Abstract
BackgroundIntraoperative confocal microscopy can enable high-resolution cross-sectional imaging of intact tissues as a non-invasive real-time alternative to gold-standard histology. However, all current means of intraoperative confocal microscopy are hindered by a limited field of view (FOV), presenting a challenge for evaluating gliomas, which are highly heterogeneous.ObjectiveThis study explored the use of image mosaicking with handheld dual-axis confocal (DAC) microscopy of fresh human glioma specimens.MethodsIn this preliminary technical feasibility study, fresh human glioma specimens from 6 patients were labeled with a fast-acting topical stain (acridine orange) and imaged using a newly developed DAC microscope prototype.ResultsIn comparison to individual image frames with small fields of view, mosaicked images from a DAC microscope correlate better with gold-standard H&E-stained histology images, including the ability to visualize gradual transitions from areas of dense cellularity to sparse cellularity within the tumor.ConclusionLS-DAC microscopy provides high-resolution, high-contrast images of glioma tissues that agree with corresponding H&E histology. Compared with individual image frames, mosaicked images provide more accurate representations of the overall cytoarchitecture of heterogeneous glioma tissues. Further investigation is needed to evaluate the ability of high-resolution mosaicked microscopy to improve the extent of glioma resection and patient outcomes.
Highlights
Extent of resection is one of the strongest predictors of overall survival, progression-free survival, and quality of life in both low-grade [1,2,3,4,5] and high-grade [6, 7] gliomas [8]
All 6 lesions were diagnosed as gliomas, in which 4 were World Health Organization (WHO) grade IV, 1 was grade III, and 1 was grade I diffuse gliomas (Table 1)
This report describes our first experience with using a handheld LS-DAC microscope, with image mosaicking, to image fresh human glioma tissues resected from human patients
Summary
Extent of resection is one of the strongest predictors of overall survival, progression-free survival, and quality of life in both low-grade [1,2,3,4,5] and high-grade [6, 7] gliomas [8]. Several intraoperative imaging techniques have been developed to improve glioma resection. Neuronavigation based on preoperative magnetic resonance imaging (MRI) is the standard of care, but this technique is often inaccurate due to brain shift caused by cerebrospinal fluid loss, cerebral edema, and resection-induced deformations. While intraoperative MRI circumvents brain-shift artifacts, it is not commonly used in routine clinical practice due to its high costs and prolonged surgical times. Fluorescence image-guided surgery (FIGS) utilizing conventional wide-field surgical microscopy is another clinically accepted technique for neurosurgical guidance and has been shown to be an effective method to improve the extent of resection in high-grade gliomas [10]. Intraoperative confocal microscopy can enable high-resolution crosssectional imaging of intact tissues as a non-invasive real-time alternative to goldstandard histology. All current means of intraoperative confocal microscopy are hindered by a limited field of view (FOV), presenting a challenge for evaluating gliomas, which are highly heterogeneous
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