Tag: Confocal microscopy

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Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas

intraoperative_probe_based_confocal_laser

Neurosurgery 79:604–612, 2016

The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection.

OBJECTIVE: To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas.

METHODS: In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment.

RESULTS: The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy “normal” tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed.

CONCLUSION: We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins.

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Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas

J Neurosurg 115:740–748, 2011. DOI: 10.3171/2011.6.JNS11252

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

Neurosurgery 68[ONS Suppl 2]:ons282–ons290, 2011. DOI: 10.1227/NEU.0b013e318212464e

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 neoproliferation, 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.

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