Molecular Imaging of Glucose Metabolism for Intraoperative Fluorescence Guidance During Glioma Surgery.

Purpose: This study evaluated the use of molecular imaging of fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as a discriminatory marker for intraoperative tumor border identification in a murine glioma model.

Procedures: 2-NBDG was assessed in GL261 and U251 orthotopic tumor-bearing mice. Intraoperative fluorescence of topical and intravenous 2-NBDG in normal and tumor regions was assessed with an operating microscope, handheld confocal laser scanning endomicroscope (CLE), and benchtop confocal laser scanning microscope (LSM).

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials.

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence.

Immediate Label-Free Ex Vivo Evaluation of Human Brain Tumor Biopsies With Confocal Reflectance Microscopy.

Confocal microscopy utilizing fluorescent dyes is widely gaining use in the clinical setting as a diagnostic tool. Reflectance confocal microscopy is a method of visualizing tissue specimens without fluorescent dyes while relying on the natural refractile properties of cellular and subcellular structures. We prospectively evaluated 76 CNS lesions with confocal reflectance microscopy (CRM) to determine cellularity, architecture, and morphological characteristics.

Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer.

Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities.

Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed.

Sulforhodamine 101 selectively labels human astrocytoma cells in an animal model of glioblastoma.

Sulforhodamine 101 (SR101) is a useful tool for immediate staining of astrocytes. We hypothesized that if the selectivity of SR101was maintained in astrocytoma cells, it could prove useful for glioma research. Cultured astrocytoma cells and acute slices from orthotopic human glioma (n=9) and lymphoma (n=6) xenografts were incubated with SR101 and imaged with confocal microscopy.

Laser scanning confocal endomicroscopy in the neurosurgical operating room: a review and discussion of future applications.

Laser scanning confocal endomicroscopy (LSCE) is an emerging technology for examining brain neoplasms in vivo. While great advances have been made in macroscopic fluorescence in recent years, the ability to perform confocal microscopy in vivo expands the potential of fluorescent tumor labeling, can improve intraoperative tissue diagnosis, and provides real-time guidance for tumor resection intraoperatively. In this review, the authors highlight the technical aspects of confocal endomicroscopy and fluorophores relevant to the neurosurgeon, provide a comprehensive summary of LSCE in animal and human neurosurgical studies to date, and discuss the future directions and potential for LSCE in neurosurgery.

Cationized ferritin as a magnetic resonance imaging probe to detect microstructural changes in a rat model of non-alcoholic steatohepatitis.

Purpose: The goal of this work was to detect disease-related microstructural changes to the liver using magnetic resonance imaging. Chronic liver disease can cause microstructural changes in the liver that reduce plasma access to the perisinusoidal space--the site of exchange between the blood plasma and the hepatic parenchyma. The reduced plasma access to the perisinusoidal space inhibits hepatic function and contributes to the ∼30,000 chronic liver disease-related deaths per year.

Toxicity, biodistribution, and ex vivo MRI detection of intravenously injected cationized ferritin.

The goal of the work was to establish the toxicity and biodistribution of the superparamagnetic protein cationized ferritin (CF) after intravenous injection. Intravenously injected CF has been used to target the extracellular matrix with high specificity in the kidney glomerulus, allowing measurements of individual glomeruli using T2*-weighted MRI. For the routine use of CF as an extracellular matrix-specific tracer, it is important to determine whether CF is toxic.