Compact ring resonators of silicon nanorods for strong optomechanical interaction.

Optomechanical interaction in microstructures plays a more and more important role in the fields of quantum technology, information processing, and sensing, among others. It is still a challenge to obtain a strong optomechanical interaction in a compact device. Here, we propose and demonstrate that compact ring resonators consisting of silicon nanorods can realize strong optomechanical interaction even surpassing that of most optical microcavities. The proposed ring resonators can well confine infrared optical waves by the quasi-bound states in the continuum. Meanwhile, each nanorod in the resonator acts as a mechanical resonator of GHz resonating frequency, thus realizing an optomechanical coupling rate of up to 1.8 MHz. We have found that the interaction area can be extended by increasing the number of nanorods while maintaining the optomechanical interaction strength. Finally, we have studied the influence of supporting structures for suspended nanorods on the optomechanical interaction properties. The proposed ring resonators of silicon nanorods offer a promising platform for the study of optomechanical interaction.

5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience.

Background: Achieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy. Objective: The aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas. Materials and methods: A prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the "asleep-awake-asleep" protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery. Results: In 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca's area was identified in 23 cases and Wernicke's area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2-3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis. Conclusion: 5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course.

Strong optomechanical coupling in chain-like waveguides of silicon nanoparticles with quasi-bound states in the continuum.

We propose and demonstrate that strong optomechanical coupling can be achieved in a chain-like waveguide consisting of silicon nanorods. By employing quasi-bound states in the continuum and mechanical resonances at a frequency around 10 GHz, the optomechanical coupling rate can be above 2 MHz and surpass most microcavities. We have also studied cases with different optical wave numbers and size parameters of silicon, and a robust coupling rate has been verified, benefiting the experimental measurements and practical applications. The proposed silicon chain-like waveguide of strong optomechanical coupling may pave new ways for research on photon-phonon interaction with microstructures.

Prediction of Intraoperative Fluorescence of Brain Gliomas: Correlation between Tumor Blood Flow and the Fluorescence.

INTRODUCTION: The prediction of the fluorescent effect of 5-aminolevulinic acid (5-ALA) in patients with diffuse gliomas can improve the selection of patients. The degree of enhancement of gliomas has been reported to predict 5-ALA fluorescence, while, at the same time, rarer cases of fluorescence have been described in non-enhancing gliomas. Perfusion studies, in particular arterial spin labeling perfusion, have demonstrated high efficiency in determining the degree of malignancy of brain gliomas and may be better for predicting fluorescence than contrast enhancement. The aim of the study was to investigate the relationship between tumor blood flow, measured by ASL, and intraoperative fluorescent glow of gliomas of different grades. MATERIALS AND METHODS: Tumoral blood flow was assessed in 75 patients by pCASL (pseudo-continuous arterial spin labeling) within 1 week prior to surgery. In all cases of tumor removal, 5-ALA had been administered preoperatively. Maximum values of tumoral blood flow (TBF max) were measured, and normalized tumor blood flow (nTBF) was calculated. RESULTS: A total of 76% of patients had significant contrast enhancement, while 24% were non-enhancing. The histopathology revealed 17 WHO grade II gliomas, 12 WHO grade III gliomas and 46 glioblastomas. Overall, there was a relationship between the degree of intraoperative tumor fluorescence and ASL-TBF (Rs = 0.28, p = 0.02 or the TBF; Rs = 0.34, p = 0.003 for nTBF). Non-enhancing gliomas were fluorescent in 9/18 patients, with nTBF in fluorescent gliomas being 54.58 ± 32.34 mL/100 mg/s and in non-fluorescent gliomas being 52.99 ± 53.61 mL/100 g/s (p > 0.05). Enhancing gliomas were fluorescent in 53/57 patients, with nTBF being 170.17 ± 107.65 mL/100 g/s in fluorescent and 165.52 ± 141.71 in non-fluorescent gliomas (p > 0.05). CONCLUSION: Tumoral blood flow levels measured by non-contrast ASL perfusion method predict the fluorescence by 5-ALA; however, the additional value beyond contrast enhancement is not clear. ASL is, however, useful in cases with contraindication to contrast.

Rapid estimation of tumor cell percentage in brain tissue biopsy samples using inline cartridge extraction mass spectrometry.

Tumor cell percentage (TCP) is an essential characteristic of biopsy samples that directly affects the sensitivity of molecular testing in clinical practice. Apart from clarifying diagnoses, rapid evaluation of TCP combined with various neuronavigation systems can be used to support decision making in neurosurgery. It is known that ambient mass spectrometry makes it possible to rapidly distinguish healthy from malignant tissues. In connection with this, here we demonstrate the possibility of using non-imaging ambient mass spectrometry to evaluate TCP in glial tumor tissues with a high degree of confidence. Molecular profiles of histologically annotated human glioblastoma tissue samples were obtained using the inline cartridge extraction ambient mass spectrometry approach. XGBoost regressors were trained to evaluate tumor cell percentage. Using cross-validation, it was estimated that the TCP was determined by the regressors with a precision of approximately 90% using only low-resolution data. This result demonstrates that ambient mass spectrometry provides an accurate method todetermine TCP in dissected tissues even without implementing mass spectrometry imaging. The application of such techniques offers the possibility to automate routine tissue screening and TCP evaluation to boost the throughput of pathology laboratories. Rapid estimation of tumor cell percentage during neurosurgery.

A review of dielectric optical metasurfaces for spatial differentiation and edge detection.

Dielectric metasurfaces-based planar optical spatial differentiator and edge detection have recently been proposed to play an important role in the parallel and fast image processing technology. With the development of dielectric metasurfaces of different geometries and resonance mechanisms, diverse on-chip spatial differentiators have been proposed by tailoring the dispersion characteristics of subwavelength structures. This review focuses on the basic principles and characteristic parameters of dielectric metasurfaces as first- and second-order spatial differentiators realized via the Green's function approach. The spatial bandwidth and polarization dependence are emphasized as key properties by comparing the optical transfer functions of metasurfaces for different incident wavevectors and polarizations. To present the operational capabilities of a two-dimensional spatial differentiator in image information acquisition, edge detection is described to illustrate the practicability of the device. As an application example, experimental demonstrations of edge detection for different biological cells and a flower mold are discussed, in which a spatial differentiator and objective lens or camera are integrated in three optical pathway configurations. The realization of spatial differentiators and edge detection with dielectric metasurfaces provides new opportunities for ultrafast information identification in biological imaging and machine vision.

Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a.

Gliomas are fast growing and highly invasive brain tumors, characterized by tumor microenvironment acidification that drives glioma cell growth and migration. Channels containing Acid-sensing Ion Channel 1a subunit (ASIC1a) mediate amiloride-sensitive cation influx in late stage glioma cells, but not in normal astrocytes. Thus, selective targeting of ASIC1a can be a perspective strategy for glioma treatment. Here, ASIC1a expression in U251 MG and A172 glioma cells, but not in normal astrocytes, was demonstrated. Recombinant analog of mambalgin-2 from black mamba Dendroaspis polylepis inhibited amiloride-sensitive currents at ASIC1a both in Xenopus laevis oocytes and in U251 MG cells, while its mutants with impaired activity towards this channel did not. Mambalgin-2 inhibited U251 MG and A172 glioma cells growth with EC50 in the nanomolar range without affecting the proliferation of normal astrocytes. Notably, mambalgin-2 mutants did not affect glioma cell proliferation, pointing on ASIC1a as the main molecular target of mambalgin-2 in U251 MG and A172 cells. Mambalgin-2 induced a cell cycle arrest, inhibited Cyclin D1 and cyclin-dependent kinases (CDK) phosphorylation and caused apoptosis in U251 MG and A172 cells. Moreover, mambalgin-2 inhibited the growth of low-passage primary cells from a patient with glioblastoma. Altogether, our data point to mambalgin-2 as a useful hit for the development of new drugs for glioma treatment.

Investigation of Inter- and Intratumoral Heterogeneity of Glioblastoma Using TOF-SIMS.

Glioblastoma (GBM) is one of the most aggressive human cancers with a median survival of less than two years. A distinguishing pathological feature of GBM is a high degree of inter- and intratumoral heterogeneity. Intertumoral heterogeneity of GBM has been extensively investigated on genomic, methylomic, transcriptomic, proteomic and metabolomics levels, however only a few studies describe intratumoral heterogeneity because of the lack of methods allowing to analyze GBM samples with high spatial resolution. Here, we applied TOF-SIMS (Time-of-flight secondary ion mass spectrometry) for the analysis of single cells and clinical samples such as paraffin and frozen tumor sections obtained from 57 patients. We developed a technique that allows us to simultaneously detect the distribution of proteins and metabolites in glioma tissue with 800 nm spatial resolution. Our results demonstrate that according to TOF-SIMS data glioma samples can be subdivided into clinically relevant groups and distinguished from the normal brain tissue. In addition, TOF-SIMS was able to elucidate differences between morphologically distinct regions of GBM within the same tumor. By staining GBM sections with gold-conjugated antibodies against Caveolin-1 we could visualize border between zones of necrotic and cellular tumor and subdivide glioma samples into groups characterized by different survival of the patients. Finally, we demonstrated that GBM contains cells that are characterized by high levels of Caveolin-1 protein and cholesterol. This population may partly represent a glioma stem cells. Collectively, our results show that the technique described here allows to analyze glioma tissues with a spatial resolution beyond reach of most of other omics approaches and the obtained data may be used to predict clinical behavior of the tumor.

Optical analog computing of spatial differentiation and edge detection with dielectric metasurfaces.

We propose and demonstrate that optical analog computing of spatial differentiation and edge detection can be realized with a single layer of dielectric metasurface. The optical transfer function for second-order derivation is obtained by engineering the spatial dispersion of electric dipole resonance supported by the silicon nanodisks in the metasurface. Benefiting from this unique mechanism of electric dipole resonance, spatial differentiation can be performed for two dimensions and arbitrary polarization with a large spatial bandwidth and high efficiency at the visible wavelength. Explicitly, we have numerically validated the application with one-dimensional spatial functions as well as an image, and the results show excellent performance. Our study can facilitate the research of optical computing with artificial nanostructures.

Inline cartridge extraction for rapid brain tumor tissue identification by molecular profiling.

The development of perspective diagnostic techniques in medicine requires efficient high-throughput biological sample analysis methods. Here, we present an inline cartridge extraction that facilitates the screening rate of mass spectrometry shotgun lipidomic analysis of tissue samples. We illustrate the method by its application to tumor tissue identification in neurosurgery. In perspective, this high-performance method provides new possibilities for the investigation of cancer pathogenesis and metabolic disorders.

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy.

Introduction: Acridine orange (AO) was first extracted from coal tar in the late nineteenth century and was used as a fluorescent dye. In this paper, we review emergent research about novel applications of AO for fluorescence surgery and cancer therapy. Materials and methods: We performed a systematic search in the MEDLINE, PubMed, Cochrane library, Google Scholar, Embase, Web of Science, and Scopus database using combinations of the term "acridine orange" with the following: "surgical oncology," "neuropathology," "microsurgery," "intraoperative fluorescence," "confocal microscopy," "pathology," "endomicroscopy," "guidance," "fluorescence guidance," "oncology," "surgery," "neurooncology," and "photodynamic therapy." Peer-reviewed articles published in English were included in this review. We have also scanned references for relevant articles. Results: We have reviewed studies on the various application of AO in microscopy, endomicroscopy, intraoperative fluorescence guidance, photodynamic therapy, sonodynamic therapy, radiodynamic therapy. Conclusion: Although the number of studies on the clinical use of AO is limited, pilot studies have demonstrated the safety and feasibility of its application as an intraoperative fluorescent dye and as a novel photo- and radio-sensitizator. Further clinical studies are necessary to more definitively assess the clinical benefit AO-based fluorescence guidance, therapy for sarcomas, and to establish feasibility of this new approach for the treatment of other tumor types.

Cross-Polarization Optical Coherence Tomography for Brain Tumor Imaging.

This paper considers valuable visual assessment criteria for distinguishing between tumorous and non-tumorous tissues, intraoperatively, using cross-polarization OCT (CP OCT)-OCT with a functional extension, that enables detection of the polarization properties of the tissues in addition to their conventional light scattering. Materials and Methods: The study was performed on 176 ex vivo human specimens obtained from 30 glioma patients. To measure the degree to which the typical parameters of CP OCT images can be matched to the actual histology, 100 images of tumors and white matter were selected for visual analysis to be undertaken by three "single-blinded" investigators. An evaluation of the inter-rater reliability between the investigators was performed. Application of the identified visual CP OCT criteria for intraoperative use was performed during brain tumor resection in 17 patients. Results: The CP OCT image parameters that can typically be used for visual assessment were separated: (1) signal intensity; (2) homogeneity of intensity; (3) attenuation rate; (4) uniformity of attenuation. The degree of match between the CP OCT images and the histology of the specimens was significant for the parameters "signal intensity" in both polarizations, and "homogeneity of intensity" as well as the "uniformity of attenuation" in co-polarization. A test based on the identified criteria showed a diagnostic accuracy of 87-88%. Intraoperative in vivo CP OCT images of white matter and tumors have similar signals to ex vivo ones, whereas the cortex in vivo is characterized by indicative vertical striations arising from the "shadows" of the blood vessels; these are not seen in ex vivo images or in the case of tumor invasion. Conclusion: Visual assessment of CP OCT images enables tumorous and non-tumorous tissues to be distinguished. The most powerful aspect of CP OCT images that can be used as a criterion for differentiation between tumorous tissue and white matter is the signal intensity. In distinguishing white matter from tumors the diagnostic accuracy using the identified visual CP OCT criteria was 87-88%. As the CP OCT data is easily associated with intraoperative neurophysiological and neuronavigation findings this can provide valuable complementary information for the neurosurgeon tumor resection.

A vascular-task response dependency and its application in functional imaging of brain tumors.

PURPOSE: Preoperative functional MRI (fMRI) is limited by a muted BOLD response caused by abnormal vasoreactivity and resultant neurovascular uncoupling adjacent to malignant brain tumors. We propose to overcome this limitation and more accurately identify eloquent areas adjacent to brain tumors by independently assessing vasoreactivity using breath-holding and incorporating these data into the fMRI analysis. METHODS: Local vasoreactivity using a breath-holding paradigm with the same timing as the functional motor and language tasks was determined in 16 patients (9 glioblastomas, 1 anaplastic astrocytoma, 5 low grade astrocytomas, and 1 metastasis) and 6 healthy control subjects. We derived an fMRI model based on an observed vaso-task response dependency that takes into account the altered hemodynamics adjacent to brain tumors. RESULTS: In both healthy controls and brain tumor subjects, we found a statistical dependency between breath-hold and task BOLD response. In tumor subjects, activation maps that take into account this vaso-task dependency demonstrated clinically meaningful areas of activation that were not seen using the task-only analysis in about half of the cases studied. This included localization of language areas adjacent to brain tumors. CONCLUSIONS: The present preliminary results demonstrate that neurovascular uncoupling known to affect the accuracy of BOLD fMRI adjacent to brain tumors may be, at least partially, overcome by incorporating an observed vaso-task dependency in the BOLD signal analysis.

Terahertz spectroscopy of gelatin-embedded human brain gliomas of different grades: a road toward intraoperative THz diagnosis.

We applied terahertz (THz)-pulsed spectroscopy to study ex vivo the refractive index and absorption coefficient of human brain gliomas featuring different grades, as well as perifocal regions containing both intact and edematous tissues. Glioma samples from 26 patients were considered and analyzed according to further histological examination. In order to fix tissues for the THz measurements, we applied gelatin embedding, which allows for sustaining their THz response unaltered, as compared to that of the freshly excised tissues. We observed a statistical difference between the THz optical constants of intact tissues and gliomas of grades I to IV, while the response of edema was similar to that of tumor. The results of this paper justify a potential of THz technology in the intraoperative label-free diagnosis of human brain gliomas for ensuring the gross-total resection.

Nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography.

We present the nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography (OCT). It employs an experimental training algorithm based on imaging of a test-object, made of the colloidal suspension of the monodisperse nanoparticles and contains the microscale inclusions. The geometry and the scattering properties of the test-object are known a priori allowing us to set the criteria for the training algorithm. Using a wide set of the wavelet kernels and the wavelet-domain filtration approaches, the appropriate filter is constructed based on the test-object imaging. We apply the proposed approach and chose an efficient wavelet denoising procedure by considering the combinations of the decomposition basis from five wavelet families with eight types of the filtration threshold. We demonstrate applicability of the wavelet-filtering for the in vitro OCT image of human brain meningioma. The observed results prove high efficiency of the proposed OCT image denoising technique.

Relative Abundance of Proteins in Blood Plasma Samples from Patients with Chronic Cerebral Ischemia.

A comparative protein profile analysis of 17 blood plasma samples from patients with ischemia and 20 samples from healthy volunteers was carried out using ultra-high resolution mass spectrometry. The analysis of measurements was performed using the proteomics search engine OMSSA. Normalized spectrum abundance factor (NSAF) in the biological samples was assessed using SearchGUI. The findings of mass spectrometry analysis of the protein composition of blood plasma samples demonstrate that the depleted samples are quite similar in protein composition and relative abundance of proteins. By comparing them with the control samples, we have found a small group of 44 proteins characteristic of the blood plasma samples from patients with chronic cerebral ischemia. These proteins contribute to the processes of homeostasis maintenance, including innate immune response unfolding, the response of a body to stress, and contribution to the blood clotting cascade.

Post-translational modifications of FDA-approved plasma biomarkers in glioblastoma samples.

Liquid chromatography-tandem mass spectrometry was used to analyze plasma proteins of volunteers (control) and patients with glioblastoma multiform (GBM). A database search was pre-set with a variable post-translational modification (PTM): phosphorylation, acetylation or ubiquitination. There were no significant differences between the control and the GBM groups regarding the number of protein identifications, sequence coverage or number of PTMs. However, in GBM plasma, we unambiguously observed a decreased fraction in post-translationally modified peptides identified with high quality. The disease-specific PTM patterns were extracted and mapped to the set of FDA-approved plasma protein markers. Decreases of 46% and 24% in the number of acetylated and ubiquitinated peptides, respectively, were observed in the GBM samples. Significance of capturing disease-associated patterns of protein modifications was envisaged.

Preoperative Stereotactic Radiosurgery of Brain Metastases: Preliminary Results.

INTRODUCTION:  Preoperative stereotactic radiosurgery (pre-SRS) is a recent advancement in the strategy for brain metastasis (BM) management, and available data demonstrate the advantages of pre-SRS before postoperative radiation treatment, including lower rates of local toxicity, leptomeningeal progression, and a high percentage of local control. The authors presented the results of pre-SRS in patients with BM. MATERIALS AND METHODS: Nineteen patients with BM (11 female and eight male) have been treated at N.N. Burdenko Medical Research Center for Neurosurgery (Moscow, Russia) and Gamma-Knife Center (Moscow, Russia) using pre-SRS. A total of 22 symptomatic metastatic lesions were preoperatively irradiated in the series. Eight patients had multiple BM (number of metastases ranged between two and seven). The median target volume for combined treatment was 14.131 cc (volumes varied between 2.995 and 57.098 cc; mean - 19.986 cc). The median of the mean target dose was 18 Gy, ranging between 12.58 and 24.36 Gy.  Results: All patients tolerated pre-SRS well, without any neurological deterioration, and surgical treatment was performed as scheduled. The median follow-up period was 6.3 months (ranging between five weeks and 22.9 months). In 17 out of 19 patients, follow-up magnetic resonance (MR) images obtained two or three months after the combined treatment demonstrated the postoperative cavity without any signs of postradiation alterations in the perifocal tissues. In two observations, peritumoral edema was present. Local recurrences were found in two cases, 5.5 and 17.4 months after treatment. Radionecrosis was present in one observation after 4.6 months of follow-up. Two patients died of disease progression and are presented as illustrative cases. CONCLUSION: The combined treatment of secondary brain tumors has proved to be the best treatment option. Preoperative stereotactic radiosurgery may decrease radiation-induced toxicity and rates of local tumor progression. The potential hazards of pre-SRS associated with the postoperative healing of irradiated soft tissues of the head were not confirmed in our study. The decision of pre-SRS should be made by the tumor board, including specialists in neurosurgery, neuro-oncology, and radiation oncology, if the diagnosis of BM is based on oncological history and visualization data.

Hiding in the Shadows: CPOX Expression and 5-ALA Induced Fluorescence in Human Glioma Cells.

Protoporphyrin IX (PpIX) is widely used in photodynamic diagnosis. To date, the details of molecular mechanisms underlying PpIX accumulation in malignant cells after 5-ALA administration remain unclear. The fluorescence of PpIX was studied in human glioma cells. Several cell cultures were established from glioma tumor tissue to study the differences between fluorescence-positive and fluorescence-negative human glioma tumors. The cell cultures demonstrated fluorescence profiles similar to those of source tumor tissues, which allows us to use these cultures in experimental research. Dynamics of the rates of synthesis and degradation of fluorescent protoporphyrin IX was studied in the cultures obtained. In addition, the expression of CPOX, an enzyme involved in PpIX synthesis, was evaluated. mRNA levels of heme biosynthesis enzymes were analyzed, and PpIX fluorescence proved to correlate with the CPOX protein level, whereas no such correlation was observed at the mRNA level. Fluorescence intensity decreased at low levels of the enzyme, which indicates its critical role in PpIX fluorescence. Finally, the fluorescence intensity proved to correlate with the proliferative activity.