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All sourcesNASA NTRSDOE OSTI
NASA NTRS1990

Ulysses mission design after Challenger

The delay of the Ulysses launch from May 1986 to October 1990, because of the Challenger disaster, has altered both the constraints under which the mission must be designed and the timing of several mission critical events. Safety and launch reliability concerns from the Shuttle have increased the effective launch window to durations greater than one hour. Fortuitously high declinations of the launch asymptote (DLA), of the order of the launch site latitude, ameliorate the impact of the new constraints on the launch window. Target overlays in the first hour of the launch window provide higher departure energies that improve mission performance and avoid a science schedule conflict at second opposition near the time of closest Jupiter approach. The mission design starts with the maximum earth departure energy that the upper stage can deliver within the launch constraints. The Jupiter arrival asymptotes are chosen from the optimal point of mission performance in the mission space defined in the Jupiter B-plane by contours mapped by the science and spacecraft constraints. More than half the orbital energy of the earth-to-Jupiter transfer orbit is lost in the Jupiter flyby, and the Jupiter gravitational assist rotates the orbit plane out of the ecliptic to an inclination of about 80 degrees.

Luthey, Joe L.↗
NASA NTRS1992

The X-windows interactive navigation data editor

A new computer program called the X-Windows Interactive Data Editor (XIDE) was developed and demonstrated as a prototype application for editing radio metric data in the orbit-determination process. The program runs on a variety of workstations and employs pull-down menus and graphical displays, which allow users to easily inspect and edit radio metric data in the orbit data files received from the Deep Space Network (DSN). The XIDE program is based on the Open Software Foundation OSF/Motif Graphical User Interface (GUI) and has proven to be an efficient tool for editing radio metric data in the navigation operations environment. It was adopted by the Magellan Navigation Team as their primary data-editing tool. Because the software was designed from the beginning to be portable, the prototype was successfully moved to new workstation environments. It was also itegrated into the design of the next-generation software tool for DSN multimission navigation interactive launch support.

Rinker, G. C.↗
NASA NTRS2002

Issues and Consequences of Atomic Oxygen Undercutting of Protected Polymers in Low Earth Orbit

Hydrocarbon based polymers that are exposed to atomic oxygen in low Earth orbit are slowly oxidized which results in recession of their surface. Atomic oxygen protective coatings have been developed which are both durable to atomic oxygen and effective in protecting underlying polymers. However, scratches, pin window defects, polymer surface roughness and protective coating layer configuration can result in erosion and potential failure of protected thin polymer films even though the coatings are themselves atomic oxygen durable. This paper will present issues that cause protective coatings to become ineffective in some cases yet effective in others due to the details of their specific application. Observed in-space examples of failed and successfully protected materials using identical protective thin films will be discussed and analyzed. Proposed approaches to prevent the failures that have been observed will also be presented.

Banks, Bruce A.↗
NASA NTRS2012

Fast Paced, Low Cost Projects at MSFC

What does an orbiting microsatellite, a robotic lander and a ruggedized camera and telescope have in common? They are all fast paced, low cost projects managed by Marshall Space Flight Center (MSFC) teamed with successful industry partners. MSFC has long been synonymous with human space flight large propulsion programs, engineering acumen and risk intolerance. However, there is a growing portfolio/product line within MSFC that focuses on these smaller, fast paced projects. While launching anything into space is expensive, using a managed risk posture, holding to schedule and keeping costs low by stopping at egood enough f were key elements to their success. Risk is defined as the possibility of loss or failure per Merriam Webster. The National Aeronautics and Space Administration (NASA) defines risk using procedural requirement 8705.4 and establishes eclasses f to discern the acceptable risk per a project. It states a Class D risk has a medium to significant risk of not achieving mission success. MSFC, along with industry partners, has created a niche in Class D efforts. How did the big, cautious MSFC succeed on these projects that embodied the antithesis of its heritage in human space flight? A key factor toward these successful projects was innovative industry partners such as Dynetics Corporation, University of Alabama in Huntsville (UAHuntsville), Johns Hopkins Applied Physics Laboratory (JHU APL), Teledyne Brown Engineering (TBE), Von Braun Center for Science and Innovation (VCSI), SAIC, and Jacobs. Fast Affordable Satellite Technology (FastSat HSV01) is a low earth orbit microsatellite that houses six instruments with the primary scientific objective of earth observation and technology demonstration. The team was comprised of Dynetics, UAHuntsvile, SAIC, Goddard Space Flight Center (GSFC) and VCSI with the United States Air Force Space Test Program as the customer. The team completed design, development, manufacturing, environmental test and integration in one year. FastSat HSV01 also deployed a Poly Picosatellite Orbital Deployer (PPOD) for a separate nano ]satellite class spacecraft (Cubesat: Nano Sail Demonstration) in partnership with Ames Research Center. The Robotic lunar lander is a MSFC JHU APL partnership that led to the development of a flexible architecture for landers to support robotic missions to a wide range of lunar and asteroid destinations. The team started with the goal of meeting NASA agency directives that led to the creation of a test bed focusing on GN&C and software to demonstrate the descent and landing on any airless body for the final 30 to 60 meters. The team created a complex technology demonstration as well as Guidance Control and Navigation (GN&C) algorithms providing autonomous control of the lander. The team uses a green propellant of 90% hydrogen peroxide and has completed 18 successful test flights. The International Space Station (ISS) SERVIR Environmental Research and Visualization System (ISERV) is a technology demonstration payload to assist the SERVIR project with environmental monitoring for disaster relief and humanitarian efforts. The ISERV project was a partnership with TBE. The ISERV payload consists of a commercial off the shelf camera, telescope, and MSFC developed power distribution box and interfaces on ISS with the Window Observational Research Facility in the US Lab. MSFC has identified three key areas that enabled the low cost mission success to include culture, partnering, and cost/schedule control. This paper will briefly discuss these three Class D efforts, FastSat HSV-01, the Robotic Lunar Lander and the ISERV camera system, the lessons learned, their successes and challenges.

Watson-Morgan, Lisa↗
NASA NTRS2010

Spacecraft Power Source Installation at Launch Complex

For certain space missions, an assembly must be integrated onto the spacecraft as late as possible in the launch vehicle processing flow. 12This late integration can be driven for a variety of reasons including thermal or hazardous materials constraints. This paper discusses the process of integrating an assembly onto a spacecraft as late as one week prior to the opening of the launch window. Consideration is given to achieving sufficient access for hardware integration, methods of remotely securing hardware to the spacecraft, maintaining spacecraft cleanliness throughout the integration process, and electrically integrating the component to the spacecraft. Specific examples are taken from the remote mechanical, electrical, and fluid cooling system integration of the power source onto the Mars Science Laboratory (MSL) Rover at the Atlas V Vertical Integration Facility (VIF) at Cape Canaveral Air Force Station, Florida.

Lytal, Paul↗
NASA NTRS2016

Aerocapture Design Study for a Titan Polar Orbiter

In 2014 a team at NASA Goddard Space Flight Center (GSFC) studied the feasibility of using active aerocapture to reduce the chemical Delta V requirements for inserting a small scientific satellite into Titan polar orbit. The scientific goals of the mission would be multi-spectral imaging and active radar mapping of Titan's surface and subsurface. The study objectives were to: (i) identify and select from launch window opportunities and refine the trajectory to Titan; (ii) study the aerocapture flight path and refine the entry corridor; (iii) design a carrier spacecraft and systems architecture; (iv) develop a scientific and engineering plan for the orbital portion of the mission. Study results include: (i) a launch in October 2021 on an Atlas V vehicle, using gravity assists from Earth and Venus to arrive at Titan in January 2031; (ii) initial aerocapture via an 8-km wide entry corridor to reach an initial 350X6000 km orbit, followed by aerobraking to reach a 350X1500 km orbit, and a periapse raise maneuver to reach a final 1500 km circular orbit; (iii) a three-part spacecraft system consisting of a cruise stage, radiator module, and orbiter inside a heat shield; (iv) a 22-month mission including station keeping to prevent orbital decay due to Saturn perturbations, with 240 Gb of compressed data returned. High-level issues identified include: (i) downlink capability - realistic downlink rates preclude the desired multi-spectral, global coverage of Titan's surface; (ii) power - demise of the NASA ASRG (Advanced Stirling Radioisotope Generator) program, and limited availability at present of MMRTGs (Multi-Mission Radioisotope Generators) needed for competed outer planet missions; (iii) thermal - external radiators must be carried to remove 4 kW of waste heat from MMRTGs inside the aeroshell, requiring heat pipes that pass through the aeroshell lid, compromising shielding ability; (iv) optical navigation to reach the entry corridor; (v) the NASA requirement of continuous critical event coverage for the orbiter, especially during the peak heating of the aerocapture when the radio link will be broken. In conclusion, although Titan aerocapture allows for considerable savings in propellant mass, this comes at a cost of increased mission complexity. Further architecture study and refinement is required to reduce high-level mission risks and to elucidate the optimum architecture.

Nixon, Conor A.↗
DOE OSTI2020

Extended Plate Wall System Expands Adoption of High-R Envelope Solutions

For decades, the residential building industry has worked to expand opportunities to increase the thermal resistance of walls. Multiple high-R wall construction methods have been developed, yet market adoption remains low because of perceived complexity and cost. One appealing solution is an extended plate wall system (EPW). Framing for top and bottom plates is one nominal dimension larger than for studs, which provides space for a 2-inch layer of foam plastic insulative sheathing (FPIS). Wood structural sheathing (OSB or plywood) is then installed on the exterior, fastened directly to the plates and nailed through the foam to the studs. In contrast to the conventional method of installing FPIS as a fully exterior layer, the EPW greatly simplifies air sealing, installation and detailing of windows and doors, an application of a weather resistive barrier, and attachment of cladding.

Building America↗
DOE OSTI2020

Extended Plate Wall System Expands Adoption of High-R Envelope Solution

For decades, the residential building industry has worked to expand opportunities to increase the thermal resistance of walls. Multiple high-R wall construction methods have been developed, yet market adoption remains low because of perceived complexity and cost. One appealing solution is an extended plate wall system (EPW). Framing for top and bottom plates is one nominal dimension larger than for studs, which provides space for a 2-inch layer of foam plastic insulative sheathing (FPIS). Wood structural sheathing (OSB or plywood) is then installed on the exterior, fastened directly to the plates and nailed through the foam to the studs. In contrast to the conventional method of installing FPIS as a fully exterior layer, the EPW greatly simplifies air sealing, installation and detailing of windows and doors, an application of a weather resistive barrier, and attachment of cladding.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2018

Opening up the QCD axion window

We present a new mechanism to deplete the energy density of the QCD axion, making decay constants as high as f a ≃ 10 17 GeV viable for generic initial conditions. In our setup, the axion couples to a massless dark photon with a coupling that is moderately stronger than the axion coupling to gluons. Dark photons are produced copiously through a tachyonic instability when the axion field starts oscillating, and an exponential suppression of the axion density can be achieved. For a large part of the parameter space this dark radiation component of the universe can be observable in upcoming CMB experiments. Such dynamical depletion of the axion density ameliorates the isocurvature bound on the scale of inflation. The depletion also amplifies the power spectrum at scales that enter the horizon before particle production begins, potentially leading to axion miniclusters.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
NASA NTRS1983

Anodizing Process

This anodizing process traces its origin to the 1960's when Reynolds Metals Company, under contract with Goddard Space Flight Center, developed a multipurpose anodizing electrolyte (MAE) process to produce a hard protective finish for spacecraft aluminum. MAE produces a high-density, abrasion-resistant film prior to the coloring step, in which the pores of the film are impregnated with a metallic form of salt. Tru-Color product applications include building fronts, railing, curtain walls, doors and windows.

Source record↗
NASA NTRS2007

Effects of RAM Exposure on a Low Earth Orbit BroadBand Radiometer (BBR): CERES Experience and Implications for EarthCARE

In order to best detect real changes in the Earth's climate system it is estimated that space based instrumentation measuring the global Earth Radiation Budget (ERB) must remain calibrated with a stability of 0.3% per decade. This level of stability is beyond the specified accuracy of existing ERB programs such as the Clouds and the Earth's Radiant Energy System (CERES, using three broadband radiometric scanning channels: the shortwave (SW 0.3 - 5?m), total (0.3 - >100 micron), and window (8 - 12 micron)). When in low earth orbit, it has been shown that optical response to blue-UV radiance can be reduced significantly (> 3%) due to UV hardened contaminants deposited on the surface of the optics. Evidence suggests that exposure of telescope optics to the forward looking ram direction is the primary cause of this contamination build up. With typical onboard calibration lamps emitting very low energy in the blue-UV region, this darkening is not directly measurable using standard internal calibration techniques. This paper describes a study using a model of ram exposure induced contaminant deposition and darkening, in conjunction standard established in-flight vicarious and internal calibration techniques to derive the spectral shape of the darkening to which a broadband instrument is subjected. The results of the model when applied to the CERES instruments are shown. These findings are of great importance to the EarthCARE project, whose BBR uses one broadband telescope permanently looking forward at 45 degrees, with continual exposure to the ram direction. Specific attention may therefore be needed in the design of BBR optics and on-board calibration in order to prevent or compensate for the spectral darkening seen in the CERES project.

Matthews, Grant↗
NASA NTRS2006

CMOS imager for pointing and tracking applications

Systems and techniques to realize pointing and tracking applications with CMOS imaging devices. In general, in one implementation, the technique includes: sampling multiple rows and multiple columns of an active pixel sensor array into a memory array (e.g., an on-chip memory array), and reading out the multiple rows and multiple columns sampled in the memory array to provide image data with reduced motion artifact. Various operation modes may be provided, including TDS, CDS, CQS, a tracking mode to read out multiple windows, and/or a mode employing a sample-first-read-later readout scheme. The tracking mode can take advantage of a diagonal switch array. The diagonal switch array, the active pixel sensor array and the memory array can be integrated onto a single imager chip with a controller. This imager device can be part of a larger imaging system for both space-based applications and terrestrial applications.

Pain, Bedabrata↗
NASA NTRS2017

Development of Multi-Sensor Global Cloud and Radiance Composites for DSCOVR EPIC Imager with Subpixel Definition

The Deep Space Climate Observatory (DSCOVR) enables analysis of the daytime Earth radiation budget via the onboard Earth Polychromatic Imaging Camera (EPIC) and National Institute of Standards and Technology Advanced Radiometer (NISTAR). EPIC delivers adequate spatial resolution imagery but only in shortwave bands (317-780 nm), while NISTAR measures the top-of-atmosphere (TOA) whole-disk radiance in shortwave and longwave broadband windows. Accurate calculation of albedo and outgoing longwave flux requires a high-resolution scene identification such as the radiance observations and cloud properties retrievals from low earth orbit (LEO, including NASA Terra and Aqua MODIS, Suomi-NPP VIIRS, and NOAA AVHRR) and geosynchronous (GEO, including GOES east and west, METEOSAT, INSAT-3D, MTSAT-2, and Himawari-8) satellite imagers. The cloud properties are derived using the Clouds and the Earth's Radiant Energy System (CERES) mission Cloud Subsystem group algorithms. These properties have to be co-located with EPIC pixels to provide the scene identification and to select anisotropic directional models (ADMs), which are then used to adjust the NISTAR-measured radiance and subsequently obtain the global daytime shortwave and longwave fluxes. This work presents an algorithm for optimal merging of selected radiance and cloud property parameters derived from multiple satellite imagers to obtain seamless global hourly composites at 5-km resolution. Selection of satellite data for each 5-km pixel is based on an aggregated rating that incorporates five parameters: nominal satellite resolution, pixel time relative to the EPIC time, viewing zenith angle, distance from day/night terminator, and probability of sun glint. To provide a smoother transition in the merged output, in regions where candidate pixel data from two satellite sources have comparable aggregated rating, the selection decision is defined by the cumulative function of the normal distribution so that abrupt changes in the visual appearance of the composite data are avoided. Higher spatial accuracy in the composite product is achieved by using the inverse mapping with gradient search during reprojection and bicubic interpolation for pixel resampling.

Khlopenkov, Konstantin V.↗
NASA NTRS2019

CMB-HD: An Ultra-Deep, High-Resolution Millimeter-Wave Survey Over Half the Sky

A millimeter-wave survey over half the sky, that spans frequencies in the range of 30 to 350 GHz, and that is both an order of magnitude deeper and of higher-resolution than currently funded surveys would yield an enormous gain in understanding of both fundamental physics and astrophysics. By providing such a deep, high-resolution millimeter-wave survey (about 0.5 Karcmin noise and 15 arcsecond resolution at 150 GHz), CMB-HD will enable major advances.It will allow 1.) the use of gravitational lensing of the primordial microwave background to map the distribution of matter on small scales (k 10 hMpc1), which probes dark matter particle properties. It will also allow 2.) measurements of the thermal and kinetic Sunyaev-Zel'dovich effects on small scales to map the gas density and gas pressure profiles of halos over a wide field,which probes galaxy evolution and cluster astrophysics. In addition, CMB-HD would allow us to cross critical thresholds in fundamental physics: 3.) ruling out or detecting any new, light (< 0:1 eV), thermal particles, which could potentially be the dark matter, and 4.) testing a wide class of multi-field models that could explain an epoch of inflation in the early Universe. Such a survey would also 5.) monitor the transient sky by mapping the full observing region every few days,which opens a new window on gamma-ray bursts, novae, fast radio bursts, and variable active galactic nuclei. Moreover, CMB-HD would 6.) provide a census of planets, dwarf planets, andasteroids in the outer Solar System, and 7.) enable the detection of exo-Oort clouds around othersolar systems, shedding light on planet formation. The combination of CMB-HD with contemporaryground and space-based experiments will also provide powerful synergies. CMB-HD willdeliver this survey in 5 years of observing 20,000 square degrees, using two new 30-meter-classoff-axis cross-Dragone telescopes to be located at Cerro Toco in the Atacama Desert. The telescopeswill field about 2.4 million detectors (600,000 pixels) in total. The CMB-HD survey willbe made publicly available, with usability and accessibility a priority.

Sehgal, Neelima↗
DOE OSTI2013

A BRIGHT IMPULSIVE SOLAR BURST DETECTED AT 30 THz

Ground- and space-based observations of solar flares from radio wavelengths to gamma-rays have produced considerable insights but raised several unsolved controversies. The last unexplored wavelength frontier for solar flares is in the range of submillimeter and infrared wavelengths. Here we report the detection of an intense impulsive burst at 30 THz using a new imaging system. The 30 THz emission exhibited remarkable time coincidence with peaks observed at microwave, mm/submm, visible, EUV, and hard X-ray wavelengths. The emission location coincides with a very weak white-light feature, and is consistent with heating below the temperature minimum in the atmosphere. However, there are problems in attributing the heating to accelerated electrons. The peak 30 THz flux is several times larger than the usual microwave peak near 9 GHz, attributed to non-thermal electrons in the corona. The 30 THz emission could be consistent with an optically thick spectrum increasing from low to high frequencies. It might be part of the same spectral component found at sub-THz frequencies whose nature remains mysterious. Further observations at these wavelengths will provide a new window for flare studies.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS2013

Enigma Version 12

Enigma Version 12 software combines model building, animation, and engineering visualization into one concise software package. Enigma employs a versatile user interface to allow average users access to even the most complex pieces of the application. Using Enigma eliminates the need to buy and learn several software packages to create an engineering visualization. Models can be created and/or modified within Enigma down to the polygon level. Textures and materials can be applied for additional realism. Within Enigma, these models can be combined to create systems of models that have a hierarchical relationship to one another, such as a robotic arm. Then these systems can be animated within the program or controlled by an external application programming interface (API). In addition, Enigma provides the ability to use plug-ins. Plugins allow the user to create custom code for a specific application and access the Enigma model and system data, but still use the Enigma drawing functionality. CAD files can be imported into Enigma and combined to create systems of computer graphics models that can be manipulated with constraints. An API is available so that an engineer can write a simulation and drive the computer graphics models with no knowledge of computer graphics. An animation editor allows an engineer to set up sequences of animations generated by simulations or by conceptual trajectories in order to record these to highquality media for presentation. Enigma Version 12 Lyndon B. Johnson Space Center, Houston, Texas 28 NASA Tech Briefs, September 2013 Planetary Protection Bioburden Analysis Program NASA's Jet Propulsion Laboratory, Pasadena, California This program is a Microsoft Access program that performed statistical analysis of the colony counts from assays performed on the Mars Science Laboratory (MSL) spacecraft to determine the bioburden density, 3-sigma biodensity, and the total bioburdens required for the MSL prelaunch reports. It also contains numerous tools that report the data in various ways to simplify the reports required. The program performs all the calculations directly in the MS Access program. Prior to this development, the data was exported to large Excel files that had to be cut and pasted to provide the desired results. The program contains a main menu and a number of submenus. Analyses can be performed by using either all the assays, or only the accountable assays that will be used in the final analysis. There are three options on the first menu: either calculate using (1) the old MER (Mars Exploration Rover) statistics, (2) the MSL statistics for all the assays, or This software implements penetration limit equations for common micrometeoroid and orbital debris (MMOD) shield configurations, windows, and thermal protection systems. Allowable MMOD risk is formulated in terms of the probability of penetration (PNP) of the spacecraft pressure hull. For calculating the risk, spacecraft geometry models, mission profiles, debris environment models, and penetration limit equations for installed shielding configurations are required. Risk assessment software such as NASA's BUMPERII is used to calculate mission PNP; however, they are unsuitable for use in shield design and preliminary analysis studies. The software defines a single equation for the design and performance evaluation of common MMOD shielding configurations, windows, and thermal protection systems, along with a description of their validity range and guidelines for their application. Recommendations are based on preliminary reviews of fundamental assumptions, and accuracy in predicting experimental impact test results. The software is programmed in Visual Basic for Applications for installation as a simple add-in for Microsoft Excel. The user is directed to a graphical user interface (GUI) that requires user inputs and provides solutions directly in Microsoft Excel workbooks. This work was done by Shannon Ryan of the USRA Lunar and Planetary Institute for Johnson Space Center. Further information is contained in a TSP (see page 1). MSC- 24582-1 Micrometeoroid and Orbital Debris (MMOD) Shield Ballistic Limit Analysis Program Lyndon B. Johnson Space Center, Houston, Texas Commercially, because it is so generic, Enigma can be used for almost any project that requires engineering visualization, model building, or animation. Models in Enigma can be exported to many other formats for use in other applications as well. Educationally, Enigma is being used to allow university students to visualize robotic algorithms in a simulation mode before using them with actual hardware.

Shores, David↗
DOE OSTI2024

Galaxy bispectrum in the spherical Fourier-Bessel basis

The bispectrum, the three-point correlation in Fourier space, is a crucial statistic for studying many effects targeted by the next-generation galaxy surveys, such as primordial non-Gaussianity (PNG) and general relativistic (GR) effects on large scales. In this work we develop a formalism for the bispectrum in the spherical Fourier-Bessel (SFB) basis—a natural basis for computing correlation functions on the curved sky, as it diagonalizes the Laplacian operator in spherical coordinates. Working in the SFB basis allows for line-of-sight effects such as redshift space distortions and GR to be accounted for exactly, i.e., without having to resort to perturbative expansions to go beyond the plane-parallel approximation. Only analytic results for the SFB bispectrum exist in the literature given the intensive computations needed. We numerically calculate the SFB bispectrum for the first time, enabled by a few techniques: We implement a template decomposition of the redshift-space kernel Z 2 into Legendre polynomials, and separately treat the PNG and velocity-divergence terms. We derive an identity to integrate a product of three spherical harmonics connected by a Dirac delta function as a simple sum and use it to investigate the limit of a homogeneous and isotropic Universe. Furthermore, we present a formalism for convolving the signal with separable window functions and use a toy spherically symmetric window to demonstrate the computation and give insights into the properties of the observed bispectrum signal. While our implementation remains computationally challenging, it is a step toward a feasible full extraction of information on large scales via a SFB bispectrum analysis.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2016

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

Purpose: The interactions of neoplastic cells with each other and the microenvironment are complex. To understand intratumoral heterogeneity, subtle differences should be quantified. Main factors contributing to heterogeneity include the gradient ischemic level within neoplasms, action of microenvironment, mechanisms of intercellular transfer of genetic information, and differential mechanisms of modifications of genetic material/proteins. This may reflect on the expression of biomarkers in the context of prognosis/stratification. Hence, a rigorous approach for assessing the spatial intratumoral heterogeneity of histological biomarker expression with accuracy and reproducibility is required, since patterns in immunohistochemical images can be challenging to identify and describe. Methods: A quantitative method that is useful for characterizing complex irregular structures is lacunarity; it is a multiscale technique that exhaustively samples the image, while the decay of its index as a function of window size follows characteristic patterns for different spatial arrangements. In histological images, lacunarity provides a useful measure for the spatial organization of a biomarker when a sampling scheme is employed and relevant features are computed. The proposed approach quantifies the segmented proliferative cells and not the textural content of the histological slide, thus providing a more realistic measure of heterogeneity within the sample space of the tumor region. The aim is to investigate in whole sections of primary pancreatic neuroendocrine neoplasms (pNENs), using whole-slide imaging and image analysis, the spatial intratumoral heterogeneity of Ki-67 immunostains. Unsupervised learning is employed to verify that the approach can partition the tissue sections according to distributional heterogeneity. Results: The architectural complexity of histological images has shown that single measurements are often insufficient. Inhomogeneity of distribution depends not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

60 APPLIED LIFE SCIENCES↗