Specific Regions Of Interest Research Articles

AtmoCube A1: airglow measurements in the mesosphere and lower thermosphere by spatial heterodyne interferometry

The Institute for Atmospheric and Environmental Research at the University of Wuppertal and the Institute of Energy and Climate Research Stratosphere at Research Center Juelich developed a CubeSat payload for atmospheric research. The payload consists of a small interferometer for the observation of airglow near 762 nm. The line intensities of the oxygen A-band are used to derive temperatures in the mesosphere and lower thermosphere region. The temperature data will be used to analyze dynamical wave structures in the atmosphere. The interferometer technology chosen to measure the ro-vibrational structure of the O2 atmospheric band near 762 nm is a spatial heterodyne interferometer originally proposed by Connes in 1958. It can be designed to deliver extraordinary spectral resolution to resolve individual emission lines. The utilization of a two-dimensional imaging detector allows for recording interferograms at adjacent locations simultaneously. Integrated in a six-unit CubeSat, the instrument is designed for limb sounding of the atmosphere. The agility of a CubeSat will be used to sweep the line-of-sight through specific regions of interest to derive a three-dimensional image of an atmospheric volume using tomographic reconstruction techniques.

Seasonal evolution of temperatures in Titan's lower stratosphere

The Cassini mission offered us the opportunity to monitor the seasonal evolution of Titan's atmosphere from 2004 to 2017, i.e. half a Titan year. The lower part of the stratosphere (pressures greater than 10 mbar) is a region of particular interest as there are few available temperature measurements, and because its thermal response to the seasonal and meridional insolation variations undergone by Titan remain poorly known. In this study, we measure temperatures in Titan's lower stratosphere between 6 mbar and 25 mbar using Cassini/CIRS spectra covering the whole duration of the mission (from 2004 to 2017) and the whole latitude range. We can thus characterize the meridional distribution of temperatures in Titan's lower stratosphere, and how it evolves from northern winter (2004) to summer solstice (2017). Our measurements show that Titan's lower stratosphere undergoes significant seasonal changes, especially at the South pole, where temperature decreases by 19 K at 15 mbar in 4 years.

Monte Carlo Analysis of Optical Interactions in Reflectance and Transmittance Finger Photoplethysmography.

Photoplethysmography (PPG) is a non-invasive photometric technique that measures the volume changes in arterial blood. Recent studies have reported limitations in developing and optimising PPG-based sensing technologies due to unavailability of the fundamental information such as PPG-pathlength and penetration depth in a certain region of interest (ROI) in the human body. In this paper, a robust computational model of a dual wavelength PPG system was developed using Monte Carlo technique. A three-dimensional heterogeneous volume of a specific ROI (i.e., human finger) was exposed at the red (660 nm) and infrared (940 nm) wavelengths in the reflectance and transmittance modalities of PPG. The optical interactions with the individual pulsatile and non-pulsatile tissue-components were demonstrated and the optical parameters (e.g., pathlength, penetration depth, absorbance, reflectance and transmittance) were investigated. Results optimised the source-detector separation for a reflectance finger-PPG sensor. The analysis with the recorded absorbance, reflectance and transmittance confirmed the maximum and minimum impact of the dermis and bone tissue-layers, respectively, in the formation of a PPG signal. The results presented in the paper provide the necessary information to develop PPG-based transcutaneous sensors and to understand the origin of the ac and dc components of the PPG signal.

CAD-CAM milled versus rapidly prototyped (3D-printed) complete dentures: An in vitro evaluation of trueness

Statement of problemComplete dentures fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM) techniques have become popular. The 2 principal CAD-CAM techniques, milling and rapid prototyping (3D printing), used in the fabrication of complete dentures have been reported to yield clinically acceptable results. However, clinical trials or in vitro studies that evaluated the accuracy of the 2 manufacturing techniques are lacking. PurposeThe purpose of this in vitro study was to compare the differences in trueness between the CAD-CAM milled and 3D-printed complete dentures. Material and methodsTwo groups of identical maxillary complete dentures were fabricated. A 3D-printed denture group (3DPD) (n=10) and a milled denture group (MDG) (n=10) from a reference maxillary edentulous model. The intaglio surfaces of the fabricated complete dentures were scanned at baseline using a laboratory scanner. The complete dentures were then immersed in an artificial saliva solution for a period of 21 days, followed by a second scan (after immersion in saliva). A third scan (after the wet-dry cycle) was then made after 21 days, during which the complete dentures were maintained in the artificial saliva solution during the day and stored dry at night. A purpose-built 3D comparison software program was used to analyze the differences in the trueness of the complete dentures. The analyses were performed for the entire intaglio surface and specific regions of interest: posterior crest, palatal vault, posterior palatal seal area, tuberosity, anterior ridge, vestibular flange, and mid-palatal raphae. Independent t tests, ANOVA, and post hoc tests were used for statistical analyses (α=.05). ResultsThe trueness of the milled prostheses was significantly better than that of the rapid prototyping group with regard to the entire intaglio surface (P<.001), posterior crest (P<.001), palatal vault (P<.001), posterior palatal seal area (P<.001), tuberosity (P<.001), anterior ridge (baseline: P<.001; after immersion in saliva: P=.001; after the wet-dry cycle: P=.011), vestibular flange (P<.001), and mid-palatal raphae (P<.001). ConclusionsThe CAD-CAM, milled complete dentures, under the present manufacturing standards, were superior to the rapidly prototyped complete dentures in terms of trueness of the intaglio surfaces. However, further research is needed on the biomechanical, clinical, and patient-centered outcome measures to determine the true superiority of one technique over the other with regard to fabricating complete dentures by CAD-CAM techniques.

Kelpie: generating full-length 'amplicons' from whole-metagenome datasets.

IntroductionWhole-metagenome sequencing can be a rich source of information about the structure and function of entire metagenomic communities, but getting accurate and reliable results from these datasets can be challenging. Analysis of these datasets is founded on the mapping of sequencing reads onto known genomic regions from known organisms, but short reads will often map equally well to multiple regions, and to multiple reference organisms. Assembling metagenomic datasets prior to mapping can generate much longer and more precisely mappable sequences but the presence of closely related organisms and highly conserved regions makes metagenomic assembly challenging, and some regions of particular interest can assemble poorly. One solution to these problems is to use specialised tools, such as Kelpie, that can accurately extract and assemble full-length sequences for defined genomic regions from whole-metagenome datasets.MethodsKelpie is a kMer-based tool that generates full-length amplicon-like sequences from whole-metagenome datasets. It takes a pair of primer sequences and a set of metagenomic reads, and uses a combination of kMer filtering, error correction and assembly techniques to construct sets of full-length inter-primer sequences.ResultsThe effectiveness of Kelpie is demonstrated here through the extraction and assembly of full-length ribosomal marker gene regions, as this allows comparisons with conventional amplicon sequencing and published metagenomic benchmarks. The results show that the Kelpie-generated sequences and community profiles closely match those produced by amplicon sequencing, down to low abundance levels, and running Kelpie on the synthetic CAMI metagenomic benchmarking datasets shows similar high levels of both precision and recall.ConclusionsKelpie can be thought of as being somewhat like an in-silico PCR tool, taking a primer pair and producing the resulting ‘amplicons’ from a whole-metagenome dataset. Marker regions from the 16S rRNA gene were used here as an example because this allowed the overall accuracy of Kelpie to be evaluated through comparisons with other datasets, approaches and benchmarks. Kelpie is not limited to this application though, and can be used to extract and assemble any genomic region present in a whole metagenome dataset, as long as it is bound by a pairs of highly conserved primer sequences.

A direct volume rendering visualization approach for serial PET-CT scans that preserves anatomical consistency.

Our aim was to develop an interactive 3D direct volume rendering (DVR) visualization solution to interpret and analyze complex, serial multi-modality imaging datasets from positron emission tomography-computed tomography (PET-CT). Our approach uses: (i) a serial transfer function (TF) optimization to automatically depict particular regions of interest (ROIs) over serial datasets with consistent anatomical structures; (ii) integration of a serial segmentation algorithm to interactively identify and track ROIs on PET; and (iii) parallel graphics processing unit (GPU) implementation for interactive visualization. Our DVR visualization more easily identifies changes in ROIs in serial scans in an automated fashion and parallel GPU computation which enables interactive visualization. Our approach provides a rapid 3D visualization of relevant ROIs over multiple scans, and we suggest that it can be used as an adjunct to conventional 2D viewing software from scanner vendors.

Generalised coherent point drift for group-wise multi-dimensional analysis of diffusion brain MRI data.

A probabilistic framework for registering generalised point sets comprising multiple voxel-wise data features such as positions, orientations and scalar-valued quantities, is proposed. It is employed for the analysis of magnetic resonance diffusion tensor image (DTI)-derived quantities, such as fractional anisotropy (FA) and fibre orientation, across multiple subjects. A hybrid Student's t-Watson-Gaussian mixture model-based non-rigid registration framework is formulated for the joint registration and clustering of voxel-wise DTI-derived data, acquired from multiple subjects. The proposed approach jointly estimates the non-rigid transformations necessary to register an unbiased mean template (represented as a 7-dimensional hybrid point set comprising spatial positions, fibre orientations and FA values) to white matter regions of interest (ROIs), and approximates the joint distribution of voxel spatial positions, their associated principal diffusion axes, and FA. Specific white matter ROIs, namely, the corpus callosum and cingulum, are analysed across healthy control (HC) subjects (K = 20 samples) and patients diagnosed with mild cognitive impairment (MCI) (K = 20 samples) or Alzheimer's disease (AD) (K = 20 samples) using the proposed framework, facilitating inter-group comparisons of FA and fibre orientations. Group-wise analyses of the latter is not afforded by conventional approaches such as tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM).

Computationally Characterizing Protein-Bound Long Noncoding RNAs and Their Secondary Structure Using Protein Interaction Profile Sequencing (PIP-Seq) in Plants.

Two major components of posttranscriptional regulation are RNA-protein interactions and RNA secondary structure. While noncoding RNAs are far more abundant than messenger RNAs in eukaryotic systems, their functions remain largely unstudied. Evidence suggests that RNA-protein interactions and RNA secondary structure also regulate the function of long noncoding RNAs (lncRNAs), which are noncoding RNAs over 200 nucleotides (nt) in length. Protein interaction profile sequencing (PIP-seq) allows researchers to perform an unbiased screen of protein-bound regions and secondary structure of RNAs throughout a transcriptome of interest. Using a peak calling approach, our pipeline is able to identify protein-protected sites (PPSs), which are putative RNA-protein interaction sites. Additionally, by taking the ratio of read coverages in double-stranded RNA (dsRNA)-seq compared to single-stranded RNA (ssRNA)-seq libraries, our analysis can also calculate an RNA secondary structure score that reflects the likelihood of a region being comprised of double- or single-stranded ribonucleotides. Researchers can also use this pipeline to look at specific regions of interest, such as known lncRNAs, and determine their protein-bound status as well as elucidate their secondary structure.

Expanding Care Economy in South Asia

Transformative care policies have recently been debated at the ILO to meet SDG targets on employment generation and decent work, gender equality, and poverty reduction through state-funded social security policies. South Asia, which houses a large proportion of unpaid care work burden, is a region of special interest. The article explores how investment in care economy can be routed through restructuring labor, gender mainstreaming macroeconomics and introducing transformative care policies. This approach closely ties with the investment in physical infrastructure that governments of India, Bangladesh and Sri Lanka have begun, which has a potential to augment care infrastructure.

The regime of Aerosol Optical Depth and Ångström exponent over Central and South Asia

Central and South Asia are regions of particular interest for studying atmospheric aerosols, being among the largest sources of desert dust aerosols globally. In this study we use the newest collection (C061) of MODIS - Aqua aerosol optical depth (AOD) at 550 nm and Ångström exponent (a) at 412/470 nm over the 15-year period between 2002 and 2017, providing the longest analyzed dataset for this region. According to our results, during spring and summer, high aerosol load (AOD up to 1.2) consisting of coarse desert dust particles, as indicated by a values as low as 0.15, is observed over the Taklamakan, Thar and Registan deserts and the region between the Aral and Caspian seas. The dust load is much lower during winter and autumn (lower AOD and higher a values compared to the other seasons). The interannual variation of AOD and a suggests that the dust load exhibits large decreasing trends (AOD slopes down to -0.22, a slopes up to 0.47 decade-1) over the Thar desert and large increasing trends between the Aral and Caspian seas (AOD and a slopes up to 0.23 decade-1 and down to -0.61 decade-1, respectively.) The AOD data are evaluated against AERONET surface-based measurements. Generally, MODIS and AERONET data are in good agreement with a correlation coefficient (R) equal to 0.835.

Social Feedback Modulates Neural Response Associated With Cognitive Bias in Individuals Expressing Anxious Symptoms

Background Social anxiety is characterized by a tendency to overestimate the likelihood of negative outcomes and consequences before, during, and after interpersonal interactions with social partners. Recent evidence suggests that a network of brain regions critical for perspective-taking, threat appraisal, and uncertainty resolution may function atypically in those prone to social anxiety. In this study, we used functional magnetic resonance imaging to examine neural activity in specific regions of interest in a sample of young adults who endorsed high or low levels of social anxiety. Methods We recruited 31 college student volunteers (age: 18–28 years), categorized as having high or low anxiety based on their Liebowitz Social Anxiety Scale-Self Report scores. These participants were each scanned while playing the iterated Prisoner’s Dilemma game with three computerized confederates, two of whom they were deceived to believe were human co-players. This study focuses on data collected during play with the presumed humans. Regions of interest were defined for the temporoparietal junction, anterior midcingulate, and dorsomedial prefrontal cortex. Average weighted mean blood-oxygen-level-dependent signals for each subject were extracted and analyzed using mixed design analyses of variance to detect group differences in activation during decision-making, anticipation, and appraisal of round outcomes during the game. Results Behavior analysis revealed that the high-anxiety group was more likely to defect than the low-anxiety group. Neuroimaging analysis showed that the high-anxiety group exhibited elevated blood-oxygen-level-dependent activity relative to the low-anxiety group in all three regions during the social feedback appraisal phase but not during decision-making or the anticipation of interaction outcomes. Conclusions These findings provide evidence that some behaviors linked to cognitive biases associated with social anxiety may be mediated by a network of regions involved in recognizing and processing directed social information. Future investigation of the neural basis of cognition and bias in social anxiety using the prisoner’s dilemma and other economic-exchange tasks is warranted. These tasks appear to be highly effective, functional magnetic resonance imaging-compatible methods of probing altered cognition and behavior associated with anxiety and related conditions.

Association between Cyclic Meditation and Creative Cognition: Optimizing Connectivity between the Frontal and Parietal Lobes.

Background:Important stages of creativity include preparation, incubation, illumination, and verification. Earlier studies have reported that some techniques of meditation promote creativity but have not specified which stage is enhanced. Here, we report the influence of cyclic meditation (CM) on creative cognition measured by a divergent thinking task. Our aim was to determine the degree of association between the two.Methods:Twenty-four university students were randomly assigned to an experimental group (CM) and controls (Supine Rest), 35 min/day for 7 days. Creativity performance was assessed pre and post using Abbreviated Torrance Test for Adults (ATTA), while 64-channel electroencephalography (EEG) was used to measure brain activity during both CM/SH and the creativity test.Results:Results indicated that CM training improved creativity performance, producing a shift to predominant gamma activity during creativity compared controls who showed delta activity. Furthermore, the experimental group showed more activation of frontal and parietal regions (EEG leads F3, F4 and P3, P4) than controls, i.e., the regions of the executive network responsible for creative cognition, our particular regions of interest where specialized knowledge is being stored.Conclusion:Improvement on creativity test performance indicates that CM increases association and strengthens the connectivity between frontal and parietal lobes, the major nodes of default mode network and executive attention network, enhancing the important stages of creativity such as preparation, incubation, and illumination.

High-permittivity pad design tool for 7T neuroimaging and 3T body imaging.

PurposeHigh‐permittivity materials in the form of flexible “dielectric pads” have proved very useful for addressing RF inhomogeneities in high field MRI systems. Finding the optimal design of such pads is, however, a tedious task, reducing the impact of this technique. We present an easy‐to‐use software tool which allows researchers and clinicians to design dielectric pads efficiently on standard computer systems, for 7T neuroimaging and 3T body imaging applications.MethodsThe tool incorporates advanced computational methods based on field decomposition and model order reduction as a framework to efficiently evaluate the B 1 + fields resulting from dielectric pads. The tool further incorporates optimization routines which can either optimize the position of a given dielectric pad, or perform a full parametric design. The optimization procedure can target either a single target field, or perform a sweep to explore the trade‐off between homogeneity and efficiency of the B 1 + field in a specific region of interest. The 3T version further allows for shifting of the imaging landmark to enable different imaging targets to be centered in the body coil.ResultsExample design results are shown for imaging the inner ear at 7T and for cardiac imaging at 3T. Computation times for all cases are approximately a minute per target field.ConclusionThe developed tool can be easily used to design dielectric pads for any 7T neuroimaging and 3T body imaging application within minutes. This bridges the gap between the advanced design methods and the practical application by the MR community.

Gray matter hypertrophy in primary insomnia: a surface-based morphometric study.

Studies have explored brain structural abnormalities in patients with primary insomnia (PI). However, most of them are based on volumetric measures, in a specific region of interest, and have small sample sizes. Here, we investigated changes in cortical morphology (thickness and volume) in PI using an advanced surface-based morphometric method. Sixty-seven patients with PI and 55 matched healthy controls were recruited for this study and underwent a structural magnetic resonance imaging scan. The reconstructed cortical surface was processed by Freesurfer 6.0. A general linear model was used to explore group differences in surface-based morphometric features. Furthermore, the association between these cortical features and clinical characteristics were assessed in the PI group. Compared to controls, PI patients showed cortical thickening in the left orbital frontal cortex (OFC), right rostral anterior cingulate cortex (rACC), left middle cingulate cortex (MCC), bilateral insula, left superior parietal lobule (SPL), and right fusiform area (FFA), and showed increased cortical volume in the left OFC, right rACC, bilateral rostral middle frontal gyrus, and right FFA. Cortical thickness in the right OFC and FFA was positively correlated with the severity of insomnia in the PI group, suggesting a right-lateralized relationship. This study was the first to explore multiple-scale cortical morphometric changes in a relatively large sample of PI patients. Our results suggest that hypertrophic cortical morphology may underlie the neuropathology of primary insomnia.

Evaluation of the effects of temperature on processed coffee beans in the presence of fungi and ochratoxin A

The coffee bean is sensitive to contamination with ocratoxigenic fungi; temperature influences the growth, and germination of these fungi, as well as the fungal toxins produced. The objectives of this study were to assess the distribution of toxigenic species, analyze the concentration of ochratoxin A (OTA) in Arabica coffee beans, and aplicate a mathematical model that considers the influence of actual temperature to predict the effects of projected temperature increase on OTA production. This toxin was, however, not detected in any of the coffee bean species analyzed here. The species with the highest incidence were Aspergillus niger and Aspergillus ochraceus. The results of the mathematical model demonstrated the influence of temperature on the production of the toxin. This information indicates the distribution of toxigenic fungal species in the regions of coffee cultivation in Minas Gerais, and thus, will assist the producers in adopting preventive measures.Practical applicationsBrazil is the largest coffee producer and exporter, which makes it a leader in the global coffee market; the state of Minas Gerais is responsible for 50% of this production. Following the global trend, Brazil has regulated the maximum permissible limit for ochratoxin A in coffee beans. This has led to a great interest in monitoring fungi and toxin production, mainly during the postharvest stage in the coffee cultivation regions of Brazil. Preventive measures can aid in the safe production of coffee beans, and the use of mathematical models capable of predicting the growth and production of fungal toxins are fundamental to informing the producers of the most favorable conditions in terms of temperature, as well as increases in ambient temperature, in specific regions of interest.

64. Skin dose in high dose rate brachytherapy for breast cancers: evaluation by in vivo dosimetry using TLD and MOSFET dosimeters

Purpose The aim of this work is to evaluate a novel approach for the verification of the real skin dose in partial breast high dose rate brachytherapy (PB-BRT), quantify the treatment planning system (TPS) overestimation and develop a methodology for routinary in vivo dosimetry (IVD). Methods Currently there is not a general acknowledged constraint for skin dose in PB-BRT. Because of our center’s experience (20 PB-BRT patients treated/year) we achieve a good cosmetic outcome if the TPS calculated skin dose is below 50% of the prescription of 32 Gy (4 Gy/fraction, twice daily). The skin dose was calculated by a TPS which overestimates it assuming a homogeneous water medium and not accounting for the finite patient dimensions. IVD was performed on patients treated with multi-catheter brachytherapy, which involves placement of 9–15 catheters through the breast. Thermoluminescent dosimeters (TLDs) were used in the IVD sessions and they were placed on the skin next to the catheters and the nipple. We are currently implementing MOSFET real time measurements to compare with TLD results and to further improve the estimation of the skin dose. Results The doses measured by TLDs were compared to those calculated by the TPS in specific region of interest (ROI). For each patient two IVD sessions were performed, and the reproducibility of TLD positioning was assessed: 60% of couples give the same value within the experimental error. 77% of measurements show a clear overestimation of skin dose by the TPS. A Gaussian fit of the percentage differences between measured and calculated doses (Fig. 1) yielded an overestimation value of (25.2 ± 7.6)%. For a first group of patients IVD sessions were performed using MOSFET dosimeters, placed on the skin following the previous arrangement of TLDs. The doses measured by MOSFETs were compared to those calculated by the TPS in specific ROIs. Preliminary results show a quantitatively similar overestimation. Conclusions Measurements in PB-BRT are necessary to quantify the real skin dose accurately. A novel approach based on IVD allows us to define dose limits, to achieve not only the tumor control but also a good cosmetic outcome to improve the quality of patient’s life. Download : Download high-res image (131KB) Download : Download full-size image

Water footprint sustainability assessment for the chemical sector at the regional level

Water resource management is an important consideration for water-intensive industries, such as the chlor-alkali sector. Water footprint is a three-component measure of freshwater consumption over the life cycle of a product, and takes into account both direct and indirect water use. This work extends the water footprint concept for products by integrating water scarcity in geographic regions where the production takes place. A general framework for water footprint sustainability analysis (WFSA) for chemical production chains is thus developed. WFSA combines the water scarcity index and water footprint, and is applied at the level of geographic regions. Two indicators are then proposed to assess the sustainability of the product and of the industrial sector in a specific region of interest. Based on this framework, some policy recommendations are proposed to enhance the sustainability of the chlor-alkali sector.

Trivariate non‐Gaussian copulas to analyze the spatial behavior of rat sightings

The brown rat lives with man in a wide variety of environmental contexts and adversely affects public health by transmission of diseases, bites, and allergies. Understanding behavioral and spatial correlation aspects of pest species can contribute to their effective management and control. Rat sightings can be described by spatial coordinates in a particular region of interest defining a spatial point pattern. In this paper, we investigate the spatial structure of rat sightings in the Latina district of Madrid (Spain) and its relation to a number of distance‐based covariates that relate to the proliferation of rats. Given a number of locations, biologically considered as attractor points, the spatial dependence is modeled by distance‐based covariates and angular orientations through copula functions. We build a particular spatial trivariate distribution using univariate margins coming from the covariate information and provide predictive distributions for such distances and angular orientations.

OA110] A 3D-printed phantom study for quantitative 99MTC-MAA SPECT/CT imaging and dosimetry in 90Y radioembolization

Purpose Radioembolization (RE) with 90Y-microspheres is a well-established treatment modality for treating liver malignancies. At a time of increasing evidence for dose–effect relationships in RE with 90Y microspheres [1] , [2] , the general consensus is that there is an urgent need for accurate dosimetry in patients undergoing RE treatment. This work aimed at estimating absorbed doses to lesions and normal liver in a novel anthropomorphic set-up. Methods AbdoMan is a 3D-printed phantom provided with a fillable liver section and multiple inserts for lesion representation. A SPECT/CT Symbia Intevo provided with the proprietary xSPECT quantitative software was used to image the phantom according to the acquisition protocol currently used for RE patients. Specific regions of interest (ROIs) were drawn on MIM 6.1.7 system. A homemade tool was developed in MATLAB for image analysis and dose calculation based on two methods: I) convolution kernel and II) local deposition method. The accuracy of the two different dosimetric methods was evaluated by comparing dose-rate volume histograms (DrVHs). Moreover, γ -index was used to compare the dose distributions obtained by the two activity-to-dose methods. Results Differences calculated by the 3D γ -index are within 2%-2 mm for all AbdoMan inserts. The dose-kernel results in a γ γ as well as several image artefacts. In particular, an apparent over-dosage (about 25%) was observed in inserts with larger diameter, most likely due to spill-in and spill-out phenomena. The DrVHs for considered ROIs are within 2%-2 mm for both methods. Conclusions In RE treatment planning the dose-kernel method proved to be more accurate with respect to deposition method based on full 3D dose distributions.

Abstract 3621: High-plex immune marker spatial profiling quantitation by NanoString Digital Spatial Profiling technology and quantitative immunofluorescence

Abstract Background: Quantitative immunofluorescence (QIF) offers the advantage of multiple target measurement on a single slide, but is limited by the number of fluorescence channels. NanoString's Digital Spatial Profiling (DSP)* can detect and quantify immune markers at higher multiplex with spatial resolution within specific regions of interest on FFPE tissue. Here, we compare NanoString DSP to automated QIF (AQUA), for immune marker compartment specific measurement. Additionally, we assess their agreement on the prognostic value of commonly used biomarkers in Non-Small Cell Lung Cancer (NSCLC). Finally, we explore the predictive value of a 30-plex panel of immune markers on two cohorts of treated patients. Methods: NanoString DSP technology uses a cocktail of primary antibodies conjugated to indexing DNA oligos. Regions of interest (ROI) on the tissue are selected with fluorescently labeled antibodies, and oligos from that region are UV cleaved and quantified on the nCounter platform. The comparator for this technology was the AQUA method of QIF. We retrospectively examined a NSCLC cohort of over 100 patients for prognostic markers and two treated patient cohorts for associations between immune markers expression and response to treatment, all in tissue microarray format. The treated cohorts included an Epidermal Growth Factor Receptor Tyrosine kinase inhibitor (EGFR TKI) treated NSCLC cohort and a melanoma immunotherapy (ITx) treated cohort. Results: Multiple immune markers (CD3, CD4, CD8, CD20, PD-L1) were assessed and a high correlation was found between NanoString DSP counts and QIF scores, when the measurements were performed in the same ROIs (tumor or stroma). The prognostic value of the immune markers tested was concordant between the two assays with high expression of CD3 assessed by either assay showing a statistically significantly better overall survival (OS). For the EGFR TKI treated NSCLC cohort none of the immune markers was correlated with response to treatment or favorable outcome. However, in the ITx treated melanoma patients, PD-L1, PD-1, CD68, CD3, CD8A and b2-microglobulin tumor expression predicted response to treatment. Each marker also predicted better outcome, but only CD8A was an independent predictive marker of prolonged survival. Conclusion: NanoString DSP offers the capacity of highly multiplexed immune marker measurements on selected compartments. It shows high concordance with AQUA, which was further validated by comparing prognostic significance. The pilot study of the Melanoma ITx cohort also illustrates the potential to simultaneously evaluate a range of markers and possibly construct new predictive signatures based on a cohort represented by very small tissue samples. *FOR RESEARCH USE ONLY. Not for use in diagnostic procedures. Citation Format: Maria I. Toki, Pok Fai Wong, Harriet Kluger, Yuting Liu, Chris Merritt, Giang Ong, Sarah Warren, Joseph M. Beechem, David L. Rimm. High-plex immune marker spatial profiling quantitation by NanoString Digital Spatial Profiling technology and quantitative immunofluorescence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3621.