Prospects for Theranostics in Neurosurgical Imaging: Empowering Confocal Laser Endomicroscopy Diagnostics via Deep Learning

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence imaging technology that has the potential to increase intraoperative precision, extend resection, and tailor surgery for malignant invasive brain tumors because of its subcellular dimension resolution. Despite its promising diagnostic potential, interpreting the gray tone fluorescence images can be difficult for untrained users. In this review, we provide a detailed description of bioinformatical analysis methodology of CLE images that begins to assist the neurosurgeon and pathologist to rapidly connect on-the-fly intraoperative imaging, pathology, and surgical observation into a conclusionary system within the concept of theranostics. We present an overview and discuss deep learning models for automatic detection of the diagnostic CLE images and discuss various training regimes and ensemble modeling effect on the power of deep learning predictive models. Two major approaches reviewed in this paper include the models that can automatically classify CLE images into diagnostic/nondiagnostic, glioma/nonglioma, tumor/injury/normal categories and models that can localize histological features on the CLE images using weakly supervised methods. We also briefly review advances in the deep learning approaches used for CLE image analysis in other organs. Significant advances in speed and precision of automated diagnostic frame selection would augment the diagnostic potential of CLE, improve operative workflow and integration into brain tumor surgery. Such technology and bioinformatics analytics lend themselves to improved precision, personalization, and theranostics in brain tumor treatment.Comment: See the final version published in Frontiers in Oncology here: https://www.frontiersin.org/articles/10.3389/fonc.2018.00240/ful

Probing High Reheating Temperature Scenarios at the LHC with Long-Lived Staus

We investigate the possibility of probing high reheating temperature scenarios at the LHC, in supersymmetric models where the gravitino is the lightest supersymmetric particle, and the stau is the next-to-lightest supersymmetric particle. In such scenarios, the big-bang nucleosynthesis and the gravitino abundance give a severe upper bound on the gluino mass. We find that, if the reheating temperature is \sim 10^8 GeV or higher, the scenarios can be tested at the LHC with an integrated luminosity of O(1 fb^{-1}) at \sqrt{s}=7 TeV in most of the parameter space.Comment: 17 pages, 5 figures, minor modification

Dietary fiber showed no preventive effect against colon and rectal cancers in Japanese with low fat intake: an analysis from the results of nutrition surveys from 23 Japanese prefectures

BACKGROUND: Since Fuchs' report in 1999, the reported protective effect of dietary fiber from colorectal carcinogenesis has led many researchers to question its real benefit. The aim of this study is to evaluate the association between diet, especially dietary fiber and fat and colorectal cancer in Japan. METHODS: A multiple regression analysis (using the stepwise variable selection method) was performed using the standardized mortality ratios (SMRs) of colon and rectal cancer in 23 Japanese prefectures as objective variables and dietary fiber, nutrients and food groups as explanatory variables. RESULTS: As for colon cancer, the standardized partial correlation coefficients were positively significant for fat (1,13, P = 0.000), seaweeds (0.41, P = 0.026) and beans (0.45, P = 0.017) and were negatively significant for vitamin A (-0.63, P = 0.003), vitamin C (-0.42, P = 0.019) and yellow-green vegetables (-0.37, P = 0.046). For rectal cancer, the standardized partial correlation coefficient in fat (0.60, P = 0.002) was positively significant. Dietary fiber was not found to have a significant relationship with either colon or rectal cancers. CONCLUSIONS: This study failed to show any protective effect of dietary fiber in subjects with a low fat intake (Japanese) in this analysis, which supports Fuchs' findings in subjects with a high fat intake (US Americans)

Improved characteristics of InGaN multiple-quantum-well light-emitting diode by GaN/AlGaN distributed Bragg reflector grown on sapphire

An InGaN multiple-quantum-well light-emitting diode (LED) containing a GaN/AlGaN distributed Bragg reflector has been grown on a sapphire substrate by metalorganic chemical vapor deposition. Comparing with the conventional LED, the output power has been improved from 79 to 120 μW under 20 mA direct current biasing condition and the external quantum efficiency has been also improved from 0.16% to 0.23% under 10 mA dc current.application/pdfjournal articl

Descriptive Strength and Range of Motion in Youth Baseball Players

# Background There are limited studies reporting descriptive strength and range of motion in youth baseball players 12 years of age or younger. # Purpose To establish normative data for external (ER) and internal (IR) rotation range of motion (ROM), total arc range of motion (TROM), and isometric rotator cuff strength in youth baseball players, and to compare between the dominant throwing arm (D) to the non-dominant arm (ND). # Study Design Cross-sectional # Methods Patient population included 50 (5 to 12-year-old) uninjured, healthy athletes. ROM measurements were performed preseason using a goniometer for IR and ER in the supine position with the shoulder in 90 degrees of abduction (abd) with scapular stabilization. Isometric strength measurements for IR and ER were collected in both neutral and 90 degrees (deg) of abduction with the use of a hand-held dynamometer and recorded in pounds (lbs) utilizing a “make” test. Descriptive statistics were obtained for all measures. # Results All data were analyzed as a single group (average age: 9.02). No significant difference in average total arc of PROM (ER+IR=Total Arc) on the D side compared to the ND side (136.7 ± 12.7 deg vs. 134.3 ± 12.3 deg). There were statistically significant differences between ER ROM (102.2 ± 7.7 deg vs. 96.8 ± 7.4 deg) and IR ROM (34.4 ± 9.0 deg vs. 37.5 ± 9.5 deg) between D versus ND arms (p= .000, .006 respectively). Mean ER strength in neutral (13.6 ± 3.4 and 12.8 ± 3.6 lbs) and 90 deg abduction (12.3 ± 3.4 and 12.5 ± 4.3 lbs) did were not significantly different between D and ND arms, respectively. Mean IR strength in neutral (18.0 ± 6.0 and 15.7 ± 4.7 lbs) and 90 deg abd (16.4 ± 5.6 and 15.0 ± 5.7 lbs) was significantly greater in the D arm vs ND arm, respectively (p=.000, .001). # Conclusion These data can provide descriptive information for clinicians who treat very young baseball players. These data show sport specific adaptations occur at very young ages (5-12) and are similar to prior reports on adolescent, high school and professional baseball players regarding upper extremity ROM and rotator cuff strength. # Level of Evidence

Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes.

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment

Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 +/- 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 +/- 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 +/- 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

High-Dose Fluorescein Reveals Unusual Confocal Endomicroscope Imaging of Low-Grade Glioma

Background: Fluorescence-guided brain tumor surgery using fluorescein sodium (FNa) for contrast is effective in high-grade gliomas. However, the effectiveness of this technique for visualizing noncontrast-enhancing and low-grade gliomas is unknown. This report is the first documented case of the concurrent use of wide-field fluorescence-guided surgery and confocal laser endomicroscopy (CLE) with high-dose FNa (40 mg/kg) for intraoperative visualization of tumor tissue cellularity in a nonenhancing glioma.Case Description: A patient underwent fluorescence-guided surgery for a left frontal lobe mass without contrast enhancement on magnetic resonance imaging. The patient received 40 mg/kg FNa intravenously at the induction of anesthesia. Surgery was performed under visualization with a Yellow 560 filter and white-light wide-field imaging. Intraoperative CLE produced high-quality images of the lesion 1.5 h after FNa injection. Frozen-section analysis demonstrated findings comparable to those of intraoperative CLE visualization and consistent with World Health Organization (WHO) glioma grades II–III. The patient recovered without complications. Analysis of the permanent histologic sections identified the tumor as an anaplastic oligodendroglioma, IDH-mutant, 1p/19q co-deleted, consistent with WHO grade III because of discrete foci of hypercellularity and increased mitotic figures, but large regions of the lesion were low grade.Conclusions: The use of high-dose FNa in this patient with a nonenhancing borderline low-grade/high-grade glioma produced actionable wide-field fluorescence imaging using the operating microscope and improved CLE visualization of tumor cellularity. Higher doses of FNa for intraoperative CLE imaging and possible simultaneous wide-field fluorescence surgical guidance in nonenhancing gliomas merit further investigation