Neurosurgical Microscope Research Articles

5-ALA–induced fluorescence as a marker for diagnostic tissue in stereotactic biopsies of intracranial lymphomas: experience in 41 patients

OBJECTIVE Stereotactic needle biopsies are usually performed for histopathological confirmation of intracranial lymphomas to guide adequate treatment. During biopsy, intraoperative histopathology is an effective tool to avoid acquisition of nondiagnostic samples. In the last years, 5-aminolevulinic acid (5-ALA)-induced fluorescence has been increasingly used for visualization of diagnostic brain tumor tissue during stereotactic biopsies. Recently, visible fluorescence was reported in the first cases of intracranial lymphomas as well. The aim of this study is thus to investigate the technical and clinical utility of 5-ALA-induced fluorescence in a large series of stereotactic biopsies for intracranial lymphoma. METHODS This prospective study recruited adult patients who underwent frameless stereotactic needle biopsy for a radiologically suspected intracranial lymphoma after oral 5-ALA administration. During biopsy, samples from the tumor region were collected for histopathological analysis, and presence of fluorescence (strong, vague, or no fluorescence) was assessed with a modified neurosurgical microscope. In tumors with available biopsy samples from at least 2 different regions the intratumoral fluorescence homogeneity was additionally investigated. Furthermore, the influence of potential preoperative corticosteroid treatment or immunosuppression on fluorescence was analyzed. Histopathological tumor diagnosis was established and all collected biopsy samples were screened for diagnostic lymphoma tissue. RESULTS The final study cohort included 41 patients with intracranial lymphoma. Stereotactic biopsies with assistance of 5-ALA were technically feasible in all cases. Strong fluorescence was found as maximum level in 30 patients (75%), vague fluorescence in 2 patients (4%), and no visible fluorescence in 9 patients (21%). In 28 cases, samples were obtained from at least 2 different tumor regions; homogenous intratumoral fluorescence was found in 16 of those cases (57%) and inhomogeneous intratumoral fluorescence in 12 (43%). According to histopathological analysis, all samples with strong or vague fluorescence contained diagnostic lymphoma tissue, resulting in a positive predictive value of 100%. Analysis showed no influence of preoperative corticosteroids or immunosuppression on fluorescence. CONCLUSIONS The data obtained in this study demonstrate the technical and clinical utility of 5-ALA-induced fluorescence in stereotactic biopsies of intracranial lymphomas. Thus, 5-ALA can serve as a useful tool to select patients not requiring intraoperative histopathology, and its application should markedly reduce operation time and related costs in the future.

Systematic histopathological analysis of different 5-aminolevulinic acid-induced fluorescence levels in newly diagnosed glioblastomas.

OBJECTIVE Glioblastoma (GBM) is characterized by distinct intratumoral histopathological heterogeneity with regard to variable tumor morphology, cell proliferation, and microvascularity. Maximum resection of a GBM results in an improved prognosis and thus represents the aim of surgery in the majority of cases. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is currently widely applied for improved intraoperative tumor visualization in patients with a GBM. Three intratumoral fluorescence levels (i.e., strong, vague, or no fluorescence) can usually be distinguished during surgery. So far, however, their exact histopathological correlates and their surgical relevance have not been clarified sufficiently. Thus, the aim of this study was to systematically analyze tissue samples from newly diagnosed GBMs with different fluorescence levels according to relevant histopathological parameters. METHODS This prospective study recruited patients who underwent 5-ALA fluorescence-guided resection of a newly diagnosed radiologically suspected GBM. Each patient received 5-ALA approximately 3 hours before surgery, and a modified neurosurgical microscope was applied for intraoperative visualization of 5-ALA-induced fluorescence. During surgery, tissue samples with strong, vague, or no fluorescence were collected. For each sample, the presence of tumor tissue, quality of tissue (compact, infiltrative, or no tumor), histopathological criteria of malignancy (cell density, nuclear pleomorphism, mitotic activity, and presence of microvascular proliferation/necrosis), proliferation rate (MIB-1 labeling index [LI]), and microvessel density (using CD34 staining) were investigated. RESULTS Altogether, 77 patients with a newly diagnosed, histopathologically confirmed GBM were included, and 131 samples with strong fluorescence, 69 samples with vague fluorescence, and 67 samples with no fluorescence were collected. Tumor tissue was detected in all 131 (100%) of the samples with strong fluorescence and in 65 (94%) of the 69 samples with vague fluorescence. However, mostly infiltrative tumor tissue was still found in 33 (49%) of 67 samples despite their lack of fluorescence. Strong fluorescence corresponded to compact tumors in 109 (83%) of 131 samples, whereas vague fluorescence was consistent with infiltrative tumors in 44 (64%) of 69 samples. In terms of the histopathological criteria of malignancy, a significant positive correlation of all analyzed parameters comprising cell density, nuclear pleomorphism, mitotic activity, microvascular proliferation, and necrosis with the 3 fluorescence levels was observed (p < 0.001). Furthermore, the proliferation rate significantly and positively correlated with strong (MIB-1 LI 28.3%), vague (MIB-1 LI 16.7%), and no (MIB-1 LI 8.8%) fluorescence (p < 0.001). Last, a significantly higher microvessel density was detected in samples with strong fluorescence (CD34 125.5 vessels/0.25 mm2) than in those with vague (CD34 82.8 vessels/0.25 mm2) or no (CD34 68.6 vessels/0.25 mm2) fluorescence (p < 0.001). CONCLUSIONS Strong and vague 5-ALA-induced fluorescence enables visualization of intratumoral areas with specific histopathological features and thus supports neurosurgeons in improving the extent of resection in patients with a newly diagnosed GBM. Despite the lack of fluorescence, tumor tissue was still observed in approximately half of the cases. To overcome this current limitation, the promising approach of complementary spectroscopic measurement of fluorescence should be investigated further.

5-Aminolevulinic acid fluorescence guided resection of malignant glioma: Hong Kong experience

5-Aminolevulinic Acid (5-ALA) induced fluorescence is useful in guiding glioma resection. The extent of 5-ALA accumulation is beyond gadolinium contrast enhancement.1,2 Supratotal resection may be achieved, potentially granting patients with better survival. We present our experience on 5-ALA guided glioma resection in Chinese ethnics. Sixteen Patients ingested 5-ALA (Gliolan, Medas Germany) 20mg/kg·m2 4h before surgery. The tumor resection was guided by fluorescence with neurosurgical microscope. Patient was monitored for general condition, especially for new neurological deficits. Postoperative MRI served as the assessment for extent of resection (EOR). High grade glioma was confirmed in 12 cases, low grade glioma in three and one inflammation. 5-ALA was used in ten patients with known malignant glioma, and in six patients with presumed diagnosis of malignant glioma. Fifteen cases had positive fluorescence. The intensity was strong in eight and moderate in seven cases. MRI suggested total resection was achieved in 9 patients, near total resection in two and five had subtotal resection. EOR was associated with duration between ingestion of 5-ALA and timing when microscope was brought in for visualization of fluorescence (p=0.038). Two patients suffered from temporary visual field defects. One patient developed hemiparesis after surgery. 5-ALA is a useful intra-operative guidance for resection. It increases the percentageof total removal of the tumor. It should be used within the window period of the action (4-12h).

Raman spectroscopy in microsurgery: impact of operating microscope illumination sources on data quality and tissue classification.

Ambient light artifacts can confound Raman spectroscopy measurements performed in a clinical setting such as during open surgery. However, requiring light sources to be turned off during intraoperative spectral acquisition can be impractical because it can slow down the procedure by requiring surgeons to acquire data under light conditions different from the routine clinical practice. Here a filter system is introduced allowing in vivo Raman spectroscopy measurements to be performed with the light source of a neurosurgical microscope turned on, without interfering with the standard procedure. Ex vivo and in vivo results on calf and human brain, respectively, show that when the new filter system is used there is no significant difference between Raman spectra acquired under pitch dark conditions or with the microscope light source turned on. This is important for the clinical translation of Raman spectroscopy because of the resulting decrease in total imaging time for each measurement and because the surgeon can now acquire spectroscopic data with no disruption of the surgical workflow.

Intraoperative fluorescein staining for benign brain tumors

ObjectiveSuccessful use of high-dose fluorescein-sodium (20mg/kg) with a standard light microscope for resection of high-grade gliomas, meningiomas, hemangioblastoma and metastases was reported. The principle of brain tumor staining by fluorescein-sodium (Fl-Na) consists in the accumulation of fluorescein in brain tumors with impaired blood-brain barrier. The aim of our study was to investigate for the first time the usefulness of high-dose fluorescein in patients operated on for benign neuroepithelial brain tumors (grade I WHO tumors) with contrast enhancement on magnetic resonance imaging. MethodsOur study included 11 patients operated on for benign neuroepithelial primary brain tumors with contrast enhancement on magnetic resonance imaging (MRI): pilocytic astrocytomas (5 patients), dysembrioplastic neuroepithelial tumors (4) and gangliogliomas grade I (2). In all cases, Fl-Na was injected intravenously (20mg/kg) just after the craniotomy using a peripheral venous line. The dural opening was performed 10min later. Microsurgical tumor resection using conventional neurosurgical microscope guided by the fluorescein staining was performed. ResultsComplete resection of the yellow-green stained tissue was achieved in 10 patients confirmed by postoperative control MRI study. Subtotal resection of the colored tissue was achieved in one case with fourth ventricle pilocytic astrocytoma because of the involvement of the medial eminence and functional constraints discovered during intraoperative neuromonitoring. Three patients have had a postoperative volume of resection greater than the tumor volume because of the planed perilesionectomy by our epilepsy surgery team. Surrounding tissue not stained by Fl-Na was obtained in these 3 cases. The histopathological examination did not find tumor tissue in the perilesional Fl-Na negative tissue. On the other hand, all 11 Fl-Na positive specimens presented signs of tumor involvement. We did not observe complications related to the use of high dose Fl-Na. ConclusionsHigh doses intravenous Fl-Na seems to be a useful intraoperative technique for delineation of benign neuroepithelial brain tumors with contrast enhancement. Further larger studies may reveal the real value of high doses Fl-Na as intraoperative method for increasing the extent of resection in these particular indications.

Detecting Surgical Tools by Modelling Local Appearance and Global Shape.

Detecting tools in surgical videos is an important ingredient for context-aware computer-assisted surgical systems. To this end, we present a new surgical tool detection dataset and a method for joint tool detection and pose estimation in 2d images. Our two-stage pipeline is data-driven and relaxes strong assumptions made by previous works regarding the geometry, number, and position of tools in the image. The first stage classifies each pixel based on local appearance only, while the second stage evaluates a tool-specific shape template to enforce global shape. Both local appearance and global shape are learned from training data. Our method is validated on a new surgical tool dataset of 2 476 images from neurosurgical microscopes, which is made freely available. It improves over existing datasets in size, diversity and detail of annotation. We show that our method significantly improves over competitive baselines from the computer vision field. We achieve 15% detection miss-rate at 10(-1) false positives per image (for the suction tube) over our surgical tool dataset. Results indicate that performing semantic labelling as an intermediate task is key for high quality detection.

Modification of collagen fiber after PDT in porcine skin models by two photons microscopy analysis

Modification of collagen fiber after PDT in porcine skin models by two photons microscopy analysis

Photodynamic therapy combined to optical clearing agents for melanoma treatment

Photodynamic therapy combined to optical clearing agents for melanoma treatment

A promising in vivo protocol for non-invasive pneumonia treatment

Methods: 190 patients with altogether 204 intracranial meningiomas that received 5-ALAprior to tumor resectionwere included. In each case, themeningioma tissue and the surrounding brain cortexwere investigated for potential PpIX fluorescence by amodified neurosurgical microscope. The tumor diagnosis was established according to the histopathological World Health Organization (WHO) criteria. Results: PpIX fluorescence was observed in 185 meningiomas (strong PpIX: 168 cases; vague PpIX: 17 cases), whereas 19 cases were PpIX negative. Visible PpIX fluorescence of the surrounding brain cortex was significantly more common in WHO grade III as compared to WHO grade I/II meningiomas (55% versus 20%). Conclusion: 5-ALA induced PpIX fluorescence is a clinically reliable marker for intraoperative visualization of intracranial meningiomas that might support the neurosurgeon to achieve complete tumor removal. The relevance of PpIX fluorescence in the surrounding brain cortex especially inWHO grade III meningiomas has to be further investigated.

Analysis of disruptive events and precarious situations caused by interaction with neurosurgical microscope.

Developments in micro-neurosurgical microscopes have improved operating precision and ensured the quality of outcomes. Using the stereoscopic magnified view, however, necessitates frequent manual adjustments to the microscope during an operation. This article reports on an investigation of the interaction details concerning a state-of-the-art micro-neurosurgical microscope. The video data from detailed observations of neurosurgeons' interaction patterns with the microscope were analysed to examine disruptive events caused by adjusting the microscope. The primary findings show that interruptions caused by adjusting the microscope handgrips and mouth switch prolong the surgery time up to 10%. Surgeons, we observed, avoid interaction with the microscope's controls, settings, and configurations by working at the edge of the view, operating on a non-focused view, and assuming unergonomic body postures. The lack of an automatic method for adjusting the microscope is a major problem that causes interruptions during micro-neurosurgery. From this understanding of disruptive events, we discuss the opportunities and limitations of interactive technologies that aim to reduce the frequency or shorten the duration of interruptions caused by microscope adjustment.

Kinetics of porphyrin fluorescence accumulation in pediatric brain tumor cells incubated in 5-aminolevulinic acid

Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) enables more complete resections of tumors in adults. 5-ALA elicits accumulation of fluorescent porphyrins in various cancerous tissues, which can be visualized using a modified neurosurgical microscope with blue light. Although this technique is well established in adults, it has not been investigated systematically in pediatric brain tumors. Specifically, it is unknown how quickly, how long, and to what extent various pediatric tumors accumulate fluorescence. The purpose of this study was to determine utility and time course of 5-ALA-induced fluorescence in typical pediatric brain tumors in vitro. Cell cultures of medulloblastoma [DAOY and UW228], cPNET [PFSK] atypical teratoid rhabdoid tumor [BT16] and ependymoma [RES196] were incubated with 5-ALA for either 60 minutes or continuously. Porphyrin fluorescence intensities were determined using a fluorescence-activated cell sorter (FACS) after 1, 3, 6, 9, 12 and 24 hours. C6 and U87 cells served as controls. All pediatric brain tumor cell lines displayed fluorescence compared to their respective controls without 5-ALA (p < 0.05). Sixty minutes of incubation resulted in peaks between 3 and 6 hours, whereas continuous incubation resulted in peaks at 12 hours or beyond. 60 minute incubation peak levels were between 52 and 91 % of maxima achieved with continuous incubation. Accumulation and clearance varied between cell types. We demonstrate that 5-ALA exposure of cell lines derived from typical pediatric central nervous system (CNS) tumors induces accumulation of fluorescent porphyrins. Differences in uptake and clearance indicate that different application modes may be necessary for fluorescence-guided resection, depending on tumor type.

Endoscopic endonasal surgery for suprasellar meningiomas: experience with 75 patients

Following the introduction of the neurosurgical microscope, the outcomes in suprasellar meningioma surgery were dramatically improved. More recently, the neurosurgical endoscope has been introduced as a visualization option during removal of skull base tumors, both transcranially and endonasally. The authors retrospectively reviewed the effectiveness of endoscopic endonasal surgery (EES) in the management of suprasellar meningiomas. Between 2002 and 2011, 75 patients (81.3% female) with suprasellar meningiomas underwent EES at the University of Pittsburgh Medical Center. The authors present the results of EES and analyze the resection rates, visual outcome, and complications. Seventy-one patients presented with primary tumors, whereas 4 were previously treated elsewhere. Their mean age was 57.3 years (range 36-88 years), and most patients presented with visual loss (81.3%). Tumors occupied the tuberculum sellae (86.7%) and planum sphenoidale (50.7%), with extension into the optic canals in 26.7% (unilateral in 21.3% and bilateral in 5.3%) and the pituitary fossa (9.3%). Gross-total tumor resection (Simpson Grade I) was achieved in 76% of the cases in the whole cohort and in 81.4% of the patients in whom it was the goal of surgery. Tumor location and extension into the optic canals was not a limitation for total resection. Tumor size, configuration, and vascular encasement were significant factors that influenced the degree of resection (p < 0.0001). Vision was improved or normalized in 85.7% of the cases. Visual deterioration following EES occurred in 2 patients (3.6%). Complications included postoperative CSF leaks (25.3% overall, 16.1% in recent years) resulting in meningitis in 4 cases. One patient had an intraoperative injury of the artery of Heubner resulting in associated neurological deficit. Another elderly patient died within 1 month after EES due to cerebral vasospasm and multisystem impairment. No patient developed postoperative cerebral contusions, hemorrhage, or seizures. During a mean follow-up period of 29 months (range 1-98 months), 4 patients have shown recurrence, but only 1 required repeat EES. With the goal of gross-total tumor resection and visual improvement, EES can achieve very good results, (comparable to microscopic approaches) for the treatment of suprasellar meningiomas. Avoidance of brain and optic nerve retraction, preservation of the vascularization of the optic apparatus, and wide decompression of the optic canals are the main advantages of EES for the treatment of suprasellar meningiomas, while CSF leaks remain a disadvantage.

Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA-induced fluorescence characteristics in different spinal tumor entities. Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification. Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy. In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.

5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

BackgroundIntraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria.MethodsWe prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status.ResultsA total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%.ConclusionsOur study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Clinical findings and management of intracranial Hydatid cyst in north of Iraq

Background and objective: Where Hydatid cyst of E. granulosus reaches 1 cm in diameter, its wall will differentiated into a thick outer laminated and thin germinal epithelium from which occasionally, daughter cysts could appear within the Hydatid. Aim:&nbsp;management of the Hydatid cyst is performed surgically by separating the two layers of the cyst keeping the inner layer intact during removal process to prevent the generation of daughter cysts at the same site in the future. Methods: We conducted the study using hematology coulter counter to analyze whole blood samples of rats after exposure to welding fumes. We investigated the effect of wielding fume exposure on some&nbsp;&nbsp; hematological parameters such as the red blood corpuscles (RBCs), white blood cells (WBCs) and platelet parameters. Fourteen male albino rats were randomly assigned to control or wielding fume inhalation. Results: Total removal of the cyst was done in thirty cases using neurosurgical microscope to separate the cyst wall. Two patients had multiple intracranial Hydatid cysts. The commonest location was in the parietal lobe (21 cases). Recurrence was seen in two cases as a result of rapture of the cyst during the first surgery, in other two cases secondary infestation was seen after 1st operation 9-12 months. Conclusion: Infection acquired in early life and symptoms usually appear later. (mebendazole) is used as prophylaxis. Pathologically there is no calcification of all cysts. radiologically pressure effect is not associated with edema. Big size lead to shift of the brain to the opposite side

Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies

Stereotactic biopsies represent a routine neurosurgical procedure for the diagnosis of intracranial lymphomas and selected diffusely infiltrating gliomas. Acquisition of tissue samples that do not allow correct tumor typing and grading is, however, not uncommon. Five-aminolevulinic acid (5-ALA) has been shown to accumulate in malignant tumor tissue. The aim of this study was to prospectively investigate the clinical usability of 5-ALA for intraoperative detection of representative tissue in stereotactic tumor biopsies. Fifty consecutive patients underwent frameless stereotactic biopsy for a suspected brain tumor. 5-ALA was administered 4 h before anesthesia. Serial biopsy samples were obtained and intraoperatively checked for 5-ALA fluorescence (strong, vague, or none) using a modified neurosurgical microscope. All samples were examined for the presence of representative tumor tissue according to neuroimaging (MRI, positron emission tomography, and/or chemical shift imaging) and histopathological parameters. Visible 5-ALA fluorescence was observed in 43/50 patients (strong in 39 and vague fluorescence in four cases). At biopsy target, 52/53 samples of glioblastomas, 9/10 samples of gliomas grade III, and 14/16 samples of lymphomas revealed strong 5-ALA fluorescence. Samples with strong 5-ALA fluorescence were only observed at, but not outside the biopsy target. All tissue samples with strong 5-ALA fluorescence were representative according to our neuroimaging and histopathological criteria (positive predictive value of 100%). Our data indicate that strong 5-ALA fluorescence is a reliable and immediately available intraoperative marker of representative tumor tissue of malignant gliomas and intracranial lymphomas in stereotactic biopsies. Thereby, the application of 5-ALA in stereotactic brain tumor biopsies may in future reduce costs for operating room and neuropathology and may decrease procedure-related morbidity.

脳神経外科用手術顕微鏡(みる)

脳神経外科用手術顕微鏡(<メカライフ特集>みる)

5‐Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement

Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling. 5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum (11)C-methionine positron emission tomography uptake (PET(max)) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI). Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET(max) in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor. The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments.

Assessment of Incomplete Clipping of Aneurysms Intraoperatively by a Near-Infrared Indocyanine Green-Video Angiography (Niicg-Va) Integrated Microscope

The objective of this article was to assess the clinical use and the completeness of clipping with total occlusion of the aneurysmal lumen, real-time assessment of vascular patency in the parent, branching and perforating vessels, intraoperative assessment of blood flow, image quality, spatial resolution and clinical value in difficult aneurysms using near infrared indocyanine green video angiography integrated on to an operative Pentero neurosurgical microscope (Carl Zeiss, Oberkochen Germany). Thirteen patients with aneurysms were operated upon. An infrared camera with near infrared technology was adapted on to the OPMI Pentero microscope with a special filter and infrared excitation light to illuminate the operating field which was designed to allow passage of the near infrared light required for excitation of indocyanine green (ICG) which was used as the intravascular marker. The intravascular fluorescence was imaged with a video camera attached to the microscope. ICG fluorescence (700-850 nm) from a modified microscope light source on to the surgical field and passage of ICG fluorescence (780-950 nm) from the surgical field, back into the optical path of the microscope was used to detect the completeness of aneurysmal clipping Incomplete clipping in three patients (1 female and 2 males) with unruptured complicated aneurysms was detected using indocyanine green video angiography. There were no adverse effects after injection of indocyanine green. The completeness of clipping was inadequately detected by Doppler ultrasound miniprobe and rigid endoscopy and was thus complemented by indocyanine green video angiography. The operative microscope-integrated ICG video angiography as a new intraoperative method for detecting vascular flow, was found to be quick, reliable, cost-effective and possibly a substitute or adjunct for Doppler ultrasonography or intraoperative DSA, which is presently the gold standard. The simplicity of the method, the speed with which the investigation can be performed, the quality of the images, and the outcome of surgical procedures have all reduced the need for angiography. This technique may be useful during routine aneurysm surgery as an independent form of angiography and/or as an adjunct to intraoperative or postoperative DSA.

Combination of FOSCAN® mediated fluorescence guided resection and photodynamic treatment as new therapeutic concept for malignant brain tumors

Abstract Photodynamic therapy (PDT), the combination of tumor-selective photosensitizers (PS) and light at the appropriate wavelength is under investigation for adjuvant therapy in brain tumors. Malignant brain tumors carry a lethal prognosis with a median survival of 15 months despite surgery, radiotherapy and chemotherapy. Recently photodynamic diagnosis mediated by FOSCAN® (meta-tetrahydroxyphenylchlorin – mTHPC) was introduced by our institution for intraoperative photo diagnosis (PDD) and fluorescence guided resection (FGR) for a more radical tumor removal. Twenty-six patients suffering from malignant brain tumors were sensitized with 0.15 mg/kg m-THPC body weight and underwent a combination of fluorescent guided resection followed by intraoperative PDT (20 J/cm2 at 652 nm) after 4 days. Intraoperative fluorescence was induced by a UV light source at 370–440 nm. A standard neurosurgical microscope was optimized for fluorescence detection. Intraoperative PDT was performed by lasers at 652 nm and 20 J/cm2. The fluorescence sensitivity and specificity in 172 tissue samples were 87.9% and 95.7%, respectively. Tumor could be predicted to an accuracy of 90.7%. Photodynamic diagnosis (PDD) proved to be useful in tumor resection accounting for a radical resection in 75% under fluorescenceguided resection as compared to 52% in the control group. The median survival time for the PDD/PDT group was 9 months as compared to the matched pair control group of 3.5 months, respectively. The side effects consisted of two severe toxic reactions to sunlight due to unintentional exposure to direct sunlight and one patient experienced a transitional brain swelling. Our results indicate that fluorescence guided surgery is feasible and proved to be of significant help in delineating tumor margins and in resection of residual tumor that could not be detected by the surgeon. The addition of intraoperative PDT significantly enhanced survival.