals were measured in millimeter steps along the preplanned trajectory during the insertion. At the region with the highest 5-aminolevulinic acid (5-ALA)-induced fluorescence, the probe was replaced by the inner cannula, and tissue samples were taken. The waiting time for pathology diagnosis was noted.

RESULTS: Measurements took 5 to 10 minutes, and the surgeon received direct visual feedback of intraoperative 5-ALA fluorescence, microcirculation, and tissue gray-whiteness. The 5-ALA fluorescence corroborated with the pathological findings which had waiting times of 45, 50, and 75 minutes. Because only 1 trajectory was required and the patient could be prepared for the end of surgery immediately after sampling, this shortened the total surgical time.

CONCLUSION: A 1-insertion stereotactic biopsy procedure with real-time optical guidance has been presented and successfully evaluated in 3 clinical cases. The method can be modified for frameless navigation and thus has great potential to improve safety and diagnostic yield for both frameless and frame-based neurosurgical biopsy procedures.

In brain tumor surgery it is difficult to distinguish the marginal zone with the naked eye. Fluorescence techniques can help identifying tumor tissue in the zone during resection and biopsy procedures. In this paper a novel system for combined real-time measurements of PpIX-fluorescence, microcirculation and tissue grey-whiteness is presented and experimentally evaluated. The system consists of a fluorescence hardware with a sensitive CCD spectrometer for PpIX peak detection, a laser Doppler system, optical probes, and a LabView software. System evaluation was done on static fluorescing material, human skin, and brain tumor tissue. The static material indicates reproducibility, the skin measurements exemplify simultaneous fluorescence and microcirculation measurement in real-time, and the tumor tissue showed PpIX peaks. These decreased over time, as expected, due to photo bleaching. In addition, the system was prepared for clinical use and thus laser- and electrical safety issues were considered. In summary, a system for multiparameter measurements during neurosurgery was successfully evaluated in an experimental environment. As a next step the system will be applied in clinical brain tumor biopsies and resections.

BACKGROUND Accurate stereotactic biopsies of brain tumors are imperative for diagnosis and tailoring of the therapy. Repetitive needle insertions enhance risks of brain lesioning, hemorrhage, and complications due to prolonged procedure.

OBJECTIVE To investigate clinical benefits of a combined 5-aminolaevulinic acid (5-ALA) fluorescence and laser Doppler flowmetry system for the detection of malignant brain tumor and blood vessels in stereotactic biopsies.

METHODS Planning of targets and trajectories was followed by optical measurements in 20 patients, using the Leksell Stereotactic System and a manual insertion device. Fluorescence spectra, microvascular blood flow, and tissue grayness were recorded each millimeter along the paths. Biopsies were taken at preplanned positions. The diagnoses were compared with the fluorescence signals. The recordings were plotted against measurement positions and compared. Sites indicating a risk of hemorrhage were counted as well as the time for the procedures.

RESULTS Signals were recorded along 28 trajectories, and 78 biopsies were collected. The final diagnosis showed 17 glioblastomas, 2 lymphomas, and 1 astrocytoma grade III. Fluorescence was seen along 23 of the paths with 4 having the peak of 5-ALA fluorescence 3 mm or more from the precalculated target. There was increased microcirculation in 40 of 905 measured positions. The measurement time for each trajectory was 5 to 10 min.

CONCLUSION The probe provided direct feedback of increased blood flow along the trajectory and of malignant tissue in the vicinity of the target. The method can increase the precision and the safety of the biopsy procedure and reduce time.

Background: Whilst modern awake intraoperative mapping has been widely accepted and implemented in the last decades in neuro-oncology, sparse reports have been published on the safety and efficiency of this approach in epilepsy surgery. Method: This article reports four cases with different locations of epileptogenic zones as examples of possible safe and efficient resections. Result: The results of the resections on seizure control were Engel 1 (no disabling seizures) in all cases and no patient experienced significant neurological deficits. Discussion: The discussion focuses on aspects of the future of epilepsy surgery in a hodotopical paradigm.

A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measurement of 5-aminolevulinic acid (5-ALA) induced fluorescence and microvascular blood flow. Along three stereotactic trajectories, fluorescence (n = 109) and laser Doppler flowmetry (LDF) (n = 144) measurements were done in millimeter increments. The recorded signals were compared to histopathology and radiology images. The median ratio of protoporphyrin IX (PpIX) fluorescence and autofluorescence (AF) in the tumor was considerably higher than the marginal zone (17.3 vs 0.9). The blood flow showed two high spots (3%) in total. The proposed setup allows simultaneous and real-time detection of tumor tissue and microvascular blood flow for tracking the vessels.

To provide guidance during stereotactic biopsy in brain tumors, fluorescence spectroscopy was used in ten patients. It was shown that the fiber optical probe could provide real-time guidance with clear fluorescence in all patients.

Laser Doppler flowmetry (LDF) has been adapted for optical guidance during stereotactic deep brain stimulation (DBS) surgery. It has been used in more than 130 DBS implantations. The necessary steps to go from experimental studies to clinical use in the neurosurgical setting are reviewed.

To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture during the biopsy procedure an application specific fiber optic probe was devel-oped. The setup incorporated an in-house developed fluorescence spectroscopy system for 5-aminolevulinic acid (5-ALA) induced protopophyrin IX (PpIX) for detection in the tumor, and laser Doppler flowmeter (LDF) system for measurement of blood perfusion. Fluorescence and blood flow were recorded millimeter-wise towards the pre-calculated target. In conclusion, the optical probe made real-time detection of tumor possible and has a potential for vessel detection during the biopsy procedures. Moreover, the PpIX fluorescence, autofluorescence and blood flow in the tumor could be studied at precise positions in the brain and the tumor. In the next step, further anal-ysis will be added.

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.

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.

During stereotactic biopsy on suspected tumors in the brain, tissue samples are harvested to determine the malignancy. To provide guidance for finding the diagnostic tumor sites and to avoid vessel rupture, an application specific probe was developed. The setup incorporated spectroscopy for detection of 5-aminolevulinic acid induced protoporphyrin (PpIX) fluorescence and blood flow using laser Doppler flowmetry. The PpIX fluorescence was significantly different in the tumor compared to the gliotic marginal zone (p < 0.05). In conclusion, the systems made real-time tumor detection and vessel tracking possible. Moreover, the autofluorescence and blood perfusion could be studied in the tumor.

Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.

Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.

Material and Methods:

A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.

Results and Conclusion:

Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.

Background

Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kg b.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance.

Methods

A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. (n = 15) dissolved in orange juice or 20 mg/kg b.w. (n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements.

Results

The binominal comparison of the diagnostic performance parameters showed no significant statistical difference (p > 0.05). The median fluorescence values in tumor were 2-3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14).

Conclusions

Application of 5 mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients.

Since getting approved for clinical application in neurosurgery 5-aminolevulinic acid (ALA), that is a fluorescence contrast agent, has attracted the interest of many neurosurgical clinics to implement it in their surgical routine. ALA naturally exists in the body and the external administration of the substance induces accumulation of a fluorophore known as protoporphyrin IX (PpIX) in the malignant cells due to a broken blood brain barrier and the altered enzyme levels in the brain tumor. The detection and visualization of PpIX in the clinical routine is conventionally performed using a modified neuro surgical microscope. As a complementary technique for detection of ALA-induced fluorescence and to perform objective and quantitative measurements, our group has developed a spectroscopy system adapted to the equipment in the operating room. The system includes a hand-held fiber optic probe which can be integrated in the neuronavigation and stereotactic systems. The main advantages of the system are the ease of use, high sensitivity, quantitative fluorescence detection and the possibility of applying a low dose of fluorescence contrast agent while obtaining equally reliable results as with the high dose. In this contribution we present our experience, gains and challenges from implementation of the system during brain tumor surgery in forty adult patients. The methods and systems are currently being adapted for implementation during operations of pediatric brain tumors.

BACKGROUND: Deep brain stimulation (DBS) requires precise and safe navigation to the chosen target. Optical measurements allow monitoring of gray-white tissue boundaries (total light intensity [TLI]) and microvascular blood flow during stereotactic procedures.

OBJECTIVE: To establish the link between TLI/blood flow and anatomy along trajectories toward the ventral intermediate nucleus (Vim) and subthalamic nucleus (STN).

METHODS: Stereotactic laser Doppler measurements were obtained with millimeter precision from the cortex toward the Vim (n = 13) and STN (n = 9). Optical trajectories of TLI and blood flow were created and compared with anatomy by superimposing the Schaltenbrandt-Wahren atlas on the patients' pre- and postoperative images. Measurements were divided into anatomic subgroups and compared statistically.

RESULTS: Typical TLI trajectories with well-defined anatomic regions could be identified for the Vim and STN. TLI was significantly lower (P < .001) and microvascular blood flow significantly higher (P = .01) in the Vim targets. Of 1285 sites, 38 showed blood flow peaks, 27 of them along the Vim trajectories. High blood flow was more common close to the sulci and in the vicinity of the caudate/putamen. Along 1 Vim trajectory, a slight bleeding was suspected during insertion of the probe and confirmed with postoperative computed tomography.

CONCLUSION: Laser Doppler is useful for intraoperative guidance during DBS implantation because simultaneous measurement of tissue grayness and microvascular blood flow can be done along the trajectory with millimeter precision. Typical but different TLI trajectories were found for the Vim and STN.

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease and related movement disorders. The success of DBS is highly dependent on electrode location, electrical parameter settings and the surgical procedure. In this paper an overview of the current status of optical measurements for intracerebral guidance performed during DBS implantation is presented. Laser Doppler perfusion monitoring and/or reflection spectroscopy measurements have been done in relation to more than 70 DBS lead implantations to wards targets in the deep brain structures. The techniques have also been compared with impedance monitoring, and simulation of the measurement depth has been done with Monte Carlo technique. These studies show that grey-white matter boundaries can be determined with a resolution higher than for both impedance measurements and magnetic resonance imaging.

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.

Glioblastoma multiforme (GBM), a highly malignant primary brain tumor, is difficult to distinguish from from its surrounding functioning tissue under direct vision in the operating field, since it grows in an infiltrative growth pattern. The main challenge in the surgical treatment of GBM is to fully resect the tumor and avoid neurological impairment. In this paper we extend previous proof-of-principle studies by extending the clinical potential of OTP with the introduction of more sophisticated multivariate analysis schemes. The aim is to distinguish tumor and healthy tissue as well as possible using singular value decomposition (SVD) and cluster analysis methods.

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 GBM 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 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 GBM. 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.

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease and related movement disorders. The success of DBS is highly dependent on electrode location, electrical parameter settings and the surgical procedure. In this paper an overview of the current status of optical measurements for intracerebral guidance performed during DBS implantation is presented. Laser Doppler perfusion monitoring and/or reflection spectroscopy measurements have been done in relation to more than 70 DBS lead implantations to wards targets in the deep brain structures. The techniques have also been compared with impedance monitoring, and simulation of the measurement depth has been done with Monte Carlo technique. These studies show that grey-white matter boundaries can be determined with a resolution higher than for both impedance measurements and magnetic resonance imaging.

The highly malignant brain tumor, glioblastoma multiforme (GBM), is difficult to fully delineate during surgical resection due to its infiltrative ingrowth and morphological similarities to surrounding functioning brain tissue. Selectiveness of GBM to 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) is reported by other researchers to visualize tumor margins under blue light microscopy. To allow objective detection of GBM, a compact and portable fiber optic based fluorescence spectroscopy system is developed. This system is able to deliver excitation laser light (405 nm) in both the continuous and pulsed mode. PpIX fluorescence peaks are detected at 635 and 704 nm, using a fiber-coupled spectrometer. It is necessary to optimize the detection efficiency of the system as the PpIX quickly photobleaches during the laser illumination. A light dose of 2.5 mJ (fluence rate = 9 mJ/mm²) is experimentally approved to excite an acceptable level of fluourescence signal arising from glioblastoma. In pulsed illumination mode, an excitation dose of 2.5 mJ, with a dark interval of 0.5 s (duty cycle 50%) shows a significantly shorter photobleaching time in comparison to the continuous illumination mode with the same laser power (p < 0.05). To avoid photobleaching (the remaining signal is more than 90% of its initial value) when measuring with 2.5 mJ delivered energy, the time for continuous and pulsed illumination should be restricted to 2.5 and 1.1 s, respectively.

Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

The highly malignant brain tumor, glioblastoma multiforme, is difficult to totally resect without aid due to its infiltrative way of growing and its morphological similarities to surrounding functioning brain under direct vision in the operating field. The need for an inexpensive and robust real-time visualizing system for resection guiding in neurosurgery has been formulated by research groups all over the world. The main goal is to develop a system that helps the neurosurgeon to make decisions during the surgical procedure. A compact fiber optic system using fluorescence spectroscopy has been developed for guiding neurosurgical resections. The system is based on a high power light emitting diode at 395 nm and a spectrometer. A fiber bundle arrangement is used to guide the excitation light and fluorescence light between the instrument and the tissue target. The system is controlled through a computer interface and software package especially developed for the application. This robust and simple instrument has been evaluated in vivo both on healthy skin but also during a neurosurgical resection procedure. Before surgery the patient received orally a low dose of 5-aminolevulinic acid, converted to the fluorescence tumor marker protoporphyrin IX in the malignant cells. Preliminary results indicate that PpIX fluorescence and brain tissue autofluorescence can be recorded with the help of the developed system intraoperatively during resection of glioblastoma multiforme.

The aim of the study was to investigate if laser Doppler perfusion monitoring (LDPM) can be used in order to differentiate between gray and white matter and to what extent microvascular perfusion can be recorded in the deep brain structures during stereotactic neurosurgery. An optical probe constructed to fit in the Leksell® Stereotactic System was used for measurements along the trajectory and in the targets (globus pallidus internus, subthalamic nucleus, zona incerta, thalamus) during the implantation of deep brain stimulation leads (n = 22). The total backscattered light intensity (TLI) reflecting the grayness of the tissue, and the microvascular perfusion were captured at 128 sites. Heartbeat-synchronized pulsations were found at all perfusion recordings. In 6 sites the perfusion was more than 6 times higher than the closest neighbor indicating a possible small vessel structure. TLI was significantly higher (p < 0.005) and the perfusion significantly lower (p < 0.005) in positions identified as white matter in the respective MRI batch. The measurements imply that LDPM has the potential to be used as an intracerebral guidance tool.