Abstract
BackgroundNoninvasive intraoperative optical biopsy that provides real-time imaging of histoarchitectural (cell resolution) features of brain tumors, especially at the margin of invasive tumors, would be of great value. To assess clinical-grade confocal laser endomicroscopy (CLE) and to prepare for its use intraoperatively in vivo, we performed an assessment of CLE ex vivo imaging in brain lesions.MethodsTissue samples from patients who underwent intracranial surgeries with fluorescein sodium (FNa)–based wide-field fluorescence guidance were acquired for immediate intraoperative ex vivo optical biopsies with CLE. Hematoxylin-eosin–stained frozen section analysis of the same specimens served as the gold standard for blinded neuropathology comparison. FNa 2 to 5 mg/kg was administered upon induction of anesthesia, and FNa 5 mg/kg was injected for CLE contrast improvement. Histologic features were identified, and the diagnostic accuracy of CLE was assessed.ResultsOf 77 eligible patients, 47 patients with 122 biopsies were enrolled, including 32 patients with gliomas and 15 patients with other intracranial lesions. The positive predictive value of CLE optical biopsies was 97% for all specimens and 98% for gliomas. The specificity of CLE was 90% for all specimens and 94% for gliomas. The second FNa injection in seven patients, a mean of 2.6 h after the first injection, improved image quality and increased the percentage of accurately diagnosed images from 67% to 93%. Diagnostic CLE features of lesional glioma biopsies and normal brain were identified. Seventeen histologic features were identified.ConclusionsResults demonstrated high specificity and positive predictive value of ex vivo intraoperative CLE optical biopsies and justify an in vivo intraoperative trial. This new portable, noninvasive intraoperative imaging technique provides diagnostic features to discriminate lesional tissue with high specificity and is feasible for incorporation into the fluorescence-guided surgery workflow, particularly for patients with invasive brain tumors.
Highlights
Complete resection within the bounds of functional safety is the goal of neurosurgical treatment for most brain tumors, especially invasive tumors, such as high-grade glioma (HGG) [1, 2]
The US Food and Drug Administration (FDA) approved the use of these systems in the brain only for experimental purposes, and previous generations of confocal laser endomicroscope (CLE) were used in only three limited trials that included in vivo and ex vivo intraoperative use [5,6,7]
We studied CLE use during routine fluorescenceguided surgery (FGS) with the operating microscope to visualize and compare CLE tissue-imaging microstructure in ex vivo samples with frozen section biopsies of brain tumors
Summary
Complete resection within the bounds of functional safety is the goal of neurosurgical treatment for most brain tumors, especially invasive tumors, such as high-grade glioma (HGG) [1, 2]. Previous generations of the confocal laser endomicroscope (CLE) demonstrated initial feasibility in visualizing brain tumor microstructure with significant diagnostic accuracy [4]. These designs were largely based on an imaging platform directly adapted from those used for gastrointestinal imaging. Cellular Features Features such as tissue architecture, cell morphology, atypical cells, and hypercellularity were more prevalent in lesional glioma biopsies than in normal and reactive brain (P
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