scholarly journals Intraoperative Confocal Microscopy for Brain Tumors: A Feasibility Analysis in Humans

2011 ◽  
Vol 68 (suppl_2) ◽  
pp. ons282-ons290 ◽  
Author(s):  
Nader Sanai ◽  
Jennifer Eschbacher ◽  
Guido Hattendorf ◽  
Stephen W. Coons ◽  
Mark C. Preul ◽  
...  

Abstract Background: The ability to diagnose brain tumors intraoperatively and identify tumor margins during resection could maximize resection and minimize morbidity. Advances in optical imaging enabled production of a handheld intraoperative confocal microscope. Objective: To present a feasibility analysis of the intraoperative confocal microscope for brain tumor resection. Methods: Thirty-three patients with brain tumor treated at Barrow Neurological Institute were examined. All patients received an intravenous bolus of sodium fluorescein before confocal imaging with the Optiscan FIVE 1 system probe. Optical biopsies were obtained within each tumor and along the tumor-brain interfaces. Corresponding pathologic specimens were then excised and processed. These data was compared by a neuropathologist to identify the concordance for tumor histology, grade, and margins. Results: Thirty-one of 33 lesions were tumors (93.9%) and 2 cases were identified as radiation necrosis (6.1%). Of the former, 25 (80.6%) were intra-axial and 6 (19.4%) were extra-axial. Intra-axial tumors were most commonly gliomas and metastases, while all extra-axial tumors were meningiomas. Among high-grade gliomas, vascular neo-proliferation, as well as tumor margins, were identifiable using confocal imaging. Meningothelial and fibrous meningiomas were distinct on confocal microcopy—the latter featured spindle-shaped cells distinguishable from adjacent parenchyma. Other tumor histologies correlated well with standard neuropathology tissue preparations. Conclusion: Intraoperative confocal microscopy is a practicable technology for the resection of human brain tumors. Preliminary analysis demonstrates reliability for a variety of lesions in identifying tumor cells and the tumor-brain interface. Further refinement of this technology depends upon the approval of tumor-specific fluorescent contrast agents for human use.

2012 ◽  
Vol 116 (4) ◽  
pp. 854-860 ◽  
Author(s):  
Jennifer Eschbacher ◽  
Nikolay L. Martirosyan ◽  
Peter Nakaji ◽  
Nader Sanai ◽  
Mark C. Preul ◽  
...  

Object Frozen-section analysis is the current standard for the intraoperative diagnosis of brain tumors. Intraoperative confocal microscopy is an emerging technology with the potential to visualize tumor histopathological features and cell morphology in real time. The authors report their findings using this new intraoperative technology in vivo with sodium fluorescein contrast during the course of 50 microsurgical tumor resections. Methods Eighty-eight regions were visualized with confocal microscopy, and corresponding biopsy samples were examined with routine neuropathological analysis. The tumors studied included meningiomas, schwannomas, gliomas of various grades, and a hemangioblastoma. The confocal microscopic features of each tumor and of various artifacts inherent to the technology were documented. A pathologist working in a blinded fashion reviewed a subset of the images in a further evaluation of the usefulness of the device as a diagnostic tool. Results Overall, intraoperative confocal imaging correlated surprisingly well with corresponding traditional histological findings, including the identification of many pathognomonic cytoarchitectural features of various brain tumors. In the blinded study, 26 (92.9%) of 28 lesions were diagnosed correctly. Conclusions Further study will be necessary for better definition of the role of intraoperative confocal microscopy as a routine adjunct for intraoperative brain tumor diagnosis.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Rashad Jabarkheel ◽  
Jonathon J Parker ◽  
Chi-Sing Ho ◽  
Travis Shaffer ◽  
Sanjiv Gambhir ◽  
...  

Abstract INTRODUCTION Surgical resection is a mainstay of treatment in patients with brain tumors both for tissue diagnosis and for tumor debulking. While maximal resection of tumors is desired, neurosurgeons can be limited by the challenge of differentiating normal brain from tumor using only microscopic visualization and tactile feedback. Additionally, intraoperative decision-making regarding how aggressively to pursue a gross total resection frequently relies on pathologic preliminary diagnosis using frozen sections which are both time consuming and fallible. Here, we investigate the potential for Raman spectroscopy (RS) to rapidly detect pediatric brain tumor margins and classify brain tissue samples equivalent to histopathology. METHODS Using a first-of-its-kind rapid acquisition RS device we intraoperatively imaged fresh ex vivo pediatric brain tissue samples (2-3 mm × 2-3 mm × 2-3 mm) at the Lucille Packard Children's Hospital. All imaged samples received standard final histopathological analysis, as RS is a nondestructive imaging technique. We curated a labeled dataset of 575 + unique Raman spectra gathered from 160 + brain samples resulting from 23 pediatric patients who underwent brain tissue resection as part of tumor debulking or epilepsy surgery (normal controls). RESULTS To our knowledge we have created the largest labeled Raman spectra dataset of pediatric brain tumors. We are developing an end-to-end machine learning model that can predict final histopathology diagnosis within minutes from Raman spectral data. Our preliminary principle component analyses suggest that RS can be used to classify various brain tumors similar to “frozen” histopathology and can differentiate normal from malignant brain tissue in the context of low-grade glioma resections. CONCLUSION Our work suggests that machine learning approaches can be used to harness the material identification properties of RS for classifying brain tumors and detecting their margins.


2006 ◽  
Vol 34 (4) ◽  
pp. 177-183 ◽  
Author(s):  
Nobusada Shinoura ◽  
Masamichi Takahashi ◽  
Ryozi Yamada

2018 ◽  
Vol 8 (11) ◽  
pp. 202 ◽  
Author(s):  
Maria Pino ◽  
Alessia Imperato ◽  
Irene Musca ◽  
Rosario Maugeri ◽  
Giuseppe Giammalva ◽  
...  

Maximal safe resection represents the gold standard for surgery of malignant brain tumors. As regards gross-total resection, accurate localization and precise delineation of the tumor margins are required. Intraoperative diagnostic imaging (Intra-Operative Magnetic Resonance-IOMR, Intra-Operative Computed Tomography-IOCT, Intra-Operative Ultrasound-IOUS) and dyes (fluorescence) have become relevant in brain tumor surgery, allowing for a more radical and safer tumor resection. IOUS guidance for brain tumor surgery is accurate in distinguishing tumor from normal parenchyma, and it allows a real-time intraoperative visualization. We aim to evaluate the role of IOUS in gliomas surgery and to outline specific strategies to maximize its efficacy. We performed a literature research through the Pubmed database by selecting each article which was focused on the use of IOUS in brain tumor surgery, and in particular in glioma surgery, published in the last 15 years (from 2003 to 2018). We selected 39 papers concerning the use of IOUS in brain tumor surgery, including gliomas. IOUS exerts a notable attraction due to its low cost, minimal interruption of the operational flow, and lack of radiation exposure. Our literature review shows that increasing the use of ultrasound in brain tumors allows more radical resections, thus giving rise to increases in survival.


2015 ◽  
Vol 11 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Fahad E Alotaibi ◽  
Gmaan A AlZhrani ◽  
Muhammad AS Mullah ◽  
Abdulrahman J Sabbagh ◽  
Hamed Azarnoush ◽  
...  

Abstract BACKGROUND Validated procedures to objectively measure neurosurgical bimanual psychomotor skills are unavailable. The NeuroTouch simulator provides metrics to determine bimanual performance, but validation is essential before implementation of this platform into neurosurgical training, assessment, and curriculum development. OBJECTIVE To develop, evaluate, and validate neurosurgical bimanual performance metrics for resection of simulated brain tumors with NeuroTouch. METHODS Bimanual resection of 8 simulated brain tumors with differing color, stiffness, and border complexity was evaluated. Metrics assessed included blood loss, tumor percentage resected, total simulated normal brain volume removed, total tip path lengths, maximum and sum of forces used by instruments, efficiency index, ultrasonic aspirator path length index, coordination index, and ultrasonic aspirator bimanual forces ratio. Six neurosurgeons and 12 residents (6 senior and 6 junior) were evaluated. RESULTS Increasing tumor complexity impaired resident bimanual performance significantly more than neurosurgeons. Operating on black vs glioma-colored tumors resulted in significantly higher blood loss and lower tumor percentage, whereas altering tactile cues from hard to soft decreased resident tumor resection. Regardless of tumor complexity, significant differences were found between neurosurgeons, senior residents, and junior residents in efficiency index and ultrasonic aspirator path length index. Ultrasonic aspirator bimanual force ratio outlined significant differences between senior and junior residents, whereas coordination index demonstrated significant differences between junior residents and neurosurgeons. CONCLUSION The NeuroTouch platform incorporating the simulated scenarios and metrics used differentiates novice from expert neurosurgical performance, demonstrating NeuroTouch face, content, and construct validity and the possibility of developing brain tumor resection proficiency performance benchmarks.


Signals ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 304-335
Author(s):  
Aditi Deshpande ◽  
Thomas Cambria ◽  
Charles Barnes ◽  
Alexandros Kerwick ◽  
George Livanos ◽  
...  

This study investigates the potential of fluorescence imaging in conjunction with an original, fused segmentation framework for enhanced detection and delineation of brain tumor margins. By means of a test bed optical microscopy system, autofluorescence is utilized to capture gray level images of brain tumor specimens through slices, obtained at various depths from the surface, each of 10 µm thickness. The samples used in this study originate from tumor cell lines characterized as Gli36ϑEGRF cells expressing a green fluorescent protein. An innovative three-step biomedical image analysis framework is presented aimed at enhancing the contrast and dissimilarity between the malignant and the remaining tissue regions to allow for enhanced visualization and accurate extraction of tumor boundaries. The fluorescence image acquisition system implemented with an appropriate unsupervised pipeline of image processing and fusion algorithms indicates clear differentiation of tumor margins and increased image contrast. Establishing protocols for the safe administration of fluorescent protein molecules, these would be introduced into glioma tissues or cells either at a pre-surgery stage or applied to the malignant tissue intraoperatively; typical applications encompass areas of fluorescence-guided surgery (FGS) and confocal laser endomicroscopy (CLE). As a result, this image acquisition scheme could significantly improve decision-making during brain tumor resection procedures and significantly facilitate brain surgery neuropathology during operation.


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi7-vi7
Author(s):  
Hideki Kuroda ◽  
Noriyuki Kijima ◽  
Tomoyoshi Nakagawa ◽  
Ryuichi Hirayama ◽  
Yoshiko Okita ◽  
...  

Abstract Background: Molecular heterogeneity among and within tumors are one of the reasons for the poor survival rate of brain tumors even with the current standard therapy. However, monolayer culture and neuro-sphere culture (NS) use exogenous growth factors, so may not show the true nature of the tumor. And the culture establishment rate is low, especially low-grade tumors. Therefore, we used the glioblastoma organoid (GBO) culture method showed by Fadi to create culture models of various brain tumors and investigated their characteristics. Methods: We examined the establishment rate in pathological and genotypic types of 56 patients who underwent brain tumor resection at our hospital between January 2020 and June 2021 and were cultured with GBO or NS. If tumor cells are increased visually at 1 month after culture, we defined establishment. Results: There were 15 cases of glioblastoma, 7 cases of anaplastic astrocytoma, 7 cases of diffuse astrocytoma, 3 cases of diffuse midline glioma, 2 cases of anaplastic oligodendroglioma, 5 cases of oligodendroglioma, and 16 cases of others. The establishment rate was 76.5% by the GBO method and 40% by the N S method. By histological type, GBO: 80% in glioblastoma, NS: 58.3% in glioblastoma, GBO: 83.3% in AA, NS: 40% in AA, and GBO: 100% in DA. The IDH mutation and pTERT mutation were investigated in GBO: IDHwt/TERT+ 87.5%, IDHwt/TERT- 64.3%, IDHmt/TERT- 100%, and in NS: IDHwt/TERT+ 75%, IDHwt/TERT- 33.3%, IDHmt/ TERT- 20% in NS. In addition, establishment was observed in GBO 2 case in medulloblastoma, 1 case in ependymoma. Discussion and Conclusion: This suggest that GBO can be used to establish culture models for low-grade tumors. In addition, GBO can establish culture earlier, so it is expected to be applicable to personalized therapies such as preclinical drug efficacy studies tailored to individual patients.


2004 ◽  
Vol 101 (6) ◽  
pp. 960-969 ◽  
Author(s):  
Alexander M. Gorbach ◽  
John D. Heiss ◽  
Leonid Kopylev ◽  
Edward H. Oldfield

Object. Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear. Methods. An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis—astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow. Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery. Conclusions. Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion.


2011 ◽  
Vol 115 (4) ◽  
pp. 740-748 ◽  
Author(s):  
Nader Sanai ◽  
Laura A. Snyder ◽  
Norissa J. Honea ◽  
Stephen W. Coons ◽  
Jennifer M. Eschbacher ◽  
...  

Object Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection. Methods Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence. Results Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses. Conclusions Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.


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