In-vivo optical detection of brain tumor and tumor margin: a combined auto-fluorescence and diffuse reflectance spectroscopic study

Abstract INTRODUCTION Optical coherence tomography (OCT) is an emerging technology with the potential to allow for rapid intraoperative detection of brain tumor margins by detecting differences in structure, intensity, spectral signal, and attenuation. OCT systems are capable of rapid imaging of large three-dimensional volumes with cellular level resolution. However, OCT imaging has previously been limited by speckle artifact and the lack of suitable contrast agents, limitations that are surmounted in this study. METHODS We prepared nude mice with orthotopic U87 glioblastoma xenografts and glass cranial windows. We also created large gold nanorods (LGNR) with plasmonic peaks tuned to the spectral range of the OCT scanner. LGNRs were injected intravenously into tumor-bearing mice and OCT imaging was performed in vivo utilizing a novel method for the removal of speckle artifact called Speckle-Free OCT (SFOCT). Fresh ex-vivo patient samples were also imaged. RESULTS >OCT and SFOCT readily distinguished tumor from normal brain with cellular level spatial resolution and to a depth of 1.5 mm. Additionally, SFOCT allowed for the highest resolution ever seen in vivo of mouse white matter architecture. Cortical layers were also readily visible in SFOCT in both live mice and in the ex-vivo human samples, representing a novel ability to interrogate cortical cytoarchitecture across a large field of view. Systemically administered LGNRs were tumor specific and provided excellent spectral contrast using OCT. Ex-vivo hyperspectral and IHC imaging confirmed the localization of LGNRs within the tumor and found that the LGNRs were largely localized within tumor associated macrophages. CONCLUSION SFOCT and LGNR enhanced OCT imaging are promising state of the art technologies for intraoperative tumor margin detection.

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Speckle modulation enables high-resolution wide-field human brain tumor margin detection and in vivo murine neuroimaging

Scientific Reports ◽

10.1038/s41598-019-45902-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Derek Yecies ◽

Orly Liba ◽

Elliott D. SoRelle ◽

Rebecca Dutta ◽

Edwin Yuan ◽

...

Keyword(s):

Brain Tumor ◽

High Resolution ◽

Human Brain ◽

Wide Field ◽

Human Brain Tumor ◽

Tumor Margin ◽

Margin Detection

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High-resolution wide-field human brain tumor margin detection and in vivo murine neuroimaging

10.1101/252080 ◽

2018 ◽

Cited By ~ 2

Author(s):

Derek Yecies ◽

Orly Liba ◽

Elliott SoRelle ◽

Rebecca Dutta ◽

Edwin Yuan ◽

...

Keyword(s):

Brain Tumor ◽

White Matter ◽

Ex Vivo ◽

Field Of View ◽

Low Grade ◽

Wide Field ◽

Tumor Margin ◽

Wide Field Of View ◽

Margin Detection

AbstractCurrent 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 effective resolution provided by speckle elimination reveals white matter fascicles and cortical layer architecture in the 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 near single-cell resolution. 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.

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Integrated Time-Resolved Fluorescence and Diffuse Reflectance Spectroscopy Instrument for Intraoperative Detection of Brain Tumor Margin

IEEE Journal of Selected Topics in Quantum Electronics ◽

10.1109/jstqe.2015.2510964 ◽

2016 ◽

Vol 22 (3) ◽

pp. 49-57 ◽

Cited By ~ 6

Author(s):

Zhaojun Nie ◽

Vinh Nguyen Du Le ◽

Derek Cappon ◽

John Provias ◽

Naresh Murty ◽

...

Keyword(s):

Brain Tumor ◽

Diffuse Reflectance ◽

Diffuse Reflectance Spectroscopy ◽

Reflectance Spectroscopy ◽

Time Resolved Fluorescence ◽

Time Resolved ◽

Tumor Margin ◽

Intraoperative Detection

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Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

Current Drug Delivery ◽

10.2174/1567201817666200210120950 ◽

2020 ◽

Vol 17 (3) ◽

pp. 229-245

Author(s):

Gang Wang ◽

Junjie Wang ◽

Rui Guan

Keyword(s):

Drug Delivery ◽

Brain Tumor ◽

Oral Delivery ◽

Safe Delivery ◽

Drug Delivery Vehicles ◽

Therapeutic Benefits ◽

Delivery Vehicles ◽

The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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Bovine serum albumin/chitosan-nanoparticle bio-complex; spectroscopic study and in vivo toxicological – Hypersensitivity evaluation

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2021.119582 ◽

2021 ◽

Vol 253 ◽

pp. 119582

Author(s):

Moataz M. Rashad ◽

Nesma M. El-Kemary ◽

Said Amer ◽

Maged El-Kemary

Keyword(s):

Bovine Serum Albumin ◽

Serum Albumin ◽

Spectroscopic Study ◽

Bovine Serum ◽

Chitosan Nanoparticle

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Diffuse intrinsic pontine glioma: current insights and future directions

Chinese Neurosurgical Journal ◽

10.1186/s41016-020-00218-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Dilakshan Srikanthan ◽

Michael S. Taccone ◽

Randy Van Ommeren ◽

Joji Ishida ◽

Stacey L. Krumholtz ◽

...

Keyword(s):

Brain Tumor ◽

Gene Mutations ◽

Pediatric Brain Tumor ◽

Diffuse Intrinsic Pontine Glioma ◽

Pontine Glioma ◽

Current Standard ◽

In Vivo Models ◽

Landscape Models

AbstractDiffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor and the leading cause of brain tumor–related death in children. As several clinical trials over the past few decades have led to no significant improvements in outcome, the current standard of care remains fractionated focal radiation. Due to the recent increase in stereotactic biopsies, tumor tissue availabilities have enabled our advancement of the genomic and molecular characterization of this lethal cancer. Several groups have identified key histone gene mutations, genetic drivers, and methylation changes in DIPG, providing us with new insights into DIPG tumorigenesis. Subsequently, there has been increased development of in vitro and in vivo models of DIPG which have the capacity to unveil novel therapies and strategies for drug delivery. This review outlines the clinical characteristics, genetic landscape, models, and current treatments and hopes to shed light on novel therapeutic avenues and challenges that remain.

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Semaphorin 3A mediated brain tumor stem cell proliferation and invasion in EGFRviii mutant gliomas

BMC Cancer ◽

10.1186/s12885-020-07694-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Dominique M. O. Higgins ◽

Maisel Caliva ◽

Mark Schroeder ◽

Brett Carlson ◽

Pavan S. Upadhyayula ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cell ◽

Brain Tumor ◽

Propidium Iodide ◽

Tumor Stem Cell ◽

Semaphorin 3A ◽

Brain Tumor Stem Cell ◽

Proliferation And Invasion ◽

Invasion Assays

Abstract Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of approximately 15 months. Semaphorin 3A (Sema3A), known for its axon guidance and antiangiogenic properties, has been implicated in GBM growth. We hypothesized that Sema3A directly inhibits brain tumor stem cell (BTSC) proliferation and drives invasion via Neuropilin 1 (Nrp1) and Plexin A1 (PlxnA1) receptors. Methods GBM BTSC cell lines were assayed by immunostaining and PCR for levels of Semaphorin 3A (Sema3A) and its receptors Nrp1 and PlxnA1. Quantitative BrdU, cell cycle and propidium iodide labeling assays were performed following exogenous Sema3A treatment. Quantitative functional 2-D and 3-D invasion assays along with shRNA lentiviral knockdown of Nrp1 and PlxnA1 are also shown. In vivo flank studies comparing tumor growth of knockdown versus control BTSCs were performed. Statistics were performed using GraphPad Prism v7. Results Immunostaining and PCR analysis revealed that BTSCs highly express Sema3A and its receptors Nrp1 and PlxnA1, with expression of Nrp1 in the CD133 positive BTSCs, and absence in differentiated tumor cells. Treatment with exogenous Sema3A in quantitative BrdU, cell cycle, and propidium iodide labeling assays demonstrated that Sema3A significantly inhibited BTSC proliferation without inducing cell death. Quantitative functional 2-D and 3-D invasion assays showed that treatment with Sema3A resulted in increased invasion. Using shRNA lentiviruses, knockdown of either NRP1 or PlxnA1 receptors abrogated Sema3A antiproliferative and pro-invasive effects. Interestingly, loss of the receptors mimicked Sema3A effects, inhibiting BTSC proliferation and driving invasion. Furthermore, in vivo studies comparing tumor growth of knockdown and control infected BTSCs implanted into the flanks of nude mice confirmed the decrease in proliferation with receptor KD. Conclusions These findings demonstrate the importance of Sema3A signaling in GBM BTSC proliferation and invasion, and its potential as a therapeutic target.

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