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Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery. [ABSTRACT FROM AUTHOR]

Autologous chimeric antigen receptor (CAR) T cells targeted to epidermal growth factor receptor variant III (CAR T-EGFRvIII) have been developed and administered experimentally to treat patients with IDH1 wildtype recurrent glioblastoma (rGBM) (NCT02209376). We report the case of a 59-year-old patient who received a single peripheral infusion of CAR T-EGFRvIII cells and survived 36 months after disease recurrence, exceeding expected survival for recurrent glioblastoma. Post-infusion histopathologic analysis of tissue obtained during a second stage surgical resection revealed immunosuppressive adaptive changes in the tumor tissue as well as reduced EGFRvIII expression. Serial brain imaging demonstrated a significant reduction in relative cerebral blood volume (rCBV), a measure strongly associated with tumor proliferative activity, at early time points following CAR T treatment. Notably, CAR T-EGFRvIII cells persisted in her peripheral circulation during 29 months of follow-up, the longest period of CAR T persistence reported in GBM trials to date. These findings in a long-term survivor show that peripherally administered CAR T-EGFRvIII cells can persist for years in the circulation and suggest that this cell therapy approach could be optimized to achieve broader efficacy in recurrent GBM patients. [ABSTRACT FROM AUTHOR]

Background: Intraoperative visualization of brain tumors with near-infrared (NIR)-fluorescent dyes is an emerging method for tumor margin approximation but are limited by existing fluorescence detection platforms. We previously showed that a dedicated NIR imaging platform outperformed a state-of-the-art neurosurgical microscope in fluorescence signal characteristics. This study examined whether conventional neurosurgical microscope NIR signal could be improved with the addition of a narrow wavelength excitation source. Methods: Imaging was conducted with a broad-spectrum neurosurgical microscope and commercial near-infrared module. Addition of an 805-nm laser was used to "boost" NIR excitation of indocyanine green (ICG). In vitro quantification was performed on serial dilutions of ICG. Patients underwent tumor resection with delayed 24-h imaging of ICG infusion. NIR fluorescence of dura, cortex, or tumor was quantified from images prior to (pre-boost) and following added excitation with the laser (post-boost). Signal to background ratio (SBR) of pre- and post-boost was calculated as a readout of image enhancement. Results: In vitro, excitation boost effected a 29% increase in mean SBR in six serial dilutions of ICG. Intraoperative boost was performed in 11 patients including meningioma, glioblastoma multiforme, and metastases. Increase in tumor fluorescence was pronounced under direct tumor visualization. Across all patients, boost excitation resulted in 35% mean improvement from pre-boost SBR (p < 0.001). Conclusion: Neurosurgical microscopes remain the preferred method of visualizing tumor during intracranial surgery. However, current modalities for NIR signal detection are suboptimal. We demonstrate that augmentation of a fluorescence microscope module with a focused excitation source is a simple mechanism of improving NIR tumor visualization. Clinical trial registration: NCT03262636 [ABSTRACT FROM AUTHOR]

Purpose: Distinguishing neoplasm from normal brain parenchyma intraoperatively is critical for the neurosurgeon. 5-Aminolevulinic acid (5-ALA) has been shown to improve gross total resection and progression-free survival but has limited availability in the USA. Near-infrared (NIR) fluorescence has advantages over visible light fluorescence with greater tissue penetration and reduced background fluorescence. In order to prepare for the increasing number of NIR fluorophores that may be used in molecular imaging trials, we chose to compare a state-of-the-art, neurosurgical microscope (System 1) to one of the commercially available NIR visualization platforms (System 2).Procedures: Serial dilutions of indocyanine green (ICG) were imaged with both systems in the same environment. Each system's sensitivity and dynamic range for NIR fluorescence were documented and analyzed. In addition, brain tumors from six patients were imaged with both systems and analyzed.Results: In vitro, System 2 demonstrated greater ICG sensitivity and detection range (System 1 1.5-251 μg/l versus System 2 0.99-503 μg/l). Similarly, in vivo, System 2 demonstrated signal-to-background ratio (SBR) of 2.6 ± 0.63 before dura opening, 5.0 ± 1.7 after dura opening, and 6.1 ± 1.9 after tumor exposure. In contrast, System 1 could not easily detect ICG fluorescence prior to dura opening with SBR of 1.2 ± 0.15. After the dura was reflected, SBR increased to 1.4 ± 0.19 and upon exposure of the tumor SBR increased to 1.8 ± 0.26.Conclusion: Dedicated NIR imaging platforms can outperform conventional microscopes in intraoperative NIR detection. Future microscopes with improved NIR detection capabilities could enhance the use of NIR fluorescence to detect neoplasm and improve patient outcome. [ABSTRACT FROM AUTHOR]

Background: Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the "oncometabolite" 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism. This study aims to assess tumor metabolism using 2D L-COSY at 7T for the detection of 2HG in IDH-mutant gliomas. Methods: Nine treatment-naï ve patients with suspected intracranial neoplasms were scanned at 7T MRI/MRS scanner using the 2D L-COSY technique. 2D-spectral processing and analyses were performed using a MATLAB-based reconstruction algorithm. Cross and diagonal peak volumes were quantified in the 2D L-COSY spectra and normalized with respect to the creatine peak at 3.0 ppm and quantified data were compared with previously-published data from six normal subjects. Detection of 2HG was validated using findings from immunohistochemical (IHC) staining in patients who subsequently underwent surgical resection. Results: 2HG was detected in both of the IDH-mutated gliomas (grade III Anaplastic Astrocytoma and grade II Diffuse Astrocytoma) and was absent in IDH wild-type gliomas and in a patient with breast cancer metastases. 2D L-COSY was also able to resolve complex and overlapping resonances including phosphocholine (PC) from glycerophosphocholine (GPC), lactate (Lac) from lipids and glutamate (Glu) from glutamine (Gln). Conclusions: This study demonstrates the ability of 2D L-COSY to unambiguously detect 2HG in addition to other neuro metabolites. These findings may aid in establishing 2HG as a biomarker of malignant progression as well as for disease monitoring in IDH-mutated gliomas. [ABSTRACT FROM AUTHOR]