Abstract
Current in vivo neuroimaging techniques provide limited field of view or spatial resolution and often require exogenous contrast. These limitations prohibit detailed structural imaging across wide fields of view and hinder intraoperative tumor margin detection. Here we present a novel neuroimaging technique, speckle-modulating optical coherence tomography (SM-OCT), which allows us to image the brains of live mice and ex vivo human samples with unprecedented resolution and wide field of view using only endogenous contrast. The increased visibility provided by speckle elimination reveals white matter fascicles and cortical layer architecture in brains of live mice. To our knowledge, the data reported herein represents the highest resolution imaging of murine white matter structure achieved in vivo across a wide field of view of several millimeters. When applied to an orthotopic murine glioblastoma xenograft model, SM-OCT readily identifies brain tumor margins with resolution of approximately 10 μm. SM-OCT of ex vivo human temporal lobe tissue reveals fine structures including cortical layers and myelinated axons. Finally, when applied to an ex vivo sample of a low-grade glioma resection margin, SM-OCT is able to resolve the brain tumor margin. Based on these findings, SM-OCT represents a novel approach for intraoperative tumor margin detection and in vivo neuroimaging.
Highlights
Brain tumors are the most common solid tumors in children and are the leading cause of pediatric cancer mortality[1]
The presence or absence of layer one axons provides an additional means by which speckle-modulating optical coherence tomography (SM-optical coherence tomography (OCT)) can resolve the tumor margin of this low-grade glioma with high spatial resolution across a field of view of several millimeters. In this proof-of concept paper we demonstrate that by significantly reducing speckle noise, SM-OCT can address fundamental shortcomings of current in vivo neuroimaging modalities used for small animal neuroscience and intraoperative tumor margin detection
SM-OCT can resolve brain tumor margins and neural structures ranging from individual axons to white matter fascicles and cortical layers across a wide field of view of several millimeters without the use of exogenous contrast agents
Summary
Brain tumors are the most common solid tumors in children and are the leading cause of pediatric cancer mortality[1]. Maximal safe resection is often limited by an inability to distinguish tumor from normal brain To address this problem, a variety of intraoperative imaging modalities have been investigated, including magnetic resonance imaging (MRI)[12,13,14,15], wide-field fluorescence[7], high-resolution fluorescence microscopy (confocal and multiphoton imaging)[16], and optical coherence tomography (OCT)[17,18,19,20,21]. Wide-field fluorescence guided brain tumor surgery, most notably with 5-aminolevulinic acid (5-ALA), has been shown to improve extent of resection for patients with glioblastoma and is incorporated into a standard surgical workflow[7]. OCT allows for rapid, wide-field, and label-free in vivo brain imaging with microscopic resolution and up to two millimeters of tissue penetration[34,35,36]. The effective resolution and image quality in these studies were significantly degraded by the presence of speckle noise that is intrinsic to OCT imaging, as well as to all coherent imaging methodologies, and arises from multiple scattering events within the light coherence time in a turbid sample, such as biological tissue
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