Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer.

This Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the United States. We repeated inoculations with irradiated SV-BR-1-GM, a breast cancer cell line with antigen-presenting activity engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), with pre-dose low-dose cyclophosphamide and post-dose local interferon alpha. Twenty-six patients were enrolled; 23 (88.5%) were inoculated, receiving a total of 79 inoculations. There were six Grade 4 and one Grade 5 adverse events noted (judged unrelated to SV-BR-1-GM). Disease control (stable disease [SD]) occurred in 8 of 16 evaluable patients; 4 showed objective regression of metastases, including 1 patient with near-complete regressions in 20 of 20 pulmonary lesions. All patients with regressions had human leukocyte antigen (HLA) matches with SV-BR-1-GM; non-responders were equally divided between matching and nonmatching (p = .01, Chi-squared), and having ≥2 HLA matches with SV-BR-1-GM (n = 6) correlated with clinical benefit. Delayed-type hypersensitivity (DTH) testing to candida antigen and SV-BR-1-GM generated positive responses (≥5 mm) in 11 (42.3%) and 13 (50%) patients, respectively. Quantifying peripheral circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) showed that a drop in CAMLs was significantly correlated with an improvement in progression-free survival (PFS; 4.1 months vs. 1.8 months, p = .0058). Eight of 10 patients significantly upregulated programmed cell death ligand 1 (PD-L1) on CTCs/CAMLs with treatment (p = .0012). These observations support the safety of the Bria-IMT regimen, demonstrate clinical regressions, imply a role for HLA matching, and identify a possible value for monitoring CAMLs in peripheral blood.

In situtumor model for longitudinal in silico imaging trials.

Objective.In this article, we introduce a computational model for simulating the growth of breast cancer lesions accounting for the stiffness of surrounding anatomical structures.Approach.In our model, ligaments are classified as the most rigid structures while the softer parts of the breast are occupied by fat and glandular tissues As a result of these variations in tissue elasticity, the rapidly proliferating tumor cells are met with differential resistance. It is found that these cells are likely to circumvent stiffer terrains such as ligaments, instead electing to proliferate preferentially within the more yielding confines of the breast's soft topography. By manipulating the interstitial tumor pressure in direct proportion to the elastic constants of the tissues surrounding the tumor, this model thus creates the potential for realizing a database of unique lesion morphology sculpted by the distinctive topography of each local anatomical infrastructure. We modeled the growth of simulated lesions within volumes extracted from fatty breast models, developed by Graffet alwith a resolution of 50µm generated with the open-source and readily available Virtual Imaging Clinical Trials for Regulatory Evaluation (VICTRE) imaging pipeline. To visualize and validate the realism of the lesion models, we leveraged the imaging component of the VICTRE pipeline, which replicates the siemens mammomat inspiration mammography system in a digital format. This system was instrumental in generating digital mammogram (DM) images for each breast model containing the simulated lesions.Results.By utilizing the DM images, we were able to effectively illustrate the imaging characteristics of the lesions as they integrated with the anatomical backgrounds. Our research also involved a reader study that compared 25 simulated DM regions of interest (ROIs) with inserted lesions from our models with DM ROIs from the DDSM dataset containing real manifestations of breast cancer. In general the simulation time for the lesions was approximately 2.5 hours, but it varied depending on the lesion's local environment.Significance.The lesion growth model will facilitate and enhance longitudinal in silico trials investigating the progression of breast cancer.

Assessing satisfaction of search in virtual mammograms for experienced and novice searchers.

Purpose: Satisfaction of search (SOS) is a phenomenon where searchers are more likely to miss a lesion/target after detecting a first lesion/target. Here, we investigated SOS for masses and calcifications in virtual mammograms with experienced and novice searchers to determine the extent to which: (1) SOS affects breast lesion detection, (2) similarity between lesions impacts detection, and (3) experience impacts SOS rates. Approach: The open virtual clinical trials framework was used to simulate the breast anatomy of patients, and up to two simulated masses and/or single-calcifications were inserted into the breast models. Experienced searchers (residents, fellows, and radiologists with breast imaging experience) and novice searchers (undergraduates who had no breast imaging experience) were instructed to search for up to two lesions (masses and calcifications) per image. Results: 2×2 mixed factors analysis of variances (ANOVAs) were run with: (1) single versus second lesion hit rates, (2) similar versus dissimilar second-lesion hit rates, and (3) similar versus dissimilar second-lesion response times as within-subject factors and experience as the between subject's factor. The ANOVAs demonstrated that: (1) experienced and novice searchers made a significant amount of SOS errors, (2) similarity had little impact on experienced searchers, but novice searchers were more likely to miss a dissimilar second lesion compared to when it was similar to a detected first lesion, (3) experienced and novice searchers were faster at finding similar compared to dissimilar second lesions. Conclusions: We demonstrated that SOS is a significant cause of lesion misses in virtual mammograms and that reader experience impacts detection rates for similar compared to dissimilar abnormalities. These results suggest that experience may impact strategy and/or recognition with theoretical implications for determining why SOS occurs.

Objective Image Quality Optimization in Augmented Reality Using Spatial Frequency Domain Models.

Augmented reality (AR) blends the digital and physical worlds by overlapping a virtual image onto the see-through physical environment. However, contrast reduction and noise superposition in an AR head-mounted display (HMD) can substantially limit image quality and human perceptual performance in both the digital and physical spaces. To assess image quality in AR, we performed human and model observer studies for various imaging tasks with targets placed in the digital and physical worlds. A target detection model was developed for the complete AR system including the optical see-through. Target detection performance using different observer models developed in the spatial frequency domain was compared with the human observer results. The non-prewhitening model with eye filter and internal noise results closely track human perception performance as measured by the area under the receiver operating characteristic curve (AUC), especially for tasks with high image noise. The AR HMD non-uniformity limits the low-contrast target (less than 0.02) observer performance for low image noise. In augmented reality conditions, the detectability of a target in the physical world is reduced due to the contrast reduction by the overlaid AR display image (AUC less than 0.87 for all the contrast levels evaluated). We propose an image quality optimization scheme to optimize the AR display configurations to match observer detection performance for targets in both the digital and physical worlds. The image quality optimization procedure is validated using both simulation and bench measurements of a chest radiography image with digital and physical targets for various imaging configurations.

A 2D Synthesized Image Improves the 3D Search for Foveated Visual Systems.

Current medical imaging increasingly relies on 3D volumetric data making it difficult for radiologists to thoroughly search all regions of the volume. In some applications (e.g., Digital Breast Tomosynthesis), the volumetric data is typically paired with a synthesized 2D image (2D-S) generated from the corresponding 3D volume. We investigate how this image pairing affects the search for spatially large and small signals. Observers searched for these signals in 3D volumes, 2D-S images, and while viewing both. We hypothesize that lower spatial acuity in the observers' visual periphery hinders the search for the small signals in the 3D images. However, the inclusion of the 2D-S guides eye movements to suspicious locations, improving the observer's ability to find the signals in 3D. Behavioral results show that the 2D-S, used as an adjunct to the volumetric data, improves the localization and detection of the small (but not large) signal compared to 3D alone. There is a concomitant reduction in search errors as well. To understand this process at a computational level, we implement a Foveated Search Model (FSM) that executes human eye movements and then processes points in the image with varying spatial detail based on their eccentricity from fixations. The FSM predicts human performance for both signals and captures the reduction in search errors when the 2D-S supplements the 3D search. Our experimental and modeling results delineate the utility of 2D-S in 3D search-reduce the detrimental impact of low-resolution peripheral processing by guiding attention to regions of interest, effectively reducing errors.

Medical image quality metrics for foveated model observers.

Purpose: A recently proposed model observer mimics the foveated nature of the human visual system by processing the entire image with varying spatial detail, executing eye movements, and scrolling through slices. The model can predict how human search performance changes with signal type and modality (2D versus 3D), yet its implementation is computationally expensive and time-consuming. Here, we evaluate various image quality metrics using extensions of the classic index of detectability expression and assess foveated model observers for search tasks. Approach: We evaluated foveated extensions of a channelized Hotelling and nonprewhitening matched filter model with an eye filter. The proposed methods involve calculating a model index of detectability ( d ' ) for each retinal eccentricity and combining these with a weighting function into a single detectability metric. We assessed different versions of the weighting function that varied in the required measurements of the human observers' search (no measurements, eye movement patterns, size of the image, and median search times). Results: We show that the index of detectability across eccentricities weighted using the eye movement patterns of observers best predicted human performance in 2D versus 3D search performance for a small microcalcification-like signal and a larger mass-like. The metric with a weighting function based on median search times was the second best predicting human results. Conclusions: The findings provide a set of model observer tools to evaluate image quality in the early stages of imaging system evaluation or design without implementing the more computationally complex foveated search model.

Computational Breast Anatomy Simulation Using Multi-Scale Perlin Noise.

Virtual clinical trials (VCTs) of medical imaging require realistic models of human anatomy. For VCTs in breast imaging, a multi-scale Perlin noise method is proposed to simulate anatomical structures of breast tissue in the context of an ongoing breast phantom development effort. Four Perlin noise distributions were used to replace voxels representing the tissue compartments and Cooper's ligaments in the breast phantoms. Digital mammography and tomosynthesis projections were simulated using a clinical DBT system configuration. Power-spectrum analyses and higher-order statistics properties using Laplacian fractional entropy (LFE) of the parenchymal texture are presented. These objective measures were calculated in phantom and patient images using a sample of 140 clinical mammograms and 500 phantom images. Power-law exponents were calculated using the slope of the curve fitted in the low frequency [0.1, 1.0] mm-1 region of the power spectrum. The results show that the images simulated with our prior and proposed Perlin method have similar power-law spectra when compared with clinical mammograms. The power-law exponents calculated are -3.10, -3.55, and -3.46, for the log-power spectra of patient, prior phantom and proposed phantom images, respectively. The results also indicate an improved agreement between the mean LFE estimates of Perlin-noise based phantoms and patients than our prior phantoms and patients. Thus, the proposed method improved the simulation of anatomic noise substantially compared to our prior method, showing close agreement with breast parenchyma measures.

Effect of socioeconomic inequalities and vulnerabilities on health-system preparedness and response to COVID-19 in Brazil: a comprehensive analysis.

BACKGROUND: COVID-19 spread rapidly in Brazil despite the country's well established health and social protection systems. Understanding the relationships between health-system preparedness, responses to COVID-19, and the pattern of spread of the epidemic is particularly important in a country marked by wide inequalities in socioeconomic characteristics (eg, housing and employment status) and other health risks (age structure and burden of chronic disease). METHODS: From several publicly available sources in Brazil, we obtained data on health risk factors for severe COVID-19 (proportion of the population with chronic disease and proportion aged ≥60 years), socioeconomic vulnerability (proportions of the population with housing vulnerability or without formal work), health-system capacity (numbers of intensive care unit beds and physicians), coverage of health and social assistance, deaths from COVID-19, and state-level responses of government in terms of physical distancing policies. We also obtained data on the proportion of the population staying at home, based on locational data, as a measure of physical distancing adherence. We developed a socioeconomic vulnerability index (SVI) based on household characteristics and the Human Development Index. Data were analysed at the state and municipal levels. Descriptive statistics and correlations between state-level indicators were used to characterise the relationship between the availability of health-care resources and socioeconomic characteristics and the spread of the epidemic and the response of governments and populations in terms of new investments, legislation, and physical distancing. We used linear regressions on a municipality-by-month dataset from February to October, 2020, to characterise the dynamics of COVID-19 deaths and response to the epidemic across municipalities. FINDINGS: The initial spread of COVID-19 was mostly affected by patterns of socioeconomic vulnerability as measured by the SVI rather than population age structure and prevalence of health risk factors. The states with a high (greater than median) SVI were able to expand hospital capacity, to enact stringent COVID-19-related legislation, and to increase physical distancing adherence in the population, although not sufficiently to prevent higher COVID-19 mortality during the initial phase of the epidemic compared with states with a low SVI. Death rates accelerated until June, 2020, particularly in municipalities with the highest socioeconomic vulnerability. Throughout the following months, however, differences in policy response converged in municipalities with lower and higher SVIs, while physical distancing remained relatively higher and death rates became relatively lower in the municipalities with the highest SVIs compared with those with lower SVIs. INTERPRETATION: In Brazil, existing socioeconomic inequalities, rather than age, health status, and other risk factors for COVID-19, have affected the course of the epidemic, with a disproportionate adverse burden on states and municipalities with high socioeconomic vulnerability. Local government responses and population behaviour in the states and municipalities with higher socioeconomic vulnerability have helped to contain the effects of the epidemic. Targeted policies and actions are needed to protect those with the greatest socioeconomic vulnerability. This experience could be relevant in other low-income and middle-income countries where socioeconomic vulnerability varies greatly. FUNDING: None. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Comparative observer effects in 2D and 3D localization tasks.

Purpose: Three-dimensional "volumetric" imaging methods are now a common component of medical imaging across many imaging modalities. Relatively little is known about how human observers localize targets masked by noise and clutter as they scroll through a 3D image and how it compares to a similar task confined to a single 2D slice. Approach: Gaussian random textures were used to represent noisy volumetric medical images. Subjects were able to freely inspect the images, including scrolling through 3D images as part of their search process. A total of eight experimental conditions were evaluated (2D versus 3D images, large versus small targets, power-law versus white noise). We analyze performance in these experiments using task efficiency and the classification image technique. Results: In 3D tasks, median response times were roughly nine times longer than 2D, with larger relative differences for incorrect trials. The efficiency data show a dissociation in which subjects perform with higher statistical efficiency in 2D tasks for large targets and higher efficiency in 3D tasks with small targets. The classification images suggest that a critical mechanism behind this dissociation is an inability to integrate across multiple slices to form a 3D localization response. The central slices of 3D classification images are remarkably similar to the corresponding 2D classification images. Conclusions: 2D and 3D tasks show similar weighting patterns between 2D images and the central slice of 3D images. There is relatively little weighting across slices in the 3D tasks, leading to lower task efficiency with respect to the ideal observer.

SimplePhy: An open-source tool for quick online perception experiments.

Because of the COVID-19 pandemic, researchers are facing unprecedented challenges that affect our ability to run in-person experiments. With mandated social distancing in a controlled laboratory environment, many researchers are searching for alternative options to conduct research, such as online experimentation. However, online experimentation comes at a cost; learning online tools for building and publishing psychophysics experiments can be complicated and time-consuming. This learning cost is unfortunate because researchers typically only need to use a small percentage of these tools' capabilities, but they still have to deal with these systems' complexities (e.g., complex graphical user interfaces or difficult programming languages). Furthermore, after the experiment is built, researchers often have to find an online platform compatible with the tool they used to program the experiment. To simplify and streamline the online process of programming and hosting an experiment, I have created SimplePhy. SimplePhy can save researchers' time and energy by allowing them to create a study in just a few clicks. All researchers have to do is select among a few experiment settings and upload the stimuli. SimplePhy is able to run most psychophysical perception experiments that require mouse clicks and button presses. In addition to collecting online behavioral data, SimplePhy can also collect information regarding the estimated viewing distance between the participant and the monitor, the screen size, and the experimental trial's timing-features not always offered in other online platforms. Overall, SimplePhy is a simple, free, open-source tool (code can be found here: https://gitlab.com/malago/simplephy ) aimed to help labs conduct their experiments online.

Under-exploration of Three-Dimensional Images Leads to Search Errors for Small Salient Targets.

Advances in 3D imaging technology are transforming how radiologists search for cancer1,2 and how security officers scrutinize baggage for dangerous objects.3 These new 3D technologies often improve search over 2D images4,5 but vastly increase the image data. Here, we investigate 3D search for targets of various sizes in filtered noise and digital breast phantoms. For a Bayesian ideal observer optimally processing the filtered noise and a convolutional neural network processing the digital breast phantoms, search with 3D image stacks increases target information and improves accuracy over search with 2D images. In contrast, 3D search by humans leads to high miss rates for small targets easily detected in 2D search, but not for larger targets more visible in the visual periphery. Analyses of human eye movements, perceptual judgments, and a computational model with a foveated visual system suggest that human errors can be explained by interaction among a target's peripheral visibility, eye movement under-exploration of the 3D images, and a perceived overestimation of the explored area. Instructing observers to extend the search reduces 75% of the small target misses without increasing false positives. Results with twelve radiologists confirm that even medical professionals reading realistic breast phantoms have high miss rates for small targets in 3D search. Thus, under-exploration represents a fundamental limitation to the efficacy with which humans search in 3D image stacks and miss targets with these prevalent image technologies.

Foveated Model Observers for Visual Search in 3D Medical Images.

Model observers have a long history of success in predicting human observer performance in clinically-relevant detection tasks. New 3D image modalities provide more signal information but vastly increase the search space to be scrutinized. Here, we compared standard linear model observers (ideal observers, non-pre-whitening matched filter with eye filter, and various versions of Channelized Hotelling models) to human performance searching in 3D 1/f2.8 filtered noise images and assessed its relationship to the more traditional location known exactly detection tasks and 2D search. We investigated two different signal types that vary in their detectability away from the point of fixation (visual periphery). We show that the influence of 3D search on human performance interacts with the signal's detectability in the visual periphery. Detection performance for signals difficult to detect in the visual periphery deteriorates greatly in 3D search but not in 3D location known exactly and 2D search. Standard model observers do not predict the interaction between 3D search and signal type. A proposed extension of the Channelized Hotelling model (foveated search model) that processes the image with reduced spatial detail away from the point of fixation, explores the image through eye movements, and scrolls across slices can successfully predict the interaction observed in humans and also the types of errors in 3D search. Together, the findings highlight the need for foveated model observers for image quality evaluation with 3D search.

Evaluation of Convolutional Neural Networks for Search in 1/f 2.8 Filtered Noise and Digital Breast Tomosynthesis Phantoms.

With the advent of powerful convolutional neural networks (CNNs), recent studies have extended early applications of neural networks to imaging tasks thus making CNNs a potential new tool for assessing medical image quality. Here, we compare a CNN to model observers in a search task for two possible signals (a simulated mass and a smaller simulated micro-calcification) embedded in filtered noise and single slices of Digital Breast Tomosynthesis (DBT) virtual phantoms. For the case of the filtered noise, we show how a CNN can approximate the ideal observer for a search task, achieving a statistical efficiency of 0.77 for the microcalcification and 0.78 for the mass. For search in single slices of DBT phantoms, we show that a Channelized Hotelling Observer (CHO) performance is affected detrimentally by false positives related to anatomic variations and results in detection accuracy below human observer performance. In contrast, the CNN learns to identify and discount the backgrounds, and achieves performance comparable to that of human observer and superior to model observers (Proportion Correct for the microcalcification: CNN = 0.96; Humans = 0.98; CHO = 0.84; Proportion Correct for the mass: CNN = 0.98; Humans = 0.83; CHO = 0.51). Together, our results provide an important evaluation of CNN methods by benchmarking their performance against human and model observers in complex search tasks.

Measurement of the useful field of view for single slices of different imaging modalities and targets.

Purpose: With three-dimensional (3-D) images displayed as stacks of 2-D images, radiologists rely more heavily on vision away from their fixation point to visually process information, guide eye movements, and detect abnormalities. Thus the ability to detect targets away from the fixation point, commonly characterized as the useful field of view (UFOV), becomes critical for these 3-D imaging modalities. We investigate how the UFOV, defined as the eccentricity, in which detection performance degrades to a given probability, varies across imaging modalities and targets. Approach: We measure the detectability of different targets at various distances from gaze locations for single slices of liver computed tomography (CT), 2-D digital mammograms (DM), and single slices of digital breast tomosynthesis (DBT) cases. Observers with varying expertise were instructed to maintain their gaze at a point while a short display of the image was flashed and an eye tracker verified observer's steady fixation. Display times were 200 and 1000 ms for CT images and 500 ms for DM and DBT images. Results: We find variations in the UFOV from 9 to 12 deg for liver CT to as small as 2.5 to 5 deg for calcification clusters in breast images (DM and DBT). We compare our results to those reported in the literature for lung nodules and discuss the differences across methods used to measure the UFOV, their dependence on case selection/task difficulty, viewing conditions, and observer expertise. We propose a complementary measure defined in terms of performance degradation relative to the peak foveal performance (relative-UFOV) to circumvent UFOV's variations with case selection/task difficulty. Conclusion: Our results highlight the variations in the UFOV across imaging modalities, target types, observer expertise, and measurement methods and suggest an additional relative-UFOV measure to more thoroughly characterize the detection performance away from point of fixation.

Migration Studies of Two Common Components of UV-curing Inks into Food Simulants.

The Rapid Alert System for Food and Feed (RASFF) has reported many cases of different UV curing inks components in foodstuffs during the last few years. These contaminants reach foodstuffs mainly by set-off, their principal migration mechanism from the package. Under this premise, this work has tried to characterize the process of migration of two common UV ink components: a photoinitiator (4-Methylbenzophenone) and a coinitiator (Ethyl-4-(dimethylamino) benzoate), from the most common plastic material used in food packaging low-density polyethylene (LDPE) into six different food simulants. The migration kinetics tests were performed at four different common storage temperatures, obtaining the key migration parameters for both molecules: the coefficients of diffusion and partition. The migration process was highly dependent on the storage conditions, the photoinitiator properties and the pH of the foodstuff.

Author Correction: The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling.

In the version of this Article originally published the same blot was inadvertently presented as both p-Rb and Cyclin A in Fig. 2a. This blot corresponds to the p-Rb panel, as can be seen in the unprocessed version of these blots in Supplementary Fig. 9. The corrected version of the panel is shown below, together with a completely uncropped image of both blots. In addition, in the 'Viral transduction' section of the Methods, the pLKO.1 plasmids encoding short hairpin RNAs targeting human Rnd1 were incorrectly listed as clones TRCN0000018338 and TRCN0000039977. The correct clone numbers are TRCN0000047434 and TRCN0000047435.

Evaluation of Search Strategies for Microcalcifications and Masses in 3D Images.

Medical imaging is quickly evolving towards 3D image modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT). These 3D image modalities add volumetric information but further increase the need for radiologists to search through the image data set. Although much is known about search strategies in 2D images less is known about the functional consequences of different 3D search strategies. We instructed readers to use two different search strategies: drillers had their eye movements restricted to a few regions while they quickly scrolled through the image stack, scanners explored through eye movements the 2D slices. We used real-time eye position monitoring to ensure observers followed the drilling or the scanning strategy while approximately preserving the percentage of the volumetric data covered by the useful field of view. We investigated search for two signals: a simulated microcalcification and a larger simulated mass. Results show an interaction between the search strategy and lesion type. In particular, scanning provided significantly better detectability for microcalcifications at the cost of 5 times more time to search while there was little change in the detectability for the larger simulated masses. Analyses of eye movements support the hypothesis that the effectiveness of a search strategy in 3D imaging arises from the interaction of the fixational sampling of visual information and the signals' visibility in the visual periphery.

Interactions of lesion detectability and size across single-slice DBT and 3D DBT.

Three dimensional image modalities introduce a new paradigm for visual search requiring visual exploration of a larger search space than 2D imaging modalities. The large number of slices in the 3D volumes and the limited reading times make it difficult for radiologists to explore thoroughly by fixating with their high resolution fovea on all regions of each slice. Thus, for 3D images, observers must rely much more on their visual periphery (points away from fixation) to process image information. We previously found a dissociation in signal detectability between 2D and 3D search tasks for small signals in synthetic textures evaluated with non-radiologist trained observers. Here, we extend our evaluation to more clinically realistic backgrounds and radiologist observers. We studied the detectability of simulated microcalcifications (MCALC) and masses (MASS) in Digital Breast Tomosynthesis (DBT) utilizing virtual breast phantoms. We compared the lesion detectability of 8 radiologists during free search in 3D DBT and a 2D single-slice DBT (center slice of the 3D DBT). Our results show that the detectability of the microcalcification degrades significantly in 3D DBT with respect to the 2D single-slice DBT. On the other hand, the detectability for masses does not show this behavior and its detectability is not significantly different. The large deterioration of the 3D detectability of microcalcifications relative to masses may be related to the peripheral processing given the high number of cases in which the microcalcification was missed and the high number of search errors. Together, the results extend previous findings with synthetic textures and highlight how search in 3D images is distinct from 2D search as a consequence of the interaction between search strategies and the visibility of signals in the visual periphery.

The role of extra-foveal processing in 3D imaging.

The field of medical image quality has relied on the assumption that metrics of image quality for simple visual detection tasks are a reliable proxy for the more clinically realistic visual search tasks. Rank order of signal detectability across conditions often generalizes from detection to search tasks. Here, we argue that search in 3D images represents a paradigm shift in medical imaging: radiologists typically cannot exhaustively scrutinize all regions of interest with the high acuity fovea requiring detection of signals with extra-foveal areas (visual periphery) of the human retina. We hypothesize that extra-foveal processing can alter the detectability of certain types of signals in medical images with important implications for search in 3D medical images. We compare visual search of two different types of signals in 2D vs. 3D images. We show that a small microcalcification-like signal is more highly detectable than a larger mass-like signal in 2D search, but its detectability largely decreases (relative to the larger signal) in the 3D search task. Utilizing measurements of observer detectability as a function retinal eccentricity and observer eye fixations we can predict the pattern of results in the 2D and 3D search studies. Our findings: 1) suggest that observer performance findings with 2D search might not always generalize to 3D search; 2) motivate the development of a new family of model observers that take into account the inhomogeneous visual processing across the retina (foveated model observers).

Foveated Model Observers to predict human performance in 3D images.

We evaluate 3D search requires model observers that take into account the peripheral human visual processing (foveated models) to predict human observer performance. We show that two different 3D tasks, free search and location-known detection, influence the relative human visual detectability of two signals of different sizes in synthetic backgrounds mimicking the noise found in 3D digital breast tomosynthesis. One of the signals resembled a microcalcification (a small and bright sphere), while the other one was designed to look like a mass (a larger Gaussian blob). We evaluated current standard models observers (Hotelling; Channelized Hotelling; non-prewhitening matched filter with eye filter, NPWE; and non-prewhitening matched filter model, NPW) and showed that they incorrectly predict the relative detectability of the two signals in 3D search. We propose a new model observer (3D Foveated Channelized Hotelling Observer) that incorporates the properties of the visual system over a large visual field (fovea and periphery). We show that the foveated model observer can accurately predict the rank order of detectability of the signals in 3D images for each task. Together, these results motivate the use of a new generation of foveated model observers for predicting image quality for search tasks in 3D imaging modalities such as digital breast tomosynthesis or computed tomography.