Identification of the Incisive Branch of the Inferior Alveolar Nerve of Edentulous Mandibles Using Cone-Beam Computerized Tomography.

This study explored the average length of the incisive branch (IB) of the inferior alveolar nerve on cone-beam computerized tomography (CBCT) with regard to patient demographics in patients with edentulous mandibles. CBCT was used in a retrospective study of edentulous mandibles to assess the presence and anatomical variation for the IB. Three independent observers measured bilateral IB lengths. In addition to demographics, IB length and port of exit data were obtained. A 1-way analysis of variance was used to test whether IB length varied by sex or port of exit, and a standard Pearson correlation was used to test for IB length and age significance, with a significance level of P < .05. Intraclass correlation coefficients showed significant agreement in IB length across all observers. No significant difference was noted between the exit port and IB length. An important effect was reported for sex, indicating women have generally shorter IB lengths (9.43 ± 3.99 vs 10.55 ± 3.92). There was a significant correlation with age, but the relationship was weak. Edentulous mandibles have an altered anatomic landscape, and establishing predictive IB dimensions aids practitioners in surgical planning.

Identification of the Incisive Branch of the Inferior Alveolar Nerve of Edentulous Mandibles Using Cone Beam Computed Tomography.

This study explored the average length of the incisive branch of the inferior alveolar nerve on cone-beam computed tomography (CBCT) regarding patient demographics in patients with edentulous mandibles. CBCT was utilized in a retrospective study of edentulous mandibles to assess the presence and anatomical variation for the incisive branch (IB). Three independent observers measured bilateral IB lengths. In addition to demographics, IB length and port of exit data were obtained. A one-way ANOVA was used to test IB length varied by sex or port of exit, and a standard Pearson's correlation was used to test for IB length and age significance with a significance level of a p-value<0.05. Intraclass correlation coefficients show significant agreement in IB length across all observers. No significant difference was noted between the exit port and IB length. An important effect was reported for sex, indicating women have generally shorter IB lengths (9.43 ± 3.99 vs 10.55 ± 3.92). There was a significant correlation with age, but the relationship was weak. Edentulous mandibles have an altered anatomic landscape and establishing predictive incisive branch dimensions aids practitioners in surgical planning.

The Relationship of Low-Serum Vitamin D and Early Dental Implant Failure.

The study is aimed to assess the effects of serum vitamin D levels and their relationship to early dental implant failures. A total of 174 implants in 109 patients were placed and serum vitamin D levels were noted on the day of implant placement. Implants were followed up until restoration, approximately 3-6 months later, and any implant failure was reported based on 50% or more bone loss or implant mobility. Eight individuals had an implant fail early and their vitamin D levels had a mean of 42.54 ng/mL compared with the successful patients' levels of 31.92 ng/mL. Although not statistically significant, there was no correlation between patients' low serum vitamin D levels and early implant failure.

Advanced Molecular Characterization Using Digital Spatial Profiling Technology on Immunooncology Targets in Methylated Compared with Unmethylated IDH-Wildtype Glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumour with a median overall survival (OS) of 12-15 months. Molecular characterization of multiple immunooncology targets in GBM may help target novel immunotherapeutic strategies. We used NanoString GeoMx® Digital Spatial Profiling (DSP) to assess multiple immunooncology protein targets in methylated versus unmethylated IDH-wild-type glioblastoma. METHODS: NanoString GeoMx® DSP technology uses multiple primary antibodies conjugated to indexing DNA oligos with a UV photocleavable linker. Tissue regions of interest (ROIs) are selected with bound fluorescent antibodies; oligos are released via a UV-mediated linker and quantitated. We used DSP multiplex analysis of 31 immunooncology proteins and controls (CD4, CD14, CD68, CD8A, B7-H3, PD-L1, CD19, FOXP3, CD44, STAT3 (phospho Y705), CD45, Pan Cytokeratin, MS4A1/CD20, CD45RO, PD1, CD3, beta-2 microglobulin, VISTA, Bcl2, GZMB, PTEN, beta-catenin, CD56, Ki-67, STAT3, AKT, p-Akt, S6, Histone H3, IgG Rabbit control, and Mouse IgG control) from ROIs in a cohort of 10 IDH-wild-type glioblastomas (5 methylated and 5 unmethylated). An nCounter platform allowed quantitative comparisons of antibodies between ROIs in MGMT methylated and unmethylated tumours. Mean protein expression counts between methylated and unmethylated GBM were compared using technical and biological replicates. RESULTS: The analysis showed 10/27 immunooncology target proteins were significantly increased in methylated versus unmethylated IDH-wild-type glioblastoma tumour core (false discovery rate (FDR) <0.1 by Benjamini-Hochberg procedure). CONCLUSIONS: NanoString GeoMx® DSP was used to analyse multiple immunooncology protein target expression in methylated versus unmethylated IDH-wild-type glioblastoma. In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.

Cross-linguistic semantic preview benefit in Basque-Spanish bilingual readers: Evidence from fixation-related potentials.

During reading, we can process and integrate information from words allocated in the parafoveal region. However, whether we extract and process the meaning of parafoveal words is still under debate. Here, we obtained Fixation-Related Potentials in a Basque-Spanish bilingual sample during a Spanish reading task. By using the boundary paradigm, we presented different parafoveal previews that could be either Basque non-cognate translations or unrelated Basque words. We prove for the first time cross-linguistic semantic preview benefit effects in alphabetic languages, providing novel evidence of modulations in the N400 component. Our findings suggest that the meaning of parafoveal words is processed and integrated during reading and that such meaning is activated and shared across languages in bilingual readers.

Semantic parafoveal-on-foveal effects and preview benefits in reading: Evidence from Fixation Related Potentials.

During reading parafoveal information can affect the processing of the word currently fixated (parafovea-on-fovea effect) and words perceived parafoveally can facilitate their subsequent processing when they are fixated on (preview effect). We investigated parafoveal processing by simultaneously recording eye movements and EEG measures. Participants read word pairs that could be semantically associated or not. Additionally, the boundary paradigm allowed us to carry out the same manipulation on parafoveal previews that were displayed until reader's gaze moved to the target words. Event Related Potentials time-locked to the prime-preview presentation showed a parafoveal-on-foveal N400 effect. Fixation Related Potentials time locked to the saccade offset showed an N400 effect related to the prime-target relationship. Furthermore, this later effect interacted with the semantic manipulation of the previews, supporting a semantic preview benefit. These results demonstrate that at least under optimal conditions foveal and parafoveal information can be simultaneously processed and integrated.

A New Columnar CsI(Tl) Scintillator for iQID detectors.

A 1650 µm thick columnar CsI(Tl) scintillator for upgrading iQID detectors, which is a high-resolution photon-counting gamma-ray and x-ray detector recently developed at the Center for Gamma-Ray Imaging (CGRI), has been studied in terms of sensitivity, spatial resolution and depth-of-interaction effects. To facilitate these studies, a new frame-parsing algorithm for processing raw event data is also proposed that has more degrees of freedom in data processing and can discriminate against a special kind of noise present in some low-cost intensifiers. The results show that in comparison with a 450 µm-thickness columnar CsI(Tl) scintillator, the 1650 µm thick CsI(Tl) scintillator provides more than twice the sensitivity at the expense of some spatial resolution degradation. The depth-of-interaction study also shows that event size and amplitude vary with scintillator thickness, which can assist in future detector simulations and 3D-interaction-position estimation.

Fisher Information Analysis of Depth-of-Interaction Estimation in Double-Sided Strip Detectors.

In very-high-spatial-resolution gamma-ray imaging applications, such as preclinical PET and SPECT, estimation of 3D interaction location inside the detector crystal can be used to minimize parallax error in the imaging system. In this work, we investigate the effect of bias voltage setting on depth-of-interaction (DOI) estimates for a semiconductor detector with a double-sided strip geometry. We first examine the statistical properties of the signals and develop expressions for likelihoods for given gamma-ray interaction positions. We use Fisher Information to quantify how well (in terms of variance) the measured signals can be used for DOI estimation with different bias-voltage settings. We performed measurements of detector response versus 3D position as a function of applied bias voltage by scanning with highly collimated synchrotron radiation at the Advanced Photon Source at Argonne National Laboratory. Experimental and theoretical results show that the optimum bias setting depends on whether or not the estimated event position will include the depth of interaction. We also found that for this detector geometry, the z-resolution changes with depth.

The iQID camera: An ionizing-radiation quantum imaging detector.

We have developed and tested a novel, ionizing-radiation Quantum Imaging Detector (iQID). This scintillation-based detector was originally developed as a high-resolution gamma-ray imager, called BazookaSPECT, for use in single-photon emission computed tomography (SPECT). Recently, we have investigated the detector's response and imaging potential with other forms of ionizing radiation including alpha, neutron, beta, and fission fragment particles. The confirmed response to this broad range of ionizing radiation has prompted its new title. The principle operation of the iQID camera involves coupling a scintillator to an image intensifier. The scintillation light generated by particle interactions is optically amplified by the intensifier and then re-imaged onto a CCD/CMOS camera sensor. The intensifier provides sufficient optical gain that practically any CCD/CMOS camera can be used to image ionizing radiation. The spatial location and energy of individual particles are estimated on an event-by-event basis in real time using image analysis algorithms on high-performance graphics processing hardware. Distinguishing features of the iQID camera include portability, large active areas, excellent detection efficiency for charged particles, and high spatial resolution (tens of microns). Although modest, iQID has energy resolution that is sufficient to discriminate between particles. Additionally, spatial features of individual events can be used for particle discrimination. An important iQID imaging application that has recently been developed is real-time, single-particle digital autoradiography. We present the latest results and discuss potential applications.

Molecular Imaging in the College of Optical Sciences - An Overview of Two Decades of Instrumentation Development.

During the past two decades, researchers at the University of Arizona's Center for Gamma-Ray Imaging (CGRI) have explored a variety of approaches to gamma-ray detection, including scintillation cameras, solid-state detectors, and hybrids such as the intensified Quantum Imaging Device (iQID) configuration where a scintillator is followed by optical gain and a fast CCD or CMOS camera. We have combined these detectors with a variety of collimation schemes, including single and multiple pinholes, parallel-hole collimators, synthetic apertures, and anamorphic crossed slits, to build a large number of preclinical molecular-imaging systems that perform Single-Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET), and X-Ray Computed Tomography (CT). In this paper, we discuss the themes and methods we have developed over the years to record and fully use the information content carried by every detected gamma-ray photon.

Imaging properties of pixellated scintillators with deep pixels.

We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10×10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm × 1mm × 20 mm pixels) made by Proteus, Inc. with similar 10×10 arrays of LSO:Ce and BGO (1mm × 1mm × 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10×10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of 176Lu in LSO:Ce and LYSO:Ce detectors.

The effect of gain variation in micro-channel plates on gamma-ray energy resolution.

A Monte Carlo simulation of micro-channel plate (MCP) with particular interest in its effect on energy resolution performance is presented. Important physical processes occurring in MCP channels are described and modeled, including secondary electron (SE) yield, SE emission, and primary electron reflection. The effects causing channel saturation are also introduced. A two dimensional Monte Carlo simulation is implemented under the assumption of unsaturated channel. Simulation results about basic MCP performances and especially gain and energy resolution performances are presented and analyzed. It's found that energy resolution as an intrinsic property of MCP cannot be improved simply by adjusting system parameters; however it can be improved by increasing input signal or number of photoelectrons (PEs) in the context of image intensifier. An initial experiment with BazookaSPECT detector and CsI(Tl) scintillator is performed to validate and correlate with the simulation results and good agreement is achieved.

Progress in BazookaSPECT: High-Resolution, Dynamic Scintigraphy with Large-Area Imagers.

We present recent progress in BazookaSPECT, a high-resolution, photon-counting gamma-ray detector. It is a new class of scintillation detector that combines columnar scintillators, image intensifiers, and CCD (charge-coupled device) or CMOS (complementary metal-oxide semiconductors) sensors for high-resolution imaging. A key feature of the BazookaSPECT paradigm is the capability to easily design custom detectors in terms of the desired intrinsic detector resolution and event detection rate. This capability is possible because scintillation light is optically amplified by the image intensifier prior to being imaging onto the CCD/CMOS sensor, thereby allowing practically any consumer-grade CCD/CMOS sensor to be used for gamma-ray imaging. Recent efforts have been made to increase the detector area by incorporating fiber-optic tapers between the scintillator and image intensifier, resulting in a 16× increase in detector area. These large-area BazookaSPECT detectors can be used for full-body imaging and we present preliminary results of their use as dynamic scintigraphy imagers for mice and rats. Also, we discuss ongoing and future developments in BazookaSPECT and the improved event-detection rate capability that is achieved using Graphics Processing Units (GPUs), multi-core processors, and new high-speed, USB 3.0 CMOS cameras.

Investigation of the possibility of gamma-ray diagnostic imaging of target compression at NIF.

The National Ignition Facility at Lawrence Livermore National Laboratory is the world's leading facility to study the physics of igniting plasmas. Plasmas of hot deuterium and tritium, undergo d(t,n)α reactions that produce a 14.1 MeV neutron and 3.5 MeV a particle, in the center of mass. As these neutrons pass through the materials surrounding the hot core, they may undergo subsequent (n,x) reactions. For example, (12)C(n,n'γ)(12)C reactions occur in remnant debris from the polymer ablator resulting in a significant fluence of 4.44 MeV gamma-rays. Imaging of these gammas will enable the determination of the volumetric size and symmetry of the ablation; large size and high asymmetry is expected to correlate with poor compression and lower fusion yield. Results from a gamma-ray imaging system are expected to be complimentary to a neutron imaging diagnostic system already in place at the NIF. This paper describes initial efforts to design a gamma-ray imaging system for the NIF using the existing neutron imaging system as a baseline for study. Due to the cross-section and expected range of ablator areal densities, the gamma flux should be approximately 10(-3) of the neutron flux. For this reason, care must be taken to maximize the efficiency of the gamma-ray imaging system because it will be gamma starved. As with the neutron imager, use of pinholes and/or coded apertures are anticipated. Along with aperture and detector design, the selection of an appropriate scintillator is discussed. The volume of energy deposition of the interacting 4.44 MeV gamma-rays is a critical parameter limiting the imaging system spatial resolution. The volume of energy deposition is simulated with GEANT4, and plans to measure the volume of energy deposition experimentally are described. Results of tests on a pixellated LYSO scintillator are also presented.

Design Considerations for the Next-Generation MAPMT-Based Monolithic Scintillation Camera.

Multi-anode photomultiplier tubes (MAPMTs) offer high spatial resolution with their small size anodes that may range from 64 to 1024 in number per tube. In order to increase detector size, MAPMT modules can be arranged in arrays and combined in a single modular scintillation camera. However, then the large number of channels that require amplification and digitization become practically not feasible unless signals are combined or reduced in some manner. Conventional approaches use resistive charge division readouts with a centroid algorithm (or a variant of it) for simplicity in the electronic circuitry implementation and fast execution. However, coupling signals from many anodes may cause significant information loss and limit achievable resolution. In this study, a new approach for optimizing readout-electronics design for MAPMTs based on an analysis of information content in the signals is presented. An adaptive read-out scheme to be used with maximum-likelihood estimation methods is proposed. This scheme achieves precision in estimating event parameters that is close to what is achieved by retaining all signals.

System Integration of FastSPECT III, a Dedicated SPECT Rodent-Brain Imager Based on BazookaSPECT Detector Technology.

FastSPECT III is a stationary, single-photon emission computed tomography (SPECT) imager designed specifically for imaging and studying neurological pathologies in rodent brain, including Alzheimer's and Parkinsons's disease. Twenty independent BazookaSPECT [1] gamma-ray detectors acquire projections of a spherical field of view with pinholes selected for desired resolution and sensitivity. Each BazookaSPECT detector comprises a columnar CsI(Tl) scintillator, image-intensifier, optical lens, and fast-frame-rate CCD camera. Data stream back to processing computers via firewire interfaces, and heavy use of graphics processing units (GPUs) ensures that each frame of data is processed in real time to extract the images of individual gamma-ray events. Details of the system design, imaging aperture fabrication methods, and preliminary projection images are presented.

Progress in BazookaSPECT.

Recent progress on a high-resolution, photon-counting gamma-ray and x-ray imager called BazookaSPECT is presented. BazookaSPECT is an example of a new class of scintillation detectors based on integrating detectors such as CCD(charge-coupled device) or CMOS(complementary metal-oxide semiconductor) sensors. BazookaSPECT is unique in that it makes use of a scintillator in close proximity to a microchannel plate-based image intensifier for up-front optical amplification of scintillation light. We discuss progress made in bringing about compact BazookaSPECT modules and in real-time processing of event data using graphics processing units (GPUs). These advances are being implemented in the design of a high-resolution rodent brain imager called FastSPECT III. A key benefit of up-front optical gain is that any CCD/CMOS sensor can now be utilized for photon counting. We discuss the benefits and feasibility of using CMOS sensors as photon-counting detectors for digital radiography, with application in mammography and computed tomography (CT). We present as an appendix a formal method for comparing various photon-counting integrating detectors using objective statistical criteria.

Recent advances in BazookaSPECT: Real-time data processing and the development of a gamma-ray microscope.

Recent advances have been made with the BazookaSPECT detector, a high-resolution CCD-based gamma camera which utilizes an MCP-based image intensifier for upfront optical gain. Operating the gamma camera at high frame rates leads to a massive amount of data throughput, thereby inducing the need for real-time processing. We have developed and implemented a list-mode algorithm which allows for real-time data acquisition and processing at high frame rates. This is accomplished with a graphics processing unit (GPU), which provides processing capabilities in addition to the CPU. We have also developed a gamma-ray microscope based on the BazookaSPECT detector and micro-coded apertures. Experimental phantom images show the gamma-ray microscope having an estimated reconstruction resolution of ~30 µm, an unprecedented resolution in gamma-ray imaging.